Kinase inhibitors for the treatment of disease

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein

Z 1 is N or CR 1 ;

Z 2 is N or CR 2 ;

Z 3 is N or CR 3 , provided that when Y is NR 4 , then two of Z 1 , Z 2 or Z 3 are N;

R 1 is H, C 1 -C 8 alkyl, halogen, or halo(C 1 -C 8 alkyl);

R 2 is H, C 1 -C 8 alkyl, halogen, or halo(C 1 -C 8 alkyl);

X 2 is O or NR 10 ;

R 10 is hydrogen or C 1 -C 8 alkyl;

R 3 is H, C 1 -C 8 alkyl, halogen, or halo(C 1 -C 8 alkyl);

Y is NR 4 ;

or taken together Y—X 4 and R 3 form unsubstituted or substituted C 6 aryl or unsubstituted or substituted 5- or 6-membered heteroaryl, wherein said substituted aryl or heteroaryl is substituted with one or more R 5 ;

R 4 is H or C 1 -C 8 alkyl;

each R 5 is independently halogen, OR 6 , NR 7 R 8 , NR 7 C(O)R 8 , SR 9 , C 1 -C 8 alkyl, C 2 -C 8 alkynyl optionally substituted with 5- or 6-membered heterocyclic, or halo(C 1 -C 8 alkyl);

each R 6 is independently hydrogen or C 1 -C 8 alkyl;

each R 7 and R 8 are independently hydrogen, C 1 -C 8 alkyl, or unsubstituted or substituted 5- or 6-membered heterocyclic, wherein said substituted heterocyclic is substituted with one or more R 16 ;

each R 9 is independently hydrogen or C 1 -C 8 alkyl;

X 1 is H, C 1 -C 8 alkyl, or halogen;

each X 3a and X 3b are independently hydrogen, C 1 -C 8 alkyl, or absent (when n is 0);

Q is C 1 -C 8 alkyl, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted 5- or 6-membered heteroaryl, unsubstituted or substituted 3- to 8-membered cycloalkyl, or unsubstituted or substituted 3- to 8-membered heterocyclic, wherein said substituted aryl, heteroaryl, cycloalkyl, or heterocyclic is substituted with one, two, or three R 11 ;

each R 11 is independently halogen, OR 12 , NR 13 R 14 , SR 15 , C 1 -C 8 alkyl, or halo(C 1 -C 8 alkyl);

each R 12 is independently hydrogen or C 1 -C 8 alkyl;

each R 13 and R 14 are independently hydrogen or C 1 -C 8 alkyl;

each R 15 is independently hydrogen or C 1 -C 8 alkyl;

n is 0, 1, 2, 3, or 4;

X 4 is unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted 5- or 6-membered heteroaryl, unsubstituted or substituted C 1 -C 8 alkyl, or unsubstituted or substituted (CH 2 ) 1-3 —C 6 -C 10 aryl,

wherein said substituted aryl, heteroaryl, or alkyl is substituted with one or more R 16 ;

each R 16 is independently halogen, OR 17 , NR 18 R 19 , SR 20 , unsubstituted or substituted C 1 -C 8 alkyl, halo(C 1 -C 8 alkyl), C(O)(C 1 -C 8 alkyl), C(O)(halo(C 1 -C 8 alkyl)), C(O)(C 2 -C 8 alkenyl), unsubstituted or substituted heterocyclic, or C(O)-unsubstituted or substituted heterocyclic, wherein said substituted alkyl or heterocyclic is substituted with one or more R 21 ;

each R 17 is independently hydrogen or C 1 -C 8 alkyl;

each R 18 and R 19 are independently hydrogen, C 1 -C 8 alkyl, C(O)(C 1 -C 8 alkyl), C(O)(C 2 -C 8 alkenyl), or C(O)-unsubstituted or substituted heterocyclic, wherein said alkyl or alkenyl is optionally substituted with one or more OH, CN, halogen, C 3 -C 8 cycloalkyl, O(C 1 -C 8 alkyl), NH 2 , NH(C 1 -C 8 alkyl), or N(C 1 -C 8 alkyl) 2 , and wherein said substituted heterocyclic is substituted with one or more R 21 ;

each R 20 is independently hydrogen or C 1 -C 8 alkyl;

each R 21 is independently C 1 -C 8 alkyl, C(O)(C 1 -C 8 alkyl), C(O)(C 2 -C 8 alkenyl), or heterocyclic;

