Pyrazole and fused pyrazole glucokinase activators

1. A compound of the formula:

or a tautomer, enantiomer or pharmaceutically acceptable salt thereof, wherein

R 1 is heteroaryl optionally substituted through available valencies with one or more substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, alkoxy, amino, (C 1-10 )alkyl, halo(C 1-10 )alkyl, amino(C 1-10 )alkyl, imino(C 1-3 )alkyl, oxa(C 1-5 )alkyl, oxo(C 1-5)alkyl, and -L 1 -R 22 ;

R 2 is hydrogen;

R 3 is -L-R 18 ;

R 4 is hydrogen;

R 5 is selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, (C 1-10 )alkoxy, amino, (C 1-10 )alkylamino, (C 1-10 )alkyl, halo(C 1-10 )alkyl, hydroxy(C 1-10 )alkyl, aza(C 1-10 )alkyl, (C 1-10 )oxaalkyl, (C 1-10 )oxoalkyl, and imino(C 1-10 )alkyl;

R 6 is selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, (C 1-10 )alkoxy, amino, (C 1-10 )alkyl, halo(C 1-10 )alkyl, hydroxy(C 1-10 )alkyl, aza(C 1-10 )alkyl, (C 1-10 )oxaalkyl, (C 1-10 )oxoalkyl, imino(C 1-10 )alkyl, and -L 1 -R 22 ;

or R 5 and R 6 together with the atoms to which they are attached form an aryl or heteroaryl ring which has 6 ring members and is optionally substituted through available valencies with one or more substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, alkoxy, amino, (C 1-10 )alkyl, halo(C 1-10 )alkyl, amino(C 1-10 )alkyl, imino(C 1-10 )alkyl, and -L 1 -R 22 ;

R 7 is selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, (C 1-10 )alkoxy, amino, (C 1-10 )alkyl, halo(C 1-10 )alkyl, hydroxy(C 1-10 )alkyl, aza(C 1-10 )alkyl, (C 1-10 )oxaalkyl, (C 1-10 )oxoalkyl, imino(C 1-10 )alkyl, and -L 1 -R 22 ;

L is —(CH 2 )—;

L 1 at each occurrence is independently absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between R 22 and the ring to which L 1 is attached, wherein, when present, L 1 is selected from the group consisting of

—(CH 2 ) s —, —NH—, —O—, —CO—, —SO 2 —, and combinations thereof;

s at each occurrence is independently selected from the group consisting of 1, 2, 3, 4, 5 and 6;

R 18 is tetrahydro-2H-pyran-4-yl; and

R 22 at each occurrence is independently selected from the group consisting of hydroxy, amino, (C 1-10 )alkyl, halo(C 1-10 )alkyl, hydroxy(C 1-10 )alkyl, (C 3-12 )cycloakyl, and phenyl optionally substituted with halo.

2. The compound of claim 1 having the formula:

or a pharmaceutically acceptable salt thereof, wherein

n′ is selected from the group consisting of 0, 1, 2 and 3; and

R 8 at each occurrence is independently selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, alkoxy, amino, (C 1-10 )alkyl, halo(C 1-10 )alkyl, amino(C 1-10 )alkyl, imino (C 1-3 )alkyl, and -L 1 -R 22 .

3. The compound or pharmaceutically acceptable salt according to claim 2 , wherein each R 8 is independently selected from the group consisting of hydrogen, halo,

(C 1-3 )alkyl,

(C 1-3 )alkylsulfonyl, and

(C 3-12 )cycloalkylsulfonyl.

4. The compound or pharmaceutically acceptable salt according to claim 2 , wherein each R 8 is independently selected from the group consisting of methylsulfonyl, cyclopropylsulfonyl, and cyclopentylsulfonyl.

5. The compound or pharmaceutically acceptable salt according to claim 2 , wherein

R 8 is -L 1 -R 22 .

6. The compound or pharmaceutically acceptable salt according to claim 2 , wherein R 8 is —SO 2 —R 22 .

7. The compound or pharmaceutically acceptable salt according to claim 2 , wherein R 8 is cyclopropylsulfonyl.

8. The compound of claim 1 having the formula:

or a pharmaceutically acceptable salt thereof, wherein

n is selected from the group consisting of 0, 1, 2, 3 and 4; and

R 8 at each occurrence is independently selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, alkoxy, amino, (C 1-10 )alkyl, halo(C 1-10 )alkyl, amino(C 1-10 )alkyl, imino(C 1-3 )alkyl, and -L 1 -R 22 .

