Pyrazolo[1,5-a]pyridine derivatives or pharmaceutically acceptable salts thereof

This application claims priority from U.S. Provisional Application No. 60/669,894, filed Apr. 11, 2005 and from U.S. Provisional Application No. 60/714,864, filed Sep. 8, 2005.

The present invention relates to a novel class of pyrazolo[1,5-a]pyridine derivatives or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising them as an active ingredient, MAPKAP-K2 (mitogen-activated protein kinase activated protein kinase 2) inhibitors comprising them as an active ingredient and novel intermediates thereof. The present invention also relates to therapeutic agents or preventing agents comprising these compounds as active ingredients for neurodegenerative/neurological disorders (including dementia), sepsis, autoimmune diseases, destructive osteopathy, inflammatory bowel disease, psoriasis, diabetes mellitus, cancer, ischemic reperfusion injury, angiodysplasia, cachexia, obesity, angiogenesis, asthma and/or chronic obstructive pulmonary disease (COPD).

MAPKAP-K2 (mitogen-activated protein kinase activated protein kinase 2) is a serine/threonine kinase and operates in immediate downstream of p38 kinase in stress-induced MAPK pathway ( FIG. 1 ).

This p38 kinase pathway is activated by various stress-related extracellular stimuli such as heat, ultraviolet ray, bacterial lipopolysaccharide or inflammatory cytokines. The activation of this pathway causes phosphorylation of transcription and initiation factors and affects cell division, apoptosis, cell differentiation, inflammatory response and infiltration of cancer cells (Martin-Blanco, Bioessays 22, 637-645).

p38 Kinase itself activates many protein kinases other than MAPKAP kinase, for example, Mnkl/2, PRAK and MSK1 ( FIG. 1 ). This pathway is particularly important for discovery of novel anti-inflammatory drugs. A selective p38 kinase inhibitor is effective for suppressing inflammatory cytokines in both cell based model and animal model of chronic inflammation (Lee et al., Immunopharmacology 47,185-201 (2000)). However, a p38 kinase-knockout mouse is embryonic lethal. Moreover, it has been proved that cells derived from such an embryo exhibit a lot of anomaly in fundamental cellular responses. As another strategy for developing anti-inflammatory drugs, there can be mentioned a drug inhibiting this pathway in the level of MAPKAP-K2. In an unstimulated cell, MAPKAP-K2 exists in the nucleus, and it is transferred to cytosol when the cell is stimulated. It is known that this kinase phosphorylates many nuclear transcription factors and cytosolic proteins such as heat-shock protein involved in cell protection and 5-lipoxygenase involved in bioprotection and inflammation (Stokoe et al., FEBS Lett. 313, 307-313 (1992); Werz et al., Proc. Natl. Acad. Sci. USA 97, 5261-5266 (2000)); Heindenreich et al., J. Biol. Chem. 274, 14434-14443 (1999)); Tan et al., EMBO J. 15, 4629-4642 (1996)); Neufeld, J. Biol. Chem. 275, 20239-20242 (2000)). All of these substrates contain a unique amino acid motif (XX-Hyd-XRXXSXX where Hyd represents a bulky hydrophobic residue) which is required for effective phosphorylation by MAPKAP-K2 (Stokoe et al., Biochem. J. 296, 843-849 (1993)).

MAPKAP-K2 is the only substrate of p38 kinase whose special function is currently identified. The special rolls of MAPKAP-K2 in mediation of inflammatory response are remarkably demonstrated in a phenotype of MAPKAP-K2 knockout mouse (MAPKAP-K2 −/− ) (Kotlyarov et al., Nature Cell Biol. 1, 94-97 (1999)). This mouse is not lethal and normal except for particularly reduced inflammatory response. Recently, it has been proved that lack of MAPKAP-K2 causes particular protection of neurons from ischemic brain injury (Wang et al., J. Biol. Chem. 277, 43968-43972 (2002)). It is considered that MAPKAP-K2 regulates translation and/or stabilization of mRNA of important inflammatory cytokines. This is likely because MAPKAP-K2 phosphorylates proteins which bind to AU-rich elements found in untranslated regions of these cytokines. Identification of these proteins is now under investigation.

Furthermore, it is reported that MAPKAP-K2 has activity of repairing anomaly in DNA induced by ultraviolet ray (Isaac A. Manke et al., Molecular Cell 17, 37-48 (2005)). Inhibition of MAPKAP-K2 activity may disable repairing damaged DNA and cause death in some types of cancer cell.

From the above, MAPKAP-K2 inhibitors are effective for neurodegenerative/neurological disorders (including dementia), sepsis, autoimmune diseases, destructive osteopathy, inflammatory bowel disease, psoriasis, diabetes mellitus, cancer, ischemic reperfusion injury, angiodysplasia, cachexia, obesity, angiogenesis, asthma and/or chronic obstructive pulmonary disease (COPD).

As MAPKAP-K2 inhibitors there have been disclosed in WO2004/054504, WO2004/054505, WO2004/055015, WO2004/055019, WO2004/058176, WO2004/058762, WO2004/099127, WO2005/009370, WO2005/007092, WO2004/076458 and WO2004/081013, but these compounds are different in structure from the compounds in the present invention.

Further, pyrazolo[1,5-a]pyridine derivatives are disclosed in WO2004/026872, WO2005/028445 and WO2005/077948. These compounds are, however, different in structure from the compound of the present invention or the compound of the present invention is not specifically disclosed in these literatures, as exemplified by the fact that WO2005/077948 describes only compounds wherein R 3 is a methyl group but no compounds wherein R 3 is a hydroxyl group or an amino group. Furthermore, the target enzymes of these compounds are also different from those of the compound of the present invention.

An object of the present invention is to provide a novel pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof valuable for a MAPKAP-K2 inhibitor.

Another object of the present invention is to provide a novel MAPKAP-K2 inhibitor or a novel therapeutic agent or preventing agents for neurodegenerative/neurological disorders (including dementia), sepsis, autoimmune diseases, destructive osteopathy, inflammatory bowel disease, psoriasis, diabetes mellitus, cancer, ischemic reperfusion injury, angiodysplasia, cachexia, obesity, angiogenesis, asthma and/or chronic obstructive pulmonary disease (COPD). A still other object of the present invention is to provide a novel intermediate of novel MAPKAP-K2 inhibitor.

The present inventors pursued zealous study, found that novel pyrazolo[1,5-a]pyridine derivatives represented by the following formula (I) and pharmaceutically acceptable salts thereof exhibit excellent MAPKAP-K2 inhibitory activity, and accomplished the present invention.

Namely, the present invention is

<1> A pyrazolo[1,5-a]pyridine derivative represented by formula (I) or pharmaceutically acceptable salt thereof:

