Diazacarbazoles and methods of use

1. A compound of formula (I) or a salt thereof:

X is CR 2 or N;

Y is CR 4 or N;

Z is CR 8 or N; provided that no more than one of X, Y and Z is N at the same time;

R 2 is H, halo, CN, CF 3 , —OCF 3 , OH, —NO 2 , C 1 -C 5 alkyl, —O(C 1 -C 5 alkyl), —S(C 1 -C 5 alkyl), or N(R 22 ) 2 ;

R 3 is H, halo, CN, —O—R 9 , —N(R 22 )—R 9 , —S(O) p —R 9 , or R 9 ;

p is 0, 1 or 2;

R 4 is H, halo, CN, CF 3 , —OCF 3 , OH, —NO 2 , —(CR 14 R 15 ) n C(═Y′)OR 11 , —(CR 14 R 15 ) n C(═Y′)NR 11 R 12 , —(CR 14 R 15 ) n NR 11 R 12 , —(CR 14 R 15 ) n OR 11 , —(CR 14 R 15 ) n S(O) p R 11 , —(CR 14 R 15 ) n NR 12 C(═Y′)R 11 , —(CR 14 R 15 ) n NR 12 C(═Y′)OR 11 , —(CR 14 R 15 ) n NR 12 C(═Y′)NR 11 R 12 , —(CR 14 R 15 ) n NR 12 SO 2 R 11 , —(CR 14 R 15 ) n OC(═Y′)R 11 , —(CR 14 R 15 n OC(═Y′)NR 11 R 12 , —(CR 14 R 15 ) n S(O) 2 NR 11 R 12 , alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R 13 groups;

each n is independently 0-5;

R 5 is H, halo, CN, CF 3 , —OCF 3 , OH, —NO 2 , —(CR 14 R 15 ) n C(═Y′)OR 11 , —(CR 14 R 15 ) n C(═Y′)NR 11 R 12 , —(CR 14 R 15 ) n NR 12 C(═Y′)R 11 , —(CR 14 R 15 ) n NR 11 R 12 , —(CR 14 R 15 ) n OR 11 , —(CR 14 R 15 ) n S(O) p R 11 , —(CR 14 R 15 ) n NR 12 C(═Y′)OR 11 , —(CR 14 R 15 ) n NR 12 C(═Y′)NR 11 R 12 , —(CR 14 R 15 ) n NR 12 SO 2 R 11 , —(CR 14 R 15 ) n OC(═Y′)R 11 , —(CR 14 R 15 ) n OC(═Y′)NR 11 R 12 , —(CR 14 R 15 ) n S(O) 2 NR 11 R 12 , alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl wherein the said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R 13 groups;

R 6 is CN, —CF 3 , —OCF 3 , halo, —C(═Y′)NR 11 R 12 , —OR 11 , —OC(═Y′)R 11, —NR 11 R 12 , —NR 12 C(═Y′)R 11 , —NR 12 C(═Y′)NR 11 R 12 , —NR 12 S(O) q R 11 , —SR 11 , —S(O)R 11 , —S(O) 2 R 11 , —OC(═Y′)NR 11 R 12 , —S(O) 2 NR 11 R 12 , alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted by one to four R 13 groups;

R 8 is H, halo, CN, NO 2 , N(R 22 ) 2 , OH, O(C 1 -C 3 alkyl), or C 1 -C 3 alkyl, wherein each said alkyl is optionally substituted with one to three fluoro groups;

each R 9 is independently alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein each member of R 9 is independently substituted with one to three R 10 groups;

each R 10 is independently H, CN, —CF 3 , —OCF 3 , —NO 2 , halo, R 11 , —OR 11 , —NR 12 C(═Y′)R 11 , —NR 12 C(═NR 12 )R 11 , 13 NR 12 S(O) q R 11 , —SR 11 , —NR 11 R 12 , oxo, —C(═Y′)OR 11 , —C(═Y′)NR 11 R 12 , 13 S(O) q R 11 , NR 12 C(Y′)OR 11 , —NR 12 C(═Y′)NR 11 R 12 , —OC( 50 Y′)R 11 , —OC(═Y′)NR 11 R 12 , or —S(O) 2 NR 11 R 12 ;

each q independently is 1 or 2;

