# US 2024/0199682 A1 · Oxysterols and methods of use thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2024/0199682 A1
- Document ID: US20240199682A1
- Status: Published application
- Kind: A1
- Application number: 18/388,390
- Filed: 2023-11-09
- Published: 2024-06-20
- Earliest claimed: 2016-10-18
- Assignees: Sage Therapeutics, Inc.
- Applicants: Sage Therapeutics, Inc.
- Inventors: Francesco G. Salituro; Albert Jean Robichaud; Gabriel Martinez Botella; Boyd L. Harrison; Andrew Griffin
- Web page: https://patentgrep.com/patent/US20240199682A1

## CPC

- C07J 9/00: 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
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/22: Anxiolytics
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 35/00: Antineoplastic agents
- C07J 17/00: Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton (cardanolide, bufanolide C07J19/00)
- C07J 43/003: {not condensed}
- C07J: STEROIDS (seco-steroids C07C)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, wherein R2, R3, R4, R5, and and R6 are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

## Claims

### Claim 1

A compound of Formula (I-59):
or a pharmaceutically acceptable salt thereof, wherein:
each of R2 and R3 is independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, or
R2 and R3, together with the carbon atom to which they are attached form a substituted or unsubstituted 3-8 membered ring;
each of R4 and R5 is independently hydrogen, halo, or —ORC, wherein RC is hydrogen or substituted or unsubstituted C1-C6 alkyl, or
R4 and R5, together with the carbon atom to which they are attached form an oxo group;
R6 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 R6 is hydrogen; and when one of is a double bond, R6 is absent;
provided that the following compounds are excluded:

### Claim at position 2

-53. (canceled)

### Claim 54 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is:

### Claim 55 (depends on 1)

A pharmaceutical composition comprising the compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

### Claim 56 (depends on 1)

A method for treating a disorder, comprising administering to a subject in need thereof an effective amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, wherein the disorder is a gastrointestinal (GI) disorder, constipation, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, a structural disorder affecting the GI tract, an anal disorder, hemorrhoids, internal hemorrhoids, external hemorrhoids, anal fissures, perianal abscesses, an anal fistula, colon polyps, cancer, colitis, diabetes, a sterol synthesis disorder, a metabolic disorder, an autoimmune disorder, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, or plaque psoriasis.

### Claim at position 6

-62. (canceled)

### Claim 63 (depends on 1)

A method for treating a CNS-related condition comprising administering to a subject in need thereof an effective amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, wherein the CNS-related condition is an adjustment disorder, an anxiety disorder, a cognitive disorder, a dissociative disorder, an eating disorder, a mood disorder, 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.

### Claim at position 8

-96. (canceled)

### Claim 97

A compound of Formula (I-61):
or a pharmaceutically acceptable salt thereof, wherein:
R1 is hydrogen or substituted or unsubstituted C1-C6 alkyl;
each of R2 and R3 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl or
R2 and R3, together with the carbon atom to which they are attached for a 3-8 substituted or unsubstituted membered ring;
each of R4 and R5 is independently hydrogen, halo, or —ORC, wherein RC is hydrogen or substituted or unsubstituted C1-C6 alkyl, or
R4 and R5, together with the carbon atom to which they are attached form an oxo group;
R6 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 R6 is hydrogen; and when one of is a double bond, R6 is absent;
provided that the following compounds are excluded:

### Claim at position 10

-136. (canceled)

### Claim 137 (depends on 97)

The compound of claim 97, or a pharmaceutically acceptable salt thereof, wherein the compound is:

### Claim 138 (depends on 97)

A pharmaceutical composition comprising the compound of claim 97, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

### Claim 139 (depends on 97)

A method for treating a disorder, comprising administering to a subject in need thereof an effective amount of the compound of claim 97, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, wherein the disorder is a gastrointestinal (GI) disorder, constipation, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, a structural disorder affecting the GI tract, an anal disorder, hemorrhoids, internal hemorrhoids, external hemorrhoids, anal fissures, perianal abscesses, an anal fistula, colon polyps, cancer, colitis, diabetes, a sterol synthesis disorder, a metabolic disorder, an autoimmune disorder, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, or plaque psoriasis.

