Azacyclic compounds

Abstract

Compounds and methods are provided for the treatment of disease conditions in which modification of serotonergic receptor activity has a beneficial effect. In the method, an effective amount of a compound is administered to a patient in need of such treatment.

1 . A compound of formula (I)  
       
         
           
           
               
               
           
         
         wherein  
         Z is  
         
           
             
             
                 
                 
             
           
         
         wherein R is a lower alkyl group, wherein said lower alkyl group is a methyl; and n is 1;  
         X 1  is methylene, vinylene, or an NH or N(lower alkyl) group; and X 2  is methylene; or, when X 1  is methylene or vinylene, X 2  is methylene or a bond; or when X 2  is methylene, X 2  is O, S, NH, or N(lower alkyl) or a bond;  
         Y 1  is methylene and Y 2  is methylene, vinylene, ethylene, propylene, or a bond; or  
         Y 1  is a bond and Y 2  is vinylene; or  
         Y 1  is ethylene and Y 2  is O, S, NH, or N(lower alkyl);  
         Ar 1  and Ar 2  independently are unsubstituted or substituted aryl or heteroaryl groups, provided that Ar 1  and Ar 2  are not simultaneously unsubstituted phenyl; and  
         W is oxygen; or  
         a pharmaceutically acceptable salt or prodrug thereof.  
       
     
     
         2 . A compound of formula (I)  
       
         
           
           
               
               
           
         
         wherein  
         Z is  
         
           
             
             
                 
                 
             
           
         
         wherein R is a hydrogen, a cyclic or straight-chained or branched acyclic organyl group, a lower hydroxyalkyl group, a lower aminoalkyl group, or an aralkyl or heteroaralkyl group; and n is 1;  
         X 1  is an NH, and X 2  is methylene;  
         Y 1  is methylene and Y 2  is methylene, vinylene, ethylene, propylene, or a bond; or  
         Y 1  is a bond and Y 2  is vinylene; or  
         Y 1  is ethylene and Y 2  is O, S, NH, or N(lower alkyl);  
         Ar 1  and Ar 2  independently are unsubstituted or substituted aryl or heteroaryl groups, provided that Ar 1  and Ar 2  are not simultaneously unsubstituted phenyl; and  
         W is oxygen; or  
         a pharmaceutically acceptable salt or prodrug thereof.  
       
     
     
         3 . A compound of formula (I)  
       
         
           
           
               
               
           
         
       
       wherein 
 Z is  
                     
 wherein R is a hydrogen, a cyclic or straight-chained or branched acyclic organyl group, a lower hydroxyalkyl group, a lower aminoalkyl group, or an aralkyl or heteroaralkyl group; and n is 1;  
 X 1  is methylene, vinylene, or an NH or N(lower alkyl) group; and  
 X 2  is methylene, or, when X 1  is methylene or vinylene, X 2  is methylene or a bond; or when X 1  is methylene, X 2  is O, S, NH, or N(lower alkyl) or a bond;  
 Y 1  is methylene and Y 2  is a bond;  
 Ar 1  and Ar 2  independently are unsubstituted or substituted aryl or heteroaryl groups, provided that Ar 1  and Ar 2  are not simultaneously unsubstituted phenyl; and  
 W is oxygen; or  
 a pharmaceutically acceptable salt or prodrug thereof.  
 
     
     
         4 . A compound of formula (I)  
       
         
           
           
               
               
           
         
         wherein  
         Z is  
         
           
             
             
                 
                 
             
           
         
         wherein R is a hydrogen, a cyclic or straight-chained or branched acyclic organyl group, a lower hydroxyalkyl group, a lower aminoalkyl group, or an aralkyl or heteroaralkyl group; and n is 1;  
         X 1  is methylene, vinylene, or an NH or N(lower alkyl) group; and  
         X 2  is methylene, or, when X 1  is methylene or vinylene, X 2  is methylene or a bond; or when X 1  is methylene, X 2  is O, S, NH, or N(lower alkyl) or a bond;  
         Y 1  is methylene and Y 2  is methylene, vinylene, ethylene, propylene, or a bond; or  
         Y 1  is a bond and Y 2  is vinylene; or  
         Y 1  is ethylene and Y 2  is O, S, NH, or N(lower alkyl);  
         Ar 1  is a 4-haloaryl, wherein said aryl is phenyl and said halo is a fluoro;  
         Ar 2  is a 4-substituted aryl, wherein said aryl is phenyl, and said phenyl is substituted with a lower alkoxy group, wherein the alkyl group of said lower alkoxy group is an isobutyl; and  
         W is oxygen; or  
         a pharmaceutically acceptable salt or prodrug thereof.  
       
     
     
         5 . A tartrate salt of a compound of formula (I)  
       
         
           
           
               
               
           
         
         wherein  
         Z is  
         
           
             
             
                 
                 
             
           
         
         wherein R is a hydrogen, a cyclic or straight-chained or branched acyclic organyl group, a lower hydroxyalkyl group, a lower aminoalkyl group, or an aralkyl or heteroaralkyl group; and n is 1;  
         X 1  is methylene, vinylene, or an NH or N(lower alkyl) group; and  
         X 2  is methylene, or, when XI is methylene or vinylene, X 2  is methylene or a bond; or when X 1  is methylene, X 2  is O, S, NH, or N(lower alkyl) or a bond;  
         Y 1  is methylene and Y 2  is methylene, vinylene, ethylene, propylene, or a bond; or  
         Y 1  is a bond and Y 2  is vinylene; or  
         Y 1  is ethylene and Y 2  is O, S, NH, or N(lower alkyl);  
         Ar 1  and Ar 2  independently are unsubstituted or substituted aryl or heteroaryl groups, provided that Ar 1  and Ar 2  are not simultaneously unsubstituted phenyl; and  
         W is oxygen.  
       
     
     
         6 . The compound of  claim 1 , wherein X 1  is an NH or N(lower alkyl) group.  
     
     
         7 . The compound of  claim 3 , wherein X 1  is an NH or N(lower alkyl) group.  
     
     
         8 . The compound of  claim 4 , wherein X 1  is an NH or N(lower alkyl) group.  
     
     
         9 . The tartrate salt of the compound of  claim 5 , wherein X 1  is an NH or N(lower alkyl) group.