Heterocyclic hydroxamic acids as protein deacetylase inhibitors and dual protein deacetylase-protein kinase inhibitors and methods of use thereof

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof,

wherein:

Z is NH or CH 2 ;

X is O, S, SO, SO 2 , CO, CR 2 R 3 , NR 4 , SO 2 NR 4 , NR 4 SO 2 , CONR 4 , NR 4 CO, NR 4 CO 2 , NR 4 (CO)NR 5 or a bond;

M is CR 6 or N;

Q 1 and Q 2 are independently N or CH;

Q 3 is CR 7 or Q 3 is NR 8 when R 1 is not present;

n is 0-6;

Y is H, CN, Cl, Br, I, F, C 1 -C 6 alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (CH 2 ) n -aryl, (CH 2 ) n -heteroaryl, OR 9 , SR 9 , COR 9 , COOR 9 , SOR 9 , SO 2 R 9 , SO 2 NR 10 R 11 , NR 10 R 11 , NR 10 SO 2 R 9 , NR 10 COR 9 , NR 10 CO 2 R 9 , CONR 10 R 11 , CO 2 NR 10 R 11 , NR 10 (CO)NR 11 , each of which may be optionally substituted and where R 10 and R 11 taken together may form a heterocyclic ring which may be optionally substituted;

R 1 is H, C 1 -C 6 alkyl, haloalkyl, aryl, aryl-alkyl, heteroaryl, heteroaryl-alkyl, heterocyclic, carbocyclic or absent, each of which may be optionally substituted;

R 2 is H, C 1 -C 6 alkyl, hydroxy, alkoxy, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 3 is H, C 1 -C 6 alkyl, alkoxy, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 4 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 5 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 6 is H, CN, Cl, Br, I, F, C 1 -C 6 alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (CH 2 ) n -aryl, (CH 2 ) n -heteroaryl, OR 9 , SR 9 , COR 9 , COOR 9 , SOR 9 , SO 2 R 9 , SO 2 NR 10 R 11 , NR 10 R 11 , NR 10 SO 2 R 9 , NR 10 COR 9 , NR 10 CO 2 R 9 , CONR 10 R 11 , CO 2 NR 10 R 11 or absent, where R 10 and R 11 taken together may form a 4-7 membered ring which may be optionally substituted;

R 7 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 8 is H, C 1 -C 6 alkyl, haloalkyl, aryl, aryl-alkyl, heteroaryl, heteroaryl-alkyl, heterocyclic, carbocyclic or absent, each of which may be optionally substituted;

R 9 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 10 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted; and

R 11 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted.

2. The compound according to claim 1 ,

wherein:

Y is NR 10 R 11 ;

R 10 is alkyl, aryl, heteroaryl, aryl-alkyl or heteroaryl-alkyl; and

R 11 is alkyl or H, and

where R 3 and R 4 taken together may form a 4-7 membered ring which is optionally substituted.

3. The compound according to claim 1 , wherein X is O, S, SO 2 , SO 2 NR 4 or CONR 4 .

4. The compound according to claim 1 ,

wherein:

R 1 is H or C 1 -C 6 alkyl;

Q 3 is NR 8 where R 8 is absent; and

M is CR 6 where R 6 is H.

5. The compound according to claim 1 ,

wherein:

R 1 is H or C 1 -C 6 alkyl;

Q 3 is CR 7 where R 7 is H; and

M is N.

6. The compound according to claim 1 , wherein Y is aryl, heteroaryl or NR 10 R 11 .

7. The compound according to claim 1 , having the formula (II):

or a pharmaceutically acceptable salt, ester or prodrug thereof,

wherein:

Ring A is an optionally substituted aryl or optionally substituted heteroaryl;

Ring B is an optionally substituted aryl or optionally substituted heteroaryl;

Ring C is an optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;

Z is N, CR 2 , O, S, C═O, SO or SO 2 ;

R 1 is H, absent, C 1 -C 6 alkyl, haloalkyl, hydroxyalkyl, carboxyalkyl, aryl, aryl-alkyl, heteroaryl, heterocyclic or carbocyclic, each of which may be optionally substituted, and wherein when Z is CR 2 , R 1 and R 2 taken together may form a 3-7 membered ring which may be optionally substituted;

