Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy

This claims priority to U.S. Patent Application No. 61/789,382, filed on Mar. 15, 2013, the entire contents of which are fully incorporated herein by reference.

The present invention relates to pyrrolidine derivatives, pharmaceutical compositions comprising such pyrrolidine derivatives, and the use of such pyrrolidine derivatives for therapeutic purposes.

The pyrrolidine motif is an important pharmacophore possessing biological activity against a number of different targets and thus has found use in various advanced pharmaceutical research compounds and clinical candidates (such as Factor Xa inhibitors, NK3 receptor antagonists, DPP-IV inhibitors, PDE-IV inhibitors, or MC4 receptorselective agonists).

A pyrrolidine compound already known in the art as type IV phosphodiesterase inhibitor (PDE-IV) is for example:

WO 9508534, US 2006074123, WO 2001047915, US 20020169196, WO 2001047879 and WO 2001047914 describe further PDE-IV inhibitors having related structures.

Further, the synthesis of certain trisubstituted pyrrolidine derivatives has been reported in Baumann Marcus, et al., ACS Comb. Sci. 2011, 13, 405-413.

Dysfunction of glutamatergic pathways has been implicated in a number of disease states in the human central nervous system (CNS) including but not limited to schizophrenia, cognitive deficits, dementia, Parkinson disease, Alzheimer disease and bipolar disorder. A large number of studies in animal models lend support to the NMDA hypofunction hypothesis of schizophrenia.

NMDA receptor function can be modulated by altering the availability of the co-agonist glycine. This approach has the critical advantage of maintaining activity-dependent activation of the NMDA receptor because an increase in the synaptic concentration of glycine will not produce an activation of NMDA receptors in the absence of glutamate. Since synaptic glutamate levels are tightly maintained by high affinity transport mechanisms, an increased activation of the glycine site will only enhance the NMDA component of activated synapses.

Two specific glycine transporters, GlyT1 and GlyT2 have been identified and shown to belong to the NaCl-dependent family of neurotransmitter transporters which includes taurine, gamma-aminobutyric acid (GABA), proline, monoamines and orphan transporters. GlyT1 and GlyT2 have been isolated from different species and shown to have only 50% identity at the amino acid level. They also have a different pattern of expression in mammalian central nervous system, with GlyT2 being expressed in spinal cord, brainstem and cerebellum and GlyT1 present in these regions as well as forebrain areas such as cortex, hippocampus, septum and thalamus. At the cellular level, GlyT2 has been reported to be expressed by glycinergic nerve endings in rat spinal cord whereas GlyT1 appears to be preferentially expressed by glial cells. These expression studies have led to the suggestion that GlyT2 is predominantly responsible for glycine uptake at glycinergic synapses whereas GlyT1 is involved in monitoring glycine concentration in the vicinity of NMDA receptor expressing synapses. Recent functional studies in rat have shown that blockade of GlyT1 with the potent inhibitor (N-[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)propyl])-sarcosine (NFPS) potentiates NMDA receptor activity and NMDA receptor-dependent long-term potentiation in rat.

Molecular cloning has further revealed the existence of three variants of GlyT1, termed GlyT-1a, GlyT-1b and GlyT-1c, each of which displays a unique distribution in the brain and peripheral tissues. The variants arise by differential splicing and exon usage, and differ in their N-terminal regions.

The physiological effects of GlyT1 in forebrain regions together with clinical reports showing the beneficial effects of GlyT1 inhibitor sarcosine in improving symptoms in schizophrenia patients suggest that selective GlyT1 inhibitors represent a new class of antipsychotic drugs.

Glycine transporter inhibitors are already known in the art, for example:

(see also Hashimoto K., Recent patents on CNS Drug Discovery, 2006, 1, 43-53; Harsing L. G. et al., Current Medicinal Chemistry, 2006, 13, 1017-1044; Javitt D. C., Molecular Psychiatry (2004) 9, 984-997; Lindsley, C. W. et al., Current Topics in Medicinal Chemistry, 2006, 6, 771-785; Lindsley C. W. et al., Current Topics in Medicinal Chemistry, 2006, 6, 1883-1896).

Further glycine transporter inhibitors are known from the following documents.

WO 2009024611 describes 4-benzylaminoquinolines of formula:

WO 2009121872 describes tetrahydroisoquinoline of formula:

WO 2010092180 describes aminotetraline derivatives of formula:

WO 2010092181 describes heterocyclic compounds of formula:

WO 2012020131 describes aminoindane derivatives of formula:

WO 2012020130 describes phenalkylamine derivatives of formula:

WO 2012020133 describes tetraline and indane derivatives of formula:

WO 2012152915 describes benzazepine derivatives of formula:

WO 2012020134 describes phenalkylamine derivatives of formula:

and of formula:

US 20130035323 describes aminochromane, aminothiochromane and amino-1,2,3,4-tetrahydroquinoline derivatives of formula:

It was one object of the present invention to provide further glycine transporter inhibitors.

The present invention relates to pyrrolidine derivatives of the formula (I)

wherein

R 1 is C 1 -C 8 -alkyl, (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl, (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl, (optionally substituted C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl, optionally substituted C 3 -C 12 -cycloalkyl, optionally substituted C 6 -C 12 -aryl, or optionally substituted C 3 -C 12 -heterocyclyl; R 2a , R 2b

are independently hydrogen, halogen, or C 1 -C 3 -alkyl; or

R 2a , R 2b

together with the carbon atom to which they are bound may form a C═O;

R 3a

is C 3 -C 12 -cycloalkyl, optionally substituted C 6 -C 12 -aryl, hydroxy, C 1 -C 6 -alkoxy, halogenated C 1 -C 6 -alkoxy, C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy, C 2 -C 6 -alkenyloxy, C 6 -C 12 -aryl-C 1 -C 4 -alkoxy, C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkoxy, optionally substituted C 6 -C 12 -aryloxy, C 3 -C 12 -heterocyclyloxy, or optionally substituted C 3 -C 12 -heterocyclyl;

R 3b is hydrogen, C 1 -C 6 -alkyl, or hydroxy; Y 1 is >CR 6 — or >N—; R 6 is hydrogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl, hydroxy-C 1 -C 6 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 6 -alkyl, or hydroxy; R 4 is —(CR 7a R 7b ) n1 OR 10 , —(CR 7c R 7d ) n2 NR 11a R 11b , —(CR 7e R 7f ) n3 R 12 , optionally substituted C 6 -C 12 -aryl, —NR 8a (CR 9a R 9b ) n4 R 13 , —NR 8b COR 14 , —NR 8c COOR 15 , —NR 8d CONR 16a R 16b , —NR 8e SO 2 R 17 , —O(CR 9c R 9d ) n5 R 18 , —COR 19 , —CONR 20a R 20b , —SO 2 R 21 , or optionally substituted C 3 -C 12 -heterocyclyl; R 7a , R 7b

are independently hydrogen or C 1 -C 6 -alkyl;

n1 is 1, 2, 3, or 4; R 10 is hydrogen, optionally substituted C 6 -C 12 -aryl, or optionally substituted C 3 -C 12 -heterocyclyl; R 7c , R 7d

are independently hydrogen or C 1 -C 6 -alkyl;

n2 is 1, 2, 3, or 4; R 11a is C 1 -C 8 -alkyl, (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl, (optionally substituted C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl, optionally substituted C 6 -C 12 -aryl, or optionally substituted C 3 -C 12 -heterocyclyl; R 11b

is hydrogen or C 1 -C 6 -alkyl;

R 7e , R 7f

are independently hydrogen or C 1 -C 6 -alkyl;

n3 is 1, 2, 3, or 4; R 12

is optionally substituted C 6 -C 12 -aryl or optionally substituted C 3 -C 12 -heterocyclyl;

R 8a , R 8b , R 8c , R 8d , R 8e

are independently hydrogen, C 1 -C 6 -alkyl, or C 1 -C 6 -alkylcarbonyl, or

R 6 and one of R 8a , R 8b , R 8c , R 8d , or R 8e

together are optionally substituted C 1 -C 5 -alkylene, wherein one or more —CH 2 — of C 1 -C 5 -alkylene may be independently replaced by a an oxygen atom or C═O;

R 9a , R 9b

are independently hydrogen, halogen, C 1 -C 6 -alkyl, hydroxy, or C 1 -C 6 -alkoxy;

n4 is 0, 1, 2, 3, or 4; R 13 is hydrogen, C 1 -C 8 -alkyl, halogenated C 1 -C 6 -alkyl, (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, optionally substituted C 3 -C 12 -cycloalkyl, C 2 -C 6 -alkenyl, optionally substituted C 3 -C 6 -cycloalkenyl, optionally substituted C 6 -C 12 -aryl, hydroxy, C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy, optionally substituted C 6 -C 12 -aryloxy, optionally substituted C 3 -C 12 -heterocyclyloxy, optionally substituted C 3 -C 12 -heterocyclyl, or tri-(C 1 -C 4 -alkyl)-silyloxy; R 14 is C 1 -C 8 -alkyl, halogenated C 1 -C 6 -alkyl, (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl, (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl, hydroxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, (optionally substituted C 6 -C 12 -aryloxy)-C 1 -C 4 -alkyl, C 1 -C 6 -alkylcarbonyl-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxycarbonyl-C 1 -C 4 -alkyl, C 1 -C 6 -alkylaminocarbonyl-C 1 -C 4 -alkyl, optionally substituted (C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl, optionally substituted C 3 -C 12 -cycloalkyl, optionally substituted C 6 -C 12 -aryl, or optionally substituted C 3 -C 12 -heterocyclyl; R 15 is C 1 -C 8 -alkyl, optionally substituted C 6 -C 12 -aryl, or optionally substituted C 3 -C 12 -heterocyclyl; R 16a is (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl, optionally substituted (C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl, optionally substituted C 6 -C 12 -aryl, or optionally substituted C 3 -C 12 -heterocyclyl; R 16b is hydrogen or C 1 -C 6 -alkyl; R 17 is (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl, (optionally substituted C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl, optionally substituted C 6 -C 12 -aryl, or optionally substituted C 3 -C 12 -heterocyclyl; R 9c , R 9d

are independently hydrogen, halogen, or C 1 -C 6 -alkyl;

n5 is 0, 1, 2, 3, or 4; R 18 is hydrogen, C 1 -C 8 -alkyl, optionally substituted C 3 -C 12 -cycloalkyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, halogenated C 1 -C 6 -alkoxycarbonyl, C 6 -C 12 -aryloxycarbonyl, C 1 -C 6 -alkylaminocarbonyl, (halogenated C 1 -C 4 -alkyl)aminocarbonyl, C 6 -C 12 -arylaminocarbonyl, optionally substituted C 6 -C 12 -aryl, C 1 -C 6 -alkylamine, (C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl)amino, (halogenated C 1 -C 6 -alkyl)amino, (C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl)amino, (C 6 -C 12 -aryl-C 1 -C 4 -alkyl)amino, C 1 -C 6 -dialkylamine, optionally substituted C 6 -C 12 -arylamine, or optionally substituted C 3 -C 12 -heterocyclyl; R 19 is optionally substituted C 6 -C 12 -aryl or optionally substituted C 3 -C 12 -heterocyclyl; R 20a is C 1 -C 8 -alkyl, (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl, (optionally substituted C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl, optionally substituted C 6 -C 12 -aryl, or optionally substituted C 3 -C 12 -heterocyclyl; R 20b is hydrogen or C 1 -C 8 -alkyl; R 21 is optionally substituted C 6 -C 12 -aryl, or optionally substituted C 3 -C 12 -heterocyclyl; and R 5a , R 5b

are independently hydrogen, halogen, or C 1 -C 3 -alkyl, or

R 5a , R 5b

together with the carbon atom to which they are bound may form a C═O,

or a physiologically tolerated salt thereof.

Said compounds of formula (I), i.e., the pyrrolidine derivatives of formula (I) and their physiologically tolerated salts, are glycine transporter inhibitors and thus useful as pharmaceuticals.

The present invention thus further relates to the compounds of formula (I) for use in therapy.

The present invention also relates to pharmaceutical compositions which comprise a carrier and a compound of formula (I).

In particular, said compounds, i.e., the pyrrolidine derivatives and their physiologically tolerated salts, are inhibitors of the glycine transporter GlyT1.

The present invention thus further relates to the compounds of formula (I) for use in inhibiting the glycine transporter.

The present invention also relates to the use of the compounds of formula (I) in the manufacture of a medicament for inhibiting the glycine transporter GlyT1 and corresponding methods of inhibiting the glycine transporter GlyT1.

Glycine transport inhibitors and in particular inhibitors of the glycine transporter GlyT1 are known to be useful in treating a variety of neurologic and psychiatric disorders.

The present invention thus further relates to the compounds of formula (I) for use in treating a neurologic or psychiatric disorder.

The present invention further relates to the compounds of formula (I) for use in treating pain.

The present invention also relates to the use of the compounds of formula (I) in the manufacture of a medicament for treating a neurologic or psychiatric disorder and corresponding methods of treating said disorders. The present invention also relates to the use of the compounds of formula (I) in the manufacture of a medicament for treating pain and corresponding methods of treating pain.

Provided that the pyrrolidine derivatives of the formula (I) of a given constitution may exist in different spatial arrangements, for example if they possess one or more centers of asymmetry, polysubstituted rings or double bonds, or as different tautomers, the invention relates to the corresponding enantiomeric mixtures, in particular racemates, diastereomeric mixtures and tautomeric mixtures, as well as to the respective essentially pure enantiomers, diastereomers and tautomers of the compounds of formula (I) and/or of their salts.

According to one embodiment, an enantiomer of the pyrrolidine derivatives of the present invention has the following formula:

wherein R 1 , R 2a , R 2b , R 3a , R 3b , R 4 , Y 1 , R 5a , R 5b are as defined herein.

According to another embodiment, an enantiomer of the pyrrolidine derivatives of the present invention has the following formula:

wherein R 1 , R 2a , R 2b , R 3a , R 3b , R 4 , Y 1 , R 5a , R 5b are as defined herein.

If Y 1 is >CR 6 — it is preferred that R 3a and R 4 are in trans position.

Accordingly, the invention relates in particular to an enantiomer of the pyrrolidine derivatives having the following formula:

wherein R 1 , R 2a , R 2b , R 3a , R 3b , R 4 , R 6 , R 5a , R 5b are as defined herein.

Preferably, the invention relates to an enantiomer of the pyrrolidine derivatives having the following formula:

wherein R 1 , R 2a , R 2b , R 3a , R 3b , R 4 , R 6 , R 5a , R 5b are as defined herein.

The physiologically tolerated salts of the pyrrolidine derivatives of the formula (I) are especially acid addition salts with physiologically tolerated acids. Examples of suitable physiologically tolerated organic and inorganic acids are hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, C 1 -C 4 -alkylsulfonic acids, such as methanesulfonic acid, cycloaliphatic sulfonic acids, such as S-(+)-10-camphor sulfonic acid, aromatic sulfonic acids, such as benzenesulfonic acid and toluenesulfonic acid, di- and tricarboxylic acids and hydroxycarboxylic acids having 2 to 10 carbon atoms, such as oxalic acid, malonic acid, maleic acid, fumaric acid, lactic acid, tartaric acid, citric acid, glycolic acid, adipic acid and benzoic acid. Other utilizable acids are described, e.g., in Fortschritte der Arzneimittelforschung [Advances in drug research], Volume 10, pages 224 ff., Birkhäuser Verlag, Basel and Stuttgart, 1966. The physiologically tolerated salts of the isoindoline derivatives also include salts of a physiologically tolerated anion with an isoindoline derivatives wherein one or more than one nitrogen atom is quaternized, e.g. with an alkyl residue (e.g. methyl or ethyl).

The present invention moreover relates to compounds of formula (I) as defined herein, wherein at least one of the atoms has been replaced by its stable, non-radioactive isotope (e.g., hydrogen by deuterium, 12 C by 13 C, 14 N by 15 N, 16 O by 18 O) and preferably wherein at least one hydrogen atom has been replaced by a deuterium atom.

Of course, such compounds contain more of the respective isotope than this naturally occurs and thus is anyway present in the compounds (I).

Stable isotopes (e.g., deuterium, 13 C, 15 N, 18 O) are nonradioactive isotopes which contain one or more additional neutron than the normally abundant isotope of the respective atom. Deuterated compounds have been used in pharmaceutical research to investigate the in vivo metabolic fate of the compounds by evaluation of the mechanism of action and metabolic pathway of the non-deuterated parent compound (Blake et al. J. Pharm. Sci. 64, 3, 367-391 (1975)). Such metabolic studies are important in the design of safe, effective therapeutic drugs, either because the in vivo active compound administered to the patient or because the metabolites produced from the parent compound prove to be toxic or carcinogenic (Foster et al., Advances in Drug Research Vol. 14, pp. 2-36, Academic press, London, 1985; Kato et al., J. Labelled Comp. Radiopharmaceut., 36(10):927-932 (1995); Kushner et al., Can. J. Physiol. Pharmacol., 77, 79-88 (1999).

Incorporation of a heavy atom particularly substitution of deuterium for hydrogen, can give rise to an isotope effect that could alter the pharmacokinetics of the drug. This effect is usually insignificant if the label is placed at a metabolically inert position of the molecule.

Stable isotope labeling of a drug can alter its physico-chemical properties such as pKa and lipid solubility. These changes may influence the fate of the drug at different steps along its passage through the body. Absorption, distribution, metabolism or excretion can be changed. Absorption and distribution are processes that depend primarily on the molecular size and the lipophilicity of the substance. These effects and alterations can affect the pharmacodynamic response of the drug molecule if the isotopic substitution affects a region involved in a ligand-receptor interaction.

Drug metabolism can give rise to large isotopic effect if the breaking of a chemical bond to a deuterium atom is the rate limiting step in the process. While some of the physical properties of a stable isotope-labeled molecule are different from those of the unlabeled one, the chemical and biological properties are the same, with one important exception: because of the increased mass of the heavy isotope, any bond involving the heavy isotope and another atom will be stronger than the same bond between the light isotope and that atom. In any reaction in which the breaking of this bond is the rate limiting step, the reaction will proceed slower for the molecule with the heavy isotope due to “kinetic isotope effect”. A reaction involving breaking a C—D bond can be up to 700 percent slower than a similar reaction involving breaking a C—H bond. If the C—D bond is not involved in any of the steps leading to the metabolite, there may not be any effect to alter the behavior of the drug. If a deuterium is placed at a site involved in the metabolism of a drug, an isotope effect will be observed only if breaking of the C—D bond is the rate limiting step. There is evidence to suggest that whenever cleavage of an aliphatic C—H bond occurs, usually by oxidation catalyzed by a mixed-function oxidase, replacement of the hydrogen by deuterium will lead to observable isotope effect. It is also important to understand that the incorporation of deuterium at the site of metabolism slows its rate to the point where another metabolite produced by attack at a carbon atom not substituted by deuterium becomes the major pathway a process called “metabolic switching”.

Deuterium tracers, such as deuterium-labeled drugs and doses, in some cases repeatedly, of thousands of milligrams of deuterated water, are also used in healthy humans of all ages, including neonates and pregnant women, without reported incident (e.g. Pons G and Rey E, Pediatrics 1999 104: 633; Coward W A et al., Lancet 1979 7: 13; Schwarcz H P, Control. Clin. Trials 1984 5(4 Suppl): 573; Rodewald L E et al., J. Pediatr. 1989 114: 885; Butte N F et al. Br. J. Nutr. 1991 65: 3; MacLennan A H et al. Am. J. Obstet. Gynecol. 1981 139: 948). Thus, it is clear that any deuterium released, for instance, during the metabolism of compounds of this invention poses no health risk.

The weight percentage of hydrogen in a mammal (approximately 9%) and natural abundance of deuterium (approximately 0.015%) indicates that a 70 kg human normally contains nearly a gram of deuterium. Furthermore, replacement of up to about 15% of normal hydrogen with deuterium has been effected and maintained for a period of days to weeks in mammals, including rodents and dogs, with minimal observed adverse effects (Czajka D M and Finkel A J, Ann. N.Y. Acad. Sci. 1960 84: 770; Thomson J F, Ann. New York Acad. Sci. 1960 84: 736; Czakja D M et al., Am. J. Physiol. 1961 201: 357). Higher deuterium concentrations, usually in excess of 20%, can be toxic in animals. However, acute replacement of as high as 15%-23% of the hydrogen in humans' fluids with deuterium was found not to cause toxicity (Blagojevic N et al. in “Dosimetry & Treatment Planning for Neutron Capture Therapy”, Zamenhof R, Solares G and Harling O Eds. 1994. Advanced Medical Publishing, Madison Wis. pp. 125-134; Diabetes Metab. 23: 251 (1997)).

Increasing the amount of deuterium present in a compound above its natural abundance is called enrichment or deuterium-enrichment. Examples of the amount of enrichment include from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 21, 25, 29, 33, 37, 42, 46, 50, 54, 58, 63, 67, 71, 75, 79, 84, 88, 92, 96, to about 100 mol %.

The hydrogens present on a particular organic compound have different capacities for exchange with deuterium. Certain hydrogen atoms are easily exchangeable under physiological conditions and, if replaced by deuterium atoms, it is expected that they will readily exchange for protons after administration to a patient. Certain hydrogen atoms may be exchanged for deuterium atoms by the action of a deuteric acid such as D 2 SO 4 /D 2 O. Alternatively, deuterium atoms may be incorporated in various combinations during the synthesis of compounds of the invention. Certain hydrogen atoms are not easily exchangeable for deuterium atoms. However, deuterium atoms at the remaining positions may be incorporated by the use of deuterated starting materials or intermediates during the construction of compounds of the invention.

Deuterated and deuterium-enriched compounds of the invention can be prepared by using known methods described in the literature. Such methods can be carried out utilizing corresponding deuterated and optionally, other isotope-containing reagents and/or intermediates to synthesize the compounds delineated herein, or invoking standard synthetic protocols known in the art for introducing isotopic atoms to a chemical structure. Relevant procedures and intermediates are disclosed, for instance in Lizondo, J et al., Drugs Fut, 21(11), 1116 (1996); Brickner, S J et al., J Med Chem, 39(3), 673 (1996); Mallesham, B et al., Org Lett, 5(7), 963 (2003); PCT publications WO1997010223, WO2005099353, WO1995007271, WO2006008754; U.S. Pat. Nos. 7,538,189; 7,534,814; 7,531,685; 7,528,131; 7,521,421; 7,514,068; 7,511,013; and US Patent Application Publication Nos. 20090137457; 20090131485; 20090131363; 20090118238; 20090111840; 20090105338; 20090105307; 20090105147; 20090093422; 20090088416; 20090082471, the methods are hereby incorporated by reference.

The organic moieties mentioned in the above definitions of the variables are—like the term halogen—collective terms for individual listings of the individual group members. The prefix C n -C m indicates in each case the possible number of carbon atoms in the group.

Unless indicated otherwise, the term “substituted” means that a radical is substituted with 1, 2 or 3, especially 1, substituent which, according to a particular embodiment of the invention, are independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, C 3 -C 6 -aryl-C 1 -C 4 -alkyl, halogenated-C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, hydroxy-(halogenated C 1 -C 4 -alkyl), C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkyl, C 3 -C 7 -cycloalkyl, C 2 -C 4 -alkenyl, —CN, C 1 -C 4 -alkoxycarbonyl, aminocarbonyl, C 1 -C 4 -alkylaminocarbonyl, alkylamino)carbonyl, C 6 -C 12 -arylaminocarbonyl, C 3 -C 12 -heterocyclylaminocarbonyl, C 6 -C 12 -aryl, oxo (═O), OH, C 1 -C 4 -alkoxy, halogenated-C 1 -C 4 -alkoxy, C 3 -C 7 -cycloalkoxy, carboxy-C 1 -C 4 -alkoxy, C 6 -C 12 -aryl-C 1 -C 4 -alkoxy, C 6 -C 12 -aryloxy, C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkoxy, SH, alkylthio, C 1 -C 4 -alkylsulfonyl, C 1 -C 4 -alkylaminosulfonyl, di-C 1 -C 4 -alkylaminosulfonyl, C 3 -C 6 -arylsulfonyl, aminosulfonyl, C 3 -C 6 -arylaminosulfonyl, C 3 -C 12 -heterocyclylaminosulfonyl, NH 2 , C 1 -C 4 -alkylamino, di-C 1 -C 4 -alkylamino, C 6 -C 12 -aryl-C 1 -C 4 -alkylamino, C 1 -C 4 -alkylcarbonylamino, C 3 -C 6 -arylcarbonylamino, C 3 -C 12 -heterocyclylcarbonylamino, C 1 -C 6 -alkylsulfonylamino, C 3 -C 6 -arylsulfonylamino, C 3 -C 12 -heterocyclylsulfonylamino and C 3 -C 12 -heterocyclyl, wherein aryl and heterocyclyl may be unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -haloalkoxy.

The term halogen denotes in each case fluorine, bromine, chlorine or iodine, in particular fluorine or chlorine.

C 1 -C 4 -Alkyl is a straight-chain or branched alkyl group having from 1 to 4 carbon atoms. Examples of an alkyl group are methyl, C 2 -C 4 -alkyl such as ethyl, n-propyl, iso-propyl, n-butyl, 2-butyl, iso-butyl or tert-butyl. C 1 -C 2 -Alkyl is methyl or ethyl, C 1 -C 3 -alkyl is additionally n-propyl or iso-propyl.

C 1 -C 6 -Alkyl is a straight-chain or branched alkyl group having from 1 to 6 carbon atoms. Examples include methyl, C 2 -C 4 -alkyl as mentioned herein and also pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl.

C 1 -C 8 -Alkyl is a straight-chain or branched alkyl group having from 1 to 8 carbon atoms. Examples include methyl, C 2 -C 4 -alkyl as mentioned herein and also pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, heptyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 1,2-dimethylpentyl, 1,2,3-trimethylbutyl 1-ethyl-2-methylbutyl, 1-methyl-2-ethylbutyl, octyl, 1-methyl-heptyl, 2-methylheptyl, 3-methyl-heptyl, 4-methyl-heptyl, 5-methylheptyl, 6-methylheptyl, 1-methyl-2-ethylpentyl, 1,1-dimethylhexyl, 1,2-dimethylhexyl, 1,3-dimethylhexyl, 1,4-dimethylhexyl, 2,2-dimethylhexyl, 2,3-dimethylhexyl, 3,3-dimethylhexyl, 4,5-dimethylhexyl, 1,2,3-trimethylpentyl, 1,2-dimethyl-3-ethylbutyl, 1-ethyl-2-ethylbutyl and 1,3-dimethyl-2-ethylbutyl.

Halogenated C 1 -C 6 -alkyl is a straight-chain or branched alkyl group having 1 to 6 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms, such as in halogenomethyl, dihalogenomethyl, trihalogenomethyl, (R)-1-halogenoethyl, (S)-1-halogenoethyl, 2-halogenoethyl, 1,1-dihalogenoethyl, 2,2-dihalogenoethyl, 2,2,2-trihalogenoethyl, (R)-1-halogenopropyl, (S)-1-halogenopropyl, 2-halogenopropyl, 3-halogenopropyl, 1,1-dihalogenopropyl, 2,2-dihalogenopropyl, 3,3-dihalogenopropyl, 3,3,3-trihalogenopropyl, (R)-2-halogeno-1-methylethyl, (S)-2-halogeno-1-methylethyl, (R)-2,2-dihalogeno-1-methylethyl, (S)-2,2-dihalogeno-1-methylethyl, (R)-1,2-dihalogeno-1-methylethyl, (S)-1,2-dihalogeno-1-methylethyl, (R)-2,2,2-trihalogeno-1-methylethyl, (S)-2,2,2-trihalogeno-1-methylethyl, 2-halogeno-1-(halogenomethyl)ethyl, 1-(dihalogenomethyl)-2,2-dihalogenoethyl, (R)-1-halogenobutyl, (S)-1-halogenobutyl, 2-halogenobutyl, 3-halogenobutyl, 4-halogenobutyl, 1,1-dihalogenobutyl, 2,2-dihalogenobutyl, 3,3-dihalogenobutyl, 4,4-dihalogenobutyl, 4,4,4-trihalogenobutyl, 1,1-dihalogenopentyl, 4,4-dihalogenopentyl etc. Particular examples include the fluorinated C 1 -C 4 alkyl groups as defined, such as trifluoromethyl.

C 3 -C 12 -Cycloalkyl-C 1 -C 4 -alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, wherein one hydrogen atom is replaced by a cycloaliphatic radical having from 3 to 12 carbon atoms such as in cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl.

C 1 -C 6 -Alkylcarbonyl-C 1 -C 4 -alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or 2 carbon atoms, wherein one hydrogen atom is replaced by a C 1 -C 6 -alkylcarbonyl group, in particular by a C 1 -C 4 -alkylcarbonyl group, such as in methylcarbonylmethyl, methylcarbonylethyl, methylcarbonylpropyl, ethylcarbonylmethyl, n-propylcarbonylmethyl, iso-propylcarbonylmethyl, n-butylcarbonylmethyl, 2-butylcarbonylmethyl or iso-butylcarbonylmethyl.

C 1 -C 6 -Alkoxycarbonyl-C 1 -C 4 -alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, wherein one hydrogen atom is replaced by a C 1 -C 6 -alkoxycarbonyl group, in particular by a C 1 -C 4 -alkoxycarbonyl group, such as in methoxycarbonylmethyl, methoxycarbonylpropyl, ethoxycarbonylmethyl, n-propoxycarbonylmethyl, n-butoxycarbonylmethyl, 2-butoxycarbonylmethyl or iso-butoxycarbonylmethyl.

C 6 -C 12 -Aryl-C 1 -C 4 -alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, wherein one hydrogen atom is replaced by C 6 -C 12 -aryl, such as in benzyl.

Hydroxy-C 1 -C 6 -alkyl is a straight-chain or branched alkyl group having 1 to 6 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, wherein one or two hydrogen atoms are replaced by one or two hydroxyl groups, such as in hydroxymethyl, (R)-1-hydroxyethyl, (S)-1-hydroxyethyl, 2-hydroxyethyl, (R)-1-hydroxypropyl, (S)-1-hydroxypropyl, 2-hydroxypropyl, 3-hydroxypropyl, (R)-2-hydroxy-1-methylethyl, (S)-2-hydroxy-1-methylethyl, 2-hydroxy-1-(hydroxymethyl)ethyl, (R)-1-hydroxybutyl, (S)-1-hydroxybutyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl, (R)-1-hydroxypentyl, (S)-1-hydroxypentyl, 2-hydroxypentyl and 4-hydroxypentyl.

Hydroxy-(halogenated C 1 -C 4 -alkyl) is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, wherein at least two, e.g. 2, 3, 4 or all of the hydrogen atoms are replaced by a number of identical or different halogen atoms and by one or two hydroxyl groups, such as in hydroxyhalogenomethyl, hydroxydihalogenomethyl, (R)-1-hydroxy-1-halogenoethyl, (S)-1-hydroxy-1-halogenoethyl, (R) 2,2-dihalogeno-1-hydroxyethyl, (S) 2,2-dihalogeno-1-hydroxyethyl, (R) 2,2,2-trihalogeno-1-hydroxyethyl, (S) 2,2,2-trihalogeno-1-hydroxyethyl (R)-1-hydroxy-1-halogenopropyl, (S)-1-hydroxy-1-halogenopropyl, (R)-2-halogeno-2-hydroxypropyl, (S)-2-halogeno-2-hydroxypropyl, 3-halogeno-2-hydroxypropyl, 1,1-dihalogeno-1-hydroxypropyl, 2,2-dihalogeno-1-hydroxypropyl, 3,3,3-trihalogeno-1-hydroxypropyl, (R)-2-halogeno-1-methyl-1-hydroxyethyl, (S)-2-halogeno-1-methyl-1-hydroxyethyl, (R)-2,2-dihalogeno-1-methyl-1-hydroxyethyl, (S)-2,2-dihalogeno-1-methyl-1-hydroxyethyl, (R)-2,2,2-trihalogeno-1-methyl-1-hydroxyethyl, (S)-2,2,2-trihalogeno-1-methyl-1-hydroxyethyl, (R)-1-(halogenomethyl)-1-hydroxyethyl, (S)-1-(halogenomethyl)-1-hydroxyethyl, (R)-1-(dihalogenomethyl)-1-hydroxyethyl, (S)-1-(dihalogenomethyl)-1-hydroxyethyl, (R)-1-(trihalogenomethyl)-1-hydroxyethyl, (S)-1-(trihalogenomethyl)-1-hydroxyethyl, etc. Particular examples include the hydroxyfluorinated C 1 -C 4 alkyl groups as defined, such as 1-(trifluoromethyl)-1-hydroxyethyl.

C 1 -C 6 -Alkoxy-C 1 -C 6 -alkyl is a straight-chain or branched alkyl group having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, more preferably 1 or 2 carbon atoms, wherein one or two hydrogen atoms are replaced by one or two alkoxy groups having 1 to 6, preferably 1 to 4, in particular 1 or 2 carbon atoms, such as in methoxymethyl, (R)-1-methoxyethyl, (S)-1-methoxyethyl, 2-methoxyethyl, (R)-1-methoxypropyl, (S)-1-methoxypropyl, 2-methoxypropyl, 3-methoxypropyl, (R)-2-methoxy-1-methylethyl, (S)-2-methoxy-1-methyl ethyl, 2-methoxy-1-(methoxymethyl)ethyl, (R)-1-methoxybutyl, (S)-1-methoxybutyl, 2-methoxybutyl, 3-methoxybutyl, 4-methoxybutyl, (R)-1-methoxypentyl, (S)-1-methoxypentyl, 2-methoxypentyl, 3-methoxypentyl, 4-methoxypentyl, (R)-1-methoxyhexyl, (S)-1-methoxyhexyl, 2-methoxyhexyl, 3-methoxyhexyl, 4-methoxyhexyl, ethoxymethyl, (R)-1-ethoxyethyl, (S)-1-ethoxyethyl, 2-ethoxyethyl, (R)-1-ethoxypropyl, (S)-1-ethoxypropyl, 2-ethoxypropyl, 3-ethoxypropyl, (R)-2-ethoxy-1-methylethyl, (S)-2-ethoxy-1-methyl ethyl, 2-ethoxy-1-(ethoxymethyl)ethyl, (R)-1-ethoxybutyl, (S)-1-ethoxybutyl, 2-ethoxybutyl, 3-ethoxybutyl, 4-ethoxybutyl, (R)-1-ethoxypentyl, (S)-1-ethoxypentyl, 2-ethoxypentyl, 3-ethoxypentyl, 4-ethoxypentyl, 5-ethoxypentyl, (R)-1-ethoxyhexyl, (S)-1-ethoxyhexyl, 2-ethoxyhexyl, 3-ethoxyhexyl and 6-ethoxybutyl.

C 6 -C 12 -Aryloxy-C 1 -C 4 -alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, wherein one hydrogen atom is replaced by a radical of the formula R—O—, wherein R is an aryl group having from 6 to 12, in particular 6 carbon atoms as defined herein. Examples include phenoxymethyl, (4-F-phenoxy)methyl.

Amino-C 1 -C 4 -alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, wherein one hydrogen atom is replaced by an amino group, such as in aminomethyl, 2-aminoethyl.

C 1 -C 6 -Alkylamino-C 1 -C 4 -alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, wherein one hydrogen atom is replaced by a C 1 -C 6 -alkylamino group, in particular by a C 1 -C 4 -alkylamino group, such as in methylaminomethyl, ethylaminomethyl, n-propylaminomethyl, iso-propylaminomethyl, n-butylaminomethyl, 2-butylaminomethyl, isobutylaminomethyl or tert-butylaminomethyl.

Di-C 1 -C 6 -Alkylamino-C 1 -C 4 -alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, wherein one hydrogen atom is replaced by a di-C 1 -C 6 -Alkylamino group, in particular by a di-C 1 -C 4 -alkylamino group, such as in dimethylaminomethyl.

C 1 -C 6 -Alkylcarbonylamino-C 1 -C 4 -alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, wherein one hydrogen atom is replaced by a C 1 -C 6 -alkylcarbonylamino group, in particular by a C 1 -C 4 -alkylcarbonylamino group, such as in methylcarbonylaminomethyl, ethylcarbonylaminomethyl, n-propylcarbonylaminomethyl, iso-propylcarbonylaminomethyl, n-butylcarbonylaminomethyl, 2-butylcarbonylaminomethyl, iso-butylcarbonylaminomethyl or tert-butylcarbonyl aminomethyl.

C 1 -C 6 -Alkylaminocarbonylamino-C 1 -C 4 -alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, wherein one hydrogen atom is replaced by a C 1 -C 6 -alkylaminocarbonylamino group, in particular by a C 1 -C 4 -alkylaminocarbonylamino group, such as in methylaminocarbonylaminomethyl, ethylaminocarbonylaminomethyl, n-propylaminocarbonylaminomethyl, iso-propylaminocarbonylaminomethyl, n-butylaminocarbonylaminomethyl, 2-butylaminocarbonylaminomethyl, iso-butylaminocarbonylaminomethyl or tertbutylaminocarbonylaminomethyl.

Di-C 1 -C 6 -alkylaminocarbonylamino-C 1 -C 4 -alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, wherein one hydrogen atom is replaced by a di-C 1 -C 6 -alkylaminocarbonylamino group, in particular by a di-C 1 -C 4 -alkylaminocarbonylamino group, such as in dimethylaminocarbonylaminomethyl, dimethylaminocarbonylaminoethyl, dimethylaminocarbonylamino-propyl.