R 11 and R 12 are independently H, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R 13 groups, wherein two geminal R 13 groups are optionally taken together with the atom to which they are attached to form a 3-6 membered ring having additional 0-2 heteroatoms selected from O, S, and N, said ring being optionally substituted with one to four R 18 groups;

R 11 and R 12 are optionally taken together with the attached N atom to form a 4-7 membered ring having additional 0-2 heteroatoms selected from O, S, and N, said ring being optionally substituted with one to four R 13 groups;

each R 13 is independently halo, CN, CF 3 , —OCF 3 , —NO 2 , oxo, —(CR 14 R 15 ) n C(═Y′)R 16 , —(CR 14R 15) n C(═Y′)OR 16 , —(CR 14 R 15 ) n C(═Y′)NR 16 R 17 , —(CR 14 R 15 ) n NR 16 R 17 , —(CR 14 R 15 ) n OR 16 , —(CR 14 R 15 ) n SR 16 , —(CR 14 R 15 ) n NR 16 C(═Y′)R 17 , —(CR 14 R 15 ) n NR 16 C(═Y′)OR 17 , —(CR 14 R 15 ) n NR 17 C(═Y′)NR 16 R 17 , —(CR 14 R 15 ) n NR 17 SO 2 R 16 , —(CR 14 R 15 ) n OC(═Y′)R 16 , —(CR 14 R 15 ) n OC(Y′)NR 16 R 17 , —(CR 14 R 15 ) n S(O)R 16 , —(CR 14 R 15 ) n S(O) 2 R 16 , —(CR 14 R 15 ) n S(O) 2 NR 16 R 17 , or R 16 ;

R 14 and R 15 are independently selected from H, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R 18 groups;

R 16 and R 17 are independently H, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R 18 groups;

R 16 and R 17 are optionally taken together with the attached N atom to form a 5-6 membered ring having additional 0-2 heteroatoms selected from O, S, and N, said ring being optionally substituted with one to four R 18 groups;

each R 18 is independently H, alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, CN, CF 3 , —OCF 3 , —NO 2 , oxo, —(CR 19 R 2 ) n C(═Y′)R 23 , —(CR 19 R 20 ) n C(═Y′)OR 23 , —(CR 19 R 20 ) n C(═Y′)NR 23 R 24 , —(CR 19 R 20 ) n NR 23 R 24 , —(CR 19 R 20 ) n OR 23 , —(CR 19 R 20 ) n —SR 23 , —(CR 19 R 20 ) n NR 24 C(═Y′)R 23 , —(CR 19 R 20 ) n NR 24 C(═Y′)OR 23 , —(CR 19 R 20 ) n NR 22 C(═Y′)NR 23 R 24 , —(CR 19 R 20 ) n NR 24 SO 2 R 23 , —(CR 19 R 20 ) n OC(═Y′)R 23 , —(CR 19 R 20 ) n OC(═Y′)NR 23 R 24 , —(CR 19 R 20 ) n S(O)R 23 , —(CR 19 R 20 ) n S(O) 2 R 23 , or —(CR 19 R 20 ) n S(O) 2 NR 23 R 24 , wherein said alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with one to four R 21 groups;

R 19 and R 20 are independently H, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R 25 groups;

R 23 and R 24 are independently H, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted with one to four R 21 groups;