X is O, S, SO, SO 2 , CO, CR 2 R 3 , NR 4 , SO 2 NR 4 , NR 4 SO 2 , CONR 4 , NR 4 CO, NR 4 CO 2 , NR 4 (CO)NR 5 or a bond;

Y is H, CN, Cl, Br, I, F, C 1 -C 6 alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (CH 2 ) n -aryl, (CH 2 ) n -heteroaryl, OR 3 , SR 3 , COR 3 , COOR 3 , SOR 3 , SO 2 R 3 , SO 2 NR 4 R 5 , NR 4 R 5 , NR 4 SO 2 R 3 , NR 4 COR 3 , NR 4 CO 2 R 3 , CONR 4 R 5 , CO 2 NR 4 R 5 , NR 4 (CO)NR 5 or absent, each of which may be optionally substituted and where R 4 and R 5 taken together may form a 4-7 membered ring which may be optionally substituted;

L is C 1 -C 9 alkylene, C 2 -C 9 alkenylene or C 2 -C 9 alkynylene, any of which is substituted or unsubstituted, wherein one or more of the carbon atoms of the alkylene, alkenylene or alkynylene is optionally replaced with O, S, SO, SO 2 , SO 2 NR 4 , NR 4 SO 2 , NR 4 , CO, CONR 4 , NR 4 CO, CO 2 NR 4 , NR 4 CO 2 , NR 4 (CO)NR 5 , a cycloalkyl or a heterocycle, with the proviso that heteroatoms are not bonded directly to alkenyl or alkynyl carbons, and that the carbon atom adjacent to X shall not be optionally replaced such that a heteroatom-heteroatom bond results;

R 2 is H, C 1 -C 6 alkyl, hydroxy, alkoxy, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 3 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 4 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocycle, any of which is substituted or unsubstituted;

R 5 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted; and

n is 1-4.

8. The compound according to claim 7 or a pharmaceutically acceptable salt thereof, wherein ring A is phenyl, pyridinyl, pyrimidinyl or pyrazinyl.

9. The compound according to claim 7 or a pharmaceutically acceptable salt thereof, wherein ring B is phenyl, pyridinyl, pyrimidinyl or pyrazinyl.

10. The compound according to claim 7 or a pharmaceutically acceptable salt thereof, wherein ring C is independently selected from a 5-membered heteroaryl or a 5-membered heterocycloalkyl.

11. The compound according to claim 7 or a pharmaceutically acceptable salt thereof, wherein Y is aryl, heteroaryl, (CH 2 ) n -aryl, (CH 2 ) n -heteroaryl, NH 2 , NH(alkyl), N(alkyl)(alkyl), N(aryl)(alkyl), NH(cycloalkyl), N(alkyl)(cycloalkyl), NH(heteroaryl), NH(heterocycle), N(alkyl)(heteroaryl), N(alkyl)(heterocycle), NH(alkylheteroaryl), NH(alkylheterocycle), N(alkyl)(alkyl heteroaryl) or N(alkyl)(alkylheterocycle).

12. The compound according to claim 1 , having the formula (III):

or a pharmaceutically acceptable salt thereof,

wherein:

Z, is N or CR 2 ;

R 1 is H, C 1 -C 6 alkyl, haloalkyl, hydroxyalkyl, carboxyalkyl, aryl, aryl-alkyl, heteroaryl, heterocyclic or carbocyclic, each of which may be optionally substituted, wherein, when Z is CR 2 , R 1 and R 2 taken together may form a 3-7 membered ring which may be optionally substituted;

Ring A is an optionally substituted phenyl, pyridinyl, pyrimidinyl, or pyrazinyl;

M 1 and M 2 are independently N or CR 3 ;

Q 1 is CR 4 , NR 5 , O or S;

Q 2 is CR 4 , NR 5 , O or S;

J is N or CR 6 ;

X is O, S, SO, SO 2 , CO, CR 7 R 8 , NR 9 , SO 2 NR 9 , NR 9 SO 2 , CONR 9 , NR 9 CO, NR 9 CO 2 , NR 9 (CO)NR 10 or a bond;

Y is H, CN, Cl, Br, I, F, C 1 -C 6 alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (CH 2 ) n -aryl, (CH 2 ) n -heteroaryl, OR 8 , SR 8 , COR 8 , COOR 8 , SOR 8 , SO 2 R 8 , SO 2 NR 9 R 10 , NR 9 R 10 , NR 9 SO 2 R 8 , NR 9 COR 8 , NR 9 CO 2 R 8 , CONR 9 R 10 , CO 2 NR 9 R 10 , or NR 9 (CO)NR 10 , each of which may be optionally substituted and where R 9 and R 10 taken together may form a heterocyclic ring which may be optionally substituted;

