Therapeutic compounds and uses thereof

• US 9,833,453 B2
• Filed: 04/26/2016
• Issued: 12/05/2017
• Est. Priority Date: 02/20/2013
• 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:
  US15/139,121
• Publication Number:
  US 20160235753A1
• Time in Patent Office: 588 Days
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 491/107 with only one oxygen atom as ring hetero atom in the oxygen-containing ring
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

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

Claims

1. A pharmaceutical composition suitable for delivery to the eye, comprising a pharmaceutically acceptable carrier and a compound of Formula (I):

2. The pharmaceutical composition of claim 1, wherein the compound of Formula (I) is a compound of Formula (II):

3. The pharmaceutical composition of claim 2, wherein R₄ is H.

4. The pharmaceutical composition of claim 2, wherein R₄ is F.

5. The pharmaceutical composition of claim 2, wherein R₄ is CH₃.

6. The pharmaceutical composition of claim 1, wherein the compound of Formula (I) is a compound of Formula (III):

7. The pharmaceutical composition of claim 6, wherein R₄ is H.

8. The pharmaceutical composition of claim 6, wherein R₄ is F.

9. The pharmaceutical composition of claim 6, wherein R₄ is CH₃.

10. The pharmaceutical composition of claim 6, wherein R₅ is H.

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

12. The pharmaceutical composition of claim 1, wherein R₂ is

13. The pharmaceutical composition of claim 12, wherein R₂ is

14. The pharmaceutical composition of claim 12, wherein R₂ is

15. The pharmaceutical composition of claim 12, wherein R₂ is

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

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

C(═

O)—

.

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

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

20. The pharmaceutical composition of claim 1, wherein the compound of Formula (I) is:

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

22. The method of claim 21, wherein the ocular disease is a retinopathy, age-related macular degeneration, corneal neovascularization, diabetic macular edema, retinal vein occlusion, or glaucoma.

23. A pharmaceutical composition for administration to an eye, comprising:

24. A method of treating an ocular disease, comprising administering the pharmaceutical composition of claim 23 to a subject in need thereof.

25. The method of claim 24, wherein the ocular disease is a retinopathy, age-related macular degeneration, corneal neovascularization, diabetic macular edema, retinal vein occlusion, or glaucoma.