OXYSTEROLS AND METHODS OF USE THEREOF
Compounds are provided according to Formula (I), and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein A, R 1 , and R 5 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-A):
or a pharmaceutically acceptable salt thereof, wherein:
A is carbocyclyl or heterocyclyl;
R 1 is C 1-6 alkyl;
R 5 is absent or hydrogen;
represents a single or double bond, wherein when one is a double bond, then the other is a single bond and R 5 is absent.
2 . A compound of Formula (I-B):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is hydrogen or C 1-6 alkyl;
R 5 is absent or hydrogen;
Z is —C(R A ) 2 —, —NR B —, —O—, or —S—;
X is halogen, C 1-6 alkyl, or —OR C ;
R A is hydrogen, halogen, or C 1-6 alkyl;
R B is hydrogen, C 1-6 alkyl, —C(O)R C , —C(O)OR C , —C(O)N(R D ) 2 , or —S(O) 2 R C ;
R C is hydrogen or C 1-6 alkyl;
each R D is independently hydrogen, C 1-6 alkyl, aryl, or heteroaryl;
m is an integer selected from 1, 2, and 3;
n is an integer selected from 1, 2, and 3;
p is an integer selected from 0, 1, 2, 3, 4, and 5; and
represents a single or double bond, wherein when one is a double bond, then the other is a single bond and R 5 is absent.
3 . The compound of claim 2 , wherein the compound is a compound of Formula (II-A), Formula (II-B), or Formula (II-C):
4 - 7 . (canceled)
8 . The compound of claim 3 , wherein the compound is of Formula (II-D), Formula (II-E), or Formula (II-F):
9 - 11 . (canceled)
12 . The compound of claim 2 , wherein the compound is of Formula (II-G) or Formula (II-H):
13 . The compound of claim 2 , wherein the compound is of Formula (II-I) or Formula (II-J):
14 - 26 . (canceled)
27 . The compound of claim 2 , wherein the compound is selected from the group consisting of:
28 . A pharmaceutically acceptable salt of the compound of claim 2 , wherein the compound is selected from the group consisting of:
29 . A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier.
30 . A method of inducing sedation or anesthesia comprising administering to a subject an effective amount of a compound according to claim 1 or pharmaceutical composition thereof.
31 . A method for treating or preventing a disorder described herein, comprising administering to a subject in need thereof an effective amount of a compound according to claim 1 or pharmaceutical composition thereof.
32 . The method according to claim 31 , wherein the disorder is a gastrointestinal (GI) disorder, structural disorders affecting the GI, anal disorders, colon polyps, cancer, colitis.
33 . The method according to claim 31 , wherein the disorder is inflammatory bowel disease.
34 . The method according to claim 31 , wherein the disorder is cancer, diabetes, or a sterol synthesis disorder.
35 . The method according to claim 31 , wherein the disorder is a metabolic disorder.
36 . A method for treating or preventing a CNS-related condition comprising administering to a subject in need thereof an effective amount of a compound according to claim 1 or pharmaceutical composition thereof.
37 - 38 . (canceled)
39 . A method for treating or preventing Smith-Lemli-Opitz Syndrome (SLOS), Desmosterolosis, Sitosterolemia, Cerebrotendinous xanthomatosis (CTX), Mevalonate Kinase Deficiency Syndromes (MKD), SC4MOL gene mutation (SMO Deficiency), Niemann-Pick disease, Autism Disorders Associated with Phenylketonuria, comprising administering to a subject in need thereof an effective amount of a compound according to claim 1 or pharmaceutical composition thereof.