L is C 1 -C 9 alkylene, C 2 -C 9 alkenylene or C 2 -C 9 alkynylene, any of which is substituted or unsubstituted, wherein one or more of the carbon atoms of the alkylene, alkenylene or alkynylene is optionally replaced with O, S, SO, SO 2 , SR 8 , SO 2 NR 9 , NR 9 SO 2 , NR 9 , CO, CONR 9 , NR 9 CO, CO 2 NR 9 , NR 9 CO 2 , a cycloalkyl or a heterocycle, with the proviso that heteroatoms are not bonded directly to alkenyl or alkynyl carbons, and that the carbon adjacent to X shall not be optionally replaced such that a heteroatom-heteroatom bond results;

R 2 is H, C 1 -C 6 alkyl, hydroxy, alkoxy, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 3 is H, CN, Cl, Br, I, F, C 1 -C 6 alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR 8 , SR 8 , COR 8 , COOR 8 , SOR 8 , SO 2 R 8 , SO 2 NR 9 R 10 , NR 9 R 10 , NR 9 SO 2 R 8 , NR 9 COR 8 , NR 9 CO 2 R 8 , CONR 9 R 10 , CO 2 NR 9 R 10 or NR 9 (CO)NR 10 , each of which may be optionally substituted and where R 9 and R 10 taken together may form a heterocyclic ring which may be optionally substituted;

R 4 is H, C 1 -C 6 alkyl, haloalkyl, hydroxyalkyl, carboxyalkyl, aryl, aryl-alkyl, heteroaryl, heterocyclic or carbocyclic, each of which may be optionally substituted;

R 5 is H, C 1 -C 6 alkyl, haloalkyl, hydroxyalkyl, carboxyalkyl, aryl, aryl-alkyl, heteroaryl, heterocyclic or carbocyclic, each of which may be optionally substituted;

R 6 is H, CN, Cl, Br, I, F, C 1 -C 6 alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR 8 , SR 8 , COR 8 , COOR 8 , SOR 8 , SO 2 R 8 , SO 2 NR 9 R 10 , NR 9 R 10 , NR 9 SO 2 R 8 , NR 9 COR 8 , NR 9 CO 2 R 8 , CONR 9 R 10 , CO 2 NR 9 R 10 or NR 9 (CO)NR 10 , each of which may be optionally substituted and where R 9 and R 10 taken together may form a heterocyclic ring which may be optionally substituted;

R 7 is H, C 1 -C 6 alkyl, alkoxy, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 8 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 9 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 10 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted; and

n is 1-4.

13. The compound according to claim 12 , or a pharmaceutically acceptable salt thereof, wherein Z is nitrogen and R 1 is H.

14. The compound according to claim 12 , or a pharmaceutically acceptable salt thereof, wherein X and Z are oriented para to each other.

15. The compound according to claim 12 , or a pharmaceutically acceptable salt thereof, wherein Y is aryl, heteroaryl, alkyl-aryl, alkyl-heteroaryl, NH 2 , NH(alkyl), N(alkyl)(alkyl), N(aryl)(alkyl), NH(cycloalkyl), N(alkyl)(cycloalkyl), NH(heteroaryl), NH(heterocycle), N(alkyl)(heteroaryl), N(alkyl)(heterocycle), NH(alkylheteroaryl), NH(alkylheterocycle), N(alkyl)(alkyl heteroaryl) or N(alkyl)(alkylheterocycle).

16. The compound according to claim 12 , or a pharmaceutically acceptable salt thereof, wherein M 1 , and M 2 are independently N or CR 3 , where R 3 is H.

17. The compound according to claim 12 , or a pharmaceutically acceptable salt thereof, wherein Q 1 is NR 5 ; Q 2 is NR 7 ; and J is CR 6 , where R 5 is absent and R 7 is H or alkyl.

18. The compound according to claim 12 , or a pharmaceutically acceptable salt thereof, wherein Q 1 is NR 5 ; Q 2 is NR 7 ; and J is CR 6 , where R 5 is alkyl and R 7 is absent.

