Oxysterols and methods of use thereof
Compounds are provided according to Formula (III): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R 2 , R 3 , R 5 , and n are as defined herein, and at least one hydrogen is replaced with a deuterium. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
1. A method of treating a CNS-related condition selected from a group consisting of an adjustment disorder, anxiety disorder, dissociative disorder, eating disorder, mood disorder, schizophrenia or other psychotic disorder, sleep disorder, substance-related disorder, personality disorder, autism spectrum disorders, multiple sclerosis, pain, seizure disorder, stroke, traumatic brain injury, movement disorder, vision impairment, hearing loss, or tinnitus, wherein the method comprises administering to a subject in need thereof an effective amount of a compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is hydrogen or deuterium;
each of R 2 and R 3 is independently deuterium or —C 1-6 alkyl;
R 4 is hydrogen or deuterium;
R 5 is absent, hydrogen, or deuterium;
n is 1 or 2;
represents a single or double bond, wherein when one is a double bond, the other is a single bond and R 5 is absent; and
at least one of R 1 , R 2 , R 3 , R 4 , or R 5 is deuterium.
2. The method according to claim 1 , wherein:
a. R 1 is hydrogen; or
b. R 1 is deuterium.
3. The method according to claim 1 , wherein R 1 is deuterium.
4. The method according to claim 1 , wherein R 1 and R 2 are deuterium.
5. The method according to claim 1 , wherein
a. one of R 2 and R 3 is deuterium and the other of R 2 and R 3 is C 1-6 alkyl; or
b. each of R 2 and R 3 is independently —C 1-6 alkyl.
6. The method according to claim 1 , wherein each of R 2 and R 3 is independently —C 1-6 alkyl.
7. The method according to claim 1 , wherein each of R 2 and R 3 is independently isopropyl, —CH 3 , or —CF 3 .
8. The method according to claim 1 , wherein R 4 is hydrogen.
9. The method according to claim 1 , wherein n is 2.
10. The method according to claim 1 , wherein represents a single bond.
11. The method according to claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-A):
or a pharmaceutically acceptable salt thereof.
12. The method according to claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-B):
or a pharmaceutically acceptable salt thereof.
13. The method according to claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-C):
or a pharmaceutically acceptable salt thereof.
14. The method according to claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-D):
or a pharmaceutically acceptable salt thereof.
15. The method according to claim 1 , wherein the compound of Formula (I) is selected from the group consisting of:
16. The method according to claim 1 , wherein the compound of Formula (I) is a pharmaceutically acceptable salt of the compound selected from the group consisting of: