Aryl cyclopropyl-amino-isoquinolinyl amide compounds
Provided herein are amino isoquinolinyl amide and sulfonamide compounds that affect the function of kinases and other proteins in a cell and that are useful as therapeutic agents. In particular, these compounds are useful in the treatment of eye diseases such as glaucoma and retinal diseases, as anti-inflammatory agents, for the treatment of cardiovascular diseases, and for diseases characterized by abnormal growth, such as cancers.
1. A compound of Formula (I):
or a pharmaceutically acceptable salt thereof,
wherein
R 1 is H, halo, —CN, —C 1-6 alkyl, —C 1-6 alkoxyl, —C 1-6 haloalkyl; —C 1-6 haloalkoxyl;
R 2 is H or halo;
X is —(C 1-5 heteroaryl)-R 3 ; and
R 3 is —C 2-6 heterocyclyl, or —C 1-6 heteroalkyl.
2. The compound of claim 1 , wherein the compound of Formula (I) is a compound of Formula (II):
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein the compound of Formula (I) is a compound of Formula (III):
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein R 1 is H, halo, —CN, —C 1-3 alkyl, —C 1-3 alkoxyl, —C 1-3 haloalkyl, —C 1-3 haloalkoxyl.
5. The compound of claim 1 , wherein R 1 is H, Cl, —CN, —CH 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , —CHF 2 , —CF 3 , or —OCF 3 .
6. The compound of claim 1 , wherein R 1 is Cl, —CN, —CH 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , —CHF 2 , —CF 3 , or —OCF 3 .
7. The compound of claim 1 , wherein R 2 is F, Cl, Br, or I.
8. The compound of claim 1 , wherein R 2 is H or F.
9. The compound of claim 1 , wherein X is —(C 3-5 heteroaryl)-R 3 .
10. The compound of claim 1 , wherein X is
11. The compound of claim 1 , wherein R 3 is —C 2-6 heterocyclyl.
12. The compound of claim 1 , wherein R 3 is —C 3-5 heterocycloalkyl.
13. The compound of claim 1 , wherein R 3 is
14. The compound of claim 1 , wherein
R 1 is H, Cl, —CN, —CH 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , —CF 3 , or —OCF 3 ;
R 2 is H or F;
X is
and R 3 is
15. The compound of claim 1 , wherein
R 1 is Cl, —CN, —CH 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , —CF 3 , or —OCF 3 ;
R 2 is H or F;
X is
and
R 3 is
16. The compound of claim 1 , selected from:
or a pharmaceutically acceptable salt thereof.
17. A pharmaceutical composition, comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
18. A pharmaceutical composition, comprising the compound of claim 2 and a pharmaceutically acceptable carrier.
19. A pharmaceutical composition, comprising the compound of claim 3 and a pharmaceutically acceptable carrier.
20. A pharmaceutical composition, comprising the compound of claim 4 and a pharmaceutically acceptable carrier.
21. A pharmaceutical composition, comprising the compound of claim 5 and a pharmaceutically acceptable carrier.
22. A pharmaceutical composition, comprising the compound of claim 6 and a pharmaceutically acceptable carrier.
23. A pharmaceutical composition, comprising the compound of claim 7 and a pharmaceutically acceptable carrier.
24. A pharmaceutical composition, comprising the compound of claim 8 and a pharmaceutically acceptable carrier.
25. A pharmaceutical composition, comprising the compound of claim 9 and a pharmaceutically acceptable carrier.
26. A pharmaceutical composition, comprising the compound of claim 10 and a pharmaceutically acceptable carrier.
27. A pharmaceutical composition, comprising the compound of claim 11 and a pharmaceutically acceptable carrier.
28. A pharmaceutical composition, comprising the compound of claim 12 and a pharmaceutically acceptable carrier.
29. A pharmaceutical composition, comprising the compound of claim 13 and a pharmaceutically acceptable carrier.
30. A pharmaceutical composition, comprising the compound of claim 14 and a pharmaceutically acceptable carrier.
31. A pharmaceutical composition, comprising the compound of claim 15 and a pharmaceutically acceptable carrier.
32. A pharmaceutical composition, comprising the compound of claim 16 and a pharmaceutically acceptable carrier.