Dimethoxyphenyl inhibitors of vesicular monoamine transporter 2

Patent metadata

Field	Value
Publication number	US-10722479-B2
Application number	US-201615550152-A
Country	US
Kind code	B2
Filing date	Feb 17, 2016
Priority date	Feb 18, 2015
Publication date	Jul 28, 2020
Grant date	Jul 28, 2020

Abstract

Described are dimethoxyphenyl inhibitors of VMAT2, pharmaceutical compositions thereof, and methods of use thereof.

First claim

What is claimed is:

1. A compound of Formula I:

or a salt thereof, wherein:
R 1 -R 2 and R 21 are independently —CH 3 , —CH 2 D, —CD 2 H, or —CD 3 ; and
(i) R 6 and R 7 are deuterium; and
R 3 -R 5 and R 8 -R 20 are, independently, hydrogen or deuterium; or

(ii) R 8 and R 9 are deuterium; and
R 3 -R 7 and R 10 -R 20 are, independently, hydrogen or deuterium; or

(iii) R 6 -R 9 are deuterium; and
R 3 -R 5 and R 10 -R 20 are, independently, hydrogen or deuterium; or

(iv) R 11 and R 12 are deuterium; and
R 3 -R 10 and R 13 -R 20 are, independently, hydrogen or deuterium; or

(v) R 13 is deuterium; and
R 3 -R 12 and R 14 -R 20 are, independently, hydrogen or deuterium; or

(vi) R 15 and R 16 are deuterium; and
R 3 -R 14 and R 17 -R 20 are, independently, hydrogen or deuterium; and

at least one of the deuteriums has a deuterium enrichment of no less than about 10%.

2. The compound as recited in claim 1 wherein R 10 and R 14 are hydrogen.

3. The compound as recited in claim 1 wherein R 1 is CD 3 .

4. The compound as recited in claim 1 wherein R 2 is CD 3 .

5. The compound as recited in claim 1 wherein R 21 is CD 3 .

6. The compound as recited in claim 1 wherein R 6 and R 7 are deuterium.

7. The compound as recited in claim 1 wherein R 8 and R 9 are deuterium.

8. The compound as recited in claim 1 wherein R 6 -R 9 are deuterium.

9. The compound as recited in claim 1 wherein R 11 and R 12 are deuterium.

10. The compound as recited in claim 1 wherein R 13 is deuterium.

11. The compound as recited in claim 1 wherein R 15 and R 16 are deuterium.

12. The compound as recited in claim 1 wherein the compound is

Assignees

• Auspex Pharmaceuticals Inc

Inventors

• Zhang Chengzhi

Classifications

• C07B59/001

  Acyclic or carbocyclic compounds · CPC title

• A61K31/138

  Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377) · 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

• A61P21/02

  Muscle relaxants, e.g. for tetanus or cramps · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title