### Claim at position 14

-145. (canceled)

### Claim 146 (depends on 97)

A method for treating a CNS-related condition comprising administering to a subject in need thereof an effective amount of the compound of claim 97, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, wherein the CNS-related condition is an adjustment disorder, an anxiety disorder, a cognitive disorder, a dissociative disorder, an eating disorder, a mood disorder, 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.

### Claim at position 16

-148. (canceled)

### Claim 149

A compound of Formula (I-62):
or a pharmaceutically acceptable salt thereof, wherein:
R1 is hydrogen or substituted or unsubstituted C1-C6 alkyl;
each of R2 and R3 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl or
R2 and R3, together with the carbon atom to which they are attached, form a 3-8 substituted or unsubstituted membered ring;
each of R4 and R5 is independently hydrogen, halo, or —ORC, wherein RC is hydrogen or substituted or unsubstituted C1-C6 alkyl, or
R4 and R5, together with the carbon atom to which they are attached form an oxo group;
R6 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 R6 is hydrogen; and when one of is a double bond, R6 is absent.

### Claim at position 18

-176. (canceled)

### Claim 177 (depends on 149)

The compound of claim 149, or a pharmaceutically acceptable salt thereof, wherein the compound is

### Claim 178 (depends on 149)

A pharmaceutical composition comprising the compound of claim 149, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

### Claim 179 (depends on 149)

A method for treating a disorder, comprising administering to a subject in need thereof an effective amount of the compound of claim 149, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, wherein the disorder is a gastrointestinal (GI) disorder, constipation, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, a structural disorder affecting the GI tract, an anal disorder, hemorrhoids, internal hemorrhoids, external hemorrhoids, anal fissures, perianal abscesses, an anal fistula, colon polyps, cancer, colitis, diabetes, a sterol synthesis disorder, a metabolic disorder, an autoimmune disorder, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, or plaque psoriasis.

### Claim at position 22

-185. (canceled)

### Claim 186 (depends on 149)

A method for treating a CNS-related condition comprising administering to a subject in need thereof an effective amount of the compound of claim 149, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, wherein the CNS-related condition is an adjustment disorder, an anxiety disorder, a cognitive disorder, a dissociative disorder, an eating disorder, a mood disorder, 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.

### Claim at position 24

-188. (canceled)

### Claim 189

A compound of Formula (I-60):
or a pharmaceutically acceptable salt thereof, wherein:
each of R2 and R3 is independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or
R2 and R3, together with the carbon atom to which they are attached form a substituted or unsubstituted 3-8 membered ring;
each of R4 and R5 is independently hydrogen, halo, or —ORC, wherein RC is hydrogen or substituted or unsubstituted C1-C6 alkyl, or
R4 and R5, together with the carbon atom to which they are attached form an oxo group;
R6 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 R6 is hydrogen; and when one of the is a double bond, R6 is absent.

### Claim at position 26

-218. (canceled)

### Claim 219 (depends on 189)

The compound of claim 189, or a pharmaceutically acceptable salt thereof, wherein the compound is:

### Claim 220 (depends on 189)

A pharmaceutical composition comprising the compound of claim 189, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

### Claim 221 (depends on 189)

A method for treating a disorder, comprising administering to a subject in need thereof an effective amount of the compound of claim 189, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, wherein the disorder is a gastrointestinal (GI) disorder, constipation, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, a structural disorder affecting the GI tract, an anal disorder, hemorrhoids, internal hemorrhoids, external hemorrhoids, anal fissures, perianal abscesses, an anal fistula, colon polyps, cancer, colitis, diabetes, a sterol synthesis disorder, a metabolic disorder, an autoimmune disorder, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, or plaque psoriasis.

### Claim at position 30

-227. (canceled)

### Claim 228 (depends on 189)

A method for treating a CNS-related condition comprising administering to a subject in need thereof an effective amount of the compound of claim 189, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, wherein the CNS-related condition is an adjustment disorder, an anxiety disorder, a cognitive disorder, a dissociative disorder, an eating disorder, a mood disorder, 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.

### Claim at position 32

-230. (canceled)