Pyrazinopyrazines and derivatives as kinase inhibitors

1. A compound of Formula I:

or a tautomer or pharmaceutically acceptable salt thereof, wherein

W 1 represents an aryl, a 3- to 8-membered carbocyclyl, a 5-, 6- or 7-membered heterocyclic or heteroaryl ring comprising carbon atoms and 1-4 heteroatoms independently selected from O, N, P(O) and S(O) r and W 1 is optionally substituted with 1-5 R a groups;

W 2 represents an aryl or a 5- or 6-membered heteroaryl ring comprising carbon atoms and 1-3 heteroatoms independently selected from O, N, P(O) and S(O) r , and W 2 is optionally substituted with 1-5 R b groups;

Q is N;

L 1 and L 2 are independently selected from a bond, C 1-6 -alkyl, O—C 0-6 -alkyl, NR 1 —C 0-6 -alkyl, C(O)NR 1 —C 0-6 -alkyl, NR 1 C(O)—C 0-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 0-6 -alkyl-S(O) r , C 0-6 -alkyl-S(O) 2 NR 1 , C 0-6 -alkyl-NR 1 S(O) 2 , C(O)—C 0-6 -alkyl, OC(O)NR 1 —C 0-6 -alkyl, NR 1 C(O)O—C 0-6 -alkyl, NR 1 C(O)NR 1 —C 0-6 -alkyl; and the linkers L 1 and L 2 can be included in either direction;

R a and R b are independently selected from halo, —CN, —NO 2 , —R 1 , —OR 2 , —O—NR 1 R 2 , —NR 1 R 2 , —NR 1 —NR 1 R 2 , —NR 1 —OR 2 , —C(O)YR 2 , —OC(O)YR 2 , —NR 1 C(O)YR 2 , —SC(O)YR 2 , —NR 1 C(═S)YR 2 , OC(═S)YR 2 , —C(═S)YR 2 , —YC(═NR 1 )YR 2 , —YC(═N—OR 1 )YR 2 , —YC(═N—NR 1 R 2 )YR 2 , —YP(═O)(YR 3 )(YR 3 ), —Si(R 3 ) 3 , —NR 1 SO 2 R 2 , —S(O) r R 2 , —SO 2 NR 1 R 2 and —NR 1 SO 2 NR 1 R 2 ; alternatively two adjacent R a or two adjacent R b groups form with the atoms to which they are attached, a 5-, 6- or 7-membered saturated, partially saturated or unsaturated ring, which is optionally substituted and which contains 0-3 heteroatoms selected from N, O, P(O) and S(O) r ;

each Y is independently a bond, —O—, —S— or —NR 1 —;

r is 0, 1 or 2;

n is 1 or 2;

each occurrence of R 1 and R 2 is independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocyclic and heteroaryl;

each occurrence of R 3 is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocyclic and heteroaryl;

alternatively, each NR 1 R 2 moiety is a 5-, 6- or 7-membered saturated, partially saturated or unsaturated ring, which is optionally substituted and which contains 0-2 additional heteroatoms selected from N, O, P(O) and S(O) r ; and

each of the foregoing alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocyclic moiety is optionally substituted.

2. The compound of claim 1 in which n is 1.

3. The compound of claim 1 in which n is 2.

4. The compound of any of claim 1 , 2 or 3 having one of the following formulae:

in which R is CH 3 or H.

5. The compound of any of claim 1 , 2 or 3 having either of the following formulae:

6. The compound of any of claim 1 , 2 or 3 having the formula:

7. The compound of claim 6 in which W 1 and W 2 are aryl optionally substituted with 1-5 R a and 1-5 R b respectively; and R is H.

8. The compound of claim 6 in which W 1 is a 5- or 6-membered heteroaryl optionally substituted with 1-5 R a and W 2 is an aryl optionally substituted with 1-5 R b respectively; and R is H.

9. The compound of any of claims 1 to 3 in which L 2 is C(O)C 0-6 alkyl.

10. The compound of claim 9 in which L 2 is C(O).

11. The compound of claim 9 in which L 2 is C(O)CH 2 .

12. The compound of claim 9 having one of the following formulae:

13. The compound of claim 12 in which W 1 and W 2 are aryl optionally substituted with 1-5 R a and 1-5 R b respectively.

14. The compound of claim 12 in which W 1 is a 5- or 6-membered heteroaryl optionally substituted with 1-5 R a , W 2 is an aryl optionally substituted with 1-5 R b .

