Oxysterols and methods of use thereof
Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R 2 , R 3 , R 4 , R 5 , and R 6 are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
1. A method for treating a CNS-related condition, comprising administering to a subject in need thereof an effective amount of a compound of Formula (I-66):
wherein:
R 1 is substituted or unsubstituted C 1 -C 6 alkyl;
R 2 is substituted or unsubstituted aralkyl, substituted or unsubstituted heteroaralkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 3 is hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
each of R 4 and R 5 is independently hydrogen, halo, or —OR C , wherein R C is hydrogen or unsubstituted or substituted C 1 -C 3 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; when both of are single bonds, then R 6 is hydrogen; and when one of is a double bond, R 6 is absent, or a pharmaceutically acceptable salt thereof; or a pharmaceutical composition comprising said compound of Formula (I-66), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier;
wherein the CNS-related condition is selected from the group consisting of schizophrenia, an autism spectrum disorder, Huntington's disease, Parkinson's disease, a seizure disorder, a mood disorder, stroke, a traumatic brain injury, a substance-related disorder, and a cognitive disorder.
2. The method according to claim 1 , wherein the CNS-related condition is a cognitive disorder.
3. The method according to claim 1 , wherein the CNS-related condition is an autism spectrum disorder.
4. The method according to claim 1 , wherein the CNS-related condition is schizophrenia.
5. The method according to claim 1 , wherein the CNS-related condition is Huntington's disease or Parkinson's disease.
6. The method according to claim 2 , wherein the cognitive disorder is Alzheimer's disease.
7. The method according to claim 1 , wherein R 1 is unsubstituted C 1 -C 6 alkyl.
8. The method according to claim 1 , wherein R 1 is —CH 3 , —CF 3 , or —CH 2 CH 3 .
9. The method according to claim 1 , wherein R 2 is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted aralkyl.
10. The method according to claim 1 , wherein R 2 is substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, or substituted or unsubstituted benzyl.
11. The method according to claim 1 , wherein R 3 is hydrogen or substituted or unsubstituted C 1 -C 6 alkyl.
12. The method according to claim 1 , wherein R 3 is hydrogen, unsubstituted C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.
13. The method according to claim 1 , wherein R 4 and R 5 are hydrogen.
14. The method according to claim 1 , wherein R 2 is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted aralkyl; and R 3 is hydrogen or substituted or unsubstituted C 1 -C 6 alkyl.
15. The method according to claim 1 , wherein R 2 is substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, or substituted or unsubstituted benzyl; and R 3 is hydrogen, —CH 3 , or —CF 3 .
16. The method according to claim 1 , wherein R 1 is —CH 3 or —CH 2 CH 3 ; R 2 is unsubstituted phenyl, unsubstituted pyridyl, or unsubstituted benzyl; and R 3 is hydrogen, —CH 3 , or —CF 3 .
17. The method according to claim 1 , wherein the compound of Formula (I-66) is selected from the group consisting of:
18. The method according to claim 1 , wherein the compound of Formula (I-66) is a pharmaceutically acceptable salt of a compound selected from the group consisting of: