Pyridine derivatives useful as kinase inhibitors

1. A compound of formula I:

wherein

Q is NR 3 ;

W is cyclopropyl, or a saturated or unsaturated 5 or 6 membered heterocyclyl containing 1 or 2 heteroatoms selected from N, O and S wherein the cyclopropyl, or saturated or unsaturated 5 or 6 membered heterocyclyl may be substituted with 1 or 2 substituents independently selected from the group consisting of C 1-4 alkyl, OH, NO 2 , NR 7 R 8 , halogen, CF 3 , CO 2 R 9 , OC 1-4 alkyl, COR 9 , SO 2 C 1-4 alkyl and a saturated or unsaturated 5 or 6 membered heterocyclyl containing 1 or 2 heteroatoms selected from the group consisting of N, O and S;

X is selected from the group consisting of NHCO and CONH;

each of Z 1 , Z 2 , Z 3 and Z 4 is independently selected from the group consisting of N and CR 1 provided that no more than two of Z 1 , Z 2 , Z 3 and Z 4 are N;

each R 1 is independently selected from the group consisting of H, halogen, CF 3 , OCF 3 , C 1-4 alkyl and OC 1-4 alkyl;

R 2 and R 17 are independently selected from the group consisting of H, C 1-4 alkyl, CF 3 , C 1-4 alkylOH and C 1-4 alkylOC 1-4 alkyl or

R 2 and R 17 together with the carbon atom to which they are attached form C 3-8 cycloalkyl or 3, 4, 5, 6, 7 or 8 membered saturated heterocyclyl;

R 3 is selected from the group consisting of H and C 1-4 alkyl;

A is N and Y is CR 3 or A is CR 3 and Y is N;

R 4 and R 5 are independently selected from the group consisting of H, C 1-4 alkyl, CF 3 , halogen and NR 9 R 10 ;

R 6 is selected from the group consisting of H, halogen, OR 11 , NR 12 R 13 , C 1-4 alkyl, C 1-4 alkylOH, CO 2 R 9 , CONR 7 R 8 , S(O) n R 14 , aryl and 5, 6 or 7 membered heterocyclyl having 1, 2 or 3 heteroatoms selected from the group consisting of N, O, S, SO and SO 2 , wherein the aryl or heterocyclyl may be substituted with 1, 2 or 3 substituents independently selected from the group consisting of C 1-4 alkyl, OH, NR 15 R 16 , halogen, CF 3 , OCF 3 , CN, OC 1-4 alkyl, OC 2-4 alkyleneOH, OC 2-4 alkyleneNR 7 R 8 , C 1-4 alkyleneOH, C 1-4 alkyleneOC 1-4 alkyl, C 1-4 alkyleneNR 7 R 8 , CONR 7 R 8 , CO 2 R 9 , NR 7 COR 9 , NR 7 SO 2 C 1-4 alkyl, N(SO 2 C 1-4 alkyl) 2 , NR 7 CONR 8 C 1-4 alkyl, SO 2 NR 9 R 10 , OP(O)(OR 7 ) 2 , SO 2 C 1-4 alkyl, aryl and heterocyclyl;

n is 0, 1 or 2;

R 7 and R 8 are independently selected from the group consisting of H, C 1-4 alkyleneOH, C 1-4 alkylene OC 1-4 alkyl, C 1-4 alkylene NR 15 R 16 , COC 1-4 alkyl and aryl; or

R 7 and R 8 together with the nitrogen to which they are attached form a 5, 6, or 7 membered heterocyclyl which contains 1 or 2 heteroatoms selected from the group consisting of N, O, S, SO and SO 2 and which may be substituted with H, C 1-4 alkyl, OR 9 or NR 9 R 10 ;

R 9 and R 10 are independently selected from the group consisting of H and C 1-4 alkyl;

R 11 is independently selected from the group consisting of H, C 1-4 alkyl, C 2-4 alkyleneOH and C 2-4 alkylene NR 7 R 8 ;

R 12 and R 13 are independently selected from the group consisting of H, C 1-4 alkyl, aryl, C 2-4 alkyleneOH, COC 1-4 alkyl, COaryl and COheterocyclyl; or

