Substituted aminoquinolones as DGKalpha inhibitors for immune activation

This application is a continuation of U.S. application Ser. No. 17/780,890, which adopts an international filing date of Nov. 24, 2020, which is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/EP2020/083198, filed internationally on Nov. 24, 2020, which claims benefit of European Application Nos.: 19212252.1, filed on Nov. 28, 2019, and 20181065.2, filed on Jun. 19, 2020.

The contents of the electronic sequence listing (777052065201SEQLIST.xml; Size: 8,897 bytes; and Date of Creation: Nov. 18, 2022) is herein incorporated by reference in its entirety.

The present invention covers substituted aminoquinolone compounds of general formula (I) as described and defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of diacylglycerol kinase alpha (DGKalpha, DGKα) regulated disorders, as a sole agent or in combination with other active ingredients.

The compounds of general formula (I) inhibit DGKα and enhance T cell mediated immune response. This is a new strategy to use the patient's own immune system to overcome immunoevasive strategies utilized by many neoplastic disorders, respectively cancer and by this enhancing anti-tumor immunity. Furthermore, said compounds are used in particular to treat disorders such as viral infections or conditions with dysregulated immune responses or other disorders associated with aberrant DGKα signaling.

The present invention further relates to the use, respectively to the use of the compounds of general formula (I) for manufacturing pharmaceutical compositions for enhancement of T cell mediated immune response.

The present invention further relates to the use, respectively to the use of the compounds of general formula (I) for manufacturing pharmaceutical compositions for the treatment of cancer.

The present invention further relates to the use, respectively to the use of the compounds of general formula (I) for manufacturing pharmaceutical compositions for the treatment or prophylaxis of fibrotic disorders, virus infections, cardiac diseases and lymphoproliferative disorders.

Diacylglycerol kinases (DGKs) represent a family of enzymes that catalyze phosphorylation of the membrane lipid sn-1,2 diacylglycerol (DAG) to form phosphatidic acid (PA) (Eichmann and Lass, Cell Mol Life Sci. 2015; 72: 3931). In T cells, DAG is formed downstream of the T cell receptor (TCR) after activation of the gamma 1 isoform of phospholipase C (PLCγ1) and cleavage of phosphatidylinositol 4,5-biphosphate (PIP2) into DAG and an additional second messenger, inositol 1,4,5-triphosphate (IP3) (Krishna and Zhong, Front. Immunol 2013, 4, 178). Whereas, IP3 is important in facilitating release of calcium from the endoplasmic reticulum, DAG interacts with other proteins important in TCR signal transduction, such as Protein kinase Cθ (Quann et al., Nat Immunol 2011(7), 647) and the Ras activating protein RasGRP1 (Krishna and Zhong, Front. Immunol 2013, 4:178). Although, three isoforms of DGK are known to be present within T cells [DGKα (DGKalpha), DGKδ (DGKdelta), and DGKζ (DGKzeta)], only two, DGKα and DGKζ, are thought to play an important role in facilitating DAG metabolism downstream of the TCR (Joshi and Koretzky, Int. J. Mol. Sci. 2013, 14, 6649).

Targeting the activity of DGKα in T cells, either by germline deletion, or with chemical inhibitors, results in enhanced and sustained signaling downstream of T cells, as assessed by prolonged phosphorylation of downstream molecules, such as extracellular signal-related kinases 1/2 (ERK1/2 (Zhong et al., Nat Immunol 2003, 4, 882; Olenchock et al., Nat Immunol 2006, 7, 1174; Riese et al., J. Biol. Chem 2011, 286, 5254). Furthermore, the overexpression of DGKα induces a state of decreased functional activity resembling an anergy-like state (Zha et al., Nat Immunol 2006, 7, 1166). In contrast, deletion of DGKα in T cells with enhanced production of effector cytokines, such as IL2 and IFNγ, and enhanced proliferation (Zhong et al., Nat Immunol 2003, 4, 882 Olenchock et al., Nat Immunol 2006, 7, 1174).

These findings suggest that DGKα might serve as a useful target for enhancing T cell anti-tumor activity. The role of DGKα in anti-tumor responses was studied recently in human tumor-infiltrating CD8+ T cells (CD8-TILs) from patients with renal cell carcinoma (RCC) (Prinz et al., J. Immunol 2012, 188, 5990). CD8-TILs from RCCs were defective in lytic granule exocytosis and their ability to kill target cells. While proximal signaling events were intact in response to TCR engagement, CD8-TILs exhibited decreased phosphorylation of ERK when compared to non-tumor-infiltrating CD8+ T cells. Treatment of CD8-TILs with an inhibitor of DGKα activity rescued killing ability of target cells, increased basal levels of phosphorylation of ERK, and increased PMA/ionomycin-stimulated phosphorylation of ERK.

In addition, Arranz-Nicolas et al show that DGK inhibitors promoted not only Ras/ERK signaling but also AP-1 (Activator protein-1) transcription, facilitated DGKα membrane localization, reduced the requirement for costimulation, and cooperated with enhanced activation following DGKζ silencing/deletion. In contrast with enhanced activation triggered by pharmacological inhibition, DGKα silencing/genetic deletion led to impaired Lck (lymphocyte-specific protein tyrosine kinase) activation and limited costimulation responses. (Arranz-Nicolas et al., Canc Immun, Immunother 2018, 67(6), 965).

In addition, antigen-specific CD8 + T cells from DGKα −/− and DGKζ −/− mice show enhanced expansion and increased cytokine production following (Lymphocytic choriomeningitis virus) infection (Shin et al. J. Immunol, 2012).

Additionally, the adoptive transfer of CAR (chimeric antigen receptor)-T cells deficient in DGKα demonstrated increased efficacy compared to wild type CAR T cells T cells in the treatment of murine mesothelioma (Riese et al., Cancer Res 2013, 73(12), 3566) and a glioblastoma xenograft mouse model (Jung et al. Cancer Res. 2018, 78(16), 4692).

Apart from T-cell regulation, DGKα also plays a role in cancer, mediating numerous aspects of cancer cell progression including survival (Bacchiocchi et al., Blood, 2005, 106(6), 2175; Yanagisawa et al. Biochim Biophys Acta 2007, 1771, 462), migration and invasion of cancer cells (Baldanzi et al., Oncogene 2008, 27, 942; Filigheddu et al., Anticancer Res 2007, 27, 1489; Rainero et al., J Cell Biol 2012, 196(2): 277). In particular, it has been reported that DGKα is over expressed in hepatocellular carcinoma (Takeishi et al., J Hepatol 2012, 57, 77) and melanoma cells (Yanagisawa et al., Biochim Biophys Acta 2007, 1771, 462) while other reports suggested that the growth of colon and breast cancer cell lines was significantly inhibited by DGKα-siRNA16 and DGKα/atypical PKC/b1 integrin signalling pathway was crucial for matrix invasion of breast carcinoma cells (Rainero et al., PLoS One 2014, 9(6): e97144) In addition, expression is also higher in lymphonodal metastasis than in breast original tumour (Hao et al., Cancer 2004, 100, 1110).

Additionally, a study testing the importance of DGKα in glioblastoma multiforme (GBM) cells found that concurrent administration of the relatively non-specific DGKα inhibitor R59022 resulted in decreased growth of intracranially injected GBM tumors. (Dominguez et al. Cancer Discov 2013, 3(7): 782).

Also, DGKα promotes esophageal squamous cell carcinoma (ESCC) progression, supporting DGKα as a potential target for ESCC therapy (Chen et al., Oncogene, 2019, 38 (14) 2533).

In addition, pharmacological inhibition of DGK diminished both airway inflammation and airway hyperresponsiveness in mice and also reduced bronchoconstriction of human airway samples in vitro by blocking T helper 2 (T H 2) differentiation (Singh et al., Sci Signal. 2019, 12, eaax3332). Furthermore, inhibition of DGKα has the potential to reverse the life-threatening Epstein-Barr virus (EBV)-associated immunopathology that occurs in patients X-linked lymphoproliferative disease (XLP-1) patients (Ruffo et al., Sci Transl Med. 2016, 13, 8, 321; Velnati et al., Eur J Med Chem. 2019, 164,378).

In addition, DGKα exacerbates cardiac injury after ischemia/reperfusioncardiac diseases (Sasaki et al., Heart Vessels, 2014, 29,110).

Taken together, the findings from these studies argue that restraining DGKα activity in T cells and tumor cells may prove valuable in generating more vigorous immune responses against pathogens and tumors and in amoiroting Th2 driven (ato) immune diseases (in re-balancing the immune-systeme). In addition, inhibiting DGKα activity has a therapeutic potential in targeting tumors directly as well as addressing fibrotic disorders, virus infection associated pathologies, cardiac diseases and lymphoproliferative disorders.

DGKα inhitors were reported in the literature. R59022 (A) was identified to act on DGKα in red blood cells (de Chaffoy de Courcelles et.al., J. Biol. Chem. Vol 260, No. 29, (1985), p 15762-70). Structurally related R59949 (B) was identified to act on DGKα in T-lymphocytes by inhibiting the transformation of 1,2-diacylglycerols to their respective phosphatidic acids (Jones et.al., J. Biol. Chem. Vol 274, No. 24, (1999), p 16846-52). Ritanserin (C), originally identified as a serotonine receptor antagonist, showed comparable activity on DGKα such as the two R cpds (A) and (B) (Boroda et.al., Bio Chem. Pharm. 123, (2017), 29-39).

A further structure, CU-3 (D) was identified as a first compound with sub-micromolar inhibitory activity on DGKα (Sakane et.al., J. Lipid Res. Vol 57, (2016), p 368-79).

AMB639752 (E) was describe as a further DGKα selective inhibitor with micromolar activity (S. Velnati et al. Eur J. Med. Chem 2019, 164, p 378-390.).

WO2020/151636 relates to azaquinolinones as PDE9 inhibitor compounds for treatment of PDE9 mediated diseases.

WO2020/143626 relates to quinolinones as PDE9 inhibitor compounds for treatment of PDE9 mediated diseases.

WO2020/182076 relates to the use of phosphodiesterase inhibitor compounds in the preparation of drugs for treating heart failure in mammals.

WO2020/006016 and WO2020/006018 describe Naphthydrinone compounds as T cell activators, which inhibit the activity of DGKα and/or DGLζ, for treatment of viral infections and proliferative disorders, such as cancer.

WO2017/019723 A1 relates to azacyanoquinolinone compounds which may be useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 9 (PDE9). It also relates to the use of the compounds for treating neurological and psychiatric disorders.

WO2004/074218 describes MIF-inhibitors and multiple uses thereof, among others for treatment of cancer.

WO2007/109251 describes the use of TNFα inhibitors for treatment of diseases, among others for treatment of cancer.

WO 2012/142498 and WO2012/009649 describe MIF-inhibitors and multiple uses thereof, among others in cancer therapy. These patent applications claim an extremely high number of compounds. However, many of these theoretical compounds are not specifically disclosed.

However, the state of the art does not describe:

the specific substituted aminoquinolone compounds of general formula (I) of the present invention as described and defined herein, i.e. compounds having a 2-oxo-1,2-dihydroquinoline core bearing:

in its 1-position a methyl- or an ethyl group, in its 3-position a cyano-, carbamoyl-, alkylcarbamoyl-, dialkylcarbamoyl- or alkoxycarbonyl group, in its 4-position a pyrolidinyl-, piperidinyl- or azepanyl group; and as a substituent of said pyrolidinyl-, piperidinyl- or azepanyl group a phenyl-, naphthyl- or 5- to 10-membered heteroaryl group, or stereoisomers, tautomers, N-oxides, hydrates, solvates, salts thereof, or mixtures of same, as described and defined herein, and as hereinafter referred to as “compounds of general formula (I)” or “compounds of the present invention”,

or their pharmacological activity.

It is desirable to provide novel compounds having prophylactic and therapeutic properties.

Accordingly, it is an object of the present invention to provide compounds and pharmaceutical compositions comprising these compounds used for prophylactic and therapeutic use in DGKα regulated disorders in a T cell immune-stimulatory or immune-modifying manner. DGKα regulated disorders comprise conditions with dysregulated immune responses, particularly in an immunologically suppressed tumor microenvironment in cancer, autoimmune diseases, viral infections as well as other disorders associated with aberrant DGKα signalling, e.g. fibrotic diseases. Said compounds can be used as sole agent or in combination with other active ingredients.

It has now been found, and this constitutes the basis of the present invention, that the compounds of the present invention have surprising and advantageous properties.

In particular, the compounds of the present invention have surprisingly been found to effectively inhibit the DGKα protein and enhance T-cell mediated immunity. Accordingly, they provide novel structures for the therapy of human and animal disorders, in particular of cancers, and may therefore be used for the treatment or prophylaxis of hyperproliferative disorders, such as cancer, for example.

In accordance with a first aspect, the present invention covers compounds of general formula (I):

in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 , —C(═O)N(H)C 2 H 5 , —C(═O)N(CH 3 ) 2 and —C(═O)OR 15 , R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 6 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —(CH 2 ) 3 —, —CH 2 —CH(OH)—CH 2 —, —(CH 2 ) 4 —, —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—, —CH 2 —CH(CH 3 )—O—, —CH 2 —O—CH 2 —, —O—(CH 2 ) 3 —, —(CH 2 ) 3 —O—, —CH 2 —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—CH 2 —, —O—CH 2 —O—, —O—C(CH 3 ) 2 —O—, —O—(CH 2 ) 2 —O—, —N(R 18 )—C(═O)—(C(R 18 )(R 19 )) m —, —N(R 18 )—C(═O)—(C(CH 2 ) 3 )—, —N(R 18 )—(C(R 18 )(R 19 )) m —, —N(R 18 )—C(═O)—O— and —N(R 18 )—C(═O)—N(R 18 )—,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and

which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 6 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 4 -C 6 -cycloalkenyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C, C 2 alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 2 -C 6 -alkenyl group is optionally substituted with a C 1 -C 4 -haloalkyl group, and wherein said C 3 -C 6 -cycloalkyl and C 4 -C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 4 -C 6 -cycloalkenyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 4 -haloalkoxy, —O—(C 1 -C 4 -alkyl)-C(═O)OR 15 , —O—(C 1 -C 4 -alkyl)-C(═O)N(R 9 )(R 10 ), C 3 -C 6 -cycloalkyloxy, —S(═O)R 14 , —S(═O) 2 R 14 , cyano, nitro, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N(R 16 )(R 20 )—C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, wherein said C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 1 -C 6 -alkoxy group is optionally substituted with a oxiran-2-yl group, and wherein said C 3 -C 6 -cycloalkyl and C 4 -C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 4 -C 6 -cycloalkenyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 2 -C 6 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 6 -cycloalkyl and 04-C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 6 represents a hydrogen atom, or a fluorine atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo, R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, hydroxy and cyano, R 8 represents a group selected from methyl and ethyl, R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 2 -C 4 -hydroxyalkyl, N≡C—(C 1 -C 4 -alkyl)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)-, C 3 -C 4 -cycloalkyl and C 2 -C 4 -haloalkyl,

or

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -haloalkyl, hydroxy and oxo,

R 11 represents a hydrogen atom or group selected from C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -haloalkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 12 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 13 represents a hydrogen atom or a group selected from C 1 -C 6 -alkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 14 represents a group selected from C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 6 -cycloalkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 15 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 16 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl and C 2 -C 4 -haloalkyl, R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo, and wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

R 18 represents a hydrogen atom or a group selected from methyl and ethyl, R 19 represents a hydrogen atom or a group selected from methyl and ethyl, R 20 represents a (4- to 7-membered heterocycloalkyl)-(C 1 -C 4 -alkyl)- group,

wherein the (4- to 7-membered heterocycloalkyl) part of said group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo,

m represents an integer selected from 1, 2 and 3, and n represents an integer selected from 1, 2 and 3, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In accordance with a variant of the first aspect, the present invention covers compounds of general formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 , —C(═O)N(H)C 2 H 5 , —C(═O)N(CH 3 ) 2 and —C(═O)OR 15 , R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl, which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group,

and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 6 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —(CH 2 ) 3 —, —(CH 2 ) 4 —, —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—, —CH 2 —O—CH 2 —, —O—(CH 2 ) 3 —, —(CH 2 ) 3 —O—, —CH 2 —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—CH 2 —, —O—CH 2 —O— and —O—(CH 2 ) 2 —O—,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 6 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 4 -C 6 -cycloalkenyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 3 )(R 13 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 6 -cycloalkyl and C 4 -C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 4 -C 6 -cycloalkenyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, —S(═O)R 11 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —C(═O)N(R 9 )(R 10 ), —C(═C)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy, wherein said C 3 -C 6 -cycloalkyl and C 4 -C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 4 -C 6 -cycloalkenyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 2 -C 6 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 6 -cycloalkyl and C 4 -C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 6 represents a hydrogen atom, or a fluorine atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo, R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, hydroxy and cyano, R 8 represents a group selected from methyl and ethyl, R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)-, C 3 -C 4 -cycloalkyl and C 2 -C 4 -haloalkyl, or R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -haloalkyl, hydroxy and oxo,

R 11 represents a hydrogen atom or group selected from C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -haloalkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 12 represents a hydrogen atom or a C 1 -C 4 -alkyl group,

R 13 represents a hydrogen atom or a group selected from C 1 -C 6 -alkyl, phenyl and 5- or 6-membered heteroaryl, wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 14 represents a group selected from C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 6 -cycloalkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 5 )(R 10 ),

R 15 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 16 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl and C 2 -C 4 -haloalkyl, R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo, and wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

and n represents an integer selected from 1, 2 and 3, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

The term “substituted” means that one or more hydrogen atoms on the designated atom or group are replaced with a selection from the indicated group, provided that the designated atom's normal valency under the existing circumstances is not exceeded. Combinations of substituents and/or variables are permissible.

The term “optionally substituted” means that the number of substituents can be equal to or different from zero. Unless otherwise indicated, it is possible that optionally substituted groups are substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom. Commonly, it is possible for the number of optional substituents, when present, to be 1, 2, 3 or 4, in particular 1, 2 or 3.

When groups in the compounds according to the invention are substituted, it is possible for said groups to be mono-substituted or poly-substituted with substituent(s), unless otherwise specified. Within the scope of the present invention, the meanings of all groups which occur repeatedly are independent from one another. It is possible that groups in the compounds according to the invention are substituted with one, two or three identical or different substituents, particularly with one substituent.

As used herein, an oxo substituent represents an oxygen atom, which is bound to a carbon atom or to a sulfur atom via a double bond.

Should a composite substituent be composed of more than one part, e.g. (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, it is possible for a given part to be attached at any suitable position of said composite substituent, e.g. it is possible for the C 1 -C 2 -alkoxy part to be attached to any suitable carbon atom of the C 1 -C 6 -alkyl part of said (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)- group. A hyphen at the beginning or at the end of such a composite substituent indicates the point of attachment of said composite substituent to the rest of the molecule. Should a ring, comprising carbon atoms and optionally one or more heteroatoms, such as nitrogen, oxygen or sulfur atoms for example, be substituted with a substituent, it is possible for said substituent to be bound at any suitable position of said ring, be it bound to a suitable carbon atom and/or to a suitable heteroatom.

The term “comprising” when used in the specification includes “consisting of”.

If within the present text any item is referred to as “as mentioned herein”, it means that it may be mentioned anywhere in the present text.

The terms as mentioned in the present text have the following meanings:

The term “halogen atom” means a fluorine, chlorine, bromine or iodine atom, particularly a fluorine, chlorine or bromine atom.

The term “C 1 -C 6 -alkyl” means a linear or branched, saturated, monovalent hydrocarbon group having 1, 2, 3, 4, 5 or 6 carbon atoms, e.g. a methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neo-pentyl, 1,1-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2,3-dimethylbutyl, 1,2-dimethylbutyl or 1,3-dimethylbutyl group, or an isomer thereof. Particularly, said group has 1, 2, 3, 4 or 5 carbon atoms (“C 1 -C 5 -alkyl”), e.g. a methyl, ethyl, propyl, isopropyl, butyl, sec-butyl isobutyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neo-pentyl, 1,1-dimethylpropyl group. More particularly, said group has 1, 2, 3 or 4 carbon atoms (“C 1 -C 4 -alkyl”), e.g. a methyl, ethyl, propyl, isopropyl, butyl, sec-butyl isobutyl, or tert-butyl group, more particularly 1, 2 or 3 carbon atoms (“C 1 -C 3 -alkyl”), e.g. a methyl, ethyl, n-propyl or isopropyl group, more particularly 1 or 2 carbon atoms (“C 1 -C 2 -alkyl”), e.g. a methyl or ethyl group.

The term “C 2 -C 4 -alkyl” means a linear or branched, saturated, monovalent hydrocarbon group having 2, 3 or 4 carbon atoms, e.g. an ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl or tert-butyl group.

The term “C 1 -C 6 -hydroxyalkyl” means a linear or branched, saturated, monovalent hydrocarbon group in which the term “C 1 -C 6 -alkyl” is defined supra, and in which 1 or 2 hydrogen atoms are replaced with a hydroxy group, e.g. a hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropan-2-yl, 2-hydroxypropan-2-yl, 2,3-dihydroxypropyl, 1,3-dihydroxypropan-2-yl, 3-hydroxy-2-methyl-propyl, 2-hydroxy-2-methyl-propyl, 1-hydroxy-2-methyl-propyl, 1-hydroxybutyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl group, 1-hydroxypentyl, 2-hydroxypentyl, 3-hydroxypentyl, 4-hydroxypentyl, 5-hydroxypentyl, 1-hydroxyhexyl, 2-hydroxyhexyl, 3-hydroxyhexyl, 4-hydroxyhexyl, 5-hydroxyhexyl, 6-hydroxyhexyl group, or an isomer thereof. Particularly, said group has 1, 2, 3 or 4 carbon atoms (“C 1 -C 4 -hydroxyalkyl”), e.g. a hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropan-2-yl, 2-hydroxypropan-2-yl, 2,3-dihydroxypropyl, 1,3-dihydroxypropan-2-yl, 3-hydroxy-2-methyl-propyl, 2-hydroxy-2-methyl-propyl, 1-hydroxy-2-methyl-propyl, 1-hydroxybutyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl group, or an isomer thereof.

The term “C 2 -C 4 -hydroxyalkyl” means a linear or branched, saturated, monovalent hydrocarbon group having 2, 3 or 4 carbon atoms, in which the term “C 2 -C 4 -alkyl” is defined supra, and in which 1 or 2 hydrogen atoms are replaced with a hydroxy group, e.g. a 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropan-2-yl, 2-hydroxypropan-2-yl, 2,3-dihydroxypropyl, 1,3-dihydroxypropan-2-yl, 3-hydroxy-2-methyl-propyl, 2-hydroxy-2-methyl-propyl, 1-hydroxy-2-methyl-propyl, 1-hydroxybutyl, 2-hydroxybutyl, 3-hydroxybutyl or 4-hydroxybutyl group, or an isomer thereof.

The term “C 1 -C 6 -haloalkyl” means a linear or branched, saturated, monovalent hydrocarbon group in which the term “C 1 -C 6 -alkyl” is as defined supra, and in which one or more of the hydrogen atoms are replaced, identically or differently, with a halogen atom. Particularly, said halogen atom is a fluorine atom. Said C 1 -C 6 -haloalkyl group is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl, 1,3-difluoropropan-2-yl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl or 6,6,6-trifluorohexyl. Particularly, said group has 1, 2, 3 or 4 carbon atoms (“C 1 -C 4 -haloalkyl”), e.g. a fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl, 1,3-difluoropropan-2-yl or 4,4,4-trifluorobutyl group.

The term “C 1 -C 6 -alkoxy” means a linear or branched, saturated, monovalent group of formula (C 1 -C 6 -alkyl)-O—, in which the term “C 1 -C 6 -alkyl” is as defined supra, e.g. a methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert-butoxy, pentyloxy, isopentyloxy or n-hexyloxy group, or an isomer thereof. Particularly, said group has 1, 2, 3 or 4 carbon atoms (“C 1 -C 4 -alkoxy”), e.g. a methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy or tert-butoxy group.

The term “C 1 -C 6 -haloalkoxy” means a linear or branched, saturated, monovalent C 1 -C 6 -alkoxy group, as defined supra, in which one or more of the hydrogen atoms is replaced, identically or differently, with a halogen atom. Particularly, said halogen atom is a fluorine atom. Said C 1 -C 6 -haloalkoxy group is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy or pentafluoroethoxy.

The term “C 2 -C 6 -alkenyl” means a linear or branched, monovalent hydrocarbon group, which contains one or two double bonds, and which has 2, 3, 4, 5 or 6 carbon atoms, it being understood that in the case in which said alkenyl group contains two double bonds, then it is possible for said double bonds to be conjugated with each other, or to form an allene. Said alkenyl group is, for example, an ethenyl (or “vinyl”), prop-2-en-1-yl (or “allyl”), prop-1-en-1-yl, but-3-enyl, but-2-enyl, but-1-enyl, pent-4-enyl, pent-3-enyl, pent-2-enyl, pent-1-enyl, hex-5-enyl, hex-4-enyl, hex-3-enyl, hex-2-enyl, hex-1-enyl, prop-1-en-2-yl (or “isopropenyl”), 2-methylprop-2-enyl, 1-methylprop-2-enyl, 2-methylprop-1-enyl, 1-methylprop-1-enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl, 3-methylbut-2-enyl, 2-methylbut-2-enyl, 1-methylbut-2-enyl, 3-methylbut-1-enyl, 2-methylbut-1-enyl, 1-methylbut-1-enyl, 1,1-dimethylprop-2-enyl, 1-ethylprop-1-enyl, 1-propylvinyl, 1-isopropylvinyl, 4-methylpent-4-enyl, 3-methylpent-4-enyl, 2-methylpent-4-enyl, 1-methylpent-4-enyl, 4-methylpent-3-enyl, 3-methylpent-3-enyl, 2-methylpent-3-enyl, 1-methylpent-3-enyl, 4-methylpent-2-enyl, 3-methylpent-2-enyl, 2-methylpent-2-enyl, 1-methylpent-2-enyl, 4-methylpent-1-enyl, 3-methylpent-1-enyl, 2-methylpent-1-enyl, 1-methylpent-1-enyl, 3-ethylbut-3-enyl, 2-ethylbut-3-enyl, 1-ethylbut-3-enyl, 3-ethylbut-2-enyl, 2-ethylbut-2-enyl, 1-ethylbut-2-enyl, 3-ethylbut-1-enyl, 2-ethylbut-1-enyl, 1-ethylbut-1-enyl, 2-propylprop-2-enyl, 1-propylprop-2-enyl, 2-isopropylprop-2-enyl, 1-isopropylprop-2-enyl, 2-propylprop-1-enyl, 1-propylprop-1-enyl, 2-isopropylprop-1-enyl, 1-isopropylprop-1-enyl, 3,3-dimethylprop-1-enyl, 1-(1,1-dimethylethyl)ethenyl, buta-1,3-dienyl, penta-1,4-dienyl or hexa-1,5-dienyl group.

The term “C 2 -C 6 -alkynyl” means a linear or branched, monovalent hydrocarbon group which contains one triple bond, and which contains 2, 3, 4, 5 or 6 carbon atoms, particularly 2, 3 oder 4 carbon atoms (“C 2 -C 4 -alkynyl”). Said C 2 -C 6 -alkynyl group is, for example, ethynyl, prop-1-ynyl, prop-2-ynyl (or “propargyl”), but-1-ynyl, but-2-ynyl, but-3-ynyl, pent-1-ynyl, pent-2-ynyl, pent-3-ynyl, pent-4-ynyl, hex-1-ynyl, hex-2-ynyl, hex-3-ynyl, hex-4-ynyl, hex-5-ynyl, 1-methylprop-2-ynyl, 2-methylbut-3-ynyl, 1-methylbut-3-ynyl, 1-methylbut-2-ynyl, 3-methylbut-1-ynyl, 1-ethylprop-2-ynyl, 3-methylpent-4-ynyl, 2-methylpent-4-ynyl, 1-methyl-pent-4-ynyl, 2-methylpent-3-ynyl, 1-methylpent-3-ynyl, 4-methylpent-2-ynyl, 1-methyl-pent-2-ynyl, 4-methylpent-1-ynyl, 3-methylpent-1-ynyl, 2-ethylbut-3-ynyl, 1-ethylbut-3-ynyl, 1-ethylbut-2-ynyl, 1-propylprop-2-ynyl, 1-isopropylprop-2-ynyl, 2,2-dimethylbut-3-ynyl, 1,1-dimethylbut-3-ynyl, 1,1-dimethylbut-2-ynyl or 3,3-dimethylbut-1-ynyl group.

The term “C 3 -C 6 -cycloalkyl” means a saturated, monovalent, monocyclic hydrocarbon ring which contains 3, 4, 5 or 6 carbon atoms. Said C 3 -C 6 -cycloalkyl group is for example a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group. Particularly, said group has 3, 4 or 5 carbon atoms (“C 3 -C 5 -cycloalkyl”), e.g. a cyclopropyl, cyclobutyl or cyclopentyl group. Particularly, said group has 3 or 4 carbon atoms (“C 3 -C 4 -cycloalkyl”), e.g. a cyclopropyl or cyclobutyl group.

The term “C 4 -C 6 -cycloalkenyl” means a monocyclic hydrocarbon ring which contains 4, 5 or 6 carbon atoms and one double bond. Particularly, said ring contains 5 or 6 carbon atoms (“C 5 -C 6 -cycloalkenyl”). Said C 4 -C 6 -cycloalkenyl group is for example, a monocyclic hydrocarbon ring, e.g. a cyclobutenyl, cyclopentenyl, cyclohexenyl or cycloheptenyl group.

The term “C 3 -C 6 -cycloalkyloxy” means a saturated, monovalent group of formula (C 3 -C 6 -cycloalkyl)-O—, in which the term “C 3 -C 6 -cycloalkyl” is as defined supra, e.g. a cyclopropyloxy, cyclobutyloxy, cyclopentyloxy or cyclohexyloxy group.

The term “4- to 7-membered heterocycloalkyl” means a monocyclic, saturated heterocycle with 4, 5, 6 or 7 ring atoms in total, which contains one or two identical or different ring heteroatoms from the series N, O and S.

Said heterocycloalkyl group, without being limited thereto, can be a 4-membered ring, such as azetidinyl, oxetanyl or thietanyl, for example; or a 5-membered ring, such as tetrahydrofuranyl, 1,3-dioxolanyl, thiolanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, 1,1-dioxidothiolanyl, 1,2-oxazolidinyl, 1,3-oxazolidinyl or 1,3-thiazolidinyl, for example; or a 6-membered ring, such as tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, 1,3-dioxanyl, 1,4-dioxanyl or 1,2-oxazinanyl, for example, or a 7-membered ring, such as azepanyl, 1,4-diazepanyl or 1,4-oxazepanyl, for example.

The term “5- to 7-membered heterocycloalkenyl” means a monocyclic, unsaturated, non-aromatic heterocycle with 5, 6 or 7 ring atoms in total, which contains one or two double bonds and one or two identical or different ring heteroatoms from the series N, O and S.

Said heterocycloalkenyl group is, for example, 4H-pyranyl, 2H-pyranyl, 2,5-dihydro-1H-pyrrolyl, [1,3]dioxolyl, 4H-[1,3,4]thiadiazinyl, 2,5-dihydrofuranyl, 2,3-dihydrofuranyl, 2,5-dihydrothiophenyl, 2,3-dihydrothiophenyl, 4,5-dihydrooxazolyl or 4H-[1,4]thiazinyl.

The term “(4- to 7-membered heterocycloalkyl)oxy” means a monocyclic, saturated heterocycloalkyl of formula (4- to 7-membered heterocycloalkyl)-O— in which the term “4- to 7-membered heterocycloalkyl” is as defined supra.

The term “nitrogen containing 4- to 7-membered heterocycloalkyl group” means a monocyclic, saturated heterocycle with 4, 5, 6 or 7 ring atoms in total, which contains one ring nitrogen atom and optionally one further ring heteroatom from the series N, O and S.

Said nitrogen containing 4- to 7-membered heterocycloalkyl group, without being limited thereto, can be a 4-membered ring, such as azetidinyl, for example; or a 5-membered ring, such as pyrrolidinyl, imidazolidinyl, pyrazolidinyl, 1,2-oxazolidinyl, 1,3-oxazolidinyl or 1,3-thiazolidinyl, for example; or a 6-membered ring, such as piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, or 1,2-oxazinanyl, for example, or a 7-membered ring, such as azepanyl, 1,4-diazepanyl or 1,4-oxazepanyl, for example.

The term “heteroaryl” means a monovalent, monocyclic or bicyclic aromatic ring having 5, 6, 8, 9 or 10 ring atoms (a “5- to 10-membered heteroaryl” group), which contains at least one ring heteroatom and optionally one, two or three further ring heteroatoms from the series: N, O and/or S, and which is bound via a ring carbon atom.

