US 12,448,409 B2
Oxysterols and methods of use thereof
Albert Jean Robichaud, Boston, MA (US); Francesco G. Salituro, Marlborough, MA (US); Gabriel Martinez Botella, Wayland, MA (US); Boyd L. Harrison, Princeton Junction, NJ (US); and John Gregory Reid, Wellington, FL (US)
Assigned to Sage Therapeutics, Inc., Cambridge, MA (US)
Filed by Sage Therapeutics, Inc., Cambridge, MA (US)
Filed on Dec. 11, 2023, as Appl. No. 18/535,256.
Application 18/535,256 is a division of application No. 17/242,860, filed on Apr. 28, 2021, granted, now 11,884,697.
Application 17/242,860 is a continuation of application No. 16/089,896, abandoned, previously published as PCT/US2017/025535, filed on Mar. 31, 2017.
Claims priority of provisional application 62/317,002, filed on Apr. 1, 2016.
Prior Publication US 2024/0270784 A1, Aug. 15, 2024
Int. Cl. A61K 31/57 (2006.01); C07J 9/00 (2006.01); C07J 17/00 (2006.01); C07J 43/00 (2006.01)
CPC C07J 9/00 (2013.01) [A61K 31/57 (2013.01); C07J 17/00 (2013.01); C07J 43/003 (2013.01)] 17 Claims
 
1. A method of:
a) inducing sedation or anesthesia;
b) treating a disorder, wherein the disorder is a gastrointestinal (GI) disorder, structural disorders affecting the GI, anal disorders, colon polyps, diabetes, a sterol synthesis disorder, colitis, inflammatory bowel disease, or a metabolic disorder;
c) treating a CNS-related condition, wherein the CNS-related condition is an adjustment disorder, an anxiety disorder, a cognitive disorder, a dissociative disorder, an eating disorder, a mood disorder, a bipolar disorder, a dysthymic disorder, suicidality, schizophrenia or another psychotic disorder, a sleep disorder, a substance-related disorder, a personality disorder, an autism spectrum disorder, a neurodevelopmental disorder, multiple sclerosis, a sterol synthesis disorder, pain, an encephalopathy secondary to a medical condition, a seizure disorder, stroke, traumatic brain injury, a movement disorder, vision impairment, hearing loss, or tinnitus; and
d) 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 a compound of Formula (I-B):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R1 is hydrogen or substituted or unsubstituted C1-6 alkyl;
R5 is absent or hydrogen;
Z is —C(RA)2—,—NRB—,—O—, or —S—;
X is halogen, substituted or unsubstituted C1-6 alkyl, or —ORC;
RA is hydrogen, halogen, or substituted or unsubstituted C1-6 alkyl;
RB is hydrogen, substituted or unsubstituted C1-6 alkyl, —C(O)RC, —C(O)ORC,—C(O)N(RD)2, or -S(O)2RC;
RC is hydrogen or substituted or unsubstituted C1-6 alkyl;
each RD is independently hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted 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
custom characterrepresents a single or double bond, wherein when one custom characteris a double bond, then the other custom characteris a single bond and R5 is absent,
or a pharmaceutical composition comprising said compound or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.