1-(1,2-Disubstituted piperidinyl)-4-substituted piperazine derivatives

Abstract

This invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereoisomeric forms thereof, as substance-P antagonists; their preparation, compositions containing them and their use as a medicine.

What is claimed:  
     
       1. A compound selected from the group consisting of: 
       4-[1-[3,5bis(trifluoromethyl) benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(2,6dimethylphenyl)-1-piperazine acetamide;  
       4-[1-[3,5bis(trifluoromethyl) benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(1-phenylcyclohexyl)-1-piperazine acetamide;  
       1-[3,5-bis(trifluoromethyl)benzoyl -2-(phenylmethyl)-4-piperidinyl]-N-(1-phenylcyclohexyl)-1-piperazine acetamide;  
       1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-[1-[(2-methyl-5-oxazolyl) methyl]-1H-benzimidazol-2-yl]-1-piperazinyl]-2-(phenylmethyl) piperidine;  
       4-[3,5-bis(trifluoromethyl)benzoyl]-2-[(4-trifluoromethylphenyl)methyl]-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-piperazine acetamide; and  
       4-[3,5-bis(trifluoromethyl)benzoyl]-2-[(3,4-dichlorophenyl) methyl]-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-piperazine acetamide;  
       or a N-oxide form, a pharmaceutically acceptable addition salt or a stereochemically isomeric form thereof.  
     
     
       2. A compound as claimed in  claim 1 , wherein the compound is (±)-(B)-trans-4-[1-[3,5-bis(trifluoromethyl) benzoyl;]-2-(phenylmethy)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-piperazine acetamide; (−)-(B)cis-4-[1-[3,5-bis(trifluoromethyl) benzoly]-2-(phenylmethy)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-piperazine acetamide; or (±)-(B)-trans-4-[1-[3,5-bis(trifluoromethyl) benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-piperazine acetamide, (L)-malic acid (1:1). 
     
     
       3. A composition comprising a pharmaceutically acceptable carrier, and as active ingredient a therapeutically effective amount of a compound as claimed in  claim 1 . 
     
     
       4. A process of preparing a composition as claimed in  claim 3 , characterized in that the pharmaceutically acceptable carrier is intimately mixed with a therapeutically effective amount of the compound.