Neuroactive 13, 17-substituted steroids as modulators for GABA type-A receptors

Patent metadata

Field	Value
Publication number	US-10160783-B2
Application number	US-201615333921-A
Country	US
Kind code	B2
Filing date	Oct 25, 2016
Priority date	Mar 1, 2013
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

The present disclosure is generally directed to neuroactive 13, 17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds.

First claim

What is claimed is:

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof;
wherein:
R 1 is H, optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituted C 2 -C 4 alkynyl;
R 2 is H, optionally substituted C 1 -C 4 alkoxy, aryloxy, optionally substituted C 2 -C 4 alkenoxy, optionally substituted C 2 -C 4 alkynoxy, or —O—C(O)—R x , where R x is optionally substituted C 1 -C 20 alkyl;
R 3 is CH═CH 2 , ethyl, CH(OH)CH 3 , CH 2 Cl, or CH 2 OH;
R 4 is optionally substituted C 2 -C 4 alkenyl, optionally substituted C 2 -C 4 alkynyl, optionally substituted cyclopropyl, or C(O)R z , where R z is C 1 -C 4 alkyl, C 2 -C 4 alkenyl or C 2 -C 4 alkynyl;
R 5 is H, ═O, or OR v , where R v is H, optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, optionally substituted C 2 -C 4 alkynyl, or optionally substituted aryl;
R 6 is H, optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituted C 2 -C 4 alkynyl;
R 7 is H, optionally substituted C 1 -C 4 alkoxy, aryloxy, morpholinyl, optionally substituted C 2 -C 4 alkenoxy, optionally substituted C 2 -C 4 alkynoxy, or —O—C(O)—R w , where R w is optionally substituted C 1 -C 20 alkyl;
R 8 is, when present, H, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, or C 2 -C 4 alkynyl;

R 9 is H or C(O)R u , where R u is optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl, or optionally substituted C 2 -C 20 alkynyl and,
wherein the C 5 —H is in the alpha configuration.

2. The compound of claim 1 , wherein R 9 is H.

3. The compound of claim 1 , wherein R 2 is H or —OCH 3 .

4. The compound of claim 1 , wherein R 5 is H or —OCH 3 .

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

6. The compound of claim 1 , wherein R 7 is H or —OCH 3 .

7. The compound of claim 1 , wherein R 4 is —CH═CH 2 or —C(O)CH 3 .

8. The compound of claim 1 , wherein R 1 is H.

9. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

10. A pharmaceutically acceptable salt of a compound of claim 1 .

11. A pharmaceutical composition comprising a compound of claim 1 , a pharmaceutically acceptable salt thereof, or a combination of two or more thereof, and a pharmaceutically acceptable carrier.

Assignees

• Univ Washington

Inventors

• Covey Douglas
• Jiang Xin

Classifications

• C07J7/007

  not substituted in position 17 alfa · CPC title

• C07J7/0005

  not substituted in position 21 · CPC title

• C07J71/0026 Primary

  cyclic ketals · CPC title

• C07J1/0011

  substituted in position 17 by a keto group · CPC title

• C07J21/008

  at position 17 · CPC title