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 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.