R 12 and R 13 together with the nitrogen to which they are attached form a 5, 6, or 7 membered heterocyclyl which contains 1 or 2 heteroatoms selected from N, O, S, SO and SO 2 and which may be substituted with C 1-4 alkyl, OR 9 or NR 9 R 10 ;

R 14 is aryl or a 5, 6, or 7 membered heterocyclyl having 1, 2 or 3 heteroatoms selected from the group consisting of N, O, S, SO and SO 2 , wherein the aryl or heterocyclyl may be substituted with 1, 2 or 3 substituents selected from the group consisting of C 1-4 alkyl, OH, NR 15 R 16 , halogen, CF 3 , OCF 3 , CN, OC 1-4 alkyl, OC 2-4 alkyleneOH, C 1-4 alkylene OH, C 1-4 alkyleneOC 1-4 alkyl, C 1-4 alkyleneNR 15 R 16 , CONR 15 R 16 , CO 2 R 9 , NR 7 SO 2 CH 3 , N(SO 2 CH 3 ) 2 , NR 7 CONR 8 C 1-4 alkyl, SO 2 NR 15 R 16 , OP(O)(OR 7 ) 2 , aryl and heterocyclyl;

R 15 and R 16 are independently selected from the group consisting of H, C 1-4 alkyl, C 1-4 alkylOH, C 1-4 alkylOC 1-4 alkyl, COC 1-4 alkyl and S(O)CH 3 ; or

R 15 and R 16 together with the nitrogen to which they are attached form a 5 or 6 membered heterocyclyl which contains 1 or 2 heteroatoms selected from N, O and S which may be substituted with C 1-4 alkyl, OR 9 or NR 9 R 10 ,

or a pharmaceutically acceptable salt thereof or stereoisomer thereof.

2. The compound according to claim 1 , wherein the compound of formula I has the formula Ia

3. The compound according to claim 1 , wherein the compound of formula I has the formula Ib

4. The compound according to claim 3 , wherein R 6 is H, halogen, CO 2 R 9 , CONR 7 R 8 , phenyl, saturated or unsaturated 5 or 6 membered heterocyclyl containing 1 or 2 heteroatoms selected from the group consisting of N, O and S, or a condensed heterocyclyl containing 1 or 2 oxygen atoms, wherein the phenyl or heterocyclyl may be substituted with 1 or 2 substituents independently selected from the group consisting of OC 1-4 alkyl, OH, NR 7 CONR 8 , NR 15 R 16 , SO 2 NR 9 R 10 , OP(O)(OH) 2 , CO 2 R 9 , C 1-4 alkylOH, C 1-4 alkyleneNR 15 R 16 and 6 membered heterocyclyl containing 1 or 2 heteroatoms selected from the group consisting of N and O.

5. The compound according to claim 1 , wherein one of R 2 and R 17 is H and the other is H or C 1-4 alkyl.

6. The compound according to claim 1 , wherein both R 4 and R 5 are H.

7. The compound according to claim 1 , wherein

both Z 2 and Z 3 are CH and Z 4 is CH or C(CH 3 ), or

one of Z 2 and Z 3 is N and Z 4 is CH.

8. The compound according to claim 1 , wherein the methylene substituted with R 2 and R 17 is of S chirality.

9. The compound according to claim 1 , wherein X is CONH.

10. The compound of claim 1 wherein X is NHCO.

11. The compound of claim 1 which is

or a pharmaceutically acceptable salt thereof or stereoisomer thereof.

12. A pharmaceutical composition comprising the compound of formula I according to claim 1 and a pharmaceutically acceptable carrier.

13. An implant which comprises the compound of formula I according to claim 1 .

14. A method of inhibiting a protein tyrosine kinase in a cell comprising contacting said cell with the compound of formula I according to claim 1 .

15. A method for controlling macrophage populations in a subject, comprising contacting said macrophage population with the compound of formula I according to claim 1 .

16. A process for the preparation of the compound of formula I according to claim 1 , which comprises the step of coupling a compound of formula II:

wherein D is NH 2 , NHR or CO 2 H, where R is C 1-4 alkyl;

with WR′,

wherein W is as defined in claim 1 , and R′ is NH 2 , NHR, CO 2 H or COCl, where R is C 1-4 alkyl.