C 1 -C 6 -Alkylsulfonylamino-C 1 -C 4 -alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, wherein one hydrogen atom is replaced by a C 1 -C 6 -alkylsulfonylamino group, in particular by a C 1 -C 4 -alkylsulfonylamino group, such as in methylsulfonylaminomethyl, ethylsulfonylaminomethyl, n-propylsulfonylaminomethyl, iso-propylsulfonylaminomethyl, n-butylsulfonylaminomethyl, 2-butylsulfonylaminomethyl, iso-butylsulfonylaminomethyl or tertbutylsulfonylaminomethyl.

(C 6 -C 12 -Aryl-C 1 -C 6 -alkyl)amino-C 1 -C 4 alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, wherein one hydrogen atom is replaced by a (C 6 -C 17 -aryl-C 1 -C 6 -alkyl)amino group, in particular a (C 6 -C 12 -aryl-C 1 -C 2 -alkyl)amino group, such as in benzylaminomethyl.

C 3 -C 12 -Heterocyclyl-C 1 -C 4 -alkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, wherein one hydrogen atom is replaced by C 3 -C 12 -heterocyclyl, such as in N-pyrrolidinylmethyl, N-piperidinylmethyl, N-morpholinylmethyl, tetrahydropyran-2-yl-methyl.

C 3 -C 12 -Cycloalkyl is a cycloaliphatic radical having from 3 to 12 carbon atoms. In particular, 3 to 6 carbon atoms form the cyclic structure, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The cyclic structure may be unsubstituted or may carry 1, 2, 3 or 4 C 1 -C 4 alkyl radicals, preferably one or more methyl radicals.

Carbonyl is >C═O.

C 1 -C 6 -Alkylcarbonyl is a radical of the formula R—C(O)—, wherein R is an alkyl radical having from 1 to 6, preferably from 1 to 4, in particular 1 or 2 carbon atoms as defined herein. Examples include acetyl, propionyl, n-butyryl, 2-methylpropionyl, pivaloyl.

Halogenated C 1 -C 6 -alkylcarbonyl is C 1 -C 6 -alkylcarbonyl as defined herein, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms. Examples include fluoromethylcarbonyl, difluoromethylcarbonyl, trifluoromethylcarbonyl. Further examples are 1,1,1-trifluoroeth-2-ylcarbonyl, 1,1,1-trifluoroprop-3-ylcarbonyl.

C 6 -C 12 -Arylcarbonyl is a radical of the formula R—C(O)—, wherein R is an aryl radical having from 6 to 12 carbon atoms as defined herein. Examples include benzoyl.

C 1 -C 6 -Alkoxycarbonyl is a radical of the formula R—O—C(O)—, wherein R is an alkyl radical having from 1 to 6, preferably from 1 to 4, in particular 1 or 2 carbon atoms as defined herein. Examples include methoxycarbonyl and tert-butoxycarbonyl.

Halogenated C 1 -C 6 -alkoxycarbonyl is a C 1 -C 6 -alkoxycarbonyl as defined herein, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms.

C 6 -C 12 -Aryloxycarbonyl is a radical of the formula R—O—C(O)—, wherein R is an aryl radical having from 6 to 12 carbon atoms as defined herein. Examples include phenoxycarbonyl.

Cyano is —C≡N.

Aminocarbonyl is NH 2 C(O)—.

C 1 -C 6 -Alkylaminocarbonyl is a radical of the formula R—NH—C(O)—, wherein R is an alkyl radical having from 1 to 6, preferably from 1 to 4, in particular 1 or 2 carbon atoms as defined herein. Examples include methylaminocarbonyl.

(Halogenated C 1 -C 4 -alkyl)aminocarbonyl is a C 1 -C 4 -alkylaminocarbonyl as defined herein, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by 1, 2, 3, 4 or a corresponding number of identical or different hydrogen atoms.

C 6 -C 12 -Arylaminocarbonyl is a radical of the formula R—NH—C(O)—, wherein R is an aryl radical having from 6 to 12 carbon atoms as defined herein. Examples include phenylaminocarbonyl.

C 2 -C 6 -Alkenyl is a singly unsaturated hydrocarbon radical having 2, 3, 4, 5 or 6 carbon atoms, e.g. vinyl, allyl (2-propen-1-yl), 1-propen-1-yl, 2-propen-2-yl, methallyl(2-methylprop-2-en-1-yl) and the like. C 3 -C 5 -Alkenyl is, in particular, allyl, 1-methylprop-2-en-1-yl, 2-buten-1-yl, 3-buten-1-yl, methallyl, 2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbut-2-en-1-yl or 2-ethylprop-2-en-1-yl, 2-hexen-1-yl.

C 3 -C 6 -Cycloalkenyl is a carbocyclic radical having at least one carbon-carbon double bond and from 3 to 6 carbon atoms. In particular, 3 to 6 carbon atoms form the cyclic structure, such as 2-cyclopenten-1-yl, 2-cyclohexen-1-yl. The cyclic structure may be unsubstituted or may carry 1, 2, 3 or 4 C 1 -C 4 alkyl radicals, preferably one or more methyl radicals.

C 2 -C 6 -Alkynyl is a singly unsaturated hydrocarbon radical having 2, 3, 4, 5 or 6 carbon atoms, e.g. ethynyl, 2-propyn-1-yl, 1-propyn-1-yl, 2-propyn-2-yl and the like. C 3 -C 5 -Alkynyl is, in particular, 2-propyn-1-yl, 2-butyn-1-yl, 3-butyn-1-yl, 2-pentyn-1-yl, 3-pentyn-1-yl, 4-pentyn-1-yl.

C 1 -C 5 -Alkylene is straight-chain or branched alkylene group having from 1 to 5 carbon atoms. Examples include methylene and ethylene. A further example is propylene.

C 2 -C 4 -Alkenylene is straight-chain or branched alkenylene group having from 2 to 4 carbon atoms.

C 2 -C 4 -Alkynylene is straight-chain or branched alkynylene group having from 2 to 4 carbon atoms. Examples include propynylene.

C 6 -C 12 -Aryl is a 6- to 12-membered, in particular 6- to 10-membered, aromatic cyclic radical which can be a monocyclic aromatic ring, for example, phenyl etc., or a fused polycyclic aromatic ring comprising a first monocyclic aromatic ring and one or more carbocycles which are saturated, partially unsaturated or aromatic, for example, naphthyl, indenyl, tetrahydronaphthyl, indanyl.

C 3 -C 12 -Arylene is an aryl diradical. Examples include phen-1,4-ylene and phen-1,3-ylene.

Hydroxy is —OH.

Oxo is ═O.

C 1 -C 6 -Alkoxy is a radical of the formula R—O—, wherein R is a straight-chain or branched alkyl group having from 1 to 6, in particular 1 to 4 carbon atoms. Examples include methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, 2-butoxy, iso-butoxy (2-methylpropoxy), tert.-butoxy pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexyloxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 1-methylpentyloxy, 2-methylpentyloxy, 3-methylpentyloxy, 4-methylpentyloxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy and 1-ethyl-2-methylpropoxy.

Halogenated C 1 -C 6 -alkoxy is a straight-chain or branched alkoxy group having from 1 to 6, preferably from 1 to 4, in particular 1 or 2 carbon atoms, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms, such as in halogenomethoxy, dihalogenomethoxy, trihalogenomethoxy, (R)-1-halogenoethoxy, (S)-1-halogenoethoxy, 2-halogenoethoxy, 1,1-dihalogenoethoxy, 2,2-dihalogenoethoxy, 2,2,2-trihalogenoethoxy, (R)-1-halogenopropoxy, (S)-1-halogenopropoxy, 2-halogenopropoxy, 3-halogenopropoxy, 1,1-dihalogenopropoxy, 2,2-dihalogenopropoxy, 3,3-dihalogenopropoxy, 3,3,3-trihalogenopropoxy, (R)-2-halogeno-1-methylethoxy, (S)-2-halogeno-1-methylethoxy, (R)-2,2-dihalogeno-1-methylethoxy, (S)-2,2-dihalogeno-1-methylethoxy, (R)-1,2-dihalogeno-1-methylethoxy, (S)-1,2-dihalogeno-1-methylethoxy, (R)-2,2,2-trihalogeno-1-methylethoxy, (S)-2,2,2-trihalogeno-1-methylethoxy, 2-halogeno-1-(halogenomethyl)ethoxy, 1-(dihalogenomethyl)-2,2-dihalogenoethoxy, (R)-1-halogenobutoxy, (S)-1-halogenobutoxy, 2-halogenobutoxy, 3-halogenobutoxy, 4-halogenobutoxy, 1,1-dihalogenobutoxy, 2,2-dihalogenobutoxy, 3,3-dihalogenobutoxy, 4,4-dihalogenobutoxy, 4,4,4-trihalogenobutoxy, etc. Particular examples include the fluorinated C 1 -C 4 alkoxy groups as defined, such as trifluoromethoxy.

C 1 -C 6 -Hydroxyalkoxy is an alkoxy radical having from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein, wherein one or two hydrogen atoms are replaced by hydroxy. Examples include 2-hydroxyethoxy, 3-hydroxypropoxy, 2-hydroxypropoxy, 1-methyl-2-hydroxyethoxy and the like.

C 1 -C 6 -Alkoxy-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4 carbon atoms, preferably 1 or 2 carbon atoms as defined herein, wherein one or two hydrogen atoms are replaced by one or two alkoxy radicals having from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methoxymethoxy, 2-methoxyethoxy, 1-methoxyethoxy, 3-methoxypropoxy, 2-methoxypropoxy, 1-methyl-1-methoxyethoxy, ethoxymethoxy, 2-ethoxyethoxy, 1-ethoxyethoxy, 3-ethoxypropoxy, 2-ethoxypropoxy, 1-methyl-1-ethoxyethoxy and the like.

Amino-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogen atom is replaced by an amino group. Examples include 2-aminoethoxy.

C 1 -C 6 -Alkylamino-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogen atom is replaced by an alkylamino group having from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methylaminomethoxy, ethylaminomethoxy, n-propylaminomethoxy, iso-propylaminomethoxy, n-butylaminomethoxy, 2-butylaminomethoxy, iso-butylaminomethoxy, tert-butylaminomethoxy, 2-(methylamino)ethoxy, 2-(ethylamino)ethoxy, 2-(n-propylamino)ethoxy, 2-(iso-propylamino)ethoxy, 2-(n-butylamino)ethoxy, 2-(2-butylamino)ethoxy, 2-(iso-butylamino)ethoxy, 2-(tertbutylamino)ethoxy.

Di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogen atom is replaced by a di-alkylamino group having from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include dimethylaminomethoxy, diethylaminomethoxy, N-methyl-N-ethylamino)ethoxy, 2-(dimethylamino)ethoxy, 2-(diethylamino)ethoxy, 2-(N-methyl-N-ethylamino)ethoxy.

C 1 -C 6 -Alkylcarbonylamino-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogen atom is replaced by an alkylcarbonylamino group wherein the alkyl group has from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methylcarbonylaminomethoxy, ethylcarbonylaminomethoxy, n-propylcarbonylaminomethoxy, iso-propylcarbonylaminomethoxy, n-butylcarbonylaminomethoxy, 2-butylcarbonylaminomethoxy, iso-butylcarbonylaminomethoxy, tert-butylcarbonylaminomethoxy, 2-(methylcarbonylamino)ethoxy, 2-(ethylcarbonylamino)ethoxy, 2-(n-propylcarbonylamino)ethoxy, 2-(iso-propylcarbonylamino)ethoxy, 2-(n-butylcarbonylamino)ethoxy, 2-(2-butylcarbonylamino)ethoxy, 2-(iso-butylcarbonylamino)ethoxy, 2-(tert-butylcarbonylamino)ethoxy.

C 6 -C 12 -Arylcarbonylamino-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogen atom is replaced by a C 6 -C 12 -arylcarbonylamino group as defined herein. Examples include 2-(benzoylamino)ethoxy.

C 1 -C 6 -Alkoxycarbonylamino-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogen atom is replaced by an alkoxycarbonylamino group wherein the alkoxy group has from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methoxycarbonylaminomethoxy, ethoxycarbonylaminomethoxy, n-propoxycarbonylaminomethoxy, iso-propoxycarbonylaminomethoxy, n-butoxycarbonylaminomethoxy, 2-butoxycarbonylaminomethoxy, iso-butoxycarbonylaminomethoxy, tertbutoxycarbonylaminomethoxy, 2-(methoxycarbonylamino)ethoxy, 2-(ethoxycarbonylamino)ethoxy, 2-(n-propoxycarbonylamino)ethoxy, 2-(iso-propoxycarbonylamino)ethoxy, 2-(n-butoxycarbonylamino)ethoxy, 2-(2-butoxycarbonylamino)ethoxy, 2-(isobutoxycarbonylamino)ethoxy, 2-(tert-butoxycarbonylamino)ethoxy.

C 2 -C 6 -Alkenyloxy is a radical of the formula R—O—, wherein R is a straight-chain or branched alkenyl group having from 2 to 6, in particular 2 to 4 carbon atoms. Examples include vinyloxy, allyloxy (2-propen-1-yloxy), 1-propen-1-yloxy, 2-propen-2-yloxy, methallyloxy (2-methylprop-2-en-1-yloxy) and the like. C 3 -C 5 -Alkenyloxy is, in particular, allyloxy, 1-methylprop-2-en-1-yloxy, 2-buten-1-yloxy, 3-buten-1-yloxy, methallyloxy, 2-penten-1-yloxy, 3-penten-1-yloxy, 4-penten-1-yloxy, 1-methylbut-2-en-1-yloxy or 2-ethylprop-2-en-1-yloxy.

C 6 -C 12 -Aryl-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogen atom is replaced by a C 6 -C 12 -aryl group as defined herein. Examples include benzyloxy.

C 1 -C 6 -Alkylsulfonylamino-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogen atom is replaced by an alkylsulfonylamino group having from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include 2-(methylsulfonylamino)ethoxy, 2-(ethylsulfonylamino)ethoxy, 2-[(2-methylpropyl)sulfonylamino]ethoxy.

(Halogenated C 1 -C 6 -alkyl)sulfonylamino-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogen atom is replaced by an alkylsulfonylamino group having from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein, wherein the alkyl group is halogenated. Examples include 2-(trifluoromethylsulfonylamino)ethoxy.

C 6 -C 12 -Arylsulfonylamino-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogen atom is replaced by a C 6 -C 12 -arylsulfonylamino group as defined herein. Examples include 2-(phenylsulfanylamino)ethoxy, 2-(naphthylsulfonylamino)ethoxy.

(C 6 -C 12 -Aryl-C 1 -C 6 -alkyl)sulfonylamino-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogen atom is replaced by a (C 6 -C 12 -aryl-C 1 -C 6 -alkyl)sulfonylamino group, preferably by a (C 6 -C 12 -aryl-C 1 -C 2 -alkyl)sulfonylamino group. Examples include 2-(benzylsulfonylamino)ethoxy.

C 3 -C 12 -Heterocyclylsulfonylamino-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogen atom is replaced by a C 3 -C 12 -heterocyclylsulfonylamino group as defined herein. Examples include 2-(pyridin-3-ylsulfonylamino)ethoxy.

C 3 -C 12 -Heterocyclyl-C 1 -C 4 -alkoxy is an alkoxy radical having from 1 to 4, preferably 1 or 2 carbon atoms as defined herein, wherein one hydrogen atom is replaced by a C 3 -C 12 -heterocyclyl group as defined herein. Examples include 2-(N-pyrrolidinyl)ethoxy, 2-(N-morpholinyl)ethoxy and 2-(N-imidazolyl)ethoxy.

C 1 -C 2 -Alkylenedioxo is a radical of the formula —O—R—O—, wherein R is a straight-chain or branched alkylene group having from 1 or 2 carbon atoms as defined herein. Examples include methylenedioxo.

C 6 -C 12 -Aryloxy is a radical of the formula R—O—, wherein R is an aryl group having from 6 to 12, in particular 6 carbon atoms as defined herein. Examples include phenoxy.

C 3 -C 12 -Heterocyclyloxy is a radical of the formula R—O—, wherein R is a C 3 -C 12 -heterocyclyl group having from 3 to 12, in particular from 3 to 7 carbon atoms as defined herein. Examples include pyridin-2-yloxy.

C 1 -C 6 -Alkylthio is a radical of the formula R—S—, wherein R is an alkyl radical having from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methylthio, ethylthio, propylthio, butylthio, pentylthio, 1-methylbutylthio, 2-methylbutylthio, 3-methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, hexylthio, 1,1-dimethylpropylthio, 1,2-dimethylpropylthio, 1-methylpentylthio, 2-methylpentylthio, 3-methylpentylthio, 4-methylpentylthio, 1,1-dimethylbutylthio, 1,2-dimethylbutylthio, 1,3-dimethylbutylthio, 2,2-dimethylbutylthio, 2,3-dimethylbutylthio, 3,3-dimethylbutylthio, 1-ethylbutylthio, 2-ethylbutylthio, 1,1,2-trimethylpropylthio, 1,2,2-trimethylpropylthio, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl.

Halogenated C 1 -C 6 -alkylthio is a radical of the formula R—S—, wherein R is a halogenated alkyl radical having from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include halogenomethylthio, dihalogenomethylthio, trihalogenomethylthio, (R)-1-halogenoethylthio, (S)-1-halogenoethylthio, 2-halogenoethylthio, 1,1-dihalogenoethylthio, 2,2-dihalogenoethylthio, 2,2,2-trihalogeno ethylthio, (R)-1-halogenopropylthio, (S)-1-halogenopropylthio, 2-halogenopropylthio, 3-halogenopropylthio, 1,1-dihalogenopropylthio, 2,2-dihalogenopropylthio, 3,3-dihalogenopropylthio, 3,3,3-trihalogenopropylthio, (R)-2-halogeno-1-methylethylthio, (S)-2-halogeno-1-methylethylthio, (R)-2,2-dihalogeno-1-methylethylthio, (S)-2,2-dihalogeno-1-methylethylthio, (R)-1,2-dihalogeno-1-methylethylthio, (S)-1,2-dihalogeno-1-methylethylthio, (R)-2,2,2-trihalogeno-1-methylethylthio, (S)-2,2,2-trihalogeno-1-methylethylthio, 2-halogeno-1-(halogenomethyl)ethylthio, 1-(dihalogenomethyl)-2,2-dihalogenoethylthio, (R)-1-halogenobutylthio, (S)-1-halogenobutylthio, 2-halogenobutylthio, 3-halogenobutylthio, 4-halogenobutylthio, 1,1-dihalogenobutylthio, 2,2-dihalogenobutylthio, 3,3-dihalogenobutylthio, 4,4-dihalogenobutylthio, 4,4,4-trihalogenobutylthio, etc. Particular examples include the fluorinated alkylthio groups as defined, such as trifluoromethylthio.

C 1 -C 6 -Alkylsulfinyl is a radical of the formula R—S(O)—, wherein R is an alkyl radical having from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methylsulfinyl, ethylsulfinyl, propylsulfinyl, butylsulfinyl, pentylsulfinyl, 1-methylbutylsulfinyl, 2-methylbutylsulfinyl, 3-methylbutylsulfinyl, 2,2-dimethylpropylsulfinyl, 1-ethylpropylsulfinyl, hexylsulfinyl, 1,1-dimethylpropylsulfinyl, 1,2-dimethylpropylsulfinyl, 1-methylpentylsulfinyl, 2-methylpentylsulfinyl, 3-methylpentylsulfinyl, 4-methylpentylsulfinyl, 1,1-dimethylbutylsulfinyl, 1,2-dimethylbutylsulfinyl, 1,3-dimethylbutylsulfinyl, 2,2-dimethylbutylsulfinyl, 2,3-dimethylbutylsulfinyl, 3,3-dimethylbutylsulfinyl, 1-ethylbutylsulfinyl, 2-ethylbutylsulfinyl, 1,1,2-trimethylpropylsulfinyl, 1,2,2-trimethylpropylsulfinyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl.

C 1 -C 6 -Alkylsulfonyl is a radical of the formula R—S(O) 2 —, wherein R is an alkyl radical having from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methylsulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl, pentylsulfonyl, 1-methylbutylsulfonyl, 2-methylbutylsulfonyl, 3-methylbutylsulfonyl, 2,2-dimethylpropylsulfonyl, 1-ethylpropylsulfonyl, hexyl sulfonyl, 1,1-dimethylpropylsulfonyl, 1,2-dimethylpropylsulfonyl, 1-methylpentylsulfonyl, 2-methylpentylsulfonyl, 3-methylpentylsulfonyl, 4-methylpentylsulfonyl, 1,1-dimethylbutylsulfonyl, 1,2-dimethylbutylsulfonyl, 1,3-dimethylbutylsulfonyl, 2,2-dimethylbutylsulfonyl, 2,3-dimethylbutylsulfonyl, 3,3-dimethylbutylsulfonyl, 1-ethylbutylsulfonyl, 2-ethylbutylsulfonyl, 1,1,2-trimethylpropylsulfonyl, 1,2,2-trimethylpropylsulfonyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl.

(Halogenated C 1 -C 6 -alkyl)sulfonyl is a C 1 -C 6 -alkylsulfonyl as defined herein, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms.

C 6 -C 12 -Arylsulfonyl is a radical of the formula R—S(O) 2 —, wherein R is an aryl radical having from 6 to 12 carbon atoms as defined herein. Examples include phenylsulfonyl.

(C 6 -C 12 -Aryl-C 1 -C 4 -alkyl)sulfonyl is a radical of the formula R—S(O) 2 —, wherein R is a C 6 -C 12 -aryl-C 1 -C 4 -alkyl radical, in particular a C 6 -C 12 -aryl-C 1 -C 2 -alkyl radical as defined herein. Examples include benzylsulfonyl.

C 3 -C 12 -Heterocyclylsulfonyl is a radical of the formula R—S(O) 2 —, wherein R is C 3 -C 12 -heterocyclyl as defined herein.

Aminosulfonyl is NH 2 —S(O) 2 —.

C 1 -C 6 -Alkylaminosulfonyl is a radical of the formula R—NH—S(O) 2 — wherein R is an alkyl radical having from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methylaminosulfonyl, ethylaminosulfonyl, n-propylaminosulfonyl, iso-propylaminosulfonyl, n-butylaminosulfonyl, 2-butylaminosulfonyl, iso-butylaminosulfonyl, tert-butylaminosulfonyl.

Di-C 1 -C 6 -alkylaminosulfonyl is a radical of the formula RR′N—S(O) 2 — wherein R and R′ are independently of each other an alkyl radical having from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include dimethylaminosulfonyl, diethylaminosulfonyl, N-methyl-N-ethylaminosulfonyl.

C 6 -C 12 -Arylaminosulfonyl is a radical of the formula R—NH—S(O) 2 — wherein R is an aryl radical having from 6 to 12, preferably 6 carbon atoms as defined herein.

Amino is NH 2 .

C 1 -C 6 -Alkylamino is a radical of the formula R—NH— wherein R is an alkyl radical having from 1 to 6, in particular from 1 to 4 carbon atoms as defined herein. Examples include methylamino, ethylamino, n-propylamino, iso-propylamino, n-butylamino, 2-butylamino, iso-butylamino, tertbutylamino.

(Halogenated C 1 -C 6 -alkyl)amino is a C 1 -C 6 -alkylamino as defined herein, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms.

Di-C 1 -C 6 -alkylamino is a radical of the formula RR′N— wherein R and R′ are independently of each other an alkyl radical having from 1 to 6, in particular from 1 to 4 carbon atoms as defined herein. Examples include dimethylamino, diethylamino, N-methyl-N-ethylamino.

Di-(halogenated C 1 -C 6 -alkyl)amino is a di-C 1 -C 6 -alkylamino as defined herein, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms.

C 1 -C 6 -Alkylcarbonylamino is a radical of the formula R—C(O)—NH—, wherein R is an alkyl radical having from 1 to 6, in particular from 1 to 4 carbon atoms as defined herein. Examples include acetamido (methylcarbonylamino), propionamido, n-butyramido, 2-methylpropionamido (iso-propylcarbonylamino), 2,2-dimethylpropionamido and the like.

(Halogenated C 1 -C 6 -alkyl)carbonylamino is a C 1 -C 6 -alkylcarbonylamino as defined herein, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms.

C 6 -C 12 -Arylcarbonylamino is a radical of the formula R—C(O)—NH—, wherein R is an aryl radical having from 6 to 12 carbon atoms as defined herein. Examples include phenylcarbonylamino.

C 2 -C 6 -Alkenylamino is a radical of the formula R—NH—, wherein R is a straight-chain or branched alkenyl group having from 2 to 6, in particular 2 to 4 carbon atoms. Examples include vinylamino, allylamino (2-propen-1-ylamino), 1-propen-1-ylamino, 2-propen-2-ylamino, methallylamino (2-methylprop-2-en-1-ylamino) and the like. C 3 -C 5 -Alkenylamino is, in particular, allylamino, 1-methylprop-2-en-1-ylamino, 2-buten-1-ylamino, 3-buten-1-ylamino, methallylamino, 2-penten-1-ylamino, 3-penten-1-ylamino, 4-penten-1-ylamino, 1-methylbut-2-en-1-ylamino or 2-ethylprop-2-en-1-ylamino.

C 6 -C 12 -Arylamino is a radical of the formula R—NH—, wherein R is an aryl group having from 6 to 12, in particular 6 carbon atoms as defined herein. Examples include phenylamine.

C 1 -C 6 -Alkylsulfonylamino is a radical of the formula R—S(O) 2 —NH—, wherein R is an alkyl radical having from 1 to 6, in particular from 1 to 4 carbon atoms as defined herein. Examples include methylsulfonylamino, ethylsulfonylamino, n-propylsulfonylamino, iso-propylsulfonylamino, n-butylsulfonylamino, 2-butylsulfonylamino, iso-butylsulfonylamino, tert-butylsulfonylamino.

(Halogenated C 1 -C 6 alkyl)sulfonylamino is a C 1 -C 6 -alkylsulfonylamino as defined herein, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms.

C 6 -C 12 -Arylsulfonylamino is a radical of the formula R—S(O) 2 —NH—, wherein R is an aryl radical having from 6 to 12 carbon atoms as defined herein. Examples include phenylsulfonylamino.

Nitro is —NO 2 .

C 3 -C 12 -Heterocyclyl is a 3- to 12-membered heterocyclic radical including a saturated heterocyclic radical, which generally has 3, 4, 5, 6, or 7 ring forming atoms (ring members), an unsaturated non-aromatic heterocyclic radical, which generally has 5, 6 or 7 ring forming atoms, and a heteroaromatic radical (heteroaryl), which generally has 5, 6 or 7 ring forming atoms. The heterocyclic radicals may be bound via a carbon atom (C-bound) or a nitrogen atom (N-bound). Preferred heterocyclic radicals comprise 1 nitrogen atom as ring member atom and optionally 1, 2 or 3 further heteroatoms as ring members, which are selected, independently of each other from O, S and N. Likewise preferred heterocyclic radicals comprise 1 heteroatom as ring member, which is selected from O, S and N, and optionally 1, 2 or 3 further nitrogen atoms as ring members.

Examples of C 3 -C 12 -heterocyclyl include:

C- or N-bound 3-4-membered, saturated rings, such as 2-oxiranyl, 2-oxetanyl, 3-oxetanyl, 2-aziridinyl, 3-thiethanyl, 1-azetidinyl, 2-azetidinyl, 3-azetidinyl;

C-bound, 5-membered, saturated rings, such as tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, tetrahydropyrrol-2-yl, tetrahydropyrrol-3-yl, tetrahydropyrazol-3-yl, tetrahydro-pyrazol-4-yl, tetrahydroisoxazol-3-yl, tetrahydroisoxazol-4-yl, tetrahydroisoxazol-5-yl, 1,2-oxathiolan-3-yl, 1,2-oxathiolan-4-yl, 1,2-oxathiolan-5-yl, tetrahydroisothiazol-3-yl, tetrahydroisothiazol-4-yl, tetrahydroisothiazol-5-yl, 1,2-dithiolan-3-yl, 1,2-dithiolan-4-yl, tetrahydroimidazol-2-yl, tetrahydroimidazol-4-yl, tetrahydrooxazol-2-yl, tetrahydrooxazol-4-yl, tetrahydrooxazol-5-yl, tetrahydrothiazol-2-yl, tetrahydrothiazol-4-yl, tetrahydrothiazol-5-yl, 1,3-dioxolan-2-yl, 1,3-dioxolan-4-yl, 1,3-oxathiolan-2-yl, 1,3-oxathiolan-4-yl, 1,3-oxathiolan-5-yl, 1,3-dithiolan-2-yl, 1,3-dithiolan-4-yl, 1,3,2-dioxathiolan-4-yl;

C-bound, 6-membered, saturated rings, such as tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, 1,3-dioxan-2-yl, 1,3-dioxan-4-yl, 1,3-dioxan-5-yl, 1,4-dioxan-2-yl, 1,3-dithian-2-yl, 1,3-dithian-4-yl, 1,3-dithian-5-yl, 1,4-dithian-2-yl, 1,3-oxathian-2-yl, 1,3-oxathian-4-yl, 1,3-oxathian-5-yl, 1,3-oxathian-6-yl, 1,4-oxathian-2-yl, 1,4-oxathian-3-yl, 1,2-dithian-3-yl, 1,2-dithian-4-yl, hexahydropyrimidin-2-yl, hexahydropyrimidin-4-yl, hexahydropyrimidin-5-yl, hexahydropyrazin-2-yl, hexahydropyridazin-3-yl, hexahydropyridazin-4-yl, tetrahydro-1,3-oxazin-2-yl, tetrahydro-1,3-oxazin-4-yl, tetrahydro-1,3-oxazin-5-yl, tetrahydro-1,3-oxazin-6-yl, tetrahydro-1,3-thiazin-2-yl, tetrahydro-1,3-thiazin-4-yl, tetrahydro-1,3-thiazin-5-yl, tetrahydro-1,3-thiazin-6-yl, tetrahydro-1,4-thiazin-2-yl, tetrahydro-1,4-thiazin-3-yl, tetrahydro-1,4-oxazin-2-yl, tetrahydro-1,4-oxazin-3-yl, tetrahydro-1,2-oxazin-3-yl, tetrahydro-1,2-oxazin-4-yl, tetrahydro-1,2-oxazin-5-yl, tetrahydro-1,2-oxazin-6-yl;

N-bound, 5-membered, saturated rings, such as tetrahydropyrrol-1-yl(pyrrolidin-1-yl), tetrahydropyrazol-1-yl, tetrahydroisoxazol-2-yl, tetrahydroisothiazol-2-yl, tetrahydroimidazol-1-yl, tetrahydrooxazol-3-yl, tetrahydrothiazol-3-yl;

N-bound, 6-membered, saturated rings, such as piperidin-1-yl, hexahydropyrimidin-1-yl, hexahydropyrazin-1-yl(piperazin-1-yl), hexahydropyridazin-1-yl, tetrahydro-1,3-oxazin-3-yl, tetrahydro-1,3-thiazin-3-yl, tetrahydro-1,4-thiazin-4-yl, tetrahydro-1,4-oxazin-4-yl(morpholin-1-yl), tetrahydro-1,2-oxazin-2-yl;

C-bound, 5-membered, partially unsaturated rings, such as 2,3-dihydrofuran-2-yl, 2,3-dihydrofuran-3-yl, 2,5-dihydrofuran-2-yl, 2,5-di-hydrofuran-3-yl, 4,5-dihydrofuran-2-yl, 4,5-dihydrofuran-3-yl, 2,3-dihydro-thien-2-yl, 2,3-dihydrothien-3-yl, 2,5-dihydrothien-2-yl, 2,5-dihydrothien-3-yl, 4,5-dihydrothien-2-yl, 4,5-dihydrothien-3-yl, 2,3-dihydro-1H-pyrrol-2-yl, 2,3-dihydro-1H-pyrrol-3-yl, 2,5-dihydro-1H-pyrrol-2-yl, 2,5-dihydro-1H-pyrrol-3-yl, 4,5-dihydro-1H-pyrrol-2-yl, 4,5-dihydro-1H-pyrrol-3-yl, 3,4-dihydro-2H-pyrrol-2-yl, 3,4-dihydro-2H-pyrrol-3-yl, 3,4-dihydro-5H-pyrrol-2-yl, 3,4-dihydro-5H-pyrrol-3-yl, 4,5-dihydro-1H-pyrazol-3-yl, 4,5-dihydro-1H-pyrazol-4-yl, 4,5-dihydro-1H-pyrazol-5-yl, 2,5-dihydro-1H-pyrazol-3-yl, 2,5-dihydro-1H-pyrazol-4-yl, 2,5-dihydro-1H-pyrazol-5-yl, 4,5-dihydroisoxazol-3-yl, 4,5-dihydroisoxazol-4-yl, 4,5-dihydroisoxazol-5-yl, 2,5-dihydroisoxazol-3-yl, 2,5-dihydroisoxazol-4-yl, 2,5-dihydroisoxazol-5-yl, 2,3-dihydroisoxazol-3-yl, 2,3-dihydroisoxazol-4-yl, 2,3-dihydroisoxazol-5-yl, 4,5-dihydroisothiazol-3-yl, 4,5-dihydroisothiazol-4-yl, 4,5-dihydroisothiazol-5-yl, 2,5-dihydroisothiazol-3-yl, 2,5-dihydroisothiazol-4-yl, 2,5-dihydroisothiazol-5-yl, 2,3-dihydroisothiazol-3-yl, 2,3-dihydroisothiazol-4-yl, 2,3-dihydroisothiazol-5-yl, 4,5-dihydro-1H-imidazol-2-yl, 4,5-dihydro-1H-imidazol-4-yl, 4,5-dihydro-1H-imidazol-5-yl, 2,5-dihydro-1H-imidazol-2-yl, 2,5-dihydro-1H-imidazol-4-yl, 2,5-dihydro-1H-imidazol-5-yl, 2,3-dihydro-1H-imidazol-2-yl, 2,3-dihydro-1H-imidazol-4-yl, 4,5-dihydro-oxazol-2-yl, 4,5-dihydrooxazol-4-yl, 4,5-dihydrooxazol-5-yl, 2,5-dihydrooxazol-2-yl, 2,5-dihydrooxazol-4-yl, 2,5-dihydrooxazol-5-yl, 2,3-dihydrooxazol-2-yl, 2,3-dihydrooxazol-4-yl, 2,3-dihydrooxazol-5-yl, 4,5-dihydrothiazol-2-yl, 4,5-dihydrothiazol-4-yl, 4,5-dihydrothiazol-5-yl, 2,5-dihydrothiazol-2-yl, 2,5-dihydrothiazol-4-yl, 2,5-dihydrothiazol-5-yl, 2,3-dihydrothiazol-2-yl, 2,3-dihydrothiazol-4-yl, 2,3-dihydrothiazol-5-yl, 1,3-dioxol-2-yl, 1,3-dioxol-4-yl, 1,3-dithiol-2-yl, 1,3-dithiol-4-yl, 1,3-oxathiol-2-yl, 1,3-oxathiol-4-yl, 1,3-oxathiol-5-yl;

