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 pharmaceutical composition comprising 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; and
a pharmaceutically acceptable carrier.
2. The pharmaceutical composition of claim 1 , wherein R 1 is hydrogen.
3. The pharmaceutical composition of claim 1 , wherein R 1 is deuterium.
4. The pharmaceutical composition of claim 1 , wherein R 1 and R 2 are deuterium.
5. The pharmaceutical composition of claim 1 , wherein one of R 2 and R 3 is deuterium and the other of R 2 and R 3 is C 1-6 alkyl.
6. The pharmaceutical composition of claim 1 , wherein each of R 2 and R 3 is independently —C 1-6 alkyl.
7. The pharmaceutical composition of claim 1 , wherein each of R 2 and R 3 is independently isopropyl, —CH 3 , or —CF 3 .
8. The pharmaceutical composition of claim 1 , wherein R 4 is hydrogen.
9. The pharmaceutical composition of claim 1 , wherein n is 1.
10. The pharmaceutical composition of claim 1 , wherein n is 2.
11. The pharmaceutical composition of claim 1 , wherein represents a single bond.
12. The pharmaceutical composition of claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-A):
or a pharmaceutically acceptable salt thereof.
13. The pharmaceutical composition of claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-B):
or a pharmaceutically acceptable salt thereof.
14. The pharmaceutical composition of claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-C):
or a pharmaceutically acceptable salt thereof.
15. The pharmaceutical composition of claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-D):
or a pharmaceutically acceptable salt thereof.
16. The pharmaceutical composition of claim 1 , wherein the compound of Formula (I) is selected from the group consisting of:
17. A method of inducing sedation or anesthesia comprising administering to a subject an effective amount of the pharmaceutical composition of claim 1 .
18. A method for treating a disorder selected from the group consisting of irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and colitis, the method comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of claim 1 .
19. The method according to claim 18 , wherein the disorder is inflammatory bowel disease.
20. A method for treating a CNS-related condition selected from the group consisting of anxiety disorder, eating disorder, sleep disorder, multiple sclerosis, pain, vision impairment, hearing loss, and tinnitus, the method comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of claim 1 .
21. A method for treating Smith-Lemli-Opitz Syndrome (SLOS), Desmosterolosis, Sitosterolemia, Cerebrotendinous xanthomatosis (CTX), Mevalonate Kinase Deficiency Syndromes (MKD), SC4MOL gene mutation (SMO Deficiency), Niemann-Pick disease, or autism disorders associated with phenylketonuria, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of claim 1 .
22. The pharmaceutical composition of claim 1 , wherein the compound of Formula (I) is a pharmaceutically acceptable salt of