Said heteroaryl group can be a 5-membered heteroaryl group, such as, for example, thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl or tetrazolyl; or a 6-membered heteroaryl group, such as, for example, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl or triazinyl; or a 9-membered heteroaryl group, such as, for example, benzofuranyl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzothiazolyl, benzotriazolyl, thiazolopyridinyl, indazolyl, indolyl, isoindolyl, indolizinyl or purinyl; or a 10-membered heteroaryl group, such as, for example, quinolinyl, quinazolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinoxalinyl or pteridinyl.

In general, and unless otherwise mentioned, the heteroaryl or heteroarylene groups include all possible isomeric forms thereof, e.g.: tautomers and positional isomers with respect to the point of linkage to the rest of the molecule. Thus, for some illustrative non-restricting examples, the term pyridinyl includes pyridin-2-yl, pyridin-3-yl and pyridin-4-yl; or the term thienyl includes thien-2-yl and thien-3-yl.

The term “C 1 -C 6 ”, as used in the present text, e.g. in the context of the definition of “C 1 -C 6 -alkyl”, “C 1 -C 6 -haloalkyl”, “C 1 -C 6 -hydroxyalkyl”, “C 1 -C 6 -alkoxy” or “C 1 -C 6 -haloalkoxy” means an alkyl group having a finite number of carbon atoms of 1 to 6, i.e. 1, 2, 3, 4, 5 or 6 carbon atoms.

Further, as used herein, the term “C 3 -C 8 ”, as used in the present text, e.g. in the context of the definition of “C 3 -C 6 -cycloalkyl”, means a cycloalkyl group having a finite number of carbon atoms of 3 to 6, i.e. 3, 4, 5 or 6 carbon atoms.

When a range of values is given, said range encompasses each value and sub-range within said range.

For example:

“C 1 -C 6 ” encompasses C 1 , C 2 , C 3 , C 4 , C 5 , C 6 , C 1 -C 6 , C 1 -C 5 , C 1 -C 4 , C 1 -C 3 , C 1 -C 2 , C 2 - C 6 , C 2 -C 5 , C 2 -C 4 , C 2 -C 3 , C 3 -C 6 , C 3 -C 5 , C 3 -C 4 , C 4 -C 6 , C 4 -C 5 , and C 5 -C 6 ;

“C 2 -C 6 ” encompasses C 2 , C 3 , C 4 , C 5 , C 6 , C 2 -C 6 , C 2 -C 5 , C 2 -C 4 , C 2 -C 3 , C 3 -C 6 , C 3 -C 5 , C 3 -C 4 , C 4 -C 6 , C 4 -C 5 , and C 5 -C 6 ;

“C 3 -C 6 ” encompasses C 3 , C 4 , C 5 , C 6 , C 3 -C 6 , C 3 -C 5 , C 3 -C 4 , C 4 -C 6 , C 4 -C 5 , and C 5 -C 6 ;

As used herein, the term “leaving group” means an atom or a group of atoms that is displaced in a chemical reaction as stable species taking with it the bonding electrons. In particular, such a leaving group is selected from the group comprising: halide, in particular fluoride, chloride, bromide or iodide, (methylsulfonyl)oxy, [(trifluoromethyl)sulfonyl]oxy, [(nonafluorobutyl)-sulfonyl]oxy, (phenylsulfonyl)oxy, [(4-methylphenyl)sulfonyl]oxy, [(4-bromophenyl)sulfonyl]oxy, [(4-nitrophenyl)sulfonyl]oxy, [(2-nitrophenyl)sulfonyl]oxy, [(4-isopropylphenyl)sulfonyl]oxy, [(2,4,6-triisopropylphenyl)sulfonyl]oxy, [(2,4,6-trimethylphenyl)sulfonyl]oxy, [(4-tert-butyl-phenyl)sulfonyl]oxy and [(4-methoxyphenyl)sulfonyl]oxy.

It is possible for the compounds of general formula (I) to exist as isotopic variants. The invention therefore includes one or more isotopic variant(s) of the compounds of general formula (I), particularly deuterium-containing compounds of general formula (I).

The term “Isotopic variant” of a compound or a reagent is defined as a compound exhibiting an unnatural proportion of one or more of the isotopes that constitute such a compound.

The term “Isotopic variant of the compound of general formula (I)” is defined as a compound of general formula (I) exhibiting an unnatural proportion of one or more of the isotopes that constitute such a compound.

The expression “unnatural proportion” means a proportion of such isotope which is higher than its natural abundance. The natural abundances of isotopes to be applied in this context are described in “Isotopic Compositions of the Elements 1997”, Pure Appl. Chem., 70(1), 217-235, 1998.

Examples of such isotopes include stable and radioactive isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine and iodine, such as 2 H (deuterium), 3 H (tritium), 11 C, 13 C, 14 O, 15 N, 17 O, 18 O, 32 P, 33 P, 33 S, 34 B, 35 B, 36 B, 18 F, 36 Cl, 82 Br, 123 I, 124 I, 125 I, 129 I and 131 I, respectively.

With respect to the treatment and/or prophylaxis of the disorders specified herein the isotopic variant(s) of the compounds of general formula (I) preferably contain deuterium (“deuterium-containing compounds of general formula (I)”). Isotopic variants of the compounds of general formula (I) in which one or more radioactive isotopes, such as 3 H or 14 C, are incorporated are useful e.g. in drug and/or substrate tissue distribution studies. These isotopes are particularly preferred for the ease of their incorporation and detectability. Positron emitting isotopes such as 18 F or 11 C may be incorporated into a compound of general formula (I). These isotopic variants of the compounds of general formula (I) are useful for in vivo imaging applications. Deuterium-containing and 13 C-containing compounds of general formula (I) can be used in mass spectrometry analyses in the context of preclinical or clinical studies.

Isotopic variants of the compounds of general formula (I) can generally be prepared by methods known to a person skilled in the art, such as those described in the schemes and/or examples herein, by substituting a reagent for an isotopic variant of said reagent, preferably for a deuterium-containing reagent. Depending on the desired sites of deuteration, in some cases deuterium from D 2 O can be incorporated either directly into the compounds or into reagents that are useful for synthesizing such compounds. Deuterium gas is also a useful reagent for incorporating deuterium into molecules. Catalytic deuteration of olefinic bonds and acetylenic bonds is a rapid route for incorporation of deuterium. Metal catalysts (i.e. Pd, Pt, and Rh) in the presence of deuterium gas can be used to directly exchange deuterium for hydrogen in functional groups containing hydrocarbons. A variety of deuterated reagents and synthetic building blocks are commercially available from companies such as for example C/D/N Isotopes, Quebec, Canada; Cambridge Isotope Laboratories Inc., Andover, Mass., USA; and CombiPhos Catalysts, Inc., Princeton, N.J., USA.

The term “deuterium-containing compound of general formula (I)” is defined as a compound of general formula (I), in which one or more hydrogen atom(s) is/are replaced by one or more deuterium atom(s) and in which the abundance of deuterium at each deuterated position of the compound of general formula (I) is higher than the natural abundance of deuterium, which is about 0.015%. Particularly, in a deuterium-containing compound of general formula (I) the abundance of deuterium at each deuterated position of the compound of general formula (I) is higher than 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80%, preferably higher than 90%, 95%, 96% or 97%, even more preferably higher than 98% or 99% at said position(s). It is understood that the abundance of deuterium at each deuterated position is independent of the abundance of deuterium at other deuterated position(s).

The selective incorporation of one or more deuterium atom(s) into a compound of general formula (I) may alter the physicochemical properties (such as for example acidity [C. L. Perrin, et al., J. Am. Chem. Soc., 2007, 129, 4490], basicity [C. L. Perrin et al., J. Am. Chem. Soc., 2005, 127, 9641], lipophilicity [B. Testa et al., Int. J. Pharm., 1984, 19(3), 271]) and/or the metabolic profile of the molecule and may result in changes in the ratio of parent compound to metabolites or in the amounts of metabolites formed. Such changes may result in certain therapeutic advantages and hence may be preferred in some circumstances. Reduced rates of metabolism and metabolic switching, where the ratio of metabolites is changed, have been reported (A. E. Mutlib et al., Toxicol. Appl. Pharmacol., 2000, 169, 102). These changes in the exposure to parent drug and metabolites can have important consequences with respect to the pharmacodynamics, tolerability and efficacy of a deuterium-containing compound of general formula (I). In some cases deuterium substitution reduces or eliminates the formation of an undesired or toxic metabolite and enhances the formation of a desired metabolite (e.g. Nevirapine: A. M. Sharma et al., Chem. Res. Toxicol., 2013, 26, 410; Efavirenz: A. E. Mutlib et al., Toxicol. Appl. Pharmacol., 2000, 169, 102). In other cases the major effect of deuteration is to reduce the rate of systemic clearance. As a result, the biological half-life of the compound is increased. The potential clinical benefits would include the ability to maintain similar systemic exposure with decreased peak levels and increased trough levels. This could result in lower side effects and enhanced efficacy, depending on the particular compound's pharmacokinetic/pharmacodynamic relationship. ML-337 (C. J. Wenthur et al., J. Med. Chem., 2013, 56, 5208) and Odanacatib (K. Kassahun et al., WO2012/112363) are examples for this deuterium effect. Still other cases have been reported in which reduced rates of metabolism result in an increase in exposure of the drug without changing the rate of systemic clearance (e.g. Rofecoxib: F. Schneider et al., Arzneim. Forsch./Drug. Res., 2006, 56, 295; Telaprevir: F. Maltais et al., J. Med. Chem., 2009, 52, 7993). Deuterated drugs showing this effect may have reduced dosing requirements (e.g. lower number of doses or lower dosage to achieve the desired effect) and/or may produce lower metabolite loads.

A compound of general formula (I) may have multiple potential sites of attack for metabolism. To optimize the above-described effects on physicochemical properties and metabolic profile, deuterium-containing compounds of general formula (I) having a certain pattern of one or more deuterium-hydrogen exchange(s) can be selected. Particularly, the deuterium atom(s) of deuterium-containing compound(s) of general formula (I) is/are attached to a carbon atom and/or is/are located at those positions of the compound of general formula (I), which are sites of attack for metabolizing enzymes such as e.g. cytochrome P 450 .

In another embodiment the present invention concerns a deuterium-containing compound of general formula (I) having 1, 2, 3 or 4 deuterium atoms, particularly with 1, 2 or 3 deuterium atoms.

Where the plural form of the word compounds, salts, polymorphs, hydrates, solvates and the like, is used herein, this is taken to mean also a single compound, salt, polymorph, isomer, hydrate, solvate or the like.

By “stable compound” or “stable structure” is meant a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.

The compounds of the present invention optionally contain one or more asymmetric centres, depending upon the location and nature of the various substituents desired. It is possible that one or more asymmetric carbon atoms are present in the (R) or (S) configuration, which can result in racemic mixtures in the case of a single asymmetric centre, and in diastereomeric mixtures in the case of multiple asymmetric centres. In certain instances, it is possible that asymmetry also be present due to restricted rotation about a given bond, for example, the central bond adjoining two substituted aromatic rings of the specified compounds.

Preferred compounds are those which produce the more desirable biological activity. Separated, pure or partially purified isomers and stereoisomers or racemic or diastereomeric mixtures of the compounds of the present invention are also included within the scope of the present invention. The purification and the separation of such materials can be accomplished by standard techniques known in the art.

Preferred compounds are those which produce the more desirable biological activity. Separated, pure or partially purified isomers and stereoisomers or racemic or diastereomeric mixtures of the compounds of the present invention are also included within the scope of the present invention. The purification and the separation of such materials can be accomplished by standard techniques known in the art.

The optical isomers can be obtained by resolution of the racemic mixtures according to conventional processes, for example, by the formation of diastereoisomeric salts using an optically active acid or base or formation of covalent diastereomers. Examples of appropriate acids are tartaric, diacetyltartaric, ditoluoyltartaric and camphorsulfonic acid. Mixtures of diastereoisomers can be separated into their individual diastereomers on the basis of their physical and/or chemical differences by methods known in the art, for example, by chromatography or fractional crystallisation. The optically active bases or acids are then liberated from the separated diastereomeric salts. A different process for separation of optical isomers involves the use of chiral chromatography (e.g., HPLC columns using a chiral phase), with or without conventional derivatisation, optimally chosen to maximise the separation of the enantiomers. Suitable HPLC columns using a chiral phase are commercially available, such as those manufactured by Daicel, e.g., Chiracel OD and Chiracel OJ, for example, among many others, which are all routinely selectable. Enzymatic separations, with or without derivatisation, are also useful. The optically active compounds of the present invention can likewise be obtained by chiral syntheses utilizing optically active starting materials.

In order to distinguish different types of isomers from each other reference is made to IUPAC Rules Section E (Pure Appl Chem 45, 11-30, 1976).

The present invention includes all possible stereoisomers of the compounds of the present invention as single stereoisomers, or as any mixture of said stereoisomers, e.g. (R)- or (S)-isomers, in any ratio. Isolation of a single stereoisomer, e.g. a single enantiomer or a single diastereomer, of a compound of the present invention is achieved by any suitable state of the art method, such as chromatography, especially chiral chromatography, for example.

Further, it is possible for the compounds of the present invention to exist as tautomers. For example, the compounds of the present invention may contain an amide moiety and can exist as an amide, or an imidic acid, or even a mixture in any amount of the two tautomers, namely:

The present invention includes all possible tautomers of the compounds of the present invention as single tautomers, or as any mixture of said tautomers, in any ratio.

Further, the compounds of the present invention can exist as N-oxides, which are defined in that at least one nitrogen of the compounds of the present invention is oxidised. The present invention includes all such possible N-oxides.

The present invention also covers useful forms of the compounds of the present invention, such as metabolites, hydrates, solvates, prodrugs, salts, in particular pharmaceutically acceptable salts, and/or co-precipitates.

The compounds of the present invention can exist as a hydrate, or as a solvate, wherein the compounds of the present invention contain polar solvents, in particular water, methanol or ethanol for example, as structural element of the crystal lattice of the compounds. It is possible for the amount of polar solvents, in particular water, to exist in a stoichiometric or non-stoichiometric ratio. In the case of stoichiometric solvates, e.g. a hydrate, hemi-, (semi-), mono-, sesqui-, di-, tri-, tetra-, penta- etc. solvates or hydrates, respectively, are possible. The present invention includes all such hydrates or solvates.

Further, it is possible for the compounds of the present invention to exist in free form, e.g. as a free base, or as a free acid, or as a zwitterion, or to exist in the form of a salt. Said salt may be any salt, either an organic or inorganic addition salt, particularly any pharmaceutically acceptable organic or inorganic addition salt, which is customarily used in pharmacy, or which is used, for example, for isolating or purifying the compounds of the present invention.

The term “pharmaceutically acceptable salt” refers to an inorganic or organic acid addition salt of a compound of the present invention. For example, see S. M. Berge, et al. “Pharmaceutical Salts,” J. Pharm. Sci. 1977, 66, 1-19.

A suitable pharmaceutically acceptable salt of the compounds of the present invention may be, for example, an acid-addition salt of a compound of the present invention bearing a nitrogen atom, in a chain or in a ring, for example, which is sufficiently basic, such as an acid-addition salt with an inorganic acid, or “mineral acid”, such as hydrochloric, hydrobromic, hydroiodic, sulfuric, sulfamic, bisulfuric, phosphoric, or nitric acid, for example, or with an organic acid, such as formic, acetic, acetoacetic, pyruvic, trifluoroacetic, propionic, butyric, hexanoic, heptanoic, undecanoic, lauric, benzoic, salicylic, 2-(4-hydroxybenzoyl)-benzoic, camphoric, cinnamic, cyclopentanepropionic, digluconic, 3-hydroxy-2-naphthoic, nicotinic, pamoic, pectinic, 3-phenylpropionic, pivalic, 2-hydroxyethanesulfonic, itaconic, trifluoromethanesulfonic, dodecylsulfuric, ethanesulfonic, benzenesulfonic, para-toluenesulfonic, methanesulfonic, 2-naphthalenesulfonic, naphthalinedisulfonic, camphorsulfonic acid, citric, tartaric, stearic, lactic, oxalic, malonic, succinic, malic, adipic, alginic, maleic, fumaric, D-gluconic, mandelic, ascorbic, glucoheptanoic, glycerophosphoric, aspartic, sulfosalicylic, or thiocyanic acid, for example.

Further, another suitably pharmaceutically acceptable salt of a compound of the present invention which is sufficiently acidic, is an alkali metal salt, for example a sodium or potassium salt, an alkaline earth metal salt, for example a calcium, magnesium or strontium salt, or an aluminium or a zinc salt, or an ammonium salt derived from ammonia or from an organic primary, secondary or tertiary amine having 1 to 20 carbon atoms, such as ethylamine, diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, dimethylaminoethanol, diethylaminoethanol, tris(hydroxymethyl)aminomethane, procaine, dibenzylamine, N-methylmorpholine, arginine, lysine, 1,2-ethylenediamine, N-methylpiperidine, N-methyl-glucamine, N,N-dimethyl-glucamine, N-ethyl-glucamine, 1,6-hexanediamine, glucosamine, sarcosine, serinol, 2-amino-1,3-propanediol, 3-amino-1,2-propanediol, 4-amino-1,2,3-butanetriol, or a salt with a quarternary ammonium ion having 1 to 20 carbon atoms, such as tetramethylammonium, tetraethylammonium, tetra(n-propyl)ammonium, tetra(n-butyl)ammonium, N-benzyl-N,N,N-trimethylammonium, choline or benzalkonium.

Those skilled in the art will further recognise that it is possible for acid addition salts of the claimed compounds to be prepared by reaction of the compounds with the appropriate inorganic or organic acid via any of a number of known methods. Alternatively, alkali and alkaline earth metal salts of acidic compounds of the present invention are prepared by reacting the compounds of the present invention with the appropriate base via a variety of known methods.

The present invention includes all possible salts of the compounds of the present invention as single salts, or as any mixture of said salts, in any ratio.

In the present text, in particular in the “Experimental Section”, for the synthesis of intermediates and of examples of the present invention, when a compound is mentioned as a salt form with the corresponding base or acid, the exact stoichiometric composition of said salt form, as obtained by the respective preparation and/or purification process, is, in most cases, unknown.

Unless specified otherwise, suffixes to chemical names or structural formulae relating to salts, such as “hydrochloride”, “trifluoroacetate”, “sodium salt”, or “x HCl”, “x CF 3 COOH”, “x Na+”, for example, mean a salt form, the stoichiometry of which salt form not being specified.

This applies analogously to cases in which synthesis intermediates or example compounds or salts thereof have been obtained, by the preparation and/or purification processes described, as solvates, such as hydrates, with (if defined) unknown stoichiometric composition.

Furthermore, the present invention includes all possible crystalline forms, or polymorphs, of the compounds of the present invention, either as single polymorph, or as a mixture of more than one polymorph, in any ratio.

Moreover, the present invention also includes prodrugs of the compounds according to the invention. The term “prodrugs” here designates compounds which themselves can be biologically active or inactive, but are converted (for example metabolically or hydrolytically) into compounds according to the invention during their residence time in the body.

The invention further includes all possible cyclodextrin clathrates, i.e alpha-, beta-, or gamma-cyclodextrins, hydroxypropyl-beta-cyclodextrins, methylbetacyclodextrins.

In accordance with a second embodiment of the first aspect, the present invention covers compounds of general formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 , —C(═O)N(H)C 2 H 5 , —C(═O)N(CH 3 ) 2 and —C(═O)OR 15 , R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —(CH 2 ) 3 —, —CH 2 —CH(OH)—CH 2 —, —(CH 2 ) 4 —, —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—, —CH 2 —CH(CH 3 )—O—, —CH 2 —O—CH 2 —, —O—(CH 2 ) 3 —, —(CH 2 ) 3 —O—, —CH 2 —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—CH 2 —, —O—CH 2 —O—, —O—C(CH 3 ) 2 —O—, —O—(CH 2 ) 2 —O—, —N(R 18 )—C(═O)—(C(R 18 )(R 19 )) m —, —N(R 18 )—C(═O)—(C(CH 2 ) 3 )—, —N(R 18 )—(C(R 18 )(R 19 )) m —, —N(R 18 )—C(═O)—O— and —N(R 18 )—C(═O)—N(R 18 )—,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 5 -cycloalkyl, C 4 -C 5 -cycloalkenyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 2 -C 4 -alkenyl group is optionally substituted with a C 1 -C 4 -haloalkyl group, and wherein said C 3 -C 5 -cycloalkyl and C 4 -C 5 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 5 -cycloalkyl, C 4 -C 5 -cycloalkenyl, C 1 -C 5 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, —O—(C 1 -C 4 -alkyl)-C(═O)OR 15 , —O—(C 1 -C 4 -alkyl)-C(═O)N(R 9 )(R 10 ), C 3 -C 5 -cycloalkyloxy, —S(═O)R 14 , —S(═O) 2 R 14 , cyano, nitro, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N(R 16 )(R 20 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a oxiran-2-yl group, and wherein said C 3 -C 5 -cycloalkyl and C 4 -C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 5 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 5 -cycloalkyl, C 4 -C 5 -cycloalkenyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 2 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —X(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 5 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl and C 4 -C 5 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 6 represents a hydrogen atom, or a fluorine atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo, R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, hydroxy and cyano, R 8 represents a group selected from methyl and ethyl, R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 2 -C 4 -hydroxyalkyl, N≡C—(C 1 -C 4 -alkyl)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)-, C 3 -C 4 -cycloalkyl and C 2 -C 4 -haloalkyl,

or

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -haloalkyl, hydroxy and oxo,

R 11 represents a hydrogen atom or group selected from C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -haloalkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 12 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 13 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 14 represents a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 3 -C 5 -cycloalkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 15 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 16 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl and C 2 -C 4 -haloalkyl, R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo, and wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

R 18 represents a hydrogen atom or a group selected from methyl and ethyl, R 19 represents a hydrogen atom or a group selected from methyl and ethyl, R 20 represents a (4- to 7-membered heterocycloalkyl)-(C 1 -C 4 -alkyl)- group,

wherein the (4- to 7-membered heterocycloalkyl) part of said group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo,

m represents an integer selected from 1, 2 and 3, and n represents an integer selected from 1, 2 and 3, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In accordance with a variant of the second embodiment of the first aspect, the present invention covers compounds of general formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 , —C(═O)N(H)C 2 H 5 , —C(═O)N(CH 3 ) 2 and —C(═O)OR 15 , R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —(CH 2 ) 3 —, —(CH 2 ) 4 —, —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—, —CH 2 —O—CH 2 —, —O—(CH 2 ) 3 —, —(CH 2 ) 3 —O—, —CH 2 —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—CH 2 —, —O—CH 2 —O— and —O—(CH 2 ) 2 —O—,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 5 -cycloalkyl, C 4 -C 5 -cycloalkenyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl and C 4 -C 5 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 5 -cycloalkyl, C 4 -C 5 -cycloalkenyl, C 1 -C 5 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl and C 4 -C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 5 -cycloalkyl, C 4 -C 5 -cycloalkenyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 2 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 5 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl and C 4 -C 5 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 6 represents a hydrogen atom, or a fluorine atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo, R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, hydroxy and cyano, R 8 represents a group selected from methyl and ethyl, R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)-, C 3 -C 4 -cycloalkyl and C 2 -C 4 -haloalkyl, or R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -haloalkyl, hydroxy and oxo,

R 11 represents a hydrogen atom or group selected from C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -haloalkyl, phenyl and 5- or 6-membered heteroaryl, wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), R 12 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 13 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 14 represents a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 3 -C 5 -cycloalkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 15 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 16 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl and C 2 -C 4 -haloalkyl, R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo, and wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

and n represents an integer selected from 1, 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In accordance with a third embodiment of the first aspect, the present invention covers compounds of general formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 , —C(═O)N(H)C 2 H 5 , —C(═O)N(CH 3 ) 2 and —C(═O)OR 15 , R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl, which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group,

and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 2 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl,

or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —CH 2 —CH(OH)—CH 2 —, —CH 2 —CH(CH 3 )—O—, —O—C(CH 3 ) 2 —O—, —N(R 18 )—C(═O)—(C(R 18 )(R 19 )) m —, —N(R 18 )—C(═O)—(C(CH 2 ) 3 )—, —N(R 18 )—(C(R 18 )(R 18 ))m-, —N(R 18 )—C(═O)—O— and —N(R 18 )—C(═O)—N(R 18 )—,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a group selected from phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 2 -C 4 -alkenyl group is optionally substituted with a C 1 -C 4 -haloalkyl group, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl,

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, —O—(C 1 -C 4 -alkyl)-C(═O)OR 15 , —O—(C 1 -C 4 -alkyl)-C(═O)N(R 9 )(R 10 ), C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, nitro, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N(R 16 )(R 20 ), —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a oxiran-2-yl group, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 5 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl and (4- to 7-membered heterocycloalkyl)oxy,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 5 -alkyl, C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

R 6 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo, R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and hydroxy, R 8 represents a group selected from methyl and ethyl, R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 2 -C 4 -hydroxyalkyl, N≡C—(C 1 -C 4 -alkyl)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)- and C 3 -C 4 -cycloalkyl,

or

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -haloalkyl, hydroxy and oxo,

R 11 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl, R 12 represents a hydrogen atom, R 13 represents a phenyl group, R 14 represents a group selected from C 1 -C 4 -alkyl and phenyl,

wherein said phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 15 represents a hydrogen atom or a C 1 -C 4 -alkyl group, and R 16 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

R 18 represents a hydrogen atom or a methyl group, R 19 represents a hydrogen atom or a methyl group, R 20 represents a (4- to 7-membered heterocycloalkyl)-(C 1 -C 4 -alkyl)- group,

wherein the (4- to 7-membered heterocycloalkyl) part of said group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group,

m represents an integer selected from 1 and 2, and n represents an integer selected from 1, 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In accordance with a variant of the third embodiment of the first aspect, the present invention covers compounds of general formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 , —C(═O)N(H)C 2 H 5 , —C(═O)N(CH 3 ) 2 and —C(═O)OR 15 , R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl, which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group,

and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 and phenyl,

wherein said C 1 -C 4 -alkoxy group is optionally substituted with a phenyl group, which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 5 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl and (4- to 7-membered heterocycloalkyl)oxy,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 5 -alkyl, C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

R 6 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo, R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl and hydroxy, R 8 represents a group selected from methyl and ethyl, R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or C 1 -C 4 -alkyl group,

or

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -haloalkyl, hydroxy and oxo,

R 11 represents a hydrogen atom or a C 1 -C 4 -haloalkyl group, R 12 represents a hydrogen atom, R 13 represents a phenyl group, R 14 represents a group selected from C 1 -C 4 -alkyl and phenyl,

wherein said phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

R 15 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 16 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

and n represents an integer selected from 1, 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In accordance with a fourth embodiment of the first aspect, the present invention covers compounds of general formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 and —C(═O)N(CH 3 ) 2 , R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl, which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group,

and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 2 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl,phenyl and 5- or 6-membered heteroaryl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from

—CH 2 —CH(OH)—CH 2 —, —CH 2 —CH(CH 3 )—O—, —O—C(CH 3 ) 2 —O—, —N(R 18 )—C(═O)—(C(R 18 )(R 19 )) m —, —N(R 18 )—C(═O)—(C(CH 2 ) 3 )—, —N(R 18 )—(C(R 18 )(R 19 )) m —, —N(R 18 )—C(═O)—O— and —N(R 18 )—C(═O)—N(R 18 )—, wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a group selected from 4- to 7-membered heterocycloalkyl and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

and wherein said phenyl and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl and C 1 -C 2 -alkoxy,

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and

wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, with a cyano group,

and wherein said C 2 -C 4 -alkenyl group is optionally substituted with a C 1 -C 4 -haloalkyl group, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl,

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, —O—(C 1 -C 4 -alkyl)-C(═O)OR 15 , —O—(C 1 -C 4 -alkyl)-C(═O)N(R 9 )(R 10 ), C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, nitro, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N(R 16 )(R 20 ), —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and, 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a oxiran-2-yl group, and wherein said C 3 -C 5 -cycloalkyl is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 5 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), 4- to 7-membered heterocycloalkyl and (4- to 7-membered heterocycloalkyl)oxy,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

R 6 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -hydroxyalkyl, R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and hydroxy, R 8 represents a group selected from methyl and ethyl, R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 2 -C 4 -hydroxyalkyl, N≡C—(C 1 -C 4 -alkyl)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)- and C 3 -C 4 -cycloalkyl,

or

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group, wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group,

R 11 represents a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl, R 12 represents a hydrogen atom, R 13 represents a phenyl group, R 14 represents a group selected from C 1 -C 4 -alkyl and phenyl, R 15 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 16 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

R 18 represents a hydrogen atom or a methyl group, R 19 represents a hydrogen atom or a methyl group, R 20 represents a (4- to 7-membered heterocycloalkyl)-(C 1 -C 4 -alkyl)- group,

wherein the (4- to 7-membered heterocycloalkyl) part of said group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group,

m represents an integer selected from 1 and 2, and n represents an integer selected from 1, 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In accordance with a variant of the fourth embodiment of the first aspect, the present invention covers compounds of general formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 and —C(═O)N(CH 3 ) 2 , R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 and phenyl,

wherein said C 1 -C 4 -alkoxy group is optionally substituted with a phenyl group,

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, with a cyano group, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, with a halogen atom,

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 5 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), 4- to 7-membered heterocycloalkyl and (4- to 7-membered heterocycloalkyl)oxy,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

R 6 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -hydroxyalkyl, R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl and hydroxy, R 8 represents a group selected from methyl and ethyl, R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or C 1 -C 4 -alkyl group,

or

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group,

R 11 represents a C 1 -C 4 -haloalkyl group, R 12 represents a hydrogen atom, R 13 represents a phenyl group, R 14 represents a group selected from C 1 -C 4 -alkyl and phenyl, R 16 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

and n represents an integer selected from 1, 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In accordance with a fifth embodiment of the first aspect, the present invention covers compounds of general formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 and —C(═O)N(CH 3 ) 2 , R 2 represents a group selected from phenyl, 1-naphthyl, 2-naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is selected from pyrazolyl, 1,2,4-oxadiazol, 1,3,4-oxadiazol, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1,3-thiazolyl, pyridinyl, pyrazinyl, indolyl, benzothiophenyl, benzofuranyl, 1,3-benzoxazolyl, indazolyl, benzimidazolyl, 1,3-benzothiazolyl, pyrrolo[2,3-b]pyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl and 1,3-thiazolo[5,4-b]pyridinyl, and which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, 1-naphthyl, 2-naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 2 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, phenyl and pyridinyl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —CH 2 —CH(OH)—CH 2 —, —CH 2 —CH(CH 3 )—O—, —O—C(CH 3 ) 2 —O—, —NH—C(═O)—CH(CH 3 )—, —N(CH 3 )—C(═O)—C(CH 3 ) 2 —, —NH—C(═O)—(C(CH 2 ) 3 )—, —NH—CH 2 —C(CH 3 ) 2 —, —N(CH 3 )—C(═O)—O— and —N(CH 3 )—C(═O)—N(CH 3 )—,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a group selected from 4- to 7-membered heterocycloalkyl and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

and wherein said phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl and C 1 -C 2 -alkoxy,

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, with a cyano group,

and wherein said C 2 -C 4 -alkenyl group is optionally substituted with a C 1 -C 4 -haloalkyl group, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, with a halogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl,

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, —O—CH 2 —C(═O)OR 15 , —O—CH 2 —C(═O)N(R 9 )(R 10 ), C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, nitro, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N(R 16 )(R 20 ), —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a oxiran-2-yl group, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 5 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), 4- to 7-membered heterocycloalkyl and (4- to 7-membered heterocycloalkyl)oxy,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

R 6 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -hydroxyalkyl, R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and hydroxy, R 8 represents a group selected from methyl and ethyl, R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 2 -C 4 -hydroxyalkyl, N≡C—(C 1 -C 4 -alkyl)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)- and C 3 -C 4 -cycloalkyl,

or

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl

group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group,

R 11 represents a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl, R 12 represents a hydrogen atom, R 13 represents a phenyl group, R 14 represents a group selected from C 1 -C 4 -alkyl and phenyl, R 15 represents a hydrogen atom or a 01-C 4 -alkyl group, R 16 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

R 20 represents a (4- to 7-membered heterocycloalkyl)-(C 1 -C 4 -alkyl)- group, and n represents an integer selected from 1, 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In accordance with a variant of the fifth embodiment of the first aspect, the present invention covers compounds of general formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 and —C(═O)N(CH 3 ) 2 , R 2 represents a group selected from phenyl, 1-naphthyl, 2-naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is selected from pyrazolyl, 1,2,4-oxadiazol, 1,3,4-oxadiazol 1,3-thiazolyl, pyridinyl, pyrazinyl, indolyl, benzothiophenyl, benzofuranyl, 1,3-benzoxazolyl, indazolyl, benzimidazolyl, 1,3-benzothiazolyl, pyrrolo[2,3-b]pyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl and 1,3-thiazolo[5,4-b]pyridinyl, and which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, 1-naphthyl, 2-naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 2 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, phenyl and pyridinyl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —CH 2 —CH(OH)—CH 2 —, —CH 2 —CH(CH 3 )—O—, —O—C(CH 3 ) 2 —O—, —NH—C(═O)—CH(CH 3 )—, —N(CH 3 )—C(═O)—C(CH 3 ) 2 —, —NH—C(═O)—(C(CH 2 ) 3 )—, —NH—CH 2 —C(CH 3 ) 2 —, —N(CH 3 )—C(═O)—O— and —N(CH 3 )—C(═O)—N(CH 3 )—,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a group selected from 4- to 7-membered heterocycloalkyl and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

and wherein said phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl and C 1 -C 2 -alkoxy,

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and

phenyl, wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from

C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, with a cyano group,

and wherein said C 2 -C 4 -alkenyl group is optionally substituted with a C 1 -C 4 -haloalkyl group, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, with a halogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl,

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, —O—CH 2 —C(═O)OR 15 , —O—CH 2 —C(═O)N(R 9 )(R 10 ), C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, nitro, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a oxiran-2-yl group, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 5 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), 4- to 7-membered heterocycloalkyl and (4- to 7-membered heterocycloalkyl)oxy,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

R 6 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -hydroxyalkyl, R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and hydroxy, R 8 represents a group selected from methyl and ethyl, R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 2 -C 4 -hydroxyalkyl, N≡C—(C 1 -C 4 -alkyl)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)- and C 3 -C 4 -cycloalkyl,

or

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl

group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group,

R 11 represents a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl, R 12 represents a hydrogen atom, R 13 represents a phenyl group, R 14 represents a group selected from C 1 -C 4 -alkyl and phenyl, R 15 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 16 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

and n represents an integer selected from 1, 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In accordance with a further variant of the fifth embodiment of the first aspect, the present invention covers compounds of general formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 and —C(═O)N(CH 3 ) 2 , R 2 represents a group selected from phenyl, 1-naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is selected from pyrazolyl, 1,2,4-oxadiazol, 1,3-thiazolyl, pyridinyl, pyrazinyl, indolyl, benzofuranyl, 1,3-benzoxazolyl, benzimidazolyl, 1,3-benzothiazolyl, pyrrolo[2,3-b]pyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl and 1,3-thiazolo[5,4-b]pyridinyl, and which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, 1-naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 ,

—N═S(═O)(R 14 ) 2 and phenyl,

wherein said C 1 -C 4 -alkoxy group is optionally substituted with a phenyl group,

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, with a cyano group,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, with a halogen atom,

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 5 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), 4- to 7-membered heterocycloalkyl and (4- to 7-membered heterocycloalkyl)oxy,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

R 6 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -hydroxyalkyl, R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl and hydroxy, R 8 represents a group selected from methyl and ethyl, R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or C 1 -C 4 -alkyl group,

or

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl

group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group,

R 11 represents a C 1 -C 4 -haloalkyl group, R 12 represents a hydrogen atom, R 13 represents a phenyl group, R 14 represents a group selected from C 1 -C 4 -alkyl and phenyl, R 16 represents a hydrogen atom or a C 1 -C 4 -alkyl group, R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

and n represents an integer selected from 1, 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In accordance with a sixth embodiment of the first aspect, the present invention covers compounds of general formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 and —C(═O)N(CH 3 ) 2 , R 2 represents a group selected from phenyl, 1-naphthyl, 2-naphthyl, 1H-pyrazol-3-yl, 1H-pyrazol-4-yl, 1H-pyrazol-5-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1H-1,2,3-triazol-4-yl, 2H-1,2,3-triazol-4-yl, 1,3-thiazol-2-yl, pyridin-3-yl, pyrazin-2-yl, 1H-indol-5-yl, 1-benzofuran-4-yl, 1-benzofuran-7-yl, 1H-indol-6-yl, benzothiophen-2-yl, 1,3-benzoxazol-2-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-6-yl, 1,3-benzoxazol-7-yl, 1H-indazol-5-yl, 1H-benzimidazol-2-yl, 1H-benzimidazol-4-yl, 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-5-yl, 1,3-benzothiazol-6-yl, 1,3-benzothiazol-7-yl, 1H-pyrrolo[2,3-b]pyridin-3-yl, quinolin-2-yl, quinolin-4-yl, quinolin-6-yl, quinolin-7-yl, isoquinolin-5-yl, isoquinolin-7-yl, isoquinolin-8-yl, quinoxalin-2-yl, quinoxalin-5-yl and 1,3-thiazolo[5,4-b]pyridin-2-yl, which group is optionally substituted, one or two times, each substituent independently selected from a fluorine, chlorine or bromine atom or a group selected from methyl, propyl, isopropyl, tert-butyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, (propan-2-yl)oxy, methoxymethyl, 2-methoxyethyl, benzyloxy, trifluormethoxy, 2,2,2-trifluoroethoxy, phenoxy, (oxolan-2-yl)methoxy, (tetrahydrofuran-2-yl)methoxy, methanesulfonyl, dimethylphosphoryl, cyano, hydroxy, dimethylamino, oxetan-3-yl, 2-oxopyrrolidin-1-yl, 4-methyl-2-oxopiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, morpholino-4-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 8-methyl-3-oxo-2,8-diazaspiro[4.5]decan-2-yl, carbamoyl, acetyl, trifluoroacetyl, benzamido, benzenesulfonamido, [dimethyl(oxido)-λ 6 -sulfanylidene]amino, phenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl and pyridin-3-yl,

or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are linked to one another in such a way that they jointly form a group selected from —CH 2 —CH(OH)—CH 2 —, —CH 2 —CH(CH 3 )—O—, —O—C(CH 3 ) 2 —O—, —NH—C(═O)—CH(CH 3 )—, —N(CH 3 )—C(═O)—C(CH 3 ) 2 —, —NH—C(═O)—(C(CH 2 ) 3 )—, —NH—CH 2 —C(CH 3 ) 2 —, —N(CH 3 )—C(═O)—O— and —N(CH 3 )—C(═O)—N(CH 3 )—,

R 3 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, sec-butyl, (oxetan-3-yl)methyl, 3,3,3-trifluoroprop-1-en-2-yl, cyclopropyl, (trifluoromethyl)cyclopropyl, cyclobutyl, 2,2-dimethylcyclobutyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, ethoxy, propoxy, 2,2-difluoroethoxy, 2,2-difluoropropoxy, cyclopropylmethoxy, (1-cyanocyclopropyl)methoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, cyano, hydroxy, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, carbamoyl, dimethylphosphoryl, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy and phenyl, R 4 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, sec-butyl, (oxetan-3-yl)methyl, trifluoromethyl, cyclopropyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, propoxy, 2-methoxyethoxy, (1-hydroxycyclopropyl)methoxy, (1-cyanocyclopropyl)methoxy, (oxiran-2-yl)methoxy, carboxymethoxy, 2-tert-butoxy-2-oxo-ethoxy, 2-amino-2-oxo-ethoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, dimethylphosphoryl, cyano, nitro, hydroxy, (cyanomethyl)(methyl)amino, (2-hydroxyethyl)amino, (2-hydroxyethyl)(methyl)amino, (2-methoxyethyl)amino, (2-methoxyethyl)(methyl)amino, cyclopropylamino, (oxetan-3-yl)amino, methyl(oxetan-3-yl)amino, methyl(oxolan-3-yl)amino, 3-hydroxyazetidin-1-yl, 2-oxopyrrolidin-1-yl, morpholino, 1,1-dioxidothiomorpholin-4-yl, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 2,2-dimethyl-2λ 6 -diazathia-1,2-dien-1-yl, [dimethyl(oxido)-λ 6 -sulfanylidene]amino, methyl(tetrahydrofuran-3-yl)amino, tetrahydrofuran-3-ylmethoxy, (tetrahydrofuran-3-ylmethyl)amino, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy, (tetrahydrofuran-3-yl)oxy, (tetrahydro-2H-pyran-3-yl)oxy, (tetrahydro-2H-pyran-4-yl)oxy and phenyl, R 5 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, cyclopropyl, methoxy, propoxy, cyclopropyloxy, methanesulfonyl, cyano, hydroxy, oxetan-3-yl and oxetan-3-yloxy, R 6 represents a hydrogen atom or a group selected from methyl and hydroxymethyl, R 7 represents a hydrogen atom or a fluorine atom or a group selected from methyl, ethyl, methoxy and hydroxy, R 8 represents a group selected from methyl and ethyl, and n represents an integer selected from 1, 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In accordance with a variant of the sixth embodiment of the first aspect, the present invention covers compounds of general formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 and —C(═O)N(CH 3 ) 2 , R 2 represents a group selected from phenyl, 1-naphthyl, 2-naphthyl, 1H-pyrazol-3-yl, 1H-pyrazol-4-yl, 1H-pyrazol-5-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,3-thiazol-2-yl, pyridin-3-yl, pyrazin-2-yl, 1H-indol-5-yl, 1-benzofuran-4-yl, 1-benzofuran-7-yl, 1H-indol-6-yl, benzothiophen-2-yl, 1,3-benzoxazol-2-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-6-yl, 1,3-benzoxazol-7-yl, 1H-indazol-5-yl, 1H-benzimidazol-2-yl, 1H-benzimidazol-4-yl, 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-5-yl, 1,3-benzothiazol-6-yl, 1,3-benzothiazol-7-yl, 1H-pyrrolo[2,3-b]pyridin-3-yl, quinolin-2-yl, quinolin-4-yl, quinolin-6-yl, quinolin-7-yl, isoquinolin-5-yl, isoquinolin-7-yl, isoquinolin-8-yl, quinoxalin-2-yl, quinoxalin-5-yl and 1,3-thiazolo[5,4-b]pyridin-2-yl, which group is optionally substituted, one or two times, each substituent independently selected from a fluorine, chlorine or bromine atom or a group selected from methyl, propyl, isopropyl, tert-butyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, (propan-2-yl)oxy, methoxymethyl, 2-methoxyethyl, benzyloxy, trifluormethoxy, 2,2,2-trifluoroethoxy, phenoxy, (oxolan-2-yl)methoxy, (tetrahydrofuran-2-yl)methoxy, methanesulfonyl, dimethylphosphoryl, cyano, hydroxy, dimethylamino, oxetan-3-yl, 2-oxopyrrolidin-1-yl, 4-methyl-2-oxopiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, morpholino-4-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 8-methyl-3-oxo-2,8-diazaspiro[4.5]decan-2-yl, carbamoyl, acetyl, trifluoroacetyl, benzamido, benzenesulfonamido, [dimethyl(oxido)-λ 6 -sulfanylidene]amino, phenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl and pyridin-3-yl,

or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are linked to one another in such a way that they jointly form a group selected from —CH 2 —CH(OH)—CH 2 —, —CH 2 —CH(CH 3 )—O—, —O—C(CH 3 ) 2 —O—, —NH—C(═O)—CH(CH 3 )—, —N(CH 3 )—C(═O)—C(CH 3 ) 2 —, —NH—C(═O)—(C(CH 2 ) 3 )—, —NH—CH 2 —C(CH 3 ) 2 —, —N(CH 3 )—C(═O)—O— and —N(CH 3 )—C(═O)—N(CH 3 )—,

R 3 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, sec-butyl, (oxetan-3-yl)methyl, 3,3,3-trifluoroprop-1-en-2-yl, cyclopropyl, (trifluoromethyl)cyclopropyl, cyclobutyl, 2,2-dimethylcyclobutyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, ethoxy, propoxy, 2,2-difluoroethoxy, 2,2-difluoropropoxy, cyclopropylmethoxy, (1-cyanocyclopropyl)methoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, cyano, hydroxy, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, carbamoyl, dimethylphosphoryl, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy and phenyl, R 4 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, sec-butyl, (oxetan-3-yl)methyl, trifluoromethyl, cyclopropyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, propoxy, 2-methoxyethoxy, (1-hydroxycyclopropyl)methoxy, (1-cyanocyclopropyl)methoxy, (oxiran-2-yl)methoxy, carboxymethoxy, 2-tert-butoxy-2-oxo-ethoxy, 2-amino-2-oxo-ethoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, dimethylphosphoryl, cyano, nitro, hydroxy, (cyanomethyl)(methyl)amino, (2-hydroxyethyl)amino, (2-hydroxyethyl)(methyl)amino, (2-methoxyethyl)amino, (2-methoxyethyl)(methyl)amino, cyclopropylamino, (oxetan-3-yl)amino, methyl(oxetan-3-yl)amino, methyl(oxolan-3-yl)amino, 3-hydroxyazetidin-1-yl, 2-oxopyrrolidin-1-yl, morpholino, 1,1-dioxidothiomorpholin-4-yl, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 2,2-dimethyl-2λ 6 -diazathia-1,2-dien-1-yl, [dimethyl(oxido)-λ 6 -sulfanylidene]amino, methyl(tetrahydrofuran-3-yl)amino, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy, (tetrahydrofuran-3-yl)oxy, (tetrahydro-2H-pyran-3-yl)oxy, (tetrahydro-2H-pyran-4-yl)oxy and phenyl, R 5 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, cyclopropyl, methoxy, propoxy, cyclopropyloxy, methanesulfonyl, cyano, hydroxy, oxetan-3-yl and oxetan-3-yloxy, R 6 represents a hydrogen atom or a group selected from methyl and hydroxymethyl, R 7 represents a hydrogen atom or a fluorine atom or a group selected from methyl, ethyl, methoxy and hydroxy, R 8 represents a group selected from methyl and ethyl, and n represents an integer selected from 1, 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In accordance with a further variant of the sixth embodiment of the first aspect, the present invention covers compounds of general formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 and —C(═O)N(CH 3 ) 2 , R 2 represents a group selected from phenyl, 1-naphthyl, 1H-pyrazol-5-yl, 1,2,4-oxadiazol-5-yl, 1,3-thiazol-2-yl, pyridin-3-yl, pyrazin-2-yl, 1H-indol-5-yl, 1-benzofuran-4-yl, 1-benzofuran-7-yl, 1,3-benzoxazol-2-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-7-yl, 1H-benzimidazol-2-yl, 1H-benzimidazol-4-yl, 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-7-yl, 1H-pyrrolo[2,3-b]pyridin-3-yl, quinolin-4-yl, isoquinolin-5-yl, isoquinolin-7-yl, isoquinolin-8-yl, quinoxalin-2-yl, quinoxalin-5-yl and 1,3-thiazolo[5,4-b]pyridin-2-yl,

which group is optionally substituted, one or two times, each substituent independently selected from a fluorine, chlorine or bromine atom or a group selected from methyl, propyl, isopropyl, tert-butyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, (propan-2-yl)oxy, benzyloxy, trifluormethoxy, 2,2,2-trifluoroethoxy, phenoxy, methanesulfonyl, dimethylphosphoryl, cyano, hydroxy, dimethylamino, 2-oxopyrrolidin-1-yl, 4-methyl-2-oxopiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, morpholino-4-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 8-methyl-3-oxo-2,8-diazaspiro[4.5]decan-2-yl, carbamoyl, trifluoroacetyl, benzamido, benzenesulfonamido, [dimethyl(oxido)-λ 6 -sulfanylidene]amino and phenyl,

R 3 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, sec-butyl, (oxetan-3-yl)methyl, cyclopropyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, propoxy, (1-cyanocyclopropyl)methoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, cyano, hydroxy, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy and phenyl, R 4 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, sec-butyl, (oxetan-3-yl)methyl, cyclopropyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, propoxy, (1-hydroxycyclopropyl)methoxy, (1-cyanocyclopropyl)methoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, cyano, 2-oxopyrrolidin-1-yl, morpholino, 1,1-dioxidothiomorpholin-4-yl, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 2,2-dimethyl-2λ 6 -diazathia-1,2-dien-1-yl, [dimethyl(oxido)-λ 6 -sulfanylidene]amino, methyl(tetrahydrofuran-3-yl)amino, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy, (tetrahydrofuran-3-yl)oxy, (tetrahydro-2H-pyran-3-yl)oxy, (tetrahydro-2H-pyran-4-yl)oxy and phenyl, R 5 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, cyclopropyl, methoxy, propoxy, cyclopropyloxy, methanesulfonyl, cyano, hydroxy, oxetan-3-yl and oxetan-3-yloxy, R 6 represents a hydrogen atom or a group selected from methyl and hydroxymethyl, R 7 represents a hydrogen atom or a fluorine atom or a group selected from methyl, ethyl and hydroxy, R 8 represents a group selected from methyl and ethyl, and n represents an integer selected from 1, 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 , —C(═O)N(H)C 2 H 5 , —C(═O)N(CH 3 ) 2 and —C(═O)OR 15 ,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 , —C(═O)N(H)C 2 H 5 and —C(═O)N(CH 3 ) 2 ,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 1 represents a group selected from cyano, —C(═O)NH 2 , —C(═O)N(H)CH 3 and —C(═O)N(CH 3 ) 2 ,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 1 represents a cyano group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 1 represents a group selected from —C(═O)NH 2 , —C(═O)N(H)CH 3 , —C(═O)N(H)C 2 H 5 and —C(═O)N(CH 3 ) 2 ,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 1 represents a group selected from —C(═O)NH 2 , —C(═O)N(H)CH 3 and —C(═O)N(CH 3 ) 2 ,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl, which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group,

and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 6 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —(CH 2 ) 3 —, —CH 2 —CH(OH)—CH 2 —, —(CH 2 ) 4 —, —O—(CH 2 ) 2 —, —(CH 2 ) 2 )—O—, —CH 2 —CH(CH 3 )—O—, —CH 2 —O—CH 2 —, —O—(CH 2 ) 3 —, —(CH 2 ) 3 —O—, —CH 2 —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—CH 2 —, —O—CH 2 —O—, —O—C(CH 3 ) 2 —O—, —O—(CH 2 ) 2 —O—, —N(R 18 )—C(═O)—(C(R 18 )(R 19 )) m —, —N(R 18 )—C(═O)—(C(CH 2 ) 3 )—, —N(R 18 )—(C(R 18 )(R 19 )) m , —N(R 18 )—C(═O)—O— and —N(R 18 )—C(═O)—N(R 18 )—, wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 6 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —(CH 2 ) 3 —, —CH 2 —CH(OH)—CH 2 —, —(CH 2 ) 4 —, —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—, —CH 2 —CH(CH 3 )—O—, —CH 2 —O—CH 2 —, —O—(CH 2 ) 3 —, —(CH 2 ) 3 —O—, —CH 2 —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—CH 2 —, —O—CH 2 —O—, —O—C(CH 3 ) 2 —O—, —O—(CH 2 ) 2 —O—, —N(R 18 )—C(═O)—(C(R 18 )(R 19 )) m —, —N(R 18 )—C(═O)—(C(CH 2 ) 3 )—, —N(R 18 )—(C(R 18 )(R 19 )) m —, —N(R 18 )—C(═O)—O— and —N(R 18 )—C(═O)—N(R 18 )—,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl, which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group,

and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 2 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from

—CH 2 —CH(OH)—CH 2 —, —CH 2 —CH(CH 3 )—O—, —O—C(CH 3 ) 2 —O—, —N(R 18 )—C(═O)—(C(R 18 )(R 19 )) m —, —N(R 18 )—C(═O)—(C(CH 2 ) 3 )—, —N(R 18 )—(C(R 18 )(R 19 )) m —, —N(R 18 )—C(═O)—O— and —N(R 18 )—C(═O)—N(R 18 )—, wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a group selected from 4- to 7-membered heterocycloalkyl and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

and wherein said phenyl and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl and C 1 -C 2 -alkoxy,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, 1-naphthyl, 2-naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is selected from pyrazolyl, 1,2,4-oxadiazol, 1,3,4-oxadiazol, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1,3-thiazolyl, pyridinyl, pyrazinyl, indolyl, benzothiophenyl, benzofuranyl, 1,3-benzoxazolyl, indazolyl, benzimidazolyl, 1,3-benzothiazolyl, pyrrolo[2,3-b]pyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl and 1,3-thiazolo[5,4-b]pyridinyl, and which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, 1-naphthyl, 2-naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 alkyl, C 3 -C 5 -cycloalkyl, G Ca haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 2 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, phenyl and pyridinyl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —CH 2 —CH(OH)—CH 2 —, —CH 2 —CH(CH 3 )—O—, —O—C(CH 3 ) 2 —O—, —NH—C(═O)—CH(CH 3 )—, —N(CH 3 )—C(═O)—C(CH 3 ) 2 —, —NH—C(═O)—(C(CH 2 ) 3 )—, —NH—CH 2 —C(CH 3 ) 2 —, —N(CH 3 )—C(═O)—O— and —N(CH 3 )—C(═O)—N(CH 3 )—,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a group selected from 4- to 7-membered heterocycloalkyl and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

and wherein said phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl and C 1 -C 2 -alkoxy,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is selected from pyrazolyl, 1,2,4-oxadiazol, 1,3,4-oxadiazol, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1,3-thiazolyl, pyridinyl, pyrazinyl, indolyl, benzothiophenyl, benzofuranyl, 1,3-benzoxazolyl, indazolyl, benzimidazolyl, 1,3-benzothiazolyl, pyrrolo[2,3-b]pyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl and 1,3-thiazolo[5,4-b]pyridinyl, and which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 2 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, phenyl and pyridinyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a group selected from 4- to 7-membered heterocycloalkyl and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

and wherein said phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl and C 1 -C 2 -alkoxy,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, 1-naphthyl, 2-naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is selected from pyrazolyl, 1,2,4-oxadiazol, 1,3,4-oxadiazol 1,3-thiazolyl, pyridinyl, pyrazinyl, indolyl, benzothiophenyl, benzofuranyl, 1,3-benzoxazolyl, indazolyl, benzimidazolyl, 1,3-benzothiazolyl, pyrrolo[2,3-b]pyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl and 1,3-thiazolo[5,4-b]pyridinyl, and which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, 1-naphthyl, 2-naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 alkyl, C 3 -C 5 -cycloalkyl, G Ca haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 2 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, phenyl and pyridinyl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —CH 2 —CH(OH)—CH 2 —, —CH 2 —CH(CH 3 )—O—, —O—C(CH 3 ) 2 —O—, —NH—C(═O)—CH(CH 3 )—, —N(CH 3 )—C(═O)—C(CH 3 ) 2 —, —NH—C(═O)—(C(CH 2 ) 3 )—, —NH—CH 2 —C(CH 3 ) 2 —, —N(CH 3 )—C(═O)—O— and —N(CH 3 )—C(═O)—N(CH 3 )—,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a group selected from 4- to 7-membered heterocycloalkyl and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

and wherein said phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl and C 1 -C 2 -alkoxy,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, 1-naphthyl, 2-naphthyl, 1H-pyrazol-3-yl, 1H-pyrazol-4-yl, 1H-pyrazol-5-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1H-1,2,3-triazol-4-yl, 2H-1,2,3-triazol-4-yl, 1,3-thiazol-2-yl, pyridin-3-yl, pyrazin-2-yl, 1H-indol-5-yl, 1-benzofuran-4-yl, 1-benzofuran-7-yl, 1H-indol-6-yl, benzothiophen-2-yl, 1,3-benzoxazol-2-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-6-yl, 1,3-benzoxazol-7-yl, 1H-indazol-5-yl, 1H-benzimidazol-2-yl, 1H-benzimidazol-4-yl, 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-5-yl, 1,3-benzothiazol-6-yl, 1,3-benzothiazol-7-yl, 1H-pyrrolo[2,3-b]pyridin-3-yl, quinolin-2-yl, quinolin-4-yl, quinolin-6-yl, quinolin-7-yl, isoquinolin-5-yl, isoquinolin-7-yl, isoquinolin-8-yl, quinoxalin-2-yl, quinoxalin-5-yl and 1,3-thiazolo[5,4-b]pyridin-2-yl,

which group is optionally substituted, one or two times, each substituent independently selected from a fluorine, chlorine or bromine atom or a group selected from methyl, propyl, isopropyl, tert-butyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, (propan-2-yl)oxy, methoxymethyl, 2-methoxyethyl, benzyloxy, trifluormethoxy, 2,2,2-trifluoroethoxy, phenoxy, (oxolan-2-yl)methoxy, (tetrahydrofuran-2-yl)methoxy, methanesulfonyl, dimethylphosphoryl, cyano, hydroxy, dimethylamino, oxetan-3-yl, 2-oxopyrrolidin-1-yl, 4-methyl-2-oxopiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, morpholino-4-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 8-methyl-3-oxo-2,8-diazaspiro[4.5]decan-2-yl, carbamoyl, acetyl, trifluoroacetyl, benzamido, benzenesulfonamido, [dimethyl(oxido)-λ 6 -sulfanylidene]amino, phenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl and pyridin-3-yl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are linked to one another in such a way that they jointly form a group selected from —CH 2 —CH(OH)—CH 2 —, —CH 2 —CH(CH 3 )—O—, —O—C(CH 3 ) 2 —O—, —NH—C(═O)—CH(CH 3 )—, —N(CH 3 )—C(═O)—C(CH 3 ) 2 —, —NH—C(═O)—(C(CH 2 ) 3 )—, —NH—CH 2 —C(CH 3 ) 2 —, —N(CH 3 )—C(═O)—O— and —N(CH 3 )—C(═O)—N(CH 3 )—,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from 1H-pyrazol-3-yl, 1H-pyrazol-4-yl, 1H-pyrazol-5-yl, 1,2,4 oxadiazol 5 yl, 1,3,4-oxadiazol-2-yl, 2H-1,2,3-triazol-4-yl, 1,3-thiazol-2-yl, pyridin-3-yl, pyrazin-2-yl, 1H-indol-5-yl, 1-benzofuran-4-yl, 1-benzofuran-7-yl, 1H-indol-6-yl, benzothiophen-2-yl, 1,3-benzoxazol-2-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-6-yl, 1,3-benzoxazol-7-yl, 1H-benzimidazol-2-yl, 1H-benzimidazol-4-yl, 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-5-yl, 1,3-benzothiazol-6-yl, 1,3-benzothiazol-7-yl, 1H-pyrrolo[2,3-b]pyridin-3-yl, quinolin-2-yl, quinolin-4-yl, quinolin-6-yl, quinolin-7-yl, isoquinolin-5-yl, isoquinolin-7-yl, isoquinolin-8-yl, quinoxalin-2-yl, quinoxalin-5-yl and 1,3-thiazolo[5,4-b]pyridin-2-yl,

which group is optionally substituted, one or two times, each substituent independently selected from a fluorine, chlorine or bromine atom or a group selected from methyl, propyl, isopropyl, tert-butyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, (propan-2-yl)oxy, methoxymethyl, 2-methoxyethyl, benzyloxy, trifluormethoxy, 2,2,2-trifluoroethoxy, phenoxy, (oxolan-2-yl)methoxy, (tetrahydrofuran-2-yl)methoxy, methanesulfonyl, dimethylphosphoryl, cyano, hydroxy, dimethylamino, oxetan-3-yl, 2-oxopyrrolidin-1-yl, 4-methyl-2-oxopiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, morpholino-4-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 8-methyl-3-oxo-2,8-diazaspiro[4.5]decan-2-yl, carbamoyl, acetyl, trifluoroacetyl, benzamido, benzenesulfonamido, [dimethyl(oxido)-λ 6 -sulfanylidene]amino, phenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl and pyridin-3-yl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are linked to one another in such a way that they jointly form a group selected from —CH 2 —CH(OH)—CH 2 —, —CH 2 —CH(CH 3 )—O—, —O—C(CH 3 ) 2 —O—, —NH—C(═O)—CH(CH 3 )—, —N(CH 3 )—C(═O)—C(CH 3 ) 2 —, —NH—C(═O)—(C(CH 2 ) 3 )—, —NH—CH 2 —C(CH 3 ) 2 —, —N(CH 3 )—C(═O)—O— and —N(CH 3 )—C(═O)—N(CH 3 )—,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, 1-naphthyl, 2-naphthyl, 1H-pyrazol-3-yl, 1H-pyrazol-4-yl, 1H-pyrazol-5-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,3-thiazol-2-yl, pyridin-3-yl, pyrazin-2-yl, 1H-indol-5-yl, 1-benzofuran-4-yl, 1-benzofuran-7-yl, 1H-indol-6-yl, benzothiophen-2-yl, 1,3-benzoxazol-2-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-6-yl, 1,3-benzoxazol-7-yl, 1H-benzimidazol-2-yl, 1H-benzimidazol-4-yl, 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-5-yl, 1,3-benzothiazol-6-yl, 1,3-benzothiazol-7-yl, 1H-pyrrolo[2,3-b]pyridin-3-yl, quinolin-2-yl, quinolin-4-yl, quinolin-6-yl, quinolin-7-yl, isoquinolin-5-yl, isoquinolin-7-yl, isoquinolin-8-yl, quinoxalin-2-yl, quinoxalin-5-yl and 1,3-thiazolo[5,4-b]pyridin-2-yl,

which group is optionally substituted, one or two times, each substituent independently selected from a fluorine, chlorine or bromine atom or a group selected from methyl, propyl, isopropyl, tert-butyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, (propan-2-yl)oxy, methoxymethyl, 2-methoxyethyl, benzyloxy, trifluormethoxy, 2,2,2-trifluoroethoxy, phenoxy, (oxolan-2-yl)methoxy, (tetrahydrofuran-2-yl)methoxy, methanesulfonyl, dimethylphosphoryl, cyano, hydroxy, dimethylamino, oxetan-3-yl, 4-methyl-2-oxopiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, morpholino-4-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 8-methyl-3-oxo-2,8-diazaspiro[4.5]decan-2-yl, carbamoyl, acetyl, trifluoroacetyl, benzamido, benzenesulfonamido, [dimethyl(oxido)-λ 6 -sulfanylidene]amino, phenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl and pyridin-3-yl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are linked to one another in such a way that they jointly form a group selected from —CH 2 —CH(OH)—CH 2 —, —CH 2 —CH(CH 3 )—O—, —O—C(CH 3 ) 2 —O—, —NH—C(═O)—CH(CH 3 )—, —N(CH 3 )—C(═O)—C(CH 3 ) 2 —, —NH—C(═O)—(C(CH 2 ) 3 )—, —NH—CH 2 —C(CH 3 ) 2 —, —N(CH 3 )—C(═O)—O— and —N(CH 3 )—C(═O)—N(CH 3 )—,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 6 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —(CH 2 ) 3 —, —(CH 2 ) 4 —, —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—, —CH 2 —O—CH 2 —, —O—(CH 2 ) 3 —, —(CH 2 ) 3 —O—, —CH 2 —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—CH 2 —, —O—CH 2 —O— and —O—(CH 2 ) 2 —O—,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 6 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —(CH 2 ) 3 —, —(CH 2 ) 4 —, —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—, —CH 2 —O—CH 2 —, —O—(CH 2 ) 3 —, —(CH 2 ) 3 —O—, —CH 2 —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—CH 2 —, —O—CH 2 —O— and —O—(CH 2 ) 2 —O—, wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and

wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 and phenyl,

wherein said C 1 -C 4 -alkoxy group is optionally substituted with a phenyl group, which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 and phenyl,

wherein said C 1 -C 4 -alkoxy group is optionally substituted with a phenyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, 1-naphthyl and 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is selected from pyrazolyl, 1,2,4-oxadiazol, 1,3-thiazolyl, pyridinyl, pyrazinyl, indolyl, benzofuranyl, 1,3-benzoxazolyl, benzimidazolyl, 1,3-benzothiazolyl, pyrrolo[2,3-b]pyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl and 1,3-thiazolo[5,4-b]pyridinyl, and which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which phenyl, 1-naphthyl and 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 and phenyl,

wherein said C 1 -C 4 -alkoxy group is optionally substituted with a phenyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, 1-naphthyl, 1H-pyrazol-5-yl, 1,2,4-oxadiazol-5-yl, 1,3-thiazol-2-yl, pyridin-3-yl, pyrazin-2-yl, 1H-indol-5-yl, 1-benzofuran-4-yl, 1-benzofuran-7-yl, 1,3-benzoxazol-2-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-7-yl, 1H-benzimidazol-2-yl, 1H-benzimidazol-4-yl, 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-7-yl, 1H-pyrrolo[2,3-b]pyridin-3-yl, quinolin-4-yl, isoquinolin-5-yl, isoquinolin-7-yl, isoquinolin-8-yl, quinoxalin-2-yl, quinoxalin-5-yl and 1,3-thiazolo[5,4-b]pyridin-2-yl,