C-bound, 6-membered, partially unsaturated rings, such as 2H-3,4-dihydropyran-6-yl, 2H-3,4-dihydropyran-5-yl, 2H-3,4-dihydropyran-4-yl, 2H-3,4-dihydropyran-3-yl, 2H-3,4-dihydropyran-2-yl, 2H-3,4-dihydrothiopyran-6-yl, 2H-3,4-dihydrothiopyran-5-yl, 2H-3,4-dihydrothiopyran-4-yl, 2H-3,4-dihydrothiopyran-3-yl, 2H-3,4-dihydrothiopyran-2-yl, 1,2,3,4-tetrahydropyridin-6-yl, 1,2,3,4-tetrahydropyridin-5-yl, 1,2,3,4-tetrahydropyridin-4-yl, 1,2,3,4-tetra-hydropyridin-3-yl, 1,2,3,4-tetrahydropyridin-2-yl, 2H-5,6-dihydropyran-2-yl, 2H-5,6-dihydropyran-3-yl, 2H-5,6-dihydropyran-4-yl, 2H-5,6-dihydropyran-5-yl, 2H-5,6-dihydropyran-6-yl, 2H-5,6-dihydrothiopyran-2-yl, 2H-5,6-dihydrothiopyran-3-yl, 2H-5,6-dihydrothiopyran-4-yl, 2H-5,6-dihydrothiopyran-5-yl, 2H-5,6-dihydrothiopyran-6-yl, 1,2,5,6-tetrahydropyridin-2-yl, 1,2,5,6-tetrahydropyridin-3-yl, 1,2,5,6-tetrahydropyridin-4-yl, 1,2,5,6-tetrahydropyridin-5-yl, 1,2,5,6-tetrahydropyridin-6-yl, 2,3,4,5-tetrahydropyridin-2-yl, 2,3,4,5-tetrahydropyridin-3-yl, 2,3,4,5-tetrahydropyridin-4-yl, 2,3,4,5-tetrahydropyridin-5-yl, 2,3,4,5-tetrahydropyridin-6-yl, 4H-pyran-2-yl, 4H-pyran-3-yl-, 4H-pyran-4-yl, 4H-thiopyran-2-yl, 4H-thiopyran-3-yl, 4H-thiopyran-4-yl, 1,4-dihydropyridin-2-yl, 1,4-dihydropyridin-3-yl, 1,4-dihydropyridin-4-yl, 2H-pyran-2-yl, 2H-pyran-3-yl, 2H-pyran-4-yl, 2H-pyran-5-yl, 2H-pyran-6-yl, 2H-thiopyran-2-yl, 2H-thiopyran-3-yl, 2H-thiopyran-4-yl, 2H-thiopyran-5-yl, 2H-thiopyran-6-yl, 1,2-dihydropyridin-2-yl, 1,2-dihydro-pyridin-3-yl, 1,2-dihydropyridin-4-yl, 1,2-dihydropyridin-5-yl, 1,2-dihydro-pyridin-6-yl, 3,4-dihydropyridin-2-yl, 3,4-dihydropyridin-3-yl, 3,4-dihydropyridin-4-yl, 3,4-dihydropyridin-5-yl, 3,4-dihydropyridin-6-yl, 2,5-dihydropyridin-2-yl, 2,5-dihydropyridin-3-yl, 2,5-dihydropyridin-4-yl, 2,5-dihydropyridin-5-yl, 2,5-dihydropyridin-6-yl, 2,3-dihydropyridin-2-yl, 2,3-dihydropyridin-3-yl, 2,3-dihydropyridin-4-yl, 2,3-dihydropyridin-5-yl, 2,3-dihydropyridin-6-yl, 2H-5,6-dihydro-1,2-oxazin-3-yl, 2H-5,6-dihydro-1,2-oxazin-4-yl, 2H-5,6-dihydro-1,2-oxazin-5-yl, 2H-5,6-dihydro-1,2-oxazin-6-yl, 2H-5,6-dihydro-1,2-thiazin-3-yl, 2H-5,6-dihydro-1,2-thiazin-4-yl, 2H-5,6-dihydro-1,2-thiazin-5-yl, 2H-5,6-dihydro-1,2-thiazin-6-yl, 4H-5,6-dihydro-1,2-oxazin-3-yl, 4H-5,6-dihydro-1,2-oxazin-4-yl, 4H-5,6-dihydro-1,2-oxazin-5-yl, 4H-5,6-dihydro-1,2-oxazin-6-yl, 4H-5,6-dihydro-1,2-thiazin-3-yl, 4H-5,6-dihydro-1,2-thiazin-4-yl, 4H-5,6-dihydro-1,2-thiazin-5-yl, 4H-5,6-dihydro-1,2-thiazin-6-yl, 2H-3,6-dihydro-1,2-oxazin-3-yl, 2H-3,6-dihydro-1,2-oxazin-4-yl, 2H-3,6-dihydro-1,2-oxazin-5-yl, 2H-3,6-dihydro-1,2-oxazin-6-yl, 2H-3,6-dihydro-1,2-thiazin-3-yl, 2H-3,6-dihydro-1,2-thiazin-4-yl, 2H-3,6-dihydro-1,2-thiazin-5-yl, 2H-3,6-dihydro-1,2-thiazin-6-yl, 2H-3,4-dihydro-1,2-oxazin-3-yl, 2H-3,4-dihydro-1,2-oxazin-4-yl, 2H-3,4-dihydro-1,2-oxazin-5-yl, 2H-3,4-dihydro-1,2-oxazin-6-yl, 2H-3,4-dihydro-1,2-thiazin-3-yl, 2H-3,4-dihydro-1,2-thiazin-4-yl, 2H-3,4-dihydro-1,2-thiazin-5-yl, 2H-3,4-dihydro-1,2-thiazin-6-yl, 2,3,4,5-tetrahydropyridazin-3-yl, 2,3,4,5-tetrahydropyridazin-4-yl, 2,3,4,5-tetrahydropyridazin-5-yl, 2,3,4,5-tetrahydropyridazin-6-yl, 3,4,5,6-tetrahydropyridazin-3-yl, 3,4,5,6-tetrahydropyridazin-4-yl, 1,2,5,6-tetrahydropyridazin-3-yl, 1,2,5,6-tetrahydropyridazin-4-yl, 1,2,5,6-tetra-hydropyridazin-5-yl, 1,2,5,6-tetrahydropyridazin-6-yl, 1,2,3,6-tetrahydro-pyridazin-3-yl, 1,2,3,6-tetrahydropyridazin-4-yl, 4H-5,6-dihydro-1,3-oxazin-2-yl, 4H-5,6-dihydro-1,3-oxazin-4-yl, 4H-5,6-dihydro-1,3-oxazin-5-yl, 4H-5,6-dihydro-1,3-oxazin-6-yl, 4H-5,6-dihydro-1,3-thiazin-2-yl, 4H-5,6-dihydro-1,3-thiazin-4-yl, 4H-5,6-dihydro-1,3-thiazin-5-yl, 4H-5,6-dihydro-1,3-thiazin-6-yl, 3,4,5-6-tetrahydropyrimidin-2-yl, 3,4,5,6-tetrahydropyrimidin-4-yl, 3,4,5,6-tetrahydropyrimidin-5-yl, 3,4,5,6-tetrahydropyrimidin-6-yl, 1,2,3,4-tetrahydropyrazin-2-yl, 1,2,3,4-tetrahydropyrazin-5-yl, 1,2,3,4-tetrahydro-pyrimidin-2-yl, 1,2,3,4-tetrahydropyrimidin-4-yl, 1,2,3,4-tetrahydropyrimidin-5-yl, 1,2,3,4-tetrahydropyrimidin-6-yl, 2,3-dihydro-1,4-thiazin-2-yl, 2,3-dihydro-1,4-thiazin-3-yl, 2,3-dihydro-1,4-thiazin-5-yl, 2,3-dihydro-1,4-thiazin-6-yl, 2H-1,3-oxazin-2-yl, 2H-1,3-oxazin-4-yl, 2H-1,3-oxazin-5-yl, 2H-1,3-oxazin-6-yl, 2H-1,3-thiazin-2-yl, 2H-1,3-thiazin-4-yl, 2H-1,3-thiazin-5-yl, 2H-1,3-thiazin-6-yl, 4H-1,3-oxazin-2-yl, 4H-1,3-oxazin-4-yl, 4H-1,3-oxazin-5-yl, 4H-1,3-oxazin-6-yl, 4H-1,3-thiazin-2-yl, 4H-1,3-thiazin-4-yl, 4H-1,3-thiazin-5-yl, 4H-1,3-thiazin-6-yl, 6H-1,3-oxazin-2-yl, 6H-1,3-oxazin-4-yl, 6H-1,3-oxazin-5-yl, 6H-1,3-oxazin-6-yl, 6H-1,3-thiazin-2-yl, 6H-1,3-oxazin-4-yl, 6H-1,3-oxazin-5-yl, 6H-1,3-thiazin-6-yl, 2H-1,4-oxazin-2-yl, 2H-1,4-oxazin-3-yl, 2H-1,4-oxazin-5-yl, 2H-1,4-oxazin-6-yl, 2H-1,4-thiazin-2-yl, 2H-1,4-thiazin-3-yl, 2H-1,4-thiazin-5-yl, 2H-1,4-thiazin-6-yl, 4H-1,4-oxazin-2-yl, 4H-1,4-oxazin-3-yl, 4H-1,4-thiazin-2-yl, 4H-1,4-thiazin-3-yl, 1,4-dihydropyridazin-3-yl, 1,4-dihydropyridazin-4-yl, 1,4-dihydropyridazin-5-yl, 1,4-dihydropyridazin-6-yl, 1,4-dihydropyrazin-2-yl, 1,2-dihydropyrazin-2-yl, 1,2-dihydropyrazin-3-yl, 1,2-dihydropyrazin-5-yl, 1,2-dihydropyrazin-6-yl, 1,4-dihydropyrimidin-2-yl, 1,4-dihydropyrimidin-4-yl, 1,4-dihydropyrimidin-5-yl, 1,4-dihydropyrimidin-6-yl, 3,4-dihydropyrimidin-2-yl, 3,4-dihydropyrimidin-4-yl, 3,4-dihydropyrimidin-5-yl or 3,4-dihydropyrimidin-6-yl;

N-bound, 5-membered, partially unsaturated rings, such as 2,3-dihydro-1H-pyrrol-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, 4,5-dihydro-1H-pyrazol-1-yl, 2,5-dihydro-1H-pyrazol-1-yl, 2,3-dihydro-1H-pyrazol-1-yl, 2,5-dihydroisoxazol-2-yl, 2,3-dihydroisoxazol-2-yl, 2,5-dihydroisothiazol-2-yl, 2,3-dihydroisoxazol-2-yl, 4,5-dihydro-1H-imidazol-1-yl, 2,5-dihydro-1H-imidazol-1-yl, 2,3-dihydro-1H-imidazol-1-yl, 2,3-dihydrooxazol-3-yl, 2,3-dihydrothiazol-3-yl;

N-bound, 6-membered, partially unsaturated rings, such as 1,2,3,4-tetrahydropyridin-1-yl, 1,2,5,6-tetrahydropyridin-1-yl, 1,4-dihydro-pyridin-1-yl, 1,2-dihydropyridin-1-yl, 2H-5,6-dihydro-1,2-oxazin-2-yl, 2H-5,6-dihydro-1,2-thiazin-2-yl, 2H-3,6-dihydro-1,2-oxazin-2-yl, 2H-3,6-dihydro-1,2-thiazin-2-yl, 2H-3,4-dihydro-1,2-oxazin-2-yl, 2H-3,4-dihydro-1,2-thiazin-2-yl, 2,3,4,5-tetrahydropyridazin-2-yl, 1,2,5,6-tetrahydropyridazin-1-yl, 1,2,5,6-tetrahydropyridazin-2-yl, 1,2,3,6-tetrahydropyridazin-1-yl, 3,4,5,6-tetrahydropyrimidin-3-yl, 1,2,3,4-tetrahydropyrazin-1-yl, 1,2,3,4-tetrahydropyrimidin-1-yl, 1,2,3,4-tetrahydropyrimidin-3-yl, 2,3-dihydro-1,4-thiazin-4-yl, 2H-1,2-oxazin-2-yl, 2H-1,2-thiazin-2-yl, 4H-1,4-oxazin-4-yl, 4H-1,4-thiazin-4-yl, 1,4-dihydropyridazin-1-yl, 1,4-dihydropyrazin-1-yl, 1,2-dihydropyrazin-1-yl, 1,4-dihydropyrimidin-1-yl or 3,4-dihydropyrimidin-3-yl;

C-bound, 5-membered, heteroaromatic rings, such as 2-furyl, 3-furyl, 5-furyl, 2-thienyl, 3-thienyl, 5-thienyl, pyrrol-2-yl, pyrrol-3-yl, pyrrol-5-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, 1,2,3-oxadiazol-imidazol-4-yl, 4-yl, 1,2,3-oxadiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4,-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-5-yl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1,3,4-thiadiazolyl-2-yl, 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl, tetrazol-5-yl;

C-bound, 6-membered, heteroaromatic rings, such as pyridin-2-yl, pyridin-3-yl (3-pyridyl), pyridin-4-yl (4-pyridyl), pyridin-5-yl, pyridazin-3-yl, pyridazin-4-yl, pyridazin-6-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrazin-2-yl, pyrazin-5-yl, 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl, 1,2,4,5-tetrazin-3-yl;

N-bound, 5-membered, heteroaromatic rings, such as pyrrol-1-yl, pyrazol-1-yl, imidazol-1-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, tetrazol-1-yl.

Heterocyclyl also includes bicyclic heterocycles, which comprise one of the described 5- or 6-membered heterocyclic rings and a further anellated, saturated or unsaturated or aromatic carbocycle, such as a benzene, cyclohexane, cyclohexene or cyclohexadiene ring, or a further anellated 5- or 6-membered heterocyclic ring, this heterocyclic ring being saturated or unsaturated or aromatic. These include quinolinyl, isoquinolinyl, indolyl, indolizinyl, isoindolyl, indazolyl, benzofuryl, benzthienyl, benzo[b]thiazolyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, imidazo[b]thiazolyl, thieno[b]pyridyl, imidazo[a]pyridyl, pyrazo[a]pyridyl and pyrrol[d]pyrimidyl. Examples of 5- or 6-membered heteroaromatic compounds comprising an anellated cycloalkenyl ring include dihydroindolyl, dihydroindolizinyl, dihydroisoindolyl, dihydroquinolinyl, dihydroisoquinolinyl, dihydrobenzofuryl, chromanyl, chromanyl, dihydropyrrolo[a]imidazolyl and tetrahydro benzothiazolyl.

C 3 -C 12 -Heteroarylene is a heteroaryl diradical. Examples include pyrid-2,5-ylene and pyrid-2,4-ylene.

With respect to the compounds' capability of inhibiting glycine transporter 1, the variables R 1 , R 2a , R 2b , R 3a , R 3b , R 4 , Y 1 , R 5a , R 5b , R 6 , R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 8a , R 8b , R 8c , R 8a , R 8d , R 8e , R 9a , R 9b , R 9c , R 9d , R 10 , R 11a , R 11b , R 12 , R 13 , R 14 , R 15 , R 16a , R 16b , R 17 , R 18 , R 19 , R 20a , R 20b , R 21 , n1, n2, n3, n4 and n5 preferably have the following meanings which, when taken alone or in combination, represent particular embodiments of the pyrrolidine derivatives of the formula (I) or any other formula disclosed herein.

R 1 is C 1 -C 8 -alkyl (e.g. methyl; ethyl, or n-propyl), (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl (e.g. cyclopropylmethyl), (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl, (optionally substituted C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl (e.g. tetrahydropyran-2-yl-methyl), optionally substituted C 3 -C 12 -cycloalkyl (e.g. cyclobutyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 4-Cl-phenyl, 3-Cl-phenyl, 2,4-dichlorophenyl, 4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 2-CN-phenyl, 2-aminocarbonyl-phenyl, or 4-OMe-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 2,5-dimethyl-furan-3-yl, 4-methyl-thiophen-2-yl, 5-methyl-thiophen-2-yl, 5-ethyl-thiophen-2-yl, 2,5-dimethyl-thiophen-3-yl, 5-Cl-thiophen-2-yl, 2-methoxycarbonyl-thiophen-3-yl, 3-methoxy-4-methoxycarbonyl-thiophen-2-yl, 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, 2-methylcarbonylamino-1,3-thiazol-5-yl, 3-pyridyl, 2-CF 3 -pyrid-5-yl, 2-(morpholin-1-yl)-pyrid-5-yl, 2-OMe-pyrid-5-yl, 1-methylcarbonyl-indolin-5-yl, 1,2-benzoxazol-5-yl, 1,4-dihydroquinoxaline-2,3-dion-6-yl, 6-chloro-imidazo[2,1-b]thiazol-5-yl, 6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl, 3H-1,3-benzoxazol-2-on-5-yl, 3,3-dimethylindolin-2-on-5-yl, indolin-2-on-5-yl, 1,3-dihydrobenzimidazol-2-on-5-yl, 1H-quinazoline-2,4-dion-6-yl, 6-Me-4H-1,4-benzoxazin-3-on-7-yl, 2,3-dihydrobenzofuran-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl, 1,3-benzodioxol-5-yl, isoquinoline-5-yl, 3,4-dihydro-1H-quinolin-2-on-6yl, 1-Me-indol-5yl, pyrrolidin-1-yl, 4-Me-piperidin-1-yl, morpholin-1-yl).

Preferably, R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-iso-propyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl).

According to one embodiment, R 1 is an optionally substituted 5-membered heterocyclic ring containing 1 or 2N and 1 O (e.g. 5-methyl-1,2-oxazol-4-yl or 3,5-dimethyl-1,2-oxazol-4-yl). According to an alternative embodiment, R 1 is an optionally substituted 5-membered heterocyclic ring containing 1 or 2 N and 1 S (e.g. 2,4-dimethyl-1,3-thiazol-5-yl or 2-methylcarbonylamino-1,3-thiazol-5-yl). According to a further alternative embodiment, R 1 is an optionally substituted 5-membered heterocyclic ring containing 1, 2 or 3 N (e.g. 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-iso-propyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl or 1-Me-1,2,3-triazol-4-yl).

Preferably, R 1 is an optionally substituted 5-membered heterocyclic ring containing 2 N which, in particular, is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 is an optionally substituted 5-membered heterocyclic ring containing 3 N which, in particular, is optionally substituted 1,2,3-triazolyl.

In connection with R 1 , substituted 5-membered heterocyclic rings containing at least 1 N atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular include 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, thiazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxycarbonyl and C 1 -C 6 -alkylcarbonylamino.

Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl.

In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl).

According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl.

According to a further particular embodiment, 1,2,3-triazolyl is substituted with C 1 -C 6 -alkyl as described herein. According to a further specific embodiment, R 1 is 1-methyl-1,2,3-triazol-4-yl.

R 2a , R 2b are independently hydrogen, halogen (e.g. F), or C 1 -C 3 -alkyl (e.g. methyl, ethyl, n-propyl, or iso-propyl), or R 2a , R 2b together with the carbon atom to which they are bound may form a C═O.

According to one particular embodiment R 2a is hydrogen, halogen (e.g. F) or C 1 -C 3 -alkyl (e.g. methyl or ethyl), and R 2b is hydrogen. Preferably, R 2a , R 2b are both hydrogen.

R 3a is C 3 -C 12 -cycloalkyl (cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), hydroxy, C 1 -C 6 -alkoxy (e.g. methoxy, ethoxy, n-propoxy, iso-propoxy, or iso-butoxy) halogenated C 1 -C 6 -alkoxy (e.g OCF 3 ), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkoxy (e.g. 2-(N-pyrrolidinyl)ethoxy, 2-(N-morpholinyl)ethoxy, or 2-(N-imidazolyl)ethoxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy or 4-F-phenoxy), C 3 -C 12 -heterocyclyloxy (e.g. pyridin-2-yloxy), or optionally substituted C 3 -C 12 -heterocyclyl (tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, 1-cyclopropyl-piperidin-4-yl, 1-cyclopropyl-piperidin-3-yl, 2-pyridyl, 3-pyridyl, 3-F-pyrid-2-yl, 1,3-oxazol-4-yl, 1,3-oxazol-2-yl, 3-F-azetidin-1-yl, morpholin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, 2-Me-piperidin-1yl, 3-Me-piperidin-1yl, 4-Me-piperidin-1yl, 4-F-piperidin-1-yl, 4,4-diF-piperidin-1yl, or azepan-1-yl).

In particular, R 3a is C 3 -C 12 -cycloalkyl (cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), C 3 -C 12 -heterocyclyloxy (e.g. pyridin-2-yloxy), or optionally substituted C 3 -C 12 -heterocyclyl (tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, 1-cyclopropyl-piperidin-4-yl, 1-cyclopropyl-piperidin-3-yl, 2-pyridyl, 3-pyridyl, 3-F-pyrid-2-yl, 1,3-oxazol-4-yl, 1,3-oxazol-2-yl, 3-F-azetidin-1-yl, morpholin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, 2-Me-piperidin-1yl, 3-Me-piperidin-1yl, 4-Me-piperidin-1yl, 4-F-piperidin-1-yl, 4,4-diF-piperidin-1yl, or azepan-1-yl).

Preferably, R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, 1-cyclopropyl-piperidin-4-yl, 1-cyclopropyl-piperidin-3-yl, 2-pyridyl, 3-pyridyl, 3-F-pyrid-2-yl, 1,3-oxazol-4-yl, 1,3-oxazol-2-yl, 3-F-azetidin-1-yl, morpholin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, 2-Me-piperidin-1yl, 3-Me-piperidin-1yl, 4-Me-piperidin-1yl, 4-F-piperidin-1-yl, 4,4-diF-piperidin-1yl, or azepan-1-yl).

According to one preferred embodiment, R 3a is optionally substituted C 6 -C 12 -aryl wherein C 6 -C 12 -aryl is phenyl, in particular phenyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. phenyl, 4-F-phenyl, 2-F-phenyl, 3-F-phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, or 2,4,5-trifluoro-phenyl).

According to a further preferred embodiment, R 3a is optionally substituted C 3 -C 12 -heterocyclyl wherein C 3 -C 12 -heterocyclyl is in particular tetrahydrofuranyl or tetrahydropyranyl, preferably unsubstituted tetrahydrofuranyl (e.g. tetrahydrofuran-2-yl) or unsubstituted tetrahydropyranyl (e.g. tetrahydropyran-2-yl).

According to an additional aspect, R 3a is not 3,4-di-O-substituted phenyl if R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl). According to a further additional aspect, there is not more than one O-bound substituent on the aryl group if R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl).

In connection with R 3a , substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy.

Preferably, the substituent(s) on C 6 -C 12 -aryl are independently selected from the group consisting of halogen.

In connection with R 3a , substituted C 6 -C 12 -aryloxy in particular includes C 6 -C 12 -aryloxy, such as phenoxy, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen and C 1 -C 4 -alkyl.

Preferably, the substituent(s) on C 6 -C 12 -aryloxy are independently selected from the group consisting of halogen.

In connection with R 3a , substituted C 3 -C 12 -heterocyclyl in particular includes C 3 -C 12 -heterocyclyl, such as pyridyl, piperidinyl, isoxazolyl, diazolyl, tetrahydrofuranyl, tetrahydropyranyl, or morpholinyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 3 -C 6 -cycloalkyl.

Preferably, the substituent(s) on C 3 -C 12 -heterocyclyl are independently selected from the group consisting of halogen.

R 3b is hydrogen, C 1 -C 6 -alkyl, or hydroxy. Preferably, R 3b is hydrogen.

Y 1 is >CR 6 — or >N—.

Preferably, Y 1 is >CR 6 —.

R 6 is hydrogen, C 1 -C 6 -alkyl (e.g. methyl, ethyl, n-propyl, iso-propyl, or iso-butyl), halogenated C 1 -C 6 -alkyl (e.g. CF 3 or CF 2 H), (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl (e.g. benzyl), hydroxy-C 1 -C 6 -alkyl (e.g. —CH 2 OH or —(CH 2 ) 2 OH), C 1 -C 4 -alkoxy-C 1 -C 6 -alkyl (e.g. methoxymethyl, 2-ethoxypropyl, or 3-ethoxypropyl), or hydroxy.

In particular, R 6 is hydrogen, C 1 -C 6 -alkyl (e.g. methyl or ethyl), C 6 -C 12 -aryl-C 1 -C 4 -alkyl (e.g. benzyl or phenethyl), hydroxy-C 1 -C 6 -alkyl (e.g. —CH 2 OH, or —(CH 2 ) 2 OH), or hydroxy, i.e., R 6 is, e.g., hydrogen, methyl, benzyl, hydroxymethyl, or hydroxy.

Preferably, R 6 is hydrogen.

According to some embodiments, Y 1 is >N—. In particular, Y 1 is >N— if R 4 is —(CR 7e R 7f ) n3 R 12 .

R 4 is —(CR 7a R 7b ) n1 OR 10 , —(CR 7c R 7d ) n2 NR 11a R 11b , —(CR 7e R 7f ) n3 R 12 , optionally substituted C 6 -C 12 - aryl, —NR 8a (CR 9a R 9b ) n4 R 13 , —NR 8b COR 14 , —NR 8c COOR 15 , —NR 8d CONR 16a R 16b , —NR 8e SO 2 R 17 , —O(CR 9c R 9d ) n5 R 18 , —COR 19 , —CONR 20a R 20b , —SO 2 R 21 , or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 1-propyl-1,2,3-triazol-4-yl, 4-butyl-1,2,3-triazolyl-1-yl, 4-chloroisoindolin-1-one, 7-(trifluoromethyl)-3,4-dihydro-1H-quinazolin-2-on-1-yl).

In particular, R 4 is —(CR 7a R 7b ) n1 OR 10 , —(CR 7c R 7d ) n2 NR 11a R 11b , (CR 7e R 7f ) n3 R 12 , optionally substituted C 6 -C 12 -aryl, —NR 8a (CR 9a R 9b ) n4 R 13 , —NR 8b COR 14 , —NR 8c COOR 15 , —NR 8d CONR 16a R 16b ), —O(CR 9c R 9d ) n5 R 18 , —COR 19 , —CONR 20a R 20b , —SO 2 R 21 , or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 1-propyl-1,2,3-triazol-4-yl, 4-butyl-1,2,3-triazolyl-1-yl, 4-chloroisoindolin-1-one, or 7-(trifluoromethyl)-3,4-dihydro-1H-quinazolin-2-on-1-yl).

Preferably, R 4 is —NR 8a (CR 9a R 9b ) n4 R 13 or —O(CR 9c R 9d ) n5 R 18 . More preferably, R 4 is —NR 8a (CR 9a R 9b ) n4 R 13 .

In connection with R 4 , substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen.

In connection with R 4 , substituted C 3 -C 12 -heterocyclyl in particular includes C 3 -C 12 -heterocyclyl, such as pyridyl, isoxazolyl, diazolyl, 1,2,3-triazolyl, dihydroquinazolyn, or isoindolinyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl and hydroxy.

In particular, R 5a , R 5b are independently hydrogen, halogen, or C 1 -C 3 — alkyl (e.g. methyl, ethyl, n-propyl, or iso-propyl) or R 5a , R 5b together with the carbon atom to which they are bound may form a C═O.

Preferably, R 5a is hydrogen, halogen or C 1 -C 3 -alkyl (e.g. methyl or ethyl), and R 5b is hydrogen. More preferably, R 5a , R 5b are both hydrogen.

According to a one embodiment, R 4 is —(CR 7a R 7b ) n1 OR 10 . Thus, the present invention relates to the pyrrolidine derivatives of the formula (Ia):

wherein R 1 , R 2a , R 2b , R 3a , R 3b , Y 1 , R 5a and R 5b are as defined herein, and

R 7a , R 7b

are independently hydrogen or C 1 -C 6 -alkyl (e.g. methyl or ethyl), in particular, hydrogen;

n1 is 1, 2, 3 or 4, in particular 1; and R 10 is hydrogen, optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-F-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, or 3-OCF 3 -phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 6-CF 3 -pyrimid-4-yl, 4-CF 3 -pyrid-2-yl, or 2-CF 3 -pyrid-4-yl).

In connection with R 10 , substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl and halogenated C 1 -C 4 -alkoxy.

In connection with R 10 , substituted C 3 -C 12 -heterocyclyl in particular includes C 3 -C 12 -heterocyclyl, such as pyridyl, pyrimidyl, or pyridazyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl.

R 2a , R 2b —in the pyrrolidine derivatives of formula (Ia)—are, in particular, hydrogen.

R 3a —in the pyrrolidine derivatives of formula (Ia)—is, in particular, C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy or 4-F-phenoxy). Preferably, R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl).

R 3b —in the pyrrolidine derivatives of formula (Ia)—is, in particular, hydrogen.

Y 1 —in the pyrrolidine derivatives of formula (Ia)—is, in particular, >CR 6 .

R 6 —in the pyrrolidine derivatives of formula (Ia)—is, in particular, hydrogen.

R 5a , R 5b —in the pyrrolidine derivatives of formula—(Ia) are, in particular, hydrogen.

Particular embodiments of the pyrrolidine derivatives of formula (Ia) result if:

R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-iso-propyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl); R 2a , R 2b

are hydrogen;

R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 7a , R 7b

are hydrogen;

n1 is 1; R 10 is hydrogen, optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-F-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, or 3-OCF 3 -phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 6-CF 3 -pyrimid-4-yl, 4-CF 3 -pyrid-2-yl, or 2-CF 3 -pyrid-4-yl); and R 5a , R 5b

are hydrogen.

According to a particular embodiment, R 1 —in the pyrrolidine derivatives of formula (Ia)—is an optionally substituted 5-membered heterocyclic ring containing 1 or 2 N and 1 O (e.g. 5-methyl-1,2-oxazol-4-yl or 3,5-dimethyl-1,2-oxazol-4-yl). According to an alternative particular embodiment, R 1 is an optionally substituted 5-membered heterocyclic ring containing 1 or 2 N and 1 S (e.g. 2,4-dimethyl-1,3-thiazol-5-yl or 2-methylcarbonylamino-1,3-thiazol-5-yl). According to a further particular alternative embodiment, R 1 is an optionally substituted 5-membered heterocyclic ring containing 1, 2 or 3 N (e.g. 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-iso-propyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl or 1-Me-1,2,3-triazol-4-yl).

Preferably, R 1 —in the pyrrolidine derivatives of formula (Ia)—is an optionally substituted 5-membered heterocyclic ring containing 2 N which, in particular, is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 —in the pyrrolidine derivatives of formula (Ia)—is an optionally substituted 5-membered heterocyclic ring containing 3 N which, in particular, is optionally substituted 1,2,3-triazolyl.

In connection with R 1 and the pyrrolidine derivatives of formula (Ia), substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular includes 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, triazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy-carbonyl and C 1 -C 6 -alkyl-carbonylamino. Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl. In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl). According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl.

In connection with R 3a and the pyrrolidine derivatives of formula (Ia), substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy. Preferably, the substituents on C 6 -C 12 -aryl are independently selected from the group consisting of halogen.

According to a preferred embodiment, R 3a —in the pyrrolidine derivatives of formula (Ia)—is C 6 -C 12 -aryl, in particular phenyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, or 2,4,5-trifluoro-phenyl).

Further preferred embodiments of pyrrolidine derivatives of formula (Ia) result if:

R 1 is 1,3-diazolyl optionally substituted with halogen or C 1 -C 4 -alkyl (e.g. 1-methyl-1,3-diazol-4-yl); R 2a , R 2b

are hydrogen;

R 3a is C 6 -C 12 -aryl, in particular phenyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, or 2,4,5-trifluoro-phenyl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 7a , R 7b

are hydrogen;

n1 is 1; R 10 is hydrogen, C 6 -C 12 -aryl (e.g. phenyl) optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl and halogenated C 1 -C 4 -alkoxy, or C 3 -C 12 -heterocyclyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl; and R 5a , R 5b

are hydrogen.

According to a further embodiment, R 4 is —(CR 7c R 2d ) n2 NR 11a R 11b . Thus, the present invention relates to the pyrrolidine derivatives of the formula (Ib):

wherein R 1 , R 2a , R 2b , R 3a , R 3b , Y 1 , R 5a and R 5b are as defined herein, and

R 7c , R 7d

are independently hydrogen or C 1 -C 6 -alkyl (e.g. methyl or ethyl), in particular, hydrogen;

n2 is 1, 2, 3, or 4, in particular, 1; R 11a is C 1 -C 8 -alkyl (e.g. methyl, ethyl, n-propyl, or n-butyl), (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. 2-methoxy-ethyl, 2-ethoxy-ethyl, 2-isopropoxy-ethyl, 1-methyl-2-methoxy-ethyl, 3-methoxypropyl, 3-ethoxy-propyl, or 3-isopropoxy-propyl), (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl (e.g. benzyl), (optionally substituted C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl, optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,5-diCl-phenyl, 3-Cl-4-F-phenyl, 3-Me-phenyl, 3-(aminomethyl)-phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-OCF 3 -phenyl, 3-OCF 3 -4-F-phenyl, 3-OCF 3 -4-Cl-phenyl, or 3-(aminocarbonyl)-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl; and R 11b is hydrogen or (e.g. methyl, ethyl, n-propyl or n-butyl).

In particular, R 11a is C 1 -C 8 -alkyl (e.g. n-propyl or n-butyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl) C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. 2-methoxy-ethyl, 2-ethoxy-ethyl, 2-isopropyloxy-ethyl, 1-methyl-2-methoxy-ethyl, 3-methoxy-propyl, 3-ethoxy-propyl, or 3-isopropyloxy-propyl), C 6 -C 12 -aryl-C 1 -C 4 -alkyl (e.g. benzyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,5-diCl-phenyl, 3-Cl-4-F-phenyl, 3-Me-phenyl, 3-(aminomethyl)-phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-OCF 3 -phenyl, 3-OCF 3 -4-F-phenyl, 3-OCF 3 -4-Cl-phenyl, or 3-(aminocarbonyl)phenyl).

In connection with R 11a substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl, substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, amino-carbonyl and halogenated C 1 -C 4 -alkoxy.

In particular, R 11b is hydrogen.

R 2a , R 2b —in the pyrrolidine derivatives of formula (Ib)—are, in particular, both hydrogen.

R 3a —in the pyrrolidine derivatives of formula (Ib)—is, in particular, C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4 Cl phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy or 4-F-phenoxy). Preferably, R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl).

R 3b —in the pyrrolidine derivatives of formula (Ib)—is, in particular, hydrogen.

Y 1 —in the pyrrolidine derivatives of formula (Ib)—is, in particular, >CR 6 .

R 6 —in the pyrrolidine derivatives of formula (Ib)—is, in particular, hydrogen.

R 5a , R 5b in the pyrrolidine derivatives of formula (Ib)—are, in particular, hydrogen.

Particular embodiments of the pyrrolidine derivatives of formula (Ib) result if:

R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl); R 2a , R 2b

are hydrogen;

R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl or 2,4,5-trifluoro-phenyl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 7c , R 7d

are hydrogen;

n2 is 1; R 11a is C 1 -C 8 -alkyl (e.g. n-propyl or n-butyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl (e.g. cyclopropylmethyl) C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. 2-methoxy-ethyl, 2-ethoxy-ethyl, 2-isopropyloxy-ethyl, 1-methyl-2-methoxy-ethyl, 3-methoxy-propyl, 3-ethoxy-propyl, or 3-isopropyloxy-propyl), C 6 -C 12 -aryl-C 1 -C 4 -alkyl (e.g. benzyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,5-diCl-phenyl, 3-Cl-4-F-phenyl, 3-Me-phenyl, 3-(aminomethyl)-phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-OCF 3 -phenyl, 3-OCF 3 -4-F-phenyl, 3-OCF 3 -4-Cl-phenyl, or 3-(aminocarbonyl)-phenyl); R 11b is hydrogen; and R 5a , R 5b are

hydrogen.

Preferably, R 1 —in the pyrrolidine derivatives of formula (Ib)—is an optionally substituted 5-membered heterocyclic ring containing 2 N which, in particular, is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 —in the pyrrolidine derivatives of formula (Ib)—is an optionally substituted 5-membered heterocyclic ring containing 3 N which, in particular, is optionally substituted 1,2,3-triazolyl.

In connection with R 1 and the pyrrolidine derivatives of formula (Ib), substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular includes 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, thiazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy-carbonyl and C 1 -C 6 -alkyl-carbonylamino. Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl. In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl). According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl.

In connection with R 3a and the pyrrolidine derivatives of formula (Ib), substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy. Preferably, the substituents on C 6 -C 12 -aryl are independently selected from the group consisting of halogen.

According to a preferred embodiment, R 3a —in the pyrrolidine derivatives of formula (Ib)—is C 6 -C 12 -aryl, in particular phenyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, or 2,4,5-trifluoro-phenyl).

Further preferred embodiments of pyrrolidine derivatives of formula (Ib) result if:

R 1 is 1,3-diazolyl optionally substituted with halogen or C (e.g. 1-methyl-1,3-diazol-4-yl); R 2a , R 2b

are hydrogen;

R 3a is C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, or 2,4,5-trifluoro-phenyl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 7c , R 7d

are hydrogen;

n2 is 1; R 11a is C 1 -C 8 -alkyl (e.g. n-propyl or n-butyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl (e.g. cyclopropylmethyl), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. 2-methoxy-ethyl, 2-ethoxy-ethyl, 2-isopropyloxy-ethyl, 1-methyl-2-methoxy-ethyl, 3-methoxy-propyl, 3-ethoxy-propyl, or 3-isopropyloxy-propyl), C 6 -C 12 -aryl-C 1 -C 4 -alkyl (e.g. benzyl), or C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, aminocarbonyl and halogenated C 1 -C 4 -alkoxy (e.g. phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,5-diCl-phenyl, 3-Cl-4-F-phenyl, 3-Me-phenyl, 3-(aminomethyl)-phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-OCF 3 -phenyl, 3-OCF 3 -4-F-phenyl, 3-OCF 3 -4-Cl-phenyl, or 3-(aminocarbonyl)-phenyl); R 11b is hydrogen; and R 5a , R 5b

are hydrogen.

According to a further embodiment, R 4 is —(CR 7e R 7f ) n3 R 12 . Thus, the present invention relates to the pyrrolidine derivatives of the formula (Ic):

wherein R 1 , R 2a , R 2b , R 3a , R 3b , Y 1 , R 5a and R 5b are as defined herein, and

R 7e , R 7f

are independently hydrogen or C 1 -C 6 -alkyl (e.g. methyl or ethyl), in particular, hydrogen;

n3 is 1, 2, 3, or 4, in particular, 1; and R 12 is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-Cl-phenyl, or 3-Br-phenyl) or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 4-CF 3 -pyrid-2-yl or 1-propyl-1,2,3-triazol-4-yl).

In connection with R 12 , substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen.

In connection with R 12 , substituted C 3 -C 12 -heterocyclyl in particular includes C 3 -C 12 -heterocyclyl, such as pyridyl or triazolyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of C 1 -C 4 -alkyl and halogenated C 1 -C 4 -alkyl.

R 2a , R 2b —in pyrrolidine derivatives of formula (Ic)—are, in particular, hydrogen.

R 3a —in pyrrolidine derivatives of formula (Ic)—is, in particular, C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy or 4-F-phenoxy). Preferably, R 3a is C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) or optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl).

R 3b —in the pyrrolidine derivatives of formula (Ic)—is, in particular, hydrogen.

Y 1 —in the pyrrolidine derivatives of formula (Ic)—is, in particular, >CR 6 .

R 6 —in the pyrrolidine derivatives of formula (Ic)—is, in particular, hydrogen or hydroxy.

R 5a , R 5b —in the pyrrolidine derivatives of formula (Ic)—are, in particular, hydrogen or together with the carbon atom to which they are bound may form a C═O.

If Y 1 —in the pyrrolidine derivatives of formula (Ic)—is >N—R 5a , R 5b together with the carbon atom to which they are bound form, in particular, a C═O.

Particular embodiments of pyrrolidine derivatives of formula (Ic) result if:

R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl); R 2a , R 2b

are hydrogen;

R 3a is C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) or optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl); R 3b is hydrogen; Y 1 is >CR 6 or >N—; R 6 is hydrogen or hydroxy; R 7e , R 7f

are hydrogen;

n3 is 1; R 12 is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-Cl-phenyl, or 3-Br-phenyl) or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 4-CF 3 -pyrid-2-yl or 1-propyl-1,2,3-triazol-4-yl); and R 5a , R 5b

are hydrogen or together with the carbon atom to which they are bound may form a C═O.

