Spiro aminic compounds with nk1 antagonist activity

Abstract

The invention concerns a spiro-amino compound of Formula (I), wherein A is selected from a 5- or 6-membered aromatic ring and a 5- or 6-membered heteroaromatic ring containing 1 to 3 nitrogen atom; X is a substituent selected from the group consisting of (C 1 -C 3 )alkyl and halogen, Y is a substituent selected from the group consisting of halogen and trifluoromethyl or a pharmaceutically acceptable salt thereof for use in the treatment of pathologies which require an antagonist of the NK1 receptor.

What is claimed is: 
     
         1 . A method for the treatment of pathologies which require an antagonist of the NK1 receptor, said method comprising the step of administering a spiro-amino compound of Formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         A is selected from a 5- or 6-membered aromatic ring and a 5- or 6-membered heteroaromatic ring containing 1 to 3 nitrogen atom, 
         X is a substituent selected from the group consisting of (C 1 -C 3 )alkyl and halogen, Y is a substituent selected from the group consisting of halogen and trifluoromethyl 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The method according to  claim 1 , wherein A of the spiro-amino compound of Formula (I) is selected from the group consisting of pyrimidinyl, pyridinyl and triazolyl, more preferably pyrimidinil. 
     
     
         3 . The method according to  claim 1 , wherein X of the spiro-amino compound of Formula (I) is chloro, fluoro or methyl, more preferably methyl. 
     
     
         4 . The method according to  claim 1 , wherein Y of the spiro-amino compound of Formula (I) is chloro or trifluoromethyl, more preferably chloro. 
     
     
         5 . The method according to  claim 1 , wherein the spiro amino compound is selected from the group consisting of:
 (S)-(5-chloro-2-(pyrimidin-2-yl)phenyl)(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone (compound 1);   (S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-methyl-2-(pyridin-2-yl)phenyl)methanone (compound 2);   (S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-fluoro-2-(pyridin-2-yl)phenyl)methanone (compound 3);   (S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone (compound 4);   (S)-(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)(5-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone (compound 5);   (S)(5-((5-chloropyridin-2-ylamino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone (compound 6);   (S)-(5-methyl-2-(pyrimidin-2-yl)phenyl)(5-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)methanone (compound 7);   (S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-methyl-2-(pyrimidin-2-yl)phenyl)methanone (compound 8); and   (S)-(5-(((5-chloropyridin-2-yl)amino)methyl)-6-azaspiro[2.5]octan-6-yl)(5-fluoro-2-(pyrimidin-2-yl)phenyl)methanone (compound 9).   
     
     
         6 . The method according to  claim 1 , wherein the pathology is selected from the group consisting of emesis, depression, eating disorders, pain, gastrointestinal disorders, inflammatory diseases and allergic disorders. 
     
     
         7 . A spiro-amino compound of Formula (II): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         8 . A pharmaceutical composition comprising a compound of Formula (II) and a pharmaceutically acceptable carrier. 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . A method for the treatment of pathologies which require an antagonist of the NK1 receptor, said method comprising the step of administering a spiro amino compound of Formula (II) or a pharmaceutically acceptable salt thereof. 
     
     
         13 . The method according to  claim 12 , wherein the pathology is selected from the group consisting of emesis, depression, eating disorders, pain, gastrointestinal disorders, inflammatory diseases and allergic disorders.