Therapeutic compounds and uses thereof

• US 10,398,703 B2
• Filed: 01/11/2018
• Issued: 09/03/2019
• Est. Priority Date: 02/15/2013
• Status: Active Grant

• Current Assignee: Kala Bio, Inc.
• Original Assignee: Kala Pharmaceuticals, Inc.
• Inventors: Ong, Winston Zapanta, Nowak, Pawel Wojciech, Askew, Ben C., Kim, Jinsoo
• Primary Examiner(s): Ward, Paul V
• Application Number:
  US15/868,894
• Publication Number:
  US 20180133225A1
• Time in Patent Office: 600 Days
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 239/88 Oxygen atoms
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 491/107 with only one oxygen atom as ring hetero atom in the oxygen-containing ring
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Described herein are compounds of Formula (I) or Formula (VI), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I) or Formula (VI) and pharmaceutical compositions thereof that are mucus penetrating. Methods of using the compounds or pharmaceutical compositions thereof for treating diseases are also provided.

Claims

1. A pharmaceutical composition, comprising a compound of Formula (I) and a pharmaceutically acceptable carrier, wherein Formula (I) is:

2. The pharmaceutical composition of claim 1, wherein m is 0.

3. The pharmaceutical composition of claim 1, wherein m is 1 and R₃ is Cl.

4. The pharmaceutical composition of claim 1, wherein m is 1 and R₃ is F.

5. The pharmaceutical composition of claim 1, wherein R₁ is CH₃.

6. The pharmaceutical composition of claim 1, wherein Z is optionally substituted isooxazolyl.

7. The pharmaceutical composition of claim 1, wherein Z is optionally substituted phenyl.

8. The pharmaceutical composition of claim 1, wherein Z is:

9. The pharmaceutical composition of claim 1, wherein Z is C_1-6 alkyl.

10. The pharmaceutical composition of claim 1, wherein Z is optionally substituted thiophenyl.

11. The pharmaceutical composition of claim 1, wherein X is a bond.

12. The pharmaceutical composition of claim 1, wherein X is —

O—

.

13. The pharmaceutical composition of claim 1, wherein X is —

C(═

O)—

.

14. The pharmaceutical composition of claim 1, wherein n is 1.

15. The pharmaceutical composition of claim 1, wherein n is 2.

16. The pharmaceutical composition of claim 1, wherein R₂ is:

17. The pharmaceutical composition of claim 1, wherein R₂ is:

18. The pharmaceutical composition of claim 1, wherein the compound is:

19. A method of treating an ocular disease, comprising administering a pharmaceutical composition according to claim 1 to a subject in need thereof.

20. The method of claim 19, wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma.

24. The pharmaceutical composition of claim 18, wherein the compound is:

25. The pharmaceutical composition of claim 18, wherein the compound is:

21. A pharmaceutical composition, comprising a compound of Formula (VI) and a pharmaceutically acceptable carrier, wherein Formula (VI) is:

22. A method of treating an ocular disease, comprising administering a pharmaceutical composition according to claim 21 to a subject in need thereof.

23. The method of claim 22, wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma.

26. The pharmaceutical composition of claim 21, wherein R₁ is H or C_1-6 alkyl.