Preferably, R 1 —in the pyrrolidine derivatives of formula (Ic)—is an optionally substituted 5-membered heterocyclic ring containing 2 N which, in particular, is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 —in the pyrrolidine derivatives of formula (Ic)—is an optionally substituted 5-membered heterocyclic ring containing 3 N which, in particular, is optionally substituted 1,2,3-triazolyl.

In connection with R 1 and the pyrrolidine derivatives of formula (Ic), substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular includes 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, thiazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy-carbonyl and C 1 -C 6 -alkyl-carbonylamino Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl. In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl). According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl.

In connection with R 3a and the pyrrolidine derivatives of formula (Ic), substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy. Preferably, the substituents on C 6 -C 12 -aryl are independently selected from the group consisting of halogen.

According to a preferred embodiment, R 3a —in the pyrrolidine derivatives of formula (Ic)—is C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) or C 6 -C 12 -aryl, in particular phenyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, or 2,4,5-trifluoro-phenyl).

Further preferred embodiments of pyrrolidine derivatives of formula (Ic) result if:

R 1 is 1,3-diazolyl optionally substituted with halogen or C 1 -C 4 -alkyl and preferably 1-methyl-1,3-diazol-4-yl; R 2a , R 2b

are hydrogen;

R 3a is C 3 -C 12 -cycloalkyl (e.g. cyclopropyl) or C 6 -C 12 -aryl optionally substituted with halogen (e.g. phenyl, 2-Br-phenyl, or 4-F-phenyl); R 3b is hydrogen; Y 1 is >CR 6 or >N—; R 6 is hydrogen or hydroxy; R 7e , R 7f

are hydrogen;

n3 is 1; R 12 is C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. phenyl, 3-Cl-phenyl, or 3-Br-phenyl), or C 3 -C 12 -heterocyclyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of C 1 -C 4 -alkyl and halogenated C 1 -C 4 -alkyl (e.g. 4-CF 3 -pyrid-2-yl or 1-propyl-1,2,3-triazol-4-yl); and R 5a , R 5b

are hydrogen or together with the carbon atom to which they are bound may form a C═O.

According to a further embodiment, R 4 is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-Cl-phenyl, or 2-Cl-phenyl).

In connection with R 4 being optionally substituted C 6 -C 12 -aryl, substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen.

R 2a , R 2b —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 6 -C 12 -aryl—are, in particular, hydrogen.

R 3a —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 6 -C 12 -aryl—is, in particular, C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy or 4-F-phenoxy). Preferably, R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl).

R 3b —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 6 -C 12 -aryl—is, in particular, hydrogen.

Y 1 —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 6 -C 12 -aryl—is, in particular, >CR 6 .

R 6 —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 6 -C 12 -aryl—is, in particular, hydrogen.

R 5a , R 5b —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 6 -C 12 -aryl—are, in particular, hydrogen.

Particular embodiments of the pyrrolidine derivatives wherein R 4 is optionally substituted C 6 -C 12 -aryl result if:

R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1 methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl); R 2a , R 2b

are hydrogen;

R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl); R 3b is hydrogen; R 4 is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-Cl-phenyl, or 2-Cl-phenyl); Y 1 is >CR 6 ; R 6 is hydrogen; and R 5a , R 5b are hydrogen.

Preferably, R 1 —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 6 -C 12 -aryl—is an optionally substituted 5-membered heterocyclic ring containing 2 N which, in particular, is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 6 -C 12 -aryl—is an optionally substituted 5-membered heterocyclic ring containing 3 N which, in particular, is optionally substituted 1,2,3-triazolyl.

In connection with R 1 and the pyrrolidine derivatives wherein R 4 is optionally substituted C 6 -C 12 -aryl, substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular includes 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, thiazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy-carbonyl and C 1 -C 6 -alkylcarbonylamino. Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl. In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl). According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl.

In connection with R 3a and the pyrrolidine derivatives wherein R 4 is optionally substituted C 6 -C 12 -aryl, substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy. Preferably, the substituents on C 6 -C 12 -aryl are independently selected from the group consisting of halogen.

According to a preferred embodiment, R 3a —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 6 -C 12 -aryl—is C 6 -C 12 -aryl, in particular phenyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, or 2,4,5-trifluoro-phenyl).

Further preferred embodiments of the pyrrolidine derivatives wherein R 4 is optionally substituted C 6 -C 12 -aryl result if:

R 1 is 1,3-diazolyl optionally substituted with halogen or C 1 -C 4 -alkyl and preferably 1-methyl-1,3-diazol-4-yl; R 2a , R 2b

are hydrogen;

R 3a is C 6 -C 12 -aryl optionally substituted with halogen (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, or 2,4,5-trifluoro-phenyl); R 3b is hydrogen; R 4 is C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. phenyl, 4-Cl-phenyl, or 2-Cl-phenyl); Y 1 is >CR 6 ; R 6 is hydrogen; and R 5a , R 5b

are hydrogen.

According to a further embodiment, R 4 is —NR 8a (CR 9a R 9b ) n4 R 13 . Thus, the present invention relates to the pyrrolidine derivatives of the formula (Id):

wherein R 1 , R 2a , R 2b , R 3a , R 3b , Y 1 , R 5a and R 5b are as defined herein, and

R 8a is hydrogen, C 1 -C 6 -alkyl (e.g. methyl, ethyl, n-propyl, iso-propyl, pentyl, or hexyl), or C 1 -C 6 -alkylcarbonyl (e.g. methylcarbonyl), or R 6 , R 8a

together are optionally substituted C 1 -C 5 -alkylene, wherein one or more —CH 2 — of C 1 -C 5 -alkylene may be independently replaced by a an oxygen atom or C═O (e.g. —C(O)OCH 2 —);

R 9a , R 9b

are independently hydrogen, halogen (e.g. F, Cl, or Br), C 1 -C 6 -alkyl (e.g. methyl, ethyl, tert-butyl, or 2,3-dimethyl-propyl), hydroxy, or C 1 -C 6 -alkoxy (e.g. methoxy or ethoxy);

n4 is 0, 1, 2, 3, or 4; and R 13 is hydrogen, C 1 -C 8 -alkyl (e.g. methyl, ethyl, n-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1 -C 6 -alkyl (e.g. —CF 3 or —CF 2 Me), (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl or cyclohexyl-methyl), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. methoxy-methyl), optionally substituted C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, 2-propyl-cyclopropyl, 1-(methoxy-methyl)-cyclopropyl, 2-phenyl-cyclopropyl, cyclopentyl, cyclopentyl, 3,3-dimethylcyclopentyl, cyclohexyl, 3,3-dimethyl-cyclohexyl, 4,4-dimethyl-cyclohexyl, 1-methyl-cyclohexyl, 1-CF 3 -cyclopropyl, 4-CF 3 -cyclohexyl, 3-CF 3 -cyclohexyl, or 4,4-diF-cyclohexyl), C 2 -C 6 -alkenyl (e.g. hex-2-enyl), optionally substituted C 3 -C 6 -cycloalkenyl (e.g. 1,3,3-trimethylcyclohexen-2-yl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-F-phenyl, 4-F-phenyl, 3-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl, 3,4-diF-phenyl, 2,3,4-triF-phenyl, 2,4-diCl-phenyl, 3,4-diCl-phenyl, 3-F-4-Cl-phenyl, 3-Cl-4-F-phenyl, 3-Cl-5-F-phenyl, 3,4-diF-5-Cl-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 3-iPr-phenyl, 3-tBu-phenyl, 3-Me-4-F-phenyl, 3-Me-4-Cl-phenyl, 3-iPr-4 Cl-phenyl, 3-(1-OH-1-CF 3 -Et)-phenyl, 3-CHF 2 -4-F-phenyl, 2-CF 3 -phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 2-F-3-CF 3 -phenyl, 2-F-5-CF 3 -phenyl, 3-F-5-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-CF 3 -4-Cl-phenyl, 3-Me-4-CF 3 -phenyl, 3-CF 3 -4-Me-phenyl, 3,4-diCF 3 -phenyl, 4-OMe-phenyl, 3-OiPr-phenyl, 3-CF 3 -4-OMe-phenyl, 3-OCH 2 CF 3 -phenyl, 3-OCF 3 -phenyl, 2-OCHF 2 -5-Cl-phenyl, 3-OCF 3 -4-F-phenyl, 3-OCF 3 -4-Cl-phenyl, 3-OBn-phenyl, 3-OPh-phenyl, 3-CN-phenyl, 4-CN-phenyl, 2-F-3-CN-phenyl, 2-F-4-CN-phenyl, 3-F-4-CN-phenyl, 2-F-5-CN-phenyl, 3-F-5-CN-phenyl, 3-Cl-4-CN-phenyl, 2-Cl-5-CN-phenyl, 3-Cl-5-CN-phenyl, 3-CN-4-Cl-phenyl, 2-Me-3-CN-phenyl, 2-Me-5-CN-phenyl, 3-Me-5-CN-phenyl, 3-CF 3 -4-CN-phenyl, 3-CN-4-OMe-phenyl, 3-CN-4-OCF 3 -phenyl, 3-phenyl-phenyl, 3-MeSO 2 -phenyl, 3-(piperidin-4-yl)phenyl, 2-methylcarbonylamino-5-Cl-phenyl, 3-(pyrid-2-yl)-phenyl, 3-(pyrid-3-yl)-4F-phenyl, 3-(pyrid-4-yl)-4F-phenyl, 3-(pyrimid-5-yl)-4F-phenyl, indan-5-yl, 2-chlor-indan-5-yl, or tetralin-6-yl), hydroxy, C 1 -C 6 -alkoxy (e.g. methoxy, ethoxy, or n-propyloxy), C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy (e.g. 2-methoxy-ethoxy), optionally substituted C 6 -C 12 -aryloxy (e.g. 4-F-phenoxy or 4-tertbutyl-phenoxy), optionally substituted C 3 -C 12 -heterocyclyloxy (e.g. pyridin-2-yloxy), optionally substituted C 3 -C 12 -heterocyclyl (e.g. propyl-furan-2-yl, 2-CF 3 -furan-5-yl, 1,2-dimethyl-5-CN-pyrrol-3-yl, 2,3-diMe-thiophen-5-yl, 2-Me-thiophen-5-yl, 2-Cl-thiophen-5-yl, 3-Cl-thiophen-2-yl, 2,5-diCl-thiophen-3-yl, 2-tetrahydropyranyl-thiophen-5-yl, 1,3-thiazol-5-yl, 4-Me-1,3-thiazol-2-yl, 2-Me-1,3-thiazol-5-yl, 5-Me-1,3-thiazol-2-yl, 4-Me-1,3-thiazol-5-yl, 2-Me-1,3-thiazol-4-yl, 4-iso-propyl-1,3-thiazol-2-yl, 2,4-diMe-1,3-thiazol-5-yl, 2-phenyl-4-Me-1,3-thiazol-5-yl, 4-phenyl-1,3-thiazol-5-yl, 2-(4-Me-phenyl)-1,3-thiazol-5-yl, 4-(4-F-phenyl)-1,3-thiazol-2-yl, 2-Cl-1,3-thiazol-4-yl, 4-Cl-1,3-thiazol-5-yl, 2-Br-1,3-thiazol-5-yl, 4-Br-1,3-thiazol-2-yl, 4-Me-5-Br-1,3-thiazol-2-yl, 2,4-dichloro-1,3-thiazol-5-yl, 1,5-dimethyl-1,2,4-triazol-3-yl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, 4-F-pyrid-2-yl, 5-F-pyrid-2-yl, 6-F-pyrid-2-yl, 4-Cl-pyrid-2-yl, 5-F-pyrid-3-yl, 2-F-pyrid-4-yl, 3,5-diCl-pyrid-4-yl, 4,5-diCl-pyrid-2-yl, 2-Cl-3F-pyrid-4-yl, 5-Me-pyrid-2-yl, 4-iPr-pyrid-2-yl, 4-Me-5-F-pyrid-2-yl, 4-CF 3 -pyrid-2-yl, 5-CF 3 -pyrid-2-yl, 6-CF 3 -pyrid-2-yl, 5-CF 3 -pyrid-3-yl, 2-yl 3,5-diF-4-CF 3 -pyrid-2-yl, 4-OCH 2 CF 3 -pyrid-2-yl, 4-OCH 2 CF 3 -5-F-pyrid-2-yl, 4-OCH 2 CF 3 -5-Cl-pyrid-2-yl, 4-OBn-5-F-pyrid-2-yl, 3-(4-F-phenyl)-pyrid-5-yl, 2-(4-F-phenyl)-pyrid-3-yl, 4-(pyrid-4-yl)-pyrid-2-yl, 4-(pyrid-3-yl)-pyrid-2-yl, 5-cyclopropyl-pyraz-2-yl, 5-cyclobutyl-pyraz-2-yl, 5-pyrrolidin-pyraz-2-yl, pyridaz-3-yl, 4-CF 3 -pyridaz-3-yl, 5-CF 3 -pyridaz-3-yl, 5-F-pyrimid-2-yl, 6-Cl-pyrimid-4-yl, 6-Me-pyrimid-4-yl, 6-Et-pyrimid-4-yl, 6-Pr-pyrimid-4-yl, 6-iPr-pyrimid-4-yl, 4-CF 3 -pyrimid-2-yl, 6-CF 3 -pyrimid-4-yl, 2-Me-6-Cl-pyrimid-4-yl, 2-Me-6-CF 3 -pyrimid-4-yl, 2-OMe-6-CF 3 -pyrimid-4-yl, 2-OMe-pyrimid-4-yl, 6-OMe-pyrimid-4-yl, 6-OEt-pyrimid-4-yl, 6-OPr-pyrimid-4-yl, 6-OiPr-pyrimid-4-yl, 6-OiBu-pyrimid-4-yl, 6-OBu-pyrimid-4-yl, 6-OBn-pyrimid-4-yl, 6-cyclobutyloxy-pyrimid-4-yl, 6-cyclopentyloxy-pyrimid-4-yl, 6-cyclohexyloxy-pyrimid-4-yl, 6-cyclopropyl-pyrimid-4-yl, 6-phenyl-pyrimid-4-yl, 6-(2-F-phenyl)-pyrimid-4-yl, 6-(3-F-phenyl)-pyrimid-4-yl, 6-(4-F-phenyl)-pyrimid-4-yl, 6-Cl-pyrimid-4-yl, 6-(2-Me-phenyl)-pyrimid-4-yl, 6-(3-Me-phenyl)-pyrimid-4-yl, 6-(4-Me-phenyl)-pyrimid-4-yl, 6-(3-Cl-phenyl)-pyrimid-4-yl, 6-(4-Cl-phenyl)-pyrimid-4-yl, 2-(morpholin-1-yl)-pyrimid-4-yl, 6-(azetidin-3-yl-methoxy)-pyrimid-4-yl, 6-(pyrrolidin-3-yl-methoxy)-pyrimid-4-yl, 6-(pyrrolidin-2-yl-methoxy)-pyrimid-4-yl, benzofuran-5-yl, 2-Me-benzofuran-3-yl, 2-Et-benzofuran-3-yl, benzothiophen-5-yl, benzothiophen-6-yl, 5-Me-benzothiophen-2-yl, 5-F-benzothiophen-2-yl, 3-Cl-benzothiophen-2-yl, benzothiazol-2-yl, isoquinolin-6-yl, isoquinolin-7-yl, quinolin-6-yl, quinolin-7-yl, 4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl, 2,3-dihydrobenzofuran-5-yl, 7H-pyrrolo[2,3-d]pyrimidin-4-yl, pyrazolo[1,5-a]pyridine-3-yl, pyrazolo[1,5-a]pyridine-7-yl, 5-methyl-imidazo[1,2-a]pyridin-8-yl, 5-methyl-imidazo[1,2-a]pyridine-3-yl, 6-chloro-2-methyl-imidazo[1,2-a]pyridin-3-yl, 6-bromo-2-methyl-imidazo[1,2-a]pyridin-3-yl, thieno[2,3-b]pyridin-2-yl, N-benzyl-indolin-6-yl, indolinon-4-yl, chroman-6-yl, 4,4-dimethylchroman-6-yl, 4,4-dimethyl-1,3-dioxan-2-yl, 2-Me-tetrahydrofuran-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl, 4-Me-tetrahydropyran-4-yl, 2,2-diMe-tetrahydropyran-4-yl, 1-iso-propyl-piperidin-4-yl, 1-ethyl-piperidin-3-yl, or 2-CF 3 -piperazin-5-yl), or tri(C 1 -C 4 -alkyl)-silyloxy.

In particular, R 9a , R 9b are independently hydrogen, halogen, C 1 -C 6 -alkyl (e.g. methyl, ethyl, tert-butyl, or 2,3-dimethyl-propyl), or C 1 -C 6 -alkoxy (e.g. methoxy).

In particular, R 13 is hydrogen, C 1 -C 8 -alkyl (e.g. methyl, ethyl, n-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1 -C 6 -alkyl (e.g. —CF 3 or —CF 2 Me), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. methoxy-methyl), optionally substituted C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, 2-propyl-cyclopropyl, 1-(methoxymethyl)-cyclopropyl, 2-phenyl-cyclopropyl, cyclopentyl, cyclopentyl, 3,3-dimethylcyclopentyl, cyclohexyl, 3,3-dimethyl-cyclohexyl, 4,4-dimethyl-cyclohexyl, 1-methyl-cyclohexyl, 1-CF 3 -cyclopropyl, 4-CF 3 -cyclohexyl, 3-CF 3 -cyclohexyl, or 4,4-diF-cyclohexyl), C 2 -C 6 -alkenyl (e.g. hex-2-enyl), optionally substituted C 3 -C 6 -cycloalkenyl (e.g. 1,3,3-trimethylcyclohexen-2-yl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-F-phenyl, 4-F-phenyl, 3-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl, 3,4-diF-phenyl, 2,3,4-triF-phenyl, 2,4-diCl-phenyl, 3,4-diCl-phenyl, 3-F-4-Cl-phenyl, 3-Cl-4-F-phenyl, 3-Cl-5-F-phenyl, 3,4-diF-5-Cl-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 3-iPr-phenyl, 3-tBu-phenyl, 3-Me-4-F-phenyl, 3-Me-4-Cl-phenyl, 3-iPr-4 Cl-phenyl, 3-(1-OH-1-CF 3 -Et)-phenyl, 3-CHF 2 -4-F-phenyl, 2-CF 3 -phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 2-F-3-CF 3 -phenyl, 2-F-5-CF 3 phenyl, 3-F-5-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-CF 3 -4-Cl-phenyl, 3-Me-4-CF 3 -phenyl, 3-CF 3 -4-Me-phenyl, 3,4-diCF 3 -phenyl, 4-OMe-phenyl, 3-OiPr-phenyl, 3-CF 3 -4-OMe-phenyl, 3-OCH 2 CF 3 -phenyl, 3-OCF 3 -phenyl, 2-OCF 2 -5-Cl-phenyl, 3-OCF 3 -4-F-phenyl, 3-OCF 3 -4-Cl-phenyl, 3-OBn-phenyl, 3-OPh-phenyl, 3-CN-phenyl, 4-CN-phenyl, 2-F-3-CN-phenyl, 2-F-4-CN-phenyl, 3-F-4-CN-phenyl, 2-F-5-CN-phenyl, 3-F-5-CN-phenyl, 3-Cl-4-CN-phenyl, 2-Cl-5-CN-phenyl, 3-Cl-5-CN-phenyl, 3-CN-4-Cl-phenyl, 2-Me-3-CN-phenyl, 2-Me-5-CN-phenyl, 3-Me-5-CN-phenyl, 3-CF 3 -4-CN-phenyl, 3-CN-4-OMe-phenyl, 3-CN-4-OCF 3 -phenyl, 3-phenyl-phenyl, 3-MeSO 2 -phenyl, 3-(piperidin-4-yl)-phenyl, 2-methylcarbonylamino-5-Cl-phenyl, 3-(pyrid-2-yl)-phenyl, 3-(pyrid-3-yl)-4F-phenyl, 3-(pyrid-4-yl)-4F-phenyl, 3-(pyrimid-5-yl)-4F-phenyl, indan-5-yl, 2-chlor-indan-5-yl, or tetralin-6-yl), C 1 -C 6 -alkoxy (e.g. methoxy, ethoxy, or n-propyloxy), C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy (e.g. 2-methoxy-ethoxy), optionally substituted C 6 -C 12 -aryloxy (e.g. 4-F-phenoxy or 4-tert-butyl-phenoxy), optionally substituted C 3 -C 12 -heterocyclyl (e.g. e.g. n-propyl-furan-2-yl, 2-CF 3 -furan-5-yl, 1,2-dimethyl-5-CN-pyrrol-3-yl, 2,3-diMe-thiophen-5-yl, 2-Me-thiophen-5-yl, 2-Cl-thiophen-5-yl, 3-Cl-thiophen-2-yl, 2,5-diCl-thiophen-3-yl, 2-tetrahydropyranyl-thiophen-5-yl, 1,3-thiazol-5-yl, 4-Me-1,3-thiazol-2-yl, 2-Me-1,3-thiazol-5-yl, 5-Me-1,3-thiazol-2-yl, 4-Me-1,3-thiazol-5-yl, 2-Me-1,3-thiazol-4-yl, 4-iso-propyl-1,3-thiazol-2-yl, 2,4-diMe-1,3-thiazol-5-yl, 2-phenyl-4-Me-1,3-thiazol-5-yl, 4-phenyl-1,3-thiazol-5-yl, 2-(4-Me-phenyl)-1,3-thiazol-5-yl, 4-(4-F-phenyl)-1,3-thiazol-2-yl, 2-Cl-1,3-thiazol-4-yl, 4-Cl-1,3-thiazol-5-yl, 2-Br-1,3-thiazol-5-yl, 4-Br-1,3-thiazol-2-yl, 4-Me-5-Br-1,3-thiazol-2-yl, 2,4-dichloro-1,3-thiazol-5-yl, 1,5-dimethyl-1,2,4-triazol-3-yl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, 4-F-pyrid-2-yl, 5-F-pyrid-2-yl, 6-F-pyrid-2-yl, 4-Cl-pyrid-2-yl, 5-F-pyrid-3-yl, 2-F-pyrid-4-yl, 3,5-diCl-pyrid-4-yl, 4,5-diCl-pyrid-2-yl, 2-Cl-3F-pyrid-4-yl, 5-Me-pyrid-2-yl, 4-iPr-pyrid-2-yl, 4-Me-5-F-pyrid-2-yl, 4-CF 3 -pyrid-2-yl, 5-CF 3 pyrid-2-yl, 6-CF 3 -pyrid-2-yl, 5-CF 3 -pyrid-3-yl, 2-CF 3 -pyrid-4-yl, 3-F-4-CF 3 -pyrid-2-yl, 4-CF 3 -5-F-pyrid-2-yl, 4-CF 3 -5-Cl-pyrid-2-yl, 3,5-diF-4-CF 3 -pyrid-2-yl, 4-OCH 2 CF 3 -pyrid-2-yl, 4-OCH 2 CF 3 -5-F-pyrid-2-yl, 4-OCH 2 CF 3 -5-Cl-pyrid-2-yl, 4-OBn-5-F-pyrid-2-yl, 3-(4-F-phenyl)-pyrid-5-yl, 2-(4-F-phenyl)-pyrid-3-yl, 4-(pyrid-4-yl)-pyrid-2-yl, 4-(pyrid-3-yl)-pyrid-2-yl, 5-cyclopropyl-pyraz-2-yl, 5-cyclobutyl-pyraz-2-yl, 5-pyrrolidin-pyraz-2-yl, pyridaz-3-yl, 4-CF 3 -pyridaz-3-yl, 5-CF 3 -pyridaz-3-yl, 5-F-pyrimid-2-yl, 6-Cl-pyrimid-4-yl, 6-Me-pyrimid-4-yl, 6-Et-pyrimid-4-yl, 6-Pr-pyrimid-4-yl, 6-iPr-pyrimid-4-yl, 4-CF 3 -pyrimid-2-yl, 6-CF 3 -pyrimid-4-yl, 2-Me-6-Cl-pyrimid-4-yl, 2-Me-6-CF 3 -pyrimid-4-yl, 2-OMe-6-CF 3 -pyrimid-4-yl, 2-OMe-pyrimid-4-yl, 6-OMe-pyrimid-4-yl, 6-OEt-pyrimid-4-yl, 6-OiPr-pyrimid-4-yl, 6-OiBu-pyrimid-4-yl, 6-OBu-pyrimid-4-yl, 6-OBn-pyrimid-4-yl, 6-cyclobutyloxy-pyrimid-4-yl, 6-cyclopentyloxy-pyrimid-4-yl, 6-cyclohexyloxy-pyrimid-4-yl, 6-cyclopropyl-pyrimid-4-yl, 6-phenyl-pyrimid-4-yl, 6-(2-F-phenyl)-pyrimid-4-yl, 6-(3-F-phenyl)-pyrimid-4-yl, 6-(4-F-phenyl)-pyrimid-4-yl, 6-Cl-pyrimid-4-yl, 6-(2-Me-phenyl)-pyrimid-4-yl, 6-(3-Me-phenyl)-pyrimid-4-yl, 6-(4-Me-phenyl)-pyrimid-4-yl, 6-(3-Cl-phenyl)-pyrimid-4-yl, 6-(4-Cl-phenyl)-pyrimid-4-yl, 6-(azetidin-3-yl-methoxy)pyrimid-4-yl, 6-(pyrrolidin-3-yl-methoxy)-pyrimid-4-yl, 6-(pyrrolidin-2-yl-methoxy)-pyrimid-4-yl, benzofuran-5-yl, 2-Me-benzofuran-3-yl, 2-Et-benzofuran-3-yl, benzothiophen-5-yl, benzothiophen-6-yl, 5-Me-benzothiophen-2-yl, 5-F-benzothiophen-2-yl, 3-Cl-benzothiophen-2-yl, benzothiazol-2-yl, isoquinolin-6-yl, isoquinolin-7-yl, quinolin-6-yl, quinolin-7-yl, 4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl, 2,3-dihydrobenzofuran-5-yl, 7H-pyrrolo[2,3-d]pyrimidin-4-yl, pyrazolo[1,5-a]pyridine-3-yl, pyrazolo[1,5-a]pyridine-7-yl, 5-methyl-imidazo[1,2-a]pyridin-3-yl, 6-chloro-2-methyl-imidazo[1,2-a]pyridin-3-yl, 6-bromo-2-methyl-imidazo[1,2-a]pyridin-3-yl, thieno[2,3-b]pyridin-2-yl, N-benzyl-indolin-6-yl, indolinon-4-yl, chroman-6-yl, 4,4-dimethylchroman-6-yl, 4,4-dimethyl-1,3-dioxan-2-yl, 2-Me-tetrahydrofuran-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl, 4-Me-tetrahydropyran-4-yl, 2,2-diMe-tetrahydropyran-4-yl, 1-isopropyl-piperidin-4-yl, 1-ethyl-piperidin-3-yl, or 2-CF 3 -piperazin-5-yl), or tri-(C 1 -C 4 -alkyl)silyloxy.

R 2a , R 2b —in the pyrrolidine derivatives of formula (Id)—are, in particular, hydrogen.

R 3a —in the pyrrolidine derivatives of formula (Id)—is, in particular, C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), hydroxy, C 1 -C 6 -alkoxy (e.g. methoxy, ethoxy, n-propoxy, iso-propoxy, or iso-butoxy), halogenated C 1 -C 6 -alkoxy (e.g OCF 3 ), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkoxy (e.g. 2-(N-pyrrolidinyl)ethoxy, 2-(N-morpholinyl)ethoxy and 2-(N-imidazolyl)ethoxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy or 4-F-phenoxy), C 3 -C 12 -heterocyclyloxy (e.g. pyridin-2-yloxy), or optionally substituted C 3 -C 12 -heterocyclyl (tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, 1-cyclopropyl-piperidin-4-yl, 1-cyclopropyl-piperidin-3-yl, 2-pyridyl, 3-pyridyl, 3-F-pyrid-2-yl, 1,3-oxazol-4-yl, or 1,3-oxazol-2-yl). Preferably, R 3a is C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), hydroxy, C 1 -C 6 -alkoxy (e.g. methoxy, ethoxy, n-propoxy, iso-propoxy, or iso-butoxy), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy or 4-F-phenoxy) or optionally substituted C 3 -C 12 -heterocyclyl (tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, 1-cyclopropyl-piperidin-4-yl, 1-cyclopropyl-piperidin-3-yl, 2-pyridyl, 3-pyridyl, 3-F-pyrid-2-yl, 1,3-oxazol-4-yl, or 1,3-oxazol-2-yl).

R 3b —in the pyrrolidine derivatives of formula (Id)—is, in particular, hydrogen or hydroxy.

Y 1 —in the pyrrolidine derivatives of formula (Id)—is, in particular, >CR 6 .

R 6 —in the pyrrolidine derivatives of formula (Id)—is, in particular, hydrogen, C 1 -C 6 -alkyl (e.g. methyl), or hydroxy-C 1 -C 6 -alkyl (e.g. —CH 2 OH).

R 5a , R 5b —in the pyrrolidine derivatives of formula (Id)—are, in particular, hydrogen.

Particular embodiments of pyrrolidine derivatives of formula (Id) result if:

R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl); R 2a , R 2b

are hydrogen;

R 3a is C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), hydroxy, C 1 -C 6 -alkoxy (e.g. methoxy, ethoxy, n-propoxy, isopropoxy, or iso-butoxy), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy or 4-F-phenoxy) or optionally substituted C 3 -C 12 -heterocyclyl (tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, 1-cyclopropyl-piperidin-4-yl, 1-cyclopropyl-piperidin-3-yl, 2-pyridyl, 3-pyridyl, 3-F-pyrid-2-yl, 1,3-oxazol-4-yl, or 1,3-oxazol-2-yl); R 3b is hydrogen or hydroxy; Y 1 is >CR 6 ; R 6 is hydrogen, C 1 -C 6 -alkyl, or hydroxy-C 1 -C 6 -alkyl (e.g. —CH 2 OH); R 8a is hydrogen, C 1 -C 6 -alkyl (e.g. methyl, ethyl, n-propyl, iso-propyl, pentyl, or hexyl), or C 1 -C 6 -alkylcarbonyl (e.g. methylcarbonyl), or R 6 , R 8a

are together optionally substituted C 1 -C 5 -alkylene, wherein one or more —CH 2 — of C 1 -C 5 -alkylene may be independently replaced by a an oxygen atom or C═O e.g. —C(O)OCH 2 —);

R 9a is hydrogen, halogen (e.g. F), C 1 -C 6 -alkyl (e.g. methyl, ethyl, tert-butyl, or 2,3-dimethyl-propyl), or C 1 -C 6 -alkoxy (e.g. methoxy or ethoxy); R 9b is hydrogen; n4 is 0, 1, 2, 3, or 4; R 13 is hydrogen, C 1 -C 8 -alkyl (e.g. methyl, ethyl, n-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1 -C 6 -alkyl (e.g. —CF 3 or —CF 2 Me), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. methoxy-methyl), optionally substituted C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, 2-propyl-cyclopropyl, 1-(methoxymethyl)-cyclopropyl, 2-phenyl-cyclopropyl, cyclopentyl, cyclopentyl, 3,3-dimethylcyclopentyl, cyclohexyl, 3,3-dimethyl-cyclohexyl, 4,4-dimethyl-cyclohexyl, 1-methyl-cyclohexyl, 1-CF 3 -cyclopropyl, 4-CF 3 -cyclohexyl, 3-CF 3 -cyclohexyl, or 4,4-diF-cyclohexyl), C 2 -C 6 -alkenyl (e.g. hex-2-enyl), optionally substituted C 3 -C 6 -cycloalkenyl (e.g. 1,3,3-trimethylcyclohexen-2-yl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-F-phenyl, 4-F-phenyl, 3-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl, 3,4-diF-phenyl, 2,3,4-triF-phenyl, 2,4-diCl-phenyl, 3,4-diCl-phenyl, 3-F-4-Cl-phenyl, 3-Cl-4-F-phenyl, 3-Cl-5-F-phenyl, 3,4-diF-5-Cl-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 3-iPr-phenyl, 3-tBu-phenyl, 3-Me-4-F-phenyl, 3-Me-4-Cl-phenyl, 3-iPr-4 Cl-phenyl, 3-(1-OH-1-CF 3 -Et)-phenyl, 3-CHF 2 -4-F-phenyl, 2-CF 3 -phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 2-F-3-CF 3 -phenyl, 2-F-5-CF 3 -phenyl, 3-F-5-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-CF 3 -4-Cl-phenyl, 3-Me-4-CF 3 -phenyl, 3-CF 3 -4-Me-phenyl, 3,4-diCF 3 -phenyl, 4-OMe-phenyl, 3-OiPr-phenyl, 3-CF 3 -4-OMe-phenyl, 3-OCH 2 CF 3 -phenyl, 3-OCF 3 -phenyl, 2-OCHF 2 -5-Cl-phenyl, 3-OCF 3 -4-F-phenyl, 3-OCF 3 -4-Cl-phenyl, 3-OBn-phenyl, 3-OPh-phenyl, 3-CN-phenyl, 4-CN-phenyl, 2-F-3-CN-phenyl, 2-F-4-CN-phenyl, 3-F-4-CN-phenyl, 2-F-5-CN-phenyl, 3-F-5-CN-phenyl, 3-Cl-4-CN-phenyl, 2-Cl-5-CN-phenyl, 3-Cl-5-CN-phenyl, 3-CN-4-Cl-phenyl, 2-Me-3-CN-phenyl, 2-Me-5-CN-phenyl, 3-Me-5-CN-phenyl, 3-CF 3 -4-CN-phenyl, 3-CN-4-OMe-phenyl, 3-CN-4-OCF 3 -phenyl, 3-phenyl-phenyl, 3-MeSO 2 -phenyl, 3-(piperidin-4-yl)phenyl, 2-methylcarbonylamino-5-Cl-phenyl, 3-(pyrid-2-yl)-phenyl, 3-(pyrid-3-yl)-4F-phenyl, 3-(pyrid-4-yl)-4F-phenyl, 3-(pyrimid-5-yl)-4F-phenyl, indan-5-yl, 2-chlor-indan-5-yl, or tetralin-6-yl), C 1 -C 6 -alkoxy (e.g. methoxy, ethoxy, or n-propoxy), C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy (e.g. 2-methoxy-ethoxy), optionally substituted C 6 -C 12 -aryloxy (e.g. 4-F-phenoxy or 4-tertbutyl-phenoxy), optionally substituted C 3 -C 12 -heterocyclyl (e.g. e.g. n-propyl-furan-2-yl, 2-CF 3 -furan-5-yl, 1,2-dimethyl-5-CN-pyrrol-3-yl, 2,3-diMe-thiophen-5-yl, 2-Me-thiophen-5-yl, 2-Cl-thiophen-5-yl, 3-Cl-thiophen-2-yl, 2,5-diCl-thiophen-3-yl, 2-tetrahydropyranyl-thiophen-5-yl, 1,3-thiazol-5-yl, 4-Me-1,3-thiazol-2-yl, 2-Me-1,3-thiazol-5-yl, 5-Me-1,3-thiazol-2-yl, 4-Me-1,3-thiazol-5-yl, 2-Me-1,3-thiazol-4-yl, 4-isopropyl-1,3-thiazol-2-yl, 2,4-diMe-1,3-thiazol-5-yl, 2-phenyl-4-Me-1,3-thiazol-5-yl, 4-phenyl-1,3-thiazol-5-yl, 2-(4-Me-phenyl)-1,3-thiazol-5-yl, 4-(4-F-phenyl)-1,3-thiazol-2-yl, 2-Cl-1,3-thiazol-4-yl, 4-Cl-1,3-thiazol-5-yl, 2-Br-1,3-thiazol-5-yl, 4-Br-1,3-thiazol-2-yl, 4-Me-5-Br-1,3-thiazol-2-yl, 2,4-dichloro-1,3-thiazol-5-yl, 1,5-dimethyl-1,2,4-triazol-3-yl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, 4-F-pyrid-2-yl, 5-F-pyrid-2-yl, 6-F-pyrid-2-yl, 4-Cl-pyrid-2-yl, 5-F-pyrid-3-yl, 2-F-pyrid-4-yl, 3,5-diCl-pyrid-4-yl, 4,5-diCl-pyrid-2-yl, 2-Cl-3F-pyrid-4-yl, 5-Me-pyrid-2-yl, 4-iPr-pyrid-2-yl, 4-Me-5-F-pyrid-2-yl, 4-CF 3 -pyrid-2-yl, 5-CF 3 -pyrid-2-yl, 6-CF 3 -pyrid-2-yl, 5-CF 3 -pyrid-3-yl, 2-CF 3 -pyrid-4-yl, 3-F-4-CF 3 -pyrid-2-yl, 4-CF 3 -5-F-pyrid-2-yl, 4-CF 3 -5-Cl-pyrid-2-yl, 3,5-diF-4-CF 3 -pyrid-2-yl, 4-OCH 2 CF 3 -pyrid-2-yl, 4-OCH 2 CF 3 -5-F-pyrid-2-yl, 4-OCH 2 CF 3 -5-Cl-pyrid-2-yl, 4-OBn-5-F-pyrid-2-yl, 3-(4-F-phenyl)-pyrid-5-yl, 2-(4-F-phenyl)-pyrid-3-yl, 4-(pyrid-4-yl)-pyrid-2-yl, 4-(pyrid-3-yl)pyrid-2-yl, 5-cyclopropyl-pyraz-2-yl, 5-cyclobutyl-pyraz-2-yl, 5-pyrrolidin-pyraz-2-yl, pyridaz-3-yl, 4-CF 3 -pyridaz-3-yl, 5-CF 3 -pyridaz-3-yl, 5-F-pyrimid-2-yl, 6-Cl-pyrimid-4-yl, 6-Me-pyrimid-4-yl, 6-Et-pyrimid-4-yl, 6-Pr-pyrimid-4-yl, 6-iPr-pyrimid-4-yl, 4-CF 3 -pyrimid-2-yl, 6-CF 3 -pyrimid-4-yl, 2-Me-6-Cl-pyrimid-4-yl, 2-Me-6-CF 3 -pyrimid-4-yl, 2-OMe-6-CF 3 -pyrimid-4-yl, 2-OMe-pyrimid-4-yl, 6-OMe-pyrimid-4-yl, 6-OEt-pyrimid-4-yl, 6-OPr-pyrimid-4-yl, 6-OiPr-pyrimid-4-yl, 6-OiBu-pyrimid-4-yl, 6-OBu-pyrimid-4-yl, 6-OBn-pyrimid-4-yl, 6-cyclobutoxy-pyrimid-4-yl, 6-cyclopentoxy-pyrimid-4-yl, 6-cyclohexyloxy-pyrimid-4-yl, 6-cyclopropyl-pyrimid-4-yl, 6-phenyl-pyrimid-4-yl, 6-(2-F-phenyl)-pyrimid-4-yl, 6-(3-F-phenyl)-pyrimid-4-yl, 6-(4-F-phenyl)-pyrimid-4-yl, 6-Cl-pyrimid-4-yl, 6-(2-Me-phenyl)-pyrimid-4-yl, 6-(3-Me-phenyl)-pyrimid-4-yl, 6-(4-Me-phenyl)-pyrimid-4-yl, 6-(3-Cl-phenyl)-pyrimid-4-yl, 6-(4-Cl-phenyl)-pyrimid-4-yl, 2-(morpholin-1-yl)-pyrimid-4-yl, 6-(azetidin-3-yl-methoxy)-pyrimid-4-yl, 6-(pyrrolidin-3-yl-methoxy)-pyrimid-4-yl, 6-(pyrrolidin-2-yl-methoxy)-pyrimid-4-yl, benzofuran-5-yl, 2-Me-benzofuran-3-yl, 2-Et-benzofuran-3-yl, benzothiophen-5-yl, benzothiophen-6-yl, 5-Me-benzothiophen-2-yl, 5-F-benzothiophen-2-yl, 3-Cl-benzothiophen-2-yl, benzothiazol-2-yl, isoquinolin-6-yl, isoquinolin-7-yl, quinolin-6-yl, quinolin-7-yl, 4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl, 2,3-dihydrobenzofuran-5-yl, 7H-pyrrolo[2,3-d]pyrimidin-4-yl, pyrazolo[1,5-a]pyridine-3-yl, pyrazolo[1,5-a]pyridine-7-yl, 5-methyl-imidazo[1,2-a]pyridin-3-yl, 6-chloro-2-methyl-imidazo[1,2-a]pyridin-3-yl, 6-bromo-2-methyl-imidazo[1,2-a]pyridin-3-yl, thieno[2,3-b]pyridin-2-yl, N-benzyl-indolin-6-yl, indolinon-4-yl, chroman-6-yl, 4,4-dimethylchroman-6-yl, 4,4-dimethyl-1,3-dioxan-2-yl, 2-Me-tetrahydrofuran-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl, 4-Me-tetrahydropyran-4-yl, 2,2-diMe-tetrahydropyran-4-yl, 1-isopropyl-piperidin-4-yl, 1-ethyl-piperidin-3-yl, or 2-CF 3 -piperazin-5-yl), or tri-(C 1 -C 4 -alkyl)-silyloxy; and R 5a , R 5b

are hydrogen.