19. A compound according to claim 1 , having the formula (IV):

or a pharmaceutically acceptable salt thereof,

wherein:

Z is N or CR 3 ;

R 1 is H, C 1 -C 6 alkyl, haloalkyl, hydroxyalkyl, carboxyalkyl, aryl, aryl-alkyl, heteroaryl, heterocyclic or carbocyclic, each of which may be optionally substituted, wherein, when Z is CR 3 , R 1 and R 3 taken together may form a 3-7 membered ring which may be optionally substituted;

R 2 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) q -aryl, heteroaryl, (CH 2 ) q -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 3 is H, C 1 -C 6 alkyl, hydroxy, alkoxy, aryl, (CH 2 ) q -aryl, heteroaryl, (CH 2 ) q -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted, where R 1 and R 3 taken together may form a 3-7 membered ring which may be optionally substituted;

each of Q 1 , Q 2 , Q 3 and Q 4 is independently N or CR 4 ;

Ring B is an optionally substituted phenyl, pyridinyl, pyrimidinyl or pyrazinyl;

Ring C is an optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;

X is O, S, SO, SO 2 , CO, CR 5 R 6 , NR 7 , SO 2 NR 7 , NR 7 SO 2 , CONR 7 , NR 7 CO, NR 7 CO 2 , NR 7 (CO)NR 8 or a bond, wherein, R 5 and R 6 taken together may form a 3-7 membered ring which may be optionally substituted;

Y is H, CN, Cl, Br, I, F, C 1 -C 6 alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (CH 2 ) q -aryl, (CH 2 ) q -heteroaryl, OR 6 , SR 6 , COR 6 , COOR 6 , SOR 6 , SO 2 R 6 , SO 2 NR 7 R 8 , NR 7 R 8 , NR 7 SO 2 R 6 , NR 7 COR 6 , NR 7 CO 2 R 7 , CONR 7 R 8 , CO 2 NR 7 R 8 , NR 7 (CO)NR 8 , or absent, each of which may be optionally substituted and where R 7 and R 8 taken together may form a heterocyclic ring which may be optionally substituted;

n is 1-5 and m is 1-5 when X is CR 5 R 6 ;

n is 2-4 and m is 1-4 when X is other than CR 5 R 6 ;

q is 2-4;

R 4 is H, CN, Cl, Br, I, F, alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR 6 , SR 6 , COR 6 , COOR 6 , SOR 6 , SO 2 R 6 , SO 2 NR 7 R 8 , NR 7 R 8 , NR 7 SO 2 R 6 , NR 7 COR 6 , NR 7 CO 2 R 6 , CONR 7 R 8 , CO 2 NR 7 R 8 or NR 7 (CO)NR 8 , each of which may be optionally substituted and where R 7 and R 8 taken together may form a heterocyclic ring which may be optionally substituted;

R 5 is H, C 1 -C 6 alkyl, alkoxy, aryl, (CH 2 ) q -aryl, heteroaryl, (CH 2 ) q -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 6 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) q -aryl, heteroaryl, (CH 2 ) q -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 7 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) q -aryl, heteroaryl, (CH 2 ) q -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 8 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) q -aryl, heteroaryl, (CH 2 ) q -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted.

20. The compound according to claim 19 , or a pharmaceutically acceptable salt thereof, wherein rings B and C taken together form a purine, pyrazolopyrimidine, pyrazolopyridine, pyrrolopyrimidine, thiazolopyrimidine, purinone, indole, pyrrolopyrimidinone or dihydropyrrolopyrimidine.

21. The compound according to claim 19 , or a pharmaceutically acceptable salt thereof, wherein Q 1 and Q 3 are N; and Q 2 and Q 4 are CR 4 where R 4 is H.

22. The compound according to claim 19 , or a pharmaceutically acceptable salt thereof, wherein Q 1 and Q 3 are CR 4 where R 4 is H; and Q 2 and Q 4 are N.

23. The compound according to claim 19 , or a pharmaceutically acceptable salt thereof, wherein Q 1 , Q 2 , Q 3 and Q 4 are CR 4 where R 4 is H.

24. The compound according to claim 19 , or a pharmaceutically acceptable salt thereof, wherein Z is N; and R 1 is H.

25. The compound according to claim 19 , or a pharmaceutically acceptable salt thereof, wherein X is O, (CO)NR 8 or S(O) 2 NR 8 ; and R 8 is H, alkyl, aryl, heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted.