[In formula (I),

R 1 represents an optionally substituted C1-C8 alkyl group, an optionally substituted C2-C8 alkenyl group, an optionally substituted C2-C8 alkynyl group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C7-C16 aralkyl group, an optionally substituted heteroarylalkyl group, an optionally substituted C3-C8 cycloalkyl group or an optionally substituted aliphatic heterocyclic group; the substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of a halogen atom, a cyano group, a nitro group, an optionally substituted C1-C8 alkyl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, —OR 1a , —SR 1b , —NR 1c R 1d , —C(═O)R 1e , —S(═O) 2 NR 1f R 1g , —C(═O)OR 1h , —C(═O)NR 1i R 1j , —NR 1k C(═O)R 1l and —NR 1m S(═O) 2 R 1n ; R 1x (x represents a, b, c, d, e, f g, h, i, j, k, l, m or n) may be identical or different, and represents a hydrogen atom, an optionally substituted C1-C8 alkyl group (when two C1-C8 alkyl groups as R 1x bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C7-C16 aralkyl group, an optionally substituted heteroarylalkyl group or an optionally substituted aliphatic heterocyclylalkyl group; when R 1 is an optionally substituted C6-C14 aryl group or an optionally substituted heteroaryl group and two or more substituents of R 1 bond to R 1 , these substituents may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring; R 2 represents a hydrogen atom, an optionally substituted C1-C8 alkyl group, an optionally substituted C2-C8 alkenyl group, an optionally substituted C2-C8 alkynyl group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C7-C16 aralkyl group, an optionally substituted C3-C8 cycloalkyl group or an optionally substituted heteroarylalkyl group; the substituent(s) of R 2 are one or more substituent(s) selected from the group consisting of a halogen atom, a cyano group, a nitro group, an optionally substituted C1-C8 alkyl group, —OR 2a , SR 2b , —NR 2c R 2d , —C(═O)R 2e , —S(═O) 2 NR 2f R 2g , —C(═O)OR 2h , —C(═O)NR 2i R 2j , —NR 2k C(═O)R 2l and —NR 2m S(═O) 2 R 2n ; R 2y (y represents a, b, c, d, e, f, g, h, i, j, k, l, m or n) may be identical or different, and represents a hydrogen atom, an optionally substituted C1-C8 alkyl group (when two C1-C8 alkyl groups as R 2y bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C7-C16 aralkyl group or an optionally substituted heteroarylalkyl group; when R 2 is an optionally substituted C6-C14 aryl group or an optionally substituted heteroaryl group and two or more substituents of R 2 bond to R 2 , these substituents may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring; R 3 represents an optionally substituted C1-C8 alkyl group, an optionally substituted C3-C8 cycloalkyl group or an optionally substituted aliphatic heterocyclic group; the substituent(s) of R 3 are one or more substituent(s) selected from the group consisting of a halogen atom, a cyano group, a nitro group, —OR 3 a, —SR 3b , —NR 3c R 3d , an optionally substituted C1-C8 alkyl group, an optionally substituted C3-C8 cycloalkyl group and an optionally substituted aliphatic heterocyclic group; R 3z (z represents a, b, c or d) may be identical or different and represents a hydrogen atom, an optionally substituted C1-C8 alkyl group (when two C1-C8 alkyl groups as R 3z bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C7-C16 aralkyl group or an optionally substituted heteroarylalkyl group; and the substituent(s) of substituent of R 1 , R 2 and R 3 are, unless specifically defined, one or more substituent(s) selected from the group consisting of a halogen atom; a hydroxyl group; a cyano group; a nitro group; an amino group; an oxo group; a carboxyl group; a trifluoromethyl group; a pentafluoroethyl group; a trifluoromethoxy group; a C1-C8 alkyl group optionally substituted with halogen atom(s), hydroxyl group(s), cyano group(s) or oxo group(s); a C3-C8 cycloalkyl group optionally substituted with methyl group(s), halogen atom(s), hydroxyl group(s), cyano group(s) or oxo group(s); a C1-C8 alkoxy group optionally substituted with halogen atom(s), hydroxyl group(s) or cyano group(s); a C3-C8 cycloalkyl-oxy group cycloalkyl-oxy group optionally substituted with methyl group(s), halogen atom(s), hydroxyl group(s) or cyano group(s); an aliphatic heterocyclic group optionally substituted with methyl group(s), halogen atom(s), hydroxyl group(s) or cyano group(s); a C6-C14 aryl group optionally substituted with methyl group(s), halogen atom(s), hydroxyl group(s) or cyano group(s); and a heteroaryl group optionally substituted with methyl group(s), halogen atom(s), hydroxyl group(s) or cyano group(s).]. <2> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to <1>, wherein: R 1 represents an optionally substituted C1-C8 alkyl group, an optionally substituted C2-C8 alkenyl group, an optionally substituted C2-C8 alkynyl group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C7-C16 aralkyl group, an optionally substituted heteroarylalkyl group, an optionally substituted C3-C8 cycloalkyl group or an optionally substituted aliphatic heterocyclic group; the substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of a halogen atom, a cyano group, a nitro group, an optionally substituted C1-C8 alkyl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, —OR 1a , —SR 1b , —NR 1c R 1d , —C(═O)R 1e , —S(═O) 2 NR 1f R 1g , —C(═O)OR 1h , —C(═O)NR 1i R 1j , —NR 1k C(═O)R 1l and —NR 1m S(═O) 2 R 1n ; R 1x (x represents a, b, c, d, e, f, g, h, i, j, k, l, m or n) may be identical or different and represents a hydrogen atom, an optionally substituted C1-C8 alkyl group (when two C1-C8 alkyl groups as R 1x bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C7-C16 aralkyl group, an optionally substituted heteroarylalkyl group or an optionally substituted aliphatic heterocyclylalkyl group; when R 1 is an optionally substituted C6-C14 aryl group or an optionally substituted heteroaryl group and two or more substituents of R 1 bond to R 1 , these substituents may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring; R 2 represents a hydrogen atom, an optionally substituted C1-C8 alkyl group, an optionally substituted C2-C8 alkenyl group, an optionally substituted C2-C8 alkynyl group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C7-C16 aralkyl group, an optionally substituted C3-C8 cycloalkyl group or an optionally substituted heteroarylalkyl group; the substituent(s) of R 2 are one or more substituent(s) selected from the group consisting of a halogen atom, a cyano group, a nitro group, an optionally substituted C1-C8 alkyl group, —OR 2a , SR 2b , —NR 2c R 2d , —C(═O)R 2e , —S(═O) 2 NR 2f R 2g , —C(═O)OR 2h , —C(═O)NR 2i R 2j , —NR 2k C(═O)R 2l and —NR 2m S(═O) 2 R 2n ; R 2y (y represents a, b, c, d, e, f, g, h, i, j, k, l, m or n) may be identical or different and represents a hydrogen atom, an optionally substituted C1-C8 alkyl group (when two C1-C8 alkyl groups as R 2y bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C7-C16 aralkyl group or an optionally substituted heteroarylalkyl group; when R 2 is an optionally substituted C6-C14 aryl group or an optionally substituted heteroaryl group and two or more substituents of R 2 bond to R 2 , these substituents may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring; R 3 represents an optionally substituted C1-C8 alkyl group, an optionally substituted C3-C8 cycloalkyl group or an optionally substituted aliphatic heterocyclic group; the substituent(s) of R 3 are one or more substituent(s) selected from the group consisting of a halogen atom, a cyano group, a nitro group, —OR 3a , —SR 3b , —NR 3c R 3d , an optionally substituted C1-C8 alkyl group, an optionally substituted C3-C8 cycloalkyl group and an optionally substituted aliphatic heterocyclic group; R 3z (z represents a, b, c or d) may be identical or different and represents a hydrogen atom, an optionally substituted C1-C8 alkyl group (when two C1-C8 alkyl groups as R 3z bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C7-C16 aralkyl group or an optionally substituted heteroarylalkyl group; and the substituent(s) of substituent of R 1 , R 2 and R 3 are, unless specifically defined, one or more substituent(s) selected from the group consisting of a halogen atom; a hydroxyl group; a cyano group; a nitro group; an amino group; a C1-C8 alkyl group optionally substituted with halogen atom(s), hydroxyl group(s), cyano group(s) or oxo group(s); a C3-C8 cycloalkyl group optionally substituted with methyl group(s), halogen atom(s), hydroxyl group(s), cyano group(s) or oxo group(s); a C1-C8 alkoxy group optionally substituted with halogen atom(s), hydroxyl group(s) or cyano group(s); a C3-C8 cycloalkyl-oxy group cycloalkyl-oxy group optionally substituted with methyl group(s), halogen atom(s), hydroxyl group(s) or cyano group(s); an aliphatic heterocyclic group optionally substituted with methyl group(s), halogen atom(s), hydroxyl group(s) or cyano group(s); a C6-C14 aryl group optionally substituted with methyl group(s), halogen atom(s), hydroxyl group(s) or cyano group(s); and a heteroaryl group optionally substituted with methyl group(s), halogen atom(s), hydroxyl group(s) or cyano group(s). <3> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to <1> or <2>, except for: compounds wherein R 1 is an unsubstituted or fluorinated C1-C6 alkyl group or an unsubstituted C3-C7 cycloalkyl group; R 2 is an unsubstituted C1-C6 alkyl group or a C1-C6 alkyl group substituted with a halogen atom, a hydroxyl group or —NR 2c R 2d or an unsubstituted C3-C7 cycloalkyl group (R 2c and R 2d , which may be identical or different, are independently a hydrogen atom, an unsubstituted or fluorinated C1-C6 alkyl group or an unsubstituted C3-C7 cycloalkyl group); and R 3 is an unsubstituted C1-C6 alkyl group: compounds wherein R 1 is an unsubstituted C1-C6 alkyl group or an unsubstituted or halogenated phenyl group; R 2 is an unsubstituted C1-C6 alkyl group or a C1-6 alkyl group substituted with a halogen atom, a —OH or —NR 2c R 2d or an unsubstituted C3-C7 cycloalkyl group (R 2c and R 2d , which may be identical or different, are independently a hydrogen atom, an unsubstituted or fluorinated C1-C6 alkyl group or an unsubstituted C3-C7 cycloalkyl group); and R 3 is an unsubstituted or fluorinated C1-C6 alkyl group or an unsubstituted C3-C7 cycloalkyl group: and compounds wherein R 1 is a C1-C8 alkyl group substituted with —NR 1c R 1d , —NR 1k —CO—R 1l or —NR 1m S(═O) 2 R 1n or a C3-C8 cycloalkyl group substituted with —NR 1c R 1d , —NR 1k —CO—R 1l or —NR 1m S(═O) 2 R 1n ; and R 3 is an unsubstituted alkyl group or an alkyl group substituted with OR 3a . <4> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to <1> or <2>, wherein: R 1 is a C1-C8 alkyl group substituted with substituent(s) other than a fluorine atom, —NR 1c R 1d , —NR 1k —CO—R 1l or —NR 1m S(═O) 2 R 1n , an optionally substituted C2-C8 alkenyl group, an optionally substituted C2-C8 alkynyl group, a C6 aryl group substituted with substituent(s) other than halogen atoms, an optionally substituted C7-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C7-C16 aralkyl group, an optionally substituted heteroarylalkyl group, a C3-C8 cycloalkyl group substituted with substituent(s) other than, —NR 1c R 1d , —NR 1k —CO—R 1l or —NR 1m S(═O) 2 R 1n , or an optionally substituted aliphatic heterocyclic group; and R 3 is a C1-C8 alkyl group substituted with substituent(s) other than a fluorine atom or —OR 3a , a substituted C3-C8 cycloalkyl group or an optionally substituted aliphatic heterocyclic group. <5> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <4>, wherein R 1 is an optionally substituted C1-C8 alkyl group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C7-C16 aralkyl group, an optionally substituted heteroarylalkyl group or an optionally substituted C3-C8 cycloalkyl group. <6> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <4>, wherein R 1 is an optionally substituted C1-C8 alkyl group, an optionally substituted C6-C14 aryl group or an optionally substituted heteroaryl group. <7> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <4>, wherein R 1 is an optionally substituted C6-C14 aryl group or an optionally substituted heteroaryl group. <8> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <4>, wherein R 1 is an optionally substituted phenyl group. <9> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <4>, wherein R 1 is an optionally substituted heteroaryl group. <10> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to <9>, wherein R 1 is a heteroaryl group wherein a phenyl group and an optionally substituted monocyclic heteroaryl ring are fused and the phenyl group bonds to the NH group at the 7 position of the pyrazolo[1,5-a]pyridine derivative of formula (I). <11> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <4>, wherein R 1 is an optionally substituted C7-C16 aralkyl group or an optionally substituted heteroarylalkyl group. <12> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <11>, wherein the substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of a fluorine atom, a chlorine atom, a cyano group, a nitro group, an optionally substituted C1-C6 alkyl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted C1-C6 alkoxy group, an optionally substituted C1-C6 alkylthio group, an optionally substituted phenyl group, an optionally substituted heteroaryl group, an optionally substituted C1-C6 acyl group, an optionally substituted C1-C6 acylamino group, an optionally substituted aminosulfonyl group (when two alkyl groups bond to the aminosulfonyl group, they may be identical or different and they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C2-C7 alkoxycarbonyl group, an optionally substituted sulfonylamino group and an optionally substituted carbamoyl group (when two alkyl groups bond to the carbamoyl group, they may be identical or different and