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 method of treatment of a chronic hyperkinetic movement disorder selected from the group consisting of Huntington's disease and chorea related to Huntington's disease comprising the administration of a therapeutically effective amount of a composition comprising 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 90% at each of the positions R 1 -R 6  in the compounds of Formula I; and 
         the positions R 7 -R 27  in the compounds of Formula I are not isotopically enriched. 
       
     
     
         2 . The composition as recited in  claim 1  wherein R 1 -R 6  each have deuterium enrichment of no less than 98%. 
     
     
         3 . The method as recited in  claim 1  wherein said chronic hyperkinetic movement disorder is Huntington's disease. 
     
     
         4 . The method as recited in  claim 1  wherein said chronic hyperkinetic movement disorder is chorea related to Huntington's disease. 
     
     
         5 . A method of treatment of a chronic hyperkinetic movement disorder selected from the group consisting of Huntington's disease and chorea related to Huntington's disease comprising the administration of a therapeutically effective amount of a compound having the structural formula: 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein each position represented as D has deuterium enrichment of no less than about 90%. 
       
     
     
         6 . The composition as recited in  claim 7  wherein each position represented as D has deuterium enrichment of no less than 98%. 
     
     
         7 . The method as recited in  claim 7  wherein said chronic hyperkinetic movement disorder is Huntington's disease. 
     
     
         8 . The method as recited in  claim 7  wherein said chronic hyperkinetic movement disorder is chorea related to Huntington's disease.