which group is optionally substituted, one or two times, each substituent independently selected from a fluorine, chlorine or bromine atom or a group selected from methyl, propyl, isopropyl, tert-butyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, (propan-2-yl)oxy, benzyloxy, trifluormethoxy, 2,2,2-trifluoroethoxy, phenoxy, methanesulfonyl, dimethylphosphoryl, cyano, hydroxy, dimethylamino, 2-oxopyrrolidin-1-yl, 4-methyl-2-oxopiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, morpholino-4-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 8-methyl-3-oxo-2,8-diazaspiro[4.5]decan-2-yl, carbamoyl, trifluoroacetyl, benzamido, benzenesulfonamido, [dimethyl(oxido)-λ 6 -sulfanylidene]amino and phenyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a 5- to 10-membered heteroaryl group,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 6 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 6 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a 5- to 10-membered heteroaryl group,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a 5- to 10-membered heteroaryl,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 )R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 and phenyl,

wherein said C 1 -C 4 -alkoxy group is optionally substituted with a phenyl group, which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a 5- to 10-membered heteroaryl group,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 and phenyl,

wherein said C 1 -C 4 -alkoxy group is optionally substituted with a phenyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a 5- to 10-membered heteroaryl group,

which 5- to 10-membered heteroaryl group is selected from pyrazolyl, 1,2,4-oxadiazol, 1,3-thiazolyl, pyridinyl, pyrazinyl, indolyl, benzofuranyl, 1,3-benzoxazolyl, benzimidazolyl, 1,3-benzothiazolyl, pyrrolo[2,3-b]pyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl and 1,3-thiazolo[5,4-b]pyridinyl, and which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which 5- to 10-membered heteroaryl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 and phenyl,

wherein said C 1 -C 4 -alkoxy group is optionally substituted with a phenyl group, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from 1H-pyrazol-5-yl, 1,2,4-oxadiazol-5-yl, 1,3-thiazol-2-yl, pyridin-3-yl, pyrazin-2-yl, 1H-indol-5-yl, 1-benzofuran-4-yl, 1-benzofuran-7-yl, 1,3-benzoxazol-2-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-7-yl, 1H-benzimidazol-2-yl, 1H-benzimidazol-4-yl, 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-7-yl, 1H-pyrrolo[2,3-b]pyridin-3-yl, quinolin-4-yl, isoquinolin-5-yl, isoquinolin-7-yl, isoquinolin-8-yl, quinoxalin-2-yl, quinoxalin-5-yl and 1,3-thiazolo[5,4-b]pyridin-2-yl,

which group is optionally substituted, one or two times, each substituent independently selected from a fluorine, chlorine or bromine atom or a group selected from methyl, propyl, isopropyl, tert-butyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, (propan-2-yl)oxy, benzyloxy, trifluormethoxy, 2,2,2-trifluoroethoxy, phenoxy, methanesulfonyl, dimethylphosphoryl, cyano, hydroxy, dimethylamino, 2-oxopyrrolidin-1-yl, 4-methyl-2-oxopiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, morpholino-4-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 8-methyl-3-oxo-2,8-diazaspiro[4.5]decan-2-yl, carbamoyl, trifluoroacetyl, benzamido, benzenesulfonamido, [dimethyl(oxido)-λ 6 -sulfanylidene]amino and phenyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl and naphthyl,

which phenyl and naphthyl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C, C 6 alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 6 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —(CH 2 ) 3 —, —(CH 2 ) 4 —, —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—, —CH 2 —O—CH 2 —, —O—(CH 2 ) 3 —, —(CH 2 ) 3 —O—, —CH 2 —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—CH 2 —, —O—CH 2 —O— and —O—(CH 2 ) 2 —O—,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 6 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl and naphthyl,

which phenyl and naphthyl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl, or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are optionally linked to one another in such a way that they jointly form a group selected from —(CH 2 ) 3 —, —(CH 2 ) 4 —, —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—, —CH 2 —O—CH 2 —, —O—(CH 2 ) 3 —, —(CH 2 ) 3 —O—, —CH 2 —O—(CH 2 ) 2 —, —(CH 2 ) 2 —O—CH 2 —, —O—CH 2 —O— and —O—(CH 2 ) 2 —O—,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl and naphthyl,

which phenyl and naphthyl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 and phenyl,

wherein said C 1 -C 4 -alkoxy group is optionally substituted with a phenyl group, which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl and naphthyl,

which phenyl and naphthyl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 and phenyl,

wherein said C 1 -C 4 -alkoxy group is optionally substituted with a phenyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl and 1-naphthyl,

which phenyl and 1-naphthyl group is optionally substituted, one, two, three or four times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, —S(═O) 2 R 14 , —P(═O)(R 14 ) 2 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═O)(R 14 ) 2 and phenyl,

wherein said C 1 -C 4 -alkoxy group is optionally substituted with a phenyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from phenyl, 1-naphthyl

which phenyl and naphthyl group is optionally substituted, one or two times, each substituent independently selected from a fluorine, chlorine or bromine atom or a group selected from methyl, propyl, isopropyl, tert-butyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, (propan-2-yl)oxy, benzyloxy, trifluormethoxy, 2,2,2-trifluoroethoxy, phenoxy, methanesulfonyl, dimethylphosphoryl, cyano, hydroxy, dimethylamino, 2-oxopyrrolidin-1-yl, 4-methyl-2-oxopiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, morpholino-4-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 8-methyl-3-oxo-2,8-diazaspiro[4.5]decan-2-yl, carbamoyl, trifluoroacetyl, benzamido, benzenesulfonamido, [dimethyl(oxido)-λ 6 -sulfanylidene]amino and phenyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 4 -C 6 -cycloalkenyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 2 -C 6 -alkenyl group is optionally substituted with a C 1 -C 4 -haloalkyl group, and wherein said C 3 -C 6 -cycloalkyl and 04-C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 5 -cycloalkyl, C 4 -C 5 -cycloalkenyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 2 -C 4 -alkenyl group is optionally substituted with a C 1 -C 4 -haloalkyl group, and wherein said C 3 -C 5 -cycloalkyl and C 4 -C 5 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 2 -C 4 -alkenyl group is optionally substituted with a C 1 -C 4 -haloalkyl group, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, with a cyano group, and wherein said C 2 -C 4 -alkenyl group is optionally substituted with a C 1 -C 4 -haloalkyl group, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —P(═O)(R 14 ), 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, with a cyano group,

and wherein said C 2 -C 4 -alkenyl group is optionally substituted with a C 1 -C 4 -haloalkyl group, and

wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, with a halogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 3 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, sec-butyl, (oxetan-3-yl)methyl, 3,3,3-trifluoroprop-1-en-2-yl, cyclopropyl, (trifluoromethyl)cyclopropyl, cyclobutyl, 2,2-dimethylcyclobutyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, ethoxy, propoxy, 2,2-difluoroethoxy, 2,2-difluoropropoxy, cyclopropylmethoxy, (1-cyanocyclopropyl)methoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, cyano, hydroxy, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, carbamoyl, dimethylphosphoryl, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy and phenyl, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 4 -C 6 -cycloalkenyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy, and wherein said C 3 -C 6 -cycloalkyl and C 4 -C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 5 -cycloalkyl, C 4 -C 5 -cycloalkenyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 3 )(R 10 ), —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl and C 4 -C 5 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, with a cyano group,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, with a halogen atom,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 3 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, sec-butyl, (oxetan-3-yl)methyl, cyclopropyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, propoxy, (1-cyanocyclopropyl)methoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, cyano, hydroxy, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy and phenyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 4 -C 6 -cycloalkenyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 4 -haloalkoxy, —O—(C 1 -C 4 -alkyl)-C(═O)OR 13 , —O—(C 1 -C 4 -alkyl)-C(═O)N(R 9 )(R 10 ), C 3 -C 6 -cycloalkyloxy, —S(═O)R 14 , —S(═O) 2 R 14 , cyano, nitro, hydroxy, —N(R 3 )(R 13 ), —N(R 16 )(R 17 ), —N(R 16 )(R 20 ), —C(═O)N(R 3 )(R 13 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 1 -C 6 -alkoxy group is optionally substituted with a oxiran-2-yl group, and wherein said C 3 -C 6 -cycloalkyl and C 4 -C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 5 -cycloalkyl, C 4 -C 5 -cycloalkenyl, C 1 -C 5 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, —O—(C 1 -C 4 -alkyl)-C(═O)OR 15 , —O—(C 1 -C 4 -alkyl)-C(═O)N(R 9 )(R 10 ), C 3 -C 5 -cycloalkyloxy, —S(═O)R 14 , —S(═O) 2 R 14 , cyano, nitro, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N(R 16 )(R 20 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy,

C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy, and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a oxiran-2-yl group,

and wherein said C 3 -C 5 -cycloalkyl and C 4 -C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, —O—(C 1 -C 4 -alkyl)-C(═O)OR 15 , —O—(C 1 -C 4 -alkyl)-C(═O)N(R 9 )(R 10 ), C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, nitro, hydroxy, —N(R 9 )(R 10 ), —N(═R 16 )(═R 17 ), —N(R 16 )(R 20 ), —N═S(═NH)(R 14 ) 2 , N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a oxiran-2-yl group, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 1 -C 5 -haloalkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, —O—(C 1 -C 4 -alkyl)-C(═O)OR 15 , —O—(C 1 -C 4 -alkyl)-C(═O)N(R 9 )(R 10 ), C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, nitro, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N(R 16 )(R 29 ), —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and, 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a oxiran-2-yl group, and wherein said C 3 -C 5 -cycloalkyl is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, —O—CH 2 —C(═O)OR 15 , —O—CH 2 —C(═O)N(R 9 )(R 10 ), C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, nitro, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N(R 16 )(R 20 ), —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a oxiran-2-yl group, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, —O—CH 2 —C(═O)OR 15 , —O—CH 2 —C(═O)N(R 9 )(R 10 ), C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, nitro, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 1 -C 4 -alkoxy group is optionally substituted with a oxiran-2-yl group, and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, sec-butyl, (oxetan-3-yl)methyl, trifluoromethyl, cyclopropyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, propoxy, 2-methoxyethoxy, (1-hydroxycyclopropyl)methoxy, (1-cyanocyclopropyl)methoxy, (oxiran-2-yl)methoxy, carboxymethoxy, 2-tert-butoxy-2-oxo-ethoxy, 2-amino-2-oxo-ethoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, dimethylphosphoryl, cyano, nitro, hydroxy, (cyanomethyl)(methyl)amino, (2-hydroxyethyl)amino, (2-hydroxyethyl)(methyl)amino, (2-methoxyethyl)amino, (2-methoxyethyl)(methyl)amino, cyclopropylamino, (oxetan-3-yl)amino, methyl(oxetan-3-yl)amino, methyl(oxolan-3-yl)amino, 3-hydroxyazetidin-1-yl, 2-oxopyrrolidin-1-yl, morpholino, 1,1-dioxidothiomorpholin-4-yl, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 2,2-dimethyl-2λ 6 -diazathia-1,2-dien-1-yl, [dimethyl(oxido)-λ 6 -sulfanylidene]amino, methyl(tetrahydrofuran-3-yl)amino, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy, (tetrahydrofuran-3-yl)oxy, (tetrahydro-2H-pyran-3-yl)oxy, (tetrahydro-2H-pyran-4-yl)oxy and phenyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 4 -C 6 -cycloalkenyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 6 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —C(═O)N(R 6 )(R 10 ), —P(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 6 -cycloalkyl and C 4 -C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 5 -cycloalkyl, C 4 -C 5 -cycloalkenyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 1 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl and C 4 -C 6 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 3 -C 5 -cycloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, —N(R 9 )(R 10 ), —N(R 16 )(R 17 ), —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy and phenyl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said C 1 -C 6 -alkyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, sec-butyl, (oxetan-3-yl)methyl, trifluoromethyl, cyclopropyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, propoxy, 2-methoxyethoxy, (1-hydroxycyclopropyl)methoxy, (1-cyanocyclopropyl)methoxy, (oxiran-2-yl)methoxy, carboxymethoxy, 2-tert-butoxy-2-oxo-ethoxy, 2-amino-2-oxo-ethoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, dimethylphosphoryl, cyano, nitro, hydroxy, (cyanomethyl)(methyl)amino, (2-hydroxyethyl)amino, (2-hydroxyethyl)(methyl)amino, (2-methoxyethyl)amino, (2-methoxyethyl)(methyl)amino, cyclopropylamino, (oxetan-3-yl)amino, methyl(oxetan-3-yl)amino, methyl(oxolan-3-yl)amino, 3-hydroxyazetidin-1-yl, 2-oxopyrrolidin-1-yl, morpholino, 1,1-dioxidothiomorpholin-4-yl, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 2,2-dimethyl-2λ 6 -diazathia-1,2-dien-1-yl, [dimethyl(oxido)-λ 6 -sulfanylidene]amino, methyl(tetrahydrofuran-3-yl)amino, tetrahydrofuran-3-ylmethoxy, (tetrahydrofuran-3-ylmethyl)amino, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy, (tetrahydrofuran-3-yl)oxy, (tetrahydro-2H-pyran-3-yl)oxy, (tetrahydro-2H-pyran-4-yl)oxy and phenyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, sec-butyl, (oxetan-3-yl)methyl, cyclopropyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, propoxy, (1-hydroxycyclopropyl)methoxy, (1-cyanocyclopropyl)methoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, cyano, 2-oxopyrrolidin-1-yl, morpholino, 1,1-dioxidothiomorpholin-4-yl, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 2,2-dimethyl-2λ 6 -diazathia-1,2-dien-1-yl, [dimethyl(oxido)-λ 6 -sulfanylidene]amino, methyl(tetrahydrofuran-3-yl)amino, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy, (tetrahydrofuran-3-yl)oxy, (tetrahydro-2H-pyran-3-yl)oxy, (tetrahydro-2H-pyran-4-yl)oxy and phenyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 4 -C 6 -cycloalkenyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 6 -alkyl)-, C 1 -C 6 -alkoxy, (C 1 -C 2 alkoxy)-(C 2 -C 6 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 6 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl and C 1 -C 6 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 6 -cycloalkyl and C 4 -C 5 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 5 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 3 -C 5 -cycloalkyl, C 4 -C 5 -cycloalkenyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -haloalkyl, (C 1 -C 2 -alkoxy)-(C 1 -C 4 -alkyl)-, C 1 -C 4 -alkoxy, (C 1 -C 2 alkoxy)-(C 2 -C 4 -alkoxy)-, C 1 -C 4 -haloalkoxy, C 3 -C 5 -cycloalkyloxy, phenoxy, —SR 14 , —S(═O)R 14 , —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl and 5- or 6-membered heteroaryl,

wherein said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group and 5- to 7-membered heterocycloalkenyl group, and wherein said 4- to 7-membered heterocycloalkyl group, 5- to 7-membered heterocycloalkenyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 5 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl and C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl and C 4 -C 5 -cycloalkenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group, and wherein said phenyl, phenoxy and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 5 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), —C(═O)N(R 9 )(R 10 ), —C(═O)R 11 , —N(R 12 )C(═O)R 13 , —N(R 12 )S(═O) 2 R 14 , —N═S(═NH)(R 14 ) 2 , —N═S(═O)(R 14 ) 2 , —P(═O)(R 14 ) 2 , 4- to 7-membered heterocycloalkyl and (4- to 7-membered heterocycloalkyl)oxy,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group and (4- to 7-membered heterocycloalkyl)oxy group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and wherein said C 1 -C 5 -alkyl, C 1 -C 4 -alkoxy group is optionally substituted with a group selected from C 3 -C 4 -cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl, —N(R 9 )(R 10 ) and oxo, and which phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ), and which C 3 -C 4 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from cyano and hydroxy,

and wherein said C 3 -C 5 -cycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 5 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 5 -alkyl, C 3 -C 5 -cycloalkyl, C 1 -C 4 -alkoxy, C 3 -C 5 -cycloalkyloxy, —S(═O) 2 R 14 , cyano, hydroxy, —N(R 9 )(R 10 ), 4- to 7-membered heterocycloalkyl and (4- to 7-membered heterocycloalkyl)oxy,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of said 4- to 7-membered heterocycloalkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 5 represents a hydrogen atom or a fluorine, chlorine or bromine atom or a group selected from methyl, cyclopropyl, methoxy, propoxy, cyclopropyloxy, methanesulfonyl, cyano, hydroxy, oxetan-3-yl and oxetan-3-yloxy,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 6 represents a hydrogen atom, or a fluorine atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 6 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -hydroxyalkyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 6 represents a hydrogen atom or a group selected from methyl and hydroxymethyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and hydroxy,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 7 represents a hydrogen atom or a fluorine atom or a group selected from methyl, ethyl, methoxy and hydroxy,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, hydroxy and cyano,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 7 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 4 -alkyl and hydroxy,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 7 represents a hydrogen atom or a fluorine atom or a group selected from ethyl, ethyl and hydroxy,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 8 represents a group selected from methyl and ethyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 8 represents a methyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 8 represents an ethyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 2 -C 4 -hydroxyalkyl, N≡C—(C 1 -C 4 -alkyl)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)-, C 3 -C 4 -cycloalkyl and C 2 -C 4 -haloalkyl, or

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -haloalkyl, hydroxy and oxo, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 2 -C 4 -hydroxyalkyl, N≡C—(C 1 -C 4 -alkyl)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)-, C 3 -C 4 -cycloalkyl and C 2 -C 4 -haloalkyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 2 -C 4 -hydroxyalkyl, N≡C—(C 1 -C 4 -alkyl)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)- and C 3 -C 4 -cycloalkyl, or R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -haloalkyl, hydroxy and oxo,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 2 -C 4 -hydroxyalkyl, N≡C—(C 1 -C 4 -alkyl)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)- and C 3 -C 4 -cycloalkyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 2 -C 4 -hydroxyalkyl, N≡C—(C 1 -C 4 -alkyl)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)- and C 3 -C 4 -cycloalkyl, or R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group, wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)-, C 3 -C 4 -cycloalkyl and C 2 -C 4 -haloalkyl,

or

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -haloalkyl, hydroxy and oxo,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)-, C 3 -C 4 -cycloalkyl and C 2 -C 4 -haloalkyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula

(I), supra, in which:

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -haloalkyl, hydroxy and oxo,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or C 1 -C 4 -alkyl group,

or

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -haloalkyl, hydroxy and oxo,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a methyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or C 1 -C 4 -alkyl group,

or

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen containing 4- to 7-membered heterocycloalkyl group,

wherein said nitrogen containing 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, hydroxy and oxo, or two substituents, which are attached to the same carbon atom of said nitrogen containing 4- to 7-membered heterocycloalkyl group, together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 11 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 11 represents a group selected from C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 11 represents a group selected from methyl and trifluoromethyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 11 represents a methyl group, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 11 represents a hydrogen atom or group selected from C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -haloalkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 11 represents a hydrogen atom or a C 1 -C 4 -haloalkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 11 represents a C 1 -C 4 -haloalkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 11 represents a trifluoromethy group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 12 represents a hydrogen atom or a C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 12 represents a hydrogen atom,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 13 represents a hydrogen atom or a group selected from C 1 -C 6 -alkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 13 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 13 represents a phenyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 14 represents a group selected from C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 6 -cycloalkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 14 represents a group selected from C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 3 -C 5 -cycloalkyl, phenyl and 5- or 6-membered heteroaryl,

wherein said phenyl group and 5- or 6-membered heteroaryl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 14 represents a group selected from C 1 -C 4 -alkyl and phenyl,

wherein said phenyl group is optionally substituted, one or two times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, cyano, hydroxy, C 1 -C 2 -alkoxy, C 3 -C 4 -cycloalkyl and —N(R 9 )(R 10 ),

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 14 represents a group selected from C 1 -C 4 -alkyl and phenyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 14 represents a group selected from methyl and phenyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 15 represents a hydrogen atom or a C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 16 represents a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl and C 2 -C 4 -haloalkyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 16 represents a hydrogen atom or a C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo, and wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group,

and wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 17 represents a 4- to 7-membered heterocycloalkyl group,

wherein said 4- to 7-membered heterocycloalkyl group is connected to the rest of the molecule via a carbon atom of the 4- to 7-membered heterocycloalkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 18 represents a hydrogen atom or a group selected from methyl and ethyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 18 represents a hydrogen atom or a methyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 19 represents a hydrogen atom or a group selected from methyl and ethyl,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 19 represents a hydrogen atom or a methyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 20 represents a (4- to 7-membered heterocycloalkyl)-(C 1 -C 4 -alkyl)- group,

wherein the (4- to 7-membered heterocycloalkyl) part of said group is optionally substituted, one, two or three times, each substituent independently selected from a halogen atom or a group selected from C 1 -C 4 -alkyl, C 3 -C 4 -cycloalkyl, C 1 -C 4 -alkoxy, hydroxy and oxo, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 20 represents a (4- to 7-membered heterocycloalkyl)-(C 1 -C 4 -alkyl)- group,

wherein the (4- to 7-membered heterocycloalkyl) part of said group is optionally substituted, one or two times, with a C 1 -C 4 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 20 represents a (4- to 7-membered heterocycloalkyl)-(C 1 -C 4 -alkyl)- group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

m represents an integer selected from 1, 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

m represents an integer selected from 1 and 2,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

m represents an integer selected from 1 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

m represents an integer selected from 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

m represents an integer of 1,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

m represents an integer of 2,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

m represents an integer of 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

n represents an integer selected from 1, 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

n represents an integer selected from 1 and 2,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

n represents an integer selected from 1 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

n represents an integer selected from 2 and 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

n represents an integer of 1,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

n represents an integer of 2,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

n represents an integer of 3,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 1 represents a group selected from cyano and —C(═O)NH 2 , R 2 represents a 5- to 10-membered heteroaryl group,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which 5- to 10-membered heteroaryl group is optionally substituted with a group selected from C 1 -C 4 -alkyl and phenyl,

wherein said phenyl group is optionally substituted with a C 1 -C 2 -alkyl group,

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl and cyano, R 4 represents a hydrogen atom or a group selected from —N(R 9 )(R 10 ) and (4- to 7-membered heterocycloalkyl)oxy, R 5 represents a hydrogen atom, R 6 represents a hydrogen atom, R 7 represents a hydrogen atom, R 8 represents a methyl group, R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 2 -C 4 -hydroxyalkyl and (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)-, and n represents an integer of 2,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 1 represents a group selected from cyano and —C(═O)NH 2 , R 2 represents a group selected from 1,2,4-oxadiazol-5-yl, 1H-pyrazol-3-yl and 1,3-benzoxazol-2-yl,

which group is optionally substituted with a group selected from C 1 -C 4 -alkyl and phenyl,

wherein said phenyl group is optionally substituted with a C 1 -C 2 -alkyl group,

R 3 represents a hydrogen atom or a fluorine atom or a group selected from methyl and cyano, R 4 represents a hydrogen atom or a group selected from (2-hydroxyethyl)amino, (2-hydroxyethyl)(methyl)amino, (2-methoxyethyl)amino and (tetrahydrofuran-3-yl)oxy, R 5 represents a hydrogen atom, R 6 represents a hydrogen atom, R 7 represents a hydrogen atom, R 6 represents a methyl group, and n represents an integer of 2,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 1 represents a group selected from cyano and —C(═O)NH 2 , R 2 represents a group selected from 1,2,4-oxadiazol-5-yl, 1H-pyrazol-3-yl and 1,3-benzoxazol-2-yl,

which group is optionally substituted with a group selected from methyl and phenyl,

wherein said phenyl group is optionally substituted with a methyl group,

R 3 represents a hydrogen atom or a fluorine atom or a group selected from methyl and cyano, R 4 represents a hydrogen atom or a group selected from (2-hydroxyethyl)amino, (2-hydroxyethyl)(methyl)amino, (2-methoxyethyl)amino and (tetrahydrofuran-3-yl)oxy, R 5 represents a hydrogen atom, R 6 represents a hydrogen atom, R 7 represents a hydrogen atom, R 8 represents a methyl group, and n represents an integer of 2,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 1 represents a group selected from cyano and —C(═O)NH 2 , R 2 represents a group selected from 1,2,4-oxadiazol-5-yl, 1H-pyrazol-3-yl and 1,3-benzoxazol-2-yl,

which group is substituted with a group selected from methyl and phenyl, wherein said phenyl group is substituted with a methyl group,

R 3 represents a hydrogen atom or a fluorine atom or a group selected from methyl and cyano, R 4 represents a hydrogen atom or a group selected from (2-hydroxyethyl)amino, (2-hydroxyethyl)(methyl)amino, (2-methoxyethyl)amino and (tetrahydrofuran-3-yl)oxy, R 5 represents a hydrogen atom, R 6 represents a hydrogen atom, R 7 represents a hydrogen atom, R 6 represents a methyl group, and n represents an integer of 2,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 1 represents a group selected from cyano and —C(═O)NH 2 ,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a 5- to 10-membered heteroaryl group,

which 5- to 10-membered heteroaryl group is connected to the rest of the molecule via a carbon atom of said 5- to 10-membered heteroaryl group, and which 5- to 10-membered heteroaryl group is optionally substituted with a group selected from C 1 -C 4 -alkyl and phenyl,

wherein said phenyl group is optionally substituted with a C 1 -C 2 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from 1,2,4-oxadiazol-5-yl, 1H-pyrazol-3-yl and 1,3-benzoxazol-2-yl,

which group is optionally substituted with a group selected from C 1 -C 4 -alkyl and phenyl,

wherein said phenyl group is optionally substituted with a C 1 -C 2 -alkyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from 1,2,4-oxadiazol-5-yl, 1H-pyrazol-3-yl and 1,3-benzoxazol-2-yl,

which group is optionally substituted with a group selected from methyl and phenyl,

wherein said phenyl group is optionally substituted with a methyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 2 represents a group selected from 1,2,4-oxadiazol-5-yl, 1H-pyrazol-3-yl and 1,3-benzoxazol-2-yl,

which group is substituted with a group selected from methyl and phenyl,

wherein said phenyl group is substituted with a methyl group,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 3 represents a hydrogen atom or a halogen atom or a group selected from C 1 -C 6 -alkyl and cyano,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 3 represents a hydrogen atom or a fluorine atom or a group selected from methyl and cyano,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a group selected from —N(R 9 )(R 10 ) and (4- to 7-membered heterocycloalkyl)oxy,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 4 represents a hydrogen atom or a group selected from (2-hydroxyethyl)amino, (2-hydroxyethyl)(methyl)amino, (2-methoxyethyl)amino and (tetrahydrofuran-3-yl)oxy,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 5 represents a hydrogen atom,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 6 represents a hydrogen atom,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 7 represents a hydrogen atom,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a further embodiment of the first aspect, the present invention covers compounds of formula (I), supra, in which:

R 9 and R 10 represent, independently from each occurrence, a hydrogen atom or a group selected from C 1 -C 4 -alkyl, C 2 -C 4 -hydroxyalkyl and (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)-,

and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.

In a particular further embodiment of the first aspect, the present invention covers combinations of two or more of the above mentioned embodiments under the heading “further embodiments of the first aspect of the present invention”.

In a particular further embodiment of the first aspect, the present invention covers combinations of two or more of the above mentioned embodiments.

The present invention covers any sub-combination within any embodiment or aspect of the present invention of compounds of general formula (I), supra.

The present invention covers the compounds of general formula (I) which are disclosed in the Example Section of this text, infra.

The compounds of general formula (I) of the present invention can be converted to any salt, preferably pharmaceutically acceptable salts, as described herein, by any method which is known to the person skilled in the art. Similarly, any salt of a compound of general formula (I) of the present invention can be converted into the free compound, by any method which is known to the person skilled in the art.

Compounds of general formula (I) of the present invention demonstrate a valuable pharmacological spectrum of action, which could not have been predicted. Compounds of the present invention have surprisingly been found to effectively inhibit DGKα and it is possible therefore that said compounds be used for the treatment or prophylaxis of diseases, preferably conditions with dysregulated immune responses, particularly cancer or other disorders associated with aberrant DGKα signaling, in humans and animals.

Disorders and conditions particularly suitable for treatment with an DGKα inhibitor of the present invention are liquid and solid tumours, such as cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, parathyroid and their distant metastases. Those disorders also include lymphomas, sarcomas, and leukaemias.

Examples of breast cancers include, but are not limited to, triple negative breast cancer, invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, and lobular carcinoma in situ.

Examples of cancers of the respiratory tract include, but are not limited to, small-cell and non-small-cell lung carcinoma, as well as bronchial adenoma and pleuropulmonary blastoma.

Examples of brain cancers include, but are not limited to, brain stem and hypophtalmic glioma, cerebellar and cerebral astrocytoma, glioblastoma, medulloblastoma, ependymoma, as well as neuroectodermal and pineal tumour.

Tumours of the male reproductive organs include, but are not limited to, prostate and testicular cancer.

Tumours of the female reproductive organs include, but are not limited to, endometrial, cervical, ovarian, vaginal, and vulvar cancer, as well as sarcoma of the uterus.

Examples of ovarian cancer include, but are not limited to serous tumour, endometrioid tumour, mucinous cystadenocarcinoma, granulosa cell tumour, Sertoli-Leydig cell tumour and arrhenoblastoma.

Examples of cervical cancer include, but are not limited to squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, neuroendocrine tumour, glassy cell carcinoma and villoglandular adenocarcinoma.

Tumours of the digestive tract include, but are not limited to, anal, colon, colorectal, esophageal, gallbladder, gastric, pancreatic, rectal, small-intestine, and salivary gland cancers.

Examples of esophageal cancer include, but are not limited to esophageal cell carcinomas and adenocarcinomas, as well as squamous cell carcinomas, leiomyosarcoma, malignant melanoma, rhabdomyosarcoma and lymphoma.

Examples of gastric cancer include, but are not limited to intestinal type and diffuse type gastric adenocarcinoma.

Examples of pancreatic cancer include, but are not limited to ductal adenocarcinoma, adenosquamous carcinomas and pancreatic endocrine tumours.

Tumours of the urinary tract include, but are not limited to, bladder, penile, kidney, renal pelvis, ureter, urethral and human papillary renal cancers.

Examples of kidney cancer include, but are not limited to renal cell carcinoma, urothelial cell carcinoma, juxtaglomerular cell tumour (reninoma), angiomyolipoma, renal oncocytoma, Bellini duct carcinoma, clear-cell sarcoma of the kidney, mesoblastic nephroma and Wilms' tumour.

Examples of bladder cancer include, but are not limited to transitional cell carcinoma, squamous cell carcinoma, adenocarcinoma, sarcoma and small cell carcinoma.

Eye cancers include, but are not limited to, intraocular melanoma and retinoblastoma.

Examples of liver cancers include, but are not limited to, hepatocellular carcinoma (liver cell carcinomas with or without fibrolamellar variant), cholangiocarcinoma (intrahepatic bile duct carcinoma), and mixed hepatocellular cholangiocarcinoma.

Skin cancers include, but are not limited to, squamous cell carcinoma, Kaposi's sarcoma, malignant melanoma, Merkel cell skin cancer, and non-melanoma skin cancer.

Head-and-neck cancers include, but are not limited to, squamous cell cancer of the head and neck, laryngeal, hypopharyngeal, nasopharyngeal, oropharyngeal cancer, salivary gland cancer, lip and oral cavity cancer and squamous cell.

Lymphomas include, but are not limited to, AIDS-related lymphoma, non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, Burkitt lymphoma, Hodgkin's disease, and lymphoma of the central nervous system.

Sarcomas include, but are not limited to, sarcoma of the soft tissue, osteosarcoma, malignant fibrous histiocytoma, lymphosarcoma, and rhabdomyosarcoma.

Leukemias include, but are not limited to, acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and hairy cell leukemia.

The term “treating” or “treatment” as stated throughout this document is used conventionally, for example the management or care of a subject for the purpose of combating, alleviating, reducing, relieving, improving the condition of a disease or disorder, such as a carcinoma.

The compounds of the present invention can be used in particular in therapy and prevention, i.e. prophylaxis, of tumour growth and metastases, especially in solid tumours of all indications and stages with or without pre-treatment of the tumour growth.

Generally, the use of chemotherapeutic agents and/or anti-cancer agents in combination with a compound or pharmaceutical composition of the present invention will serve to:

1. yield better efficacy in reducing the growth of a tumour or even eliminate the tumour as compared to administration of either agent alone, 2. provide for the administration of lesser amounts of the administered chemotherapeutic agents, 3. provide for a chemotherapeutic treatment that is well tolerated in the patient with fewer deleterious pharmacological complications than observed with single agent chemotherapies and certain other combined therapies, 4. provide for treating a broader spectrum of different cancer types in mammals, especially humans, 5. provide for a higher response rate among treated patients, 6. provide for a longer survival time among treated patients compared to standard chemotherapy treatments, 7. provide a longer time for tumour progression, and/or 8. yield efficacy and tolerability results at least as good as those of the agents used alone, compared to known instances where other cancer agent combinations produce antagonistic effects.

In addition, the compounds of general formula (I) of the present invention can also be used in combination with radiotherapy and/or surgical intervention.

In a further embodiment of the present invention, the compounds of general formula (I) of the present invention are used in combination with radiation: i.e. radiation treatment sensitizes cancers to anti-tumor immune responses by induction of tumor cell death and subsequent presentation of tumor neoantigens to tumor-reactive Tcells. As DGKα is enhancing the antigen specific activation of T cells, the overall effect results in a much stronger cancer cell attack as compared to irradiation treatment alone.

