Oxysterols and methods of use thereof
Compounds are provided according to Formula (A): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R G are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
1. A pharmaceutical composition comprising a compound of Formula (I-67):
wherein:
R 1 is substituted or unsubstituted alkyl;
each of R 2 and R 3 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or
R 2 and R 3 , together with the carbon atom to which they are attached form a substituted or unsubstituted 3-8 membered ring;
each of R 4 and R 5 is independently hydrogen, halo, or —OR c , wherein R c is hydrogen or substituted or unsubstituted C 1 -C 6 alkyl, or
R 4 and R 5 , together with the carbon atom to which they are attached form an oxo group;
R 6 is absent or hydrogen; and
represents a single or double bond, wherein when one of is a double bond, the other is a single bond and R 6 is absent; and when both of are single bonds, then R 6 is hydrogen; and
a pharmaceutically acceptable carrier.
2. The pharmaceutical composition of claim 1 , wherein R 1 is substituted or unsubstituted C 1 -C 6 alkyl.
3. The pharmaceutical composition of claim 1 , wherein R 1 is —CH 3 , —CF 3 , —CH 2 CH 3 , or —CH 2 OR A , wherein R A is substituted or unsubstituted C 1 -C 6 alkyl.
4. The pharmaceutical composition of claim 1 , wherein each of R 2 and R 3 is independently hydrogen or substituted or unsubstituted alkyl.
5. The pharmaceutical composition of claim 1 , wherein each of R 2 and R 3 is independently hydrogen, —CF 3 , or —CH 3 .
6. The pharmaceutical composition of claim 1 , wherein R 4 and R 5 , together with the carbon atom to which they are attached form an oxo group.
7. The pharmaceutical composition of claim 1 , wherein R 4 and R 5 are hydrogen.
8. The pharmaceutical composition of claim 1 , wherein R 2 is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl and R 3 is hydrogen.
9. The pharmaceutical composition of claim 1 , wherein R 2 is substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl and R 3 is hydrogen.
10. The pharmaceutical composition of claim 1 , wherein the compound of Formula (I-67) is selected from a compound of Formula (I-A67), (I-B67), or (I-C67):
11. A pharmaceutical composition comprising a pharmaceutically acceptable salt of a compound of Formula (I-67):
wherein:
R 1 is substituted or unsubstituted alkyl;
each of R 2 and R 3 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or
R 2 and R 3 , together with the carbon atom to which they are attached form a substituted or unsubstituted 3-8 membered ring;
each of R 4 and R 5 is independently hydrogen, halo, or —OR c , wherein R c is hydrogen or substituted or unsubstituted C 1 -C 6 alkyl, or
R 4 and R 5 , together with the carbon atom to which they are attached form an oxo group;
R 6 is absent or hydrogen; and
represents a single or double bond, wherein when one of is a double bond, the other is a single bond and R 6 is absent; and when both of are single bonds, then R 6 is hydrogen; and
a pharmaceutically acceptable carrier.
12. The pharmaceutical composition of claim 11 , wherein R 1 is substituted or unsubstituted C 1 -C 6 alkyl.
13. The pharmaceutical composition of claim 11 , wherein R 1 is —CH 3 , —CF 3 , —CH 2 CH 3 , or —CH 2 OR A , wherein R A is substituted or unsubstituted C 1 -C 6 alkyl.
14. The pharmaceutical composition of claim 11 , wherein each of R 2 and R 3 is independently hydrogen or substituted or unsubstituted alkyl.
15. The pharmaceutical composition of claim 11 , wherein each of R 2 and R 3 is independently hydrogen, —CF 3 , or —CH 3 .
16. The pharmaceutical composition of claim 11 , wherein R 4 and R 5 , together with the carbon atom to which they are attached form an oxo group.
17. The pharmaceutical composition of claim 11 , wherein R 4 and R 5 are hydrogen.
18. The pharmaceutical composition of claim 11 , wherein R 2 is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl and R 3 is hydrogen.
19. The pharmaceutical composition of claim 11 , wherein R 2 is substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl and R 3 is hydrogen.
20. The pharmaceutical composition of claim 11 , wherein the compound of Formula (I-67) is selected from a compound of Formula (I-A67), (I-B67), or (I-C67):