R 23 and R 24 are optionally taken together with the attached N atom to form a 5-6 membered ring having additional 0-2 heteroatoms selected from O, S, and N, said ring being optionally substituted with one to four R 21 groups;

each R 21 is independently H, alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, CN, CF 3 , —OCF 3 , —NO 2 , oxo, —C(═Y′)R 25 , —C(═Y′)OR 25 , —C(═Y′)NR 25 R 26 , —NR 25 R 26 , —OR 25 , —SR 25 , —NR 26 C(═Y′)R 25 , —NR 26 C(═Y′)OR 25 , —NR 22 C(═Y′)NR 25 R 26 , —NR 26 SO 2 R 25 , —OC(═Y′)R 25 , —OC(═Y′)NR 25 R 26 , —S(O)R 25 , —S(O) 2 R 25 , or —S(O) 2 NR 25 R 26 , wherein said alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with one to four R 25 groups;

each R 25 and R 26 is independently H, alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one to four groups selected from halo, —CN, —OCF 3 , —CF 3 , —NO 2 , —C 1 -C 6 alkyl, —OH, oxo, —SH, —O(C 1 -C 6 alkyl), —S(C 1 -C 6 alkyl), —NH 2 , —NH(C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl) 2 , —SO 2 (C 1 -C 6 alkyl), —CO 2 H, —CO 2 (C 1 -C 6 alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6 alkyl), —C(O)N(C 1 -C 6 alkyl) 2 , —N(C 1 -C 6 alkyl)C(O)(C 1 -C 6 alkyl), —NHC(O)(C 1 -C 6 alkyl), —NHSO 2 (C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl)SO 2 (C 1 -C 6 alkyl), —SO 2 NH 2 , —SO 2 NH(C 1 -C 6 alkyl), —SO 2 N(C 1 -C 6 alkyl) 2 , —OC(O)NH 2 , —OC(O)NH(C 1 -C 6 alkyl), —OC(O)N(C 1 -C 6 alkyl) 2 , —NHC(O)NH(C 1 -C 6 alkyl), —NHC(O)N(C 1 -C 6 alkyl) 2 , —N(C 1 -C 6 alkyl)C(O)NH(C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl)C(O)N(C 1 -C 6 alkyl) 2 , —NHC(O)NH(C 1 -C 6 alkyl), —NHC(O)N(C 1 -C 6 alkyl) 2 , —NHC(O)O(C 1 -C 6 alkyl), and —N(C 1 -C 6 alkyl)C(O)O(C 1 -C 6 alkyl);

R 25 and R 26 are optionally taken together with the attached N atom to form a 5-6 membered ring having additional 0-2 heteroatoms selected from O, S, and N, said ring being optionally substituted with one to four groups selected from halo, —CN, —OCF 3 , CF 3 , —NO 2 , —C 1 -C 6 alkyl, —OH, oxo, —SH, —O(C 1 -C 6 alkyl), —S(C 1 -C 6 alkyl), —NH 2 , —NH(C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl) 2 , —SO 2 (C 1 -C 6 alkyl), —CO 2 H, —CO 2 (C 1 -C 6 alkyl), —C(O)NH 2 , —C(O)NH(C 1 -C 6 alkyl), —C(O)N(C 1 -C 6 alkyl) 2 , —N(C 1 -C 6 alkyl)C(O)(C 1 -C 6 alkyl), —NHC(O)(C 1 -C 6 alkyl), —NHSO 2 (C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl)SO 2 (C 1 -C 6 alkyl), —SO 2 NH 2 , —SO 2 NH(C 1 -C 6 alkyl), —SO 2 N(C 1 -C 6 alkyl) 2 , —OC(O)NH 2 , —OC(O)NH(C 1 -C 6 alkyl), —OC(O)N(C 1 -C 6 alkyl) 2 , —NHC(O)NH(C 1 -C 6 alkyl), —NHC(O)N(C 1 -C 6 alkyl) 2 , —N(C 1 -C 6 alkyl)C(O)NH(C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl)C(O)N(C 1 -C 6 alkyl) 2 , —NHC(O)NH(C 1 -C 6 alkyl), —NHC(O)N(C 1 -C 6 alkyl) 2 , —NHC(O)O(C 1 -C 6 alkyl), and —N(C 1 -C 6 alkyl)C(O)O(C 1 -C 6 alkyl);

Y′ is independently O, NR 22 , or S; and

each R 22 is independently H or C 1 -C 5 alkyl.