Thus, the present invention also provides a method of killing a tumor, wherein conventional radiation therapy is employed previous to administering one or more of the compounds of the present invention.

The compounds of the present invention can be administered as the sole pharmaceutical agent or in combination with one or more other pharmaceutically active ingredients where the combination causes no unacceptable adverse effects. The present invention also covers such pharmaceutical combinations. For example, the compounds of the present invention can be combined with:

131I-chTNT, abarelix, abemaciclib, abiraterone, acalabrutinib, aclarubicin, adalimumab, ado-trastuzumab emtansine, afatinib, aflibercept, aldesleukin, alectinib, alemtuzumab, alendronic acid, alitretinoin, alpharadin, altretamine, amifostine, aminoglutethimide, hexyl aminolevulinate, amrubicin, amsacrine, anastrozole, ancestim, anethole dithiolethione, anetumab ravtansine, angiotensin II, antithrombin III, apalutamide, aprepitant, arcitumomab, arglabin, arsenic trioxide, asparaginase, atezolizumab, avelumab, axicabtagene ciloleucel, axitinib, azacitidine, basiliximab, belotecan, bendamustine, besilesomab, belinostat, bevacizumab, bexarotene, bicalutamide, bisantrene, bleomycin, blinatumomab, bortezomib, bosutinib, buserelin, brentuximab vedotin, brigatinib, busulfan, cabazitaxel, cabozantinib, calcitonine, calcium folinate, calcium levofolinate, capecitabine, capromab, carbamazepine carboplatin, carboquone, carfilzomib, carmofur, carmustine, catumaxomab, celecoxib, celmoleukin, cemiplimab, ceritinib, cetuximab, chlorambucil, chlormadinone, chlormethine, cidofovir, cinacalcet, cisplatin, cladribine, clodronic acid, clofarabine, cobimetinib, copanlisib, crisantaspase, crizotinib, cyclophosphamide, cyproterone, cytarabine, dacarbazine, dactinomycin, daratumumab, darbepoetin alfa, dabrafenib, dasatinib, daunorubicin, decitabine, degarelix, denileukin diftitox, denosumab, depreotide, deslorelin, dianhydrogalactitol, dexrazoxane, dibrospidium chloride, dianhydrogalactitol, diclofenac, dinutuximab, docetaxel, dolasetron, doxifluridine, doxorubicin, doxorubicin+estrone, dronabinol, durvalumab, eculizumab, edrecolomab, elliptinium acetate, elotuzumab, eltrombopag, enasidenib, endostatin, enocitabine, enzalutamide, epirubicin, epitiostanol, epoetin alfa, epoetin beta, epoetin zeta, eptaplatin, eribulin, erlotinib, esomeprazole, estradiol, estramustine, ethinylestradiol, etoposide, everolimus, exemestane, fadrozole, fentanyl, filgrastim, fluoxymesterone, floxuridine, fludarabine, fluorouracil, flutamide, folinic acid, formestane, fosaprepitant, fotemustine, fulvestrant, gadobutrol, gadoteridol, gadoteric acid meglumine, gadoversetamide, gadoxetic acid, gallium nitrate, ganirelix, gefitinib, gemcitabine, gemtuzumab, Glucarpidase, glutoxim, GM-CSF, goserelin, granisetron, granulocyte colony stimulating factor, histamine dihydrochloride, histrelin, hydroxycarbamide, I-125 seeds, lansoprazole, ibandronic acid, ibritumomab tiuxetan, ibrutinib, idarubicin, ifosfamide, imatinib, imiquimod, improsulfan, indisetron, incadronic acid, ingenol mebutate, inotuzumab ozogamicin, interferon alfa, interferon beta, interferon gamma, iobitridol, iobenguane (123I), iomeprol, ipilimumab, irinotecan, Itraconazole, ixabepilone, ixazomib, lanreotide, lansoprazole, lapatinib, lasocholine, lenalidomide, lenvatinib, lenograstim, lentinan, letrozole, leuprorelin, levamisole, levonorgestrel, levothyroxine sodium, lisuride, lobaplatin, lomustine, lonidamine, lutetium Lu 177 dotatate, masoprocol, medroxyprogesterone, megestrol, melarsoprol, melphalan, mepitiostane, mercaptopurine, mesna, methadone, methotrexate, methoxsalen, methylaminolevulinate, methylprednisolone, methyltestosterone, metirosine, midostaurin, mifamurtide, miltefosine, miriplatin, mitobronitol, mitoguazone, mitolactol, mitomycin, mitotane, mitoxantrone, mogamulizumab, molgramostim, mopidamol, morphine hydrochloride, morphine sulfate, mvasi, nabilone, nabiximols, nafarelin, naloxone+pentazocine, naltrexone, nartograstim, necitumumab, nedaplatin, nelarabine, neratinib, neridronic acid, netupitant/palonosetron, nivolumab, pentetreotide, nilotinib, nilutamide, nimorazole, nimotuzumab, nimustine, nintedanib, niraparib, nitracrine, nivolumab, obinutuzumab, octreotide, ofatumumab, olaparib, olaratumab, omacetaxine mepesuccinate, omeprazole, ondansetron, oprelvekin, orgotein, orilotimod, osimertinib, oxaliplatin, oxycodone, oxymetholone, ozogamicine, p53 gene therapy, paclitaxel, palbociclib, palifermin, palladium-103 seed, palonosetron, pamidronic acid, panitumumab, panobinostat, pantoprazole, pazopanib, pegaspargase, PEG-epoetin beta (methoxy PEG-epoetin beta), pembrolizumab, pegfilgrastim, peginterferon alfa-2b, pemetrexed, pentazocine, pentostatin, peplomycin, Perflubutane, perfosfamide, Pertuzumab, picibanil, pilocarpine, pirarubicin, pixantrone, plerixafor, plicamycin, poliglusam, polyestradiol phosphate, polyvinylpyrrolidone+sodium hyaluronate, polysaccharide-K, pomalidomide, ponatinib, porfimer sodium, pralatrexate, prednimustine, prednisone, procarbazine, procodazole, propranolol, quinagolide, rabeprazole, racotumomab, radium-223 chloride, radotinib, raloxifene, raltitrexed, ramosetron, ramucirumab, ranimustine, rasburicase, razoxane, refametinib, regorafenib, ribociclib, risedronic acid, rhenium-186 etidronate, rituximab, rolapitant, romidepsin, romiplostim, romurtide, rucaparib, samarium (153Sm) lexidronam, sargramostim, sarilumab, satumomab, secretin, siltuximab, sipuleucel sizofiran, sobuzoxane, sodium glycididazole, sonidegib, sorafenib, stanozolol, streptozocin, sunitinib, talaporfin, talimogene laherparepvec, tamibarotene, tamoxifen, tapentadol, tasonermin, teceleukin, technetium (99mTc) nofetumomab merpentan, 99mTc-HYNIC-[Tyr3]-octreotide, tegafur, tegafur+gimeracil+oteracil, temoporfin, temozolomide, temsirolimus, teniposide, testosterone, tetrofosmin, thalidomide, thiotepa, thymalfasin, thyrotropin alfa, tioguanine, tisagenlecleucel, tislelizumab, tocilizumab, topotecan, toremifene, tositumomab, trabectedin, trametinib, tramadol, trastuzumab, trastuzumab emtansine, treosulfan, tretinoin, trifluridine+tipiracil, trilostane, triptorelin, trametinib, trofosfamide, thrombopoietin, tryptophan, ubenimex, valatinib, valrubicin, vandetanib, vapreotide, vemurafenib, vinblastine, vincristine, vindesine, vinflunine, vinorelbine, vismodegib, vorinostat, vorozole, yttrium-90 glass microspheres, zinostatin, zinostatin stimalamer, zoledronic acid, zorubicin.

The compounds of the invention can further be combined with other reagents targeting the immune system, such as immune checkpoint inhibitors, e.g. aPD-1/-L1 axis antagonists. PD-1, along with its ligands PD-L1 and PD-L2, function as negative regulators of T cell activation. DGKα suppresses immune cell function. PD-L1 is overexpressed in many cancers and overexpression of PD-1 often occurs concomitantly in tumor infiltrating T cells. This results in attenuation of T cell activation and evasion of immune surveillance, which contributes to impaired antitumor immune responses. (Keir M E et al. (2008) Annu. Rev. Immunol. 26:677).

In accordance with a further aspect, the present invention covers combinations comprising one or more of the compounds of general formula (I), as described herein, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures of same, and one or more immune checkpoint inhibitors. Preferably, the immune checkpoint inhibitor is a aPD-1/-L1 axis antagonist.

The compounds of the invention can further be combined with chimeric antigen receptor T cells (CAR-T cells), such as Axicabtagen-Ciloleucel or Tisagenlecleucel. The activity of CAR-T cells can be suppressed by the tumor micro environment (TME). Knock out of DGKα by techniques such as Crispr had been shown to enhance CAR-T cell activity in a suppressive TME (Mol. Cells 2018; 41(8): 717-723).

In accordance with a further aspect, the present invention covers combinations comprising one or more compounds of general formula (I), as described herein, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures of same, with chimeric antigen receptor T cells, (CAR-T cells), CAR-NKT cells or CAR-NK cells.

Preferably, the chimeric antigen receptor T cells (CAR-T cells) are Axicabtagen-Ciloleucel or Tisagenlecleucel.

The present invention further provides the use of the compounds according to the invention for expansion of T cells including CAR-T and tumor infiltrated lymphocytes ex-vivo. Inhibition of DGKα was shown to reactivate ex vivo treated T cells (Prinz et al. (2012) J. Immunol).

In accordance with a further aspect, the present invention covers compounds of general formula (I), as described herein, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures of same, for use in the expansion of T cells including CAR-T cells, CAR-NKT cells or CAR-NK cells and tumor infiltrated lymphocytes ex-vivo.

Hence, the present invention also relates to the use of the compounds according to the invention for the expansion of T cells, including CAR-T cell, CAR-NKT cells or CAR-NK cells and tumor infiltrated lymphocytes, ex-vivo.

The present invention also comprises an ex-vivo method for the expansion of T cells, including CAR-T cells, CAR-NKT cells or CAR-NK cells and tumor infiltrated lymphocytes, contacting said T cells with compounds according to the invention.

The compounds of the invention can further be combined with inhibitors of DGKζ, such as those inhibitors of DGKζ disclosed in WO2020/006016 and WO2020/006018. As DGKζ in T cells operates in a similar fashion as DGKα, a dual inhibition profoundly enhances T cell effector functions compared with cells with deletion of either DGK isoform alone or wild-type cells (Riese et al., Cancer Res 2013, 73(12), 3566).

Compounds of the present invention can be utilized to inhibit, block, reduce or decrease DGKα activity resulting in the modulation of dysregulated immune responses e.g. to block immunosuppression and increase immune cell activation and infiltration in the context of cancer and cancer immunotherapy that will eventually lead to reduction of tumour growth.

This method comprises administering to a mammal in need thereof, including a human, an amount of a compound of this invention, or a pharmaceutically acceptable salt, isomer, polymorph, metabolite, hydrate, solvate or ester thereof; which is effective to treat the disorder. The present invention also provides methods of treating a variety of other disorders wherein DGKα is involved such as, but not limited to, disorders with dysregulated immune responses, inflammation, vaccination for infection & cancer, viral infections, obesity and diet-induced obesity, adiposity, metabolic disorders, fibrotic disorders, cardiac diseases and lymphoproliferative disorders.

These disorders have been well characterized in humans, but also exist with a similar etiology in other mammals, and can be treated by administering pharmaceutical compositions of the present invention.

In accordance with a further aspect, the present invention covers compounds of general formula (I), as described supra, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures of same, for use in the treatment or prophylaxis of diseases, in particular cancer or conditions with dysregulated immune responses or other disorders associated with aberrant DGKα signaling.

The pharmaceutical activity of the compounds according to the invention can be explained by their activity as DGKα inhibitors.

In accordance with a further aspect, the present invention covers the use of compounds of general formula (I), as described supra, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures of same, for the treatment or prophylaxis of diseases, in particular cancer or conditions with dysregulated immune responses or other disorders associated with aberrant DGKα signaling, particularly liquid and solid tumours.

In accordance with a further aspect, the present invention covers the compounds of general formula (I), as described supra, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures of same, for the use of treatment or prophylaxis of diseases, in particular cancer or conditions with dysregulated immune responses or other disorders associated with aberrant DGKα signaling, particularly liquid and solid tumours.

In accordance with a further aspect, the present invention covers the use of compounds of general formula (I), as described supra, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures of same, in a method of treatment or prophylaxis of diseases, in particular cancer or conditions with dysregulated immune responses or other disorders associated with aberrant DGKα signaling, particularly liquid and solid tumours.

In accordance with a further aspect, the present invention covers use of a compound of general formula (I), as described supra, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures of same, for the preparation of a pharmaceutical composition, preferably a medicament, for the prophylaxis or treatment of diseases, in particular cancer or conditions with dysregulated immune responses or other disorders associated with aberrant DGKα signaling, particularly liquid and solid tumours.

In accordance with a further aspect, the present invention covers a method of treatment or prophylaxis of diseases, in particular cancer or conditions with dysregulated immune responses or other disorders associated with aberrant DGKα signaling, particularly liquid and solid tumours, using an effective amount of a compound of general formula (I), as described supra, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures of same.

In accordance with a further aspect, the present invention covers pharmaceutical compositions, in particular a medicament, comprising a compound of general formula (I), as described supra, or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, a salt thereof, particularly a pharmaceutically acceptable salt, or a mixture of same, and one or more excipients), in particular one or more pharmaceutically acceptable excipient(s). Conventional procedures for preparing such pharmaceutical compositions in appropriate dosage forms can be utilized.

The present invention furthermore covers pharmaceutical compositions, in particular medicaments, which comprise at least one compound according to the invention, conventionally together with one or more pharmaceutically suitable excipients, and to their use for the above mentioned purposes.

It is possible for the compounds according to the invention to have systemic and/or local activity. For this purpose, they can be administered in a suitable manner, such as, for example, via the oral, parenteral, pulmonary, nasal, sublingual, lingual, buccal, rectal, vaginal, dermal, transdermal, conjunctival, otic route or as an implant or stent.

For these administration routes, it is possible for the compounds according to the invention to be administered in suitable administration forms.

For oral administration, it is possible to formulate the compounds according to the invention to dosage forms known in the art that deliver the compounds of the invention rapidly and/or in a modified manner, such as, for example, tablets (uncoated or coated tablets, for example with enteric or controlled release coatings that dissolve with a delay or are insoluble), orally-disintegrating tablets, films/wafers, films/lyophylisates, capsules (for example hard or soft gelatine capsules), sugar-coated tablets, granules, pellets, powders, emulsions, suspensions, aerosols or solutions. It is possible to incorporate the compounds according to the invention in crystalline and/or amorphised and/or dissolved form into said dosage forms.

Parenteral administration can be effected with avoidance of an absorption step (for example intravenous, intraarterial, intracardial, intraspinal or intralumbal) or with inclusion of absorption (for example intramuscular, subcutaneous, intracutaneous, percutaneous or intraperitoneal). Administration forms which are suitable for parenteral administration are, inter alia, preparations for injection and infusion in the form of solutions, suspensions, emulsions, lyophylisates or sterile powders.

Examples which are suitable for other administration routes are pharmaceutical forms for inhalation [inter alia powder inhalers, nebulizers], nasal drops, nasal solutions, nasal sprays; tablets/films/wafers/capsules for lingual, sublingual or buccal administration; suppositories; eye drops, eye ointments, eye baths, ocular inserts, ear drops, ear sprays, ear powders, ear-rinses, ear tampons; vaginal capsules, aqueous suspensions (lotions, mixturae agitandae), lipophilic suspensions, emulsions, ointments, creams, transdermal therapeutic systems (such as, for example, patches), milk, pastes, foams, dusting powders, implants or stents.

The compounds according to the invention can be incorporated into the stated administration forms. This can be effected in a manner known per se by mixing with pharmaceutically suitable excipients. Pharmaceutically suitable excipients include, inter alia,

fillers and carriers (for example cellulose, microcrystalline cellulose (such as, for example, Avicel), lactose, mannitol, starch, calcium phosphate (such as, for example, Di-Cafos®)), ointment bases (for example petroleum jelly, paraffins, triglycerides, waxes, wool wax, wool wax alcohols, lanolin, hydrophilic ointment, polyethylene glycols), bases for suppositories (for example polyethylene glycols, cacao butter, hard fat), solvents (for example water, ethanol, isopropanol, glycerol, propylene glycol, medium chain-length triglycerides fatty oils, liquid polyethylene glycols, paraffins), surfactants, emulsifiers, dispersants or wetters (for example sodium dodecyl sulfate), lecithin, phospholipids, fatty alcohols (such as, for example, Lanette®), sorbitan fatty acid esters (such as, for example, Span®), polyoxyethylene sorbitan fatty acid esters (such as, for example, Tween®), polyoxyethylene fatty acid glycerides (such as, for example, Cremophor®), polyoxethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, glycerol fatty acid esters, poloxamers (such as, for example, Pluronic®), buffers, acids and bases (for example phosphates, carbonates, citric acid, acetic acid, hydrochloric acid, sodium hydroxide solution, ammonium carbonate, trometamol, triethanolamine), isotonicity agents (for example glucose, sodium chloride), adsorbents (for example highly-disperse silicas), viscosity-increasing agents, gel formers, thickeners and/or binders (for example polyvinylpyrrolidone, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, carboxymethylcellulose-sodium, starch, carbomers, polyacrylic acids (such as, for example, Carbopol®); alginates, gelatine), disintegrants (for example modified starch, carboxymethylcellulose-sodium, sodium starch glycolate (such as, for example, Explotab), cross-linked polyvinylpyrrolidone, croscarmellose-sodium (such as, for example, AcDiSol®)), flow regulators, lubricants, glidants and mould release agents (for example magnesium stearate, stearic acid, talc, highly-disperse silicas (such as, for example, Aerosil®)), coating materials (for example sugar, shellac) and film formers for films or diffusion membranes which dissolve rapidly or in a modified manner (for example polyvinylpyrrolidones (such as, for example, Kollidon®), polyvinyl alcohol, hydroxypropylmethylcellulose, hydroxypropylcellulose, ethylcellulose, hydroxypropylmethylcellulose phthalate, cellulose acetate, cellulose acetate phthalate, polyacrylates, polymethacrylates such as, for example, Eudragit®)), capsule materials (for example gelatine, hydroxypropylmethylcellulose), synthetic polymers (for example polylactides, polyglycolides, polyacrylates, polymethacrylates (such as, for example, Eudragit®), polyvinylpyrrolidones (such as, for example, Kollidon®), polyvinyl alcohols, polyvinyl acetates, polyethylene oxides, polyethylene glycols and their copolymers and block copolymers), plasticizers (for example polyethylene glycols, propylene glycol, glycerol, triacetine, triacetyl citrate, dibutyl phthalate), penetration enhancers, stabilisers (for example antioxidants such as, for example, ascorbic acid, ascorbyl palmitate, sodium ascorbate, butylhydroxyanisole, butylhydroxytoluene, propyl gallate), preservatives (for example parabens, sorbic acid, thiomersal, benzalkonium chloride, chlorhexidine acetate, sodium benzoate), colourants (for example inorganic pigments such as, for example, iron oxides, titanium dioxide), flavourings, sweeteners, flavour- and/or odour-masking agents.

The present invention furthermore relates to a pharmaceutical composition which comprise at least one compound according to the invention, conventionally together with one or more pharmaceutically suitable excipient(s), and to their use according to the present invention.

In accordance with another aspect, the present invention covers pharmaceutical combinations, in particular medicaments, comprising at least one compound of general formula (I) of the present invention and at least one or more further active ingredients, in particular for the treatment and/or prophylaxis of cancer or conditions with dysregulated immune responses or other disorders associated with aberrant DGKα signaling, particularly liquid and solid tumours.

Particularly, the present invention covers a pharmaceutical combination, which comprises:

one or more first active ingredients, in particular compounds of general formula (I) as defined supra, and one or more further active ingredients, in particular in particular immune checkpoint inhibitors.

The term “combination” in the present invention is used as known to persons skilled in the art, it being possible for said combination to be a fixed combination, a non-fixed combination or a kit-of-parts.

A “fixed combination” in the present invention is used as known to persons skilled in the art and is defined as a combination wherein, for example, a first active ingredient, such as one or more compounds of general formula (I) of the present invention, and a further active ingredient are present together in one unit dosage or in one single entity. One example of a “fixed combination” is a pharmaceutical composition wherein a first active ingredient and a further active ingredient are present in admixture for simultaneous administration, such as in a formulation. Another example of a “fixed combination” is a pharmaceutical combination wherein a first active ingredient and a further active ingredient are present in one unit without being in admixture.

A non-fixed combination or “kit-of-parts” in the present invention is used as known to persons skilled in the art and is defined as a combination wherein a first active ingredient and a further active ingredient are present in more than one unit. One example of a non-fixed combination or kit-of-parts is a combination wherein the first active ingredient and the further active ingredient are present separately. It is possible for the components of the non-fixed combination or kit-of-parts to be administered separately, sequentially, simultaneously, concurrently or chronologically staggered.

Based upon standard laboratory techniques known to evaluate compounds useful for the treatment of cancer or conditions with dysregulated immune responses or other disorders associated with aberrant DGKα signaling, by standard toxicity tests and by standard pharmacological assays for the determination of treatment of the conditions identified above in mammals, and by comparison of these results with the results of known active ingredients or medicaments that are used to treat these conditions, the effective dosage of the compounds of the present invention can readily be determined for treatment of each desired indication. The amount of the active ingredient to be administered in the treatment of one of these conditions can vary widely according to such considerations as the particular compound and dosage unit employed, the mode of administration, the period of treatment, the age and sex of the patient treated, and the nature and extent of the condition treated.

The total amount of the active ingredient to be administered will generally range from about 0.001 mg/kg to about 200 mg/kg body weight per day, and preferably from about 0.01 mg/kg to about 20 mg/kg body weight per day. Clinically useful dosing schedules will range from one to three times a day dosing to once every four weeks dosing. In addition, it is possible for “drug holidays”, in which a patient is not dosed with a drug for a certain period of time, to be beneficial to the overall balance between pharmacological effect and tolerability. It is possible for a unit dosage to contain from about 0.5 mg to about 1500 mg of active ingredient, and can be administered one or more times per day or less than once a day. The average daily dosage for administration by injection, including intravenous, intramuscular, subcutaneous and parenteral injections, and use of infusion techniques will preferably be from 0.01 to 200 mg/kg of total body weight. The average daily rectal dosage regimen will preferably be from 0.01 to 200 mg/kg of total body weight. The average daily vaginal dosage regimen will preferably be from 0.01 to 200 mg/kg of total body weight. The average daily topical dosage regimen will preferably be from 0.1 to 200 mg administered between one to four times daily. The transdermal concentration will preferably be that required to maintain a daily dose of from 0.01 to 200 mg/kg. The average daily inhalation dosage regimen will preferably be from 0.01 to 100 mg/kg of total body weight.

Of course the specific initial and continuing dosage regimen for each patient will vary according to the nature and severity of the condition as determined by the attending diagnostician, the activity of the specific compound employed, the age and general condition of the patient, time of administration, route of administration, rate of excretion of the drug, drug combinations, and the like. The desired mode of treatment and number of doses of a compound of the present invention or a pharmaceutically acceptable salt or ester or composition thereof can be ascertained by those skilled in the art using conventional treatment tests.

Syntheses of Compounds

The compounds according to the invention of general formula (I) can be prepared according to the following schemes 1-19. The schemes and procedures described below illustrate synthetic routes to the compounds of general formula (I) of the invention and are not intended to be limiting. It is clear to the person skilled in the art that the order of transformations as exemplified in schemes 1-19 can be modified in various ways. The order of transformations exemplified in these schemes is therefore not intended to be limiting. In addition, interconversion of any of the substituents, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 or R 8 , can be achieved before and/or after the exemplified transformations. These modifications can be such as the introduction of protecting groups, cleavage of protecting groups, reduction or oxidation of functional groups, halogenation, metalation or substitution known to the person skilled in the art. These transformations include those which introduce a functionality which allows for further interconversion of substituents. Appropriate protecting groups and their introduction and cleavage are well-known to the person skilled in the art (see for example T. W. Greene and P. G. M. Wuts in Protective Groups in Organic Synthesis, 4 th edition, Wiley 2006). Specific examples are described in the subsequent paragraphs.

Isatoic anhydrides 1 are widely available from commercial suppliers or described in the literature. For example the isatoic anhydrides 1 can be prepared from 2-aminobenzoic acids 2 (in analogy to the procedure in Tetrahedron Lett. 2014, 55, 3607-3609) using triphosgene in an organic solvent such as THF or 1,4-dioxane or (in analogy to the procedure in Tetrahedron Lett. 2013, 54, 6897-6899) using di-tert-butyl dicarbonate and a base such as NaOH followed by treatment with 2-chloromethylpyridinium iodide and subsequent acidic workup (Scheme 1).

Alternatively, preparation of the isatoic anhydrides 1 can also be achieved (for example in analogy to the procedure in J. Org. Chem. 2014, 79, 4196-4200) using Pd-catalyzed oxidative double carbonylation of o-iodoanilines 3.

The obtained isatoic anhydrides 1 can then be alkylated at the nitrogen to obtain compounds of the general formula 4. Typically an alkylating agent such as for example an alkylbromide, alkyliodide or alkylsulfonate, a base such as disopropylethylamine, K 2 CO 3 or KOtBu in an organic solvent is used.

Alternatively the alkylated isatoic anhydrides 4 can be prepared directly from secondary anilines 5 (in analogy to the procedure in Tetrahedron Lett. 2014, 55, 3607-3609) using triphosgene in an organic solvent such as THF or 1,4-dioxane or (in analogy to the procedure in Tetrahedron Lett. 2013, 54, 6897-6899) using di-tert-butyl dicarbonate and a base such as NaOH followed by treatment with 2-chloromethylpyridinium iodide and subsequent acidic workup.

Scheme 1: Route for the preparation of compounds of the general formula 4, wherein R 3 , R 4 , R 5 and R 8 have the meaning as given for the general formula (I), supra.

Isatoic anhydrides 4 can be converted to the corresponding quinolones 7 using ethyl acetate derivatives 6 such as for example ethylcyano acetate (for R 1 ═CN), a base such as for example triethylamine in an organic solvent such as for example THF (Scheme 2).

Hydroxy quinolones 7 can be converted to the corresponding halides 8 using for example phosphoryl chloride (X=chloro) or phosphoryl bromide (Hal=bromo).

Scheme 2: Route for the preparation of compounds of the general formula 8, wherein R 1 , R 3 , R 4 , R 5 and R 8 have the meaning as given for the general formula (I), supra and X has the meaning as chloro or bromo.

Halides of the general formula 8 can be reacted with amines 9 to yield compounds of the general formula 10. Typically the reaction is performed in an organic solvent such as for example isopropanol and a base such as for example diisopropylethylamine or triethylamine. Many amines of the general formula 9 are commercially available or described in the literature (Scheme 3).

Scheme 3: Route for the preparation of compounds of general formula 10, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and n have the meaning as given for the general formula (I), supra and X has the meaning as chloro or bromo.

Nitriles of the general formula 11 can be converted to the amides of the general formula 12. Typically the reaction is performed with palladium(II)acetate and acetaldoxime in an organic solvent such as for example ethanol (see for example J. Med. Chem. 2016, 59, 6281ff, Degorce et al.) (Scheme 4).

Scheme 4: Route for the preparation of compounds of general formula 12, wherein R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and n have the meaning as given for the general formula (I), supra.

Compounds of the general formula 15 can be formed from compounds of the general formula 13 and compounds of the general formula 14 (which are commercially available or described in the literature) by a light promoted, nickel catalyzed reaction as described in J. Am. Chem. Soc. 2016, 138, 8084-8087 and Org. Lett. 2016, 18, 4012, and known to one skilled in the art (Scheme 5). Preferentially, compounds of general formula 13 are reacted with compounds of the general formula 14 in the presence of a photoredox catalyst such as Ir(4′,6′-dF-5-CF 3 -ppy) 2 (4,4′-dtbbpy)PF 6 , a nickel precatalyst such as nickel II chloride dimethoxyethane adduct, and a ligand such as 4,4′-Di-tert-butyl-2,2′-bipyridine, with a base such as sodium carbonate, 2,6-dimethoxypyridine, 2,2,6,6-tertramethylpiperidine or lithium carbonate, with additives such as tris(trimehylsilyl)silane, in a solvent or solvent mixture such as dimethoxyethane, N,N-dimethylacetamide/trifluorotoluene or 1,3-dimethyl-2-imidazolidinone/trifluorotoluene, irradiated with light generated by two 40 W Kessil LED aquarium lights, at a temperature between 0° C. and the boiling point of the respective solvent. Ideally the reaction is performed between room temperature and 35° C. to afford compounds of ge neral formula 15.

Scheme 5: Route for the preparation of compounds of general formula 15, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and n have the meaning as given for the general formula (I), supra.

Isatoic anhydrides 4 can be converted to the corresponding quinolones 16 using diethylmalonate, a base such as for example triethylamine in an organic solvent such as for example THF (Scheme 6).

Hydroxy quinolones 16 can be converted to the corresponding halides 17 using for example phosphoryl chloride (X=chloro) or phosphoryl bromide (X=bromo).

Halides of the general formula 17 can be reacted with amines 9 to yield compounds of the general formula 18. Typically the reaction is performed in an organic solvent such as for example isopropanol and with a base such as for example diisopropylethylamine.

Scheme 6: Route for the preparation of compounds of general formula 18, wherein R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and n have the meaning as given for the general formula (I), supra and X has the meaning as chloro or bromo.

Esters of the general formula 18 can be converted to the corresponding carboxylic acids 19 using classical ester hydrolysis conditions. Typically LiOH, KOH or NaOH in water/ethanol/THF at elevated temperatures is used for this reaction (Scheme 7).

The carboxylic acids of the general formula 19 and amines of general formula 20 can be converted to the corresponding amides 21 using standard amide forming reaction known to the person skilled in the art. For a review see for example Chem. Rev. 2011, 111, 6557-6602. Compounds of general formula 20 are commercially available or described in the literature.

Scheme 7: Route for the preparation of compounds of general formula 21, wherein R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and n have the meaning as given for the general formula (I), supra, and the amine of general formula 20 has the meaning of NH 3 , H 2 NCH 3 , HNC 2 H 5 or HN(CH 3 ) 2 .

Compounds of the general formula 26 can be prepared from ketones 22 via formation of the corresponding sulfonates 23 followed by a Suzuki coupling leading to compounds of the general formula 24 (Scheme 8). Subsequent hydrogenation to compounds of the general formula 25 followed by cleavage of the tertbutyloxycarbonyl protecting group leads to amines of the general formula 26. All reaction types are known to the person skilled in the art. Instead of a tertbutyloxycarbonyl other suitable protecting groups can be used for this sequence known to the skilled person (see for example P. G. M. Wuts and T. W. Greene in “Protective Groups in Organic Synthesis”, 4 th edition, Wiley 2006). Compounds of general formula 22 are commercially available or described in the literature.

Typical conditions for the conversion of 22 to compounds of the general formula 23 are known to the skilled person. For example, 22 is reacted with a sulfonylation reagent such as for example nonafluorobutanesulfonyl fluoride (for LG-O=[(nonafluorobutyl)sulfonyl]oxy or N,N-phenylbistrifluoromethane-sulfon imide (for LG-O=[(trifluoromethyl)sulfonyl]oxy, a base such as bis-(trimethylsilyl)-lithiumamid in an organic solvent such as THF (see for example procedure in WO2017/158619).

Typical conditions for the Suzuki reaction converting compounds of the general formula 23 to compounds of the general formula 24 are known to the skilled person. For example, 23 can be reacted with a boronic acid derivative R 2 —B(OR) 2 to give a compound of formula 24. The boronic acid derivative may be a boronic acid (R═—H) or an ester of the boronic acid, e.g. its isopropyl ester (R═—CH(CH 3 ) 2 ), preferably an ester derived from pinacol in which the boronic acid intermediate forms a 2-aryl-4, 4, 5,5-tetramethyl-1,3,2-dioxaborolane (R—R═—C(CH 3 ) 2 —C(CH 2 ) 2 —). The coupling reaction is catalyzed by palladium catalysts, e.g. by Pd(0) catalysts such as tetrakis(triphenylphosphine)palladium(0) [Pd(PPh 3 ) 4 ], tris(dibenzylideneacetone)di-palladium(0) [Pd 2 (dba) 3 ], or by Pd(II) catalysts such as dichlorobis(triphenylphosphine)-palladium(II) [Pd(PPh 3 ) 2 Cl 2 ], palladium(II) acetate and triphenylphosphine or 4,5-bis(diphenylphosphosphino)-9,9-dimethylxanthene as a ligand or by [1,1′-bis(diphenylphosphino)ferrocene]palladium dichloride. The reaction is preferably carried out in a mixture of a solvent such as 1,2-dimethoxyethane, dioxane, DMF, DME, THF, or isopropanol with water and in the presence of a base like potassium carbonate, sodium bicarbonate or potassium phosphate. For a review see D. G. Hall, Boronic Acids, 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim, ISBN 3-527-30991-8 and references cited therein). The reaction is performed at temperatures ranging from room temperature (i.e. approx. 20° C.) to the boiling point of the respective solvent. Further on, the reaction can be performed at temperatures above the boiling point using pressure tubes and a microwave oven. The reaction is preferably completed after 1 to 36 hours of reaction time.

