Therapeutic compounds and uses thereof
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.
1. A pharmaceutical composition suitable for delivery to the eye, comprising a pharmaceutically acceptable carrier and a compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is H or optionally substituted C 1-6 alkyl;
R 2 is optionally substituted bicyclic heterocyclyl having 1 or 2 heteroatoms;
X is a bond, —O—, or —C(═O)—;
Y is N;
R 3 is optionally substituted heteroaryl; and
n is 0, 1, 2, 3, or 4.
2. The pharmaceutical composition of claim 1 , wherein the compound of Formula (I) is a compound of Formula (II):
or a pharmaceutically acceptable salt thereof, wherein:
each instance of R 4 is independently H, optionally substituted C 1-6 alkyl, F, Cl, Br, I, CN, OH, or alkoxy;
R 5 is H or a nitrogen protecting group; and
m is 0, 1, 2, 3, 4, or 5.
3. The pharmaceutical composition of claim 2 , wherein R 4 is H.
4. The pharmaceutical composition of claim 2 , wherein R 4 is F.
5. The pharmaceutical composition of claim 2 , wherein R 4 is CH 3 .
6. The pharmaceutical composition of claim 1 , wherein the compound of Formula (I) is a compound of Formula (III):
or a pharmaceutically acceptable salt thereof, wherein:
each instance of R 4 is independently H, optionally substituted C 1-6 alkyl, F, Cl, Br, I, CN, OH, or alkoxy;
R 5 is H or a nitrogen protecting group; and
m is 0, 1, 2, 3, or 4.
7. The pharmaceutical composition of claim 6 , wherein R 4 is H.
8. The pharmaceutical composition of claim 6 , wherein R 4 is F.
9. The pharmaceutical composition of claim 6 , wherein R 4 is CH 3 .
10. The pharmaceutical composition of claim 6 , wherein R 5 is H.
11. The pharmaceutical composition of claim 1 , wherein R 1 is CH 3 .
12. The pharmaceutical composition of claim 1 , wherein R 2 is
wherein p, q, s, and t are independently 0, 1, 2, 3, or 4.
13. The pharmaceutical composition of claim 12 , wherein R 2 is
14. The pharmaceutical composition of claim 12 , wherein R 2 is
15. The pharmaceutical composition of claim 12 , wherein R 2 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:
or a pharmaceutically acceptable salt thereof.
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:
or a pharmaceutically acceptable salt thereof.
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.