C7 substituted oxysterols and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11926646-B2
Application number	US-202117476153-A
Country	US
Kind code	B2
Filing date	Sep 15, 2021
Priority date	Sep 30, 2016
Publication date	Mar 12, 2024
Grant date	Mar 12, 2024

Abstract

Compounds are provided according to Formula (A):

and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R 1A , R 1B , n, R 2A , R 2B , R 3 , and R 4 are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

First claim

What is claimed is:

1. A method of treating a CNS-related condition, wherein the CNS-related condition is related to NMDA-modulation and is selected from the group consisting of an adjustment disorder, anxiety disorder, cognitive disorder, dissociative disorder, eating disorder, mood disorder, schizophrenia or other psychotic disorder, sleep disorder, substance-related disorder, personality disorder, autism spectrum disorders, neurodevelopmental disorder, multiple sclerosis, sterol synthesis disorders, pain, encephalopathy secondary to a medical condition, seizure disorder, stroke, traumatic brain injury, movement disorder, vision impairment, hearing loss, or tinnitus, comprising administering to a subject in need thereof an effective amount of a compound of Formula (B):

or a pharmaceutically acceptable salt thereof, wherein:
each of R 1a and R 1B is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, wherein the carbocyclyl may be saturated or partially saturated, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or R 1A and R 1B , together with the carbon atom to which they are attached form a 3-8 membered ring;
n is 1 or 2;
each of R 2A and R 2B is independently hydrogen, halo, —OR C , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, wherein R C is hydrogen or substituted or unsubstituted alkyl, or R 2A and R 2B , together with the carbon atom to which they are attached form an oxo group, wherein R 2A and R 2B are not both simultaneously hydrogen;
R 3 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or —OR A , wherein R A is substituted or unsubstituted alkyl;
R 4 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 4 is hydrogen; and when one of the is a double bond, R 4 is absent, or
a pharmaceutical composition comprising said compound of Formula (B) or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

2. The method according to claim 1 , wherein n is 1.

3. The method according to claim 1 , where n is 2.

4. The method according to claim 1 , wherein each of R 1A and R 1B is independently unsubstituted or substituted alkyl.

5. The method according to claim 1 , wherein each of R 1A and R 1B is independently selected from the group consisting of haloalkyl, alkoxyalkyl, —CH 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , —CF 3 and —CH 2 OCH 3 .

6. The method according to claim 1 , wherein R 1A and R 1B , together with the carbon atom to which they are attached form a 3-8 membered ring.

7. The method according to claim 1 , wherein R 1A is hydrogen and R 1B is alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl.

8. The method according to claim 1 , wherein each of R 2A and R 2B is independently substituted or unsubstituted alkyl.

9. The method according to claim 1 , wherein R 3 is substituted or unsubstituted alkyl.

10. The method according to claim 1 , wherein the compound is selected from the group consisting of

11. The method according to claim 1 , wherein the compound is a pharmaceutically acceptable salt of a compound selected from the group consisting of:

Assignees

• Sage Therapeutics Inc

Inventors

• Salituro Francesco G
• Robichaud Albert Jean
• Martinez Botella Gabriel
• Griffin Andrew
• Harrison Boyd L
• La Daniel

Classifications

• C07J31/006 Primary

  not covered by C07J31/003 · CPC title

• C07J9/005

  containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton · CPC title

• C07J9/00 Primary

  Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane · CPC title

• C07J7/002

  not substituted in position 16 · CPC title

• C07J41/0061

  one of the carbon atoms being part of an amide group · CPC title