Typical conditions for the hydrogenation reaction converting compounds of the general formula 24 to compounds of the general formula 25 are known to the skilled person. For example, 24 can be reacted with hydrogen and a catalyst such as 10% palladium on activated carbon in an organic solvent such as methanol or ethanol (see for example Bioorganic and medicinal chemistry letters, 2000, 10, 1625-1628).

Compounds of the general formula 26 can be prepared from the Boc protected amines 25 via removal of the tertbutyloxycarbonyl protecting group under acidic conditions (for example with trifluoroacetic acid or hydrochloric acid) known to the person skilled in the art. Instead of a tertbutyloxycarbonyl other suitable protecting groups can be used for this sequence known to the skilled person (see for example P. G. M. Wuts and T. W. Greene in “Protective Groups in Organic Synthesis”, 4 th edition, Wiley 2006).

Scheme 8: Route for the preparation of compounds of general formula 26, wherein R 2 , R 6 and n have the meaning as given for the general formula (I), supra and LG-O has the meaning of a sulfonyloxy leaving group such as for example [(trifluoromethyl)sulfonyl]oxy or [(nonafluoro-butyl)sulfonyl]oxy.

Alternatively compounds of the general formula 26 can be prepared from ketones 22 via a Grignard type reaction (via compounds of general formula 27) known to the skilled person followed by reductive removal of the hydroxyl group (via compounds of general formula 28) and removal of the tertbutyloxycarbonyl protecting group under acidic conditions (for example with trifluoroacetic acid or hydrochloric acid) known to the person skilled in the art (Scheme 9). Instead of a tertbutyloxycarbonyl other suitable protecting groups can be used for this sequence known to the skilled person (see for example P. G. M. Wuts and T. W. Greene in “Protective Groups in Organic Synthesis”, 4 th edition, Wiley 2006). Compounds of general formula 22 are commercially available or described in the literature.

For example, the compounds of the general formula 22 can be reacted with an organometallic reagent R 2 -[Metal] such as for example [Metal]=MgBr or MgCl or Li in an organic solvent such as THF or diethyl ether to yield compounds of the general formula 27 (see for example procedure in Bioorganic and Medicinal Chemistry Letters, 2012, 22, 2560-2564).

In a subsequent reaction hydroxyl compounds of the general formula 27 can be converted to compounds of the general formula 28. Procedures are known to the skilled person. For example triethylsilane, trifluoroacetic acid in an organic solvent such as dichloromethane (see for example procedures in US2005/9838) or hydrogenation conditions such as hydrogen on 10% Pd/C in an alcohol such as for example methanol (see for example WO2011/70080) can be used.

In a subsequent step compounds of the general formula 26 can be prepared from the Boc protected amines 28 via removal of the tertbutyloxycarbonyl protecting group under acidic conditions (for example with trifluoroacetic acid or hydrochloric acid) known to the person skilled in the art.

Scheme 9: Alternative route for the preparation of compounds of general formula 26, wherein R 2 , R 6 and n have the meaning as given for the general formula (I), supra.

Hydroxy compounds of the general formula 29 can be prepared from the Boc protected amines 27 via removal of the tertbutyloxycarbonyl protecting group under acidic conditions (for example with trifluoroacetic acid or hydrochloric acid) known to the person skilled in the art (Scheme 10). Instead of a tertbutyloxycarbonyl other suitable protecting groups can be used for this sequence known to the skilled person (see for example P. G. M. Wuts and T. W. Greene in “Protective Groups in Organic Synthesis”, 4 th edition, Wiley 2006).

Scheme 10: Route for the preparation of compounds of general formula 29, wherein R 2 , R 6 and n have the meaning as given for the general formula (I), supra.

Fluoro compounds of the general formula 31 can be prepared from alcohols 27 via a fluorination reaction followed by removal of the tertbutyloxycarbonyl protecting group under acidic conditions (for example with trifluoroacetic acid or hydrochloric acid) known to the person skilled in the art (Scheme 11). Instead of a tertbutyloxycarbonyl other suitable protecting groups can be used for this sequence known to the skilled person (see for example P. G. M. Wuts and T. W. Greene in “Protective Groups in Organic Synthesis”, 4 th edition, Wiley 2006). For example, the alcohols 27 can be reacted with a fluorination reagent such as diethylamino-sulfur trifluoride in an organic solvent such as dichloromethane to yield compounds of the general formula 30 (see for example procedure in WO2015/74064).

Scheme 11: Route for the preparation of compounds of general formula 31, wherein R 2 , R 6 and n have the meaning as given for the general formula (I), supra.

Compounds of the general formula 37 can be prepared from the corresponding esters of general formula 32 via arylation to compounds of the general formula 33 (Scheme 12). The esters 33 can be transformed to the corresponding aldehydes 34 and subsequently converted to olefins via an olefination reaction such as for example a Wittig type reaction. Compounds of the general formula 35 can then be hydrogenated to furnish compounds of the general formula 36. Removal of the tertbutyloxycarbonyl protecting group under acidic conditions (for example with trifluoroacetic acid or hydrochloric acid) furnishes compounds of general formula 37. Instead of a tertbutyloxycarbonyl other suitable protecting groups can be used for this sequence known to the skilled person (see for example P. G. M. Wuts and T. W. Greene in “Protective Groups in Organic Synthesis”, 4 th edition, Wiley 2006). All reactions of this sequence are known to the person skilled in the art. Compounds of general formula 32 are commercially available or described in the literature.

Typical conditions for the conversion of esters 32 to esters 33 are for example a base such as n-butyllithium and N-cyclohexyl-cyclohexanamine, a palladium catalyst such as tris(dibenzylideneacetone)dipalladium(0) chloroform complex and a ligand such as tris tert-butylphosphoniumtetrafluoroborate in an organic solvent such as toluene at elevated temperature (see for example procedure in WO2005/87752).

The conversion of the esters 33 to the aldehydes 34 is typically performed in a two-step procedure. In the first step the ester is reduced to the corresponding alcohols. Typical reaction conditions are a reducing agent such as for example LiAlH 4 /diethyl ether in an organic solvent such as for example THF or diethylether (see for example Journal of Medicinal Chemistry, 1994, 37, 113-124). In the second step the alcohols are oxidized to the corresponding aldehydes 34. Typical reaction conditions are for example Swern oxidation conditions such as DMSO, oxalyl chloride, a base such as trimethylamine in an organic solvent such as dichloromethane (see for example Journal of Medicinal Chemistry, 1994, 37, 113-124). Alternative reduction/oxidation conditions are known to the persons skilled in the art.

Typical reaction conditions for the conversion of aldehydes 34 to olefins 35 are known to the skilled person. For example, Wittig type reaction conditions such as an alkyltriphenylphosphonium bromide, a base such as sodium t-butanolate in an organic solvent such as tetrahydrofuran can be used (see for example Organic Letters, 2008, 10, 4561-4564).

Typical hydrogenation conditions for the conversion of olefins 35 to alkanes 36 are known to the skilled person. For example, hydrogen a catalyst such as 10% palladium on activated carbon in an organic solvent such as for example methanol or ethanol (see for example Bioorganic and Medicinal Chemistry, 2005, 13, 5623-5634).

Typical reaction conditions for the deprotection of the terlbutyloxycarbonyl protecting group in compounds of the general formula 36 are an acid such as for example trifluoroacetic acid or hydrochloric acid giving rise to compound of the general formula 37.

Scheme 12: Route for the preparation of compounds of general formula 37, wherein R 2 , R 6 and n have the meaning as given for the general formula (I), supra and R has the meaning of methyl, ethyl or tertbutyl and Y has the meaning of methyl and ethyl.

Alternatively compounds of the general formula 34 can be prepared from the corresponding nitriles 38 via arylation with bromides 14 to compounds of the general formula 39 and subsequent reduction of the nitriles 39 to aldehydes 34. All reactions are known to the person skilled in the art (Scheme 13).

Typical conditions for the conversion of nitriles 38 to nitriles 39 are for example a base such as sodium hexamethyldisilazane in an organic solvent such as toluene and subsequent addition of bromides 14, a palladium catalyst such as palladium diacetate and a ligand such as 2,2′-bis-(diphenylphosphino)-1,1′-binaphthyl in an organic solvent such as toluene (see for example Journal of the American Chemical Society, 2002, 124, 9330-9331).

Typical reaction conditions for the conversion of nitriles 38 to aldehydes 34 are a reducing agent such as diisobutylaluminium hydride in an organic solvent such as toluene (see for example Tetrahedron Letters, 2011, 52, 6058-6060).

Scheme 13: Route for the preparation of compounds of general formula 34, wherein R 2 , R 6 and n have the meaning as given for the general formula (I), supra.

Compounds of the general formula 43 can be prepared from aldehydes 34 via reduction of aldehydes 34 to their corresponding alcohols 35 and subsequent transformation to halides 41 (X=Br, I) (Scheme 14). Halides 41 can then be reduced to the compounds of the general formula 42. Removal of the tertbutyloxycarbonyl protecting group under acidic conditions (for example with trifluoroacetic acid or hydrochloric acid) furnishes compounds of general formula 43. Instead of a tertbutyloxycarbonyl other suitable protecting groups can be used for this sequence known to the skilled person (see for example P. G. M. Wuts and T. W. Greene in “Protective Groups in Organic Synthesis”, 4 th edition, Wiley 2006). All reactions of this sequence are known to the person skilled in the art.

In the first step the aldehydes 34 are reduced to the corresponding alcohols 40. Typical reaction conditions are a reducing agent such as for example LiAlH 4 /diethyl ether in an organic solvent such as for example THF or diethylether (see for example Journal of Medicinal Chemistry, 1994, 37, 113-124).

The reaction conditions for the conversion of alcohols of the general formula 40 to the corresponding halides 41 are known to the skilled person. For X=Br typically a bromination reagent such as N-Bromosuccinimide, triphenylphosphine in an organic solvent such as dichloromethane is used (see for example European Journal of Medicinal Chemistry, 2016, 109, 75-88 or procedures in WO2006/50506). For Hal=I typically an iodination reagent such as iodine, triphenylphosphine with or without a base such as 1H-imidazole in an organic solvent such as THF, dichloromethane or toluene is used (see for example Organic and Biomolecular Chemistry, 2014, 12, 783-794).

The reaction conditions for the conversion of halides 41 to the corresponding compounds of general formula 42 are known to the skilled person. Typically for example for Hal=bromo a hydrogen source such as sodium tetrahydroborate in an organic solvent such as dimethyl sulfoxide is used (see for example Organic Letters, 2006, 8, 3813-3816). Typically for example for X=iodo a hydrogen source such as hydrogen, a catalyst such as 10% palladium on activated carbon, a base such as triethylamine in an organic solvent such as methanol or ethanol is used (see for example procedure in patent US2015/232481).

Typical reaction conditions for the deprotection of the tertbutyloxycarbonyl protecting group in compounds of the general formula 42 are an acid such as for example trifluoroacetic acid or hydrochloric acid giving rise to compound of the general formula 43.

Scheme 14: Route for the preparation of compounds of general formula 43, wherein R 2 , R 6 and n have the meaning as given for the general formula (I), supra and X has the meaning of iodo or bromo.

Benzoxazoles of the general formula 46 can be prepared from carboxylic acids 44 and 2-aminophenols 45 via a condensation reaction followed by removal of the tertbutyloxycarbonyl protecting group under acidic conditions (for example with trifluoroacetic acid or hydrochloric acid) known to the person skilled in the art (Scheme 15). Instead of a tertbutyloxycarbonyl other suitable protecting groups can be used for this sequence known to the skilled person (see for example P. G. M. Wuts and T. W. Greene in “Protective Groups in Organic Synthesis”, 4 th edition, Wiley 2006). For example, the carboxylic acid 44 and the 2-aminophenols 45 can be reacted in polyphosphoric acid at elevated temperature to yield compounds of the general formula 46. Compounds of general formula 44 or 45 are commercially available or described in the literature.

Scheme 15: Route for the preparation of compounds of general formula 46, wherein R 6 , R 7 , and n have the meaning as given for the general formula (I), supra, p represents an integer of 0, 1, 2 or 3, and R′ represents a substituent of the heteroaryl group R 2 , as defined for the compounds of general formula (I), supra.

Benzothiazoles of the general formula 50 can be prepared from carboxylic acids 47 and 2-aminothiophenols 48 via a condensation reaction followed by removal of the tertbutyloxycarbonyl protecting group under acidic conditions (for example with trifluoroacetic acid or hydrochloric acid) known to the person skilled in the art (Scheme 16). Instead of a tertbutyloxycarbonyl other suitable protecting groups can be used for this sequence known to the skilled person (see for example P. G. M. Wuts and T. W. Greene in “Protective Groups in Organic Synthesis”, 4 th edition, Wiley 2006). For example, the carboxylic acid 47 and the 2-aminophenols 48 can be reacted with a base such as triethylamine or diisopropylethylamine and propylphosphonic anhydride (T3P) at elevated temperature to yield compounds of the general formula 49. Compounds of general formula 47 or 48 are commercially available or described in the literature.

Scheme 16: Route for the preparation of compounds of general formula 50, wherein R 6 , R 7 and n have the meaning as given for the general formula (I), supra, p represents an integer of 0, 1, 2 or 3, and R′ represents a substituent of the heteroaryl group R 2 , as defined for the compounds of general formula (I), supra.

Benzimidazoles of the general formula 52 can be prepared from carboxylic acids 44 and 1,2-diaminobenzoles 51 via a condensation known to the person skilled in the art (Scheme 17). For example, the carboxylic acid 44 and the 1,2-diaminobenzoles 51 can be reacted in polyphosphoric acid at elevated temperature to yield compounds of the general formula 52 (see for example European Journal of Medicinal Chemistry, 2017, 126, 24-35). Compounds of general formula 44 or 51 are commercially available or described in the literature.

Scheme 17: Route for the preparation of compounds of general formula 52, wherein R 6 , R 7 and n have the meaning as given for the general formula (I), supra, p represents an integer of 0, 1, 2 or 3, and R′ represents a substituent of the heteroaryl group R 2 , as defined for the compounds of general formula (I), supra.

Generally, the order of synthetic steps to generate inventive compounds of formula (I) or to build up the amine parts of inventive compounds of formula (I) such as 26 (Schemes 8, 9), 29

(Scheme 10), 31 (Scheme 11), 37 (Scheme 12), 43 (Scheme 14), 46 (Scheme 15), 50 (Scheme 16) or 52 (Scheme 17) could be exchanged. The synthetic conditions necessary to do transformations from 53 to 56 are usually comparable or could easily be adjusted by a person skilled in the art (Scheme 18 and 19). Precursors such as 53 or 57 can be generated according to the procedures described before (Schemes 3 and 6).

Scheme 18: Route for the preparation of compounds of general formula 56, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and n have the meaning as given for the general formula (I), supra.

Scheme 19: Route for the preparation of compounds of general formula 59, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and n have the meaning as given for the general formula (I), supra, p represents an integer of 0, 1, 2 or 3, and R′ represents a substituent of the heteroaryl group R 2 , as defined for the compounds of general formula (I), supra, and V represents a group selected from NH, NR′, O and SH, wherein R′ represents a substituent of the heteroaryl group R 2 , as defined for the compounds of general formula (I), supra.

In accordance with a second aspect, the present invention covers methods of preparing compounds of general formula (I), said methods comprising the step of allowing an intermediate compound of general formula (II):

in which R 1 , R 3 , R 4 , R 5 and R 8 are as defined for the compound of general formula (I) as defined supra, and X has the meaning of chloro or bromo,

to react with a compound of general formula (III):

in which R 2 , R 6 , R 7 , and n are as defined for the compound of general formula (I) as defined supra,

thereby giving a compound of general formula (I):

in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined supra.

In accordance with a second embodiment of the second aspect, the present invention covers methods of preparing compounds of general formula (I-b), which are compounds of general formula (I) in which R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra, and R 1 represents a carbamoyl group, said methods comprising the step of allowing a compound of general formula (I-a):

which is a compound of general formula (I) in which R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra, and R 1 represents a cyano group,

to react with palladium(II)acetate and acetaldoxime,

thereby giving a compound of general formula (I-b):

in which R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined supra, and R 1 represents a carbamoyl group.

In accordance with a third embodiment of the second aspect, the present invention covers methods of preparing compounds of general formula (I), said methods comprising the step of allowing an intermediate compound of general formula (IV):

in which R 1 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra,

to react with a compound of general formula (V):

in which R 2 is as defined for the compound of general formula (I) as defined supra,

in the presence of a photoredox catalyst and a nickel precatalyst,

thereby giving a compound of general formula (I):

in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 5 and n are as defined supra.

In accordance with a fourth embodiment of the second aspect, the present invention covers methods of preparing compounds of general formula (I-d), which are compounds of general formula (I) in which R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra, and R 1 represents a —C(═O)NH 2 , —C(═O)N(H)CH 3 , —C(═O)N(H)C 2 H 5 or —C(═O)N(CH 3 ) 2 group, said methods comprising the step of allowing a compound of general formula (I-c):

which is a compound of general formula (I) in which R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra, and R 1 represents a carboxyl group,

to react with a compound of general formula (VI):

which compound is NH 3 , H 2 NCH 3 , H 2 NCH 2 CH 3 or HN(CH 3 ) 2 , or salts thereof, thereby giving a compound of general formula (I-d):

which is a compound of general formula (I) in which R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined supra, and R 1 represents a group —C(═O)NH 2 , —C(═O)N(H)CH 3 , —C(═O)N(H)C 2 H 5 or —C(═O)N(CH 3 ) 2 .

In accordance with a fifth embodiment of the second aspect, the present invention covers methods of preparing compounds of general formula (I-e), which are compounds of general formula (I) in which R 1 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined supra, and R 2 represents a group

in which “*” represents the point of attachment of said group to the rest of the molecule, V represents a group O, S, NH or NR′, R′ represents a substituent of the group R 2 as defined for the compounds of formula (I) as defined supra, and p represents an integer of 0, 1, 2 or 3, said methods comprising the step of allowing a compound of general formula (VII):

in which R 1 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra,

to react with a compound of general formula (VIII):

in which R′ represents a substituent of the group R 2 as defined for the compounds of formula (I) as defined supra, p represents an integer of 0, 1, 2 or 3, V represents a group OH, SH, NH 2 or N(H)R′, and R′ represents a substituent of the group R 2 as defined for the compounds of formula (I) as defined supra,

thereby giving a compound of general formula (I-e):

in which R 1 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined supra, and R 2 represents a group

in which “*” represents the point of attachment of said group to the rest of the molecule, V represents a group O, S, NH or NR′, R′ represents a substituent of the group R 2 as defined for the compounds of formula (I) as defined supra, and p represents an integer of 0, 1, 2 or 3.

In accordance with a third aspect, the present invention covers methods of preparing compounds of general formula (I), said methods comprising the step of allowing an intermediate compound of general formula (II):

in which R 1 , R 3 , R 4 , R 5 and R 8 are as defined for the compound of general formula (I) as defined supra, and X has the meaning of chloro or bromo,

to react with a compound of general formula (III):

in which R 2 , R 6 , R 7 , and n are as defined for the compound of general formula (I) as defined supra,

thereby giving a compound of general formula (I):

in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined supra,

then optionally converting said compound into solvates, salts and/or solvates of such salts using the corresponding (i) solvents and/or (ii) bases or acids.

In accordance with a second embodiment of the third aspect, the present invention covers methods of preparing compounds of general formula (I-b), which are compounds of general formula (I) in which R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra, and R 1 represents a carbamoyl group, said methods comprising the step of allowing a compound of general formula (I-a):

which is a compound of general formula (I) in which R 2 , R 3 , R 4 , R 6 , R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra, and R 1 represents a cyano group,

to react with with palladium(II)acetate and acetaldoxime,

thereby giving a compound of general formula (I-b):

in which R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined supra, and R 1 represents a carbamoyl group,

then optionally converting said compound into solvates, salts and/or solvates of such salts using the corresponding (i) solvents and/or (ii) bases or acids.

In accordance with a third embodiment of the third aspect, the present invention covers methods of preparing compounds of general formula (I), said methods comprising the step of allowing an intermediate compound of general formula (IV):

in which R 1 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra,

to react with a compound of general formula (V):

in which R 2 is as defined for the compound of general formula (I) as defined supra, in the presence of a photoredox catalyst and a nickel precatalyst,

thereby giving a compound of general formula (I):

in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined supra,

then optionally converting said compound into solvates, salts and/or solvates of such salts using the corresponding (i) solvents and/or (ii) bases or acids.

In accordance with a fourth embodiment of the third aspect, the present invention covers methods of preparing compounds of general formula (I-d), which are compounds of general formula (I) in which R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra, and R 1 represents a —C(═O)NH 2 , —C(═O)N(H)CH 3 , —C(═O)N(H)C 2 H 5 or —C(═O)N(CH 3 ) 2 group, said methods comprising the step of allowing a compound of general formula (I-c):

which is a compound of general formula (I) in which R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra, and R 1 represents a carboxyl group,

to react with a compound of general formula (VI):

which compound is NH 3 , H 2 NCH 3 , H 2 NCH 2 CH 3 or HN(CH 3 ) 2 , or salts thereof,

thereby giving a compound of general formula (I-d):

which is a compound of general formula (I) in which R 2 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined supra, and R 1 represents a group —C(═O)NH 2 , —C(═O)N(H)CH 3 , —C(═O)N(H)C 2 H 3 or —C(═O)N(CH 3 ) 2 ,

then optionally converting said compound into solvates, salts and/or solvates of such salts using the corresponding (i) solvents and/or (ii) bases or acids.

In accordance with a fifth embodiment of the second aspect, the present invention covers methods of preparing compounds of general formula (I-e), which are compounds of general formula (I) in which R 1 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined supra, and R 2 represents a group

in which “*” represents the point of attachment of said group to the rest of the molecule, V represents a group O, S, NH or NR′, R′ represents a substituent of the group R 2 as defined for the compounds of formula (I) as defined supra, and p represents an integer of 0, 1, 2 or 3, said methods comprising the step of allowing a compound of general formula (VII):

in which R 1 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra,

to react with a compound of general formula (VIII):

in which R′ represents a substituent of the group R 2 as defined for the compounds of formula (I) as defined supra, p represents an integer of 0, 1, 2 or 3, V represents a group OH, SH, NH 2 or N(H)R′, and R′ represents a substituent of the group R 2 as defined for the compounds of formula (I) as defined supra,

thereby giving a compound of general formula (I-e):

in which R 1 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined supra, and R 2 represents a group

in which “*” represents the point of attachment of said group to the rest of the molecule, V represents a group O, S, NH or NR′, R′ represents a substituent of the group R 2 as defined for the compounds of formula (I) as defined supra, and p represents an integer of 0, 1, 2 or 3,

then optionally converting said compound into solvates, salts and/or solvates of such salts using the corresponding (i) solvents and/or (ii) bases or acids.

The present invention covers methods of preparing compounds of the present invention of general formula (I), said methods comprising the steps as described in the Experimental Section herein.

In accordance with a fourth aspect, the present invention covers intermediate compounds which are useful for the preparation of the compounds of general formula (I), supra.

Particularly, the inventions covers the intermediate compounds of general formula (II):

in which R 1 , R 3 , R 4 , R 5 and R 8 are as defined for the compound of general formula (I) as defined supra, and X has the meaning of chloro or bromo.

In accordance with a fifth aspect, the present invention covers the use of intermediate compounds for the preparation of a compound of general formula (I) as defined supra.

Particularly, the inventions covers the use of intermediate compounds of general formula (II):

in which R 1 , R 3 , R 4 , R 5 and R 8 are as defined for the compound of general formula (I) as defined supra, and X has the meaning of chloro or bromo, for the preparation of a compound of general formula (I) as defined supra.

Particularly, the inventions covers the use of intermediate compounds of general formula (III):

in which R 2 , R 6 , R 7 , and n are as defined for the compound of general formula (I) as defined supra, for the preparation of a compound of general formula (I) as defined supra.

Particularly, the inventions covers the use of intermediate compounds of general formula (IV):

in which R 1 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra, for the preparation of a compound of general formula (I) as defined supra.

Particularly, the inventions covers the use of intermediate compounds of general formula (V):

in which R 2 is as defined for the compound of general formula (I) as defined supra, for the preparation of a compound of general formula (I) as defined supra.

Particularly, the inventions covers the use of intermediate compounds of general formula (VI):

which compounds are NH 3 , H 2 NCH 3 , H 2 NCH 2 CH 3 or HN(CH 3 ) 2 , or salts thereof, for the preparation of a compound of general formula (I) as defined supra.

Particularly, the inventions covers the use of intermediate compounds of general formula (VII):

in which R 1 , R 3 , R 4 , R 5 , R 6 R 7 , R 8 and n are as defined for the compound of general formula (I) as defined supra, for the preparation of a compound of general formula (I) as defined supra.

Particularly, the inventions covers the use of intermediate compounds of general formula (VIII):

in which R′ represents a substituent of the group R 2 as defined for the compounds of formula (I) as defined supra, p represents an integer of 0, 1, 2 or 3, V represents a group OH, SH, NH 2 or N(H)R′, and R′ represents a substituent of the group R 2 as defined for the compounds of formula (I) as defined supra, for the preparation of a compound of general formula (I) as defined supra.

The present invention covers the intermediate compounds which are disclosed in the Example Section of this text, infra.

The present invention covers the use of intermediate compounds which are disclosed in the Example Section of this text, infra.

The present invention covers any sub-combination within any embodiment or aspect of the present invention of intermediate compounds of general formulae (II), (Ill), (IV), (V), (VI), (VII) and (VIII), supra.

FIG. 1 : human DGKα M1 to S735 plus C-terminal Flag-Tag, DGKa_hu_1, as described under SEQ ID No. 1.

FIG. 2 : human DGKα M1 to S735 plus N-terminal Avi-Tag and C-terminal Flag-Tag, DGKa_hu_1Avi, as described under SEQ ID No. 2.

FIG. 3 : SIINFEKL amino acid sequence, as described under SEQ ID No. 3.

FIG. 4 : GCCACC DNA sequence.

FIG. 5 : Flag-Tag sequence, as described under SEQ ID No. 4.

FIG. 6 : OVA-30 peptide sequence, as described under SEQ ID No. 5.

NMR peak forms are stated as they appear in the spectra, possible higher order effects have not been considered. The multiplicities are stated according to the signal form which appears in the spectrum, NMR-spectroscopic effects of a higher order were not taken into consideration. Multiplicity of the NMR signals: s=singlet, d=doublet, t=triplet, q=quartet, quin=quintet, spt=septed, br=broad signal, m=multiplet. NMR signals: shift in [ppm]. Combinations of multiplicity could be e.g. dd=doublet from doublet.

Chemical names were generated using the ACD/Name software from ACD/Labs. In some cases generally accepted names of commercially available reagents were used in place of ACD/Name generated names.

Table 1 lists the abbreviations used in this paragraph and in the Examples section as far as they are not explained within the text body. Other abbreviations have their meanings customary per se to the skilled person.

The various aspects of the invention described in this application are illustrated by the following examples which are not meant to limit the invention in any way.

The example testing experiments described herein serve to illustrate the present invention and the invention is not limited to the examples given.

Experimental Section—General Part

All reagents, for which the synthesis is not described in the experimental part, are either commercially available, or are known compounds or may be formed from known compounds by known methods by a person skilled in the art.

The compounds and intermediates produced according to the methods of the invention may require purification. Purification of organic compounds is well known to the person skilled in the art and there may be several ways of purifying the same compound. In some cases, no purification may be necessary. In some cases, the compounds may be purified by crystallization. In some cases, impurities may be stirred out using a suitable solvent. In some cases, the compounds may be purified by chromatography, particularly flash column chromatography, using for example prepacked silica gel cartridges, e.g. Biotage SNAP cartridges KP-Sil® or KP-NH® in combination with a Biotage autopurifier system (SP4® or Isolera Four®) and eluents such as gradients of hexane/ethyl acetate or DCM/methanol. In some cases, the compounds may be purified by preparative HPLC using for example a Waters autopurifier equipped with a diode array detector and/or on-line electrospray ionization mass spectrometer in combination with a suitable prepacked reverse phase column and eluents such as gradients of water and acetonitrile which may contain additives such as trifluoroacetic acid, formic acid or aqueous ammonia.

In some cases, purification methods as described above can provide those compounds of the present invention which possess a sufficiently basic or acidic functionality in the form of a salt, such as, in the case of a compound of the present invention which is sufficiently basic, a trifluoroacetate or formate salt for example, or, in the case of a compound of the present invention which is sufficiently acidic, an ammonium salt for example. A salt of this type can either be transformed into its free base or free acid form, respectively, by various methods known to the person skilled in the art, or be used as salts in subsequent biological assays. It is to be understood that the specific form (e.g. salt, free base etc.) of a compound of the present invention as isolated and as described herein is not necessarily the only form in which said compound can be applied to a biological assay in order to quantify the specific biological activity.

Chromatographic Conditions:

LC-MS (Method 1): Instrument: Waters Acquity UPLCMS SingleQuad; column: Acquity UPLC BEH C18 1.7 μm, 50×2.1 mm; eluent A: water+0.1 vol. % formic acid (99%), eluent B: acetonitrile; gradient: 0-1.6 min. 1-99% B, 1.6-2.0 min. 99% B; flow 0.8 ml/min; temperature: 60° C.; DAD scan: 210-400 nm.

LC-MS (Method 2): Instrument: Waters Acquity UPLCMS SingleQuad; column: Acquity UPLC BEH C18 1.7 μm, 50×2.1 mm; eluent A: water+0.2 vol. % aqueous ammonia (32%), eluent B: acetonitrile; gradient: 0-1.6 min. 1-99% B, 1.6-2.0 min. 99% B; flow 0.8 ml/min; temperature: 60° C.; DAD scan: 210-400 nm.

LC-MS (Method 3): Instrument: Agilent 1290 UPLCMS 6230 TOF; column: BEH C 18 1.7 μm, 50×2.1 mm; eluent A: water+0.05 vol. % formic acid (99%; eluent B: acetonitrile+0.05 vol. % formic acid (99%); gradient: 0-1.7 min. 2-90% B, 1.7-2.0 min. 90% B; flow 1.2 ml/min; temperature: 60° C.; DAD scan: 190-400 nm.

Experimental Section—Intermediates

Intermediate 1

2-(4-methylpiperidin-4-yl)-1,3-benzoxazole

A mixture of 500 mg 4-methylpiperidine-4-carboxylic acid (3.5 mmol, CAS 919354-20-4) and 381 mg 2-aminophenol (3.5 mmol, CAS 95-55-6) in 1.14 g polyphosphoric acid was stirred for 5 h at 180° C. Water was added carefully at about 80° C. and after cooling to rt, sodium hydroxide solution was added to get to pH=10. The solution was extracted 3 times with ethyl acetate. The combined organic phases were washed with water and brine and dried over sodium sulfate. After evaporation of the solvent, 230 mg of the title compound were obtained (29% yield).

1 H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.35 (s, 3H); 1.53-1.62 (m, 2H); 2.15-2.24 (m, 2H); 2.56-2.60 (m, 2H); 2.77-2.85 (m, 2H); 7.31-7.38 (m, 2H); 7.66-7.73 (m, 2H).

Intermediate 15

ethyl 1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidine-4-carboxylate

To a solution of 3 g 4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile (13.7 mmol, CAS 150617-68-8, Synthesis described in WO2012009649, example 1 compound III) and 7.2 mL N,N-diisopropylethylamine (41 mmol) in 60 mL 2-propanol was added 2.5 mL ethyl piperidine-4-carboxylate (16 mmol, CAS 1126-09-6) and the reaction was stirred for 2 h at 90° C. After this time, water was added and the reaction was extracted with dichloromethane. The organic phase dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography (silica, dichloromethane/ethanol gradient 0-3%) to give 4.22 g of the title compound (91% yield).

1 H NMR (400 MHz, CHLOROFORM-d) δ ppm: 1.32 (m, 3H), 2.03 (m, 2H), 2.16 (m, 2H), 2.64 (m, 1H), 3.50 (m, 2H), 3.69 (s, 3H), 3.80 (dt, 2H), 4.22 (m, 2H), 7.26 (m, 1H), 7.37 (m, 1H), 7.65 (m, 1H), 7.81 (m, 1H).