2. The compound of claim 1 wherein X is CR 2 .

3. The compound of claim 2 wherein R 2 is H.

4. The compound of claim 3 wherein Y is CR 4 .

5. The compound of claim 4 wherein R 4 is H.

6. The compound of claim 5 wherein Z is CR 8 .

7. The compound of claim 6 wherein R 8 is H.

8. The compound of claim 7 wherein R 3 is Br.

9. The compound of claim 7 wherein R 3 is H.

10. The compound of claim 7 wherein R 3 is R 9 .

11. The compound of claim 10 wherein R 9 is C 1 -C 6 alkyl, C 2 -C 3 alkynyl, C 6 aryl, or 5-6 membered monocyclic or 8-10-membered bicyclic heteroaryl having 1 to 2 ring atoms selected from N, O and S; and wherein each member of R 9 is independently substituted with one to two R 10 groups.

12. The compound of claim 11 wherein R 9 is isopropyl, propynyl, phenyl, pyrazolyl, furanyl, thienyl, pyridyl, imidazolyl, pyrimidinyl, benzothienyl, thiazolyl, tetrahydrothienopyridinyl, tetrahydrothiazolopyridinyl, isothiazolyl, tetrahydropyridinyl, tetrahydroisoquinolinyl, triazolyl, dihydrobenzodioxinyl, dihydroindolyl, oxazolyl, or tetrahydrobenzothienyl, wherein each member of R 9 is independently substituted with one to two R 10 groups.

13. The compound of claim 12 wherein R 10 is halo, R 11 , —OR 11 , CN, —CF 3 , —OCF 3 , —NR 12 C(═O)R 11 , —NR 12 S(O) q R 11 , —SR 11 , —NR 11 R 12 , —C(═O)NR 11 R 12 , oxo, —S(O) q R 11 , —S(O) 2 NR 11 R 12 , or —C(═O)OR 11 , wherein R 11 and R 12 are optionally taken together with the attached N atom to form a 4-7 membered ring having additional 0-2 heteroatoms selected from O, S, and N, said ring being optionally substituted with one to four R 13 groups.

14. The compound of claim 12 wherein R 10 is R 11 .

15. The compound of claim 14 wherein R 11 is C 1 -C 6 alkyl, or 4-6 membered monocyclic or 8-10 membered bicyclic heterocyclyl having 1 to 2 heteroatoms selected from N and O, wherein said alkyl and heterocyclyl are optionally substituted with one to four R 13 groups, wherein two geminal R 13 groups are optionally taken together with the atom to which they are attached to form a six-membered ring having 0-2 heteroatom selected from O, S, and N, said ring being optionally substituted with one to four R 18 groups.

16. The compound of claim 15 wherein R 11 is C 1 -C 6 alkyl, wherein alkyl is optionally substituted with one to two R 13 groups and wherein each R 13 is independently halo, CN, CF 3 , —OCF 3 , oxo, —(CR 14 R 15 ) n C(O)OR 16 , —(CR 14 R 15 ) n C(O)NR 16 R 17 , —(CR 14 R 15 ) n NR 16 R 17 , —(CR 14 R 15 ) n OR 16 , —(CR 14 R 15 ) n NR 16 C(O)R 17 , —(CR 14 R 15 ) n S(O) 2 NR 16 R 17 , or R 16 .

17. The compound of claim 15 wherein R 11 is 4-6 membered monocyclic or 8-10 membered bicyclic heterocyclyl having 1 to 2 heteroatoms selected from N and O, wherein said alkyl and heterocyclyl are optionally substituted with one to two R 13 groups and wherein each R 13 is independently halo, CN, CF 3 , —OCF 3 , oxo, —(CR 14 R 15 ) n C(O)OR 16 , —(CR 14 R 15 ) n C(O)NR 16 R 17 , —(CR 14 R 15 ) n NR 16 R 17 , —(CR 14 R 15 ) n OR 16 , —(CR 14 R 15 ) n NR 16 C(O)R 17 , —(CR 14 R 15 ) n S(O) 2 NR 16 R 17 , or R 16 .

