Neuroactive substituted cyclopent[a]anthracenes as modulators for GABA type-A receptors

Patent metadata

Field	Value
Publication number	US-9562026-B2
Application number	US-201414203678-A
Country	US
Kind code	B2
Filing date	Mar 11, 2014
Priority date	Mar 14, 2013
Publication date	Feb 7, 2017
Grant date	Feb 7, 2017

Abstract

The present disclosure is generally directed to neuroactive substituted cyclopent[a]anthracenes 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,
R 2 is H,
R 3 is H, ═O, ═CHCN, ═CHCO 2 R t , where R t is optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituded C 2 -C 4 alkynyl, —CN, β-OH, β-OR s , where R s is optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituted C 2 -C 4 alkynyl, β-NO 2 , spiroepoxy, or C(O)R r , where R r is optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituted C 2 -C 4 alkynyl;
R 4 is methyl;
R 5 is H,
R 6 is H,
R 7 is H,
R 8 is H,
R 9 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 10 is H,
R 11 is H or C(O)R e , where R e is optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl, or optionally substituted C 2 -C 20 alkynyl; and,
- - - denotes an optional double bond with the proviso that when present R 3 is not ═O, ═CHCN or ═CHCO 2 R t .

2. The compound of claim 1 , wherein R 11 is H.

3. The compound of claim 1 , wherein R 3 is ═O.

4. The compound of claim 1 , wherein R 3 is spiroepoxy.

5. The compound of claim 1 , wherein R 3 is β-CN.

6. The compound of claim 1 , wherein a double bond is present between C 2 -C 3 .

7. The compound of claim 6 , wherein R 3 is —CN.

8. The compound of claim 1 , having the structure (I-a):

wherein R 3 is ═O, ═CHCN, ═CHCO 2 R t , where R t is optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituted C 2 -C 4 alkynyl, —CN, β-OH, β-OR s , where R s is optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituted C 2 -C 4 alkynyl, β-NO 2 , spiroepoxy, or C(O)R r , where R r is optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 4 alkenyl, or optionally substituted C 2 -C 4 alkynyl; and,
- - - denotes an optional double bond, with the proviso that when present, R 3 is not ═O, ═CHCN or ═CHCO 2 R t .

9. The compound of claim 1 having the structure:

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1 having the structure:

or a pharmaceutically acceptable salt thereof.

11. The compound of claim 1 having the structure:

or a pharmaceutically acceptable salt thereof.

12. The compound of claim 1 having the structure:

or a pharmaceutically acceptable salt thereof.

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

14. A method of inducing anesthesia in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof.

Assignees

• Univ Washington

Inventors

• Covey Douglas

Classifications

• C07C2603/42

  containing only six-membered rings · CPC title

• C07C2603/40

  containing four condensed rings · CPC title

• C07C49/423

  a keto group being part of a condensed ring system · CPC title

• C07D303/14 Primary

  by free hydroxyl radicals · CPC title

• C07C49/513

  a keto group being part of a condensed ring system · CPC title