15. The compound of claim 12 in which n is 1.

16. The compound of claim 12 in which n is 2.

17. The compound of claim 1 in which L 1 is a bond.

18. The compound of claim 2 in which L 1 is a bond.

19. The compound of claim 3 in which L 1 is a bond.

20. The compound of claim 1 in which L 1 is C(O)C 0-6 alkyl.

21. The compound of claim 2 in which L 1 is C(O)C 0-6 alkyl.

22. The compound of claim 3 in which L 1 is C(O)C 0-6 alkyl.

23. The compound of claim 1 in which L 1 is C(O)NHC 0-6 alkyl.

24. The compound of claim 2 in which L 1 is C(O)NHC 0-6 alkyl.

25. The compound of claim 3 in which L 1 is C(O)NHC 0-6 alkyl.

26. The compound of claim 1 in which L 2 is CH 2 or CH(CH 3 ).

27. The compound of claim 2 in which L 2 is CH 2 or CH(CH 3 ).

28. The compound of claim 3 in which L 2 is CH 2 or CH(CH 3 ).

29. The compound, tautomer or salt of claim 1 selected from the following;

1-(2-chloro-3,6-difluorobenzyl)-7-[3-(morpholin-4-yl)phenyl]-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine;

3-[8-(2-chloro-3,6-difluorobenzyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl]-N-[3-(dimethylamino)propyl]benzamide;

1-(2-chloro-3,6-difluorobenzyl)-7-{3-[(4-methylpiperazin-1-yl)methyl]phenyl}-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine;

1-(2-chloro-3,6-difluorobenzyl)-7-[2-(piperazin-1-yl)pyrimidin-5-yl]-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine;

{4-[8-(2-chloro-3,6-difluorobenzyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl]phenyl}(4-methylpiperazin-1-yl)methanone;

1-(2-chloro-3,6-difluorobenzyl)-7-[3-(morpholin-4-ylmethyl)phenyl]-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine;

1-(2-chloro-3,6-difluorobenzyl)-7-[4-(morpholin-4-ylmethyl)phenyl]-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine;

1-(2-chloro-3,6-difluorobenzyl)-7-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine;

3-{4-[8-(2-chloro-3,6-difluorobenzyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl]phenyl}propanehydrazide;

1-(2,5-dichlorobenzyl)-7-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine;

{3-[8-(2-chloro-3,6-difluorobenzyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl]phenyl}(4-methylpiperazin-1-yl)methanone;

4-[8-(2-chloro-3,6-difluorobenzyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl]-N-[2-(morpholin-4-yl)ethyl]benzamide;

{4-[8-(2-chloro-3,6-difluorobenzyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl]phenyl}[4-(pyrrolidin-1-yl)piperidin-1-yl]methanone;

2-{3-[8-(2-chloro-3,6-difluorobenzyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl]phenyl}acetamide;

1-(2-chloro-3,6-difluorobenzyl)-7-[2-(4-methylpiperazin-1-yl)pyridine-4-yl]-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine;

1-(2-chloro-3,6-difluorobenzyl)-7-[1-(piperidin-4-yl)-1H-pyrazol-3-yl]-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine

4-[8-(2-chloro-3,6-difluorobenzyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl]-N-[3-(dimethylamino)propyl]benzamide;

4-[8-(2-chloro-3,6-difluorobenzyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl]-N-[2-(diethylamino)ethyl]benzamide;

{4-[8-(2-chloro-3,6-difluorobenzyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl]phenyl}[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]methanone;

1-(2,6-dichlorobenzyl)-7-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine;

1-(2,5-difluorobenzyl)-7-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine;

1-[5-chloro-2-(trifluoromethyl)benzyl]-7-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine;

9-(2-chloro-3,6-difluorobenzyl)-2-[3-(morpholin-4-yl)phenyl]-6,7,8,9-tetrahydro-5H-pyrazino[2,3-b][1,4]diazepine;

3-[9-(2-chloro-3,6-difluorobenzyl)-6,7,8,9-tetrahydro-5H-pyrazino[2,3-b][1,4]diazepin-2-yl]-N-[2-(morpholin-4-yl)ethyl]benzamide;

{3-[9-(2-chloro-3,6-difluorobenzyl)-6,7,8,9-tetrahydro-5H-pyrazino[2,3-b][1,4]diazepin-2-yl]phenyl}[4-(2-hydroxyethyl)piperazin-1-yl]methanone;

9-(2-chloro-3,6-difluorobenzyl)-2-(2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-6,7,8,9-tetrahydro-5H-pyrazino[2,3-b][1,4]diazepine;

6-[9-(2-chloro-3,6-difluorobenzyl)-6,7,8,9-tetrahydro-5H-pyrazino[2,3-b][1,4]diazepin-2-yl]-N-methylquinazolin-2-amine; and,

9-(2-chloro-3,6-difluorobenzyl)-2-{-4-[2-(1H-imidazol-1-yl)ethoxy]phenyl}-6,7,8,9-tetrahydro-5H-pyrazino[2,3-b][1,4]diazepine.

30. The compound of any of claim 1 to 3 or 17 - 25 in which W 1 is aryl.

31. The compound of any of claim 1 to 3 or 17 - 25 in which W 1 is 5- or 6-membered heteroaryl.

32. The compound of any of claim 1 to 3 or 17 - 25 in which W 1 is a 5-, 6- or 7-membered heterocyclyl.

33. The compound of any of claim 1 to 3 or 17 - 25 in which W 1 is a 3- to 8-membered carbocyclyl.

34. A composition comprising a compound of any of claim 1 - 3 , 30 - 33 , 4 - 6 , 7 - 14 , 15 - 16 , or 17 - 29 ; or a pharmaceutically acceptable salt thereof and a pharmaceutical carrier, diluent or vehicle.