9. The compound or pharmaceutically acceptable salt according to claim 8 , wherein each R 8 is independently selected from the group consisting of hydrogen, halo,

(C 1-3 )alkyl,

(C 1-3 )alkylsulfonyl, and

(C 3-12 )cycloalkylsulfonyl.

10. The compound or pharmaceutically acceptable salt according to claim 8 , wherein each R 8 is independently selected from the group consisting of methylsulfonyl, cyclopropylsulfonyl, and cyclopentylsulfonyl.

11. The compound or pharmaceutically acceptable salt according to claim 8 , wherein

R 8 is -L l -R 22 .

12. The compound or pharmaceutically acceptable salt according to claim 8 , wherein R 8 is —SO 2 —R 22 .

13. The compound or pharmaceutically acceptable salt according to claim 8 , wherein R 8 is cyclopropylsulfonyl.

14. The compound of claim 1 having the formula:

or a pharmaceutically acceptable salt thereof, wherein

n′ is selected from the group consisting of 0, 1, 2 and 3; and

R 8 at each occurrence is independently selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, alkoxy, amino, (C 1-10 )alkyl, halo(C 1-10 )alkyl, amino(C 1-10 )alkyl, imino(C 1-3 )alkyl, and -L 1 -R 22 .

15. The compound or pharmaceutically acceptable salt according to claim 14 , wherein each R 8 is independently selected from the group consisting of hydrogen, halo,

(C 1-3 )alkyl,

(C 1-3 )alkylsulfonyl, and

(C 3-12 )cycloalkylsulfonyl.

16. The compound or pharmaceutically acceptable salt according to claim 14 , wherein R 8 is selected from the group consisting of methylsulfonyl, cyclopropylsulfonyl, and cyclopentylsulfonyl.

17. The compound or pharmaceutically acceptable salt according to claim 14 , wherein

R 8 is -L 1 -R 22 .

18. The compound or pharmaceutically acceptable salt according to claim 14 , wherein R 8 is —SO 2 —R 22 .

19. The compound or pharmaceutically acceptable salt according to claim 14 , wherein R 8 is cyclopropylsulfonyl.

20. The compound or pharmaceutically acceptable salt according to claim 1 , wherein R 1 is selected from the group consisting of thiazolyl, pyrazinyl, pyrazolyl, and pyridyl, each optionally substituted through available valencies with one or more substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, alkoxy, amino, (C 1-10 )alkyl, halo(C 1-10 )alkyl, amino(C 1-10 )alkyl, imino(C 1-3 )alkyl, oxa(C 1-5 )alkyl, oxo(C 1-5 )alkyl, and -L 1 -R 22 .

21. The compound or pharmaceutically acceptable salt according to claim 1 , wherein R 1 is selected from the group consisting of thiazol-2-yl, 2-pyridyl, 5-methyl-thiazol-2-yl, 6-methyl-pyrid-2-yl, 4-methyl-pyrid-2-yl, 5-bromo-6-methyl-pyrid-2-yl, 5-phenyl-pyrid-2-yl, benzothiazol-2-yl, a nicotinic acid methyl ester, 5-bromo-pyrid-2-yl, 2-pyrazinyl, 1-methyl-pyrazol-3-yl, and 5-fluoro-thiazol-2-yl.

22. The compound or pharmaceutically acceptable salt according to claim 1 , wherein R 1 is selected from the group consisting of:

wherein

R 14 is selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, alkoxy, amino, (C 1-10 )alkyl, halo(C 1-10 )alkyl, amino(C 1-10 )alkyl, imino(C 1-3 )alkyl, oxa(C 1-5 )alkyl, oxo(C 1-5 )alkyl, and -L 1 -R 22 ; and

R 14a is selected from the group consisting of hydrogen, (C 1-10 )alkyl, halo(C 1-10 )alkyl, amino(C 1-10 )alkyl, imino(C 1-3 )alkyl, oxa(C 1-5 )alkyl, and oxo(C 1-5 )alkyl.

23. The compound or pharmaceutically acceptable salt according to claim 1 , wherein R 5 is selected from the group consisting of hydrogen, halo, and (C 1-3 )alkyl.