they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring). <13> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1 > to <(1 1>, wherein the substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of a fluorine, atom a chlorine atom, a cyano group, a nitro group, an optionally substituted C1-C6 alkylthio group, an optionally substituted C1-C6 acyl group, an optionally substituted C1-C6 acylamino group, an optionally substituted aminosulfonyl group (when two alkyl groups bond to the aminosulfonyl group, they may be identical or different and they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C2-C7 alkoxycarbonyl group, an optionally substituted sulfonylamino group and an optionally substituted carbamoyl group (when two alkyl groups bond to the carbamoyl group, they may be identical or different and they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring). <14> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <1 1>, wherein the substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of a fluorine atom, a chlorine atom, a cyano group, a nitro group, an optionally substituted phenyl group and an optionally substituted heteroaryl group. <15> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <11>, wherein the substituent(s) of R 1 are a substituent selected from the group consisting of an optionally substituted phenyl group and an optionally substituted heteroaryl group; and the substituent(s) of R 1 may contain one or more substituent(s) selected from the group consisting of a fluorine atom, a chlorine atom, a cyano group and a nitro group. <16> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1 > to <11>, wherein the substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of a fluorine atom; a chlorine atom; a cyano group; a C1-C6 alkyl group(s) optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group and a cyano group; a C3-C8 cycloalkyl group(s) optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group and a cyano group; a C1-C6 alkyl group(s) substituted with a C1-6 alkoxy group optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group and a cyano group; and a C1-C6 alkyl group(s) substituted with a C3-C6 cycloalkyl-oxy group optionally substituted with one or more substituent(s) selected from the group consisting of a methyl group, a halogen atom, a hydroxyl group, a cyano group and an oxo group. <17> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any one of <1> to <11>, wherein: the substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of: a C1-C6 alkyl group(s) optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group and a cyano group; a C3-C8 cycloalkyl group(s) optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group and a cyano group; a C1-C6 alkyl group(s) substituted with a C1-C6 alkoxy group optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group and a cyano group; a C1-C6 alkyl group substituted with a C3-C6 cycloalkyl-oxy group cycloalkyl-oxy group optionally substituted with one or more substituent(s) selected from the group consisting of a methyl group, a halogen atom, a hydroxyl group, a cyano group and an oxo group; and the substituent(s) of R 1 may contain one or more substituent(s) selected from the group consisting of a fluorine atom, a chlorine atom and a cyano group. <18> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <1 1>, wherein: the substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of: a C1-C6 alkyl group(s) optionally substituted with one or more substituent(s) selected from the group consisting of a carboxyl group, an oxo group and a C1-C6 alkoxy group optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group and a cyano group; a C1-6 alkyl group(s) optionally substituted with a heteroaryl group optionally substituted with one or more substituent(s) selected from the group consisting of a methyl group, a halogen atom, a hydroxyl group and a cyano group; and a C1-C6 alkyl group(s) optionally substituted with an aliphatic heterocyclic group optionally substituted with one or more substituent(s) selected from the group consisting of a methyl group, a halogen atom, a hydroxyl group and a cyano group; and the substituent(s) of R 1 may contain one or more substituent(s) selected from the group consisting of a fluorine atom, a chlorine atom, a cyano group and a methyl group. <19> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <11>, wherein the substituent(s) of R 1 are C1-C6 alkyl group(s) optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group and a cyano group. <20> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <11>, wherein the substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of: a fluorine atom; a chlorine atom; a cyano group; a C1-C6 alkoxy group(s) optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group and a cyano group; a C1-C6 alkoxy group(s) substituted with an aliphatic heterocyclic group optionally substituted with one or more substituent(s) selected from the group consisting of a methyl group, a halogen atom, a hydroxyl group and a cyano group; a C1-C6 alkoxy group(s) substituted with a C1-C6 alkoxy group(s) optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group, and a cyano group; and a C1-C6 alkoxy group(s) substituted with a C3-C6 cycloalkyl-oxy group cycloalkyl-oxy group optionally substituted with one or more substituent(s) selected from the group consisting of a methyl group, a halogen atom, a hydroxyl group, a cyano group and an oxo group. <21> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <11>, wherein the substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of: a C1-6 alkoxy group(s) optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group and a cyano group; a C1-C6 alkoxy group(s) substituted with an aliphatic heterocyclic group optionally substituted with one or more substituent(s) selected from the group consisting of a methyl group, a halogen atom, a hydroxyl group and a cyano group; a C1-C6 alkoxy group(s) substituted with a C1-C6 alkoxy group optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group and a cyano group; and a C1-6 alkoxy group(s) substituted with a C3-C6 cycloalkyl-oxy group cycloalkyl-oxy group optionally substituted with one or more substituent(s) selected from the group consisting of a methyl group, a halogen atom, a hydroxyl group, a cyano group and an oxo group; and the substituent(s) of R 1 may contain one or more substituent(s) selected from the group consisting of a fluorine atom, a chlorine atom and a cyano group. <22> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <11>, wherein the substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of: a C1-C6 alkoxy group(s) optionally substituted with one or more substituent(s) selected from the group consisting of a carboxyl group, an oxo group and a C1-C6 alkoxy group(s) optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group and a cyano group; and a C1-C6 alkoxy group(s) optionally substituted with a heteroaryl group optionally substituted with one or more substituent(s) selected from the group consisting of a methyl group, a halogen atom, a hydroxyl group and a cyano group; and the substituent(s) of R 1 may contain one or more substituent(s) selected from the group consisting of a fluorine atom, a chlorine atom, a cyano group and a methyl group. <23> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <1 1>, wherein the substituent(s) of R 1 are C1-C6 alkoxy group(s) optionally substituted with one or more substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group and a cyano group. <24> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <23>, wherein R 2 is a hydrogen atom, an optionally substituted C1-C8 alkyl group, an optionally substituted C2-C8 alkenyl group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C7-C16 aralkyl group, an optionally substituted heteroarylalkyl group, or an optionally substituted C3-C8 cycloalkyl group. <25> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <23>, wherein R 2 is a hydrogen atom, an optionally substituted C1-C6 alkyl group, an optionally substituted C2-C6 alkenyl group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C7-C12 phenylalkyl group or an optionally substituted C3-C6 cycloalkyl group. <26> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <23>, wherein R 2 is a hydrogen atom, an optionally substituted C1-C6 alkyl group, an optionally substituted C2-C6 alkenyl group, or an optionally substituted C3-C6 cycloalkyl group. <27> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <23>, wherein R is an optionally substituted C1-C6 alkyl group or an optionally substituted C2-C6 alkenyl group. <28> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <23>, wherein R 2 is an optionally substituted C1-C4 alkyl group. <29> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <23, wherein R 2 is a hydrogen atom. <30> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <23>, wherein R 2 is an optionally substituted phenyl group or an optionally substituted heteroaryl group. <31> The pyrazolo[ 1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <4) and <24> to <30>, wherein the substituent(s) of R 2 are one or more substituent(s) selected from the group consisting of a halogen atom, a cyano group, a nitro group, a hydroxyl group, an optionally substituted amino group (when two alkyl groups bond to the amino group, they may be identical or different and may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C1-C6 alkyl group, an optionally substituted C1-C6 alkoxy group, an optionally substituted C1-C6 acyl group, an optionally substituted aminosulfonyl group (when two alkyl groups bond to the aminosulfonyl group, they may be identical or different and may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted sulfonylamino group and an optionally substituted carbamoyl group (when two alkyl groups bond to the carbamoyl group, they may be identical or different and may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring). <32> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <4>and <24> to <30>, wherein the substituent(s) of R 2 are one or more substituent(s) selected from the group consisting of a halogen atom, a cyano group, a nitro group, a hydroxyl group, an optionally substituted amino group (when two alkyl groups bond to the amino group, they may be identical or different and may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C1-C6 acyl group and an optionally substituted carbamoyl group (when two alkyl groups bond to the carbamoyl group, they may be identical or different and may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring). <33> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <4> and claims <24> to <30>, wherein the substituent(s) of R 2 are one or more substituent(s) selected from the group consisting of a halogen atom, a cyano group, a nitro group, a hydroxyl group, an optionally substituted amino group (when two alkyl groups bond to the amino group, they may be identical or different and may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C1-C6 alkyl group and an optionally substituted C1-C6 alkoxy group. <34> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <33>, wherein R 3 is an optionally substituted C1-C8 alkyl group, an optionally substituted C3-C8 cycloalkyl group or an optionally substituted aliphatic heterocyclic group. <35> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <33>, wherein R 3 is an optionally substituted C3-C8 cycloalkyl group or an optionally substituted aliphatic heterocyclic group having 1 to 4 nitrogen atom(s) as heteroatoms. <36> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <33>, wherein R 3 is an optionally substituted C5-C6 cycloalkyl group, an optionally substituted piperidyl group, an optionally substituted pyrrolidinyl group or an optionally substituted hexahydroazepinyl group. <37> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <> to <33>, wherein R 3 is an optionally substituted cyclohexyl group, an optionally substituted piperidyl group or an optionally substituted pyrrolidinyl group. <38> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <33>, wherein R 3 is an optionally substituted piperidyl group. <39> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <33>, wherein R 3 is an optionally substituted C1-C4 alkyl group. <40> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <4> and <34> to <39>, wherein the substituent(s) of R 3 are one or more substituent(s) selected from the group consisting of a fluorine atom, a hydroxyl group, a cyano group, an optionally substituted C1-C6 alkyl group and an optionally substituted amino group (when two alkyl groups bond to the amino group, they may be identical or different and may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring). <41> The pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <4> and <34> to <39>, wherein the substituent(s) of R 3 are one or more substituent(s) selected from the group consisting of a fluorine atom; a hydroxyl group; a cyano group; an optionally substituted amino group (when two alkyl groups bond to the amino group, they may be identical or different and may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring); a C5-C6 cycloalkyl group optionally substituted with an optionally substituted amino group (when two alkyl groups bond to the amino group, they may be identical or different and may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring); a piperazino group optionally substituted with C1-C6 alkyl group(s) optionally substituted with fluorine atom(s) or hydroxyl group(s), a piperidyl group optionally substituted with C1-C6 alkyl group(s) optionally substituted with fluorine atom(s) or hydroxyl group(s) or a pyrrolidinyl group optionally substituted with C1-C6 alkyl group(s) optionally substituted with fluorine atom(s) or hydroxyl group(s). <42> A pyrazolo[1,5-a]pyridine derivative represented by formula (6) or salt thereof:

