Neuroactive 19-alkoxy-17-substituted steroids, prodrugs thereof, and methods of treatment using same

Patent metadata

Field	Value
Publication number	US-9630986-B2
Application number	US-201314132386-A
Country	US
Kind code	B2
Filing date	Dec 18, 2013
Priority date	Dec 18, 2012
Publication date	Apr 25, 2017
Grant date	Apr 25, 2017

Abstract

The present disclosure is generally directed to neuroactive 19-alkoxy-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-g):

or a pharmaceutically acceptable salt thereof;
wherein:
R 1 is selected from (C 1 -C 4 alkyl)-O, spirooxirane, cyano, ═O, nitro, (C 1 -C 4 alkyl)C(O), and HO(C 1 -C 4 alkyl)C(O);
R 2 is ═O, H, or OR a , where R a is selected from H, optionally substituted C 1 -C 4 alkyl, or optionally substituted aryl, with the proviso that when R 2 is ═O, R 8 is not present;
R 3 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 b is methyl;
R 8 , when present, is H or optionally substituted C 1 -C 4 alkyl;

- - - denotes an optional, additional C—C bond, resulting in a C═C bond between C 16 -C 17 , with the proviso that when present, the R 1 is not ═O or spirooxirane.

2. The compound of claim 1 , wherein the R 3 group is selected from the group consisting of H, methyl, and trifluoromethyl.

3. The compound of claim 1 , wherein R 2 is ═O, methoxy or H.

4. The compound of claim 1 , wherein R 1 is beta-cyano.

5. The compound of claim 1 selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

6. The compound of claim 1 , wherein
R 1 is selected from (C 1 -C 4 alkyl)-O, spirooxirane, cyano, ═O, (C 1 -C 4 alkyl)C(O), and HO(C 1 -C 4 alkyl)C(O).

7. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

8. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

9. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

10. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

11. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

12. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising a compound of formula:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

14. A pharmaceutical composition comprising a compound of formula:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

15. A pharmaceutical composition comprising a compound of formula:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

16. A pharmaceutical composition comprising a compound of formula:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

17. A pharmaceutical composition comprising a compound of formula:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

18. A pharmaceutical composition comprising a compound of formula:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

Assignees

• Univ Washington
• Sage Therapeutics Inc

Inventors

• Covey Douglas
• Robichaud Albert Jean

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P43/00

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

• A61P25/20

  Hypnotics; Sedatives · CPC title

• A61P25/32

  Alcohol-abuse · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title