Compounds

Abstract

Heterocyclic amides useful as inhibitors of dipeptylpeptidase-IV (DPP-IV) enzyme, process for the preparation thereof and intermediates therefore.

1 . A compound of formula (I) 
       
         
           
           
               
               
           
         
         wherein 
         R is pyridazinyl, pyrimidinyl or pyrazinyl, optionally mono- or disubstituted independently by C 1-4  alkyl, C 1-4  alkoxy, halogen, trihalogenomethyl, methylthio, nitro, cyano, C 2-5  alkoxycarbonyl or carboxamido; 
         B is a group of formula (1), (2), (3), or (4) 
       
       
         
           
           
               
               
           
         
         and 
         Z is a group of formula (A), (B), (C), (D), (E), or (F); 
       
       
         
           
           
               
               
           
         
         or a salt, isomer, tautomer, or hydrate thereof. 
       
     
     
         2 . The compounds according to  claim 1  wherein R is pyridazinyl, pyrimidinyl or pyrazinyl, optionally independently mono- or disubstituted with C 1-4  alkyl, C 1-4  alkoxy, halogen, trihalogenomethyl, methylthio, nitro, or cyano; or a salt, isomer, tautomer, or hydrate thereof. 
     
     
         3 . The compound according to  claim 1  wherein R is pyridazinyl, pyrimidinyl or pyrazinyl, optionally independently mono- or disubstituted with C 1-4  alkyl, C 1-4  alkoxy, halogen, nitro, cyano, C 2-5  alkoxycarbonyl or carboxamido;
 Z is a group of formula (A) or formula (B); 
 or a salt, isomer, tautomer, or hydrate thereof. 
 
     
     
         4 . The compound according to  claim 3  wherein R is pyrimidinyl, pyrazinyl, or pyridazinyl, optionally independently mono- or disubstituted with C 1-4 alkyl, C 1-4  alkoxy, halogen, nitro, or cyano; or a salt, isomer, tautomer, or hydrate thereof. 
     
     
         5 . The compound according to  claim 4  wherein R is pyrimidinyl, pyrazinyl, or pyridazinyl, substituted with nitro or cyano, and B is a group of formula (1) or (2); or a salt, isomer, tautomer, or hydrate thereof. 
     
     
         6 . A compound selected from the group consisting of:
 (4R)-3-(2-{[8-(2-Pyrimidinyl)-8-azabicyclo[3.2.1]oct-3-yl]exo-amino}acetyl)thiazolidine-4-carbonitrile and   (4R)-3-(2-{[8-(2-Pyrazinyl)-8-azabicyclo[3.2.1]octan-3-yl]-exo-amino}acetyl)thiazolidine-4-carbonitrile;   or a salt, or hydrate, or solvate thereof.   
     
     
         7 . A pharmaceutical composition comprising a compound according to  claim 1  or a salt, isomer, tautomer, or hydrate thereof, together with a pharmaceutically acceptable support material or diluent. 
     
     
         8 . A pharmaceutical composition comprising a compound according to  claim 2  or a salt, isomer, tautomer, or hydrate thereof, together with a pharmaceutically acceptable support material or diluent. 
     
     
         9 . A pharmaceutical composition comprising a compound according to  claim 3  or a salt, isomer, tautomer, or hydrate thereof, together with a pharmaceutically acceptable support material or diluent. 
     
     
         10 . A pharmaceutical composition comprising a compound according to  claim 4  or a salt, isomer, tautomer, or hydrate thereof, together with a pharmaceutically acceptable support material or diluent. 
     
     
         11 . A pharmaceutical composition comprising a compound according to  claim 5  or a salt, isomer, tautomer, or hydrate thereof, together with a pharmaceutically acceptable support material or diluent. 
     
     
         12 . A pharmaceutical composition comprising a compound according to  claim 6  or a salt, or hydrate thereof, together with a pharmaceutically acceptable support material or diluent.