wherein R 2 is as defined in formula (I).

<43> A pyrazolo[1,5-a]pyridine derivative represented by formula (7) or salt thereof:

wherein R 2 as defined in formula (I) and W represents a halogen atom.

<44> A pyrazolo[1,5-a]pyridine derivative represented by formula (8) or salt thereof:

wherein R 1 and R 2 are as defined in formula (I).

<45> A pyrazolo[1,5-a]pyridine derivative represented by formula (9) or salt thereof:

wherein R 1 and R 2 are as defined in formula (I) and P represents a protective group of an amino group.

<46> A pyrazolo[1,5-a]pyridine derivative represented by formula (10) or salt thereof:

wherein R 1 and R 2 are as defined in formula (I) and Boc represents tert-butoxycarbonyl.

<47> A pyrazolo[1,5-a]pyridine derivative represented by formula (11) or salt thereof:

wherein R 1 and R 2 are as defined in formula (I), P represents a protective group of an amino group and L represents perfluoroalkylsulfonyl.

<48> A pyrazolo[1,5-a]pyridine derivative represented by formula (12) or salt thereof:

wherein R 1 and R 2 are as defined in formula (I), Boc represents tert-butoxycarbonyl and Tf represents trifluoromethanesulfonyl.

<49> A pyrazolo[1,5-a]pyridine derivative represented by formula (13) or salt thereof:

wherein R 1 , R 2 and R 3 are as defined in formula (I) and P represents a protective group of an amino group.

<50> A pyrazolo[1,5-a]pyridine derivative represented by formula (14) or salt thereof:

wherein R 1 , R 2 and R 3 are as defined in formula (I) and Boc represents tert-butoxycarbonyl.

<51> The pyrazolo[1,5-a]pyridine derivative represented by any of formulae (8) to (14) or salt thereof according to any of <44> to <50> except a compound wherein R 1 is a C1-C8 alkyl group optionally substituted with —NR 1c R 1d , —NR 1k —CO—R 1l or —NR 1m S(═O) 2 R 1n ; or a C3-C8 cycloalkyl group optionally substituted with —NR 1c R 1d , —NR 1k —CO—R 1l or —NR 1m S(═O) 2 R 1n . <52> A pharmaceutical composition comprising the pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <41> and a pharmaceutically acceptable carrier. <53> A MAPKAP-K2 inhibitor comprising the pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <41> as an active ingredient. <54> A treating or preventing agent comprising the pyrazolo[1,5-a]pyridine derivative or pharmaceutically acceptable salt thereof according to any of <1> to <41> as an active ingredient for neurodegenerative/neurological disorders (including dementia), sepsis, autoimmune diseases, destructive osteopathy, inflammatory bowel disease, psoriasis, diabetes mellitus, cancer, ischemic reperfusion injury, angiodysplasia, cachexia, obesity, angiogenesis, asthma and/or chronic obstructive pulmonary disease (COPD). <55> The treating or preventing agent according to <54>, wherein the autoimmune disease is rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis, graft-versus-host disease, diabetes mellitus or Crohn's disease.

FIG. 1 is a Figure illustrating p38MAPK cascade.

Each compound of the present invention represented by formula (I) is defined as follows:

“C1-C8 Alkyl” in the present description represents either a straight or branched chain alkyl group having 1 to 8 carbon atoms. It includes, not limited thereto, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, 2-methylpentyl, 4-methylpentyl, 3-hexyl, n-hexyl, n-heptyl, 2-methylhexyl, 5-methylhexyl, 2-methyl-2-hexyl, 6 -methylheptyl, n-octyl and the like. Preferably it is an alkyl group having 1 to 6 carbon atoms. More preferably it is an alkyl group having 1 to 4 carbon atoms, including, not limited thereto, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl and the like.

“C2-C8 Alkenyl” in the present description means a straight or branched chain alkenyl group having 2 to 8 carbon atoms. It includes, not limited thereto, for example, vinyl, allyl, 1-propenyl, 2-butenyl, 3-butenyl, 2-methyl-1-propenyl, 4-pentenyl, 5-hexenyl, 4-methyl-3-pentenyl and the like. Preferably it is an alkenyl group having 2 to 6 carbon atoms. More preferably it is an alkenyl group having 2 to 4 carbon atoms, including, for example, vinyl, allyl, isopropenyl, 1-propenyl, 2-butenyl, 1-butenyl, 2-methyl-1-propenyl and the like.

“C2-C8 Alkynyl” in the present description means a straight or branched chain alkynyl group having 2 to 8 carbon atoms. It includes, not limited thereto, for example, ethynyl, propargyl, 3-methylpropargyl, 1-butynyl, 2-butynyl-1-yl, pentynyl, hexynyl and the like. Preferably it is an alkynyl group having 2 to 6 carbon atoms. More preferably it is an alkynyl group having 2 to 4 carbon atom, including, not limited thereto, for example, ethynyl, propargyl, 1-propynyl, 1-butynyl and the like.

“C3-C8 Cycloalkyl group” in the present description means a partially unsaturated or saturated cycloalkyl group having 3 to 8 carbon atoms. It includes, not limited thereto, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl and the like. Preferably, it is an cycloalkyl group having 3 to 6 carbon atoms, including, not limited thereto, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.

“C6-C14 Aryl” in the present description means an aryl group having 6 to 14 carbon atoms which contains one ring or in which an aromatic ring is fused with one or two or more of saturated or unsaturated ring. It includes, not limited thereto, for example, phenyl, naphthyl, anthracenyl, 5-indanyl, 5,6,7,8-tetrahydro-2-naphthyl and the like. Preferably it is an aryl group having 6 to 10 carbon atoms, including, not limited thereto, for example, phenyl, naphthyl, 5-indanyl and the like. More preferably it is a phenyl group or the like.

“Heteroaryl” in the present description means a heterocyclic group with aromaticity containing 1 to 4 atoms selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom as heteroatoms. It includes, not limited thereto, for example, monovalent groups comprising furan, thiophene, pyrrole, oxazole, thiazole, isothiazole, imidazole, pyrazole, triazole, thiadiazole, oxadiazole, tetrazole, pyridine, pyrazine, pyrimidine, pyridazine, benzofuran, dibenzofuran, benzothiophene, indole, benzimidazole, benzothiazole, benzoxazole, quinoline, isoquinoline, quinazoline, quinoxaline, purine, pteridine, phenoxazine, phenothiazine, acridine, carbazole, cinnoline, dithiazole, indazole, isoindole, isoxazole, naphthyridine, oxathiazole, phthalazine, tetrazine, thiatriazole, triazine and the like. Preferably it is, not limited thereto, for example, a monovalent group comprising furan, thiophene, pyrrole, oxazole, thiazole, isothiazole, imidazole, pyrazole, triazole, pyridine, pyrimidine, pyrazine, pyridazine, benzothiazole, benzoxazole, benzothiophene, benzofuran, indole, indazole, quinoline, phthalazine, quinoxaline, quinazoline, cinnoline, isoindole or the like. More preferably it is, not limited thereto, for example, a monovalent group comprising furan, thiophene, pyrrole, oxazole, thiazole, imidazole, pyrazole, pyridine, pyrimidine, pyrazine, pyridazine, benzothiazole, benzoxazole, benzothiophene, benzofuran, indole, indazole, quinoline, phthalazine, quinoxaline, quinazoline, cinnoline or the like.

“Aliphatic heterocyclic group” in the present description means a partially unsaturated or saturated aliphatic heterocyclic group containing 1 to 4 atoms selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom as heteroatoms. Also, the aliphatic heterocyclic group may contain 1 or 2 of —C(═O)— or —C(═S)— in the ring. An aliphatic heterocyclic group which is fused with an aromatic hydrocarbon or an aromatic heterocycle is also included in the aliphatic heterocyclic group. It includes, not limited thereto, for example, monovalent groups and the like comprising piperidine, pyrrolidine, pyrroline, tetrahydrofuran, dihydropyran, hexahydroazepine, piperazine, quinuclidine, morpholine, thiomorpholine, oxazoline, dioxane, pyran, 2-pyrrolidone, tetrahydro-3H-pyrazol-3-one, 1,2,3,4-tetrahydroisoquinoline, 1,2,3,4-tetrahydroquinoline, 4,5,6,7-tetrahydro-1H-pyrazolo[5,4-c]pyridine, 4,5,6,7-tetrahydro-1H-pyrolo[2,3-c]pyridine, 4,5,6,7-tetrahydrothieno[2,3-c]pyridine, 4,5,6,7-tetrahydro-2H-pyrolo[3,4-c]pyridine, 4,5,6,7-tetrahydrofuro[3,2-c]pyridine, 1,2,3,4-tetrahydro[2,7]naphthyridine, 4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine, 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine and the like. Preferably, it is, not limited thereto, for example, a monovalent group comprising piperidine, pyrrolidine, pyrroline, tetrahydrofuran, hexahydroazepine, piperazine, morpholine, oxazoline, dioxane, pyran, 1,2,3,4-tetrahydroisoquinoline or the like. More preferably it means a partially unsaturated or saturated aliphatic heterocyclic group containing 1 to 3 heteroatoms at least one of which is a nitrogen atom. Such a group includes, not limited thereto, for example, monovalent groups comprising piperidine, pyrrolidine, pyrroline, hexahydroazepine, piperazine, morpholine, oxazoline and the like. More preferably, it is a monovalent group comprising piperidine, pyrrolidine, hexahydroazepine, piperazine, morpholine or the like.