18. The compound of claim 12 wherein R 10 is —OR 11 .

19. The compound of claim 18 wherein R 11 is H, C 1 -C 4 alkyl, or 4-6 membered monocyclic or 8-10 membered bicyclic heterocyclyl having 1 to 2 nitrogen atoms, wherein said alkyl or heterocyclyl is optionally substituted with one to two R 13 groups, wherein each R 13 is independently halo, CN, CF 3 , —OCF 3 , oxo, —(CR 14 R 15 ) n C(O)OR 16 , —(CR 14 R 15 ) n C(O)NR 16 R 17 , —(CR 14 R 15 ) n NR 16 R 17 , —(CR 14 R 15 ) n OR 16 , —(CR 14 R 15 ) n NR 16 C(O)R 17 , —(CR 14 R 15 ) n S(O) 2 NR 16 R 17 , or R 16 .

20. The compound of claim 19 wherein R 5 is H.

21. The compound of claim 19 wherein R 5 is —(CR 14 R 15 ) n C(O)NR 11 R 12 , —(CR 14 R 15 ) n NR 12 C(O)R 11 , —(CR 14 R 15 ) n NR 11 R 12 , —(CR 14 R 15 ) n OR 11 , C 1 -C 6 alkyl, or 4-6 membered monocyclic or 7-10 membered bicyclic heterocyclyl having 1 to 2 nitrogen atoms, wherein said alkyl or heterocyclyl is optionally substituted with one to two R 13 groups; wherein R 14 and R 15 are H; n is 0-2; each R 11 is independently H, C 1 -C 4 alkyl, or 5-6 membered monocyclic heterocyclyl having 1 to 2 nitrogen atoms, wherein said alkyl or heterocyclyl is optionally substituted with one to two R 13 groups; and R 13 is OH, O(C 1 -C 3 alkyl), or C 1 -C 3 alkyl.

22. The compound of claim 21 wherein R 6 is CN, halo, —C(O)NR 11 R 12 , —OR 11 , —NR 11 R 12 , —NR 12 C(O)R 11 , C 1 -C 3 alkyl, C 3 -C 6 cycloalkyl, 5-6 membered heterocyclyl having 1 to 2 heteroatoms, C 6 aryl, or 5-6 membered heteroaryl having 1 to 2 heteroatoms; wherein said alkyl is substituted with one to two R 13 groups except H; and said cycloalkyl, aryl, heterocyclyl or heteroaryl is optionally substituted by one to two R 13 groups; wherein heteroatoms are selected from N, O and S; wherein each R 12 is H or C 1 -C 3 alkyl and each R 11 is independently H or C 1 -C 3 alkyl optionally substituted by one to two R 13 groups.

23. The compound of claim 22 wherein R 6 is CN.

24. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

25. The compound of claim 1 , wherein it is selected from:

26. A compound of the following formula or a pharmaceutically acceptable salt thereof:

27. A compound of the following formula or a pharmaceutically acceptable salt thereof:

28. A compound of the following formula or a pharmaceutically acceptable salt thereof:

29. A compound of the following formula or a pharmaceutically acceptable salt thereof:

30. A compound of the following formula or a pharmaceutically acceptable salt thereof:

31. A compound of the following formula or a pharmaceutically acceptable salt thereof:

32. A compound of the following formula or a pharmaceutically acceptable salt thereof:

33. A compound of the following formula or a pharmaceutically acceptable salt thereof:

34. A compound of the following formula or a pharmaceutically acceptable salt thereof:

35. A compound of the following formula or a pharmaceutically acceptable salt thereof:

36. A compound of the following formula or a pharmaceutically acceptable salt thereof:

37. A compound of the following formula or a pharmaceutically acceptable salt thereof: