Compositions and methods for treating CNS disorders

Patent metadata

Field	Value
Publication number	US-10426837-B2
Application number	US-201715660114-A
Country	US
Kind code	B2
Filing date	Jul 26, 2017
Priority date	Jan 26, 2015
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

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 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.

2. The compound 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 compound of claim 2 , wherein the compound of Formula (I-c) is selected from the group consisting of:

4. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.

5. A method of inducing sedation and/or anesthesia in a human subject in need thereof, comprising administering to the human subject a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the human subject experiences sedation and/or anesthesia within two hours of administration.

6. The method of claim 5 , wherein the subject experiences sedation and/or anesthesia within one hour of administration.

7. The method of claim 5 , wherein the subject experiences sedation and/or anesthesia instantaneously.

8. The method of claim 5 , wherein the compound is administered by intravenous administration.

9. The method of claim 5 , wherein the compound is administered chronically.

10. The method of claim 5 , wherein the compound is administered in combination with another therapeutic agent.

Assignees

• Sage Therapeutics Inc

Inventors

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

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P27/16

  Otologicals · CPC title

• A61P25/30

  for treating abuse or dependence · CPC title

• A61P25/28

  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 · CPC title