Compound useful for the treatment of degenerative and inflammatory diseases

1. A compound according to Formula I:

wherein

Cy1 is C 6-10 aryl, or 5-10 membered heteroaryl;

R 1 is selected from C 1-6 alkyl and C 3-7 cycloalkyl, each of which may optionally be substituted with one or more halo, CN, or OH;

each R 2 is independently selected from halo, CN, OH, C 1-6 alkyl (optionally substituted with one or more groups selected from halo, CN, OH, C 1-4 alkoxy), or C 1-6 alkoxy (optionally substituted with one or more groups selected from halo, CN, OH, or C 1-4 alkoxy);

L is absent or is selected from —O—, —C(O)—, —N(R 5 )—, —CON(R 5 )—, —SO 2 N(R 5 )—, —S(O) 2 —, —N(R 5 )CO—, —N(R 5 )SO 2 ;

Y is absent or is C 1-4 alkylene (optionally substituted with one or more halo, or CN);

R 3 is selected from H, halo, CN, C 6-10 aryl (optionally substituted with one or more independently selected R 3a groups), C 3-7 cycloalkyl (optionally substituted with one or more independently selected R 3a groups), 4-7 membered heterocycloalkyl (optionally substituted with one or more independently selected R 3a groups), and 5-10 membered heteroaryl (optionally substituted with one or more independently selected R 3a groups); or

R 3 is selected from —OR 3b , —NHR 3b , —C(═O)R 3b , —C(═O)NHR 3b and —SO 2 NHR 3b ;

each R 3a is independently selected from OH, halo, CN, oxo, C 1-4 alkyl (optionally substituted with one or more halo, C 1-4 alkoxy, or CN), C 1-4 alkoxy (optionally substituted with one or more halo, or C 1-4 alkoxy), amino (optionally substituted with C 1-4 alkyl, or C 3-7 cycloalkyl), —C(═O)NH 2 (optionally substituted with C 1-4 alkyl, or C 3-7 cycloalkyl), C 1-4 thioalkoxy, 4-7 membered heterocycloalkyl, —S(O)R 6 , —S(O) 2 R 6 , —C(═O)R 6 , —C(═O)OR 6 , or —NHC(═O)R 6 ;

R 3b is independently selected from C 1-6 alkyl, phenyl (optionally substituted with one or more halo, or C 1-4 alkyl), C 3-7 cycloalkyl, or 4-7 membered heterocycloalkyl (optionally substituted with one or more halo, or C 1-4 alkyl);

R 4 is H, halo, CN, or C 1-4 alkyl;

R 5 is H or C 1-4 alkyl;

R 6 is H, or C 1-4 alkyl;

the subscript m is 0, 1 or 2;

or a pharmaceutically acceptable salt, or a solvate, or a solvate of the pharmaceutically acceptable salts.

2. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein m is 1.

3. A compound or pharmaceutically acceptable salt thereof, according to claim 2 , wherein R 2 is OH, CN, halo, C 1-6 alkyl optionally substituted with one or more halo, or C 1-6 alkoxy optionally substituted with one or more halo.

4. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein Cy1 is phenyl.

5. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein Cy1 is pyridyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, thiazolyl, furanyl, indolyl, indazolyl, benzimidazolyl, benzofuranyl, benzodioxanyl, benzoxazolyl, quinolinyl, or isoquinolinyl.

6. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein the compound is according to Formula IIa or IIb:

wherein R 3 , R 4 , L and Y are as described in claim 1 , and X is CH, CF or N.

7. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein the compound is according to Formulae IIIa-IIIj:

wherein X and R 3 are as described in claim 1 .

8. A compound or pharmaceutically acceptable salt thereof, according to claim 7 , wherein the compound is according to Formula IIIc, IIId, IIIi or IIIf, and R 3 is selected from:

wherein R 3a is as described in claim 1 .

9. A compound or pharmaceutically acceptable salt thereof according to claim 8 , wherein R 3a is H, halo, C 1-4 alkyl, —S(O) 2 Me, or —C(═O)OMe.

10. A compound or pharmaceutically acceptable salt thereof according to claim 7 , wherein the compound is according to any one or Formulae IIIe-IIIh, wherein R 3 is:

wherein R 3a is as described in claim 1 .

