Purinone compounds as kinase inhibitors
View Patent ↗Disclosed herein are compounds of Formula (I) that are useful as inhibitors of Bruton's tyrosine kinase: where R 6 -R 10 are as defined herein. Also disclosed are pharmaceutical compositions that include the compounds. The compounds may be used, for example, to treat autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
1. A compound of Formula (I) having the structure:
wherein:
R 9 is substituted heteroaryl;
R 10 is H, substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted C 3 -C 8 cycloalkyl;
R 6 is L-J-W;
R 7 is V-Q-W;
R 8 is X-A-W; or R 7 and R 8 taken together form a bond;
L and J are each optionally present and when present are each independently substituted or unsubstituted C 1 -C 6 alkylene, substituted or unsubstituted C 3 -C 6 cycloalkylene, substituted or unsubstituted C 1 -C 6 heteroalkylene, substituted or unsubstituted C 2 -C 7 heterocycloalkylene, substituted or unsubstituted C 6 -C 12 arylene, substituted or unsubstituted C 3 -C 12 heteroarylene, —CO—, —O—, or —S—;
V and Q are each optionally present and when present are each independently substituted or unsubstituted C 1 -C 6 alkylene, substituted or unsubstituted C 3 -C 6 cycloalkylene, substituted or unsubstituted C 1 -C 6 heteroalkylene, substituted or unsubstituted C 2 -C 7 heterocycloalkylene, substituted or unsubstituted C 6 -C 12 arylene, substituted or unsubstituted C 3 -C 12 heteroarylene, —CO—, —O—, or —S—;
X and A are each optionally present and when present are each independently substituted or unsubstituted C 1 -C 6 alkylene, substituted or unsubstituted C 3 -C 6 cycloalkylene, substituted or unsubstituted C 1 -C 6 heteroalkylene, substituted or unsubstituted C 2 -C 7 heterocycloalkylene, substituted or unsubstituted C 6 -C 12 arylene, substituted or unsubstituted C 3 -C 12 heteroarylene, —CO—, —O—, or —S—;
W is H, or NR 25 R 26 ;
R 25 and R 26 are each independently H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 6 -C 12 aryl, or substituted or unsubstituted C 3 -C 12 heteroaryl;
or a pharmaceutically acceptable solvate or pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 9 is substituted pyridyl, substituted thiazolyl, substituted thiadiazolyl, substituted isothiazolyl, or substituted benzothiazolyl, substituted pyrimidyl, substituted pyrazinyl, substituted pyridazinyl, substituted or unsubstituted triazinyl, substituted or unsubstituted quinolinyl, or substituted isoquinolinyl.
3. The compound of claim 2 , wherein L-J-W, V-Q-W, and X-A-W are each H.
4. The compound of claim 2 , wherein V-Q-W and X-A-W are H; and R 6 is L-J-W.
5. The compound of claim 4 , wherein L-J-W is H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, (C 1 -C 6 dialkylamino)C 1 -C 6 alkyl, ((C 1 -C 6 alkyl)(C 3 -C 6 cycloalkyl)amino)C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkylC 3 -C 6 cycloalkyl, or C 1 -C 4 alkyl(C 2 -C 7 heterocycloalkyl).
6. The compound of claim 5 , wherein L-J-W is substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, (C 1 -C 6 dialkylamino)C 1 -C 6 alkyl, or ((C 1 -C 6 alkyl)(C 3 -C 6 cycloalkyl)amino)C 1 -C 6 alkyl.
7. The compound of claim 2 , wherein L-J-W and X-A-W are H; and R 7 is V-Q-W.
8. The compound of claim 7 , wherein V-Q-W is H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, (C 1 -C 6 dialkylamino)C 1 -C 6 alkyl, ((C 1 -C 6 alkyl)(C 3 -C 6 cycloalkyl)amino)C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkylC 3 -C 6 cycloalkyl, or C 1 -C 4 alkyl(C 2 -C 7 heterocycloalkyl).
9. The compound of claim 8 , wherein V-Q-W is substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, (C 1 -C 6 dialkylamino)C 1 -C 6 alkyl, or ((C 1 -C 6 alkyl)(C 3 -C 6 cycloalkyl)amino)C 1 -C 6 alkyl.