26. The compound according to claim 19 , or a pharmaceutically acceptable salt thereof, wherein n is 3; m is 1; and R 2 is H or alkyl.

27. A compound according to claim 1 , having the formula (V):

or a pharmaceutically acceptable salt thereof,

wherein:

Z is N or CR 2 ;

R 1 is H, C 1 -C 6 alkyl, haloalkyl, hydroxyalkyl, carboxyalkyl, aryl, aryl-alkyl, heteroaryl, heterocyclic or carbocyclic, each of which may be optionally substituted;

each of Q 1 , Q 2 , Q 3 , and Q 4 is independently N or CR 3 ;

Ring B is an optionally substituted phenyl, pyridinyl, pyrimidinyl or pyrazinyl;

Ring C is an optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;

R 2 is H, C 1 -C 6 alkyl, hydroxy, alkoxy, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted, where R 1 and R 3 taken together may form a 3-7 membered ring which may be optionally substituted;

X is (CR 4 R 5 ) n , SO 2 , CO, NR 6 CO or absent;

Y is H, CN, Cl, Br, I, F, C 1 -C 6 alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (CH 2 ) n -aryl, (CH 2 ) n -heteroaryl, aryl, OR 6 , SR 6 , COR 6 , COOR 6 , SOR 6 , SO 2 R 6 , SO 2 NR 7 R 8 , NR 7 R 8 , NR 7 SO 2 R 6 , NR 7 COR 6 , NR 7 CO 2 R 6 , CONR 7 R 8 , CO 2 NR 7 R 8 or absent, and where R 7 and R 8 taken together may form a 4-7 membered ring which may be optionally substituted;

n=1-4;

R 3 is H, CN, Cl, Br, I, F, C 1 -C 6 alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR 6 , SR 6 , COR 6 , COOR 6 , SOR 6 , SO 2 R 6 , SO 2 NR 7 R 8 , NR 7 R 8 , NR 7 SO 2 R 6 , NR 7 COR 6 , NR 7 CO 2 R 6 , CONR 7 R 8 , CO 2 NR 7 R 8 or NR 7 (CO)NR 8 , each of which may be optionally substituted and where R 7 and R 8 taken together may form a heterocyclic ring which may be optionally substituted;

R 4 is H, C 1 -C 6 alkyl, aryl, heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 5 is H, C 1 -C 6 alkyl, aryl, heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 6 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 7 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted; and

R 8 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted.

28. The compound according to claim 27 , or a pharmaceutically acceptable salt thereof, wherein rings B and C taken together form a purine, pyrazolopyrimidine, pyrazolopyridine, pyrrolopyrimidine, thiazolopyrimidine, purinone, indole, pyrrolopyrimidinone or dihydropyrrolopyrimidine.

29. The compound according to claim 27 , or a pharmaceutically acceptable salt thereof, wherein Z is N, and R 1 is H.

30. The compound according to claim 27 , or a pharmaceutically acceptable salt thereof, wherein Q 1 , Q 2 , Q 3 and Q 4 are CR 3 where R 3 is H.

31. The compound according to claim 27 , or a pharmaceutically acceptable salt thereof, wherein X is CR 4 R 5 , SO 2 , CO, NR 4 CO or absent.

32. The compound according to claim 27 , or a pharmaceutically acceptable salt thereof, wherein Y is aryl, heteroaryl, (CH 2 ) n -aryl, (CH 2 ) n -heteroaryl or NR 7 R 8 .

33. A compound according to claim 1 , having the formula (VI):

or a pharmaceutically acceptable salt, ester or prodrug thereof,

wherein:

Ring A is an optionally substituted aryl or optionally substituted heteroaryl;

Z is N or CR 3 ;

R 1 is H, C 1 -C 6 alkyl, haloalkyl, hydroxyalkyl, carboxyalkyl, aryl, aryl-alkyl, heteroaryl, heterocyclic or carbocyclic, each of which may be optionally substituted;

R 2 is an optionally substituted C 1 -C 6 alkyl, acyl, aryl or heteroaryl;

Q 1 and Q 2 are independently N or CR 4 ;

M is NR 5 , CR 6 R 7 , O or S;

J is O, S or absent;