11. A compound or pharmaceutically acceptable salt thereof according to claim 10 , wherein R 3a is H, CN, or halo.

12. A compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein X is N, CH, or CF.

13. A compound according to claim 1 , wherein the compound is:

N-(4-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

N-(4-(4-(benzyloxy)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

N-(4-(1-benzyl-1H-indol-5-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

N-(4-(1H-indol-5-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

4-(2-(cyclopropanecarboxamido)pyrazolo[1,5-a]pyridin-4-yl)-N-phenethylbenzamide

4-(2-(cyclopropanecarboxamido)pyrazolo[1,5-a]pyridin-4-yl)-N-(2-phenoxyethyl)benzamide

N-(4-(4-(pyridin-3-ylmethoxy)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

N-(4-(4-((6-cyanopyridin-3-yl)methoxy)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

Cyclopropanecarboxylic acid {4-[4-(1,1-dioxo-thiomorpholin-4-ylmethyl)-phenyl]-pyrazolo[1,5-a]pyridin-2-yl}-amide

Cyclopropanecarboxylic acid {4-[4-(1,1-dioxo-thiomorpholin-4-ylmethyl)-phenyl]-3-fluoro-pyrazolo[1,5-a]pyridin-2-yl}-amide

Cyclopropanecarboxylic acid {4-[4-(1,1-dioxo-thiomorpholin-4-ylmethyl)-phenyl]-3-bromo-pyrazolo[1,5-a]pyridin-2-yl}-amide

Cyclopropanecarboxylic acid {4-[4-(1,1-dioxo-thiomorpholin-4-ylmethyl)-phenyl]-3-chloro-pyrazolo[1,5-a]pyridin-2-yl}-amide

Cyclopropanecarboxylic acid {4-[4-(piperidine-1-carbonyl)-phenyl]-pyrazolo[1,5-a]pyridin-2-yl}-amide

N-(4-(4-((4-(methylsulfonyl)piperazin-1-yl)methyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

N-(3-chloro-4-(4-(piperidine-1-carbonyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

N-(4-(4-((4-(methylsulfonyl)piperidin-1-yl)methyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

N-(4-(3-fluoro-4-((4-(methylsulfonyl)piperidin-1-yl)methyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

N-(3-chloro-4-(4-((4-(methylsulfonyl)piperidin-1-yl)methyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

N-(3-chloro-4-(3-fluoro-4-((4-(methylsulfonyl)piperidin-1-yl)methyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

N-4-(3-fluoro-4-((4-(methylsulfonyl)piperazin-1-yl)methyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

methyl 4-(acetamidopyrazolo[1,5-a]pyridin-4-yl)benzyl)piperazine-1-carboxylate

N-(4-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

(R)—N-(4-(4-((2-methyl-4-(methylsulfonyl)piperazin-1-yl)methyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-((4-(methylsulfonyl)piperazin-1-yl)methyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(5-fluoro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-{4-[4-(1,1-Dioxo-thiomorpholin-4-ylmethyl)-3-fluoro-phenyl]-pyrazolo[1,5-a]pyridin-2-yl}-acetamide

N-(4-(3-fluoro-4-((4-(2,2,2-trifluoroethyl)piperazin-1-yl)methyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(3-fluoro-4-((4-(methylsulfonyl)piperidin-1-yl)methyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(6-(2-(1H-pyrazol-1-yl)ethyl 1H-pyrazol-1-yl)ethoxy)-5-fluoropyridin-3-yl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-(4,4-dimethyloxazolidine-3-carbonyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-(azetidine-1-carbonyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-(2-(azetidin-1-yl)-2-oxoethyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-(2-(3,3-difluoroazetidin-1-yl)-2-oxoethyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-(2-oxo-2-(piperidin-1-yl)ethyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-(2-morpholino-2-oxoethyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-(2-((2S,6R)-2,6-dimethylmorpholino)-2-oxoethyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-(2-(4,4-dimethyloxazolidin-3-yl)-2-oxoethyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-(piperidine-1-carbonyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-(3,3-difluoroazetidine-1-carbonyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-(morpholine-4-carbonyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

N-(4-(4-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

(R)—N-(4-(4-((2-methyl-4-(methylsulfonyl)piperazin-1-yl)methyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

N-(4-(4-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)acetamide

(R)—N-(4-(4-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

(S)—N-(4-(4-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide, or

N-(4-(4-(2-oxa-5-azaspiro[3.5]nonan-5-ylmethyl)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide.

14. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 .

15. The pharmaceutical composition according to claim 14 comprising a further therapeutic agent.