Imidazopyridine kinase inhibitors

1. A compound of formula (I):

wherein:

X 1 is H or halo;

R 1 is H, halo or haloalkyl;

R 2 is H or O-alkyl;

each R 3 is the same or different and is independently selected from H, halo, alkyl, haloalkyl and O-alkyl;

one of R 4 and R 5 is selected from H, halo, alkyl and O-alkyl, and the other is a moiety selected from:

—O—(CHR 7 ) a —R 8   (i)

wherein:

(i) each R 7 is the same or different and is independently selected from H, alkyl and OH;

 a is 0, 1, 2 or 3;

 R 8 is selected from NH 2 , N(H)alkyl, N(alkyl) 2 and a group of formula (iv):

wherein:

Ring D is a 5-6 membered N-heterocycle optionally including 1 or 2 additional heteroatoms selected from N, O and S and

R 14 is selected from H, halo, alkyl, OH, O-alkyl, oxo, SO 2 alkyl, alkylene-O-alkyl and alkylene-SO 2 alkyl;

(ii) b is 0, 1, 2 or 3;

 each R 9 is the same or different and is independently selected from H, alkyl and OH;

 Ring A is selected from 5-10 membered heterocycles including 1, 2 or 3 heteroatoms selected from N, O and S and 5-6 membered heteroaryls including 1, 2 or 3 heteroatoms selected from N, O and S;

 n is 0, 1 or 2;

 each R 10 is the same or different and is independently selected from halo, alkyl, haloalkyl, OH, O-alkyl, oxo, NH 2 , N(H)alkyl, N(alkyl) 2 , N(alkylene-O-alkyl) 2 , C(O)alkyl, SO 2 alkyl, alkylene-O-alkyl, alkylene-NH 2 , alkylene-N(H)alkyl, alkylene-N(alkyl) 2 , alkylene-C(O)alkyl, and alkylene-SO 2 alkyl;

(iii) c is 0, 1 or 2;

 each R 12 is the same or different and is independently H or alkyl;

 Ring B is selected from cyclohexylene, 5-6 membered heterocycle including 1, 2 or 3 heteroatoms selected from N, O and S and 5-6 membered heteroaryl including 1, 2 or 3 heteroatoms selected from N, O and S;

 q is 0 or 1;

 R 11 is halo, alkyl or haloalkyl;

 Ring C is a 5-10 membered heterocycle including 1, 2 or 3 heteroatoms selected from N, O and S;

 p is 0, 1 or 2;

 each R 13 is the same or different and is independently selected from halo, alkyl, haloalkyl, OH, O-alkyl, oxo, NH 2 , N(H)alkyl, N(alkyl) 2 , N(alkylene-O-alkyl) 2 , C(O)alkyl, SO 2 alkyl, alkylene-O-alkyl, alkylene-NH 2 , alkylene-N(H)alkyl, alkylene-N(alkyl) 2 , alkylene-C(O)alkyl, and alkylene-SO 2 alkyl; and

each R 6 is the same or different and is independently selected from H, halo, alkyl, haloalkyl, O-alkyl and O-haloalkyl;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein X 1 is halo and R 1 is H.

3. The compound according to claim 1 wherein R 2 is H or O—C 1-3 alkyl.

4. The compound according to claim 1 wherein at least one R 3 is H and the other is selected from H, halo, C 1-3 alkyl, haloC 1-3 alkyl and O—C 1-3 alkyl.

5. The compound according to claim 1 wherein one of R 4 and R 5 is selected from H, halo, alkyl and O-alkyl, and the other is a moiety:

—O—(CHR 7 ) a —R 8   (i).

6. The compound according to claim 1 , wherein R 4 is H and R 5 is a moiety:

—O—(CHR 7 ) a —R 8   (i).

7. The compound according to claim 1 , wherein a is 2 or 3 and each R 7 is the same or different and is independently H or OH.

8. The compound according to claim 1 , wherein R 8 is selected from N(alkyl) 2 and a group of formula (iv):

9. The compound according to claim 1 , wherein one of R 4 and R 5 is selected from H, halo, alkyl and O-alkyl, and the other is a moiety:

10. The compound according to claim 1 , wherein R 5 is H and R 4 is a moiety:

11. The compound according to claim 1 , wherein b is 0, 1 or 2 and each R 9 is H.

12. The compound according to claim 1 , wherein Ring A is selected from 5-6 membered heterocycle or heteroaryl including 1 or 2 heteroatoms selected from N, O and S.

