Therapeutic compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-9827248-B2
Application number	US-201615139099-A
Country	US
Kind code	B2
Filing date	Apr 26, 2016
Priority date	Feb 15, 2013
Publication date	Nov 28, 2017
Grant date	Nov 28, 2017

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.

First claim

What is claimed is:

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

or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is H or C 1-6 alkyl;
R 2 is of the formula:

p is 1, q is 1, s is 1, and t is 2; p is 1, q is 1, s is 1, and t is 3; p is 1, q is 1, s is 2, and t is 2; p is 1, q is 1, s is 2, t is 3; p is 1, q is 1, s is 3, and t is 3; p is 1, q is 1, s is 1, and t is 1; p is 1, q is 2, s is 1, t is 2; p is 1, q is 2, s is 1, and t is 3; p is 1, q is 2, s is 2, and t is 2; p is 1, q is 2, s is 2, and t is 3; p is 1, q is 2, s is 3, and t is 3; p is 2, q is 2, s is 1, t is 1; p is 2, q is 2, s is 1, and t is 2; p is 2, q is 2, s is 1, and t is 3; p is 2, q is 2, s is 2, and t is 2; p is 2, q is 2, s is 2, and t is 3; or p is 2, q is 2, s is 3, and t is 3;
X is a bond, —O—, or —C(═O)—;
each instance of R 3 is H, F, CI, Br, I, CN, or OH;
Y is N;
Z is unsubstituted aliphatic, substituted aliphatic, unsubstituted heterocyclylalkyl, substituted heterocyclylalkyl, unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, substituted heteroaryl, unsubstituted quinolyl, or substituted quinolyl;
m is independently 0, 1, 2, 3, or 4; and
n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

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

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

4. The pharmaceutical composition of claim 1 , wherein m is 1 and R 3 is F.

5. The pharmaceutical composition of claim 1 , wherein R 1 is CH 3 .

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

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

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

wherein e, f, and h are independently 1, 2, or 3.

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

10. The pharmaceutical composition of claim 1 , wherein Z is unsubstituted thiophenyl or 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 the compound is:

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

18. The method of claim 17 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma.

19. A pharmaceutical composition for administration to an eye comprising a compound of Formula VI and a pharmaceutically acceptable carrier:

or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is H or optionally substituted C 1-6 alkyl;
R 2 is heterocyclyl;
X is a bond, —O—, or —C(═O)—;
each instance of R 3 is independently H, F, Cl, Br, I, CN, or OH;
Y is N;
Z is unsubstituted aliphatic, substituted aliphatic, unsubstituted heterocyclylalkyl, substituted heterocyclylalkyl, unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, substituted heteroaryl, unsubstituted quinolyl, or substituted quinolyl;
m is independently 0, 1, 2, 3, or 4 ; and
n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

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

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

Assignees

• Kala Pharmaceuticals Inc

Inventors

• Ong Winston Zapanta
• Nowak Pawel Wojciech
• Askew Ben C
• Kim Jinsoo

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• C07D491/107 Primary

  with only one oxygen atom as ring hetero atom in the oxygen-containing ring · CPC title