24. The compound or pharmaceutically acceptable salt according to claim 1 , wherein R 6 is selected from the group consisting of hydrogen, halo, (C 1-3 )alkyl, (C 1-3 )alkylsulfony, and (C 3-6 )cycloalkylsulfonyl.

25. The compound or pharmaceutically acceptable salt according to claim 1 , wherein

R 6 is -L l -R 22 .

26. The compound or pharmaceutically acceptable salt according to claim 1 , wherein R 7 is selected from the group consisting of hydrogen, halo, and (C 1-3 )alkyl.

27. The compound or pharmaceutically acceptable salt according to claim 1 , wherein

R 7 is -L l -R 22 .

28. The compound or pharmaceutically acceptable salt according to claim 1 , wherein each R 22 is independently selected from the group consisting of (C 1-5 )alkyl optionally substituted with halo; (C 3-6 )cycloalkyl; and phenyl optionally substituted with halo.

29. The compound or pharmaceutically acceptable salt according to claim 1 , wherein R 22 is cyclopropyl.

30. The compound or pharmaceutically acceptable salt according to claim 1 , wherein

R 22 is amino.

31. The compound or pharmaceutically acceptable salt according to claim 1 , wherein L 1 is —SO 2 —.

32. The compound according to claim 1 , wherein the compound is in the form of a pharmaceutically acceptable salt.

33. A compound according to claim 1 , which is selected from the following group of compounds:

2-(3-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-N-(5-methoxythiazolo[5,4-b]pyridin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(3-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-N-(5-methoxythiazolo[5,4-b]pyridin-2-yl)-3-(tetrahydro -2H-pyran-4-yl)propanamide;

(R)-2-(3 -(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-N-(5-methoxythiazolo[5,4-b]pyridin-2-yl)-3-(tetrahydro -2H-pyran-4-yl)propanamide ;

N-(5-chlorothiazol-2-yl)-2-(4-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

N-(5-chlorothiazol-2-yl)-2-(4-(cyclopentylsulfonyl)-1H-pyrazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

4-chloro-1-(1-(5-chlorothiazol-2-ylamino)-1-oxo-3-(tetrahydro -2H-pyran-4-yl)propan-2-yl)-N-cyclopropyl-1H-pyrazole-3-carboxamide;

N-(5-chlorothiazol-2-yl)-2-(4-(cyclopropanesulfonamido)-1H-pyrazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

N-(5-chlorothiazol-2-yl)-2-(5-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-6-(difluoromethoxy)-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

6-(2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamido)nicotinamide;

2-(4-(cyclopropylsulfonyl)-5-methoxy-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(6-amino-4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(6-cyano-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

4-(cyclopropylsulfonyl)-1-(1-(5-fluorothiazol-2-ylamino)-1-oxo-3-(tetrahydro-2H-pyran-4-yl)propan-2-yl)-1H-indazole-6-carboxylic acid;

2-(5-chloro-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(7-chloro-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-N-(5-methoxythiazolo[5,4-b]pyridin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-N-(5-methoxythiazolo[5,4-b]pyridin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-N-(5-methoxythiazolo[5,4-b]pyridin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-3,5-dimethyl-1H-pyrazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(4-chlorophenylsulfonyl)-1H-pyrazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(4-chlorophenylsulfonyl)-1H-pyrazol-1-yl)-N-(5-methoxythiazolo[5,4-b]pyridin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopentylsulfonyl)-1H-pyrazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-N-(5-chlorothiazol-2-yl)-2-(4-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

N-(5-fluorothiazol-2-yl)-2-(4-(methylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-N-(5-chlorothiazol-2-yl)-2-(4-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopentylsulfonyl)-1H-pyrazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopentylsulfonyl)-1H-pyrazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

N-(5-chloropyridin-2-yl)-2-(4-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-N-(5-chlorothiazol-2-yl)-2-(5-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-N-(5-chlorothiazol-2-yl)-2-(5-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(tert-butylsulfonyl)-1H-pyrazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(tert-butylsulfonyl)-1H-pyrazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(tert-butylsulfonyl)-1H-pyrazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-N-(5-chlorothiazol-2-yl)-2-(4-(cyclopentylsulfonyl)-1H-pyrazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

N-(5-chlorothiazol-2-yl)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

N-(5-chlorothiazol-2-yl)-2-(6-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-N-(5-chlorothiazol-2-yl)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-N-(5-chlorothiazol-2-yl)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