X 5 is unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted 5- to 8-membered heteroaryl, or unsubstituted or substituted C 1 -C 8 alkyl, wherein said substituted aryl, heteroaryl, or alkyl is substituted with one or more R 22 ;

each R 22 is independently halogen, OR 23 , NR 24 R 25 , SR 26 , C 1 -C 8 alkyl, halo(C 1 -C 8 alkyl), C(O)(C 1 -C 8 alkyl), C(O)(C 2 -C 8 alkenyl), unsubstituted or substituted heterocyclic, unsubstituted or substituted C 6 -C 10 aryl, or C(O)-unsubstituted or substituted heterocyclic, wherein said substituted heterocyclic or aryl is substituted with one or more R 27 ;

or two or more R 22 , together with the atoms to which they attach, form an unsubstituted or substituted 3- to 8-membered cycloalkyl, or unsubstituted or substituted 5- to 6-membered heterocyclic, wherein said cycloalkyl or heterocyclic is substituted with one or more R 27 ;

each R 23 is independently hydrogen or C 1 -C 8 alkyl;

each R 24 and R 25 are independently hydrogen, C 1 -C 8 alkyl, C(O)(C 1 -C 8 alkyl), or C(O)(C 2 -C 8 alkenyl), wherein said alkyl or alkenyl is optionally substituted with one or more OH, CN, halogen, C 3 -C 8 cycloalkyl, O(C 1 -C 8 alkyl), NH 2 , NH(C 1 -C 8 alkyl), or N(C 1 -C 8 alkyl) 2 ;

each R 26 is independently hydrogen or C 1 -C 8 alkyl;

each R 27 is independently halogen, C 1 -C 8 alkyl, C(O)(C 1 -C 8 alkyl), C(O)(C 2 -C 8 alkenyl), NR 29 C(O)(C 1 -C 8 alkyl), or NR 29 C(O)(C 2 -C 8 alkenyl); and

each R 29 is hydrogen or C 1 -C 8 alkyl.

2. The compound of claim 1 , selected from formulae IIa, IIb, III, and IV:

or a pharmaceutically acceptable salt thereof, wherein s is 1, 2, 3, or 4.

3. The compound of claim 1 , selected from formulae Va and Vb:

or a pharmaceutically acceptable sat thereof.

4. The compound of claim 1 , selected from formulae VIa and VIb:

or a pharmaceutically acceptable salt thereof, wherein u is 0, 1, 2, 3, 4, or 5.

5. The compound of claim 1 , selected from formulae VIIa and VIIb:

or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 , selected from formulae VIIIa and VIIIb:

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 , selected from formulae IXa and IXb:

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 , selected from formulae Xa and Xb:

or a pharmaceutically acceptable salt thereof, wherein w is 0, 1, or 2.

9. The compound of claim 1 , selected from formulae XIa and XIb:

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1 , wherein X 1 is hydrogen or halogen.

11. The compound of claim 1 , wherein n is 0, 1, or 2.

12. The compound of claim 1 , wherein X 3a and X 3b are each hydrogen or one of X 3a or X 3b is methyl and the remaining X 3a or X 3b is hydrogen.

13. The compound of claim 1 , wherein Q is unsubstituted or substituted phenyl or unsubstituted or substituted 5- or 6-membered heteroaryl.

14. The compound of claim 1 , wherein X 4 is substituted phenyl or methyl.

15. The compound of claim 1 , wherein X 5 is substituted phenyl or methyl.

16. A compound selected from:

17. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutical carrier, diluent, or excipient.

18. The compound of claim 13 , wherein Q is unsubstituted phenyl.

19. The compound of claim 13 , wherein the heteroaryl is pyridyl or thienyl.

20. The compound of claim 4 , wherein u is 1 or 2.

21. The compound of claim 20 , wherein one R 16 is OCH 3 .

22. The compound of claim 20 , wherein one R 16 is substituted heterocyclic or NR 18 R 19 .

23. The compound of claim 22 , wherein the substituted heterocyclic is methylpiperazine.

24. The compound of claim 22 , wherein one R 16 is NHC(O)(C 2 -C 4 alkenyl) optionally substituted with NH 2 , NH(C 1 -C 3 alkyl), or N(C 1 -C 3 alkyl) 2 .

25. The compound of claim 20 , wherein one R 16 is OCH 3 , and the other R 16 is substituted heterocyclic or NR 18 R 19 .

26. The compound of claim 25 , wherein the substituted heterocyclic is methylpiperazine.

27. The compound of claim 25 , wherein one R 16 is NHC(O)(C 2 -C 4 alkenyl) optionally substituted with NH 2 , NH(C 1 -C 3 alkyl), or N(C 1 -C 3 alkyl) 2 .