Heterocyclic kinase inhibitors

1. A compound having a structure of Formula I-E:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is halogen, —CN, —OR 10 , —S(O) n R 11 , —NR 12 R 13 , —C(O)R 14 , alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

n is an integer from 0 to 2;

L 1 is a bond, alkylene, heteroalkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene;

R 2 is —NR 12 R 13 ;

R 3 is hydrogen;

R 4 and R 5 are independently hydrogen or R 6 , or R 4 and R 5 are taken together to form a 5, 6 or 7 membered ring, wherein the 5, 6, or 7 membered ring is optionally substituted with (R 6 ) q ;

z is 1;

q is an integer from 0 to 5;

each of R 6 is independently hydrogen, halogen, —CN, —OR 10 , —S(O) n R 11 , —NR 12 R 13 , —C(O)R 14 , alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

each of R 7 and R 8 is independently hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocyclyalkyl, or R 7 and R 8 taken together form a cycloalkyl, heterocycloalkyl or aryl ring;

R 9 is —NR 12 R 13 , where R 12 and R 13 are taken together to form a 5, 6, 7 or 8 membered ring, wherein the 5, 6, 7, or 8 membered ring contains 0, 1, 2 or 3 ring heteroatoms selected from N, S, or O in addition to the nitrogen atom of —NR 12 R 13 ; and further wherein the 5, 6, 7, or 8 membered ring is optionally substituted;

each R 10 is independently hydrogen, —C(O)R 15 , alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

each R 11 is independently —NR 16 R 17 , alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

each R 12 is independently hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

each R 13 is independently hydrogen, —S(O) n R 18 , —C(O)R 19 , alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

or R 12 and R 13 are taken together to form a 5, 6, 7, or 8 membered ring, wherein the 5, 6, 7, or 8 membered ring contains 0, 1, 2 or 3 ring heteroatoms selected from N, S, or O in addition to the nitrogen atom of —NR 12 R 13 ; and further wherein the 5, 6, 7, or 8 membered ring is optionally substituted;

each R 14 is independently —NR 20 R 21 , hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

each R 15 is independently —NR 22 R 23 , hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

each of R 16 and R 17 is independently hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; or R 16 and R 17 are taken together to form a 5, 6, 7, or 8 membered ring, wherein the 5, 6, 7, or 8 membered ring contains 0, 1, 2 or 3 ring heteroatoms selected from N, S, or O in addition to the nitrogen atom of —NR 16 R 17 ; and further wherein the 5, 6, 7, or 8 membered ring is optionally substituted;

each R 18 is independently hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

each R 19 is independently —NR 24 R 25 , hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;

each of R 20 and R 21 is independently hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, or R 20 and R 21 are taken together to form a 5, 6, 7, or 8 membered ring, wherein the 5, 6, 7, or 8 membered ring contains 0, 1, 2 or 3 ring heteroatoms selected from N, S, or O in addition to the nitrogen atom of —NR 20 R 21 ; and further wherein the 5, 6, 7, or 8 membered ring is optionally substituted;

each R 22 and R 23 are independently hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, or R 22 and R 23 are taken together to form a 5, 6, 7, or 8 membered ring, wherein the 5, 6, 7, or 8 membered ring contains 0, 1, 2 or 3 ring heteroatoms selected from N, S, or O in addition to the nitrogen atom of —NR 22 R 23 ; and further wherein the 5, 6, 7, or 8 membered ring is optionally substituted;

each R 24 and R 25 are independently hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, or R 24 and R 25 are taken together to form a 5, 6, 7, or 8 membered ring, wherein the 5, 6, 7, or 8 membered ring contains 0, 1, 2 or 3 ring heteroatoms selected from N, S, or O in addition to the nitrogen atom of —NR 24 R 25 ; and further wherein the 5, 6, 7, or 8 membered ring is optionally substituted; and

W is CR 6 or N.

2. The compound of claim 1 , wherein R 1 is alkynyl, aryl, or heteroaryl.

3. The compound of claim 1 , wherein L 1 is a bond, and R 1 is alkynyl, aryl, or heteroaryl.

4. The compound of claim 1 , wherein R 1 is bicyclic heteroaryl.

5. The compound of claim 1 , wherein R 4 and R 5 are taken together to form a 6-membered ring.

6. The compound of claim 1 , wherein R 2 is —NH 2 .

7. The compound of claim 1 , wherein R 7 is alkyl.

8. The compound of claim 1 , wherein R 7 and R 8 are hydrogen.

9. The compound of claim 1 , wherein W is CH.

10. The compound of claim 1 , wherein the compound has a structure of one of the following formulae:

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

14. The compound of claim 11 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

15. The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

16. A pharmaceutical composition comprising a compound of any one of claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , or 15 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.