Benzoquinoline inhibitors of vesicular monoamine transporter 2

Abstract

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier together with compounds of structural Formula I 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein:
 in each compound of Formula I, R 1 -R 27  are independently selected from the group consisting of hydrogen and deuterium; 
 the composition has deuterium enrichment of at least 10% at each of the positions R 1 -R 6  in the compounds of Formula I; 
 the positions R 7 -R 27  in the compounds of Formula I are not isotopically enriched; and 
 the pharmaceutical composition is an oral dosage form. 
 
       
     
     
         2 . The composition as recited in  claim 1  wherein R 1 -R 6  each have deuterium enrichment of no less than 50%. 
     
     
         3 . The composition as recited in  claim 1  wherein R 1 -R 6  each have deuterium enrichment of no less than 90%. 
     
     
         4 . The composition as recited in  claim 1  wherein R 1 -R 6  each have deuterium enrichment of no less than 98%. 
     
     
         5 . The pharmaceutical composition as recited in  claim 1 , wherein said oral dosage form is a tablet or capsule. 
     
     
         6 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier together with compounds of structural Formula I 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein:
 in each compound of Formula I, R 1 -R 27  are independently selected from the group consisting of hydrogen and deuterium; 
 the composition has deuterium enrichment of at least 10% at each of the positions R 1 -R 6  in the compounds of Formula I; 
 the positions R 7 -R 27  in the compounds of Formula I are not isotopically enriched; and 
 the pharmaceutical composition is a parenteral dosage form. 
 
       
     
     
         7 . The pharmaceutical composition as recited in  claim 6 , wherein said parenteral dosage form is formulated for intravenous dosage.