According to a particular embodiment, R 1 —in the pyrrolidine derivatives of formula (Id)—is an optionally substituted 5-membered heterocyclic ring containing 1 or 2 N and 1 O (e.g. 5-methyl-1,2-oxazol-4-yl or 3,5-dimethyl-1,2-oxazol-4-yl). According to a further particular embodiment, R 1 —in the pyrrolidine derivatives of formula (Id)—is an optionally substituted 5-membered heterocyclic ring containing 1 or 2 N and 1 S (e.g. 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl). According to a further particular embodiment, R 11 —in the pyrrolidine derivatives of formula (Id)—is an optionally substituted 5-membered heterocyclic ring containing 1, 2 or 3 N (e.g. 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, or 1-Me-1,2,3-triazol-4-yl).

Preferably, R 1 —in the pyrrolidine derivatives of formula (Id)—is an optionally substituted 5-membered heterocyclic ring containing 2 N and, in particular, R 1 is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 —in the pyrrolidine derivatives of formula (Id)—is an optionally substituted 5-membered heterocyclic ring containing 3 N and, in particular, R 1 is optionally substituted 1,2,3-triazolyl.

In connection with R 1 and the pyrrolidine derivatives of formula (Id), substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular includes 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, triazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxycarbonyl and C 1 -C 6 -alkyl-carbonylamino. Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl. In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl). According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl. According to a further particular embodiment, 1,2,3-triazolyl is substituted with C 1 -C 6 -alkyl as described herein. According to a further specific embodiment, R 1 is 1-methyl-1,2,3-triazol-4-yl.

In connection with R 3a and the pyrrolidine derivatives of formula (Id), substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy. Preferably, the substituent(s) on C 6 -C 12 -aryl are independently selected from the group consisting of halogen.

In connection with R 3a and the pyrrolidine derivatives of formula (Id), substituted C 6 -C 12 -aryloxy in particular includes is C 6 -C 12 -aryloxy, such as phenoxy, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen and C 1 -C 4 -alkyl.

In connection with R 3a and the pyrrolidine derivatives of formula (Id), substituted C 3 -C 12 -heterocyclyl in particular includes C 3 -C 12 -heterocyclyl, such as pyridyl, piperidinyl, isoxazolyl, diazolyl, tetrahydrofuranyl, tetrahydropyranyl, or morpholinyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl or C 3 -C 6 -cycloalkyl.

According to a preferred embodiment, R 3a —in the pyrrolidine derivatives of formula (Id)—is C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, or cyclohexyl), C 6 -C 12 -aryl, in particular phenyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, or 2,4,5-trifluoro-phenyl), or hydroxy, C 1 -C 6 -alkoxy (e.g. methoxy, or iso-butoxy), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), C 6 -C 12 -aryloxy (e.g. 4-F-phenoxy) optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, or C 3 -C 12 -heterocyclyl, in particular tetrahydrofuranyl or tetrahydropyranyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen and C 3 -C 6 -cycloalkyl (tetrahydropyran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, 1-cyclopropyl-piperidin-4-yl, 1-cyclopropyl-piperidin-3-yl, 2-pyridyl, 3-pyridyl, 3-F-pyrid-2-yl, 1,3-oxazol-4-yl, or 1,3-oxazol-2-yl).

According to a preferred embodiment, R 9a , R 9b —in the pyrrolidine derivatives of formula (Id)—are independently hydrogen, halogen (e.g. F), C 1 -C 6 -alkyl (e.g. methyl, ethyl, tert-butyl, or 2,3-dimethyl-propyl), or C 1 -C 6 -alkoxy (e.g. methoxy).

More preferably, R 9a is hydrogen, halogen (e.g. F), C 1 -C 6 -alkyl (e.g. methyl, ethyl, tert-butyl, or 2,3-dimethyl-propyl), or C 1 -C 6 -alkoxy (e.g. methoxy) and R 9b is hydrogen.

In connection with R 13 , substituted C 3 -C 12 -cycloalkyl in particular includes C 3 -C 12 -cycloalkyl, such as cyclopropyl, cyclopentyl, or cyclohexyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl and C 6 -C 12 -aryl.

In connection with R 13 , substituted C 3 -C 6 -cycloalkenyl in particular includes C 3 -C 6 -cycloalkenyl, such as cyclohexenyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of C 1 -C 4 -alkyl.

In connection with R 13 , substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, hydroxy-(halogenated C 1 -C 4 -alkyl), CN, C 6 -C 12 -aryl, C 1 -C 4 -alkoxy, halogenated C 1 -C 4 -alkoxy, C 6 -C 12 aryl-C 1 -C 4 -alkoxy, C 6 -C 12 -aryloxy, C 1 -C 4 -alkyl-sulfonyl, C 1 -C 4 -alkyl-carbonylamino and C 3 -C 12 -heterocyclyl.

In connection with R 13 , substituted C 6 -C 12 -aryloxy in particular includes C 6 -C 12 -aryloxy, such as phenoxy, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen and C 1 -C 4 -alkyl.

In connection with R 13 , substituted C 3 -C 12 -heterocyclyl in particular includes C 3 -C 12 -heterocyclyl, such as furanyl, pyrrolyl, thiophenyl, oxazolyl, diazolyl, thiazolyl, triazolyl, pyridyl pyrimidyl, pyrazyl, pyridazyl, benzofuranyl, benzothiophenyl, benzothiazolyl, quinolinyl or isoquinolinyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, C 6 -C 12 -aryl-C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, hydroxy, CN, C 6 -C 12 -aryl optionally substituted with halogen and C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, halogenated C 1 -C 4 -alkoxy, C 3 -C 6 -cycloalkoxy, C 6 -C 12 aryl-C 1 -C 4 -alkoxy, C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkoxy and C 3 -C 12 -heterocyclyl.

According to a preferred embodiment, R 13 is hydrogen, C 1 -C 8 -alkyl (e.g. methyl, ethyl, n-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1 -C 6 -alkyl (e.g. —CF 3 or —CF 2 Me), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. methoxy-methyl), C 3 -C 12 -cycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl and C 6 -C 12 -aryl (e.g. cyclopropyl, 2-propyl-cyclopropyl, 1-(methoxy-methyl)-cyclopropyl, 2-phenyl-cyclopropyl, cyclopentyl, 1-methyl-cyclohexyl, 1-CF 3 -cyclopropyl, 4-CF 3 -cyclohexyl, or 4,4-diF-cyclohexyl), or C 2 -C 6 -alkenyl (e.g. hex-2-enyl), C 3 -C 6 -cycloalkenyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of C 1 -C 4 -alkyl (e.g. 1,3,3-trimethylcyclohexen-2-yl), or C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, hydroxy-(halogenated C 1 -C 4 -alkyl), CN, C 6 -C 12 -aryl, C 1 -C 4 -alkoxy, halogenated C 1 -C 4 -alkoxy, C 6 -C 12 aryl-C 1 -C 4 -alkoxy, C 6 -C 12 -aryloxy, C 1 -C 4 -alkyl-sulfonyl, C 1 -C 4 -alkyl-carbonylamino and C 3 -C 12 -heterocyclyl, (e.g. phenyl, 2-F-phenyl, 4-F-phenyl, 3-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl, 3,4-diF-phenyl, 2,3,4-triF-phenyl, 2,4-diCl-phenyl, 3,4-diCl-phenyl, 3-F-4-Cl-phenyl, 3-Cl-4-F-phenyl, 3-Cl-5-F-phenyl, 3,4-diF-5-Cl-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 3-iPr-phenyl, 3-tBu-phenyl, 3-Me-4-F-phenyl, 3-Me-4-Cl-phenyl, 3-iPr-4 Cl-phenyl, 3-(1-OH-1-CF 3 -Et)-phenyl, 3-CHF 2 -4-F-phenyl, 2-CF 3 -phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 2-F-3-CF 3 -phenyl, 2-F-5-CF 3 -phenyl, 3-F-5-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-CF 3 -4-Cl-phenyl, 3-Me-4-CF 3 -phenyl, 3-CF 3 -4-Me-phenyl, 3,4-diCF 3 -phenyl, 4-OMe-phenyl, 3-OiPr-phenyl, 3-CF 3 -4-OMe-phenyl, 3-OCH 2 CF 3 -phenyl, 3-OCF 3 -phenyl, 2-OCHF 2 -5-Cl-phenyl, 3-OCF 3 -4-F-phenyl, 3-OCF 3 -4-Cl-phenyl, 3-OBn-phenyl, 3-OPh-phenyl, 3-CN-phenyl, 4-CN-phenyl, 2-F-3-CN-phenyl, 2-F-4-CN-phenyl, 3-F-4-CN-phenyl, 2-F-5-CN-phenyl, 3-F-5-CN-phenyl, 3-Cl-4-CN-phenyl, 2-Cl-5-CN-phenyl, 3-Cl-5-CN-phenyl, 3-CN-4-Cl-phenyl, 2-Me-3-CN-phenyl, 2-Me-5-CN-phenyl, 3-Me-5-CN-phenyl, 3-CF 3 -4-CN-phenyl, 3-CN-4-OMe-phenyl, 3-CN-4-OCF 3 -phenyl, 3-phenyl-phenyl, 3-MeSO 2 -phenyl, 3-(piperidin-4-yl)phenyl, 2-methylcarbonylamino-5-Cl-phenyl, 3-(pyrid-2-yl)-phenyl, 3-(pyrid-3-yl)-4F-phenyl, 3-(pyrid-4-yl)-4F-phenyl, 3-(pyrimid-5-yl)-4F-phenyl, indan-5-yl, 2-chlor-indan-5-yl, or tetralin-6-yl), or C 1 -C 6 -alkoxy (e.g. methoxy, ethoxy, or n-propoxy), C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy (e.g. 2-methoxy-ethoxy), C 6 -C 12 -aryloxy optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen and C 1 -C 4 -alkyl (e.g. 4-F-phenoxy or 4-tertbutyl-phenoxy), or C 3 -C 12 -heterocyclyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, C 6 -C 12 -aryl-C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, hydroxy, CN, C 6 -C 12 -aryl optionally substituted with halogen and C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, halogenated C 1 -C 4 -alkoxy, C 3 -C 6 -cycloalkoxy, C 6 -C 12 aryl-C 1 -C 4 -alkoxy, C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkoxy and C 3 -C 12 -heterocyclyl (e.g. propyl-furan-2-yl, 2-CF 3 -furan-5-yl, 1,2-dimethyl-5-CN-pyrrol-3-yl, 2,3-diMe-thiophen-5-yl, 2-Me-thiophen-5-yl, 2-Cl-thiophen-5-yl, 3-Cl-thiophen-2-yl, 2,5-diCl-thiophen-3-yl, 2-tetrahydropyranyl-thiophen-5-yl, 1,3-thiazol-5-yl, 4-Me-1,3-thiazol-2-yl, 2-Me-1,3-thiazol-5-yl, 5-Me-1,3-thiazol-2-yl, 4-Me-1,3-thiazol-5-yl, 2-Me-1,3-thiazol-4-yl, 4-isopropyl-1,3-thiazol-2-yl, 2,4-diMe-1,3-thiazol-5-yl, 2-phenyl-4-Me-1,3-thiazol-5-yl, 4-phenyl-1,3-thiazol-5-yl, 2-(4-Me-phenyl)-1,3-thiazol-5-yl, 4-(4-F-phenyl)-1,3-thiazol-2-yl, 2-Cl-1,3-thiazol-4-yl, 4-Cl-1,3-thiazol-5-yl, 2-Br-1,3-thiazol-5-yl, 4-Br-1,3-thiazol-2-yl, 4-Me-5-Br-1,3-thiazol-2-yl, 2,4-dichloro-1,3-thiazol-5-yl, 1,5-dimethyl-1,2,4-triazol-3-yl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, 4-F-pyrid-2-yl, 5-F-pyrid-2-yl, 6-F-pyrid-2-yl, 4-Cl-pyrid-2-yl, 5-F-pyrid-3-yl, 2-F-pyrid-4-yl, 3,5-diCl-pyrid-4-yl, 4,5-diCl-pyrid-2-yl, 2-Cl-3F-pyrid-4-yl, 5-Me-pyrid-2-yl, 4-iPr-pyrid-2-yl, 4-Me-5-F-pyrid-2-yl, 4-CF 3 -pyrid-2-yl, 5-CF 3 -pyrid-2-yl, 6-CF 3 -pyrid-2-yl, 5-CF 3 -pyrid-3-yl, 2-CF 3 -pyrid-4-yl, 3-F-4-CF 3 -pyrid-2-yl, 4-CF 3 -5-F-pyrid-2-yl, 4-CF 3 -5-Cl-pyrid-2-yl, 3,5-diF-4-CF 3 -pyrid-2-yl, 4-OCH 2 CF 3 -pyrid-2-yl, 4-OCH 2 CF 3 -5-F-pyrid-2-yl, 4-OCH 2 CF 3 -5-Cl-pyrid-2-yl, 4-OBn-5-F-pyrid-2-yl, 3-(4-F-phenyl)pyrid-5-yl, 2-(4-F-phenyl)-pyrid-3-yl, 4-(pyrid-4-yl)-pyrid-2-yl, 4-(pyrid-3-yl)-pyrid-2-yl, 5-cyclopropyl-pyraz-2-yl, 5-cyclobutyl-pyraz-2-yl, 5-pyrrolidin-pyraz-2-yl, pyridaz-3-yl, 4-CF 3 -pyridaz-3-yl, 5-CF 3 -pyridaz-3-yl, 5-F-pyrimid-2-yl, 6-Cl-pyrimid-4-yl, 6-Me-pyrimid-4-yl, 6-Et-pyrimid-4-yl, 6-Pr-pyrimid-4-yl, 6-iPr-pyrimid-4-yl, 4-CF 3 -pyrimid-2-yl, 6-CF 3 -pyrimid-4-yl, 2-Me-6-Cl-pyrimid-4-yl, 2-Me-6-CF 3 -pyrimid-4-yl, 2-OMe-6-CF 3 -pyrimid-4-yl, 2-OMe-pyrimid-4-yl, 6-OMe-pyrimid-4-yl, 6-OEt-pyrimid-4-yl, 6-OPr-pyrimid-4-yl, 6-OiPr-pyrimid-4-yl, 6-OiBu-pyrimid-4-yl, 6-OBu-pyrimid-4-yl, 6-OBn-pyrimid-4-yl, 6-cyclobutyloxy-pyrimid-4-yl, 6-cyclopentyloxy-pyrimid-4-yl, 6-cyclohexyloxy-pyrimid-4-yl, 6-cyclopropyl-pyrimid-4-yl, 6-phenyl-pyrimid-4-yl, 6-(2-F-phenyl)-pyrimid-4-yl, 6-(3-F-phenyl)-pyrimid-4-yl, 6-(4-F-phenyl)pyrimid-4-yl, 6-Cl-pyrimid-4-yl, 6-(2-Me-phenyl)-pyrimid-4-yl, 6-(3-Me-phenyl)-pyrimid-4-yl, 6-(4-Me-phenyl)-pyrimid-4-yl, 6-(3-Cl-phenyl)-pyrimid-4-yl, 6-(4-Cl-phenyl)-pyrimid-4-yl, 2-(morpholin-1-yl)-pyrimid-4-yl, 6-(azetidin-3-yl-methoxy)-pyrimid-4-yl, 6-(pyrrolidin-3-ylmethoxy)-pyrimid-4-yl, 6-(pyrrolidin-2-yl-methoxy)-pyrimid-4-yl, benzofuran-5-yl, 2-Me-benzofuran-3-yl, 2-Et-benzofuran-3-yl, benzothiophen-5-yl, benzothiophen-6-yl, 5-Me-benzothiophen-2-yl, 5-F-benzothiophen-2-yl, 3-Cl-benzothiophen-2-yl, benzothiazol-2-yl, isoquinolin-6-yl, isoquinolin-7-yl, quinolin-6-yl, quinolin-7-yl, 4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl, 2,3-dihydrobenzofuran-5-yl, 7H-pyrrolo[2,3-d]pyrimidin-4-yl, pyrazolo[1,5-a]pyridine-3-yl, pyrazolo[1,5-a]pyridine-7-yl, 5-methyl-imidazo[1,2-a]pyridin-3-yl, 6-chloro-2-methyl-imidazo[1,2-a]pyridin-3-yl, 6-bromo-2-methyl-imidazo[1,2-a]pyridin-3-yl, thieno[2,3-b]pyridin-2-yl, N-benzyl-indolin-6-yl, indolinon-4-yl, chroman-6-yl, 4,4-dimethylchroman-6-yl, 4,4-dimethyl-1,3-dioxan-2-yl, 2-Me-tetrahydrofuran-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl, 4-Me-tetrahydropyran-4-yl, 2,2-diMe-tetrahydropyran-4-yl, 1-isopropyl-piperidin-4-yl, 1-ethyl-piperidin-3-yl, or 2-CF 3 -piperazin-5-yl), or tri-(C 1 -C 4 -alkyl)silyloxy.

Further preferred embodiments of the pyrrolidine derivatives of formula (Id) result if:

R 1 is 1,3-diazolyl optionally substituted with halogen or C 1 -C 4 -alkyl (e.g. 1-methyl-1,3-diazol-4-yl), or 1,2,3-triazolyl optionally substituted with C 1 -C 4 -alkyl (e.g. 1-methyl-1,2,3-triazol-4-yl); R 2a , R 2b

are hydrogen;

R 3a is C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, or cyclohexyl) C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, or 2,4,5-trifluoro-phenyl), or hydroxy, C 1 -C 6 -alkoxy (e.g. methoxy, or iso-butoxy), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), C 6 -C 12 -aryloxy (e.g. 4-F-phenoxy) optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, or C 3 -C 12 -heterocyclyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen or C 3 -C 6 -cycloalkyl (e.g. tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, 1-cyclopropyl-piperidin-4-yl, 1-cyclopropyl-piperidin-3-yl, 2-pyridyl, 3-pyridyl, 3-F-pyrid-2-yl, 1,3-oxazol-4-yl, or 1,3-oxazol-2-yl); R 3b is hydrogen or hydroxy; Y 1 is >CR 6 ; R 6 is hydrogen, C 1 -C 6 -alkyl (e.g. methyl), or hydroxy-C 1 -C 6 -alkyl (e.g. —CH 2 OH); R 8a is hydrogen, C 1 -C 6 -alkyl (e.g. methyl, ethyl, n-propyl, iso-propyl, pentyl, or hexyl), or C 1 -C 6 -alkylcarbonyl (e.g. methylcarbonyl), or R 6 , R 8a

are together optionally substituted C 1 -C 5 -alkylene, wherein one or more —CH 2 — of C 1 -C 5 -alkylene may be independently replaced by a an oxygen atom or C═O e.g. —C(O)OCH 2 —);

R 9a is hydrogen, halogen, C 1 -C 6 -alkyl (e.g. methyl, ethyl, tert-butyl, or 2,3-dimethyl-propyl), or C 1 -C 6 -alkoxy (e.g. methoxy or ethoxy); R 9b is hydrogen; n4 is 0, 1, 2, 3, or 4; R 13 is hydrogen, C 1 -C 8 -alkyl (e.g. methyl, ethyl, n-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1 -C 6 -alkyl (e.g. —CF 3 or —CF 2 Me), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. methoxy-methyl), C 3 -C 12 -cycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl and C 6 -C 12 -aryl (e.g. cyclopropyl, 2-propyl-cyclopropyl, 1-(methoxy-methyl)cyclopropyl, 2-phenyl-cyclopropyl, cyclopentyl, cyclopentyl, 3,3-dimethylcyclopentyl, cyclohexyl, 3,3-dimethyl-cyclohexyl, 4,4-dimethyl-cyclohexyl, 1-methyl-cyclohexyl, 1-CF 3 -cyclopropyl, 4-CF 3 -cyclohexyl, 3-CF 3 -cyclohexyl, or 4,4-diF-cyclohexyl), or C 2 -C 6 -alkenyl (e.g. hex-2-enyl), C 3 -C 6 -cycloalkenyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of C 1 -C 4 -alkyl (e.g. 1,3,3-trimethylcyclohexen-2-yl), or C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, hydroxy-(halogenated C 1 -C 4 -alkyl), CN, C 6 -C 12 -aryl, C 1 -C 4 -alkoxy, halogenated C 1 -C 4 -alkoxy, C 6 -C 12 aryl-C 1 -C 4 -alkoxy, C 6 -C 12 -aryloxy, C 1 -C 4 alkyl sulfonyl, C 1 -C 4 -alkylcarbonylamino and C 3 -C 12 -heterocyclyl, (e.g. phenyl, 2-F-phenyl, 4-F-phenyl, 3-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl, 3,4-diF-phenyl, 2,3,4-triF-phenyl, 2,4-diCl-phenyl, 3,4-diCl-phenyl, 3-F-4-Cl-phenyl, 3-Cl-4-F-phenyl, 3-Cl-5-F-phenyl, 3,4-diF-5-Cl-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 3-iPr-phenyl, 3-tBu-phenyl, 3-Me-4-F-phenyl, 3-Me-4-Cl-phenyl, 3-iPr-4 Cl-phenyl, 3-(1-OH-1-CF 3 -Et)-phenyl, 3-CHF 2 -4-F-phenyl, 2-CF 3 -phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 2-F-3-CF 3 -phenyl, 2-F-5-CF 3 -phenyl, 3-F-5-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-CF 3 -4-Cl-phenyl, 3-Me-4-CF 3 -phenyl, 3-CF 3 -4-Me-phenyl, 3,4-diCF 3 -phenyl, 4-OMe-phenyl, 3-OiPr-phenyl, 3-CF 3 -4-OMe-phenyl, 3-OCH 2 CF 3 -phenyl, 3-OCF 3 -phenyl, 2-OCHF 2 -5-Cl-phenyl, 3-OCF 3 -4-F-phenyl, 3-OCF 3 -4-Cl-phenyl, 3-OBn-phenyl, 3-OPh-phenyl, 3-CN-phenyl, 4-CN-phenyl, 2-F-3-CN-phenyl, 2-F-4-CN-phenyl, 3-F-4-CN-phenyl, 2-F-5-CN-phenyl, 3-F-5-CN-phenyl, 3-Cl-4-CN-phenyl, 2-Cl-5-CN-phenyl, 3-Cl-5-CN-phenyl, 3-CN-4-Cl-phenyl, 2-Me-3-CN-phenyl, 2-Me-5-CN-phenyl, 3-Me-5-CN-phenyl, 3-CF 3 -4-CN-phenyl, 3-CN-4-OMe-phenyl, 3-CN-4-OCF 3 -phenyl, 3-phenyl-phenyl, 3-MeSO 2 -phenyl, 3-(piperidin-4-yl)-phenyl, 2-methylcarbonylamino-5-Cl-phenyl, 3-(pyrid-2-yl)-phenyl, 3-(pyrid-3-yl)-4F-phenyl, 3-(pyrid-4-yl)-4F-phenyl, 3-(pyrimid-5-yl)-4F-phenyl, indan-5-yl, 2-chlor-indan-5-yl, or tetralin-6-yl), or C 1 -C 6 -alkoxy (e.g. methoxy, ethoxy, or n-propoxy), C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy (e.g. 2-methoxy-ethoxy), C 6 -C 12 -aryloxy optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen and C 1 -C 4 -alkyl (e.g. 4-F-phenoxy or 4-tertbutyl-phenoxy), or C 3 -C 12 -heterocyclyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, C 6 -C 12 -aryl-C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, hydroxy, CN, C 6 -C 12 -aryl optionally substituted with halogen and C 1 -C 1 -alkyl, C 1 -C 4 -alkoxy, halogenated C 1 -C 4 -alkoxy, C 3 -C 6 -cycloalkoxy, C 6 -C 12 aryl-C 1 -C 4 -alkoxy, C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkoxy and C 3 -C 12 -heterocyclyl (e.g. e.g. n-propyl-furan-2-yl, 2-CF 3 -furan-5-yl, 1,2-dimethyl-5-CN-pyrrol-3-yl, 2,3-diMe-thiophen-5-yl, 2-Me-thiophen-5-yl, 2-Cl-thiophen-5-yl, 3-Cl-thiophen-2-yl, 2,5-diCl-thiophen-3-yl, 2-tetrahydropyranyl-thiophen-5-yl, 1,3-thiazol-5-yl, 4-Me-1,3-thiazol-2-yl, 2-Me-1,3-thiazol-5-yl, 5-Me-1,3-thiazol-2-yl, 4-Me-1,3-thiazol-5-yl, 2-Me-1,3-thiazol-4-yl, 4-isopropyl-1,3-thiazol-2-yl, 2,4-diMe-1,3-thiazol-5-yl, 2-phenyl-4-Me-1,3-thiazol-5-yl, 4-phenyl-1,3-thiazol-5-yl, 2-(4-Me-phenyl)-1,3-thiazol-5-yl, 4-(4-F-phenyl)-1,3-thiazol-2-yl, 2-Cl-1,3-thiazol-4-yl, 4-Cl-1,3-thiazol-5-yl, 2-Br-1,3-thiazol-5-yl, 4-Br-1,3-thiazol-2-yl, 4-Me-5-Br-1,3-thiazol-2-yl, 2,4-dichloro-1,3-thiazol-5-yl, 1,5-dimethyl-1,2,4-triazol-3-yl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, 4-F-pyrid-2-yl, 5-F-pyrid-2-yl, 6-F-pyrid-2-yl, 4-Cl-pyrid-2-yl, 5-F-pyrid-3-yl, 2-F-pyrid-4-yl, 3,5-diCl-pyrid-4-yl, 4,5-diCl-pyrid-2-yl, 2-Cl-3F-pyrid-4-yl, 5-Me-pyrid-2-yl, 4-iPr-pyrid-2-yl, 4-Me-5-F-pyrid-2-yl, 4-CF 3 -pyrid-2-yl, 5-CF 3 -pyrid-2-yl, 6-CF 3 -pyrid-2-yl, 5-CF 3 -pyrid-3-yl, 2-CF 3 -pyrid-4-yl, 3-F-4-CF 3 -pyrid-2-yl, 4-CF 3 -5-F-pyrid-2-yl, 4-CF 3 -5-Cl-pyrid-2-yl, 3,5-diF-4-CF 3 -pyrid-2-yl, 4-OCH 2 CF 3 -pyrid-2-yl, 4-OCH 2 CF 3 -5-F-pyrid-2-yl, 4-OCH 2 CF 3 -5-Cl-pyrid-2-yl, 4-OBn-5-F-pyrid-2-yl, 3-(4-F-phenyl)-pyrid-5-yl, 2-(4-F-phenyl)-pyrid-3-yl, 4-(pyrid-4-yl)pyrid-2-yl, 4-(pyrid-3-yl)-pyrid-2-yl, 5-cyclopropyl-pyraz-2-yl, 5-cyclobutyl-pyraz-2-yl, 5-pyrrolidin-pyraz-2-yl, pyridaz-3-yl, 4-CF 3 -pyridaz-3-yl, 5-CF 3 -pyridaz-3-yl, 5-F-pyrimid-2-yl, 6-Cl-pyrimid-4-yl, 6-Me-pyrimid-4-yl, 6-Et-pyrimid-4-yl, 6-Pr-pyrimid-4-yl, 6-iPr-pyrimid-4-yl, 4-CF 3 -pyrimid-2-yl, 6-CF 3 -pyrimid-4-yl, 2-Me-6-Cl-pyrimid-4-yl, 2-Me-6-CF 3 -pyrimid-4-yl, 2-OMe-6-CF 3 -pyrimid-4-yl, 2-OMe-pyrimid-4-yl, 6-OMe-pyrimid-4-yl, 6-OEt-pyrimid-4-yl, 6-OPr-pyrimid-4-yl, 6-OiPr-pyrimid-4-yl, 6-OiBu-pyrimid-4-yl, 6-6-OBn-pyrimid-4-yl, 6-cyclobutyloxy-pyrimid-4-yl, 6-cyclopentyloxy-pyrimid-4-yl, 6-cyclohexyloxy-pyrimid-4-yl, 6-cyclopropyl-pyrimid-4-yl, 6-phenyl-pyrimid-4-yl, 6-(2-F-phenyl)-pyrimid-4-yl, 6-(3-F-phenyl)-pyrimid-4-yl, 6-(4-F-phenyl)pyrimid-4-yl, 6-Cl-pyrimid-4-yl, 6-(2-Me-phenyl)-pyrimid-4-yl, 6-(3-Me-phenyl)-pyrimid-4-yl, 6-(4-Me-phenyl)-pyrimid-4-yl, 6-(3-Cl-phenyl)-pyrimid-4-yl, 6-(4-Cl-phenyl)pyrimid-4-yl, 2-(morpholin-1-yl)-pyrimid-4-yl, 6-(azetidin-3-yl-methoxy)-pyrimid-4-yl, 6-(pyrrolidin-3-yl-methoxy)-pyrimid-4-yl, 6-(pyrrolidin-2-yl-methoxy)-pyrimid-4-yl, benzofuran-5-yl, 2-Me-benzofuran-3-yl, 2-Et-benzofuran-3-yl, benzothiophen-5-yl, benzothiophen-6-yl, 5-Me-benzothiophen-2-yl, 5-F-benzothiophen-2-yl, 3-Cl-benzothiophen-2-yl, benzothiazol-2-yl, isoquinolin-6-yl, isoquinolin-7-yl, quinolin-6-yl, quinolin-7-yl, 4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl, 2,3-dihydrobenzofuran-5-yl, 7H-pyrrolo[2,3-d]pyrimidin-4-yl, pyrazolo[1,5-a]pyridine-3-yl, pyrazolo[1,5-a]pyridine-7-yl, 5-methyl-imidazo[1,2-a]pyridin-3-yl, 6-chloro-2-methyl-imidazo[1,2-a]pyridin-3-yl, 6-bromo-2-methyl-imidazo[1,2-a]pyridin-3-yl, thieno[2,3-b]pyridin-2-yl, N-benzyl-indolin-6-yl, indolinon-4-yl, chroman-6-yl, 4,4-dimethylchroman-6-yl, 4,4-dimethyl-1,3-dioxan-2-yl, 2-Me-tetrahydrofuran-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl, 4-Me-tetrahydropyran-4-yl, 2,2-diMe-tetrahydropyran-4-yl, 1-isopropyl-piperidin-4-yl, 1-ethyl-piperidin-3-yl, or 2-CF 3 -piperazin-5-yl), or tri-(C 1 -C 4 -alkyl)-silyloxy; and R 5a , R 5b

are hydrogen.

According to a particularly preferred embodiment of the pyrrolidine derivatives of the formula (Id), R 3a is phenyl, 4-F-phenyl, tetrahydrofuran-2-yl or tetrahydropyran-2-yl.

According to a further particularly preferred embodiment of the pyrrolidine derivatives of the formula (Id), R 13 is a group of the formula (Id1):

wherein

X is >CH— or >N—;

Z is >C—R 13c or >N—;

R 13b is halogen (e.g. fluoro or chloro), C 1 -C 4 -alkyl (e.g. methyl, ethyl, n-propyl, iso-propyl, tert-butyl), halogenated C 1 -C 4 -alkyl (e.g. CHF 2 , CF 3 ), hydroxy-(halogenated C 1 -C 4 -alkyl) (e.g. 1-OH-1-CF 3 -Et), C 6 -C 12 -aryl-C 1 -C 4 -alkyl (e.g. benzyl), C 3 -C 6 -cycloalkyl (e.g. cyclopropyl), CN, C 6 -C 12 -aryl optionally substituted with halogen or C 1 -C 4 -alkyl (e.g. phenyl, 2-F-phenyl, 4-F-phenyl, 3-F-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl), C 1 -C 4 -alkoxy (e.g. methoxy, ethoxy, n-propoxy, iso-propoxy), halogenated C 1 -C 4 -alkoxy (e.g. —OCHF 2 , —OCH 2 CF 3 , —OCF 3 ), C 3 -C 6 -cycloalkoxy (e.g. cyclobutoxy, cyclopentyloxy, cyclohexyloxy), C 6 -C 12 aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkoxy (e.g. pyrrolid-3-yl-methoxy, pyrrolid-2-yl-methoxy, azetid-3-yl-methoxy), C 6 -C 12 -aryloxy (e.g. phenoxy), C 1 -C 4 -alkyl-sulfonyl (e.g. methylsulfonyl), C 1 -C 4 -alkyl-carbonylamino (e.g. 2-methylcarbonylamino) or C 3 -C 12 -heterocyclyl (e.g. piperidin-4-yl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, pyrimid-5-yl); and

R 13c is hydrogen or halogen (e.g. fluoro, chloro).

Especially preferred among the pyrrolidine derivatives of the formula (Id) wherein R 13 is a group of the formula (Id1) are those wherein X is >CH— or >N—, and Z is >C—R 13c . According this embodiment it is particularly preferred if X is >CH—, Z is >C—R 13c and R 13c is hydrogen or fluoro, especially fluoro, or X is >N—, Z is >C—R 13c and R 13c is hydrogen or fluoro, especially fluoro.

In the pyrrolidine derivatives of the formula (Id) wherein R 13 is a group of the formula (Id1), R 8a , n4, R 9a and R 9b are as defined herein. Preferably, R 8a is hydrogen n4 is, in particular, 0 or 1, with n4=0 being particularly preferred. R 9a and R 9b are preferably both hydrogen if n4 is 1.