“Aralkyl” in the present description is a group comprising an aryl group and an alkyl group in combination. It includes, not limited thereto, for example, benzyl, phenethyl, (2-naphthyl)methyl, 3-phenylpropyl, 4-phenylbutyl, 5-(1-naphthyl)pentyl and the like. Preferably it is a group comprising a phenyl or naphthyl group as its aryl moiety and an alkyl group having 1 to 6 carbon atoms in combination. More preferably it is a group comprising a phenyl group as its aryl moiety and an alkyl group having 1 to 4 carbon atoms in combination, including, not limited thereto, for example, benzyl, phenethyl, 3-phenylpropyl, 4-phenylbutyl and the like.

“Heteroarylalkyl” in the present description is a group comprising a heteroaryl group and an alkyl group in combination. Preferably it is a group comprising a 5- to 10-membered monocyclic or bicyclic heteroaryl group having 1 to 3 heteroatoms selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom, and an alkyl group having 1 to 4 carbon atoms in combination. More preferably it is, not limited thereto, for example, 2-furylmethyl, 3-furylmethyl, 2-(2-thienyl)ethyl, 2-(3-thienyl)propyl, 2-methyl-1-(1-pyrrolyl)propyl, 1-(2-pyrrolyl)ethyl or the like.

“Aliphatic heterocyclylalkyl” in the present description is a group comprising an aliphatic heterocycle and an alkyl group in combination. Preferably it is a group comprising a partially unsaturated or saturated aliphatic heterocycle having 1 to 3 atoms selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom as heteroatoms, and an alkyl group having 1 to 4 carbon atoms in combination. More preferably it is, not limited thereto, for example, 3-piperidylmethyl, 3-pyrrolidylmethyl, 2-(4-piperidyl)ethyl, 2-(2-tetrahydrofuryl)propyl, 1-(2-morpholinyl)ethyl, morpholinomethyl, 1-(1-pyrrolidonyl)ethyl or the like.

“C1-C8 Alkoxy” in the present description represents either a straight or branched chain alkoxy group having 1 to 8 carbon atoms. It includes, not limited thereto, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, n-pentyloxy, n-hexyloxy n-heptyloxy and the like. Preferably it is an alkoxy group having 1 to 6 carbon atoms. More preferably it is an alkoxy group having 1 to 4 carbon atoms, including, not limited thereto, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy and the like.

“Alicyclic hydrocarbyloxy” in the present description is a group comprising an cycloalkyl group and an oxy group in combination. It includes, not limited thereto, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclopentenyloxy, cyclohexyloxy, cyclohexenyloxy, cycloheptyloxy, cyclooctyloxy and the like. Preferably it is an cycloalkyl-oxy group cycloalkyl-oxy group having 3 to 8 carbon atoms. More preferably it is an alkoxy group having 3 to 6 carbon atoms, including, not limited thereto, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy and the like.

“C1-C6 Alkylthio” in the present description is a group comprising a C1-C6 alkyl and a thio group in combination. It includes, not limited thereto, for example, methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, sec-butylthio, isobutylthio, tert-butylthio, n-pentylthio, isopentylthio, neopentylthio, tert-pentylthio, 2-methylpentylthio, 4-methylpentylthio, 3-hexylthio, n-hexylthio, n-heptylthio and the like. Preferably it is an alkylthio group having 1 to 4 carbon atoms. More preferably, it is an alkylthio group having 1 to 3 carbon atoms, including, not limited thereto, for example, methylthio, ethylthio, n-propylthio, isopropylthio and the like.

“C1-C6 Acyl” in the present description is an acyl group comprising an alkyl having 1 to 6 carbon atoms or an alicyclic group having 1 to 6 carbon atoms. Preferably it is, not limited thereto, for example, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl or the like.

“C1-C6 Acylamino” in the present description is a group comprising a C1-C6 acyl and an amino group in combination. Preferably it is, not limited thereto, for example, acetylamino, propionylamino, butyrylamino, isobutyrylamino, valerylamino, isovalerylamino, pivaloylamino or the like.

“C2-C7 Alkoxycarbonyl” in the present description is a group comprising a C1-C6 alkoxy and a carbonyl group in combination. Preferably it is, not limited thereto, for example, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl or the like.

“C7-C12 Phenylalkyl group” in the present description is a group comprising phenyl and a C1-C6 alkyl group in combination. Preferably it is, not limited thereto, for example, benzyl, phenethyl, 2-phenylpropyl, 3-phenylpropyl, 4-phenylbutyl or the like.

“Protective group for an amino group” in the present description is a protective group for an amino group generally used in this field (Reference: Protective Groups in Organic Synthesis, 3rd edition, John Wiley & Sons Inc.). Preferably it is, not limited thereto, for example, tert-butoxycarbonyl, benzyloxycarbonyl, methoxycarbonyl, ethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, acetyl, trifluoroacetyl, pivaloyl, benzoyl, 2,4,6-trimethylbenzoyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, tert-butyl, methoxymethyl, 2-trimethylsilylethoxymethyl, benzyloxymethyl or the like. More preferably it is, not limited thereto, for example, alkoxycarbonyl such as tert-butoxycarbonyl, benzyloxycarbonyl, methoxycarbonyl, ethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl or the like. Further preferably it is tert-butoxycarbonyl.

“Perfluoroalkylsulfonyl” in the present description is a polyfluorinated alkylsulfonyl group which is generally used for transforming a hydroxyl group to a leaving group in this field. Preferably it is, not limited thereto, for example, trifluoromethanesulfonyl, nonafluorobutanesulfonyl or the like. More preferably, it is trifluoromethanesulfonyl.

“Halogen atom” in the present description means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. Preferably it is a fluorine atom, a chlorine atom or a bromine atom, and more preferably it is a fluorine atom or a chlorine atom.

“C1-C8 Alkyl group (when two C1-C8 alkyl groups as R 1x , R 2y or R 3z bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring)” as R 1x , R 2y or R 3z in the present description includes, not limited thereto, for example, 1-pyrrolidinyl, 2-methyl-1-pyrrolidinyl, 1-piperidyl, morpholino, thiomorpholino, piperazino and the like. Preferably it is, not limited thereto, for example, 1-pyrrolidinyl, 1-piperidyl, morpholino, piperazino or the like.

“C1-C8 Alkyl group optionally substituted with oxo group(s)” included in “C1-C8 alkyl group optionally substituted with halogen atom(s), hydroxyl group(s) or oxo group(s)” as the substituent of substituent(s) of R 1 , R 2 or R 3 in the present description includes, not limited thereto, for example, an acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a valeryl group, an isovaleryl group, a 2-oxopropyl group, a 3-oxobutyl group, a pivaloyl group and the like. Preferably it is, not limited thereto, for example, an acetyl group, a propionyl group, an isobutyryl group, a valeryl group, an isovaleryl group, a pivaloyl group or the like.

With respect to R 1 and R 2 in the present description, the case wherein “when R 1 or R 2 is an optionally substituted C6-C14 aryl group or an optionally substituted heteroaryl group, and two or more substituents of R 1 or R 2 bond to R 1 or R 2 , these substituents may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring” includes, not limited thereto, for example, chromane, indoline, isochromane, isoindoline, 2H,3H-benzo[e]1,4-dioxine, 2H-benzo[d]1,3-dioxolene, 2H,3H,4H-benzo[e]thiine, 2H,3H,4H-benzo[e]1,4-oxazine and the like. Preferably it is, not limited thereto, for example, chromane, indoline, isochromane, isoindoline, 2H,3H-benzo[e]1,4-dioxine, 2H-benzo[d]1,3-dioxolene or the like.

In the above definition, “C” in for example “C1” represents a carbon atom and the subsequent numeral represents the number of carbon atoms. For example, “C1-C6” represents the range of number of carbon atoms from 1 to 6. Needless to say, in the present invention, each group different in number of carbon atoms means the same type of group having each specified number of carbon atoms. For example, “C1-C6 alkyl group” means an alkyl group, which is defined for “C1-C8 alkyl group”, having 1 to 6 carbon atoms. The number of carbon atoms in other groups is interpreted in the same way.

