Compositions and methods for treating CNS disorders

Patent metadata

Field	Value
Publication number	US-11147877-B2
Application number	US-201916545727-A
Country	US
Kind code	B2
Filing date	Aug 20, 2019
Priority date	Jan 26, 2015
Publication date	Oct 19, 2021
Grant date	Oct 19, 2021

Abstract

Described herein are neuroactive steroids of the Formula (I):

or a pharmaceutically acceptable salt thereof; wherein , A, R 1 , R 2 , and R 3 are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use, e.g., for treating a subject suffering from a disease or disorder described herein.

First claim

What is claimed is:

1. A method of therapeutic treatment for a CNS-related disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I-c):

wherein:
n is 0, 1, 2, 3, 4, or 5;
Ring A is aryl or heteroaryl;
R 3A is C 1-6 alkyl;
R 1 is hydrogen, C 1-3 alkyl, C 2-6 alkenyl, or C 3-6 carbocyclyl;
R 2 is absent or hydrogen;
R a is halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, —C(O)R A , —C(O)OR A , —C(O)NR B R C , —S(O) 2 R D , or —OR Y , wherein R Y is hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, —C(O)R A , —C(O)OR A , —C(O)NR B R C , or —S(O) 2 R D ;
R A is hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
each of R B and R C is independently hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, or taken together with the atom to which they are attached form a ring; and
R D is hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl, wherein the CNS-related disorder is selected from epilepsy, status epilepticus, depression, and tremor.

2. The method of claim 1 , wherein the compound of Formula (I-c) is a compound of Formula (I-c-i), (I-c-ii), (I-c-iii), or (I-c-iv):

3. The method of claim 1 , wherein the compound of Formula (I-c) is selected from

4. The method of claim 1 , wherein the compound is administered orally.

5. The method of claim 1 , wherein the compound is administered intramuscularly.

6. The method of claim 1 , wherein the CNS-related disorder is depression, and wherein the depression is postpartum depression.

7. The method of claim 1 , wherein the CNS-related disorder is tremor, and wherein the tremor is essential tremor.

8. A method of inducing sedation and/or anesthesia in a subject, comprising administering to the subject an effective amount of a compound of Formula (I-c):

wherein:
n is 0, 1, 2, 3, 4, or 5;
Ring A is aryl or heteroaryl;
R 3A is C 1-6 alkyl;
R 1 is hydrogen, C 1-3 alkyl, C 2-6 alkenyl, or C 3-6 carbocyclyl;
R 2 is absent or hydrogen;
R a is halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, —C(O)R A , —C(O)OR A , —C(O)NR B R C , —S(O) 2 R D , or —OR Y , wherein R Y is hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, —C(O)R A , —C(O)OR A , —C(O)NR B R C , or —S(O) 2 R D ;
R A is hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
each of R B and R C is independently hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, or taken together with the atom to which they are attached form a ring; and
R D is hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl, wherein the compound is administered orally or intramuscularly.

9. The method of claim 8 , wherein the compound of Formula (I-c) is a compound of Formula (I-c-i), (I-c-ii), (I-c-iii), or (I-c-iv):

10. The method of claim 8 , wherein the compound of Formula (I-c) is selected from

11. The method of claim 8 , wherein the compound is administered orally.

12. The method of claim 8 , wherein the compound is administered intramuscularly.

Assignees

• Sage Therapeutics Inc

Inventors

• Robichaud Albert Jean
• Martinez Botella Gabriel
• Salituro Francesco G
• Harrison Boyd L

Classifications

• C07J7/007

  not substituted in position 17 alfa · CPC title

• C07J7/009

  by only one oxygen atom doubly bound · CPC title

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P25/22

  Anxiolytics · CPC title

• C07J13/007

  with double bond in position 17 (20) · CPC title