Heterocyclic compounds useful for kinase inhibition

1. A compound having the structure (I) or an N-oxide, N,N′-dioxide, N,N′,N″-trioxide, or a pharmaceutically acceptable salt

thereof:

wherein:

Q is O;

W is C 6 -C 12 aryl;

X is absent;

Y is NH;

Z 1 and Z 2 are N;

Z 3 is NR S , wherein R 5 is hydrogen or C 1 -C 6 alkyl;

R 1 is C 3 -C 12 heteroaryl having 1-3 heteroatoms; optionally substituted with hydrogen, halogen, C 1 -C 6 alkyl, —CF 3 , —OH, C 1 -C 6 alkoxy, —NR 10 R 11 , and —SO m R 12 , wherein R 10 and R 11 are independently selected from a group consisting of hydrogen, C 1 -C 6 alkyl, —SO 2 R 12 , —S(O)R 12 , and —COR 12 and R 12 is C 1 -C 6 alkyl or C 3 -C 12 heteroaryl having 1-3 heteroatoms and m is 0, 1 or 2;

each R 2 and R 3 are independently selected from a group consisting of C 1 -C 6 alkoxy, C 1 -C 6 alkyl, C 3 -C 12 cycloalkyl, and halogen; p is 1 or 2; or, optionally, R 2 and R 3 are joined to form a five to seven membered carbocycle;

R 4 is independently selected from a group consisting of hydrogen, halogen, C 1 -C 6 alkyl; and n is 1 or 2.

2. The compound of claim 1 , wherein W is phenyl.

3. The compound of claim 1 , wherein R 1 is pyridine or pyrimidine, optionally substituted with hydrogen, halogen, C 1 -C 6 alkyl, —CF 3 , —OH, C 1 -C 6 alkoxy, —NR 10 R 11 , and —SO m R 12 , wherein R 10 and R 11 are independently selected from a group consisting of hydrogen, C 1 -C 6 alkyl, —SO 2 R 12 , —S(O)R 12 , and —COR 12 and R 12 is C 1 -C 6 alkyl or C 3 -C 12 heteroaryl having 1-3 heteroatoms and m is 0, 1 or 2.

4. The compound of claims 1 , wherein R 4 is hydrogen.

5. The compound of claim 1 , wherein each R 2 and R 3 are independently selected from a group consisting of C 1 -C 6 alkyl, and halogen; or, optionally, R 2 and R 3 are joined to form a five to seven membered carbocycle.

6. The compound of claim 1 , wherein the compound having structure (I) is selected from the group consisting of:

7. The compound of claim 1 , having the structure (II)

or an N-oxide, N,N′-dioxide, N,N′,N″-trioxide, or a pharmaceutically acceptable salt thereof:

wherein

R 8 and R 9 is independently selected from the group consisting of hydrogen, halogen, C 1 -C 6 alkyl, CF 3 , —OH, C 1 -C 6 alkoxy, —NR 10 R 11 , and —SO m R 12 , wherein R 10 and R 11 are independently selected from a group consisting of hydrogen, C 1 -C 6 alkyl, SO 2 R 12 , —S(O)R 12 , and COR 12 , and R 12 is C 1 -C 6 alkyl or C 3 -C 12 heteroaryl having 1-3 heteroatoms and m is 0, 1 or 2.

8. The compound of claim 7 , wherein

each R 2 and R 3 are independently selected from a group consisting of C 1 -C 6 alkoxy, C 1 -C 6 alkyl, and halogen; p is 1 or 2; or, optionally, R 2 and R 3 are joined to form a five to seven membered carbocycle.

9. The compound of claim 8 , wherein R 8 and R 9 are independently selected from the group consisting of C 1 -C 6 alkoxy, —NR 10 R 11 , and —SO m R 12 , and m is 0, 1 or 2.

10. The compound of claim 8 , wherein each R 2 and R 3 are independently selected from a group consisting of C 1 -C 6 alkyl, and halogen and p is 1 or 2; or, optionally, R 2 and R 3 are joined to form a five to seven membered carbocycle.

11. The compound of claim 8 , wherein the compound having structure (II) is selected from the group consisting of

12. A pharmaceutical composition comprising a compound of claim 1 , in a pharmaceutically acceptable carrier.