R 1 represents an optionally substituted C1-C8 alkyl group, an optionally substituted C2-C8 alkenyl group, an optionally substituted C2-C8 alkynyl group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C7-C16 aralkyl group, an optionally substituted heteroarylalkyl group, an optionally substituted C3-C8 cycloalkyl group or an optionally substituted aliphatic heterocyclic group. Preferably it is an optionally substituted C1-C8 alkyl group, an optionally substituted C2-C8 alkenyl group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C7-C16 aralkyl group, an optionally substituted heteroarylalkyl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group or the like. More preferably it is an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C7-C16 aralkyl group, an optionally substituted heteroarylalkyl group or the like. Further preferably it is an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group or the like, and even more preferably it is an optionally substituted phenyl group, an optionally substituted heteroaryl group or the like. The optionally substituted heteroaryl group as R 1 is preferably a heteroaryl group wherein a monocyclic aryl group and an optionally substituted monocyclic heteroaryl group are fused with each other and the aryl group is bonded to the NH group at the 7-position of the pyrazolo[1,5-a]pyridine derivative represented by formula (I). The monocyclic aryl group is a phenyl group or the like. Preferably the heteroaryl group is, not limited thereto, for example, benzothiazol-4-yl, benzothiazol-5-yl, benzothiazol-6-yl, benzothiazol-7-yl, benzoxazol-4-yl, benzoxazol-5-yl, benzoxazol-6-yl, benzoxazol-7-yl, benzimidazol-4-yl, benzimidazol-5-yl, benzimidazol-6-yl, benzimidazol-7-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, indazol-7-yl, benzothiophen-4-yl, benzothiophen-5-yl, benzothiophen-6-yl, benzothiophen-7-yl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl or the like. More preferably, it is benzothiazol-5-yl, benzothiazol-6-yl, benzoxazol-5-yl, benzoxazol-6-yl, benzimidazol-5-yl, benzimidazol-6-yl, indazol-5-yl, indazol-6-yl, benzothiophen-5-yl, benzothiophen-6-yl, indol-5-yl, indol-6-yl or the like.

The substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of a halogen atom, a cyano group, a nitro group, an optionally substituted C1-C8 alkyl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, —OR 1a , —SR 1b , —NR 1c R 1d , —C(═O)R 1e , —S(═O) 2 NR 1f R 1g , —C(═O)OR 1h , —C(═O)NR 1i R 1j , —NR 1k C(═O)R 1l , —NR 1m S(═O) 2 R 1n and the like. Preferably it is 1 to 5 substituents selected from the group consisting of a halogen atom, a cyano group, an optionally substituted C1-C8 alkyl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, —OR 1a , —NR 1c R 1d , —C(═O)R 1e , —S(═O) 2 NR 1f R 1g , —C(═O)OR 1h , —C(═O)NR 1i R 1j , —NR 1k C(═O)R 1l , —NR 1m S(═O) 2 R 1n and the like. More preferably it is 1 to 4 substituents selected from the group consisting of a halogen atom, an optionally substituted C1-C6 alkyl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, —OR 1a , —NR 1c R 1d , —(═O) 2 NR 1f , R 1g , —C(═O)OR 1h , —C(═O)NR 1i R 1j , —NR 1k C(═O)R 1l , —NR 1m S(═O) 2 R 1n and the like. Further preferably it is 1 to 3 substituents selected from the group consisting of a halogen atom, an optionally substituted C1-C4 alkyl group, an optionally substituted C3-C6 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted phenyl group, an optionally substituted heteroaryl group, —OR 1a , —NR 1c R 1d , —S(═O) 2 NR 1f R 1g , —C(═O)OR 1h , —C(═O)NR 1i R 1j , —NR 1k C(═O)R 1l , —NR 1m S(═O) 2 R 1n and the like.

R 1x (x represents a, b, c, d, e, f. g, h, i, j, k, l, m or n) may be identical or different, and represents a hydrogen atom, an optionally substituted C1-C8 alkyl group (when two C1-C8 alkyl groups as R 1x bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C7-C16 aralkyl group, an optionally substituted heteroarylalkyl group or an optionally substituted aliphatic heterocyclylalkyl group. Preferably R 1x is a hydrogen atom, an optionally substituted C1-C4 alkyl group (when two C1-C4 alkyl groups as R 1x bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted phenyl group, an optionally substituted heteroaryl group, an optionally substituted C3-C6 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted phenylalkyl group, an optionally substituted heteroarylalkyl group or an optionally substituted aliphatic heterocyclylalkyl group. More preferably R 1x is a hydrogen atom, an optionally substituted C1-C4 alkyl group (when two C1-C4 alkyl groups as R 1x bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted heteroarylalkyl group or an optionally substituted aliphatic heterocyclylalkyl group.

When R 1 is an optionally substituted C6-C14 aryl group or an optionally substituted heteroaryl group and two or more substituents of R 1 bond to R 1 , these substituents may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring.

R 2 represents a hydrogen atom, an optionally substituted C1-C8 alkyl group, an optionally substituted C2-C8 alkenyl group, an optionally substituted C2-C8 alkynyl group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C7-C16 aralkyl group, an optionally substituted C3-C8 cycloalkyl group or an optionally substituted heteroarylalkyl group. Preferably it is a hydrogen atom, an optionally substituted C1-C6 alkyl group, an optionally substituted C2-C6 alkenyl group, an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C3-C8 cycloalkyl group or the like. More preferably it is a hydrogen atom, an optionally substituted C1-C4 alkyl group, an optionally substituted phenyl group, an optionally substituted heteroaryl group, an optionally substituted C3-C6 cycloalkyl group or the like. Further preferably it is a hydrogen atom, an optionally substituted C1-C4 alkyl group or the like.

The substituent(s) of R 2 are one or more substituent(s) selected from the group consisting of a halogen atom, a cyano group, a nitro group, an optionally substituted C1-C8 alkyl group, —OR 2a , —SR 2b , —NR 2c R 2d , —C(═O)R 2e , —S(═O) 2 NR 2f R 2g , —C(═O)OR 2h , —C(═O)NR 2i R 2j , —NR 2k C(═O)R 2l and —NR 1m S(═O) 2 R 1n . Preferably the substituent(s) of R 2 are 1 to 5 substituent(s) selected from the group consisting of a halogen atom, a cyano group, an optionally substituted C1-C6 alkyl group, —OR 2 a, —NR 2c R 2d , —S(═O) 2 NR 2f R 2g , —C(═O)OR 2h , —C(═O)NR 2i R 2j , —NR 2k C(═O)R 2l , —NR 1m S(═O) 2 R 1n and the like, more preferably 1 to 3 substituent(s) selected from the group consisting of a halogen atom, an optionally substituted C1-C4 alkyl group, —OR 2a , NR 2c R 2d , —C(═O)OR 2h , —C(═O)NR 2i R 2j , —NR 2k C(═O)R 2l and the like.

R 2 y (y represents a, b, c, d, e, f, g, h, i, j, k, l, m or n) may be identical or different, and represents a hydrogen atom, an optionally substituted C1-C8 alkyl group (when two C1-C8 alkyl groups as R 2y bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C7-C16 aralkyl group or an optionally substituted heteroarylalkyl group. Preferably R 2y is a hydrogen atom, an optionally substituted C1-C4 alkyl group (when two C1-C4 alkyl groups as R 2y bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted phenyl group, an optionally substituted heteroaryl group, an optionally substituted C3-C6 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted phenylalkyl group, an optionally substituted heteroarylalkyl group or the like. More preferably R 2y is a hydrogen atom, an optionally substituted C1-C4 alkyl group (when two C1-C4 alkyl groups as R 2y bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted heteroarylalkyl group or the like.

When R 2 is an optionally substituted C6-C14 aryl group or an optionally substituted heteroaryl group and two or more substituents of R 2 bond to R 2 , these substituents may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring.

R 3 represents an optionally substituted C1-C8 alkyl group, an optionally substituted C3-C8 cycloalkyl group or an optionally substituted aliphatic heterocyclic group. Preferably it is an optionally substituted C3-C6 cycloalkyl group, an optionally substituted aliphatic heterocyclic group or the like. More preferably it is a C3-C8 cycloalkyl group substituted with an optionally substituted amino group, an optionally substituted aliphatic heterocyclic group having 1 to 4 nitrogen atoms as heteroatoms or the like.

The substituent(s) of R 3 are one or more substituent(s) selected from the group consisting of a halogen atom, a cyano group, a nitro group, —OR 3a , —SR 3b , —NR 3c R 3d , an optionally substituted C1-C8 alkyl group, an optionally substituted C3-C8 cycloalkyl group and an optionally substituted aliphatic heterocyclic group.

When R 3 is an optionally substituted C1-C8 alkyl group, preferred substituents of R 3 are 1 to 3 substituent(s) selected from the group consisting of —OR 3a , —NR 3c R 3d , a C3-C8 cycloalkyl group optionally substituted with an optionally substituted amino group and an optionally substituted aliphatic heterocyclic group. Further, in addition to these substituents, R 3 may be substituted with 1 to 5 substituent(s) selected from the group consisting of a halogen atom, a cyano group, an optionally substituted C1-C6 alkyl group and the like. More preferred substituents of R 3 in the case wherein R 3 is an optionally substituted C1-C8 alkyl group are 1 to 2 substituent(s) selected from the group consisting of —OR 3a , —NR 3c R 3d , a C5-C6 cycloalkyl group optionally substituted with an amino group and an optionally substituted aliphatic heterocyclic group containing 1 to 2 nitrogen atom(s). Here, in addition to these substituents, R 3 may be further substituted with 1 to 4 substituent(s) selected from the group consisting of a fluorine atom, a cyano group, an optionally substituted C1-C4 alkyl group and the like.

When R 3 is an optionally substituted C3-C8 cycloalkyl group, preferred substituents of R 3 are 1 to 3 substituent(s) selected from the group consisting of —OR 3a , —NR 3c R 3d , a C1-C6 alkyl group substituted with an optionally substituted amino group and an optionally substituted aliphatic heterocyclic group. Further, in addition to these substituents, R 3 may be substituted with 1 to 5 substituent(s) selected from the group consisting of a halogen atom, a cyano group, an optionally substituted C1-C6 alkyl group and the like. More preferred substituents of R 3 are, in the case wherein R 3 is an optionally substituted C3-C8 aliphatic hydrocarbon group, 1 to 2 substituent(s) selected from the group consisting of —OR 3a , —NR 3c R 3d , a C1-C6 alkyl group optionally substituted with an amino group and an optionally substituted aliphatic heterocyclic group containing 1 to 2 nitrogen atom(s). Here, in addition to these substituents, R 3 may be further substituted with 1 to 4 substituent(s) selected from the group consisting of a fluorine atom, a cyano group, an optionally substituted C1-C4 alkyl group and the like.

