Heterocyclic compounds and uses thereof
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
n is 0, 1, or 2;
m is 0, 1, or 2, wherein m and n are not simultaneously 0;
W is —O— or —NH—;
R 1 is —OR;
each R is independently C 1-4 alkyl or C 1-4 fluoroalkyl;
R 2 is —CF 3 , Cl, or Br;
G is —NR 3 —;
R 3 is —C(O)—R, —C(O)OR, —C(O)NHR, —SO 2 —R, —SO 2 NH 2 , —C(O)—C 1-4 alkylene-OH or —SO 2 —C 1-4 alkylene-OH;
and
R 5 is hydrogen or —C(O)OR.
2. A compound of formula I-a:
or a pharmaceutically acceptable salt thereof, wherein:
n is 0, 1, or 2;
m is 0, 1, or 2, wherein m and n are not simultaneously 0;
W is —O— or —NH—;
R 1 is —OR;
each R is independently C 1-4 alkyl or C 1-4 fluoroalkyl;
R 2 is —CF 3 , Cl, or Br;
G is —NR 3 —; and
R 3 is —C(O)—R, —C(O)OR, —C(O)NHR, —SO 2 —R, —SO 2 NH 2 , —C(O)—C 1-4 alkylene-OH or —SO 2 —C 1-4 alkylene-OH.
3. The compound according to claim 1 , wherein W is —NH—.
4. The compound according to claim 3 , wherein R 2 is —CF 3 .
5. The compound according to claim 1 , wherein said compound is of formula III:
or a pharmaceutically acceptable salt thereof.
6. The compound according to claim 1 , wherein said compound is of formula III-a:
or a pharmaceutically acceptable salt thereof.
7. The compound according to claim 5 , wherein W is —NH—.
8. The compound according to claim 5 , wherein R 2 is —CF 3 .
9. The compound according to claim 5 , wherein at least one of definitions (a), (b), and (c) apply:
(a) W is —O— or —NH—;
(b) R 2 is —CF 3 or Cl; and
(c) R 3 is —C(O)CH 3 or —SO 2 CH 3 .
10. The compound according to claim 9 , wherein at least two of definitions (a), (b), and (c) apply.
11. The compound according to claim 9 , wherein all three of definitions (a), (b), and (c) apply.
12. The compound according to claim 5 , wherein at least one of definitions (a), (b), and (c) apply:
(a) W is —NH—;
(b) R 2 is —CF 3 or Cl; and
(c) R 3 is —C(O)CH 3 .
13. The compound according to claim 12 , wherein at least two of definitions (a), (b), and (c) apply.
14. The compound according to claim 13 , wherein all three of definitions (a), (b), and (c) apply.
15. The compound according to claim 5 , wherein at least one of definitions (a), (b), and (c) apply:
(a) W is —NH—;
(b) R 2 is —CF 3 or Cl; and
(c) R 3 is —SO 2 CH 3 .
16. The compound according to claim 15 , wherein at least two of definitions (a), (b), and (c) apply.
17. The compound according to claim 5 , wherein at least one of definitions (a), (b), and (c) apply:
(a) W is —O—;
(b) R 2 is —CF 3 or Cl; and
(c) R 3 is —C(O)CH 3 .
18. The compound according to claim 17 , wherein at least two of definitions (a), (b), and (c) apply.
19. The compound according to claim 5 , wherein at least one of definitions (a), (b), and (c) apply:
(a) W is —O—;
(b) R 2 is —CF 3 or Cl; and
(c) R 3 is —SO 2 CH 3 .
20. The compound according to claim 1 , selected from:
or a pharmaceutically acceptable salt thereof.
21. A composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
22. The composition according to claim 21 , in combination with an additional therapeutic agent.
23. The composition according to claim 22 , wherein the additional therapeutic agent is a chemotherapeutic agent.
24. The compound according to claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
25. A composition comprising a compound according to claim 24 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.