Granted Patent B2

US 12,448,409 · App. 18/535,256 · Granted Oct 21, 2025

Inventors: Albert Jean Robichaud (Boston, MA); Francesco G. Salituro (Marlborough, MA); Gabriel Martinez Botella (Wayland, MA); Boyd L. Harrison (Princeton Junction, NJ); John Gregory Reid (Wellington, FL)

Assignee: Sage Therapeutics, Inc.

C07J9/00A61K31/57C07J17/00C07J43/003

Abstract

Claims (40)

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), SC 4 MOL 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):

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is hydrogen or substituted or unsubstituted C 1-6 alkyl;

R 5 is absent or hydrogen;

Z is —C(R A ) 2 —,—NR B —,—O—, or —S—;

X is halogen, substituted or unsubstituted C 1-6 alkyl, or —OR C ;

R A is hydrogen, halogen, or substituted or unsubstituted C 1-6 alkyl;

R B is hydrogen, substituted or unsubstituted 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 substituted or unsubstituted C 1-6 alkyl;

each R D is independently hydrogen, substituted or unsubstituted C 1-6 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

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,

or a pharmaceutical composition comprising said compound or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

2. The method of claim 1 , wherein the compound is a compound of Formula (II-A), Formula (II-B), or Formula (II-C):

or a pharmaceutically acceptable salt thereof.

3. The method of claim 1 , wherein p is an integer selected from 0, 1, or 2.

4. The method of claim 2 , wherein the compound is of Formula (II-D), Formula (II-E), or Formula (II-F):

or a pharmaceutically acceptable salt thereof.

5. The method of claim 1 , wherein R 1 is substituted or unsubstituted C 1-6 alkyl.

6. The method of claim 5 , wherein R 1 is —CH 3 or —CH 2 CH 3 .

7. The method of claim 1 , wherein the compound is of Formula (II-G) or Formula (II-H):

or a pharmaceutically acceptable salt thereof.

8. The method of claim 1 , wherein the compound is of Formula (II-I) or Formula (II-J):

or a pharmaceutically acceptable salt thereof.

9. The method of claim 1 , wherein Z is —CH 2 —,—CF 2 —, or —C(CH 3 ) 2 —.

10. The method of claim 1 , wherein Z is —NH—,—NCH 3 —, or —NC(O)CH 3 —.

11. The method of claim 1 , wherein m is 1, n is 2, and Z is —O—.

12. The method of claim 1 , wherein m is 2 and n is 2.

13. The method of claim 1 , wherein m is 3 and n is 1.

14. The method of claim 1 , wherein m is 3, n is 1, and Z is —O—.

15. The method of claim 1 , wherein m is 2, n is 2, and Z is —O— or —NR B —.

16. The method of claim 1 , wherein the compound is selected from the group consisting of:

17. The method of claim 1 , wherein the pharmaceutically acceptable salt is a pharmaceutically acceptable salt of:

Assignments (1)

Continuity (4)

References Cited (329)