According to a further embodiment, R 4 is —NR 8b COR 14 . Thus, the present invention relates to the pyrrolidine derivatives of the formula (Ie):

wherein R 1 , R 2a , R 2b , R 3a , R 3b , Y 1 , R 5a and R 5b are as defined herein, and

R 8b is hydrogen, C 1 -C 6 -alkyl (e.g. methyl, ethyl, iso-propyl, or n-butyl), or C 1 -C 6 alkylcarbonyl (e.g. methylcarbonyl), or R 6 , R 8b

together are optionally substituted C 1 -C 5 -alkylene, wherein one or more —CH 2 — of C 1 -C 5 -alkylene may be independently replaced by a an oxygen atom or C═O; and

R 14 is C 1 -C 8 -alkyl (e.g. pentyl, n-butyl, or hexyl), halogenated C 1 -C 6 -alkyl (e.g. 1,1-diF-butyl, 3,3-diF-butyl, 4,4,4-triF-butyl, 1,1-diF-pentyl, or 4,4-diF-pentyl), (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl), (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl (e.g. benzyl), hydroxy-C 1 -C 6 -alkyl (e.g. hydroxyl-methyl or 1-hydroxy-pentyl), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. methoxy-methyl, ethoxy-methyl, or ethoxy-ethyl), (optionally substituted C 6 -C 12 -aryloxy)-C 1 -C 4 -alkyl (e.g. phenoxy-methyl or (4-F-phenoxy)-methyl), C 1 -C 6 -alkylcarbonyl-C 1 -C 4 -alkyl (e.g. 2-methylcarbonyl-ethyl or 3-methylcarbonyl-propyl), C 1 -C 6 -alkoxycarbonyl-C 1 -C 4 -alkyl (e.g. 3-methoxycarbonyl-propyl), C 1 -C 6 -alkylaminocarbonyl-C 1 -C 4 -alkyl (e.g. 3-methylaminocarbonyl-propyl), optionally substituted (C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl (e.g. 2-pyridyl-methyl), optionally substituted C 3 -C 12 -cycloalkyl (e.g. 1-CF 3 -cyclopropyl or 4-CF 3 -cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl, 3,5-diCl-phenyl, 2-Cl-4-F-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-CF 3 -phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 2-OMe-phenyl, 3-OMe-phenyl, 2-CN-phenyl, or 3-CN-phenyl, 4-CN-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 3-Cl-pyridazin-6-yl, 2-Cl-pyrazin-5-yl, or 2-CF 3 -pyrazin-5-yl).

In particular, R 8b is hydrogen.

In particular, R 14 is C 1 -C 8 -alkyl (e.g. pentyl, n-butyl, or hexyl), halogenated C 1 -C 6 -alkyl (e.g. 1,1-diF-butyl, 3,3-diF-butyl, 4,4,4-triF-butyl, 1,1-diF-pentyl, or 4,4-diF-pentyl), (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl), hydroxy-C 1 -C 6 -alkyl (e.g. hydroxylmethyl or 1-hydroxy-pentyl), (optionally substituted C 6 -C 12 -aryloxy)-C 1 -C 4 -alkyl (e.g. phenoxy-methyl or (4-F-phenoxy)-methyl), C 1 -C 6 -alkylcarbonyl-C 1 -C 4 -alkyl (e.g. 2-methylcarbonyl-ethyl or 3-methylcarbonyl-propyl), C 1 -C 6 -alkoxycarbonyl-C 1 -C 4 -alkyl (e.g. 3-methoxycarbonyl-propyl), optionally substituted C 3 -C 12 -cycloalkyl (e.g. 1-CF 3 -cyclopropyl or 4-CF 3 -cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl, 3,5-diCl-phenyl, 2-Cl-4-F-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-CF 3 -phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 2-OMe-phenyl, 3-OMe-phenyl, 2-CN-phenyl, or 3-CN-phenyl, 4-CN-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 3-Cl-pyridazin-6-yl, 2-Cl-pyrazin-5-yl, or 2-CF 3 -pyrazin-5-yl).

R 2a , R 2b —in pyrrolidine derivatives of formula (Ie)—are hydrogen.

R 3a —in pyrrolidine derivatives of formula (Ie)—is C 3 -C 12 -cycloalkyl (cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenyloxy or 4-F-phenyloxy), or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl). Preferably R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl) or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl).

R 3b —in pyrrolidine derivatives of formula (Ie)—is hydrogen or hydroxy. Preferably, R 3b is hydrogen.

Y 1 —in pyrrolidine derivatives of formula (Ie)—is >CR 6 .

R 6 —in pyrrolidine derivatives of formula (Ie)—is hydrogen.

R 5a , R 5b —in pyrrolidine derivatives of formula (Ie)—are hydrogen.

Particular embodiments of pyrrolidine derivatives of formula (Ie) result if:

R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl); R 2a , R 2b

are hydrogen;

R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl) or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 8b is hydrogen; R 14 is C 1 -C 8 -alkyl (e.g. pentyl, n-butyl, or hexyl), halogenated C 1 -C 6 -alkyl (e.g. 1,1-diF-butyl, 3,3-diF-butyl, 4,4,4-triF-butyl, 1,1-diF-pentyl, or 4,4-diF-pentyl), (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl), hydroxy-C 1 -C 6 -alkyl (e.g. hydroxylmethyl or 1-hydroxy-pentyl), (optionally substituted C 6 -C 12 -aryloxy)-C 1 -C 4 -alkyl (e.g. phenoxy-methyl or (4-F-phenoxy)-methyl), C 1 -C 6 -alkylcarbonyl-C 1 -C 4 -alkyl (e.g. 2-methylcarbonyl-ethyl or 3-methylcarbonyl-propyl), C 1 -C 6 -alkoxycarbonyl-C 1 -C 4 -alkyl (e.g. 3-methoxycarbonyl-propyl), optionally substituted C 3 -C 12 -cycloalkyl (e.g. 1-CF 3 -cyclopropyl or 4-CF 3 -cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl, 3,5-diCl-phenyl, 2-Cl-4-F-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-CF 3 -phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 2-OMe-phenyl, 3-OMe-phenyl, 2-CN-phenyl, or 3-CN-phenyl, 4-CN-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 3-Cl-pyridazin-6-yl, 2-Cl-pyrazin-5-yl, or 2-CF 3 -pyrazin-5-yl); and R 5a , R 5b

are hydrogen.

Preferably, R 1 —in the pyrrolidine derivatives of formula (Ie)—is an optionally substituted 5-membered heterocyclic ring containing 2 N which, in particular, is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 —in the pyrrolidine derivatives of formula (Ie)—is an optionally substituted 5-membered heterocyclic ring containing 3 N which, in particular, is optionally substituted 1,2,3-triazolyl.

In connection with R 1 and the pyrrolidine derivatives of formula (Ie), substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular includes 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, thiazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy-carbonyl and C 1 -C 6 -alkyl-carbonylamino. Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl. In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl). According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl.

In connection with R 3a and the pyrrolidine derivatives of formula (Ie), substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy.

According to a preferred embodiment, R 3a —in the pyrrolidine derivatives of formula (Ie)—is C 6 -C 12 -aryl, in particular phenyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen and C 1 -C 4 -alkoxy (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl) or C 3 -C 12 -heterocyclyl (e.g. 2-pyridyl).

In connection with R 14 , substituted C 6 -C 12 -aryloxy-C 1 -C 4 -alkyl in particular includes C 6 -C 12 -aryloxy-C 1 -C 4 -alkyl, such as benzyloxy, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen.

In connection with R 14 , substituted C 3 -C 12 -cycloalkyl in particular includes C 3 -C 12 -cycloalkyl, such as cyclopropyl or cyclohexyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl.

In connection with R 14 , substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, CN and C 1 -C 4 -alkoxy. Preferably the substituents on C 6 -C 12 -aryl are independently selected from the group consisting of C 1 -C 4 -alkyl and CN.

In connection with R 14 , substituted C 3 -C 12 -heterocyclyl in particular includes C 3 -C 12 -heterocyclyl, such as pyridazyl or pyrazyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen and halogenated C 1 -C 4 -alkyl.

According to a preferred embodiment, R 14 is C 1 -C 8 -alkyl (e.g. pentyl, n-butyl, or hexyl), halogenated C 1 -C 6 -alkyl (e.g. 1,1-diF-butyl, 3,3-diF-butyl, 4,4,4-triF-butyl, 1,1-diF-pentyl, or 4,4-diF-pentyl), (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl), hydroxy-C 1 -C 6 -alkyl (e.g. hydroxyl-methyl or 1-hydroxy-pentyl), (halogenated C 6 -C 12 -aryloxy)-C 1 -C 4 -alkyl (e.g. 4-F-phenoxy)-methyl), C 1 -C 6 -alkylcarbonyl-C 1 -C 4 -alkyl (e.g. 2-methylcarbonyl-ethyl or 3-methylcarbonyl-propyl), C 1 -C 6 -alkoxycarbonyl-C 1 -C 4 -alkyl (e.g. 3-methoxycarbonyl-propyl), C 3 -C 12 -cycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl (e.g. 1-CF 3 -cyclopropyl or 4-CF 3 -cyclohexyl), C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, CN and C 1 -C 4 -alkoxy (e.g. phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl, 3,5-diCl-phenyl, 2-Cl-4-F-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-CF 3 -phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 2-OMe-phenyl, 3-OMe-phenyl, 2-CN-phenyl, 3-CN-phenyl, or 4-CN-phenyl), or C 3 -C 12 -heterocyclyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen and halogenated C 1 -C 4 -alkyl (e.g. 3-Cl-pyridazin-6-yl, 2-Cl-pyrazin-5-yl, or 2-CF 3 -pyrazin-5-yl).

Further preferred embodiments of the pyrrolidine derivatives of formula (Ie) result if:

R 1 is 1,3-diazolyl optionally substituted with halogen or C 1 -C 4 -alkyl (e.g 1-methyl-1,3-diazol-4-yl); R 2a , R 2b

are hydrogen;

R 3a is C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen and C 1 -C 4 -alkoxy (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl) or C 3 -C 12 -heterocyclyl (e.g. 2-pyridyl)yl; R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 8b is hydrogen; R 14 is C 1 -C 8 -alkyl (e.g. pentyl or n-butyl), halogenated C 1 -C 6 -alkyl (e.g. 1,1-diF-butyl, 3,3-diF-butyl, 4,4,4-triF-butyl, 1,1-diF-pentyl, or 4,4-diF-pentyl), (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl), hydroxy-C 1 -C 6 -alkyl (e.g. hydroxylmethyl or 1-hydroxy-pentyl), (halogenated C 6 -C 12 -aryloxy)-C 1 -C 4 -alkyl (e.g. 4-F-phenoxy)methyl), C 1 -C 6 -alkylcarbonyl-C 1 -C 4 -alkyl (e.g. 2-methylcarbonyl-ethyl or 3-methylcarbonyl-propyl), C 1 -C 6 -alkoxycarbonyl-C 1 -C 4 -alkyl (e.g. 3-methoxycarbonylpropyl), C 3 -C 12 -cycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl (e.g. 1-CF 3 -cyclopropyl or 4-CF 3 -cyclohexyl), C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, CN and C 1 -C 4 -alkoxy (e.g. phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl, 3,5-diCl-phenyl, 2-Cl-4-F-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-CF 3 -phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 2-OMe-phenyl, 3-OMe-phenyl, 2-CN-phenyl, or 3-CN-phenyl, 4-CN-phenyl), or C 3 -C 12 -heterocyclyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen and halogenated C 1 -C 4 -alkyl(e.g. 3-Cl-pyridazin-6-yl, 2-Cl-pyrazin-5-yl, or 2-CF 3 -pyrazin-5-yl); and R 5a , R 5b

are hydrogen.

According to a particularly preferred embodiment, R 3a is phenyl, or halogenated phenyl (e.g. 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl), 4-OMe-phenyl, or pyrid-2-yl.

According to a further embodiment, R 4 is —NR 8c COOR 15 . Thus, the present invention relates to the pyrrolidine derivatives of the formula (If):

wherein R 1 , R 2a , R 2b , R 3a , R 3b , Y 1 , R 5a and R 5b are as defined herein, and

R 8c is hydrogen, C 1 -C 6 -alkyl (e.g. methyl, ethyl, iso-propyl, or n-butyl), or C 1 -C 6 -alkylcarbonyl (e.g. methylcarbonyl), or R 6 , R 8c

together are optionally substituted C 1 -C 5 -alkylene, wherein one or more —CH 2 — of C 1 -C 5 -alkylene may be independently replaced by a an oxygen atom or C═O. Preferably R 8c is hydrogen; and

R 15 is C 1 -C 8 -alkyl (e.g. ethyl, n-propyl, n-butyl, iso-butyl, or tert-butyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 2-Cl-4-F-phenyl or 2-Me-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 6-pyridazyl or 5-pyrazyl).

In particular, R 15 is C 1 -C 8 -alkyl (e.g. ethyl, n-propyl, n-butyl, iso-butyl, or tert-butyl), or optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 2-Cl-4-F-phenyl or 2-Me-phenyl). Preferably, R 15 is C 1 -C 6 -alkyl (e.g. ethyl, n-propyl, n-butyl, iso-butyl, or tert-butyl) or C 6 -C 12 -aryl (e.g. phenyl).

R 2a , R 2b —in the pyrrolidine derivatives of formula (If)—are, in particular, hydrogen.

R 3a —in the pyrrolidine derivatives of formula (If)—is, in particular, C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenyloxy or 4-F-phenyloxy), or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl). Preferably R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4 Cl phenyl 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl).

R 3b —in the pyrrolidine derivatives of formula (If)—is, in particular, hydrogen.

Y 1 —in the pyrrolidine derivatives of formula (If)—is, in particular, >CR 6 .

R 6 —in the pyrrolidine derivatives of formula (If)—is, in particular, hydrogen.

R 5a , R 5b —in the pyrrolidine derivatives of formula (If)—are, in particular, hydrogen.

Particular embodiments of the pyrrolidine derivatives of formula (If) result if:

R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl); R 2a , R 2b

are hydrogen;

R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 8c is hydrogen; R 15 is C 1 -C 8 -alkyl (e.g. ethyl, n-propyl, n-butyl, iso-butyl, or tert-bu) or C 6 -C 12 -aryl (e.g. phenyl); and R 5a , R 5b

are hydrogen.

Preferably, R 1 —in the pyrrolidine derivatives of formula (If)—is an optionally substituted 5-membered heterocyclic ring containing 2 N which, in particular, is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 —in the pyrrolidine derivatives of formula (If)—is an optionally substituted 5-membered heterocyclic ring containing 3 N which, in particular, is optionally substituted 1,2,3-triazolyl.

In connection with R 1 and the pyrrolidine derivatives of formula (If), substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular includes 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, thiazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy-carbonyl and C 1 -C 6 -alkyl-carbonylamino Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl. In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl). According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl.

In connection with R 3a and the pyrrolidine derivatives of formula (If), substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy. Preferably, the substituent(s) on C 6 -C 12 -aryl are independently selected from the group consisting of halogen.

According to a particular embodiment, R 3a —in the pyrrolidine derivatives of formula (If)—is C 6 -C 12 -aryl, in particular phenyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen.

Further preferred embodiments of pyrrolidine derivatives of formula (If) result if:

R 1 is 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl (e.g. 1-methyl-1,3-diazol-4-yl); R 2a , R 2b

are hydrogen;

R 3a is C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. phenyl, or 4-F-phenyl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 8c is hydrogen; R 15 is C 1 -C 8 -alkyl (e.g. ethyl, n-propyl, n-butyl, iso-butyl, or tert-butyl) or C 6 -C 12 -aryl (e.g. phenyl); and R 5a , R 5b

are hydrogen;

According to a further embodiment, R 4 is —NR 8d CONR 16a R 16b . Thus, the present invention relates to the pyrrolidine derivatives of the formula (Ig):

wherein R 1 , R 2a R 2b , R 3a , R 3b , Y 1 , R 5a and R 5b are as defined herein, and

R 8d is hydrogen, C 1 -C 6 -alkyl (e.g. methyl, ethyl, iso-propyl, or n-butyl), or C 1 -C 6 -alkylcarbonyl (e.g. methylcarbonyl), or R 6 , R 8d

together are optionally substituted C 1 -C 5 -alkylene, wherein one or more —CH 2 — of C 1 -C 5 -alkylene may be independently replaced by a an oxygen atom or C═O;

R 16a is (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl (e.g. benzyl or (2-Cl-phenyl)-methyl), optionally substituted (C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl (e.g. 2-pyridyl-methyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 3-F-phenyl, 2F-phenyl, 4-Cl-phenyl, or 2-Cl-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (2-pyridyl, 5-pyrazyl, or 6-pyridazyl); and R 16b is hydrogen or C 1 -C 6 -alkyl (e.g. methyl, ethyl, iso-propyl, or n-butyl).

In particular, R 8d is hydrogen.

In particular, R 16a is (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl (e.g. benzyl or (2-Cl-phenyl)methyl) or optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 3-F-phenyl, 2F-phenyl, 4-Cl-phenyl, or 2-Cl-phenyl).

In particular, R 16b is hydrogen.

R 2a , R 2b —in the pyrrolidine derivatives of formula (Ig)—are, in particular, hydrogen.

R 3a —in the pyrrolidine derivatives of formula (Ig)—is, in particular, C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 3 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 3 -C 12 -aryloxy (e.g. phenyloxy or 4-F-phenyloxy), or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl). Preferably R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl).

R 3b —in the pyrrolidine derivatives of formula (Ig)—is, in particular, hydrogen.

Y 1 —in the pyrrolidine derivatives of formula (Ig)—is, in particular, >CR 6 .

R 6 —in the pyrrolidine derivatives of formula (Ig)—is, in particular, hydrogen.

R 5a , R 5b —in the pyrrolidine derivatives of formula (Ig)—are, in particular, hydrogen.

Particular embodiments of the pyrrolidine derivatives of formula (If) result if:

R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl); R 2a , R 2b

are hydrogen;

R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 8d is hydrogen; R 16a is (optionally substituted C 3 -C 12 -aryl)-C 1 -C 4 -alkyl (e.g. benzyl or (2-Cl-phenyl)-methyl) or optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 3-F-phenyl, 2F-phenyl, 4-Cl-phenyl, or 2-Cl-phenyl); R 16b is hydrogen; and R 5a , R 5b

are hydrogen.

Preferably, R 1 —in the pyrrolidine derivatives of formula (Ig)—is an optionally substituted 5-membered heterocyclic ring containing 2 N which, in particular, is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 —in the pyrrolidine derivatives of formula (Ig)—is an optionally substituted 5-membered heterocyclic ring containing 3 N which, in particular, is optionally substituted 1,2,3-triazolyl.

In connection with R 1 and the pyrrolidine derivatives of formula (Ig), substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular includes 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, thiazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy-carbonyl and C 1 -C 6 -alkyl-carbonylamino. Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl. In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl). According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl.

In connection with R 3a and the pyrrolidine derivatives of formula (Ig), substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy. Preferably, the substituent(s) on C 6 -C 12 -aryl are independently selected from the group consisting of halogen.

According to a preferred embodiment, R 3a —in the pyrrolidine derivatives of formula (Ig)—is C 6 -C 12 -aryl, in particular phenyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. 4-F-phenyl).

In connection with R 16a , substituted C 6 -C 12 -aryl-C 1 -C 4 -alkyl in particular includes C 3 -C 12 -aryl-C 1 -C 4 -alkyl, such as benzyl, wherein C 6 -C 12 -aryl, such as phenyl, is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen.

In connection with R 16a , substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen.

According to a preferred embodiment, R 16a is C 6 -C 12 -aryl-C 1 -C 4 -alkyl or C 6 -C 12 -aryl, with C 6 -C 12 -aryl being optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. benzyl or (2-Cl-phenyl)-methyl and phenyl, 4-F-phenyl, 3-F-phenyl, 2F-phenyl, 4-Cl-phenyl, or 2-Cl-phenyl).

Preferred embodiments of the pyrrolidine derivatives of formula (Ig) result if:

R 1 is 1,3-diazolyl optionally substituted with halogen or C 1 -C 4 -alkyl (e.g. 1-methyl-1,3-diazol-4-yl); R 2a , R 26

are hydrogen;

R 3a is C 6 -C 12 aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. 4-F-phenyl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 8d is hydrogen; R 16a is C 6 -C 12 -aryl-C 1 -C 4 -alkyl or C 6 -C 12 -aryl, with C 6 -C 12 -aryl being optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. benzyl or (2-Cl-phenyl)-methyl and phenyl, 4-F-phenyl, 3-F-phenyl, 2F-phenyl, 4-Cl-phenyl, or 2-Cl-phenyl); R 16b is hydrogen; and R 5a , R 5b

are hydrogen.

According to a further embodiment, R 4 is —O(CR 9e R 9d ) n5 R 18 . Thus, the present invention relates to the pyrrolidine derivatives of the formula (Ih):

wherein R 1 , R 2a , R 2b , R 3a , R 3b , Y 1 , R 5a and R 5b are as defined herein, and

R 9c , R 9d

are independently hydrogen, halogen (e.g. F), or C 1 -C 6 -alkyl (e.g. methyl or ethyl);

n5 is 0, 1, 2, 3, or 4; and R 18 is hydrogen, optionally substituted C 1 -C 8 -alkyl (e.g. methyl, ethyl, iso-propyl or pentyl), optionally substituted C 3 -C 12 -cycloalkyl (e.g. cyclopropyl or cyclohexyl), C 1 -C 6 -alkylcarbonyl (e.g. methylcarbonyl), C 1 -C 6 -alkoxycarbonyl (e.g. methoxycarbonyl or n-butoxycarbonyl), halogenated C 1 -C 6 -alkoxycarbonyl (e.g. —C(O)OCF 3 ), C 6 -C 12 -aryloxycarbonyl (e.g. phenoxycarbonyl), C 1 -C 6 -alkylaminocarbonyl (e.g. n-propylaminocarbonyl or n-butylaminocarbonyl), (halogenated C 1 -C 4 -alkyl)aminocarbonyl (e.g. 2,2-diF-ethylaminocarbonyl), C 6 -C 12 -arylaminocarbonyl (e.g. phenylaminocarbonyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-F-phenyl, 4-F-phenyl, 4-Me-phenyl, 3-MeSO 2 -phenyl, or 4-MeSO 2 -phenyl), C 1 -C 6 -alkylamine (e.g. n-propylamine), (C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl)amino (e.g. cyclopropylmethyl-amino), (halogenated C 1 -C 6 -alkyl)amino (e.g. 2,2,2-triF-ethylamine), (C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl)amino (e.g. 2-methoxyethylamine), (C 6 -C 12 -aryl-C 1 -C 4 -alkyl)amino (e.g. benzylamine), C 1 -C 6 -dialkylamine (e.g. dimethylamino), optionally substituted C 6 -C 12 -arylamino (e.g. 4-Cl-phenylamine), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 4-CF 3 -pyrid-2-yl or 6-CF 3 -pyrimid-4-yl).

In particular, R 9c , R 9d are hydrogen.

In particular, n5 is 0, 1, or 2.

In particular, R 18 is hydrogen, optionally substituted C 1 -C 8 -alkyl (e.g. methyl, ethyl, isopropyl, or pentyl), C 1 -C 6 -alkoxycarbonyl (e.g. methoxycarbonyl or n-butoxycarbonyl), C 1 -C 6 -alkylaminocarbonyl (e.g. n-propylaminocarbonyl or n-butylaminocarbonyl), (halogenated C 1 -C 6 -alkyl)aminocarbonyl (e.g. 2,2-diF-ethylaminocarbonyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-F-phenyl, 4-F-phenyl, 4-Me-phenyl, 3-MeSO 2 -phenyl, or 4-MeSO 2 -phenyl), C 1 -C 6 -alkylamine (e.g. n-propylamine), (halogenated C 1 -C 6 -alkyl)amino (e.g. 2,2,2-triF-ethylamine), optionally substituted C 6 -C 12 -arylamine (e.g. 4-Cl-phenylamine), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 4-CF 3 -pyrid-2-yl or 6-CF 3 -pyrimid-4-yl).

R 2a , R 2b in pyrrolidine derivatives of formula (Ih) are, in particular, hydrogen.

R 3a —in the pyrrolidine derivatives of formula (Ih)—is, in particular, C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy or 4-F-phenoxy), or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl). Preferably, R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 3-F-azetidin-1-yl, morpholin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, 2-Me-piperidin-1-yl, 3-Me-piperidin-1-yl, 4-Me-piperidin-1-yl, 4-F-piperidin-1-yl, 4,4-diF-piperidin-1-yl, or azepan-1-yl).

R 3b —in the pyrrolidine derivatives of formula (Ih)—is, in particular, hydrogen.

Y 1 —in the pyrrolidine derivatives of formula (Ih)—is, in particular, >CR 6 .

R 6 —in the pyrrolidine derivatives of formula (Ih)—is, in particular, hydrogen or C 6 -C 12 -aryl-C 1 -C 4 -alkyl (e.g. benzyl). According to a particular embodiment, R 6 is hydrogen or benzyl. Preferably, R 6 is hydrogen.

R 5a , R 5b —in the pyrrolidine derivatives of formula (Ih)—are, in particular, hydrogen.

Particular embodiments of pyrrolidine derivatives of formula (Ih) result if:

R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl); R 2a , R 2b

are hydrogen;

R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 3-F-azetidin-1-yl, morpholin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, 2-Me-piperidin-1yl, 3-Me-piperidin-1yl, 4-Me-piperidin-1yl, 4-F-piperidin-1-yl, 4,4-diF-piperidin-1yl, or azepan-1-yl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 9c , R 9d

are hydrogen;

n5 is 0, 1, or 2; R 18 is hydrogen, optionally substituted C 1 -C 8 -alkyl (e.g. methyl, ethyl, iso-propyl, or pentyl), C 1 -C 6 -alkoxycarbonyl (e.g. methoxycarbonyl or butoxycarbonyl), C 1 -C 6 -alkylaminocarbonyl (e.g. n-propylaminocarbonyl or n-butylaminocarbonyl), (halogenated C 1 -C 4 -alkyl)aminocarbonyl (e.g. 2,2-diF-ethylaminocarbonyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-F-phenyl, 4-F-phenyl, 4-Me-phenyl, 3-MeSO 2 -phenyl, or 4-MeSO 2 -phenyl), C 1 -C 6 -alkylamine (e.g. n-propylamine), (halogenated C 1 -C 6 -alkyl)amino (e.g. 2,2,2-triF-ethylamine), optionally substituted C 6 -C 12 -arylamine (e.g. 4-Cl-phenylamine), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 4-CF 3 -pyrid-2-yl or 6-CF 3 -pyrimid-4-yl); and R 5a , R 5b

are hydrogen.

Preferably, R 1 —in the pyrrolidine derivatives of formula (Ih)—is an optionally substituted 5-membered heterocyclic ring containing 2 N which, in particular, is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 —in the pyrrolidine derivatives of formula (Ih)—is an optionally substituted 5-membered heterocyclic ring containing 3 N which, in particular, is optionally substituted 1,2,3-triazolyl.

In connection with R 1 and the pyrrolidine derivatives of formula (Ih), substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular includes 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, thiazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy-carbonyl and C 1 -C 6 -alkyl-carbonylamino. Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl. In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl). According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl.

In connection with R 3a and the pyrrolidine derivatives of formula (Ih), substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy. Preferably, the substituent(s) on C 6 -C 12 -aryl are independently selected from the group consisting of halogen.

In connection with R 3a and the pyrrolidine derivatives of formula (Ih), substituted C 3 -C 12 -heterocyclyl in particular includes C 3 -C 12 -heterocyclyl, such as azetidinyl, morpholinyl, pyrrolidinyl, piperidinyl, or azepanyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy. Preferably, the substituent(s) on C 3 -C 12 -heterocyclyl are independently selected from the group consisting of halogen and C 1 -C 4 -alkyl.

According to a preferred embodiment, R 3a —in the pyrrolidine derivatives of formula (Ih)—is C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. 4-F-phenyl), or C 3 -C 12 -heterocyclyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen and C 1 -C 4 -alkyl (e.g. 3-F-azetidin-1-yl, morpholin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, 2-Me-piperidin-1yl, 3-Me-piperidin-1yl, 4-Me-piperidin-1yl, 4-F-piperidin-1-yl, 4,4-diF-piperidin-1yl, or azepan-1-yl).

In connection with R 18 , substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkyl-sulfonyl.

In connection with R 18 , substituted C 6 -C 12 -arylamine in particular includes C 6 -C 12 -arylamine, such as phenylamine, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen.

In connection with R 18 , substituted C 3 -C 12 -heterocyclyl in particular includes C 3 -C 12 -heterocyclyl, such as 2-pyridyl or 4-pyrimidyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl.

According to a preferred embodiment, R 18 is hydrogen, C 1 -C 8 -alkyl (e.g. methyl, ethyl, iso-propyl, or pentyl), C 1 -C 6 -alkoxycarbonyl (e.g. methoxycarbonyl or n-butoxycarbonyl), C 1 -C 6 -alkylaminocarbonyl (e.g. n-propylaminocarbonyl or n-butylaminocarbonyl), (halogenated C 1 -C 4 -alkyl)aminocarbonyl (e.g. 2,2-diF-ethylaminocarbonyl), C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkyl-sulfonyl (e.g. phenyl, 3-F-phenyl, 4-F-phenyl, 4-Me-phenyl, 3-MeSO 2 -phenyl, or 4-MeSO 2 -phenyl), or C 1 -C 6 -alkylamine (e.g. n-propylamine), (halogenated C 1 -C 6 -alkyl)amino (e.g. 2,2,2-triF-ethylamine), C 6 -C 12 -arylamine optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. 4-Cl-phenylamine), or C 3 -C 12 -heterocyclyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl (e.g. 4-CF 3 -pyrid-2-yl or 6-CF 3 -pyrimid-4-yl).

Further preferred embodiments of the pyrrolidine derivatives of formula (Ih) result if:

R 1 is 1,3-diazolyl optionally substituted with halogen or C 1 -C 4 -alkyl (e.g. 1-methyl-1,3-diazol-4-yl); R 2a , R 2b

are hydrogen;

R 3a C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. 4-F-phenyl), or C 3 -C 12 -heterocyclyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen and C 1 -C 4 -alkyl (e.g. 3-F-azetidin-1-yl, morpholin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, 2-Me-piperidin-1yl, 3-Me-piperidin-1yl, 4-Me-piperidin-1yl, 4-F-piperidin-1-yl, 4,4-diF-piperidin-1-yl, or azepan-1-yl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 9c , R 9d

are hydrogen;

n5 is 0, 1, or 2; R 18 is hydrogen, C 1 -C 8 -alkyl (e.g. methyl, ethyl, iso-propyl, or pentyl), C 1 -C 6 -alkoxycarbonyl (e.g. methoxycarbonyl or n-butoxycarbonyl), C 1 -C 6 -alkylaminocarbonyl (e.g. n-propylaminocarbonyl or n-butylaminocarbonyl), (halogenated C 1 -C 4 -alkyl)aminocarbonyl (e.g. 2,2-diF-ethylaminocarbonyl), C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkyl-sulfonyl (e.g. phenyl, 3-F-phenyl, 4-F-phenyl, 4-Me-phenyl, 3-MeSO 2 -phenyl, or 4-MeSO 2 -phenyl), or C 1 -C 6 -alkylamine (e.g. n-propylamine), (halogenated C 1 -C 6 -alkyl)amino (e.g. 2,2,2-triF-ethylamine), C 6 -C 12 -arylamine optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. 4-Cl-phenylamine), or C 3 -C 12 -heterocyclyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl (e.g. 4-CF 3 -pyrid-2-yl or 6-CF 3 -pyrimid-4-yl); and R 5a , R 5b

are hydrogen.

According to a further embodiment, R 4 is —COR 19 . Thus, the present invention relates to the pyrrolidine derivatives of the formula (Ii):

wherein R 1 , R 2a , R 2b , R 3a , R 3b , Y 1 , R 5a and R 6b are as defined herein, and

R 19 is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-F-phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,4-diF-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 3-OCF 3 -phenyl, or 4-OCF 3 -phenyl) or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 2-pyridyl or 6-pyrimidyl).

In particular, R 19 is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-F-phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,4-diF-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 3-OCF 3 -phenyl, or 4-OCF 3 -phenyl).

R 2a , R 2b —in the pyrrolidine derivatives of formula (Ii)—are, in particular, hydrogen.

R 3a —in the pyrrolidine derivatives of formula (Ii)—is, in particular, C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy or 4-F-phenoxy), or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl). Preferably, R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl).

R 3b —in the pyrrolidine derivatives of formula (Ii)—is, in particular, hydrogen.

Y 1 —in the pyrrolidine derivatives of formula (Ii)—is, in particular, >CR 6 .

R 6 —in the pyrrolidine derivatives of formula (Ii)—is, in particular, hydrogen.

R 5a , R 5b —in the pyrrolidine derivatives of formula (Ii)—are, in particular, hydrogen.

Particular embodiments of the pyrrolidine derivatives of formula (Ii) result if

R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl); R 2a , R 2b

are hydrogen;

R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 19 is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-F-phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,4-diF-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 3-OCF 3 -phenyl, or 4-OCF 3 -phenyl); and R 5a , R 5b

are hydrogen.

Preferably, R 1 —in the pyrrolidine derivatives of formula (Ii)—is an optionally substituted 5-membered heterocyclic ring containing 2 N which, in particular, is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 —in the pyrrolidine derivatives of formula (Ii)—is an optionally substituted 5-membered heterocyclic ring containing 3 N which, in particular, is optionally substituted 1,2,3-triazolyl.

In connection with R 1 and the pyrrolidine derivatives of formula (Ii), substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular includes 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, thiazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy-carbonyl and C 1 -C 6 -alkyl-carbonylamino Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl. In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl). According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl.

In connection with R 3a and the pyrrolidine derivatives of formula (Ii), substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy. Preferably, the substituent(s) on C 6 -C 12 -aryl are independently selected from the group consisting of halogen.

According to a preferred embodiment, R 3a —in the pyrrolidine derivatives of formula (Ii)—is C 6 -C 12 -aryl, in particular phenyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. 4-F-phenyl).

In connection with R 19 , substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl and halogenated C 1 -C 4 -alkoxy.

According to a preferred embodiment, R 19 is C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl and halogenated C 1 -C 4 -alkoxy (e.g phenyl, 3-F-phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,4-diF-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 3-OCF 3 -phenyl, or 4-OCF 3 -phenyl).

Further preferred embodiments of the pyrrolidine derivatives of formula (Ii) result if:

R 1 is 1,3-diazolyl optionally substituted with halogen or C 1 -C 4 -alkyl (e.g. 1-methyl-1,3-diazol-4-yl); R 2a , R 2b

are hydrogen;

R 3a is C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. 4-F-phenyl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 19 C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl and halogenated C 1 -C 4 -alkoxy (e.g phenyl, 3-F-phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,4-diF-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 3-OCF 3 -phenyl, or 4-OCF 3 -phenyl); and R 5a , R 5b

are hydrogen.

According to a further particular embodiment R 4 is —CONR 20a R 20b . Thus, the present invention relates to the pyrrolidine derivatives of the formula (II):

wherein R 1 , R 2a , R 2b , R 3a , R 3b , Y 1 , R 5a and R 5b are as defined herein, and

R 20a is C 1 -C 8 -alkyl (e.g. n-propyl, n-butyl, hexyl, pentyl, or 6-Me-heptyl), (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. 2-methoxy-ethyl, 2-ethoxy-ethyl, 2-isopropyloxy-ethyl, 1-methyl-2-methoxy-ethyl, 3-methoxy-propyl, 3-ethoxy-propyl, or 3-isopropyloxy-propyl), (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl (e.g. benzyl, (4-F-phenyl)methyl, (3-Cl-phenyl)methyl, (4-Cl-phenyl)methy 1, (3,4-diF-phenyl)methy 1, (3-Cl-4-F-phenyl)methyl, (3-CF 3 -phenyl)methyl, (2-Cl-4-CF 3 -phenyl)methyl, (2-Cl-5-CF 3 -phenyl)methyl, or (3-OCF 3 -phenyl)methyl)), (optionally substituted C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl (e.g. (pyrid-2-yl)-methyl or (4-CF 3 -pyrid-2-yl)methyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,5-diCl-phenyl, 3-Cl-4-F-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-CN-phenyl, 3-OCF 3 -phenyl, 3-OCF 3 -4-F-phenyl, or 3-OCF 3 -4-Cl-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 4-CF 3 -pyrid-2-yl); and R 20b is hydrogen or C 1 -C 8 -alkyl (e.g. methyl, ethyl, or n-butyl).

In particular, R 20a is C 1 -C 8 -alkyl (e.g. n-propyl, n-butyl, hexyl, pentyl, or 6-Me-heptyl), (C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. 2-methoxy-ethyl, 2-ethoxy-ethyl, 2-isopropyloxy-ethyl, 1-methyl-2-methoxy-ethyl, 3-methoxy-propyl, 3-ethoxy-propyl, or 3-isopropyloxy-propyl), (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl (e.g. benzyl, (4-F-phenyl)methyl, (3-Cl-phenyl)methyl, (4-Cl-phenyl)methyl, (3,4-diF-phenyl)methyl, (3-Cl-4-F-phenyl)methyl, (3-CF 3 -phenyl)methyl, (2-Cl-4-CF 3 -phenyl)methyl, (2-Cl-5-CF 3 -phenyl)methyl, or (3-OCF 3 -phenyl)methyl)), (optionally substituted C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl (e.g. (pyrid-2-yl)-methyl or (4-CF 3 -pyrid-2-yl)methyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,5-diCl-phenyl, 3-Cl-4-F-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-CN-phenyl, 3-OCF 3 -phenyl, 3-OCF 3 -4-F-phenyl, or 3-OCF 3 -4-Cl-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 4-CF 3 -pyrid-2-yl).

R 2a , R 2b —in the pyrrolidine derivatives of formula (Il)—are, in particular, hydrogen.

R 3a —in the pyrrolidine derivatives of formula (Il)—is, in particular, C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy or 4-F-phenoxy), or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl). Preferably, R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl).