When R 3 is an optionally substituted aliphatic heterocyclic group, preferred substituents of R 3 are 1 to 5 substituent(s) selected from the group consisting of —OR 3a , —NR 3c R 3d , a halogen atom, a cyano group, an optionally substituted C1-C6 alkyl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group and the like. More preferred substituents of R 3 in the case wherein R 3 is an optionally substituted aliphatic heterocyclic group are 1 to 4 substituent(s) selected from the group consisting of —OR 3a , —NR 3c R 3d , a fluorine atom, a cyano group, an optionally substituted C1-C4 alkyl group, an optionally substituted C3-C6 cycloalkyl group, an optionally substituted aliphatic heterocyclic group and the like.

R 3z (z represents a, b, c or d) may be identical or different and represents a hydrogen atom, an optionally substituted C1-C8 alkyl group (when two C1-C8 alkyl groups as R 3z bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted C6-C14 aryl group, an optionally substituted heteroaryl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted C7-C16 aralkyl group or an optionally substituted heteroarylalkyl group. Preferably R 3z is a hydrogen atom, an optionally substituted C1-C4 alkyl group (when two C1-C4 alkyl groups as R 3z bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted phenyl group, an optionally substituted heteroaryl group, an optionally substituted C3-C6 cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted phenylalkyl group, an optionally substituted heteroarylalkyl group or the like. More preferably R 3z is a hydrogen atom, an optionally substituted C1-C4 alkyl group (when two C1-C4 alkyl groups as R 3z bond to one nitrogen atom, they may bond to each other via an oxygen atom, a nitrogen atom, a sulfur atom or a single bond to form a ring), an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted heteroarylalkyl group or the like.

The substituent(s) of substituent(s) of R 1 , R 2 or R 3 are, unless specifically defined, one or more substituent(s) selected from the group consisting of a halogen atom; a hydroxyl group; a cyano group; a nitro group; an amino group; a C1-C8 alkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 9 halogen atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C3-C8 cycloalkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 9 halogen atom(s), 1 to 2 hydroxyl group(s),1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C1-C8 alkoxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 9 halogen atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); a C3-C8 cycloalkyl-oxy group cycloalkyl-oxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 2 methyl group(s), 1 to 9 halogen atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); an aliphatic heterocyclic group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 8 halogen atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); a C6-C14 aryl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 5 halogen atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); and a heteroaryl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 5 halogen atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s).

Preferably the substituent(s) of substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of a halogen atom; a hydroxyl group; an amino group; a C1-C6 alkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C3-C8 cycloalkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C1-C6 alkoxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); a C3-C8 cycloalkyl-oxy group cycloalkyl-oxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); an aliphatic heterocyclic group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 6 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); a C6-C14 aryl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 5 halogen atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); a heteroaryl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 5 halogen atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); and the like. When halogen atom(s) are included as the substituent(s) of substituent(s) of R 1 , the number of the substituents is preferably 1 to 8. When the substituent(s) of substituent(s) of R 1 are selected only from the substituents other than halogen atoms, the number of the substituents is preferably 1 to 3. More preferred substituent(s) of substituent(s) of R 1 are one or more substituent(s) selected from the group consisting of halogen atom; a hydroxyl group; an amino group; a C1-C4 alkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 5 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C3-C6 cycloalkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C1-C4 alkoxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); a C3-C6 cycloalkyl-oxy groupcycloalkyl-oxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); an aliphatic heterocyclic group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 6 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); and the like. Here, when halogen atom(s) are included as the substituent(s) of substituent(s) of R 1 , the number of the substituents is preferably 1 to 6, while when the substituent(s) of substituent(s) of R 1 are selected only from the substituents other than halogen atoms, the number of the substituents is preferably 1 to 2.

Preferably the substituent(s) of substituent(s) of R 2 are one or more substituent(s) selected from the group consisting of a halogen atom; a hydroxyl group; a cyano group; a nitro group; an amino group; a C1-C6 alkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 9 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C3-C8 cycloalkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 9 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C1-C6 alkoxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 9 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); a C3-C8 cycloalkyl-oxy group cycloalkyl-oxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 9 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); an aliphatic heterocyclic group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 6 halogen atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); and the like. When halogen atom(s) are included as the substituent(s) of substituent(s) of R 2 , the number of the substituents is preferably 1 to 8. When the substituent(s) of substituent(s) of R 2 are selected only from the substituents other than halogen atoms, the number of the substituents is preferably 1 to 3. More preferably, the substituent(s) of substituent(s) of R 2 are one or more substituent(s) selected from the group consisting of a halogen atom; a hydroxyl group; a cyano group; a nitro group; an amino group; a C1-C4 alkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C3-C6 cycloalkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C1-C4 alkoxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); a C3-C6 cycloalkyl-oxy groupcycloalkyl-oxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); an aliphatic heterocyclic group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 6 halogen atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); and the like. Here, when halogen atom(s) are included as the substituent(s) of substituent(s) of R 2 , the number of the substituents is preferably 1 to 8, while when the substituent(s) of substituent(s) of R 2 are selected only from the substituents other than halogen atoms, the number of the substituents is preferably 1 to 3. Further preferably, the substituent(s) of substituent(s) of R 2 are one or more substituent(s) selected from the group consisting of 1 to 5 halogen atom(s); 1 to 2 hydroxyl group(s); 1 to 2 cyano group(s); 1 to 2 amino group(s); a C1-C4 alkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 5 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C1-C4 alkoxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 5 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); an aliphatic heterocyclic group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 6 halogen atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); and the like. Here, when halogen atom(s) are included as the substituent(s) of substituent(s) of R 2 , the number of the substituents is preferably 1 to 6, while when the substituent(s) of substituent(s) of R 2 are selected only from the substituents other than halogen atoms, the number of the substituents is preferably 1 to 2.

Preferably the substituent(s) of substituent(s) of R 3 are one or more substituent(s) selected from the group consisting of a halogen atom; a hydroxyl group; an amino group; a C1-C6 alkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 9 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C3-C8 cycloalkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 9 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C1-C6 alkoxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 9 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); a C3-C8 cycloalkyl-oxy groupcycloalkyl-oxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 9 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); an aliphatic heterocyclic group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 6 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); a C6-C14 aryl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 2 methyl group(s), 1 to 5 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); a heteroaryl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 5 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); and the like. When halogen atom(s) are included as the substituent(s) of substituent(s) of R 3 , the number of the substituents is preferably 1 to 8. When the substituent(s) of substituent(s) of R 3 are selected only from the substituents other than halogen atoms, the number of the substituents is preferably 1 to 3. More preferably, the substituent(s) of substituent(s) of R3 are one or more substituent(s) selected from the group consisting of a halogen atom; a hydroxyl group; an amino group; a C1-C4 alkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C3-C6 cycloalkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C1-C4 alkoxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); a C3-C6 cycloalkyl-oxy groupcycloalkyl-oxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 7 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); a aliphatic heterocyclic group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 6 fluorine atom(s) and 1 to 2 hydroxyl group(s); a phenyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 5 fluorine atom(s) and 1 to 2 hydroxyl group(s); a heteroaryl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 5 fluorine atom(s) and 1 to 2 hydroxyl group(s); and the like. Here, when halogen atom(s) are included as the substituent(s) of substituent(s) of R 3 , the number of the substituents is preferably 1 to 8, while when the substituent(s) of substituent(s) of R 3 are selected only from the substituents other than halogen atoms, the number of the substituents is preferably 1 to 3. Further preferably, the substituent(s) of substituent(s) of R 3 are one or more substituent(s) selected from the group consisting of a halogen atom; a hydroxyl group; an amino group; a C1-C4 alkyl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 5 fluorine atom(s), 1 to 2 hydroxyl group(s), 1 to 2 cyano group(s) and 1 to 2 oxo group(s); a C1-C4 alkoxy group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 5 fluorine atom(s), 1 to 2 hydroxyl group(s) and 1 to 2 cyano group(s); an aliphatic heterocyclic group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 6 fluorine atom(s) and 1 to 2 hydroxyl group(s); a heteroaryl group optionally substituted with one or more substituent(s) selected from the group consisting of 1 to 4 methyl group(s), 1 to 5 fluorine atom(s) and 1 to 2 hydroxyl group(s); and the like. Here, when halogen atom(s) are included as the substituent(s) of substituent(s) of R 3 , the number of the substituents is preferably 1 to 6, while, when the substituent(s) of substituent(s) of R 3 are selected only from the substituents other than halogen atoms, the number of the substituents is preferably 1 to 2.

Preferred compounds for the pyrazolo[1,5-a]pyridine derivative represented by formula (I) are a compound comprising a combination of group(s) defined above for R 1 to R 3 and preferred group(s) described above for R 1 to R 3 ; a compound comprising a combination of preferred group(s) described above for R 1 to R 3 ; and the like.

The compound of the present invention may contain an acidic group(s) in the molecule. In this case, it may be converted to a pharmaceutically acceptable salt if necessary. As such salts, there may be mentioned salts with non-toxic cations. For example, there may be mentioned salts with alkali metal ions such as Na + and K + , alkaline earth metal ions such as Mg 2+ and Ca 2+ , metal ions such as Al 3+ and Zn 2+ , and organic bases such as ammonia, triethylamine, ethylenediamine, propanediamine, pyrrolidine, piperidine, piperazine, pyridine, lysine, choline, ethanolamine, N,N-dimethylethanolamine, 4-hydroxypiperidine, glucosamine and N-methylglucamine.

