Therapeutic compounds and uses thereof
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.
1. A pharmaceutical composition, comprising a compound of Formula (I) and a pharmaceutically acceptable carrier, wherein Formula (I) is:
or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is H or C 1-6 alkyl;
R 2 is an optionally substituted oxetanyl, or optionally substituted spiro bicyclic heterocyclyl wherein one or two atoms in the heterocyclic ring are independently O or N;
X is a bond, —O—, or —C(═O)—;
each instance of R 3 is independently H, F, Cl, Br, I, CN, or OH;
Z is optionally substituted aliphatic, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted quinolyl;
m is 0, 1, 2, 3, or 4; and
n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
2. The pharmaceutical composition of claim 1 , wherein m is 0.
3. The pharmaceutical composition of claim 1 , wherein m is 1 and R 3 is Cl.
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 optionally substituted isooxazolyl.
7. The pharmaceutical composition of claim 1 , wherein Z is optionally 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 optionally 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 R 2 is:
wherein p and q are independently 0, 1, 2, 3, or 4.
17. The pharmaceutical composition of claim 1 , wherein R 2 is:
wherein p, q, s, and t are independently 0, 1, 2, 3, or 4.
18. The pharmaceutical composition of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
19. A method of treating an ocular disease, comprising administering a pharmaceutical composition according to claim 1 to a subject in need thereof.
20. The method of claim 19 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma.
21. A pharmaceutical composition, comprising a compound of Formula (VI) and a pharmaceutically acceptable carrier, wherein Formula (VI) is:
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 CH;
Z is C 1-6 alkyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally 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.
22. A method of treating an ocular disease, comprising administering a pharmaceutical composition according to claim 21 to a subject in need thereof.
23. The method of claim 22 , wherein the ocular disease is a retinopathy, age-related macular degeneration, or glaucoma.
24. The pharmaceutical composition of claim 18 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
25. The pharmaceutical composition of claim 18 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
26. The pharmaceutical composition of claim 21 , wherein R 1 is H or C 1-6 alkyl.