R 3b —in the pyrrolidine derivatives of formula (Il)—is, in particular, hydrogen.

Y 1 —in the pyrrolidine derivatives of formula (Il)—is, in particular, >CR 6 .

R 6 —in the pyrrolidine derivatives of formula (Il)—is, in particular, hydrogen.

R 5a , R 5b —in the pyrrolidine derivatives of formula (Il)—are, in particular, hydrogen.

Particular embodiments of the pyrrolidine derivatives of formula (Il) result if:

R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl); R 2a , R 2b

are hydrogen;

R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 20a is C 1 -C 8 -alkyl (e.g. n-propyl, n-butyl, hexyl, pentyl, or 6-Me-heptyl), (C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. 2-methoxy-ethyl, 2-ethoxy-ethyl, 2-isopropyloxy-ethyl, 1-methyl-2-methoxy-ethyl, 3-methoxy-propyl, 3-ethoxy-propyl, or 3-isopropyloxy-propyl), (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl (e.g. benzyl, (4-F-phenyl)methyl, (3-Cl-phenyl)methyl, (4-Cl-phenyl)methyl, (3,4-diF-phenyl)methyl, (3-Cl-4-F-phenyl)methyl, (3-CF 3 -phenyl)methyl, (2-Cl-4-CF 3 -phenyl)methyl, (2-Cl-5-CF 3 -phenyl)methyl, or (3-OCF 3 -phenyl)methyl)), (optionally substituted C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl (e.g. (pyrid-2-yl)-methyl or (4-CF 3 -pyrid-2-yl)methyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,5-diCl-phenyl, 3-Cl-4-F-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-CN-phenyl, 3-OCF 3 -phenyl, 3-OCF 3 -4-F-phenyl, or 3-OCF 3 -4-Cl-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 4-CF 3 -pyrid-2-yl); R 20b is hydrogen or C 1 -C 8 -alkyl (e.g. methyl, ethyl, or n-butyl); and R 5a , R 5b

are hydrogen.

Preferably, R 1 —in the pyrrolidine derivatives of formula (Il)—is an optionally substituted 5-membered heterocyclic ring containing 2 N which, in particular, is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 —in the pyrrolidine derivatives of formula (Il)—is an optionally substituted 5-membered heterocyclic ring containing 3 N which, in particular, is optionally substituted 1,2,3-triazolyl.

In connection with R 1 and the pyrrolidine derivatives of formula (Il), substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular includes 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, thiazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy-carbonyl and C 1 -C 6 -alkyl-carbonylamino. Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl. In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl). According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl.

In connection with R 3a and the pyrrolidine derivatives of formula (Il), substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy. Preferably, the substituent(s) on C 6 -C 12 -aryl are independently selected from the group consisting of halogen.

According to a preferred embodiment, R 3a —in the pyrrolidine derivatives of formula (Il)—is C 6 -C 12 -aryl, in particular phenyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. 4-F-phenyl).

In connection with R 20a , substituted C 6 -C 12 -aryl-C 1 -C 4 -alkyl in particular includes C 6 -C 12 -aryl-C 1 -C 4 -alkyl, such as benzyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, halogenated C 1 -C 4 -alkyl and halogenated C 1 -C 4 -alkoxy.

In connection with R 20a , substituted C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkyl in particular includes C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkyl, such as pyridyl-methyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl.

In connection with R 20a , substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, CN and halogenated C 1 -C 4 -alkoxy.

In connection with R 20a , substituted C 3 -C 12 -heterocyclyl in particular includes C 3 -C 12 -heterocyclyl, such as pyridyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl.

According to a preferred embodiment, R 20a is C 1 -C 8 -alkyl (e.g. n-propyl, n-butyl, hexyl, pentyl, or 6-Me-heptyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. 2-methoxy-ethyl, 2-ethoxy-ethyl, 2-isopropyloxy-ethyl, 1-methyl-2-methoxy-ethyl, 3-methoxy-propyl, 3-ethoxy-propyl, or 3-isopropyloxy-propyl), C 6 -C 12 -aryl-C 1 -C 4 -alkyl wherein C 6 -C 12 -aryl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, halogenated C 1 -C 4 -alkyl and halogenated C 1 -C 4 -alkoxy (e.g. benzyl, (4-F-phenyl)methyl, (3-Cl-phenyl)methyl, (4-Cl-phenyl)methyl, (3,4-diF-phenyl)methyl, (3-Cl-4-F-phenyl)methyl, (3-CF 3 -phenyl)methyl, (2-Cl-4-CF 3 -phenyl)methyl, (2-Cl-5-CF 3 -phenyl)methyl, or (3-OCF 3 -phenyl)methyl)), or C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkyl wherein C 3 -C 12 -heterocyclyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl (e.g. (pyrid-2-yl)-methyl or (4-CF 3 -pyrid-2-yl)methyl), or C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, CN and halogenated C 1 -C 4 -alkoxy (e.g. phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,5-diCl-phenyl, 3-Cl-4-F-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-CN-phenyl, 3-OCF 3 -phenyl, 3-OCF 3 -4-F-phenyl, or 3-OCF 3 -4-Cl-phenyl), or C 3 -C 12 -heterocyclyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl (e.g. 4-CF 3 -pyrid-2-yl).

Further preferred embodiments of the pyrrolidine derivatives of formula (Il) result if

R 1 is 1,3-diazolyl optionally substituted with halogen or C 1 -C 4 -alkyl (e.g. 1-methyl-1,3-diazol-4-yl); R 2a , R 2b

are hydrogen;

R 3a is C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. 4-F-phenyl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 20a is C 1 -C 8 -alkyl (e.g. n-propyl, n-butyl, hexyl, pentyl, or 6-Me-heptyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. 2-methoxy-ethyl, 2-ethoxy-ethyl, 2-isopropyloxy-ethyl, 1-methyl-2-methoxy-ethyl, 3-methoxy-propyl, 3-ethoxy-propyl, or 3-isopropyloxy-propyl), C 6 -C 12 -aryl-C 1 -C 4 -alkyl wherein C 6 -C 12 -aryl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, halogenated C 1 -C 4 -alkyl and halogenated C 1 -C 4 -alkoxy (e.g. benzyl, (4-F-phenyl)methyl, (3-Cl-phenyl)methyl, (4-Cl-phenyl)methyl, (3,4-diF-phenyl)methyl, (3-Cl-4-F-phenyl)methyl, (3-CF 3 -phenyl)methyl, (2-Cl-4-CF 3 -phenyl)methyl, (2-Cl-5-CF 3 -phenyl)methyl, or (3-OCF 3 -phenyl)methyl)), or C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkyl wherein C 3 -C 12 -heterocyclyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl (e.g. (pyrid-2-yl)-methyl or (4-CF 3 -pyrid-2-yl)methyl), or C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, CN and halogenated C 1 -C 4 -alkoxy (e.g. phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,5-diCl-phenyl, 3-Cl-4-F-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-CN-phenyl, 3-OCF 3 -phenyl, 3-OCF 3 -4-F-phenyl, or 3-OCF 3 -4-Cl-phenyl), or C 3 -C 12 -heterocyclyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogenated C 1 -C 4 -alkyl (e.g. 4-CF 3 -pyrid-2-yl); R 20b is hydrogen or C 1 -C 8 -alkyl (e.g. n-butyl); and R 5a , R 5b

are hydrogen.

According to a further embodiment, R 4 is —SO 2 R 21 . Thus, the present invention relates to the pyrrolidine derivatives of the formula (Im):

wherein R 1 , R 2a , R 3a , R 3b , Y 1 , R 5a and R 5b are as defined herein, and

R 21 is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, or 4-Me-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 2-pyridyl).

In particular, R 21 is C 6 -C 12 -aryl (e.g. phenyl).

R 2a , R 2b —in the pyrrolidine derivatives of formula (Im)—are, in particular, hydrogen.

R 3a —in the pyrrolidine derivatives of formula (Im)—is, in particular, C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy or 4-F-phenoxy), or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl). Preferably, R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl).

R 3b —in the pyrrolidine derivatives of formula (Im)—is, in particular, hydrogen. Y 1 —in the pyrrolidine derivatives of formula (Im)—is, in particular, >CR 6 . R 6 —in the pyrrolidine derivatives of formula (Im)—is, in particular, hydrogen. R 5a , R 5b —in the pyrrolidine derivatives of formula (Im)—are, in particular, hydrogen.

Particular embodiments of the pyrrolidine derivatives of formula (Im) result if:

R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl); R 2a , R 2b

are hydrogen;

R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl);

R 3b is hydrogen;

Y 1 is >CR 6 ; R 6 is hydrogen; R 5a , R 5b

are hydrogen; and

R 21 is C 6 -C 12 -aryl (e.g. phenyl).

Preferably, R 1 —in the pyrrolidine derivatives of formula (Im)—is an optionally substituted 5-membered heterocyclic ring containing 2 N which, in particular, is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 —in the pyrrolidine derivatives of formula (Im)—is an optionally substituted 5-membered heterocyclic ring containing 3 N which, in particular, is optionally substituted 1,2,3-triazolyl.

In connection with R 1 and the pyrrolidine derivatives of formula (Im), substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular includes 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, thiazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy-carbonyl and C 1 -C 6 -alkyl-carbonylamino. Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl. In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl). According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl.

According to a preferred embodiment, R 3a —in the pyrrolidine derivatives of formula (Im)—is C 6 -C 12 -aryl (e.g. phenyl).

Further preferred embodiments of the pyrrolidine derivatives of formula (Im) result if:

R 1 is 1,3-diazolyl optionally substituted with halogen or C 1 -C 4 -alkyl (e.g. 1-methyl-1,3-diazol-4-yl); R 2a , R 2b

are hydrogen;

R 3a is C 6 -C 12 -aryl (e.g. phenyl); R 3b is hydrogen; Y 1 is >CR 6 ; R 6 is hydrogen; R 21 is C 6 -C 12 -aryl (e.g. phenyl); and R 5a , R 5b

are hydrogen.

According to a further embodiment R 4 is optionally substituted C 3 -C 12 -heterocyclyl (e.g. 4-chloroisoindolin-1-one; 7-(trifluoromethyl)-3,4-dihydro-1H-quinazolin-2-on-1-yl, 4-butyl-1,2,3-triazol-1-yl, 1-propyl-1,2,3-triazol-4-yl, 5-(4-CF 3 -phenyl)-4,5-dihydroisooxazol-3-yl, 5-(4-CF 3 -phenyl)-oxazol-2-yl, or 5-(3-Cl-phenyl)-imidazol-2-yl).

R 3a —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 3 -C 12 -heterocyclyl—is, in particular, C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 3 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (e.g. cyclopropylmethoxy or cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy or 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy or 4-F-phenoxy), or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl). Preferably, R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl) or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl).

R 3b —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 3 -C 12 -heterocyclyl—is, in particular, hydrogen.

Y 1 —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 3 -C 12 -heterocyclyl—is, in particular, >CR 6 .

R 6 —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 3 -C 12 -heterocyclyl—is, in particular, hydrogen.

R 5a , R 5b —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 3 -C 12 -heterocyclyl—are, in particular, hydrogen.

Particular embodiments of the pyrrolidine derivatives of the invention result if:

R 1 is an optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-2-methoxycarbonyl-pyrrol-5-yl, 1-methyl-pyrrol-3-yl, 5-methyl-1,2-oxazol-4-yl, 3,5-dimethyl-1,2-oxazol-4-yl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,3-diazol-4-yl, 1-methyl-1,2-diazol-5-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-4-yl, 1,5-dimethyl-1,2-diazol-4-yl, 1,3-dimethyl-1,2-diazol-5-yl, 1,3-dimethyl-5-Cl-1,2-diazol-4-yl, 1-isopropyl-3-methyl-1,2-diazol-4-yl, 1-Me-3-CF 3 -1,2-diazol-4-yl, 1-cyclopentyl-3-Me-1,2-diazol-4-yl, 1,3,5-trimethyl-1,2-diazol-4-yl, 1-CHF 2 -3,5-dimethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-5-yl, 1-methyl-5-Cl-1,3-diazol-4-yl, 1-Me-1,2,3-triazol-4-yl, 2,4-dimethyl-1,3-thiazol-5-yl, or 2-methylcarbonylamino-1,3-thiazol-5-yl); R 2a , R 2b

are hydrogen;

R 3a is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl) or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl); R 3b is hydrogen; R 4 is optionally substituted C 3 -C 12 -heterocyclyl (e.g. 4-chloroisoindolin-1-one; 7-(trifluoromethyl)-3,4-dihydro-1H-quinazolin-2-on-1-yl, 4-butyl-1,2,3-triazol-1-yl, 1-propyl-1,2,3-triazol-4-yl, 5-(4-CF 3 -phenyl)-4,5-dihydroisooxazol-3-yl, 5-(4-CF 3 -phenyl)-oxazol-2-yl, or 5-(3-Cl-phenyl)-imidazol-2-yl); Y 1 is >CR 6 ; R 6 is hydrogen; and R 5a , R 5b

are hydrogen.

Preferably, R 1 —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 3 -C 12 -heterocyclyl—is an optionally substituted 5-membered heterocyclic ring containing 2 N which, in particular, is optionally substituted 1,3-diazolyl.

According to a further preferred embodiment, R 1 —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 3 -C 12 -heterocyclyl—is an optionally substituted 5-membered heterocyclic ring containing 3 N which, in particular, is optionally substituted 1,2,3-triazolyl.

In connection with R 1 and the pyrrolidine derivatives wherein R 4 is optionally substituted C 3 -C 12 -heterocyclyl, substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S in particular includes 5-membered heterocyclic rings, such as pyrrolyl, isoxazolyl, pyrazolyl, imidazolyl, thiazolyl and triazolyl, which are substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy-carbonyl and C 1 -C 6 -alkyl-carbonylamino. Preferably, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of halogen and C 1 -C 6 -alkyl. In particular, the substituent(s) on the heterocyclic ring are independently selected from the group consisting of C 1 -C 6 -alkyl, especially C 1 -C 4 -alkyl (e.g. methyl). According to a particular embodiment, 1,3-diazolyl is substituted with halogen or C 1 -C 6 -alkyl as described herein. According to a specific embodiment, R 1 is 1-methyl-1,3-diazol-4-yl.

In connection with R 3a and the pyrrolidine derivatives wherein R 4 is optionally substituted C 3 -C 12 -heterocyclyl, substituted C 6 -C 12 -aryl in particular includes C 6 -C 12 -aryl, such as phenyl or naphthyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and C 1 -C 4 -alkoxy. Preferably, the substituent(s) on C 6 -C 12 -aryl are independently selected from the group consisting of halogen.

In connection with R 3a and the pyrrolidine derivatives wherein R 4 is optionally substituted C 3 -C 12 -heterocyclyl, substituted C 3 -C 12 -heterocyclyl in particular includes C 3 -C 12 -heterocyclyl, such as pyridyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and halogenated C 1 -C 4 -alkyl.

According to a preferred embodiment, R 3a —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 3 -C 12 -heterocyclyl—is C 6 -C 12 -aryl, in particular phenyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen (e.g. phenyl, 4-F-phenyl), or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl).

In connection with R 4 , substituted C 3 -C 12 -heterocyclyl in particular includes C 3 -C 12 -heterocyclyl, such as triazolyl or isoindolinonyl, which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 4 -alkyl and halogenated C 1 -C 4 -alkyl.

According to a preferred embodiment, R 4 —in the pyrrolidine derivatives wherein R 4 is optionally substituted C 3 -C 12 -heterocyclyl—is C 3 -C 12 -heterocyclyl substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl and halogenated C 1 -C 4 -alkyl (e.g. 4-chloroisoindolin-1-onyl, 7-(trifluoromethyl)-3,4-dihydro-1H-quinazolin-2-on-1-yl, 4-butyl-1,2,3-triazol-1-yl, or 1-propyl-1,2,3-triazol-4-yl).

Further preferred embodiments of the pyrrolidine derivatives wherein R 4 is optionally substituted C 3 -C 12 -heterocyclyl result if:

R 1 is 1,3-diazolyl optionally substituted with halogen or C 1 -C 4 -alkyl (e.g. 1-methyl-1,3-diazol-4-yl); R 2a , R 2b

are hydrogen;

R 3a is C 6 -C 12 -aryl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, or C 3 -C 12 -heterocyclyl (e.g. pyrid-2-yl); R 3b is hydrogen; R 4 is C 3 -C 12 -heterocyclyl substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, C 1 -C 6 -alkyl and halogenated C 1 -C 4 -alkyl (e.g. 4-chloroisoindolin-1-one; 7-(trifluoromethyl)-3,4-dihydro-1H-quinazolin-2-on-1-yl, 4-butyl-1,2,3-triazol-1-yl, 1-propyl-1,2,3-triazol-4-yl, 5-(4-CF 3 -phenyl)-4,5-dihydroisooxazol-3-yl, 5-(4-CF 3 -phenyl)-oxazol-2-yl, or 5-(3-Cl-phenyl)-imidazol-2-yl); Y 1 is >CR 6 ; R 6 is hydrogen; and R 5a , R 5b

are hydrogen.

Particular embodiments of pyrrolidine derivatives of the invention result if

R 1 is optionally substituted 5-membered heterocyclic ring containing at least 1 N ring atom and optionally 1 or 2 further heteroatoms selected from N, O and S (e.g. 1-methyl-1,3-diazol-4-yl or 1-methyl-1,2,3-triazol-4-yl; R 2a , R 2b

are hydrogen;

R 3a is C 3 -C 12 -cycloalkyl (cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-Cl-phenyl, 2-Br-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 4-OMe-phenyl, or 2,4,5-trifluoro-phenyl)hydroxy, C 1 -C 6 -alkoxy (e.g. methoxy, ethoxy, n-propyloxy, iso-propoxy, or iso-butoxy) C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkoxy (cyclopropylmethoxy, cyclohexylmethoxy), C 2 -C 6 -alkenyloxy (e.g. allyloxy, 2-methylprop-2-en-1-oxy), C 6 -C 12 -aryl-C 1 -C 4 -alkoxy (e.g. benzyloxy), optionally substituted C 6 -C 12 -aryloxy (e.g. phenoxy, 4-F-phenoxy); R 3b is hydrogen or hydroxy; Y 1 is >CR 6 — or >N—; R 6 is hydrogen, C 1 -C 6 -alkyl (e.g. methyl or ethyl), C 3 -C 12 -aryl-C 1 -C 21 -alkyl (e.g. benzyl or phenethyl), hydroxy-C 1 -C 6 -alkyl (e.g. —CH 2 OH, or —(CH 2 ) 2 OH), or hydroxy; R 4 is —(CR 7a R 7b ) n1 OR 10 , —(CR 7c R 7d ) n2 NR 11a R 11b , —(CR 7e R 7f ) n3 R 12 , optionally substituted C 6 -C 12 -aryl, —NR 8a (CR 9a R 9b ) n4 R 13 , —NR 8b COR 14 , —NR 8c COOR 15 , —NR 8d CONR 16a R 16b , —O(CR 9c R 9d ) n5 R 18 , —COR 19 , —CONR 20a R 20b , —SO 2 R 21 , or optionally substituted C 3 -C 12 heterocyclyl (e.g. 1-propyl-1,2,3-triazol-4-yl, 4-butyl-1,2,3-triazolyl-1-yl, 4-chloroisoindolin-1-one, or 7-(trifluoromethyl)-3,4-dihydro-1H-quinazolin-2-on-1-yl); R 7a , R 7b

are hydrogen, or

n1 is 1; R 10 is hydrogen, optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-F-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, or 3-OCF 3 -phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 6-CF 3 -pyrimid-4-yl, 4-CF 3 -pyrid-2-yl, or 2-CF 3 -pyrid-4-yl); R 7c , R 7d

are hydrogen, or

n2 is 1; R 11a is C 1 -C 8 -alkyl (e.g. methyl, ethyl, n-propyl, n-butyl, or n-heptyl), C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl) C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (2-methoxy-ethyl, 2-ethoxy-ethyl, 2-isopropyloxy-ethyl, 1-methyl-2-methoxy-ethyl, 3-methoxy-propyl, 3-ethoxy-propyl, or 3-isopropyloxy-propyl), C 6 -C 12 -aryl-C 1 -C 4 -alkyl (e.g. benzyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,5-diCl-phenyl, 3-Cl-4-F-phenyl, 3-Me-phenyl, 3-(aminomethyl)-phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-OCF 3 -phenyl, 3-OCF 3 -4-F-phenyl, 3-OCF 3 -4-Cl-phenyl, or 3-(aminocarbonyl)-phenyl); R 11b is hydrogen; R 7e , R 7f

are hydrogen, or

n3 is 1; R 12 is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-Cl-phenyl, or 3-Br-phenyl) or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 4-CF 3 -pyrid-2-yl or 1-propyl-1,2,3-triazol-4-yl); R 8a , R 8b , R 8c , R 8d , R 8e

are independently hydrogen or C 1 -C 6 -alkyl (e.g. pentyl or hexyl), or

R 6 and one of R 8a , R 8b , R 8c , R 8d , or R 8e

together are optionally substituted C 1 -C 5 -alkylene, wherein one or more —CH 2 — of C 1 -C 5 -alkylene may be independently replaced by a an oxygen atom or C═O;

R 9a , R 9b

are independently hydrogen, halogen, C 1 -C 6 -alkyl (e.g. methyl, ethyl, tert-butyl, 2,3-dimethyl-propyl), or C 1 -C 6 -alkoxy (e.g. methoxy or ethoxy);

n4 is 0, 1, 2, 3, or 4; R 13 is hydrogen, C 1 -C 8 -alkyl (e.g. methyl, ethyl, n-butyl, tert-butyl, pentyl, or hexyl), halogenated C 1 -C 6 -alkyl (e.g. —CF 3 or —CF 2 Me), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. methoxy-methyl), optionally substituted C 3 -C 12 -cycloalkyl (e.g. cyclopropyl, 2-propyl-cyclopropyl, 1-(methoxymethyl)-cyclopropyl, 2-phenyl-cyclopropyl, cyclopentyl, 1-methyl-cyclohexyl, 1-CF 3 -cyclopropyl, 4-CF 3 -cyclohexyl, or 4,4-diF-cyclohexyl), C 2 -C 6 -alkenyl (e.g. hex-2-enyl), optionally substituted C 3 -C 6 -cycloalkenyl (e.g. 1,3,3-trimethylcyclohexen-2-yl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-F-phenyl, 4-F-phenyl, 3-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl, 3,4-diF-phenyl, 2,3,4-triF-phenyl, 2,4-diCl-phenyl, 3,4-diCl-phenyl, 3-F-4-Cl-phenyl, 3-Cl-4-F-phenyl, 3-Cl-5-F-phenyl, 3,4-diF-5-Cl-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 3-iPr-phenyl, 3-tBu-phenyl, 3-Me-4-F-phenyl, 3-Me-4-Cl-phenyl, 3-iPr-4 Cl-phenyl, 3-(1-OH-1-CF 3 -Et)-phenyl, 3-CHF 2 -4-F-phenyl, 2-CF 3 -phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 2-F-3-CF 3 -phenyl, 2-F-5-CF 3 -phenyl, 3-F-5-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-CF 3 -4-Cl-phenyl, 3-Me-4-CF 3 -phenyl, 3-CF 3 -4-Me-phenyl, 3,4-diCF 3 -phenyl, 4-OMe-phenyl, 3-OiPr-phenyl, 3-CF 3 -4-OMe-phenyl, 3-OCH 2 CF 3 -phenyl, 3-OCF 3 -phenyl, 2-OCHF 2 -5-Cl-phenyl, 3-OCF 3 -4-F-phenyl, 3-OCF 3 -4-Cl-phenyl, 3-OBn-phenyl, 3-OPh-phenyl, 3-CN-phenyl, 4-CN-phenyl, 2-F-3-CN-phenyl, 2-F-4-CN-phenyl, 3-F-4-CN-phenyl, 2-F-5-CN-phenyl, 3-F-5-CN-phenyl, 3-Cl-4-CN-phenyl, 2-Cl-5-CN-phenyl, 3-Cl-5-CN-phenyl, 3-CN-4-Cl-phenyl, 2-Me-3-CN-phenyl, 2-Me-5-CN-phenyl, 3-Me-5-CN-phenyl, 3-CF 3 -4-CN-phenyl, 3-CN-4-OMe-phenyl, 3-CN-4-OCF 3 -phenyl, 3-phenyl-phenyl, 3-MeSO 2 -phenyl, 3-(piperidin-4-yl)-phenyl, 2-methylcarbonylamino-5-Cl-phenyl, 3-(pyrid-2-yl)-phenyl, 3-(pyrid-3-yl)-4F-phenyl, 3-(pyrid-4-yl)-4F-phenyl, 3-(pyrimid-5-yl)-4F-phenyl, indan-5-yl, or tetralin-6-yl), C 1 -C 6 -alkoxy (e.g. methoxy, ethoxy, or n-propoxy), C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy (e.g. 2-methoxy-ethoxy), optionally substituted C 6 -C 12 -aryloxy (e.g. 4-F-phenoxy or 4-tertbutyl-phenoxy), optionally substituted C 3 -C 12 -heterocyclyl (e.g. e.g. propyl-furan-2-yl, 2-CF 3 -furan-5-yl, 1,2-dimethyl-5-CN-pyrrol-3-yl, 2,3-diMe-thiophen-5-yl, 2-Me-thiophen-5-yl, 2-Cl-thiophen-5-yl, 3-Cl-thiophen-2-yl, 2,5-diCl-thiophen-3-yl, 2-tetrahydropyranyl-thiophen-5-yl, 1,3-thiazol-5-yl, 4-Me-1,3-thiazol-2-yl, 2-Me-1,3-thiazol-5-yl, 5-Me-1,3-thiazol-2-yl, 4-Me-1,3-thiazol-5-yl, 2-Me-1,3-thiazol-4-yl, 4-isopropyl-1,3-thiazol-2-yl, 2-phenyl-4-Me-1,3-thiazol-5-yl, 4-phenyl-1,3-thiazol-5-yl, 2-(4-Me-phenyl)-1,3-thiazol-5-yl, 4-(4-F-phenyl)-1,3-thiazol-2-yl, thiazol-4-yl, 4-Cl-1,3-thiazol-5-yl, 2-Br-1,3-thiazol-5-yl, 4-Br-1,3-thiazol-2-yl, 4-Me-5-Br-1,3-thiazol-2-yl, 2,4-dichloro-1,3-thiazol-5-yl, 1,5-dimethyl-1,2,4-triazol-3-yl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, 4-F-pyrid-2-yl, 5-F-pyrid-2-yl, 6-F-pyrid-2-yl, 4-Cl-pyrid-2-yl, 5-F-pyrid-3-yl, 2-F-pyrid-4-yl, 3,5-diCl-pyrid-4-yl, 4,5-diCl-pyrid-2-yl, 2-Cl-3F-pyrid-4-yl, 5-Me-pyrid-2-yl, 4-iPr-pyrid-2-yl, 4-Me-5-F-pyrid-2-yl, 4-CF 3 -pyrid 2-yl-5-CF 3 -pyrid-2-yl, 6-CF 3 -pyrid-2-yl, 5-CF 3 -pyrid-3-yl, 2-CF 3 -pyrid-4-yl, 3-F-4-CF 3 -pyrid-2-yl, 4-CF 3 -5-F-pyrid-2-yl 4-CF 3 -5-Cl-pyrid-2-yl, 3,5-diF-4-CF 3 -pyrid-2-yl, 4-OCH 2 CF 3 -pyrid-2-yl, 4-OCH 2 CF 3 -5-F-pyrid-2-yl, 4-OCH 2 CF 3 -5-Cl-pyrid-2-yl, 4-OBn-5-F-pyrid-2-yl, 3-(4-F-phenyl)-pyrid-5-yl, 2-(4-F-phenyl)-pyrid-3-yl, 4-(pyrid-4-yl)-pyrid-2-yl, 4-(pyrid-3-yl)-pyrid-2-yl, 5-cyclopropyl-pyraz-2-yl, 5-cyclobutyl-pyraz-2-yl, 5-pyrrolidin-pyraz-2-yl, pyridaz-3-yl, 4-CF 3 -pyridaz-3-yl, 5-CF 3 -pyridaz-3-yl, 5-F-pyrimid-2-yl, 6-Cl-pyrimid-4-yl, 6-Me-pyrimid-4-yl, 6-Et-pyrimid-4-yl, 6-Pr-pyrimid-4-yl, 6-iPr-pyrimid-4-yl, 2-Me-6-Cl-pyrimid-4-yl, 2-Me-6-CF 3 -pyrimid-4-yl, 2-OMe-6-CF 3 -pyrimid-4-yl, 2-OMe-pyrimid-4-yl, 6-OMe-pyrimid-4-yl, 6-OEt-pyrimid-4-yl, 6-OPr-pyrimid-4-yl, 6-OiPr-pyrimid-4-yl, 6-OiBu-pyrimid-4-yl, 6-OBu-pyrimid-4-yl, 6-OBn-pyrimid-4-yl, 6-cyclobutyloxy-pyrimid-4-yl, 6-cyclopentyloxy-pyrimid-4-yl, 6-cyclohexyloxy-pyrimid-4-yl, 6-cyclopropyl-pyrimid-4-yl, 6-phenyl-pyrimid-4-yl, 6-(2-F-phenyl)-pyrimid-4-yl, 6-(3-F-phenyl)-pyrimid-4-yl, 6-(4-F-phenyl)-pyrimid-4-yl, 6-Cl-pyrimid-4-yl, 6-(2-Me-phenyl)pyrimid-4-yl, 6-(3-Me-phenyl)-pyrimid-4-yl, 6-(4-Me-phenyl)-pyrimid-4-yl, 6-(3-Cl-phenyl)-pyrimid-4-yl, 6-(4-Cl-phenyl)-pyrimid-4-yl, 2-(morpholin-1-yl)-pyrimid-4-yl, 6-(azetidin-3-yl-methoxy)-pyrimid-4-yl, 6-(pyrrolidin-3-yl-methoxy)-pyrimid-4-yl, 6-(pyrrolidin-2-yl-methoxy)-pyrimid-4-yl, benzofuran-5-yl, 2-Me-benzofuran-3-yl, 2-Et-benzofuran-3-yl, benzothiophen-5-yl, benzothiophen-6-yl, 5-Me-benzothiophen-2-yl, 5-F-benzothiophen-2-yl, 3-Cl-benzothiophen-2-yl, benzothiazol-2-yl, isoquinolin-6-yl, isoquinolin-7-yl, quinolin-6-yl, quinolin-7-yl, 4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl, dihydrobenzofuran-5-yl, 7H-pyrrolo[2,3-d]pyrimidin-4-yl, pyrazolo[1,5-a]pyridine-3-yl, pyrazolo[1,5-a]pyridine-7-yl, imidazo[1,2-a]pyridin-8-yl, 5-methyl-imidazo[1,2-a]pyridin-3-yl, 6-chloro-2-methyl-imidazo[1,2-a]pyridin-3-yl, 6-bromo-2-methyl-imidazo[1,2-a]pyridin-3-yl, thieno[2,3-b]pyridin-2-yl, N-benzyl-indolin-6-yl, indolinon-4-yl, chroman-6-yl, 4,4-dimethylchroman-6-yl, 4,4-dimethyl-1,3-dioxan-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl, 4-Me-tetrahydropyran-4-yl, 2,2-diMe-tetrahydropyran-4-yl, 1-isopropyl-piperidin-4-yl, or 2-CF 3 -piperazin-5-yl), or tri-(C 1 -C 4 -alkyl)-silyloxy; R 14 is C 1 -C 8 -alkyl (e.g. pentyl, n-butyl, or hexyl), halogenated C 1 -C 6 -alkyl (e.g. 1,1-diF-butyl, 3,3-diF-butyl, 4,4,4-triF-butyl, 1,1-diF-pentyl, or 4,4-diF-pentyl), (optionally substituted C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl), hydroxy-C 1 -C 6 -alkyl (e.g. hydroxylmethyl or 1-hydroxy-pentyl), (optionally substituted C 6 -C 12 -aryloxy)-C 1 -C 4 -alkyl (e.g. phenoxy-methyl or (4-F-phenoxy)-methyl), C 1 -C 6 -alkylcarbonyl-C 1 -C 4 -alkyl (e.g. 2-methylcarbonyl-ethyl or 3-methylcarbonyl-propyl), C 1 -C 6 -alkoxycarbonyl-C 1 -C 4 -alkyl (e.g. 3-methoxycarbonyl-propyl), optionally substituted C 3 -C 12 -cycloalkyl (e.g. 1-CF 3 -cyclopropyl or 4-CF 3 -cyclohexyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diCl-phenyl, 3,5-diCl-phenyl, 2-Cl-4-F-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-CF 3 -phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 2-Cl-4-CF 3 -phenyl, 2-OMe-phenyl, 3-OMe-phenyl, 2-CN-phenyl, or 3-CN-phenyl, 4-CN-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 3-Cl-pyridazin-6-yl, 2-Cl-pyrazin-5-yl, or 2-CF 3 -pyrazin-5-yl); R 15 is C 1 -C 6 -alkyl (e.g. ethyl, n-propyl, n-butyl, iso-butyl, or tert-bu) or C 6 -C 12 -aryl (e.g. phenyl); R 16a is (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl (e.g. benzyl or (2-Cl-phenyl)-methyl) or optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 3-F-phenyl, 2F-phenyl, 4-Cl-phenyl, or 2-Cl-phenyl); R 16b is hydrogen; R 9c , R 9d

are hydrogen;

n5 is 0, 1, or 2; R 18 is hydrogen, optionally substituted C 1 -C 8 -alkyl (e.g. methyl, ethyl, iso-propyl, or pentyl), C 1 -C 6 -alkoxycarbonyl (e.g. methoxycarbonyl or n-butoxycarbonyl), C 1 -C 6 -alkylaminocarbonyl (e.g. n-propylaminocarbonyl or n-butylaminocarbonyl), (halogenated C 1 -C 4 -alkyl)aminocarbonyl (e.g. 2,2-diF-ethylaminocarbonyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-F-phenyl, 4-F-phenyl, 4-Me-phenyl, 3-MeSO 2 -phenyl, or 4-MeSO 2 -phenyl), C 1 -C 6 -alkylamine (e.g. propylamine), (halogenated C 1 -C 6 -alkyl)amino (e.g. 2,2,2-triF-ethylamine), optionally substituted C 6 -C 12 -arylamine (e.g. 4-Cl-phenylamine), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 4-CF 3 -pyrid-2-yl or 6-CF 3 -pyrimid-4-yl); R 19 is optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 3-F-phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,4-diF-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 3-OCF 3 -phenyl, or 4-OCF 3 -phenyl); R 20a is C 1 -C 8 -alkyl (e.g. n-propyl, n-butyl, hexyl, pentyl, or 6-Me-heptyl), (C 3 -C 12 -cycloalkyl)-C 1 -C 4 -alkyl (e.g. cyclopropyl-methyl), C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl (e.g. 2-methoxy-ethyl, 2-ethoxy-ethyl, 2-isopropoxy-ethyl, 1-methyl-2-methoxy-ethyl, 3-methoxy-propyl, 3-ethoxy-propyl, or 3-isopropoxy-propyl), (optionally substituted C 6 -C 12 -aryl)-C 1 -C 4 -alkyl (e.g. benzyl, (4-F-phenyl)methyl, (3-Cl-phenyl)methyl, (4-Cl-phenyl)methyl, (3,4-diF-phenyl)methyl, (3-Cl-4-F-phenyl)methyl, (3-CF 3 -phenyl)methyl, (2-Cl-4-CF 3 -phenyl)methyl, (2-Cl-5-CF 3 -phenyl)methyl, or (3-OCF 3 -phenyl)methyl)), (optionally substituted C 3 -C 12 -heterocyclyl)-C 1 -C 4 -alkyl (e.g. (pyrid-2-yl)-methyl or (4-CF 3 -pyrid-2-yl)methyl), optionally substituted C 6 -C 12 -aryl (e.g. phenyl, 4-F-phenyl, 3-Cl-phenyl, 3,5-diCl-phenyl, 3-Cl-4-F-phenyl, 3-Me-phenyl, 3-CF 3 -phenyl, 4-CF 3 -phenyl, 2-Cl-3-CF 3 -phenyl, 3-Cl-4-CF 3 -phenyl, 3-CF 3 -4-F-phenyl, 3-CN-phenyl, 3-OCF 3 -phenyl, 3-OCF 3 -4-F-phenyl, or 3-OCF 3 -4-Cl-phenyl), or optionally substituted C 3 -C 12 -heterocyclyl (e.g. 4-CF 3 -pyrid-2-yl). R 20b is hydrogen or C 1 -C 8 -alkyl (e.g. methyl, ethyl, or n-butyl); R 21 is C 6 -C 12 -aryl (e.g phenyl); and R 5a , R 5b

are hydrogen; or

R 5a , R 5b

together with the carbon atom to which they are bound may form a C═O.

Further particular compounds of the present invention are the individual pyrrolidine derivatives of the formula (Id2) as listed in the following tables 1 to 8 and physiologically tolerated salts thereof:

Table 1 Compounds of the formula (Id2) wherein X is ═CH—, Z is ═CR 13c —, R 13c is H and the combination of R 1 , R 3a and R 13b for a compound in each case corresponds to one line of Table A (A-1 to A-344).

Table 2 Compounds of the formula (Id2) wherein X is ═CH—, Z is ═CR 13c —, R 13c is F and the combination of R 1 , R 3a and R 13b for a compound in each case corresponds to one line of Table A (A-1 to A-344).

Table 3 Compounds of the formula (Id2) wherein X is ═CH—, Z is ═CR 13c —, R 13c is Cl and the combination of R 1 , R 3a and R 13b for a compound in each case corresponds to one line of Table A (A-1 to A-344).