N-(5-chlorothiazol-2-yl)-2-(4-(cyclopropylsulfonyl)-6-fluoro-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-6-methoxy-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-6-hydroxy-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-6-hydroxy-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-5-methoxy-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-5-methoxy-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-5-methoxy-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-6-methoxy-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

N-(3-cyanopyridin-2-yl)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-5-(difluoromethoxy)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(3,5-difluoropyridin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-5-methoxy-1H-indazol-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-6-methoxy-1H-indazol-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-5-methoxy-1H-indazol-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-5-methoxy-1H-indazol-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(6-amino-4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(6-cyano-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(6-chloro-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(6-chloro-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-6-fluoro-1H-indazol-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-6-fluoro-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(6-cyano-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(6-cyano-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-6-(2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamido)nicotinamide;

(R)-6-(2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamido)nicotinamide;

(S)-2-(4-(cyclopropylsulfonyl)-5-methoxy-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-5-methoxy-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(6-amino-4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(6-amino-4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-6-fluoro-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(6-methylpyridazin-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

6-(2-(4-(cyclopropylsulfonyl)-6-fluoro-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamido)nicotinamide;

(R)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(6-cyano-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(6-chloro-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-6-methyl-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-6-fluoro-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(pyrimidin-4-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

N-(5-cyanothiazol-2-yl)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

N-(5-cyanopyrimidin-2-yl)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-6-methoxy-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-6-methoxy-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-6-hydroxy-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(6-cyano-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(6-cyano-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(1,5-dimethyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

N-(5-cyanopyridin-2-yl)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-N-(5-cyanothiazol-2-yl)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-N-(5-cyanothiazol-2-yl)-2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(6-chloro-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(6-amino-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-6-(difluoromethoxy)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-5-hydroxy-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(6-chloro-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(1-(methylsulfonyl)-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(6-fluoropyridin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-5-fluoro-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(5-bromo-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-5-fluoro-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-5-fluoro-1H-indazol-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-5-fluoro-1H-indazol-1-yl)-N-(1-ethyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-5-methyl-1H-indazol-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(4-(cyclopropylsulfonyl)-5-methyl-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(6-amino-4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(6-amino-4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-5-fluoro-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-5-fluoro-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

2-(6-amino-4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-l-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(S)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

(R)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide; and

a pharmaceutically acceptable salt of any one of the aforementioned compounds.

34. A compound according to claim 1 , which is 2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

35. A compound according to claim 1 , which is (S)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

36. A compound according to claim 1 , which is (R)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

37. A compound according to claim 1 , which is 6-(2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamido)nicotinamide or a pharmaceutically acceptable salt thereof.

38. A compound according to claim 1 , which is (S)-6-(2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamido)nicotinamide or a pharmaceutically acceptable salt thereof.

39. A compound according to claim 1 , which is (R)-6-(2-(4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamido)nicotinamide or a pharmaceutically acceptable salt thereof.

40. A compound according to claim 1 , which is 2-(4-(cyclopropylsulfonyl)-5-methoxy-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

41. A compound according to claim 1 , which is (S)-2-(4-(cyclopropylsulfonyl)-5-methoxy-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

42. A compound according to claim 1 , which is (R)-2-(4-(cyclopropylsulfonyl)-5-methoxy-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

43. A compound according to claim 1 , which is 2-(6-amino-4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

44. A compound according to claim 1 , which is (R)-2-(6-amino-4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

45. A compound according to claim 1 , which is (S)-2-(6-amino-4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

46. A compound according to claim 1 , which is 2-(6-cyano-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

47. A compound according to claim 1 , which is (S)-2-(6-cyano-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

48. A compound according to claim 1 , which is (R)-2-(6-cyano-4-(cyclopropylsulfonyl)-1H-indazol-1-yl)-N-(1-methyl-1H-pyrazol-3-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

49. A compound according to claim 1 , which is 2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

50. A compound according to claim 1 , which is (S)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

51. A compound according to claim 1 , which is (R)-2-(4-(cyclopropylsulfonyl)-1H-pyrazolo[3,4-c]pyridin-1-yl)-N-(pyrazin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide or a pharmaceutically acceptable salt thereof.

52. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt as defined in any one of the preceding claims, and a pharmaceutically acceptable excipient.