13. The compound according to claim 1 , wherein n is 0 or 1 and R 10 is selected from halo, alkyl, haloalkyl, O-alkyl, oxo, NH 2 , N(H)alkyl, N(alkyl) 2 , SO 2 alkyl, alkylene-N(alkyl) 2 and alkylene-SO 2 alkyl.

14. The compound according to claim 1 wherein one of R 4 and R 5 is selected from H, halo, alkyl and O-alkyl, and the other is a moiety:

15. The compound according to claim 1 , wherein R 5 is H, F, Cl or methyl and R 4 is a moiety (iii-a):

16. The compound according to claim 1 , wherein R 5 is H and R 4 is a moiety (iii-b):

17. The compound according to claim 1 , wherein Ring B is selected from 5-6 membered N-heterocycle or N-heteroaryl optionally including 1 or 2 additional heteroatoms selected from N, O and S.

18. The compound according to claim 1 , wherein Ring C is selected from 5-6 membered and 9-10 membered N-heterocycles optionally including 1 or 2 additional heteroatoms selected from N, O and S.

19. The compound according to claim 1 , wherein p is 0 or 1.

20. The compound according to claim 1 , wherein each R 13 is the same or different and is independently selected from alkyl, haloalkyl, OH, O-alkyl, oxo, NH 2 , N(H)alkyl, N(alkyl) 2 , SO 2 alkyl, alkylene-NH 2 , alkylene-N(H)alkyl, alkylene-N(alkyl) 2 and alkylene-SO 2 alkyl.

21. The compound according to claim 1 , wherein at least one R 6 is H.

22. A compound selected from:

3-[3-(2-{[4-(1,4′-bipiperidin-1′-yl)-2-(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)benzamide;

N-(2,6-difluorophenyl)-3-[3-(2-{[4-{4-[4-(2-fluoroethyl)-1-piperazinyl]-1-piperidinyl}-2-(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamide;

N-(2,6-difluorophenyl)-3-(3-{2-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamide;

N-(2,6-difluorophenyl)-3-(3-{2-[(5-methyl-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamide;

N-(2,6-difluorophenyl)-2-(ethyloxy)-5-(3-{2-[(5-methyl-2-(methyloxy)-4-{-4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamide;

N-(2,6-difluorophenyl)-2-(ethyloxy)-5-(3-{2-[(5-methyl-2-(methyloxy)-4-{1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamide; and

N-(2,6-difluorophenyl)-5-(7-fluoro-3-{2-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide;

N-(2,6-difluorophenyl)-5-(3-{2-[(2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide;

N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide;

and pharmaceutically acceptable salts thereof.

23. N-(2,6-difluorophenyl)-3-[3-(2-{[4-{4-[4-(2-fluoroethyl)-1-piperazinyl]-1-piperidinyl}-2-(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamide

or a pharmaceutically acceptable salt thereof.

24. N-(2,6-difluorophenyl)-3-[3-(2-{[4-{4-[4-(2-fluoroethyl)-1-piperazinyl]-1-piperidinyl}-2-(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamide

25. N-(2,6-difluorophenyl)-5-(3-{2-[(2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide

or a pharmaceutically acceptable salt thereof.

26. N-(2,6-difluorophenyl)-5-(3-{2-[(2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide

27. N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide

or a pharmaceutically acceptable salt thereof.

28. N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide

29. N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide monocitric acid salt.

30. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.

31. The pharmaceutical composition according to claim 30 further comprising a chemotherapeutic agent.

32. The pharmaceutical composition according to claim 30 , wherein the compound is

N-(2,6-difluorophenyl)-5-(3-{2-[(2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide or a pharmaceutically acceptable salt thereof.

33. The pharmaceutical composition according to claim 30 , wherein the compound is

N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide or a pharmaceutically acceptable salt thereof.

34. The pharmaceutical composition according to claim 30 , wherein the compound is

N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide.

35. The pharmaceutical composition according to claim 30 , wherein the compound is

N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide monocitric acid salt.

36. A process for preparing a compound according to claim 1 comprising reacting a compound of formula (V):

with an aniline of formula (VI):

wherein all variables are as defined in claim 1 , to prepare a compound of formula (I).

37. A process for preparing a compound according to claim 1 comprising reacting a compound of formula (XV):

wherein R a is alkyl or cycloalkyl, and

with an aniline of formula (IX):

wherein all variables are as defined in claim 1 , to prepare a compound of formula (I).