Oxysterols and methods of use thereof
Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R 1 , R 2 , R 3 , and R 6 , R 11a , and R 11b are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
1. A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is hydrogen or C 1 -C 6 alkyl;
each of R 2 and R 3 is independently hydrogen, C 1 -C 6 alkyl, or carbocyclyl, or R 2 and R 3 , together with the carbon atom to which they are attached, form a 3-8 membered ring;
R 6 is absent or hydrogen;
R 11a is hydrogen or C 1 -C 6 alkyl and R 11b is OH or C 1 -C 6 alkyl, or R 11a and R 11b are joined together to form oxo; and
represents a single or double bond, wherein when one is a double bond, the other is a single bond; and when one of the is a double bond, R 6 is absent.
2. The compound of claim 1 , wherein R 1 is C 1 -C 6 alkyl.
3. The compound of claim 1 , wherein R 1 is hydrogen, methyl, ethyl, —CHF 2 , —CF 3 , —CH 2 OCH 3 , or —CH 2 OCH 2 CH 3 .
4. The compound of claim 1 , wherein R 1 is unsubstituted C 1 -C 6 alkyl.
5. The compound of claim 1 wherein R 1 is hydrogen.
6. The compound of claim 1 , wherein R 1 is —CH 3 .
7. The compound of claim 1 , wherein R 1 is —CH 2 CH 3 .
8. The compound of claim 1 , wherein each of R 2 and R 3 is independently hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, —CF 3 , or —CH 2 CF 3 .
9. The compound of claim 8 , wherein each of R 2 and R 3 is independently methyl, isopropyl, or tert-butyl.
10. The compound of claim 8 , wherein R 2 is hydrogen, methyl, ethyl, or —CF 3 .
11. The compound of claim 1 , wherein R 3 is methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, —CF 3 , or —CH 2 CF 3 .
12. The compound of claim 1 , wherein R 11a is hydrogen and R 11b is —OH.
13. The compound of claim 1 , wherein R 11a is C 1 -C 6 alkyl and R 11b is —OH.
14. The compound of claim 1 , wherein R 11a and R 11b are joined together to form oxo.
15. The compound of claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-A) or Formula (I-B):
or a pharmaceutically acceptable salt thereof.
16. The compound of claim 1 , wherein the compound of Formula (I) is a compound of Formula (II-A) or Formula (II-B):
or a pharmaceutically acceptable salt thereof.
17. A compound selected from the group consisting of:
18. A pharmaceutically acceptable salt of a compound selected from the group consisting of:
19. The compound of claim 1 , wherein the compound of Formula (I) is a compound of Formula (III):
or a pharmaceutically acceptable salt thereof.
20. A pharmaceutical composition comprising a compound of claim 1 , or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.