COMT Inhibiting Methods and Compositions

Abstract

This invention relates to compounds, pharmaceutical compositions and their use for treating neuropsychiatric and neurodegenerative disorders. In particular, the invention relates to inhibitors of catechol-O-methyltransferase and their use as therapeutics for central nervous system disease.

1 . A compound of formula I, or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         X is selected from hydrogen; chloro; bromo, iodo and cyclopropyl; 
         Z is selected from hydrogen and fluoro; 
         R 1  and R 2  are each independently selected from hydrogen; C 1-4  alkyl; aryl; substituted aryl; arylalkyl and heterocycle; 
         R 3  and R 4  are each independently selected from hydrogen; C 1 -C 4  alkyl; aryl and arylalkyl; 
         R 5  is selected from aryl, heteroaryl, heterocycle, C 1 -C 10  alkyl or C 1 -C 10  cycloaklyl, optionally substituted with one or more groups selected from hydrogen; mono-, di-, or trihalomethyl; C 1 -C 4  alkyl; C 3 -C 10  cycloalkyl; halo; heteroaryl; cyano; nitro; aryloxy; 
         aryl; alkoxy; arylalkoxy and NHC(O)R, wherein R is C 1 -C 4  alkyl; and 
         Y is (CR 6 R 7 ) n , wherein n is from 0-3, and R 6  and R 7  are independently selected from hydrogen; 
         C 1 -C 6  alkyl; C 3 -C 5  cycloalkyl; C 1 -C 4  alkylhydroxyl; mono- di-, or trihaloalkyl; and aryl; R 6  and R 7  may also come together to form a C 3 -C 6  cycloalkyl; or 
         when R 5  is phenyl, one of R 6  or R 7  comes together with R 5  to form a bicycle