Aryl cyclopropyl-amino-isoquinolinyl amide compounds
Provided herein are arylcyclopropyl amino-isoquinoline amide compounds. In particular, the disclosure provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the disclosure are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, diseases characterized by abnormal growth, such as cancers, and inflammatory diseases. The disclosure further provides compositions containing isoquinoline amide compounds.
1. A compound of Formula (III):
or a tautomer, a stereoisomer, or a pharmaceutically acceptable salt thereof,
wherein:
X 1 , X 2 and X 3 are H;
Y is —NR N1 C(O)—;
Z is a direct bond;
R is pyridyl; and
R N1 is H.
2. The compound of claim 1 , selected from:
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , selected from:
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , selected from:
or a pharmaceutically acceptable salt thereof.
5. A composition, comprising the compound of claim 1 .
6. A composition, comprising the compound of claim 2 .
7. A composition, comprising the compound of claim 3 .
8. A composition, comprising the compound of claim 4 .
9. A pharmaceutical composition, comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
10. A pharmaceutical composition, comprising the compound of claim 2 and a pharmaceutically acceptable excipient.
11. A pharmaceutical composition, comprising the compound of claim 3 and a pharmaceutically acceptable excipient.
12. A pharmaceutical composition, comprising the compound of claim 4 and a pharmaceutically acceptable excipient.
13. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the compound of claim 1 .
14. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the compound of claim 2 .
15. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the compound of claim 3 .
16. A method of treating an ocular disorder in a subject in need thereof, comprising administering to the subject the compound of claim 4 .
17. A method of reducing intraocular pressure in a subject in need thereof, comprising administering to the subject the compound of claim 1 .
18. A method of reducing intraocular pressure in a subject in need thereof, comprising administering to the subject the compound of claim 2 .
19. A method of reducing intraocular pressure in a subject in need thereof, comprising administering to the subject the compound of claim 3 .
20. A method of reducing intraocular pressure in a subject in need thereof, comprising administering to the subject the compound of claim 4 .
21. A method of modulating kinase activity in a cell, comprising contacting the cell with a compound of claim 1 .
22. The method of claim 21 , wherein the cell is in a subject.
23. The method of claim 22 , wherein the subject is a human subject.