SUBSTITUTED 3-ISOBUTYL-9,10-DIMETHOXY-1,3,4,6,7,11B-HEXAHYDRO-2H-PYRIDO[2,1-A]ISOQUIN-OLIN-2-OL COMPOUNDS AND METHODS RELATING THERETO

• US 20080167337A1
• Filed: 11/08/2007
• Published: 07/10/2008
• Est. Priority Date: 11/08/2006
• Status: Active Grant

• Current Assignee: Neurocrine Biosciences Inc.
• Original Assignee: Neurocrine Biosciences Inc.
• Inventors: Gano, Kyle W.
• Granted Patent: US 8,039,627 B2
• Time in Patent Office: Days
• US Class Current: 514/294
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Substituted 3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol compounds are disclosed that are inhibitors of the vesicular monoamine transporter 2 (VMAT2). The compounds of this invention have the structure:

wherein R₁ is as defined herein, including stereoisomers and pharmaceutically acceptable salts and solvates thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use in a subject in need thereof.

Claims

1. 2-Amino-3-methyl-butyric acid-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester or a stereoisomer, pharmaceutically acceptable salt or solvate thereof.

2. A compound of claim 1 wherein the compound is 2-Amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester or a stereoisomer, pharmaceutically acceptable salt or solvate thereof.

3. A compound of claim 1 wherein the compound is (S)-2-Amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester or a stereoisomer, pharmaceutically acceptable salt or solvate thereof.

4. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or diluent.

5. A pharmaceutical composition of claim 4 wherein the compound is (S)-2-Amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester or a stereoisomer, pharmaceutically acceptable salt or solvate thereof.

6. A method of treating hyperkinetic disorders comprising administering to a subject in need thereof a pharmaceutically effective amount of a pharmaceutical composition according to claim 4.

7. A method according to claim 6 wherein the hyperkinetic disorder is Huntington'"'"'s disease, tardive dyskinesia, Tourette'"'"'s syndrome or tics.