LC-MS (Method 1): R t =1.10 min; MS (ESIpos): m/z=340 [M+H] +

Intermediate 16

1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidine-4-carboxylic acid

To 4.21 g ethyl 1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidine-4-carboxylate (12.4 mmol, intermediate 15) in 350 mL THF and 80 mL ethanol was added 74 mL lithium hydroxide (1.0 M, 74 mmol) and the mixture was stirred for 3 h at rt. The reaction mixture was diluted with water, and adjusted to pH=3-4 with hydrogen chloride (4M) and extracted with dichloromethane. The combined organic phases were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. 3.81 g of the title compound were obtained (94% yield, 95% purity).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.86 (m, 2H), 2.02 (br dd, 2H), 2.64 (m, 1H), 3.44 (m, 2H), 3.57 (s, 3H), 3.72 (m, 2H), 7.34 (m, 1H), 7.56 (m, 1H), 7.73 (m, 1H), 7.82 (m, 1H), 12.37 (br s, 1H).

LC-MS (Method 1): R t =0.84 min; MS (ESIpos): m/z=312 [M+H] +

Intermediate 17

ethyl 1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)-4-fluoropiperidine-4-carboxylate

To a solution of 1 g 4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile (4.57 mmol, CAS 150617-68-8, Synthesis described in WO2012009649, example 1 compound Ill) and 2.4 mL N,N-diisopropylethylamine (14 mmol) in 17 mL 2-propanol was added 1.06 g ethyl 4-fluoropiperidine-4-carboxylate hydrogen chloride salt (1:1) (5.03 mmol, CAS 845909-49-1) and the reaction was stirred for 2 h at 90° C. in the microwave. The reaction was allowed to cool to rt and poured into water. The precipitate was filtered off, washed with ethanol and dried in vacuum. The title compound was obtained in 78% yield (1.34 g, 95% purity).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.27 (t, 3H), 2.13 (m, 2H), 2.32 (m, 2H), 3.58 (s, 3H), 3.68 (m, 4H), 4.25 (q, 2H), 7.35 (td, 1H), 7.58 (m, 1H), 7.75 (m, 1H), 7.87 (m, 1H).

LC-MS (Method 1): R t =1.09 min; MS (ESIpos): m/z=358 [M+H] +

Intermediate 18

1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)-4-fluoropiperidine-4-carboxylic acid

To 1 g of ethyl 1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)-4-fluoropiperidine-4-carboxylate (2.8 mmol, intermediate 17) in 80 mL THF and 20 mL ethanol was added 17 mL lithium hydroxide (1.0 M, 17 mmol) and the mixture was stirred for 3 h at rt. The reaction was diluted with water and adjusted to pH=3-4 with hydrogen chloride (4M). The organic solvents were evaporated, the precipitate was filtered off, washed with water and dried in vacuum. 782 mg of the title compound were obtained (81% yield, 95% purity).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 2.10 (m, 2H), 2.33 (m, 2H), 3.58 (s, 3H), 3.67 (m, 4H), 7.35 (m, 1H), 7.58 (m, 1H), 7.75 (m, 1H), 7.86 (m, 1H), 13.49 (m, 1H).

LC-MS (Method 1): R t =0.79 min; MS (ESIpos): m/z=330 [M+H] +

Intermediate 19

7-bromo-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione

To a solution of 50 g 7-bromo-2H-3,1-benzoxazine-2,4(1H)-dione (207 mmol, CAS 76561-16-5) and 72 mL N,N-diisopropylethylamine (413 mmol) in 400 mL N,N-dimethylacetamide was added 39 mL iodomethane (620 mmol) at rt and was stirred overnight. The reaction was cooled to 0° C. and 200 mL water was slowly added. The solid that precipitated from this procedure was collected by filtration, washed with water and dried in an oven at 50° C. 48.1 g of the title compound were obtained (91% yield).

1 H-NMR (400 MHz, DMSO-d6) δ [ppm]: 3.46 (s, 3H); 7.52 (dd, 1H); 7.70 (d, 1H); 7.90 (d, 1H).

Intermediate 20

7-bromo-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

A solution of 40 g 7-bromo-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (156 mmol, intermediate 19) in 320 mL THF was slowly treated with 170 mL triethylamine (1.2 mol) followed by the addition of 25 mL ethyl cyanoacetate (234 mmol, CAS 105-56-6) at rt. The reaction was heated at 60° C. and stirred at that temperature over night. Further 25 mL ethyl cyanoacetate (234 mmol) were added and the reaction was stirred at 70° C. for further 5 h. After cooling to rt, water was added and THF was evaporated in vacuum. The mixture was acidified to pH=1 by addition of hydrochloric acid (2 M) and extracted with ethyl acetate 3 times. The combined organic layers were evaporated in vacuum and the residue was stirred first with hexane, decanted and then stirred with a small amount ethyl acetate/hexane. The residue was filtered and 46 g of the title material were obtained in two crops (106% yield).

1 H-NMR (400 MHz, DMSO-d6) δ [ppm]: 3.51 (s, 3H); 6.67 (bs, 1H); 7.46 (dd, 1H); 7.71 (d, 1H); 7.96 (d, 1H).

Intermediate 21

7-bromo-4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

A mixture of 16 g 7-bromo-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile (57 mmol, intermediate 20) and 100 mL phosphorus trichloride (1.05 mol) was stirred at 90° C. overnight. After cooling to rt, hexane was added and the reaction was filtered. The solid was washed with sat. sodium bicarbonate solution and water. The obtained residue was dried in an oven at 50° C. overnight to give 13.2 g of the title compound (77% yield).

1 H-NMR (400 MHz, DMSO-d6) δ [ppm]: 3.64 (s, 3H); 7.66 (dd, 1H); 7.94-7.98 (m, 2H).

Intermediate 22

tert-butyl 4-[4-(2,2,2-trifluoroethoxy)phenyl]piperidine-1-carboxylate

A mixture of 4 g 1-bromo-4-(2,2,2-trifluoroethoxy)benzene (15.7 mmol, CAS 106854-77-7), 8.29 g tert-butyl 4-bromopiperidine-1-carboxylate (31.4 mmol, CAS 180695-79-8), 4.8 mL 1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane (16 mmol), 176 mg bis{3,5-difluoro-2-[5-(trifluoromethyl)pyridin-2-yl]phenyl}iridium(I)hexafluorophosphate-4,4-di-tert-butyl-2,2-bipyridine (1:1:1) (157 μmol, CAS 870987-63-6), 11 mL 2,2,6,6-tetramethylpiperidine (63 mmol), 103 mg 1,2-dimethoxyethane-dichloronickel (1:1) (471 μmol) and 126 mg 4,4′-di-tert-butyl-2,2′-bipyridine (471 μmol) was stirred in a mixture of 150 mL N,N-dimethylacetamide and 300 mL (trifluoromethyl)benzene and degassed with argon. The reaction was stirred and irradiated at 455 nm for 6 h. The mixture was concentrated under reduced pressure, 500 mL water was added and extracted with ethyl acetate (3×). The combined organic phases were washed with water, dried and concentrated under reduced pressure. The residue was purified by flash chromatography (silica, hexane/ethyl acetate gradient 0-30%) to give 1.9 g of the title compound (34% yield).

1 H NMR (400 MHz, CHLOROFORM-d) δ ppm: 1.49 (m, 9H), 1.58 (m, 2H), 1.80 (br d, 2H), 2.61 (m, 1H), 2.80 (m, 2H), 4.23 (m, 2H), 4.34 (m, 2H), 6.91 (m, 2H), 7.15 (m, 2H).

LC-MS (Method 2): R=1.48 min; MS (ESIpos): m/z=304.3 [M+H] +

Intermediate 23

4-[4-(2,2,2-trifluoroethoxy)phenyl]piperidine

To a solution of 1.8 g tert-butyl 4-[4-(2,2,2-trifluoroethoxy)phenyl]piperidine-1-carboxylate (4.76 mmol, intermediate 22) in 31 mL dichloromethane was added 3.7 mL trifluoroacetic acid (48 mmol) and the mixture was stirred overnight at rt. The mixture was cooled down to rt, concentrated under reduced pressure and the residue was diluted with toluene (2×). The solvent was evaporated to give 2.0 g TFA salt of the title compound (154% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.83 (m, 4H), 2.80 (m, 1H), 3.01 (m, 2H), 3.37 (m, 2H), 4.71 (m, 2H), 7.01 (m, 2H), 7.18 (m, 2H), 8.67 (m, 1H).

LC-MS (Method 2): R t =1.15 min; MS (ESIpos): m/z=260.7 [M+H] +

Intermediate 24

tert-butyl 4-{4-[(propan-2-yl)oxy]phenyl}piperidine-1-carboxylate

A mixture of 4.3 g 1-bromo-4-[(propan-2-yl)oxy]benzene (19.0 mmol, CAS 6967-88-0), 10 g tert-butyl 4-bromopiperidine-1-carboxylate (38.0 mmol, CAS 180695-79-8), 5.9 mL 1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane (19 mmol), 213 mg bis{3,5-difluoro-2-[5-(trifluoromethyl)pyridin-2-yl]phenyl}iridium(I)hexafluorophosphate-4,4′-di-tert-butyl-2,2′-bipyridine (1:1:1) (190 μmol, CAS 870987-63-6), 13 mL 2,2,6,6-tetramethylpiperidine (76 mmol), 125 mg 1,2-dimethoxyethane-dichloronickel (1:1) (570 μmol) and 153 mg 4,4′-di-tert-butyl-2,2′-bipyridine (570 μmol) was stirred in a mixture of 150 mL N,N-dimethylacetamide and 300 mL (trifluoromethyl)benzene and degassed with argon. The reaction was stirred and irradiated at 455 nm 50% (˜223 W) for 10 h. The mixture was concentrated under reduced pressure, 500 mL water was added and extracted with ethyl acetate (3×). The combined organic phases were washed with water, dried and concentrated under reduced pressure. The residue was purified by flash chromatography (silica, hexane/ethyl acetate gradient 0-50%) to give 3.3 g of the title compound (54% yield).

1 H NMR (400 MHz, CHLOROFORM-d) δ ppm: 1.32 (d, 6H); 1.48 (s, 9H); 1.53-1.61 (m, 2H); 1.75-1.83 (m, 2H); 2.57 (tt, 1H); 3.28-3.37 (m, 2H); 3.62-3.73 (m, 2H); 4.50 (spt, 1H); 6.80-6.85 (m, 2H); 7.06-7.12 (m, 2H).

LC-MS (Method 2): R t =1.54 min; MS (ESIpos): m/z=320.3 [M+H] +

Intermediate 25

4-{4-[(propan-2-yl)oxy]phenyl}piperidine

To a solution of 3.3 g tert-butyl 4-{4-[(propan-2-yl)oxy]phenyl}piperidine-1-carboxylate (9.81 mmol, intermediate 24) in 63 mL dichloromethane was added 7.6 mL trifluoroacetic acid (98 mmol) and the mixture was stirred overnight at rt. The mixture was cooled down to rt, concentrated under reduced pressure and the residue was diluted with toluene (2×). The solvent was evaporated to give 3.9 g TFA salt of the title compound (85% purity, 154% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.24 (d, 6H); 1.51-1.69 (m, 2H); 1.85-1.93 (m, 2H); 2.75 (tt, 1H); 3.16-3.27 (m, 2H); 3.31-3.40 (m, 2H); 4.51-4.60 (m, 1H); 6.86 (d, 2H); 7.11 (d, 2H).

LC-MS (Method 2): R t =1.23 min; MS (ESIpos): m/z=220.8 [M+H] +

Intermediate 26

4-(4-bromopiperidin-1-yl)-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

A solution of 2.58 g 4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile (11.8 mmol, CAS 150617-68-8, Synthesis described in WO2012009649, example 1—compound III), 8.66 g 4-bromopiperidine hydrogen bromide salt (1:1) (35.4 mmol, CAS 54288-70-9) and 4.9 mL triethylamine (35 mmol) in 77 mL 2-propanol was stirred for 6 h at 90° C. After this time, the solvent was removed by evaporation and the residue was concentrated by flash chromatography (silica, dichloromethane/methanol gradient 0-3%). The fractions containing the desired material were pooled and the solvent was removed by evaporation. The residue was taken up into ethyl acetate at 50° C. The title compound was obtained by fractionated crystallization of this solution. 3.65 g of the title compound was obtained (85% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 2.10-2.23 (m, 2H); 2.33-2.44 (m, 2H); 3.48-3.60 (m+s, 5H); 3.67-3.78 (m, 2H); 4.69-4.78 (m, 1H); 7.31-7.37 (m, 1H); 7.57 (d, 1H); 7.71-7.77 (m, 1H); 7.85 (dd, 1H).

Intermediate 27

tert-butyl 4-[4-(propan-2-yl)phenyl]piperidine-1-carboxylate

In analogy to intermediate 24, 2 mL 1-bromo-4-(propan-2-yl)benzene (13 mmol, CAS 586-61-8) and 7 g tert-butyl 4-bromopiperidine-1-carboxylate (26.5 mmol, CAS 180695-79-8) were converted in 10 h. After workup, purification was performed by flash chromatography (silica, hexane/ethyl acetate gradient 0-50%) to give 1.88 g of the title compound (47% yield, 80 purity).

1 H NMR (400 MHz, CHLOROFORM-d) δ ppm: 1.24 (d, 6H); 1.54-1.60 (m, 2H); 1.77-1.86 (m, 2H); 2.61 (tt, 1H); 2.73-2.84 (m, 2H); 2.88 (spt, 1H); 4.15-4.29 (m, 2H); 7.10-7.20 (m, 4H).

Intermediate 28

4-[4-(propan-2-yl)phenyl]piperidine

A solution of 1.8 g tert-butyl 4-[4-(propan-2-yl)phenyl]piperidine-1-carboxylate (5.6 mmol, intermediate 27) in 36 mL dichloromethane and 4.3 mL trifluoroacetic acid (56 mmol) was stirred for 14 h at 70° C. The solvent was evaporated and the residue was taken up into 100 mL methanol. 1 g palladium on charcoal (10%) was added and the suspension was shaked under a hydrogen atmosphere for several hours. The catalyst was filtered off, the solvent was evaporated and 1.1 g of the title compound was obtained (95% purity)

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.17 (d, 6H); 1.51-1.59 (m, 2H); 1.69-1.82 (m, 2H); 1.87-1.96 (m, 2H); 2.73-2.90 (m, 2H); 3.32-3.41 (m, 2H); 7.10-7.16 (m, 2H); 7.17-7.23 (m, 2H).

Intermediate 29

tert-butyl 4-(1-methyl-1H-indol-5-yl)piperidine-1-carboxylate

A mixture of 600 mg 5-bromo-1-methyl-1H-indole (2.85 mmol, CAS 10075-52-2), 1.51 g tert-butyl 4-bromopiperidine-1-carboxylate (5.7 mmol, CAS 180695-79-8), 0.88 mL 1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane (2.9 mmol), 64.1 mg bis{3,5-difluoro-2-[5-(trifluoromethyl)pyridin-2-yl]phenyl}iridium(I)hexafluorophosphate-4,4′-di-tert-butyl-2,2′-bipyridine (1:1:1) (57.1 μmol, CAS 870987-63-6), 0.67 mL 2,6-dimethylpyridine (5.7 mmol), 3.14 mg 1,2-dimethoxyethane-dichloronickel (1:1) (14.3 μmol) and 3.8 mg 4,4′-di-tert-butyl-2,2′-bipyridine (14 μmol) was stirred in 60 mL 1,2-dimethoxyethane and degassed with argon. The reaction was stirred and irradiated at 455 nm 50% (˜223 W) for 16 h. The mixture was diluted with half concentrated sodium bicarbonate solution and extracted with ethyl acetate (3×). The combined organic phases were washed with water, dried and concentrated under reduced pressure. The residue was purified by RP-HPLC (column: X-Bridge C18 5 μm 100×30 mm, mobile phase: acetonitrile/water gradient) to give 570 mg of the title compound (48% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.42 (s, 9H); 1.46-1.58 (m, 2H); 1.72-1.83 (m, 2H); 2.72 (tt, 1H); 2.76-2.91 (m, 2H); 3.75 (s, 3H); 4.00-4.16 (m, 2H); 6.33 (dd, 1H); 7.03 (dd, 1H); 7.26 (d, 1H); 7.31-7.35 (m, 1H); 7.35-7.39 (m, 1H).

Intermediate 30

1-methyl-5-(piperidin-4-yl)-1H-indole

A solution of 570 mg tert-butyl 4-(1-methyl-1H-indol-5-yl)piperidine-1-carboxylate (1.7 mmol, intermediate 29) in 11 mL dichloromethane and 1.3 mL trifluoroacetic acid (17.2 mmol) was stirred overnight at rt. The reaction mixture was concentrated under reduced pressure, the residue was treated with toluene and the mixture was evaporated to dryness to give 450 mg of the title compound (85% purity, 104% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.62-1.73 (m, 1H); 1.74-1.92 (m, 2H); 1.89-2.05 (m, 1H); 2.72-2.97 (m, 2H); 2.98-3.11 (m, 1H); 3.20-3.34 (m, 2H); 3.32-3.50 (m, 1H); 6.85-6.97 (m, 1H); 6.97-7.12 (m, 1H); 7.23-7.39 (m, 1H); 8.19-8.40 (m, 1H); 8.53-8.72 (m, 1H).

Intermediate 51

2-(4-ethylpiperidin-4-yl)-1,3-benzoxazole

A mixture of 1.5 g 4-ethylpiperidine-4-carboxylic acid (9.54 mmol, CAS 1227465-48-6) and 1.04 g 2-aminophenol (9.54 mmol, CAS 95-55-6) in 5.54 g polyphosphoric acid was stirred for 2 h at 180° C. Water was added carefully and after cooling to rt, an aqueous solution of potassium hydroxide was added to adjusted pH=10. The solution was extracted with ethyl acetate 3 times. The combined organic phases were washed with water and brine, dried over sodium sulfate and the filtrate was concentrated under reduced pressure to give 740 mg of the title compound (93% purity, 31% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 0.64 (t, 3H); 1.45-1.62 (m, 2H); 1.66-1.82 (m, 2H); 2.18-2.33 (m, 2H); 2.82 (dt, 2H); 7.12-7.44 (m, 1H); 7.26-7.41 (m, 1H); 7.44-7.53 (m, 1H); 7.51-7.99 (m, 1H); 7.59-7.93 (m, 1H).

Intermediate 52

5-methyl-2-(4-methylpiperidin-4-yl)-1,3-benzoxazole

A mixture of 3.08 g 2-amino-4-methylphenol (25.0 mmol, CAS 95-84-1) and 4.50 g 4-methylpiperidine-4-carboxylic acid hydrogen chloride salt (1:1) (25.0 mmol, CAS 919354-20-4) in 24 mL polyphosphoric acid was stirred for 2 h at 180° C. Water was added carefully and after cooling to rt, an aqueous solution of potassium hydroxide was added to adjusted pH=10. The solution was extracted with ethyl acetate two times. The combined organic phases were washed with water and brine, dried over sodium sulfate and the filtrate was concentrated under reduced pressure to give 2.20 g of the title compound (95% purity, 36% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ [ppm]: 1.33 (s, 3H); 1.49-1.70 (m, 2H); 2.07-2.28 (m, 2H); 2.41 (s, 3H); 2.51-2.61 (m, 2H); 2.74-2.89 (m, 2H); 7.15 (dt, 1H); 7.42-7.61 (m, 2H).

Intermediate 53

5-methyl-2-(3-methylpiperidin-4-yl)-1,3-benzoxazole

A mixture of 430 mg 2-amino-4-methylphenol (3.49 mmol, CAS 95-84-1) and 500 mg 3-methylpiperidine-4-carboxylic acid (3.49 mmol, CAS 885951-69-9) in 6 mL polyphosphoric acid was stirred for 2 h at 180° C. Water was added carefully and after cooling to rt, an aqueous solution of potassium hydroxide was added to adjusted pH=10. The solution was extracted with ethyl acetate two times. The combined organic phases were washed with water and brine, dried over sodium sulfate and the filtrate was concentrated under reduced pressure to give 550 mg of the title compound (90% purity, 62% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ [ppm]: 1.33 (s, 3H); 1.48-1.67 (m, 2H); 2.07-2.28 (m, 2H); 2.41 (s, 3H); 2.51-2.62 (m, 2H); 2.67-2.85 (m, 2H); 7.07-7.24 (m, 1H); 7.40-7.67 (m, 2H).

Intermediate 54

(rac)-tert-butyl 4-[4-(propan-2-yl)phenyl]azepane-1-carboxylate

A mixture of 1.8 g tert-butyl 4-hydroxyazepane-1-carboxylate (8.36 mmol, CAS 478832-21-2) and 2.12 g oxalylchloride was stirred in 61 mL diethyl ether at 0° C. for 30 minutes and rt for 14 hours. Then, the reaction was coiled again to 0° C. and water was added very carefully. After warming to rt, the two phases were separated and the aqueous layer was extracted with diethyl ether (3×). The combined organic layers were evaporate in vacuum to obtain 2.24 g [1-(tert-butoxycarbonyl)azepan-4-yl]oxy)(oxo)acetic acid. 800 mg of this [1-(tert-butoxycarbonyl)azepan-4-yl]oxy)(oxo)acetic acid (2.78 mmol), 280 μL 1-bromo-4-(propan-2-yl)benzene (1.9 mmol, CAS 586-61-8), 720 mg cesium carbonate (3.71 mmol), 20.3 mg bis{3,5-difluoro-2-[5-(trifluoromethyl)pyridin-2-yl]phenyl}iridium(I)hexafluorophosphate, 24.9 mg 4,4′-di-tert-butyl-2,2′-bipyridine (92.8 μmol) and 20.3 mg 1,2-dimethoxyethane-dibromonickel (1:1) (471 μmol) was stirred in a mixture of 46 mL tetrahydropyran and 9.2 mL dimethylsulfoxide and degassed with argon. The reaction was stirred and irradiated at 455 nm for 6 h at 70° C. The mixture was concentrated under reduced pressure, 500 mL water was added and extracted with ethyl acetate (3×). The combined organic phases were washed with water, dried and concentrated under reduced pressure. The residue was purified by flash chromatography (silica, hexane/ethyl acetate gradient 0-25%). The impure product was purified by RP-HPLC (column: Chromatorex 125×30 mm, 10 μm mobile phase: acetonitrile/water (0.2 vol. % ammonia 32%)-gradient) to give 116 mg of the title compound (100% purity, 20% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ [ppm]: 1.17 (d, 6); 1.19-1.28 (m, 1H); 1.42 (d, 9H); 1.45-1.48 (m, 1H): 1.47-1.71 (m, 2H); 1.72-1.93 (m, 3H); 2.53-2.64 (m, 1H); 2.77-2.93 (m, 1H); 3.09-3.30 (m, 1H); 3.34-3.46 (m, 2H); 3.48-3.73 (m, 1H); 6.92-7.27 (m, 4H).

Intermediate 55

(rac)-4-[4-(propan-2-yl)phenyl]azepane

To a solution of 110 mg tert-butyl 4-[4-(propan-2-yl)phenyl]azepane-1-carboxylate (3.29 mmol, intermediate 54) in 2 mL dichloromethane was added 254 μL trifluoroacetic acid (3.29 mmol) and the mixture was stirred overnight at rt. The mixture was concentrated under reduced pressure and the residue was diluted with toluene (2×). The solvent was evaporated to give 145 mg TFA salt of the title compound (95% purity, 193% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ [ppm]: 1.13-1.21 (m, 6H) 1.63-2.01 (m, 6H) 2.72-2.91 (m, 2H) 3.06-3.32 (m, 4H) 7.11-7.22 (m, 4H).

Intermediate 56

(rac)-2-(azepan-4-yl)-1,3-benzoxazole

449 mg 2-aminophenol (4.11 mmol, CAS 95-55-6) and 1.00 g 1-(tert-butoxycarbonyl)azepane-4-carboxylic acid (4.11 mmol, CAS 868284-36-0) were solubilised in 0.72 mL polyphosphoric acid and the mixture was stirred for 3 h at 180° C. The reaction mixture was cooled down to rt, treated with water and the mixture was adjusted to pH=10 with an aqueous solution of potassium hydroxide. The aqueous phase was extracted with ethyl acetate two times, the combined organic phases were washed with water and brine, filtered through a water resistant filter, the filtrate was concentrated under reduced pressure to give 460 mg of the title compound (95% purity, 49% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ [ppm]: 1.54-1.66 (m, 1H) 1.70-1.80 (m, 1H) 1.87-1.97 (m, 2H) 2.09-2.19 (m, 2H) 2.64-2.94 (m, 4H) 3.21-3.30 (m, 2H) 7.27-7.41 (m, 2H) 7.62-7.72 (m, 2H).

Intermediate 57

(rac)-tert-butyl 4-{4-[(propan-2-yl)oxy]phenyl}azepane-1-carboxylate

A mixture of 230 μL1-bromo-4-[(propan-2-yl)oxy]benzene (1.4 mmol, CAS 1852254-64-8), 1.16 g tert-butyl 4-bromoazepan-1-carboxylate (4.18 mmol), 430 μL 1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane (1.4 mmol), 31.3 mg bis{3,5-difluoro-2-[5-(trifluoromethyl)pyridin-2-yl]phenyl}iridium(I)hexafluorophosphate (27.9 μmol), 1.87 mg 4,4′-di-tert-butyl-2,2′-bipyridine (1:1:1) (6.97 μmol, CAS 870987-63-6), 591 mg sodium carbonate (5.58 mmol), 1.53 g 1,2-dimethoxyethane-dichloronickel (1:1) (6.97 μmol) was stirred in 9 mL N,N-dimethylacetamide and 28 mL trifluorotoluene and degassed under argon. The reaction was stirred and irradiated by two Kessil LED Aquarium lights (each 40 W) 455 nm for 14 h at 35° C. The mixture was concentrated under reduced pressure, water was added and the aqueous phase was extracted with ethyl acetate two times. The combined organic phases were washed with an aqueous solution of sodium bicarbonate and water, dried over sodium sulfate and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (silica, hexane/ethyl acetate gradient 0-20%) to give 351 mg of the title compound (85% purity, 44% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ [ppm]: 1.23 (d, 6H) 1.42 (d, 9H) 1.47-1.61 (m, 2H) 1.62-1.75 (m, 2H) 1.77-1.92 (m, 2H) 2.51-2.61 (m, 2H) 3.11-3.25 (m, 1H) 3.35-3.47 (m, 2H) 3.48-3.62 (m, 1H) 4.53 (dt, 1H) 6.76-6.86 (m, 2H) 7.02-7.10 (m, 2H).

Intermediate 58

(rac)-4-{4-[(propan-2-yl)oxy]phenyl}azepane

300 mg of tert-butyl 4-{4-[(propan-2-yl)oxy]phenyl}azepane-1-carboxylate (intermediate 57, 855 μmol) was solubilised in 5.5 mL dichloromethane, treated with 660 μL trifluoroacetic acid (8.5 mmol) and the mixture was stirred overnight at rt. The reaction mixture was concentrated under reduced pressure, to the residue was added toluene and the solution was evaporated to give 400 mg of the title compound, which was obtained as a TFA salt (85% purity, 170% yield).

1 H-NMR (400 MHz, DMSO-d 6 ): δ [ppm]: 1.23 (d, 6H), 1.55-1.73 (m, 1H), 1.83-1.96 (m, 4H), 2.69-2.84 (m, 1H), 3.00-3.46 (m, 5H), 4.54 (dt, 1H), 6.71-6.96 (m, 2H), 6.97-7.26 (m, 2H), 8.41-8.78 (m, 2H).

Intermediate 59

tert-butyl 5-[(1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonyl)oxy]-2,3,4,7-tetrahydro-1H-azepine-1-carboxylate

5.00 g of tert-butyl 4-oxoazepane-1-carboxylate (22.3 mmol, CAS 188975-88-4) was solubilised in 350 mL tetrahydrofurane, 33 mL bis-(trimethylsilyl)-lithiumamide (1.0 M in THF, 33 mmol) was added dropwise at −70° C. and the solution was stirred for 45 min. at −70° C. 6 mL nonafluorobutane-1-sulfonyl fluoride (33 mmol, CAS 375-72-4) was added dropwise and the solution was stirred overnight at rt. The reaction mixture was quenched with an aqueous solution of sodium bicarbonate and extracted with ethyl acetate three times. The combined organic phases were washed with water and brine, dried over sodium sulfate and the filtrate was concentrated under reduced pressure to give 13.0 g of the title compound (95% purity, 112% yield).

1 H-NMR (400 MHz, DMSO-d 6 ): δ [ppm]: 1.29-1.44 (m, 9H), 1.77-1.91 (m, 1H), 2.51-2.64 (m, 2H), 3.47 (t, 2H), 3.90 (br dd, 1H), 3.94-4.15 (m, 1H), 6.07 (t, 1H).

Intermediate 60

tert-butyl 5-(4-methoxyphenyl)-2,3,4,7-tetrahydro-1H-azepine-1-carboxylate

1.00 g tert-butyl 5-[(1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonyl)oxy]-2,3,4,7-tetrahydro-1H-azepine-1-carboxylate (intermediate 59, 1.92 mmol) and 379 mg (4-methoxyphenyl)boronic acid (2.49 mmol, CAS 5720-07-0) were solubilised in 24 mL toluene and 4.9 mL ethanol, 1.9 mL sodium carbonate solution (2.0 M in water, 3.8 mmol), 163 mg lithium chloride (3.84 mmol) and 222 mg tetrakis(triphenylphosphine)palladium(0) (192 μmol) were added and the mixture was heated for 7 h at 90° C. The reaction mixture was diluted with water and the aqueous phase was extracted with ethyl acetate three times. The combined organic layers were washed with water and brine, dried over sodium sulfate, filterated and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (silica, hexane/ethyl acetate gradient 0-25%) to give 405 mg of the title compound (95% purity, 66% yield).

1 H-NMR (400 MHz, DMSO-d 6 ): δ [ppm]: 1.32-1.44 (m, 9H), 1.72-1.85 (m, 2H), 2.54-2.63 (m, 2H), 3.52 (t, 2H), 3.73 (s, 3H), 3.94 (br dd, 2H), 6.87 (d, 2H), 7.16-7.38 (m, 2H).

Intermediate 61

(rac)-tert-butyl 4-(4-methoxyphenyl)azepane-1-carboxylate

400 mg tert-butyl 5-(4-methoxyphenyl)-2,3,4,7-tetrahydro-1H-azepine-1-carboxylate (intermediate 60, 1.25 mmol) was dissolved in 10 mL methanol, 40 mg palladium on carbon (10%, 376 μmol) was added and the mixture was stirred under hydrogen atmosphere for 4 h at rt. The reaction mixture was filtered through celite (celite pad prewashed with water), the filter cake was washed with less methanol three times. The filtrate was concentrated under reduced pressure to give 370 mg of the title compound (95% purity, 92% yield).

1 H-NMR (400 MHz, DMSO-d e ): δ [ppm]: 1.42 (d, 9H), 1.52-1.95 (m, 6H), 2.52-2.62 (m, 1H), 3.12-3.26 (m, 1H), 3.38-3.47 (m, 1H), 3.49-3.65 (m, 1H), 3.70 (s, 3H), 6.83 (dd, 2H), 7.01-7.24 (m, 2H).

Intermediate 62

(rac)-4-(4-methoxyphenyl)azepane

To a solution of 360 mg tert-butyl 4-(4-methoxyphenyl)azepane-1-carboxylate (intermediate 61, 1.12 mmol) in 7.2 mL dichloromethane was added 860 μL trifluoroacetic acid (110 mmol) and the mixture was stirred overnight at rt. The mixture was concentrated under reduced pressure and the residue was diluted with toluene (2×). The solvent was evaporated to give 400 mg of the title compound as a TFA salt (85% purity, 148% yield).

1 H-NMR (400 MHz, DMSO-d e ): δ [ppm]: 1.55-1.82 (m, 2H), 1.83-2.04 (m, 4H), 2.69-2.86 (m, 1H), 3.00-3.19 (m, 2H), 3.20-3.41 (m, 3H), 3.71 (s, 3H), 6.62-6.96 (m, 2H), 7.05-7.26 (m, 2H).

Intermediate 63

tert-butyl 5-(4-chlorophenyl)-2,3,4,7-tetrahydro-1H-azepine-1-carboxylate

1.00 g tert-butyl 5-[(1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonyl)oxy]-2,3,4,7-tetrahydro-1H-azepine-1-carboxylate (intermediate 59, 1.92 mmol) and 390 mg (4-chlorophenyl)boronic acid (2.49 mmol, CAS 1679-18-1) were solubilised in 24 mL toluene and 4.9 mL ethanol, 1.9 mL sodium carbonate solution (2.0 M in water, 3.8 mmol), 163 mg lithium chloride (3.84 mmol) and 222 mg tetrakis(triphenylphosphine)palladium(0) (192 μmol) were added and the mixture was heated for 7 h at 90° C. The reaction mixture was diluted with water and the aqueous phase was extracted with ethyl acetate three times. The combined organic layers were washed with water and brine, dried over sodium sulfate, filterated and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (silica, hexane/ethyl acetate gradient 0-25%) to give 277 mg of the title compound (95% purity, 45% yield).

