Fluoroalkyl-oxadiazoles and uses thereof
Provided herein are compounds identified as inhibitors of HDAC6 activity having the formula: or a pharmaceutically acceptable salt thereof, that can be used to treat various diseases and disorders.
1. A compound having the formula:
or a pharmaceutically acceptable salt thereof,
wherein:
X 1 is S;
R a is selected from the group consisting of H, halogen, and C 1-3 alkyl;
R 1 is
R 2 is selected from the group consisting of alkyl, alkoxy, and cycloalkyl, each of which is optionally substituted;
R 3 is H or alkyl;
R 4 is selected from the group consisting of alkyl, —(SO 2 )R 2 , —(SO 2 )NR 2 R 3 , and —(CO)R 2 ; and
R 5 is heteroaryl.
2. The compound of claim 1 , wherein R a is H.
3. The compound of claim 1 , wherein R 1 is
4. The compound of claim 1 , wherein R 4 is —(SO 2 )R 2 .
5. The compound of claim 4 , wherein —(SO 2 )R 2 is —(SO 2 )alkyl, —(SO 2 )alkyleneheterocyclyl, —(SO 2 )haloalkyl, —(SO 2 )haloalkoxy, or —(SO 2 )cycloalkyl.
6. The compound of claim 1 , wherein the heteroaryl is a 5- to 6-membered heteroaryl.
7. The compound of claim 6 , wherein the 5- to 6-membered heteroaryl is selected from the group consisting of
wherein R b is halogen, alkyl, alkoxy, cycloalkyl, —CN, haloalkyl, or haloalkoxy; and m is 0 or 1.
8. The compound of claim 7 , wherein R b is F, Cl, —CH 3 , —CH 2 CH 3 , —CF 3 , —CHF 2 , —CF 2 CH 3 , —CN, —OCH 3 , —OCH 2 CH 3 , —OCH(CH 3 ) 2 , —OCF 3 , —OCHF 2 , —OCH 2 CF 2 H, and cyclopropyl.
9. A compound of Formula (Ik):
or a pharmaceutically acceptable salt thereof,
wherein:
R b is H, halogen, alkyl, cycloalkyl, —CN, haloalkyl, or haloalkoxy; and
R 4 is alkyl, alkoxy, haloalkyl, or cycloalkyl, each of which is optionally substituted.
10. The compound of claim 9 , wherein R b is H, halogen, haloalkyl, or haloalkoxy.
11. The compound of claim 9 , wherein R 4 is optionally substituted alkyl or cycloalkyl.
12. The compound of claim 9 , having the structure:
or a pharmaceutically acceptable salt thereof,
wherein:
R b is H, halogen, alkyl, cycloalkyl, —CN, haloalkyl, or haloalkoxy; and
R 4 is alkyl, alkoxy, haloalkyl, or cycloalkyl, each of which is optionally substituted.
13. The compound of claim 12 , wherein R b is H, halogen, haloalkyl, or haloalkoxy.
14. The compound of claim 12 , wherein R 4 is optionally substituted alkyl or cycloalkyl.
15. The compound of claim 14 , wherein R 4 is alkyl.
16. The compound of claim 9 , having the structure:
or a pharmaceutically acceptable salt thereof,
wherein:
R b is H, halogen, alkyl, cycloalkyl, —CN, haloalkyl, or haloalkoxy; and
R 4 is alkyl, alkoxy, haloalkyl, or cycloalkyl, each of which is optionally substituted.
17. The compound of claim 16 , wherein R b is H, halogen, haloalkyl, or haloalkoxy.
18. The compound of claim 16 , wherein R 4 is optionally substituted alkyl.
19. The compound of claim 1 of formula:
or a pharmaceutically acceptable salt thereof.
20. The compound of claim 1 of formula:
or a pharmaceutically acceptable salt thereof.
21. The compound of claim 1 of formula:
or a pharmaceutically acceptable salt thereof.
22. The compound of claim 1 of formula:
or a pharmaceutically acceptable salt thereof.
23. The compound of claim 1 of formula:
or a pharmaceutically acceptable salt thereof.
24. The compound of claim 1 of formula:
or a pharmaceutically acceptable salt thereof.
25. The compound of claim 1 of formula:
or a pharmaceutically acceptable salt thereof.
26. The compound of claim 1 of formula:
or a pharmaceutically acceptable salt thereof.
27. The compound of claim 1 of formula:
or a pharmaceutically acceptable salt thereof.
28. The compound of claim 1 of formula:
or a pharmaceutically acceptable salt thereof.