10. The compound of claim 7 , wherein V is absent, a substituted or unsubstituted C 1 -C 6 alkylene, or substituted or unsubstituted C 3 -C 6 cycloalkylene; and Q is absent, a substituted or unsubstituted C 1 -C 6 alkylene, substituted or unsubstituted C 3 -C 6 cycloalkylene, substituted or unsubstituted C 1 -C 6 heteroalkylene, substituted or unsubstituted C 2 -C 7 heterocycloalkylene, substituted or unsubstituted C 6 -C 12 arylene, or substituted or unsubstituted C 3 -C 12 heteroarylene.
11. The compound of claim 10 , wherein V is —CH 2 —.
12. The compound of claim 11 , wherein Q is substituted or unsubstituted C 1 -C 6 alkylene, substituted or unsubstituted C 3 -C 6 cycloalkylene, substituted or unsubstituted C 1 -C 6 heteroalkylene, substituted or unsubstituted C 2 -C 7 heterocycloalkylene, substituted or unsubstituted C 6 -C 12 arylene, or substituted or unsubstituted C 3 -C 12 heteroarylene.
13. The compound of claim 12 , wherein Q is substituted or unsubstituted C 1 -C 6 alkylene, cyclopropyl, pyrrolidinyl, piperidinyl, piperizinyl, morpholinyl, imidazolyl, pyridinyl, or phenyl.
14. The compound of claim 10 , wherein V is absent.
15. The compound of claim 14 , wherein Q is substituted or unsubstituted C 1 -C 6 alkylene, substituted or unsubstituted C 3 -C 6 cycloalkylene, substituted or unsubstituted C 1 -C 6 heteroalkylene, substituted or unsubstituted C 2 -C 7 heterocycloalkylene, substituted or unsubstituted C 6 -C 12 arylene, or substituted or unsubstituted C 3 -C 12 heteroarylene.
16. The compound of claim 15 , wherein Q is —CH 2 — and W is NR 25 R 26 .
17. The compound of claim 16 , wherein R 25 is H, substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted C 3 -C 6 cycloalkyl; and R 26 is substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 6 -C 12 aryl, or substituted or unsubstituted C 3 -C 12 heteroaryl.
18. The compound of claim 17 , wherein R 25 and R 26 are —CH 3 .
19. The compound of claim 17 , wherein R 25 and R 26 are cyclopropyl.
20. The compound of claim 17 , wherein R 25 is —CH 3 and R 26 is cyclopropyl.
21. The compound of claim 2 , wherein R 7 and R 8 taken together form a bond; and R 6 is L-J-W.
22. The compound of claim 21 , wherein L-J-W is H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, (C 1 -C 6 dialkylamino)C 1 -C 6 alkyl, ((C 1 -C 6 alkyl)(C 3 -C 6 cycloalkyl)amino)C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkylC 3 -C 6 cycloalkyl, or C 1 -C 4 alkyl(C 2 -C 7 heterocycloalkyl).
23. The compound of claim 22 , wherein L-J-W is substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, (C 1 -C 6 dialkylamino)C 1 -C 6 alkyl, or ((C 1 -C 6 alkyl)(C 3 -C 6 cycloalkyl)amino)C 1 -C 6 alkyl.
24. The compound of any one of claims 1 - 23 , wherein R 9 is substituted pyridyl.
25. The compound of any one of claims 1 - 23 , wherein R 9 is substituted thiazolyl.
26. The compound of any one of claims 1 - 25 , wherein R 10 is H.
27. The compound of any one of claims 1 - 25 , wherein R 10 is CH 3 .
28. A compound having the structure:
29. A pharmaceutical composition comprising a therapeutically effective amount of a compound of any one of claims 1 - 27 and 28 , or a pharmaceutically acceptable salt or pharmaceutically acceptable solvate thereof, and a pharmaceutically acceptable excipient.
30. The pharmaceutical composition of claim 29 that is formulated for a route of administration selected from oral administration, parenteral administration, buccal administration, nasal administration, topical administration, or rectal administration.