Therapeutic compounds and uses thereof

• US 10,285,991 B2
• Filed: 12/14/2017
• Issued: 05/14/2019
• 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:
  US15/842,695
• Publication Number:
  US 20180104246A1
• Time in Patent Office: 516 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 method of treating an ocular disease in an eye of a subject, comprising injecting a compound of Formula (I):

2. The method of claim 1, wherein the compound of Formula (I) is a compound of Formula (II) or Formula (III):

3. The method of claim 1, wherein R₁ is CH₃.

4. The method of claim 1, wherein R₂ is

5. The method of claim 1, wherein X is a bond.

6. The method of claim 1, wherein X is —

C(═

O)—

.

7. The method of claim 1, wherein n is 2.

8. The method of claim 1, wherein n is 1.

9. The method of claim 2, wherein at least one instance of R₄ is CH₃.

10. The method of claim 2, wherein at least one instance of R₄ is F.

11. The method of claim 2, wherein at least one instance of R₄ is H.

12. The method of claim 2, wherein R₅ is H.

13. The method of claim 4, wherein R₂ is

14. The method of claim 4, wherein R₂ is

15. The method of claim 4, wherein R₂ is

16. The method of claim 1, wherein the compound of Formula (I) is:

17. The method of claim 1, wherein the compound, or pharmaceutically acceptable salt thereof, is in the form of a pharmaceutical composition.

18. The method of claim 1, wherein the ocular disease is a growth factor-associated disorder.

19. The method of claim 18, therein the growth factor is vascular endothelial growth factor.

20. The method of claim 1, wherein the ocular disease is at the front of the eye of the subject.

21. The method of claim 20, wherein the front of the eye ocular disease is post-surgical inflammation, uveitis, an infection, aphakia, pseudophakia, astigmatism, blepharospasm, cataract, a conjunctival disease, conjunctivitis, a corneal disease, corneal ulcer, a dry eye syndrome, an eyelid disease, a lacrimal apparatus disease, lacrimal duct obstruction, myopia, presbyopia, a pupil disorder, corneal neovascularization, a refractive disorders, strabismus, and glaucoma.

22. The method of claim 1, wherein the ocular disease is at the back of the eye of the subject.

23. The method of claim 22, wherein the back of the eye ocular disease is intraocular melanoma, acute macular neuroretinopathy, Behcet'"'"'s disease, choroidal neovascularization, uveitis, diabetic uveitis, histoplasmosis, an infection, macular degeneration, edema, multifocal choroiditis, ocular trauma which affects a posterior ocular site or location, ocular tumors, a retinal disorder, diabetic retinopathy, proliferative vitreoretinopathy (PVR), retinal arterial occlusive disease, retinal detachment, uveitic retinal disease, sympathetic opthalmia, Vogt Koyanagi-Harada (VKH) syndrome, uveal diffusion, a posterior ocular condition caused by or influenced by an ocular laser treatment, posterior ocular conditions caused by or influenced by a photodynamic therapy, photocoagulation, radiation retinopathy, a epiretinal membrane disorder, branch retinal vein occlusion, anterior ischemic optic neuropathy, non-retinopathy diabetic retinal dysfunction, retinitis pigmentosa, retinoblastoma, and glaucoma.

24. The method of claim 1, wherein the compound is injected intraocular, intrastromal, intravitreal, or intracameral.

25. The method of claim 1, wherein the compound of Formula (I) is

26. The method of claim 1, wherein the compound of Formula (I) is