The compound of the present invention may contain one or more chiral carbon atoms, and in this case it includes optically active forms and racemic forms. When the compound of the present invention exists in trans form and cis form, it includes the trans form and the cis form.

As examples of compound represented by formula (I) of the present invention, there may be mentioned compounds listed in the following Table A.

The pyrazolo[1,5-a]pyridine derivatives represented by the above formula (I) exist in tautomeric forms represented, for example, by the following formula (II):

(wherein, R 1 , R 2 and R 3 are as defined in the above formula (I)).

These tautomers are also included in the scope of the present invention.

The compounds of the present invention can be synthesized by the following methods. In each formula, R 1 , R 2 and R 3 are as defined in formula (I). Reagents and solvents shown as conditions in chemical formulae are mere examples, as mentioned in the text. Each substituent may be, if necessary, protected with a suitable protective group and deprotection may be carried out in an appropriate step. Each of abbreviations of substituents, reagents and solvents in the text and tables represent the following.

Me: methyl Et: ethyl Boc: tert-butoxycarbonyl DMAP: 4-N,N-dimethylaminopyridine THF: tetrahydrofuran DHP: dihydropyran THP: tetrahydropyranyl Ph: phenyl TFA: trifluoroacetic acid Tf: trifluoromethanesulfonyl

1) Syntheses of Compounds 1-4

Compounds represented by formulae 1-4 are known compounds and can be synthesized by methods known for ones skilled in the art, for example, by the steps shown above. Compound 3 can be synthesized according to “R. G. Jones and M. J. Mann, J. Am. Chem. Soc. 1953, 75, 4048-4052” while compound 4 can be synthesized according to “R. G. Jones, J. Am. Chem. Soc. 1949, 71, 3994-4000.”

2) Synthesis of Compound of Formula (6) from Compound 4

Compound of formula (6) can be obtained by reaction of compound 4 with a monosubstituted malonic diester in the presence of an appropriate base (for example, sodium ethoxide) in an appropriate organic solvent (for example, ethanol) at a temperature from 0° C. to the refluxing temperature of the solvent.

3) Synthesis of Compound of Formula (7) from Compound Formula (6)

Compound of formula (7) can be obtained by halogenation of compound of formula (6) with an appropriate halogenating agent (for example, phosphoryl oxychloride) in the presence of an appropriate base (for example, N,N-dimethylaniline) or without base in an appropriate organic solvent (for example, acetonitrile) or without solvent at a temperature from 0° C. to 140° C. followed by hydrolysis with an aqueous solution containing an appropriate base (for example, sodium hydroxide) in an appropriate organic solvent (for example, 1,4-dioxane) at a temperature from 0° C. to the refluxing temperature of the solvent.

4) Synthesis of Compound of Formula (8) from Compound of Formula (7)

Compound of formula (8) can be obtained by reaction of compound of formula (7) with an amine derivative represented as R 1 NH 2 in the presence of an appropriate base (for example, pyridine) or without base in an appropriate organic solvent (for example, 2-propanol) or without solvent at a temperature from 0° C. to 140° C.

5) Synthesis of Compound of Formula (9) from Compound of Formula (8)

Compound of formula (9) can be obtained by reaction of compound of formula (7) with an appropriately activated reagent for introducing a P-group (di-tert-butyl dicarbonate when P is Boc) in the presence of an appropriate base (for example, triethylamine) or without base in the presence of an appropriate catalyst (for example, 4-N,N-dimethylaminopyridine) or without catalyst in an appropriate organic solvent (for example, 1,4-dioxane) at a temperature from 0° C. to the refluxing temperature of the solvent followed by hydrolysis in an appropriate solvent (for example, 1,4-dioxane) by adding an aqueous solution containing an appropriate base (for example, sodium hydroxide) or an aqueous solution containing no base at a temperature from 0° C. to the refluxing temperature of the solvent.

6) Synthesis of Compound of Formula (11) from Compound of Formula (9)

Compound of formula (11) can be obtained by reaction of compound of formula (9) with an appropriately activated reagent for introducing an L-group (a triflating agent (for example, trifluoromethanesulfonic anhydride) when L is Tf) in the presence of an appropriate base (for example, triethylamine) in an appropriate organic solvent (for example, pyridine) at a temperature from 0° C. to 50° C.

7) Synthesis of Compound of Formula (13) from Compound of Formula (11)

Compound of formula (13) can be obtained by reaction of compound of formula (11) with an amine derivative represented as R 3 NH 2 in an appropriate organic solvent (for example, tetrahydrofuran) or without solvent in the presence of an appropriate base (for example, triethylamine) or without base at a temperature from room temperature to the refluxing temperature of the solvent.

Compound of formula (13) can be also obtained by reaction of compound of formula (9) with an activating agent (for example, bromotris(pyrrolidino)phosphonium hexafluorophosphate or benzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate) and an amine derivative represented as R 3 NH 2 in an appropriate organic solvent (for example, 1,4-dioxane or N,N-dimethylformamide) in the presence of an appropriate base (for example, triethylamine) at a temperature from 0° C. to the refluxing temperature of the solvent according to the literature (Journal of Organic Chemistry, 2005, 70, 1957-1960).

8) Synthesis of Compound of Formula (14) from Compound of Formula (13)

Compound of formula (14) can be obtained by reaction of compound of formula (13) with an appropriate deprotecting agent (a strong acid (for example, trifluoroacetic acid) when P is Boc) in an appropriate organic solvent (for example, dichloromethane) or without solvent at a temperature from 0° C. to the refluxing temperature of the solvent.

Pyrazolo[1,5-a]pyridine derivatives represented by formulae (5)-(10), (13) and (14) also exist in tautomeric forms as the above formula (II).

Preferred examples of R 1 -R 3 in pyrazolo[1,5-a]pyridine derivatives represented by formulae (5)-(14) and the like include the preferred groups described for R 1 -R 3 in the final products, that is, pyrazolo[1,5-a]pyridine derivatives represented by formula (I). Preferred examples of pyrazolo[1,5-a]pyridine derivatives represented by formulae (5)-(14) and the like include a compound comprising a combination of group(s) defined for R 1 -R 3 and preferred group(s) described for R 1 -R 3 ; a compound comprising a combination of preferred groups described for R 1 -R 3 ; and the like.

A formulation comprising the compound of the present invention or the pharmaceutically acceptable salt thereof as an active ingredient is prepared by using carriers, excipients or other additives usually used for formulation. As carriers and excipients used for formulation, either solid or liquid may be used, and for example, there may be mentioned lactose, magnesium stearate, starch, talc, gelatin, agar, pectin, gum arabic, olive oil, sesame oil, cacao butter, ethylene glycol and others conventionally used. The formulation may be administered either orally as tablets, pills, capsules, granule, powder, liquid or the like or parenterally through injection such as an intravenous injection and an intramuscular injection, suppository, percutaneous administration or the like.

As diseases for which the MAPKAP-K2 inhibitor of the present invention is effective, there may be mentioned neurodegenerative/neurological disorders (including dementia), sepsis, autoimmune diseases, destructive osteopathy, inflammatory bowel disease, psoriasis, diabetes mellitus, cancer, ischemic reperfusion injury, angiodysplasia, cachexia, obesity, angiogenesis, asthma and/or chronic obstructive pulmonary disease (COPD).

As autoimmune diseases, specifically, there may be mentioned rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis, graft-versus-host disease, diabetes mellitus or Crohn's disease.

The dose of the compound of present invention is, although it varies depending on the kind of disease, the administration route, the age and sex of patient and the degree of disease, usually 1-500 mg/day for one adult.

The present invention will be explained with specific examples. However, the present invention is not limited to these examples.

The compound number given to each compound in the following examples corresponds to the compound number given to the compound mentioned as preferred example in Table A. The structures of novel compounds isolated were confirmed by 1 H-NMR and/or mass analysis measured on a single quadrupole instrumentation equipped with an electrospray source or other appropriate analytical methods.

For 1 H-NMR spectra (400 MHz, DMSO-d 6 or CDCl 3 ), chemical shifts (δ:ppm) and coupling constants (J:Hz) are shown. Each of the following abbreviation represents the followings: s=singlet, d=doublet, t=triplet, q=quartet, brs=broad singlet, m=multiplet. For results of mass analysis, M + +H, that is, the measured value observed as the molecular mass of compound (M) with one proton (H + ) added, is shown. “HPLC retention time” represents the retention time (unit: min) of compound in HPLC analysis under the following analytical conditions.

Conditions for HPLC (High Performance Liquid Chromatography)

Instrumental system: Hewlett-Packard 1100HPLC

Column: Cadenza CD-C18 (Imtakt) 100 mm×4.6 mm (i.d.)

Solvent: A: H 2 O/acetonitrile=95/5, 0.05% TFA

B: H 2 O/acetonitrile=5/95, 0.05% TFA

Flow rate: 1.0 mL/min

Gradient:

0 to 1 min; Solvent B: 10%, Solvent A: 90%

1 to 13 min; Solvent B: from 10% to 70%, Solvent A: from 90% to 30%

13 to 14 min; Solvent B: from 70% to 100%, Solvent A: from 30% to 0%

14 to 16 min; Solvent B: 100%, Solvent A: 0%

16 to 19 min; Solvent B: from 100% to 10%, Solvent A: from 0% to 90%

The compound of the present invention is valuable for a MAPKAP-K2 inhibitor or its intermidiate.

Further, by using the compound of the present invention, there is provided a novel MAPKAP-K2 inhibitor or a novel medicine for treating or preventing neurodegenerative/neurological disorders (including dementia), inflammatory diseases, sepsis, autoimmune diseases, destructive osteopathy, diabetes mellitus, cancer, ischemic reperfusion injury, angiodysplasia, cachexia, obesity, angiogenesis, asthma and/or chronic obstructive pulmonary disease (COPD).