Therapeutic compounds and uses thereof
Described herein are compounds of Formula (I) pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Methods of using the compounds or pharmaceutical compositions thereof for treating diseases are also provided.
1. A compound of Formula (II):
or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is hydrogen or optionally substituted C 1-6 alkyl;
R 2 is:
(1) a heterocyclyl when:
(a) X is —O—, or —C(═O)— and n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; or
(b) X is a bond and n is 6, 7, 8, 9, or 10; or
(2) an eight or nine membered heterocyclyl, when X is a bond and n is 0, 1, 2, 3, 4, or 5;
wherein each instance of R 3 is independently hydrogen, F, Cl , Br, I, CN, and OH;
Y is CH or N;
m is independently 0, 1, 2, 3, or 4;
each instance of R 4 is independently hydrogen, optionally substituted C 1-6 alkyl, F, Cl, Br, I, or CN; and
j is 0, 1, or 2.
2. The compound of claim 1 , wherein the compound is of Formula (II-a):
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein the compound is of Formula (II-b):
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein the compound is of Formula (II-c):
or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 , wherein the compound is of Formula (II-c1):
or a pharmaceutically acceptable salt thereof.
6. The compound of claim 1 , wherein the compound is of Formula (II-c2):
or a pharmaceutically acceptable salt thereof.
7. The compound of claim 1 , wherein the compound is of Formula (II-c3):
or a pharmaceutically acceptable salt thereof.
8. The compound of claim 1 , wherein the compound is of Formula (II-c4):
or a pharmaceutically acceptable salt thereof.
9. A compound of Formula (III-c):
or a pharmaceutically acceptable salt thereof,
wherein:
R 2 is:
(1) a heterocyclyl when:
(a) X is —O—, or —C(═O)— and n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; or
(b) X is a bond and n is 6, 7, 8, 9, or 10; or
(2) an eight or nine membered heterocyclyl, when X is a bond and n is 0, 1, 2, 3, 4, or 5; and
Y is CH or N.
10. The compound of claim 9 , wherein the compound is of Formula (III-c1):
or a pharmaceutically acceptable salt thereof.
11. The compound of claim 9 , wherein the compound is of Formula (III-c2):
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 9 , wherein the compound is of Formula (III-c3):
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 9 , wherein the compound is of Formula (III-c4):
or a pharmaceutically acceptable salt thereof.
14. A compound of Formula (IV-a1-ii):
or a pharmaceutically acceptable salt thereof;
wherein R 2 is a heterocyclyl;
Y is CH is N; and
Z 1 is branched or unbranched, acyclic of cyclic C 1-6 alkyl.
15. The compound of claim 14 , wherein the compound is of Formula (IV-a1-iii):
or a pharmaceutically acceptable salt thereof.
16. The compound of claim 14 , wherein the compound is of Formula (IV-a1-iv):
or a pharmaceutically acceptable salt thereof.
17. A compound of Formula (V):
or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is hydrogen or optionally substituted C 1-6 alkyl;
R 2 is:
(1) a heterocyclyl when:
(a) X is —O—, of —C(═O)— and n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; or
(b) X is a bond and n is 6,7, 8, 9, or 10; or
(2) an eight or nine membered heterocyclyl, when X is a bond and n is 0, 1, 2, 3, 4, or 5;
wherein each instance of R 3 is independently hydrogen, F, Cl, Br, I, CN, or OH;
m is independently 0, 1, 2, 3, or 4,
Y is CH or N; and
each of e and f is independently 1, 2, or 3.
18. The compound of claim 17 , wherein the compound is of Formula (V-a):
or a pharmaceutically acceptable salt thereof.
19. The compound of claim 17 , wherein the compound is of Formula (V-a1):
or a pharmaceutically acceptable salt thereof.
20. The compound of claim 17 , wherein the compound is of Formula (V-a1-i):
or a pharmaceutically acceptable salt thereof.
21. The compound of claim 17 , wherein the compound is of Formula (V-a1-ii):
or a pharmaceutically acceptable salt thereof.
22. The compound of claim 17 , wherein the compound is of Formula (V-a1-iii):
or a pharmaceutically acceptable salt thereof.
23. The compound of claim 17 , wherein the compound is of Formula (V-a1-iv):
or a pharmaceutically acceptable salt thereof.
24. The compound of claim 17 , wherein the compound is of Formula (V-b):
or a pharmaceutically acceptable salt thereof.
25. The compound of claim 17 , wherein the compound is of Formula (V-b1):
or a pharmaceutically acceptable salt thereof.
26. The compound of claim 17 , wherein the compound is of Formula (V-b1-i):
or a pharmaceutically acceptable salt thereof.
27. The compound of claim 17 , wherein the compound is of Formula (V-b1-ii):
or a pharmaceutically acceptable salt thereof.
28. The compound of claim 17 , wherein the compound is of Formula (V-b1-iii):
or a pharmaceutically acceptable salt thereof.
29. The compound of claim 17 , wherein the compound is of Formula (V-b1-iv):
or a pharmaceutically acceptable salt thereof.
30. The compound of claim 1 , wherein R 2 is of formula:
wherein each instance of p and q is independently 0, 1, 2, 3, or 4.
31. The compound of claim 30 , wherein R 2 is of the formula:
32. The compound of claim 1 , wherein R 2 is of the formula:
wherein each instance of p, q, s, and t is independently 0, 1, 2, 3, or 4.
33. The compound of claim 32 , wherein R 2 is of the formula:
34. A compound of one of the following formulae:
35. A pharmaceutical composition comprising a compound of one of claims 1 , 9 , 14 , 17 , or 34 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
36. The pharmaceutical composition of claim 35 , wherein the pharmaceutical composition is suitable for delivery to the eye.
37. The compound of one of claims 1 , 9 , 14 , or 17 , wherein R 1 is methyl.
38. The compound of claim 32 , wherein R 2 is of the formula:
39. The compound of any one of claims 1 , 9 , or 17 , wherein R 2 is a spiro-heterocyclyl when X is a bond, —O—, or —C(═O)— and n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.