1 H-NMR (400 MHz, DMSO-d 6 ): δ [ppm]: 1.38 (br d, 9H), 1.76-1.88 (m, 2H), 2.56-2.62 (m, 2H), 3.52 (t, 2H), 3.96 (br dd, 2H), 5.91-6.23 (m, 1H), 7.23-7.55 (m, 4H).

Intermediate 64

(rac)-tert-butyl 4-(4-chlorophenyl)azepane-1-carboxylate

420 mg tert-butyl 5-(4-chlorophenyl)-2,3,4,7-tetrahydro-1H-azepine-1-carboxylate (intermediate 63, 1.36 mmol) was dissolved in 10 mL methanol, 42 mg palladium on carbon (10%, 250 μmop was added and the mixture was stirred under hydrogen atmosphere for 1 h at rt. The reaction mixture was filtered through celite (celite pad prewashed with water), the filter cake was washed with less methanol three times. The filtrate was concentrated under reduced pressure to give 220 mg of the title compound (95% purity, 49% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.42 (s, 9H), 1.53-1.95 (m, 6H), 2.55-2.70 (m, 1H), 3.12-3.26 (m, 1H), 3.33-3.48 (m, 2H), 3.50-3.65 (m, 1H), 7.16-7.24 (m, 2H), 7.28-7.36 (m, 2H).

Intermediate 65

(rac)-4-(4-chlorophenyl)azepane

To a solution of 205 mg tert-butyl 4-(4-chlorophenyl)azepane-1-carboxylate (intermediate 64, 629 μmol) in 4.0 mL dichloromethane was added 480 μL trifluoroacetic acid (6.3 mmol) and the mixture was stirred overnight at rt. The mixture was concentrated under reduced pressure and the residue was diluted with toluene (2×). The solvent was evaporated to give 175 mg of the title compound as a TFA salt (85% purity, 113% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.62-2.03 (m, 6H), 2.77-2.89 (m, 1H), 3.05-3.20 (m, 2H), 3.20-3.37 (m, 2H), 7.23-7.29 (m, 2H), 7.34-7.40 (m, 2H).

Intermediate 66

2-(4-ethylpiperidin-4-yl)-5-methyl-1,3-benzoxazole

1.18 g 2-amino-4-methylphenol (9.54 mmol, CAS 95-84-1) and 1.50 g 4-ethylpiperidine-4-carboxylic acid (9.54 mmol, CAS 1227465-48-6) were solubilised in 3.0 mL polyphosphoric acid and the mixture was stirred for 2 h at 180° C. The reaction mixture was cooled down to rt, treated with water and the mixture was adjusted to pH=10 with an aqueous solution of potassium hydroxide. The aqueous phase was extracted with ethyl acetate two times, the combined organic phases were washed with water and brine and filtered through a waterresistant filter. The filtrate was concentrated under reduced pressure to give 840 mg of the title compound (97 purity, 35% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 0.63 (t, 3H), 1.53 (ddd, 2H), 1.69 (q, 2H), 2.23 (br d, 2H), 2.41 (s, 3H), 2.45-2.50 (m, 2H), 2.81 (dt, 2H), 3.33 (br s, 1H), 7.13-7.17 (m, 1H), 7.47-7.52 (m, 1H), 7.49-7.57 (m, 1H).

Intermediate 67

tert-butyl 4-[(1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonyl)oxy]-3,6-dihydropyridine-1(2H)-carboxylate

5.30 g tert-butyl 4-oxopiperidine-1-carboxylate (25.3 mmol, CAS 79099-07-3) was solubilised in 400 mL tetrahydrofurane, 38 mL bis-(trimethylsilyl)-lithiumamide (1.0 M in THF, 38 mmol) was added dropwise at −70° C. and the solution was stirred for 45 min. at −70° C. 6.8 mL nonafluorobutane-1-sulfonyl fluoride (38 mmol, CAS 375-72-4) was added dropwise and the solution was stirred overnight at rt. The reaction mixture was quenched with an aqueous solution of sodium bicarbonate and extracted with ethyl acetate three times. The combined organic phases were washed with water and brine, dried over sodium sulfate and the filtrate was concentrated under reduced pressure to give 13.0 g of the title compound (93% purity, 99% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.42 (s, 9H), 2.31-2.37 (m, 2H), 2.38-2.44 (m, 2H), 3.58-3.63 (m, 2H), 3.95-4.00 (m, 1H).

Intermediate 68

tert-butyl 6-methoxy-3′,6′-dihydro[3,4′-bipyridine]-1′(2′H)-carboxylate

1.50 g tert-butyl 4-[(1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonyl)oxy]-3,6-dihydropyridine-1(2H)-carboxylate (intermediate 67, 2.96 mmol) and 589 mg (6-methoxypyridin-3-yl)boronic acid (3.85 mmol, CAS 163105-89-3) were solubilised in 37 mL toluene and 7.5 mL ethanol, 3.0 mL sodium carbonate solution (2.0 M in water, 5.9 mmol), 251 mg lithium chloride (5.92 mmol) and 342 mg tetrakis(triphenylphosphine)palladium(0) (296 μmol) were added and the mixture was heated for 7 h at 90° C. The reaction mixture was diluted with water and the aqueous phase was extracted with ethyl acetate three times. The combined organic layers were washed with water and brine, dried over sodium sulfate and filterated. The filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (silica, dichloromethane/ethanol gradient 0-3%) to give 420 mg of the title compound (80% purity, 48% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.38-1.47 (m, 11H), 2.41-2.47 (m, 2H), 3.53 (br t, 1H), 3.57-3.63 (m, 1H), 3.84 (s, 3H), 3.98 (br s, 1H), 6.08-6.16 (m, 1H), 6.72-6.83 (m, 1H), 7.80 (dd, 1H), 8.22 (d, 1H).

Intermediate 69

6-methoxy-1′,2′,3′,6′-tetrahydro-3,4′-bipyridine

To a solution of 350 mg tert-butyl 6-methoxy-3′,6′-dihydro[3,4′-bipyridine]-1′(2′H)-carboxylate (intermediate 68, 1.15 mmol) in 7.4 mL dichloromethane was added 880 μL trifluoroacetic acid (11 mmol) and the mixture was stirred for 4 h at rt. The mixture was concentrated under reduced pressure and the residue was diluted with toluene (2×). The solvent was evaporated to give 330 mg of the title compound as a TFA salt (85% purity, 128% yield).

LC-MS (Method 2): Rt=0.85 min; MS (ESIpos): m/z=191.7 [M+H]+

Intermediate 70

4-(6-methoxy-3′,6′-dihydro[3,4′-bipyridin]-1′(2′H)-yl)-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

167 mg 4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile (765 μmol, CAS 150617-68-8), 218 mg 6-methoxy-1′,2′,3′,6′-tetrahydro-3,4′-bipyridine (1.15 mmol, intermediate 69) and 210 μL triethylamine (1.5 mmol) were solubilised in 5.0 mL 2-propanol and the mixture was stirred for 4 h at 90° C. The reaction mixture was diluted with ethyl acetate, the organic layer was washed with water and brine, dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to give 30 mg of the title compound (95% purity, 10% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 2.81 (br s, 2H), 3.58 (s, 3H), 3.82-3.87 (m, 5H), 4.34 (br d, 2H), 6.33 (s, 1H), 6.85 (d, 1H), 7.34 (s, 1H), 7.56-7.61 (m, 1H), 7.75 (s, 1H), 7.85-7.92 (m, 2H), 8.32 (d, 1H).

Intermediate 71

tert-butyl 6-methyl-3′,6′-dihydro[3,4′-bipyridine]-1(2′H)-carboxylate

1.00 g tert-butyl 4-[(1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonyl)oxy]-3,6-dihydropyridine-1(2H)-carboxylate (intermediate 67, 1.97 mmol) and 351 mg (6-methylpyridin-3-yl)boronic acid (2.57 mmol, CAS 659742-21-9) were solubilised in 25 mL toluene and 5 mL ethanol, 2.0 mL sodium carbonate solution (2.0 M in water, 3.9 mmol), 167 mg lithium chloride (3.95 mmol) and 228 mg tetrakis(triphenylphosphine)palladium(0) (197 μmol) were added and the mixture was heated for 6 h at 90° C. The reaction mixture was diluted with water and the aqueous phase was extracted with ethyl acetate three times. The combined organic layers were washed with water and brine, dried over sodium sulfate, filterated and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (silica, dichloromethane/ethanol gradient 0-1%) to give 155 mg of the title compound (95% purity, 27% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.42 (s, 9H), 2.43-2.47 (m, 5H), 3.54 (t, 2H), 3.99 (br s, 2H), 6.20 (br s, 1H), 7.22 (d, 1H), 7.53-7.65 (m, 2H), 7.71 (dd, 1H).

Intermediate 72

6-methyl-1′,2′,3′,6′-tetrahydro-3,4′-bipyridine

To a solution of 150 mg tert-butyl 6-methyl-3′,6′-dihydro[3,4′-bipyridine]-1′(2′H)-carboxylate (519 μmol, intermediate 71) in 3.3 mL dichloromethane was added 400 μL trifluoroacetic acid (5.2 mmol) and the mixture was stirred for 4 h at rt. The mixture was concentrated under reduced pressure and the residue was diluted with toluene (2×). The solvent was evaporated to give 210 mg of the title compound as a TFA salt (95% purity, 220% yield).

LC-MS (Method 2): Rt=0.75 min; MS (ESIpos): m/z=175.6 [M+H]+

Intermediate 73

1-methyl-4-(6-methyl-3′,6′-dihydro[3,4′-bipyridin]-1′(2′H)-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile

167 mg 4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile (765 μmol, CAS 150617-68-8), 200 mg 6-methyl-1′,2′,3′,6′-tetrahydro-3,4′-bipyridine (1.15 mmol, intermediate 72) and 210 μL triethylamine (1.5 mmol) were solubilised in 4.2 mL 2-propanol and the mixture was stirred for 4 h at 90° C. The reaction mixture was diluted with ethyl acetate, the organic layer was washed with water and brine, dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to give 41 mg of the title compound (95% purity, 14% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 2.47 (s, 3H), 2.83 (br d, 2H), 3.59 (s, 3H), 3.85 (t, 2H), 4.36 (br d, 2H), 6.39-6.43 (m, 1H), 7.27 (d, 1H), 7.31-7.37 (m, 1H), 7.58 (d, 1H), 7.75 (ddd, 1H), 7.82 (dd, 1H), 7.88 (dd, 1H), 8.62 (d, 1H).

Intermediate 74

tert-butyl 3′,6′-dihydro[3,4′-bipyridine]-1′(2′H)-carboxylate

1.00 g tert-butyl 4-[(1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonyl)oxy]-3,6-dihydropyridine-1(2H)-carboxylate (1.97 mmol, intermediate 67) and 315 mg pyridin-3-ylboronic acid (2.57 mmol, CAS 1692-25-7) were solubilised in 25 mL toluene and 5 mL ethanol, 2.0 mL sodium carbonate solution (2.0 M in water, 3.9 mmol), 167 mg lithium chloride (3.95 mmol) and 228 mg tetrakis(triphenylphosphine)palladium(0) (197 μmol) were added and the mixture was heated for 4 h at 90° C. The reaction mixture was diluted with water and the aqueous phase was extracted with ethyl acetate three times. The combined organic layers were washed with water and brine, dried over sodium sulfate, filterated and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (silica, dichloromethane/ethanol gradient 0-1%) to give 155 mg of the title compound (95% purity, 27% yield).

LC-MS (Method 2): Rt=1.12 min; MS (ESIpos): m/z=261.8 [M+H]+

Intermediate 75

1′,2′,3′,6′-tetrahydro-3,4′-bipyridine

To a solution of 170 mg tert-butyl 6-methyl-3′,6′-dihydro[3,4′-bipyridine]-1′(2′H)-carboxylate (intermediate 74, 62 μmol) in 4.0 mL dichloromethane was added 480 μL trifluoroacetic acid (6.2 mmol) and the mixture was stirred overnight at rt. The mixture was concentrated under reduced pressure and the residue was diluted with toluene (2×). The solvent was evaporated to give 250 mg of the title compound as a TFA salt (90% purity, 226% yield).

LC-MS (Method 2): Rt=0.64 min; MS (ESIpos): m/z=161.5 [M+H]+

Intermediate 76

4-(3′,6′-dihydro[3,4′-bipyridin]-112′H)-yl)-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

167 mg 4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile (765 μmol, CAS 150617-68-8), 184 mg 1′,2′,3′,6′-tetrahydro-3,4′-bipyridine (intermediate 75, 1.15 mmol) and 210 μL triethylamine (1.5 mmol) were solubilised in 4.2 mL 2-propanol and the mixture was stirred for 4 h at 90° C. The reaction mixture was diluted with et hyl acetate, the organic layer was washed with water and brine, dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (silica, dichloromethane/ethanol gradient 0-3%) to give 62 mg of the title compound (95% purity, 22% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 2.08 (s, 1H), 2.86 (br s, 2H), 3.59 (s, 3H), 3.85 (t, 2H), 4.37 (br d, 2H), 6.47 (br s, 1H), 7.30-7.46 (m, 2H), 7.58 (d, 1H), 7.70-7.80 (m, 1H), 7.85-7.96 (m, 2H), 8.51 (dd, 1H), 8.77 (d, 1H).

Intermediate 77

4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methylquinolin-2(1H)-one

1.00 g 4-chloro-1-methylquinolin-2(1H)-one (5.16 mmol, CAS 32262-17-2) was solubilised in 40 mL dimethylsulfoxide, 2.7 mL N,N-diisopropylethylamine (15 mmol) and 6.77 g 2-(piperidin-4-yl)-1,3-benzothiazole (31.0 mmol, CAS 51784-73-7) were added and the mixture was stirred overnight at 110° C. The reaction mixture was diluted with water and the aqueous phase was extracted with dichloromethane three times. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (silica, dichloromethane/methanol gradient 0-50%) to give 1.64 g of the title compound (85% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 2.07-2.21 (m, 2H), 2.24-2.33 (m, 2H), 2.86-2.98 (m, 2H), 3.37-3.47 (m, 1H), 3.57 (m+s, 5H), 6.07 (s, 1H), 7.29 (td, 1H), 7.40-7.46 (m, 1H), 7.48-7.55 (m, 2H), 7.58-7.65 (m, 1H), 7.83 (dd, 1H), 7.96-8.01 (m, 1H), 8.10 (dd, 1H).

Intermediate 78

4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-3-bromo-1-methylquinolin-2(1H)-one

1.00 g 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methylquinolin-2(1H)-one (intermediate 77, 2.66 mmol) was solubilised in 45 mL acetonitrile, 569 mg N-bromosuccinimide (3.20 mmol) was added and the mixture was stirred for 3.5 h at rt. The reaction mixture was concentrated under reduced pressure and the residue was purified by flash chromatography (silica, dichloromethane/methanol gradient 0-10%) to give 1.00 g of the title compound (83% yield).

LC-MS (Method 1): R t =1.43 min; MS (ESIpos): m/z=454 [M+H]+

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 2.13 (qd, 2H) 2.22-2.31 (m, 2H) 3.37-3.49 (m, 1H) 3.57-3.67 (m, 2H) 3.69 (s, 3H) 7.34-7.40 (m, 1H) 7.41-7.46 (m, 1H) 7.49-7.55 (m, 1H) 7.56-7.61 (m, 1H) 7.65-7.72 (m, 1H) 7.96-8.02 (m, 1H) 8.03-8.08 (m, 1H) 8.08-8.14 (m, 1H).

Intermediate 79

methyl 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate

357 mg 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-3-bromo-1-methylquinolin-2(1H)-one (intermediate 78, 786 μmol) was dissolved in 12 mL methanol and 1.2 mL tetrahydrofurane, 65 mg 1,1′bis(diphenylphosphino)ferrocene-palladium(II)dichloride-dichloromethane complex (1.6 mmol) and 220 μL triethylamie (1.6 mmol) were added and the mixture was stirred for 22 h at 100° C. (15 bar) under carbon monooxide atmosphere. The reaction mixture was cooled down to rt and atmospheric pressure, diluted with dichloromethane and the suspension was filtered. The filter cake was washed with less dichloromethane three times and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (silica, dichloromethane/methanol gradient 0-5%) to give 312 mg of the title compound (92% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 2.05-2.19 (m, 2H) 2.21-2.30 (m, 2H) 3.05 (br t, 2H) 3.38-3.48 (m, 3H) 3.59 (s, 3H) 3.84 (s, 3H) 7.32-7.40 (m, 1H) 7.40-7.47 (m, 1H) 7.48-7.54 (m, 1H) 7.56 (d, 1H) 7.65-7.73 (m, 1H) 7.94 (dd, 1H) 7.99 (d, 1H) 8.07-8.15 (m, 1H).

LC-MS (Method 1): R t =1.34 min; MS (ESIpos): m/z=435 [M+H] +

Intermediate 80

4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid

254 mg methyl 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate (intermediate 79, 586 μmol) was dissolved in 20 mL tetrahydrofurane and 20 mL ethanol, 12 mL lithium hydroxide solution (1.0 M in water, 12 mmol) and the mixture was stirred for 12 h at 80° C. The reaction mixture was cooled d own to rt, diluted with water and adjusted to pH=5 with hydrogen chloride solution (1M in water) and the aqueous phase was extracted with dichloromethane three times. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (silica, dichloromethane/methanol gradient 0-3%) to give 100 mg of the title compound (41% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 1.98-2.23 (m, 3H) 2.25-2.36 (m, 2H) 2.86-2.99 (m, 1H) 3.53 (br d, 2H) 3.55-3.61 (m, 3H) 7.22-7.32 (m, 1H) 7.38-7.46 (m, 1H) 7.47-7.58 (m, 2H) 7.59-7.66 (m, 1H) 7.91 (dd, 1H) 7.84 (dd, 1H) 7.79-7.88 (m, 1H) 7.95-8.02 (m, 1H) 8.07-8.15 (m, 1H).

Intermediate 81

8-fluoro-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione

5.00 g 8-fluoro-2H-3,1-benzoxazine-2,4(1H)-dione (26.2 mmol, CAS174463-53-7) was dissolved in 200 mL dimethyl formamide, cooled down to 0° C., 2.4 mL iodomethane (39 mmol) and then 1.45 g sodium hydride (65% purity, 39.3 mmol) were added dropwise and the mixture was stirred overnight at rt. The reaction mixture was diluted with water, the aqueous phase was extracted with ethyl acetate two times. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (silica, hexane/ethyl acetate gradient 0-25%) to give 2.40 g of the title compound (95% purity, 45% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 3.61 (d, 3H), 7.33 (td, 1H), 7.76 (ddd, 1H), 7.80-7.92 (m, 1H).

Intermediate 82

8-fluoro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

2.40 g 8-fluoro-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (intermediate 81, 11.7 mmol) was solubilised in 27 mL tetrahydrofurane and 13 mL triethylamine (93 mmol) was added dropwise at rt. Then 1.9 mL ethyl cyanoacetate (18 mmol) was added and the mixture was stirred overnight at 70° C. The reaction mixture was cooled down to rt and concentrated under reduced pressure. The residue was diluted with less ethyl acetate and water, the mixture was adjusted to pH=1 with hydrogen chloride solution (2 M in water) and the resulting solid was filtered off. The filter cake was washed with less water and dried in vacuum to give 2.40 g of the title compound (95% purity, 99% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 3.68 (d, 3H), 7.25 (td, 1H), 7.58 (ddd, 1H), 7.89 (dt, 1H).

Intermediate 83

4-chloro-8-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

1.80 g 8-fluoro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile (intermediate 82, 7.84 mmol) was suspended in 7.3 mL phosphoryl chloride (78 mmol) and the mixture was stirred for 20 h at 90° C. The reaction mixture was cooled d own to rt, diluted with ice water and adjusted to pH=10 with sodium bicarbonate (solid). The resulting solid was filtered off to give 1.50 g of the title compound (95% purity, 77% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 3.80 (d, 3H), 7.48 (td, 1H), 7.77-7.84 (m, 1H), 7.95 (dt, 1H).

Intermediate 84

8-bromo-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione

90.0 g 8-bromo-2H-3,1-benzoxazine-2,4(1H)-dione (372 mmol, CAS 331646-98-1) was solubilised in 720 mL N,N-dimethylacetamide, 130 mL N,N-diisoprpylethylamine and 69 mL iodomethane (1.1 mol) was added and the suspension was stirred overnight at rt. The reaction mixture was diluted with 3 L water and the resulting solid was filtered off. The filter cake was washed with ethanol and then with hexane to give 86.1 g of the title compound (90% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 3.64 (s, 3H), 7.26 (t, 1H), 8.00 (dd, 1H), 8.09 (dd, 1H).

Intermediate 85

8-bromo-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

40 g 8-bromo-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (intermediate 84, 156 mmol) was dissolved in 320 mL tetrahydrofurane, 170 mL triethylamine (1.2 mol) and then 50 mL ethyl cyanoacetate (470 mmol) were added and the mixture was stirred for 24 h at 70° C. The reaction mixture was cooled down to rt and concentrated under reduced pressure. The residue was diluted with water and ethyl acetate and the mixture was adjusted to pH=1 with hydrogen chloride solution (2 N in water). The suspension was filtered and the filter cake was washed with water and less ethyl acetate to give 36.01 g of the title compound (83% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 3.63-3.73 (m, 3H) 6.09-6.42 (m, 1H) 7.21 (dt, 1H) 7.83-8.12 (m, 2H).

Intermediate 86

8-bromo-4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

35.6 g 8-bromo-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile (intermediate 85, 127 mmol) was suspended in 120 mL phosphoryl chloride (1.3 mol) and the mixture was stirred overnight at 90° C. The reaction mixture was cooled down to rt, diluted with 125 mL hexane and the suspension was filtered. The filter cake was diluted carefully with sodium bicarbonate solution (2 M in water) and the suspension was stirred for 10 min. at rt. The basic suspension was filtered, the filter cake was washed with water and ethyl acetate and dried in a vacuum oven at 50° C. The solid was suspended in dichloromethane and crystallized, filtered the solid off and dried the solid in vacuum at 100° C. to give 6.12 g of the title compound (16% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 3.80 (s, 3H) 7.29-7.51 (m, 1H) 8.01-8.32 (m, 2H).

Intermediate 87

8-chloro-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione

4.00 g 8-fluoro-2H-3,1-benzoxazine-2,4(1H)-dione (19.2 mmol, CAS 63497-60-9) was dissolved in 33 mL dimethyl formamide, cooled down to 0° C., 6. 7 mL N,N-diisoprpylamine and then 3.6 mL iodomethane (58 mmol) were added dropwise and the mixture was stirred overnight at rt. The suspension was concentrated under reduced pressure (to half-amount), then diluted with ice water and the resulting solid was filtered. The filter cake was washed with water and then with less hexane and concentrated in vacuum to give 4.40 g of the title compound (90% purity, 97% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 3.64 (s, 3H) 7.34 (t, 1H) 7.79-8.06 (m, 2H).

Intermediate 88

8-chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

4.35 g 8-chloro-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (intermediate 87, 18.5 mmol) was solubilised in 45 mL 2-methyl tetrahydrofurane, 21 mL triethylamine (150 mmol) and then 7.9 mL ethyl cyanoacetate (74 mmol) were added carefully and the suspension was stirred for 18 h at 80° C. The reaction mixture was concentrated under reduced pressure, the residue was diluted with water and ethyl acetate and the mixture was adjusted to pH=1 with hydrogen chloride solution (2 M in water). The resulting solid was filtered and the filter cake was washed with less hexane to give 3.87 g of the title compound (99% purity, 88% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 3.68 (s, 3H) 7.25 (t, 1H) 7.75 (dd, 1H) 7.91-8.10 (m, 1H).

Intermediate 89

4,8-dichloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

3.80 g 8-chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile (intermediate 88, 16.2 mmol) was suspended in 23 mL phosphoryl chloride (16.2 mmol) and the mixture was stirred overnight at 90° C. The reaction mixture was cooled down to rt, diluted with 400 mL ice water and the aqueous phase was extracted with dichloromethane three times. The combined organic phases were washed with sodium bicarbonate solution (2 M in water, filtered through a waterresistant filter and the filtrate was concentrated under reduced pressure. The residue was suspended in a mixture of 25 mL dichloromethane and of 25 mL ethanol and the suspension was stirred for 1 h at rt. The solid was filtered off and dried in vacuum oven to give 1.66 g of the title compound (94% purity, 38% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 3.81 (s, 3H) 7.40-7.62 (m, 1H) 7.95-8.03 (m, 1H) 8.05-8.19 (m, 1H).

Intermediate 90

1,6-dimethyl-2H-3,1-benzoxazine-2,4(1H)-dione

10.0 g 6-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (53.6 mmol, CAS 4692-99-3) was solubilised in 100 mL N,N-dimethylacetamide, 19 mL N,N-diisoprpylethylamine (110 mmol) and 10 mL iodomethane (160 mmol) was added and the suspension was stirred overnight at rt. The reaction mixture was diluted with water and the resulting solid was filtered off. The filter cake was washed with ethanol and then with hexane to give 9.10 g of the title compound (95% purity, 85% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 2.37 (s, 3H), 3.44 (s, 3H), 7.35 (d, 1H), 7.68 (dd, 1H), 7.82 (d, 1H).

Intermediate 91

4-hydroxy-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

9.10 g 1,6-dimethyl-2H-3,1-benzoxazine-2,4(1H)-dione (intermediate 90, 45.2 mmol) was solubilised in 100 mL tetrahydrofurane, 50 mL triethylamine (360 mmol) and then 7.2 mL ethyl cyanoacetate (68 mmol) were added carefully and the suspension was stirred for 24 h at 70° C. The reaction mixture was diluted with water and ethyl acetate and the mixture was adjusted to pH=1 with hydrogen chloride solution (2 N in water). The resulting solid was filtered and the filter cake was washed with less hexane to give 8.00 g of the title compound (95% purity, 78% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 2.38 (s, 3H), 3.53 (s, 6H), 7.45 (d, 1H), 7.59 (dd, 1H), 7.90 (d, 1H).

Intermediate 92

4-chloro-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

8.00 g 4-hydroxy-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile (intermediate 91, 35.5 mmol) was suspended in 33 mL phosphoryl chloride (350 mmol) and the mixture was stirred overnight at 90° C. The reaction mixture was cooled down to rt, diluted with 4 L ice water and the aqueous phase was adjusted to pH=10 with sodium bicarbonate (solid). The resulting solid was filtered off, the filter cake was washed with less water and ethyl acetate. The impure solid was purified by flash chromatography (silica, dichloromethane/ethanol gradient 0-1%) to give 2.90 g of the title compound (94% purity, 38% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 2.44 (s, 3H), 3.65 (s, 3H), 7.65 (d, 1H), 7.79 (br d, 1H), 7.86-7.90 (m, 1H).

Intermediate 93

6-bromo-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione

20.0 g 6-bromo-2H-3,1-benzoxazine-2,4(1H)-dione (82.6 mmol, CAS 4692-98-2) was solubilised in 160 mL N,N-dimethylacetamide, 29 mL N,N-diisoprpylethylamine (170 mmol) and 15 mL iodomethane (250 mmol) were added and the suspension was stirred for 72 h at rt. The reaction mixture was diluted with water and the resulting solid was filtered off. The filter cake was washed with ethanol and dried in a vacuum oven at 100° C. to give 20.7 g of the title compound (98% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 3.45 (s, 3H) 7.42 (d, 1H) 7.98-8.04 (m, 1H) 8.06-8.11 (m, 1H).

LC-MS (Method 1): R t =0.95 min; MS (ESIpos): m/z=256 [M+H] +

Intermediate 94

6-bromo-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

4.42 g 6-bromo-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (intermediate 93, 17.3 mmol) was solubilised in 35 mL tetrahydrofurane, 19 mL triethylamine (140 mmol) and then 3.5 mL ethyl cyanoacetate (33 mmol) were added carefully and the suspension was stirred 72 h at 90° C. The reaction mixture was cooled down to rt, diluted with water and ethyl acetate (1:1) and the mixture was adjusted to pH=1 with hydrogen chloride solution (2 M in water). The resulting solid was filtered and the filter cake was washed with less water and ethyl acetate to give 3.24 g of the title compound (67% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 3.49 (s, 3H) 7.44 (d, 1H) 7.75-7.92 (m, 1H) 8.06-8.38 (m, 1H).

LC-MS (Method 1): R t =0.75 min; MS (ESIpos): m/z=279 [M+H] +

Intermediate 95

6-bromo-4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

3.23 g 6-bromo-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile (intermediate 94, 11.6 mmol) was suspended in 22 mL phosphoryl chloride (230 mmol) and the mixture was stirred overnight at 90° C. The reaction mixture was cooled down to rt, diluted with 4 L ice water and the aqueous phase was adjusted to pH=10 with sodium bicarbonate (solid). The resulting solid was filtered off, the filter cake was washed with less water and ethanol and dried in a vacuum oven at 100° C. to give 3.10 g of the title compound (94% purity, 90% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 3.65 (s, 4H) 7.70 (d, 1H) 8.06 (dd, 1H) 8.11-8.28 (m, 1H).

LC-MS (Method 1): R t =1.14 min; MS (ESIpos): m/z=297 [M+H] +

Intermediate 96

6-methyl-2-(4-methylpiperidin-4-yl)-1,3-benzoxazole

860 mg 2-amino-5-methylphenol (6.98 mmol, CAS 2835-98-5) and 1.00 g 4-methylpiperidine-4-carboxylic acid (6.98 mmol, CAS 162648-32-0) were suspended in 10 mL polyphosphoric acid and the mixture was stirred for 4 h at 180° C. The hot reaction mixture was added dropwise into water and the mixture was adjusted to pH=10 with potassium hydroxide solution (1 M in water). The aqueous phase was extracted with ethyl acetate three times, the combined organic phases were washed with brine, filtered through a waterresistant filter and the filtrate was concentrated under reduced pressure to give 880 mg of the title compound (95% purity, 52% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.33 (s, 3H), 1.56 (ddd, 2H), 2.17 (dt, 2H), 2.42 (s, 3H), 2.52-2.60 (m, 2H), 2.74-2.85 (m, 2H), 7.13-7.17 (m, 1H), 7.48-7.50 (m, 1H), 7.56 (d, 1H).

Intermediate 97

6-methoxy-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione

To a solution of 4.6 g 6-methoxy-2H-3,1-benzoxazine-2,4(1H)-dione (22.6 mmol, CAS 37795-77-0) and 7.9 mL N,N-diisopropylethylamine (45 mmol) in 42 mL N,N-dimethylacetamide was added 4.2 mL iodomethane (68 mmol) at rt and was stirred overnight. The reaction was added to 1000 mL water. The solid that precipitated from this procedure was collected by filtration, washed with water, ethanol and hexane and dried in vacuum. 4.3 g of the title compound were obtained (87% yield).

1 H NMR (DMSO-d 6 ) δ [ppm]: 3.45 (s, 3H); 3.84 (s, 3H); 7.39-7.49 (m, 3H).

Intermediate 98

4-hydroxy-6-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

A suspension of 4.3 g 6-methoxy-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (intermediate 97, 19.7 mmol) in 45 mL THF was slowly treated with 22 mL triethylamine (160 mmol) followed by the addition of 3.2 mL ethyl cyanoacetate (30 mmol) and was stirred for 24 h at 70° C. After cooling to rt, ethyl acetate and water were added and the mixture was acidified to pH=1 by addition of hydrochloric acid (2 N). The resulting precipitate was collected by filtration to give 2.7 g of the title compound (57% yield).

1 H NMR (400 MHz, DMSO-d 6 ) δ [ppm]: 3.53 (s, 3H); 3.83 (s, 3H); 7.38 (dd, 1H); 7.47-7.51 (m, 1H); 7.57 (d, 1H).

Intermediate 99

4-chloro-6-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile

A mixture of 2.7 g 4-hydroxy-6-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile (intermediate 98, 11.7 mmol) and 11 mL phosphoric trichloride (120 mmol) was stirred for 10 h at 90° C. After cooling to rt, ice water (2000 ml) w as added carefully and the mixture was adjusted to pH=10 with sodium carbonate. The precipitate was collected by filtration to obtain 2.6 g of a crude solid. This solid was purified by flash chromatography (silica; dichloromethane/methanol gradient 0-3%) to give 700 mg of the title compound (23% yield).

1 H NMR (400 MHz, DMSO-d 6 ) b [ppm]: 3.6