Table 4 Compounds of the formula (Id2) wherein X is ═N—, Z is ═CR 13c —, R 13c is H and the combination of R 1 , R 3a and R 13b for a compound in each case corresponds to one line of Table A (A-1 to A-344).

Table 5 Compounds of the formula (Id2) wherein X is ═N—, Z is ═CR 13c —, R 13c is F and the combination of R 1 , R 3a and R 13b for a compound in each case corresponds to one line of Table A (A-1 to A-344).

Table 6 Compounds of the formula (Id2) wherein X is ═N—, Z is ═CR 13c —, R 13c is Cl and the combination of R 1 , R 3a and R 13b for a compound in each case corresponds to one line of Table A (A-1 to A-44).

Table 7 Compounds of the formula (Id2) wherein X is ═N—, Z is ═N— and the combination of R 1 , R 3a and R 13b for a compound in each case corresponds to one line of Table A (A-1 to A-344).

Further particular compounds of the present invention are the pyrrolidine derivatives disclosed in preparation examples and physiologically tolerated salts thereof. These include for each preparation example the exemplified compound as well as the corresponding free base and any other physiologically tolerated salts of the free base (if the exemplified compound is a salt), or any physiologically tolerated salt of the free base (if the exemplified compound is a free base). These further include enantiomers, diastereomers, tautomers and any other isomeric forms of said compounds, be they explicitly or implicitly disclosed.

It is noted that the following compounds of formula (Il)

wherein R 1 , R 3a and R 14 are as defined in the following table

R 1 R 3a R 14 4-F—Ph 4-CF 3 —Ph 2-OMe—Ph 2-OMe-4-OCF 3 —Ph 4-F-phenyl 4-CF 3 -phenyl 2-OMe-phenyl 2-OMe-4-OCF 3 -phenyl 4-F-phenyl 4-CF 3 -phenyl 4-F-phenyl 4-F-phenyl 2-OMe-phenyl 4-F-phenyl 4-OMe-phenyl 4-F-phenyl 2-furyl 4-F-phenyl

are described in Baumann Marcus, et al., ACS Comb. Sci. 2011, 13, 405-413 and therefore the present invention does not encompass these compounds and physiologically tolerated salts thereof per se. However, the present invention does encompass pharmaceutical compositions comprising such pyrrolidine derivatives, and the use of such pyrrolidine derivatives for therapeutic purposes, as described herein.

The compounds of the formula (I) can be prepared by analogy to methods which are well known in the art. Suitable methods for the preparation of compounds of formula (I) are outlined in the following schemes.

The process depicted in scheme 1 is useful for obtaining pyrrolidine derivatives, wherein Y 1 is >CH— and R 4 is —N(CR 9a R 9b ) n4 R 13 , —NHCOR 14 or —NHCONHR 16a .

In scheme 1, the variables R 1 , R 3a , R 13 , R 14 , R 16a are as defined herein.

As shown in the above scheme 1, the intermediate of general formula 1 can be alkylated to give compounds of formula 2. Alternatively, 1 can be transformed to compounds 3 via reductive amination or can yield amides of formula 4 by coupling reaction with the corresponding acid. Reaction with isocyanates of formula 5 affords compounds of formula 6.

The process depicted in scheme 2 is useful for obtaining pyrrolidine derivatives, wherein Y 1 is >CH— and R 4 is —(CR 7c R 7d ) n2 NR 11a R 11b or —CONR 20a R 20b .

As shown in the above scheme 2, cycloaddition followed by benzyl deprotection afford pyrrolidine 7. Sulfonylation, methylester hydrolysis and coupling with amines yield compounds of formula 8. Reduction of compounds of formula 8 affords the corresponding amines 9.

The process depicted in scheme 3 is useful for obtaining pyrrolidine derivatives, wherein Y 1 is >CH— and R 4 is —(CR 7a R 7b ) n1 NR 10 .

As shown in the above scheme 3, reduction with LiAlH 4 of intermediate 10 affords the corresponding alcohol which then can be transformed in the alkoxy derivatives of formula 11 via Mitsunobu coupling.

The process depicted in scheme 4 is useful for obtaining pyrrolidine derivatives, wherein Y 1 is >CH— and R 4 is —COR 19 .

As shown in the above scheme 4, the pyrrolidine intermediate 12 can be converted in the corresponding Weinreb amide. Treatment of the Weinreb amide with Grignard reagents affords the ketones of formula 13.

The process depicted in scheme 5 is useful for obtaining pyrrolidine derivatives, wherein Y 1 is >CH— and R 4 is —O(CR 9c R 9d ) n5 R 18 .

As shown in the above scheme 5, alkylation of alcohol 14 affords the compounds of formula 15.

Schemes 1 to 5 refer also to the preparation of the enantiomers, diastereomers, tautomers and any other isomeric forms of said compounds, be they explicitly or implicitly disclosed.

The acid addition salts of the pyrrolidine derivatives of formula (I) are prepared in a customary manner by mixing the free base with a corresponding acid, optionally in solution in an organic solvent, for example a lower alcohol, such as methanol, ethanol or propanol, an ether, such as methyl tert-butyl ether or diisopropyl ether, a ketone, such as acetone or methyl ethyl ketone, or an ester, such as ethyl acetate.

The compounds of the formula (I) are capable of inhibiting the activity of glycine transporter, in particular glycine transporter 1 (GlyT1).

The utility of the compounds in accordance with the present invention as inhibiting the glycine transporter activity, in particular GlyT1 activity, may be demonstrated by methodology known in the art. For instance, human GlyT1c expressing recombinant hGlyT1c_5_CHO cells can be used for measuring glycine uptake and its inhibition (IC 50 ) by a compound of formula (I).

Amongst the compounds of the formula (I) those are preferred which achieve effective inhibition at low concentrations. In particular, compounds of the formula (I) are preferred which inhibit glycine transporter 1 (GlyT1) at a level of IC 50 <1 μMol, more preferably at a level of IC 50 <0.5 μMol, particularly preferably at a level of IC 50 <0.2 μMol and most preferably at a level of IC 50 <0.1 μMol.

The compounds of formula (I) display good to moderate metabolic stability.

The metabolic stability of a compound can be measured for example by incubating a solution of this compound with liver microsomes from particular species (for example rat, dog or human) and determining the half-life of the compound under these conditions (R S Obach, Curr Opin Drug Discov Devel. 2001, 4, 36-44). It is possible in this connection to conclude from an observed longer half-life that the metabolic stability of the compound is improved. The stability in the presence of human liver microsomes is of particular interest because it makes it possible to predict the metabolic degradation of the compound in the human liver. Compounds with increased metabolic stability (measured in the liver microsome test) are therefore probably also degraded more slowly in the liver. The slower metabolic degradation in the liver may lead to higher and/or longer-lasting concentrations (active levels) of the compound in the body, so that the elimination half-life of the compounds of the invention is increased. Increased and/or longer-lasting active levels may lead to a better activity of the compound in therapeutic treatment. In addition, an improved metabolic stability may lead to an increased bioavailability after oral administration, because the compound is subject, after absorption in the intestine, to less metabolic degradation in the liver (so-called first pass effect). An increased oral bioavailability may, owing to an increased concentration (active level) of the compound, lead to a better activity of the compound after oral administration.

Amongst the compounds of the formula (I) those are particularly preferred which display good to moderate metabolic stability towards human liver microsomes. In particular, compounds of the formula (I) are preferred which display a microsomal clearance at a level of mCl <1000 μl/min/mg, more preferably at a level of mCl <500 μl/min/mg, particularly preferably at a level of mCl <100 μl/min/mg and most preferably at a level of mCl <50 μl/min/mg.

The compounds of the formula (I) according to the present invention are thus useful as pharmaceuticals.

The present invention therefore also relates to pharmaceutical compositions which comprise an inert carrier and a compound of the formula (I).

The present invention also relates to the use of the compounds of the formula (I) in the manufacture of a medicament for inhibiting the glycine transporter GlyT1, and to corresponding methods of inhibiting the glycine transporter GlyT1.

The NMDA receptor is central to a wide range of CNS processes, and its role in a variety of diseases in humans or other species has been described. GlyT1 inhibitors slow the removal of glycine from the synapse, causing the level of synaptic glycine to rise. This in turn increases the occupancy of the glycine binding site on the NMDA receptor, which increases activation of the NMDA receptor following glutamate release from the presynaptic terminal Glycine transport inhibitors and in particular inhibitors of the glycine transporter GlyT1 are thus known to be useful in treating a variety of neurologic and psychiatric disorders. Further, glycine A receptors play a role in a variety of diseases in humans or other species. Increasing extracellular glycine concentrations by inhibiting glycine transport may enhance the activity of glycine A receptors. Glycine transport inhibitors and in particular inhibitors of the glycine transporter GlyT1 are thus useful in treating a variety of neurologic and psychiatric disorders.

The present invention thus further relates to the use of the compounds of the formula (I) for the manufacture of a medicament for treating a neurologic or psychiatric disorder, and to corresponding methods of treating said disorders.

According to a particular embodiment, the disorder is associated with glycinergic or glutamatergic neurotransmission dysfunction.

According to a further particular embodiment, the disorder is one or more of the following conditions or diseases: schizophrenia or a psychotic disorder including schizophrenia (paranoid, disorganized, catatonic or undifferentiated), schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, shared psychotic disorder, psychotic disorder due to a general medical condition and substance-induced psychotic disorder, including both the positive and the negative symptoms of schizophrenia and other psychoses; cognitive disorders including dementia (associated with Alzheimer's disease, ischemia, multi-infarct dementia, trauma, vascular problems or stroke, HIV disease, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeldt-Jacob disease, perinatal hypoxia, other general medical conditions or substance abuse); delirium, amnestic disorders or cognitive impairment including age related cognitive decline; anxiety disorders including acute stress disorder, agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, panic attack, panic disorder, post-traumatic stress disorder, separation anxiety disorder, social phobia, specific phobia, substance-induced anxiety disorder and anxiety due to a general medical condition; substance-related disorders and addictive behaviors (including substance-induced delirium, persisting dementia, persisting amnestic disorder, psychotic disorder or anxiety disorder; tolerance, dependence or withdrawal from substances including alcohol, amphetamines, cannabis, cocaine, hallucinogens, inhalants, nicotine, opioids, phencyclidine, sedatives, hypnotics or anxiolytics); obesity, bulimia nervosa and compulsive eating disorders; bipolar disorders, mood disorders including depressive disorders; depression including unipolar depression, seasonal depression and post-partum depression, premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PDD), mood disorders due to a general medical condition, and substance-induced mood disorders; learning disorders, pervasive developmental disorder including autistic disorder, attention deficit disorders including attention-deficit hyperactivity disorder (ADHD) and conduct disorder; movement disorders, including akinesias and akinetic-rigid syndromes (including Parkinson's disease, drug-induced parkinsonism, postencephalitic parkinsonism, progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, parkinsonism-ALS dementia complex and basal ganglia calcification), medication-induced parkinsonism (such as neuroleptic-induced parkinsonism, neuroleptic malignant syndrome, neuroleptic-induced acute dystonia, neuroleptic-induced acute akathisia, neuroleptic-induced tardive dyskinesia and medication-induced postural tremor), Gilles de la Tourette's syndrome, epilepsy, muscular spasms and disorders associated with muscular spasticity or weakness including tremors; dyskinesias [including tremor (such as rest tremor, postural tremor and intention tremor), chorea (such as Sydenham's chorea, Huntington's disease, benign hereditary chorea, neuroacanthocytosis, symptomatic chorea, drug-induced chorea and hemiballism), myoclonus (including generalised myoclonus and focal myoclonus), tics (including simple tics, complex tics and symptomatic tics), and dystonia (including generalised dystonia such as iodiopathic dystonia, drug-induced dystonia, symptomatic dystonia and paroxymal dystonia, and focal dystonia such as blepharospasm, oromandibular dystonia, spasmodic dysphonia, spasmodic torticollis, axial dystonia, dystonic writer's cramp and hemiplegic dystonia)]; urinary incontinence; neuronal damage including ocular damage, retinopathy or macular degeneration of the eye, tinnitus, hearing impairment and loss, and brain edema; emesis; and sleep disorders including insomnia and narcolepsy.

According to a further particular embodiment, the disorder is pain, in particular chronic pain and especially neuropathic pain.

Pain can be classified as acute and chronic pain. Acute pain and chronic pain differ in their etiology, pathophysiology, diagnosis and treatment.

Acute pain, which occurs following tissue injury, is self-limiting, serves as an alert to ongoing tissue damage and following tissue repair it will usually subside. There are minimal psychological symptoms associated with acute pain apart from mild anxiety. Acute pain is nociceptive in nature and occurs following chemical, mechanical and thermal stimulation of A-delta and C-polymodal pain receptors.

Chronic pain, on the other hand, serves no protective biological function. Rather than being the symptom of tissue damage it is a disease in its own right. Chronic pain is unrelenting and not self-limiting and can persist for years, perhaps decades after the initial injury. Chronic pain can be refractory to multiple treatment regimes. Psychological symptoms associated with chronic pain include chronic anxiety, fear, depression, sleeplessness and impairment of social interaction. Chronic non-malignant pain is predominantly neuropathic in nature and involves damage to either the peripheral or central nervous systems.

Acute pain and chronic pain are caused by different neuro-physiological processes and therefore tend to respond to different types of treatments. Acute pain can be somatic or visceral in nature. Somatic pain tends to be a well localised, constant pain and is described as sharp, aching, throbbing or gnawing. Visceral pain, on the other hand, tends to be vague in distribution, paroxysmal in nature and is usually described as deep, aching, squeezing or colicky in nature. Examples of acute pain include post-operative pain, pain associated with trauma and the pain of arthritis. Acute pain usually responds to treatment with opioids or non-steroidal anti-inflammatory drugs.

Chronic pain, in contrast to acute pain, is described as burning, electric, tingling and shooting in nature. It can be continuous or paroxysmal in presentation. The hallmarks of chronic pain are chronic allodynia and hyperalgesia. Allodynia is pain resulting from a stimulus that normally does not ellicit a painful response, such as a light touch. Hyperalgesia is an increased sensitivity to normally painful stimuli. Primary hyperalgesia occurs immediately within the area of the injury. Secondary hyperalgesia occurs in the undamaged area surrounding the injury. Examples of chronic pain include complex regional pain syndrome, pain arising from peripheral neuropathies, post-operative pain, chronic fatigue syndrome pain, tension-type headache, pain arising from mechanical nerve injury and severe pain associated with diseases such as cancer, metabolic disease, neurotropic viral disease, neurotoxicity, inflammation, multiple sclerosis or any pain arising as a consequence of or associated with stress or depressive illness.

Although opioids are cheap and effective, serious and potentially life-threatening side effects occur with their use, most notably respiratory depression and muscle rigidity. In addition the doses of opioids which can be administered are limited by nausea, emesis, constipation, pruritis and urinary retention, often resulting in patients electing to receive sub-optimal pain control rather than suffer these distressing side-effects. Furthermore, these side-effects often result in patients requiring extended hospitalisation. Opioids are highly addictive and are scheduled drugs in many territories.

The compounds of formula (I) are particularly useful in the treatment of schizophrenia, bipolar disorder, depression including unipolar depression, seasonal depression and post-partum depression, premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PDD), learning disorders, pervasive developmental disorder including autistic disorder, attention deficit disorders including Attention-Deficit/Hyperactivity Disorder, tic disorders including Tourette's disorder, anxiety disorders including phobia and post traumatic stress disorder, cognitive disorders associated with dementia, AIDS dementia, Alzheimer's, Parkinson's, Huntington's disease, spasticity, myoclonus, muscle spasm, tinnitus and hearing impairment and loss are of particular importance.

Particular cognitive disorders are dementia, delirium, amnestic disorders and cognitive impairment including age-related cognitive decline.

Particular anxiety disorders are generalized anxiety disorder, obsessive-compulsive disorder and panic attack.

Particular schizophrenia or psychosis pathologies are paranoid, disorganized, catatonic or undifferentiated schizophrenia and substance-induced psychotic disorder.

Particular neurologic disorders that can be treated with the compounds of the formula (I) include in particular a cognitive disorder such as dementia, cognitive impairment, attention deficit hyperactivity disorder.

Particular psychiatric disorders that can be treated with the compounds of the formula (I) include in particular an anxiety disorder, a mood disorder such as depression or a bipolar disorder, schizophrenia, a psychotic disorder.

Within the context of the treatment, the use according to the invention of the compounds of the formula (I) involves a method. In this method, an effective quantity of one or more compounds or the formula (I), as a rule formulated in accordance with pharmaceutical and veterinary practice, is administered to the individual to be treated, preferably a mammal, in particular a human being. Whether such a treatment is indicated, and in which form it is to take place, depends on the individual case and is subject to medical assessment (diagnosis) which takes into consideration signs, symptoms and/or malfunctions which are present, the risks of developing particular signs, symptoms and/or malfunctions, and other factors.

As a rule, the treatment is effected by means of single or repeated daily administration, where appropriate together, or alternating, with other drugs or drug-containing preparations.

The invention also relates to the manufacture of pharmaceutical compositions for treating an individual, preferably a mammal, in particular a human being. Thus, the compounds of the formula (I) are customarily administered in the form of pharmaceutical compositions which comprise an inert carrier (e.g. a pharmaceutically acceptable excipient) together with at least one compound according to the invention and, where appropriate, other drugs. These compositions can, for example, be administered orally, rectally, transdermally, subcutaneously, intravenously, intramuscularly or intranasally.

Examples of suitable pharmaceutical formulations are solid medicinal forms, such as powders, granules, tablets, in particular film tablets, lozenges, sachets, cachets, sugar-coated tablets, capsules, such as hard gelatin capsules and soft gelatin capsules, suppositories or vaginal medicinal forms, semisolid medicinal forms, such as ointments, creams, hydrogels, pastes or plasters, and also liquid medicinal forms, such as solutions, emulsions, in particular oil-in-water emulsions, suspensions, for example lotions, injection preparations and infusion preparations, and eyedrops and eardrops. Implanted release devices can also be used for administering inhibitors according to the invention. In addition, it is also possible to use liposomes or microspheres.

When producing the compositions, the compounds according to the invention are optionally mixed or diluted with one or more carriers (excipients). Carriers (excipients) can be solid, semisolid or liquid materials which serve as vehicles, carriers or medium for the active compound.

Suitable carriers (excipients) are listed in the specialist medicinal monographs. In addition, the formulations can comprise pharmaceutically acceptable auxiliary substances, such as wetting agents; emulsifying and suspending agents; preservatives; antioxidants; antiirritants; chelating agents; coating auxiliaries; emulsion stabilizers; film formers; gel formers; odor masking agents; taste corrigents; resin; hydrocolloids; solvents; solubilizers; neutralizing agents; diffusion accelerators; pigments; quaternary ammonium compounds; refatting and overfatting agents; raw materials for ointments, creams or oils; silicone derivatives; spreading auxiliaries; stabilizers; sterilants; suppository bases; tablet auxiliaries, such as binders, fillers, glidants, disintegrants or coatings; propellants; drying agents; opacifiers; thickeners; waxes; plasticizers and white mineral oils. A formulation in this regard is based on specialist knowledge as described, for example, in Fiedler, H. P., Lexikon der Hilfsstoffe für Pharmazie, Kosmetik and angrenzende Gebiete [Encyclopedia of auxiliary substances for pharmacy, cosmetics and related fields], 4 th edition, Aulendorf: ECV-Editio-Cantor-Verlag, 1996.

The compounds of formula (I) may also be suitable for combination with other therapeutic agents.

Thus, the present invention also provides:

i) a combination comprising a compound of formula (I) with one or more further therapeutic agents;

ii) a pharmaceutical composition comprising a combination product as defined in i) above and at least one carrier, diluent or excipient;

iii) the use of a combination as defined in i) above in the manufacture of a medicament for treating or preventing a disorder, disease or condition as defined herein;

iv) a combination as defined in i) above for use in treating or preventing a disorder, disease or condition as defined herein;

v) a kit-of-parts for use in the treatment of a disorder, disease or condition as defined herein, comprising a first dosage form comprising a compound of formula (I) and one or more further dosage forms each comprising one or more further therapeutic agents for simultaneous therapeutic administration,

vi) a combination as defined in i) above for use in therapy;

vii) a method of treatment or prevention of a disorder, disease or condition as defined herein comprising administering an effective amount of a combination as defined in i) above;

viii) a combination as defined in i) above for treating or preventing a disorder, disease or condition as defined herein.

The combination therapies of the invention may be administered adjunctively. By adjunctive administration is meant the coterminous or overlapping administration of each of the components in the form of separate pharmaceutical compositions or devices. This regime of therapeutic administration of two or more therapeutic agents is referred to generally by those skilled in the art and herein as adjunctive therapeutic administration; it is also known as add-on therapeutic administration. Any and all treatment regimes in which a patient receives separate but coterminous or overlapping therapeutic administration of the compounds of formula (I) and at least one further therapeutic agent are within the scope of the current invention. In one embodiment of adjunctive therapeutic administration as described herein, a patient is typically stabilized on a therapeutic administration of one or more of the components for a period of time and then receives administration of another component.

The combination therapies of the invention may also be administered simultaneously. By simultaneous administration is meant a treatment regime wherein the individual components are administered together, either in the form of a single pharmaceutical composition or device comprising or containing both components, or as separate compositions or devices, each comprising one of the components, administered simultaneously. Such combinations of the separate individual components for simultaneous combination may be provided in the form of a kit-of-parts.

In a further aspect, the invention provides a method of treatment of a psychotic disorder by adjunctive therapeutic administration of compounds of formula (I) to a patient receiving therapeutic administration of at least one antipsychotic agent. In a further aspect, the invention provides the use of compounds of formula (I) in the manufacture of a medicament for adjunctive therapeutic administration for the treatment of a psychotic disorder in a patient receiving therapeutic administration of at least one antipsychotic agent. The invention further provides compounds of formula (I) for use for adjunctive therapeutic administration for the treatment of a psychotic disorder in a patient receiving therapeutic administration of at least one antipsychotic agent.

In a further aspect, the invention provides a method of treatment of a psychotic disorder by adjunctive therapeutic administration of at least one antipsychotic agent to a patient receiving therapeutic administration of compounds of formula (I). In a further aspect, the invention provides the use of at least one antipsychotic agent in the manufacture of a medicament for adjunctive therapeutic administration for the treatment of a psychotic disorder in a patient receiving therapeutic administration of compounds of formula (I). The invention further provides at least one antipsychotic agent for adjunctive therapeutic administration for the treatment of a psychotic disorder in a patient receiving therapeutic administration of compounds of formula (I).

In a further aspect, the invention provides a method of treatment of a psychotic disorder by simultaneous therapeutic administration of compounds of formula (I) in combination with at least one antipsychotic agent. The invention further provides the use of a combination of compounds of formula (I) and at least one antipsychotic agent in the manufacture of a medicament for simultaneous therapeutic administration in the treatment of a psychotic disorder. The invention further provides a combination of compounds of formula (I) and at least one antipsychotic agent for simultaneous therapeutic administration in the treatment of a psychotic disorder. The invention further provides the use of compounds of formula (I) in the manufacture of a medicament for simultaneous therapeutic administration with at least one antipsychotic agent in the treatment of a psychotic disorder. The invention further provides compounds of formula (I) for use for simultaneous therapeutic administration with at least one antipsychotic agent in the treatment of a psychotic disorder. The invention further provides the use of at least one antipsychotic agent in the manufacture of a medicament for simultaneous therapeutic administration with compounds of formula (I) in the treatment of a psychotic disorder. The invention further provides at least one antipsychotic agent for simultaneous therapeutic administration with compounds of formula (I) in the treatment of a psychotic disorder.

In further aspects, the invention provides a method of treatment of a psychotic disorder by simultaneous therapeutic administration of a pharmaceutical composition comprising compounds of formula (I) and at least one mood stabilising or antimanic agent, a pharmaceutical composition comprising compounds of formula (I) and at least one mood stabilising or antimanic agent, the use of a pharmaceutical composition comprising compounds of formula (I) and at least one mood stabilising or antimanic agent in the manufacture of a medicament for the treatment of a psychotic disorder, and a pharmaceutical composition comprising compounds of formula (I) and at least one mood stabilising or antimanic agent for use in the treatment of a psychotic disorder.

Antipsychotic agents include both typical and atypical antipsychotic drugs. Examples of antipsychotic drugs that are useful in the present invention include, but are not limited to: butyrophenones, such as haloperidol, pimozide, and droperidol; phenothiazines, such as chlorpromazine, thioridazine, mesoridazine, trifluoperazine, perphenazine, fluphenazine, thiflupromazine, prochlorperazine, and acetophenazine; thioxanthenes, such as thiothixene and chlorprothixene; thienobenzodiazepines; dibenzodiazepines; benzisoxazoles; dibenzothiazepines; imidazolidinones; benziso-thiazolyl-piperazines; triazine such as lamotrigine; dibenzoxazepines, such as loxapine; dihydroindolones, such as molindone; aripiprazole; and derivatives thereof that have antipsychotic activity.

Examples of tradenames and suppliers of selected antipsychotic drugs are as follows: clozapine (available under the tradename CLOZARIL®, from Mylan, Zenith Goldlinc, UDL, Novartis); olanzapine (available under the tradename ZYPREX®, from Lilly); ziprasidone (available under the tradename GEODON®, from Pfizer); risperidone (available under the tradename RISPERDAL®, from Janssen); quetiapine fumarate (available under the tradename SEROQUEL®, from AstraZeneca); haloperidol (available under the tradename HALDOL®, from OrthoMcNeil); chlorpromazine (available under the tradename THORAZINE®, from SmithKline Beecham (GSK)); fluphenazine (available under the tradename PROLIXIN®, from Apothecon, Copley, Schering, Teva, and American Pharmaceutical Partners, Pasadena); thiothixene (available under the tradename NAVANE®, from Pfizer); trifluoperazine (10-[3-(4-methyl-1-piperazinyl)propyl]-2-(trifluoromethyl)phenothiazine dihydrochloride, available under the tradename STELAZINE®, from Smith Klein Beckman); perphenazine (available under the tradename TRILAFON®; from Schering); thioridazine (available under the tradename MELLARIL®; from Novartis, Roxane, HiTech, Teva, and Alpharma); molindone (available under the tradename MOBAN®, from Endo); and loxapine (available under the tradename LOXITANE (D; from Watson). Furthermore, benperidol (Glianimon®), perazine (Taxilan®) or melperone (Eunerpan®) may be used. Other antipsychotic drugs include promazine (available under the tradename SPARINE®), triflurpromazine (available under the tradename VESPRIN®), chlorprothixene (available under the tradename TARACTAN®), droperidol (available under the tradename INAPSINE®), acetophenazine (available under the tradename TINDAL®), prochlorperazine (available under the tradename COMPAZINE®), methotrimeprazine (available under the tradename NOZINAN®), pipotiazine (available under the tradename PIPOTRIL®), ziprasidone, and hoperidone.

In a further aspect, the invention provides a method of treatment of a neurodegenerative disorder such as Alzheimer Disease by adjunctive therapeutic administration of compounds of formula (I) to a patient receiving therapeutic administration of at least one agent suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease. In a further aspect, the invention provides the use of compounds of formula (I) in the manufacture of a medicament for adjunctive therapeutic administration for the treatment of a neurodegenerative disorder such as Alzheimer Disease in a patient receiving therapeutic administration of at least one agent suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease. The invention further provides compounds of formula (I) for use for adjunctive therapeutic administration for the treatment of a neurodegenerative disorder such as Alzheimer Disease in a patient receiving therapeutic administration of at least one agent suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease.

In a further aspect, the invention provides a method of treatment of a neurodegenerative disorder such as Alzheimer Disease by adjunctive therapeutic administration of at least one agent suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease to a patient receiving therapeutic administration of compounds of formula (I). In a further aspect, the invention provides the use of at least one agent suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease in the manufacture of a medicament for adjunctive therapeutic administration for the treatment of a neurodegenerative disorder such as Alzheimer Disease in a patient receiving therapeutic administration of compounds of formula (I). The invention further provides at least one agent suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease for adjunctive therapeutic administration for the treatment of a neurodegenerative disorder such as Alzheimer Disease in a patient receiving therapeutic administration of compounds of formula (I).

In a further aspect, the invention provides a method of treatment of a neurodegenerative disorder such as Alzheimer Disease by simultaneous therapeutic administration of compounds of formula (I) in combination with at least one agent suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease. The invention further provides the use of a combination of compounds of formula (I) and at least one agent suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease in the manufacture of a medicament for simultaneous therapeutic administration in the treatment of a neurodegenerative disorder such as Alzheimer Disease. The invention further provides a combination of compounds of formula (I) and at least one agent suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease for simultaneous therapeutic administration in the treatment of a neurodegenerative disorder such as Alzheimer Disease. The invention further provides the use of compounds of formula (I) in the manufacture of a medicament for simultaneous therapeutic administration with at least one agent suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease in the treatment of a neurodegenerative disorder such as Alzheimer Disease. The invention further provides compounds of formula (I) for use for simultaneous therapeutic administration with at least one agent suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease in the treatment of a neurodegenerative disorder such as Alzheimer Disease. The invention further provides the use of at least one agent suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease in the manufacture of a medicament for simultaneous therapeutic administration with compounds of formula (I) in the treatment of a neurodegenerative disorder such as Alzheimer Disease. The invention further provides at least one agent suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease for simultaneous therapeutic administration with compounds of formula (I) in the treatment of a neurodegenerative disorder such as Alzheimer Disease.

Examples of agents suitable for the treatment of a neurodegenerative disorder such as Alzheimer Disease that are useful in the present invention include, but are not limited to: cholinesterase inhibitors, agents targeting nicotinic or muscarinic acethylcholine receptors, NMDA receptors, amyloid formation, mitochondrial dysfunctions, disease associated calpain activity, neuroinflamation, tumor necrosis factor receptors, NF-kappaB, peroxisome proliferator activator receptor gamma, Apolipoprotein E variant 4 (ApoE4), disease-associated increase of the HPA axis, epileptic discharges, vascular dysfunction, vascular risk factors, and oxidative stress.

Suitable cholinesterase inhibitors which may be used in combination with the compounds of the inventions include for example tacrine, donepezil, galantamine and rivastigmine.

Suitable NMDA receptors targeting agents which may be used in combination with the compounds of the inventions include for example memantine.

Suitable agents affecting increased HPA axis activity which may be used in combination with the compounds of the inventions include for example CRF1 antagonists or V1b antagonists.

In a further aspect therefore, the invention provides a method of treatment of pain by adjunctive therapeutic administration of compounds of formula (I) to a patient receiving therapeutic administration of at least one agent suitable for the treatment of pain. In a further aspect, the invention provides the use of compounds of formula (I) in the manufacture of a medicament for adjunctive therapeutic administration for the treatment of pain in a patient receiving therapeutic administration of at least one agent suitable for the treatment of pain. The invention further provides compounds of formula (I) for use for adjunctive therapeutic administration for the treatment of pain in a patient receiving therapeutic administration of at least one agent suitable for the treatment of pain.

In a further aspect, the invention provides a method of treatment of pain by adjunctive therapeutic administration of at least one agent suitable for the treatment of pain to a patient receiving therapeutic administration of compounds of formula (I). In a further aspect, the invention provides the use of at least one agent suitable for the treatment of pain in the manufacture of a medicament for adjunctive therapeutic administration for the treatment of pain in a patient receiving therapeutic administration of compounds of formula (I). The invention further provides at least one agent suitable for the treatment of pain for adjunctive therapeutic administration for the treatment of pain in a patient receiving therapeutic administration of compounds of formula (I).

In a further aspect, the invention provides a method of treatment of pain by simultaneous therapeutic administration of compounds of formula (I) in combination with at least one agent suitable for the treatment of pain. The invention further provides the use of a combination of compounds of formula (I) and at least one agent suitable for the treatment of pain in the manufacture of a medicament for simultaneous therapeutic administration in the treatment of pain. The invention further provides a combination of compounds of formula (I) and at least one agent suitable for the treatment of pain for simultaneous therapeutic administration in the treatment of pain. The invention further provides the use of compounds of formula (I) in the manufacture of a medicament for simultaneous therapeutic administration with at least one agent suitable for the treatment of pain in the treatment of pain. The invention further provides compounds of formula (I) for use for simultaneous therapeutic administration with at least one agent suitable for the treatment of pain in the treatment of pain. The invention further provides the use of at least one agent suitable for the treatment of pain in the manufacture of a medicament for simultaneous therapeutic administration with compounds of formula (I) in the treatment of pain. The invention further provides at least one agent suitable for the treatment of pain for simultaneous therapeutic administration with compounds of formula (I) in the treatment of pain.

Examples of agents suitable for the treatment of pain that are useful in the present invention include, but are not limited to: NSAIDs (Nonsteroidal Antiinflammatory Drugs), anticonvulsant drugs such as carbamazepine and gabapentin, sodium channel blockers, antidepressant drugs, cannabinoids and local anaesthetics.

Suitable agents used in combination with the compounds of the inventions include for example celecoxib, etoricoxib, lumiracoxib, paracetamol, tramadol, methadone, venlafaxine, imipramine, duloxetine, bupropion, gabapentin, pregabalin, lamotrigine, fentanyl, parecoxib, nefopam, remifentanil, pethidine, diclofenac, rofecoxib, nalbuphine, sufentanil, pethidine, diamorphine and butorphanol.

It will be appreciated by those skilled in the art that the compounds according to the invention may advantageously be used in conjunction with one or more other therapeutic agents, for instance, antidepressant agents such as 5HT3 antagonists, serotonin agonists, NK-1 antagonists, selective serotonin reuptake inhibitors (SSRI), noradrenaline re-uptake inhibitors (SNRI), tricyclic antidepressants, dopaminergic antidepressants, H3 antagonists, 5HT1A antagonists, 5HT1B antagonists, 5HT1D antagonists, D1 agonists, M1 agonists and/or anticonvulsant agents, as well as cognitive enhancers.

Suitable 5HT3 antagonists which may be used in combination of the compounds of the inventions include for example ondansetron, granisetron, metoclopramide.

Suitable serotonin agonists which may be used in combination with the compounds of the invention include sumatriptan, rauwolscine, yohimbine, metoclopramide.

Suitable SSRIs which may be used in combination with the compounds of the invention include fluoxetine, citalopram, femoxetine, fluvoxamine, paroxetine, indalpine, sertraline, zimeldine.

Suitable SNRIs which may be used in combination with the compounds of the invention include venlafaxine and reboxetine.

Suitable tricyclic antidepressants which may be used in combination with a compound of the invention include imipramine, amitriptiline, chlomipramine and nortriptiline.

Suitable dopaminergic antidepressants which may be used in combination with a compound of the invention include bupropion and amineptine.

Suitable anticonvulsant agents which may be used in combination of the compounds of the invention include for example divalproex, carbamazepine and diazepam.

The following examples serve to explain the invention without limiting it.

The compounds were characterized by mass spectrometry, generally recorded via HPLC-MS in a fast gradient on C18-material (electrospray-ionisation (ESI) mode).

Preparation Examples

APCI for atmospheric pressure chemical ionization; AcOH for acetic acid; Boc for tert-butoxy carbonyl; Bu for butyl; DCI for desorption chemical ionization; DCM for dichloromethane; dimethylsulfoxide for dimethyl sulfoxide; eq for equivalent(s); ESI for electrospray ionization; EtOAc for ethyl acetate; HATU for [o-(azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate]; HCl for hydrochloric acid; HPLC for high performance liquid chromatography; id for internal diameter; LCMS for liquid chromatography/mass spectrometry; MeOH for methanol; MgSO4 for magnesium sulfate; MP for macroporous resin; NaOAc for sodium acetate; PS for polymer supported; psi for pounds per square inch; SFC for supercritical fluid chromatography; SPE for solid phase extraction, and tBu for tert-butyl.

Similarly indicates that that reactants may be substituted for other the reactants described, the temperature may vary by 50° C., the equivalents may differ by upto 2 fold, or any combination thereof.

Preparative HPLC Procedure:

Samples were purified by preparative HPLC on a Phenomenex® Luna® C8(2) 5 μm 100 Å AXIA™ column (30 mm×75 mm) A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/minute (0-0.5 minutes 10% A, 0.5-7.0 minutes linear gradient 10-95% A, 7.0-10.0 minutes 95% A, 10.0-12.0 minutes linear gradient 95-10% A). Samples were injected in 1.5 mL dimethyl sulfoxide:methanol (1:1). With specified samples, ammonium acetate was used instead of trifluoroacetic acid. A custom purification system was used, consisting of the following modules: Waters LC4000 preparative pump; Waters 996 diode-array detector; Waters 717+ autosampler; Waters SATIN module, Alltech Varex III evaporative light-scattering detector; Gilson 506C interface box; and two Gilson FC204 fraction collectors. The system was controlled using Waters Millennium32 software, automated using an Abbott developed Visual Basic application for fraction collector control and fraction tracking. Fractions were collected based upon UV signal threshold and selected fractions subsequently analyzed by flow injection analysis mass spectrometry using positive APCI ionization on a Finnigan LCQ using 70:30 methanol:10 mM NH 4 OH(aqueous) at a flow rate of 0.8 mL/minute. Loop-injection mass spectra were acquired using a Finnigan LCQ running LCQ Navigator 1.2 software and a Gilson 215 liquid handler for fraction injection controlled by an Abbott developed Visual Basic application.

For chiral compounds the absolute configuration is indicated in their chemical names. A chemical name with “trans” or no stereochemistry information does not refer to a chiral compound (even if the corresponding formula depicts a chiral compound).