Substituted thieno[2,3-b]pyrazine compounds as modulators of B-Raf kinase activity

1. A compound according to Formula I

or a pharmaceutically acceptable salt thereof, wherein:

one of R1 and R2 is H; halogen; hydroxy; CN; amino; (1-2C)alkyl; (1-2C)alkylcarbonyl; (1-2C)alkoxy; or (di)[(1-2C)alkyl]amino, the alkyl group of which is optionally substituted with hydroxy;

and the other R1 and R2 is H; halogen; hydroxy; CN; amino; (1-6C)alkyl; (1-6C)alkoxy; (di)[(1-6C)alkyl]amino, the alkyl group of which is optionally substituted with one or more hydroxy, (di)[(1-4C)alkyl]amino, (1-6C)alkoxy, (2-5C)heterocycloalkyl or (2-5C)heteroaryl; (1-6C)alkylcarbonyl; (2-5C)heterocycloalkyl, optionally substituted with one or more groups selected from hydroxy, amino, (1-6C)alkyloxycarbonylamino or (1-6C)alkyl, the alkyl group of which is optionally substituted with hydroxy; (2-5C)heteroaryl or (2-5C)heteroarylamino, both optionally substituted with halogen, CN, (1-6C)alkoxy, (di)[(1-6C)alkyl]amino or (1-6C)alkyl; phenyl or phenylamino, both optionally substituted with halogen, CN, (1-6C)alkyl, (1-6C)alkoxy or (di)[(1-6C)alkyl]amino; or (2-5C)heterocycloalkylamino;

R3 is H; amino; halogen; hydroxy; cyano; (1-6C)alkyl; (2-6C)alkenyl; (2-6C)alkynyl; (di)[(1-4C)alkyl]amino; (1-4C)alkylcarbonylamino, the alkyl group of which optionally is substituted with halogen; or phenylalkyl, the phenyl group of which is optionally substituted with halogen;

R4 is (1-4C)alkyl; halogen; or cyano;

R5 and R6 are independently H or halogen;

X is NHCO; CONH; N═C(CN); NHCH 2 ; NHSO 2 ; SO 2 NH; or CO;

Y is CONH; NHCO; NHCONH; NHSO 2 ; or SO 2 NH;

ar ring is an aryl ring selected from (2-5C)heteroaryl substituted with one or more groups selected from halogen, (1-6C)alkyl, phenyl, (2-5C)heterocycloalkyl, or (di)[(1-6C)alkyl]amino optionally substituted with (1-6C)alkoxy, OH, or (di)[(1-6C)alkyl]amino; or phenyl having Formula II

wherein:

R7 and R11 are independently H; halogen; (1-6C)alkyl; (di)[(1-6C)alkyl]amino; or amino;

R8, R9 and R10 are independently H; halogen; amino; (1-6C)alkyl, optionally substituted with one or more CN, aminocarbonyl, halogen, hydroxy, phenyl or (2-5C)heterocycloalkyl; (1-6C)alkoxy, optionally substituted with one or more halogen, hydroxy or (1-6)alkoxy; (di)[(1-6C)alkyl]amino, optionally substituted with phenyl; (2-5C)heteroaryl; (2-5C)heterocycloalkyl, optionally substituted with cyano or (1-6C)alkyl; (di)[(1-6C)alkyl]amino); (1-6C)alkylcarbonyl: or phenylamino.

2. The compound according to claim 1 wherein the ar ring is phenyl having Formula II

.

3. The compound according to claim 2 wherein R8 in the phenyl ring is (1-4C)alkyl, optionally substituted with one or more CN, aminocarbonyl or halogen; (1-4C)alkoxy; (di)[(1-4C)alkyl]amino; or (2-5C)heteroaryl.

4. The compound according to claim 3 wherein R8 in the phenyl ring is (1-4C)alkyl, optionally substituted with one or more CN or halogen.

5. The compound according to claim 2 wherein R7, R9, R10 and R11 are H.

6. The compound according to claim 1 wherein R1 is H; halogen; hydroxy; CN; amino; (1-2C)alkyl; (1-2C)alkylcarbonyl; (1-2C)alkoxy; or (di)[(1-2C)alkyl]amino, the alkyl group of which is optionally substituted with hydroxy; and

R2 is H; halogen; hydroxy; CN; amino; (1-6C)alkyl; (di)[(1-6C)alkyl]amino, the alkyl group of which is optionally substituted with one or more hydroxy, (di)[(1-4C)alkylamino, (1-6C)alkoxy, (2-5C)heterocycloalkyl or (2-5C)heteroaryl; (1-4C)alkylcarbonyl; (1-4C)alkoxy, optionally substituted with (di)[(1-4C)alkyl]amino; (2-5C)heterocycloalkyl, optionally substituted with one or more groups selected from hydroxy, amino, (1-6C)alkyloxycarbonylamino), or (1-4C)alkyl, the alkyl group of which is optionally substituted with hydroxy; (2-5C)heteroaryl, optionally substituted with halogen, CN, (1-4C)alkoxy, (di)[(1-4C)alkyl]amino or (1-4C)alkyl; phenyl, optionally substituted with halogen, CN, (1-4C)alkyl, (1-4C)alkoxy or (di)[(1-4C)alkyl]amino; (2-5C)heteroarylamino; phenylamino; or (2-5C)heterocycloalkylamino.

7. The compound according to claim 6 wherein R1 is H; halogen; hydroxy; CN; amino; (1-2C)alkyl; (1-2C)alkylcarbonyl; (1-2C)alkoxy; or (di)[(1-2C)alkyl]amino, the alkyl group of which is optionally substituted with hydroxy; and

R2 is H; halogen; hydroxy; CN; amino; (1-6C)alkyl; (1-6C)alkoxy; (di)[(1-6C)alkyl]amino, the alkyl group of which is optionally substituted with one or more hydroxy, (di)[(1-4C)alkylamino, (1-6C)alkoxy, (2-5C)heterocycloalkyl or (2-5C)heteroaryl; or (2-5C)heteroaryl.

8. The compound according to claim 7 wherein R2 is H or (di)[(1-2C)alkyl]amino, the alkyl group of which is optionally substituted with hydroxy.

9. The compound according to claim 6 wherein R1 is H or (di)[(1-2C)alkyl]amino, the alkyl group of which is optionally substituted with hydroxy.

10. The compound according to claim 1 wherein X and Y are independently NHCO or CONH.

11. The compound according to claim 10 wherein X is NHCO.

12. The compound according to claim 11 wherein Y is CONH.

13. The compound according to claim 1 wherein the ar ring is (2-5C)heteroaryl substituted with one or more groups selected from (1-6C)alkyl, phenyl, (di)[(1-4C)alkyl]amino or pyrrolidinyl.

14. The compound according to claim 1 wherein at least one of R1 or R2 is H.

15. The compound according to claim 1 wherein R3 is H, amino or (di)[(1-4C)alkyl]amino.

16. The compound according to claim 1 wherein R5 and R6 are independently H.

17. A pharmaceutical composition comprising the compound of claim 1 in combination with a pharmaceutically acceptable carrier or diluent.