X is O, S, SO, SO 2 , CO, CR 8 R 9 , NR 10 , SO 2 NR 10 , NR 10 SO 2 , CONR 10 , NR 9 CO, NR 10 CO 2 , NR 10 (CO)NR 11 or absent;

Y is H, CN, Cl, Br, I, F, C 1 -C 6 alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (CH 2 ) n -aryl, (CH 2 ) n -heteroaryl, OR 9 , SR 9 , COR 9 , COOR 9 , SOR 9 , SO 2 R 9 , SO 2 NR 10 R 11 , NR 10 R 11 , NR 10 SO 2 R 9 , NR 10 COR 9 , NR 10 CO 2 R 9 , CONR 10 R 11 , CO 2 NR 10 R 11 or absent, where R 10 and R 11 taken together may form a 4-7 membered ring which may be optionally substituted;

L is C 1 -C 9 alkylene, C 2 -C 9 alkenylene or C 2 -C 9 alkynylene, any of which is substituted or unsubstituted, wherein one or more of the carbon atoms of the alkylene, alkenylene or alkynylene is optionally replaced with O, S, SO, SO 2 , SO 2 NR 10 , NR 10 SO 2 , NR 10 , CO, CONR 10 , NR 10 CO, CO 2 NR 10 , NR 10 CO 2 , cycloalkyl or heterocyclic, with the proviso that heteroatoms are not bonded directly to alkenyl or alkynyl carbons, and that the carbon adjacent to X shall not be optionally replaced such that a heteroatom-heteroatom bond results;

R 3 is H, C 1 -C 6 alkyl, hydroxy, alkoxy, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted, where R 1 and R 3 taken together may form a 3-7 membered ring which may be optionally substituted;

R 4 is H, CN, Cl, Br, I, F, C 1 -C 6 alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl OR 9 , SR 9 , COR 9 , COOR 9 , SOR 9 , SO 2 R 9 , SO 2 NR 10 R 11 , NR 10 R 11 , NR 10 SO 2 R 11 , NR 10 COR 9 , NR 10 CO 2 R 9 , CONR 10 R 11 or CO 2 NR 10 R 11 , where R 10 and R 11 taken together may form a 4-7 membered ring which may be optionally substituted;

R 5 is an optionally substituted C 1 -C 6 alkyl, acyl, aryl or heteroaryl;

R 6 is H, C 1 -C 6 alkyl, hydroxy, alkoxy, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocycle;

R 7 is H, C 1 -C 6 alkyl, hydroxy, alkoxy, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted, where R 6 and R 7 taken together may form a 3-7 membered ring which may be optionally substituted;

R 8 is H, C 1 -C 6 alkyl, alkoxy, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocycle, any of which is substituted or unsubstituted;

R 9 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 10 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted;

R 11 is H, C 1 -C 6 alkyl, aryl, (CH 2 ) n -aryl, heteroaryl, (CH 2 ) n -heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted; and

n is 1-4.

34. The compound according to claim 33 , or a pharmaceutically acceptable salt thereof, wherein Z is N; and R 1 is H.

35. The compound according to claim 33 , or a pharmaceutically acceptable salt thereof, wherein Q 1 and Q 2 are independently N or CR 4 where R 4 is H.

36. The compound according to claim 33 , or a pharmaceutically acceptable salt thereof, wherein M is CR 6 R 7 where R 6 and R 7 are alkyl, or taken together form a 3, 4, or 5 membered ring.

37. The compound according to claim 33 , or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl.

38. The compound according to claim 33 , or a pharmaceutically acceptable salt thereof, wherein X and Z are oriented para to each other.

39. The compound according to claim 33 , or a pharmaceutically acceptable salt thereof, wherein X is O, CR 8 R 9 or CONR 10 .

40. The compound according to claim 33 , or a pharmaceutically acceptable salt thereof, wherein J is O or absent.

41. The compound according to claim 33 , or a pharmaceutically acceptable salt thereof, wherein Y is aryl, heteroaryl, (CH 2 ) n -aryl, (CH 2 ) n -heteroaryl or NR 7 R 8 .

42. The compound according to claim 33 , or a pharmaceutically acceptable salt thereof, wherein L is C 3 -C 8 alkylene.

43. A pharmaceutical composition comprising a compound of any one of formulae (I) through (VI) or a pharmaceutically acceptable salt thereof in combination with a diluent or excipient.