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 method of treating an ocular disease in a subject in need thereof, comprising administering to the subject a compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is hydrogen or optionally substituted C 1-6 alkyl;
R 2 is
X is a bond, —O—, or —C(═O)—;
Y is CH;
R 3 is optionally substituted heteroaryl; and
n is 0, 1, 2, 3, or 4.
2. The method of claim 1 , wherein the compound is of Formula (II):
or a pharmaceutically acceptable salt thereof, wherein:
each instance of R 4 is independently selected from the group consisting of hydrogen, optionally substituted C 1-6 alkyl, F, Cl, Br, I, CN, OH, and alkoxy;
R 5 is hydrogen or a nitrogen protecting group; and
m is 0, 1, 2, 3, 4, or 5.
3. The method of claim 1 , wherein the compound is of Formula (II-a):
or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the compound is: of Formula (II-b):
or a pharmaceutically acceptable salt thereof;
of Formula (II-b1):
or a pharmaceutically acceptable salt thereof;
of Formula (II-b2):
or a pharmaceutically acceptable salt thereof;
of Formula (II-b3):
or a pharmaceutically acceptable salt thereof; or
of Formula (II-b4):
or a pharmaceutically acceptable salt thereof.
5. The method of claim 1 , wherein the compound is of Formula (II-c):
or a pharmaceutically acceptable salt thereof.
6. The method of claim 1 , wherein the compound is: of Formula (II-d):
or a pharmaceutically acceptable salt thereof;
of Formula (II-d1):
or a pharmaceutically acceptable salt thereof;
of Formula (II-d2):
or a pharmaceutically acceptable salt thereof;
of Formula (II-d3):
or a pharmaceutically acceptable salt thereof; or
of Formula (II-d4):
or a pharmaceutically acceptable salt thereof.
7. The method of claim 1 , wherein the compound is of Formula (III):
or a pharmaceutically acceptable salt thereof, wherein:
each instance of R 4 is independently selected from the group consisting of hydrogen, optionally substituted C 1-6 alkyl, F, Cl, Br, I, CN, OH, and alkoxy;
R 5 is hydrogen or nitrogen protecting group; and
m is 0, 1, 2, 3, or 4.
8. The method of claim 1 , wherein the compound is of Formula (III-a):
or a pharmaceutically acceptable salt thereof.
9. The method of claim 1 , wherein the compound is: of Formula (III-b):
or a pharmaceutically acceptable salt thereof;
of Formula (III-b1):
or a pharmaceutically acceptable salt thereof;
of Formula (III-b2):
or a pharmaceutically acceptable salt thereof;
of Formula (III-b3):
or a pharmaceutically acceptable salt thereof; or
of Formula (III-b4):
or a pharmaceutically acceptable salt thereof.
10. The method of claim 1 , wherein the compound is of Formula (III-c):
or a pharmaceutically acceptable salt thereof.
11. The method of claim 1 , wherein the compound is: of Formula (III-d):
or a pharmaceutically acceptable salt thereof;
of Formula (III-d1):
or a pharmaceutically acceptable salt thereof;
of Formula (III-d2):
or a pharmaceutically acceptable salt thereof;
of Formula (III-d3):
or a pharmaceutically acceptable salt thereof; or
of Formula (III-d4):
or a pharmaceutically acceptable salt thereof.
12. The method of claim 2 , wherein R 5 is hydrogen.
13. The method of claim 1 , wherein R 2 is
14. The method of claim 1 , wherein R 2 is
15. The method of claim 1 , wherein R 2 is
16. The method of claim 1 , having one of the following structures:
or a pharmaceutically acceptable salt thereof.
17. The method of claim 1 , wherein the compound is suitable for delivery to an eye of the subject.
18. The method of claim 1 , wherein the ocular disease is retinopathy.
19. The method of claim 1 , wherein the ocular disease is age-related macular degeneration (AMD).
20. The method of claim 1 , wherein the ocular disease is glaucoma.
21. The method of claim 1 , wherein the compound is administered topically.
22. The method of claim 1 , wherein the compound is administered orally.
23. The method of claim 1 , wherein the compound is administered to an eye of the subject.