Aryl cyclopropyl-amino-isoquinolinyl amide compounds

Patent metadata

Field	Value
Publication number	US-12018012-B2
Application number	US-202217722832-A
Country	US
Kind code	B2
Filing date	Apr 18, 2022
Priority date	Mar 31, 2017
Publication date	Jun 25, 2024
Grant date	Jun 25, 2024

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Aerie Pharmaceuticals Inc

Inventors

• Delong Mitchell A
• Sturdivant Jill M
• Lichorowic Cynthia L
• Kornilov Andriy

Classifications

• C07D409/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• C07C69/76

  Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title