Spiro-piperidine compounds and medicinal use thereof

Abstract

The present invention relates to a spiro-piperidine compound represented by formula (I): wherein R 1 represents hydrogen, an aliphatic hydrocarbon group which may have a substituent(s) or a cyclic group which may have a substituent(s); and ring A represents a 5- to 8-membered cyclic group which may have a substituent(s), a salt thereof, an N-oxide thereof, a quaternary ammonium salt thereof or a solvate thereof, or a prodrug thereof. The compounds represented by formula (I) have chemokine antagonistic action, so that they are useful for prevention and/or treatment of various inflammatory diseases, immune diseases such as autoimmune diseases or allergic diseases, or HIV infection.

1 . A spiro-piperidine compound represented by formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1  represents hydrogen, an aliphatic hydrocarbon group which may have a substituent(s) or a cyclic group which may have a substituent(s); and 
         ring A represents 
       
       
         
           
           
               
               
           
         
         wherein, R 2  and R 5  each independently represents hydrogen, an aliphatic hydrocarbon group which may have a substituent(s), hydroxyl which may be protected, carboxy which may be protected, carbamoyl which may be protected, or a cyclic group which may have a substituent(s), 
         a salt thereof, an N-oxide thereof, a quaternary ammonium salt thereof or a solvate thereof, or a prodrug thereof. 
       
     
     
         2 - 6 . (canceled) 
     
     
         7 . The spiro-piperidine compound according to  claim 1 , wherein R 1  is a C1-10 aliphatic hydrocarbon group which may have a substituent(s), a salt thereof, an N-oxide thereof, a quaternary ammonium salt thereof or a solvate thereof, or a prodrug thereof. 
     
     
         8 . The spiro-piperidine compound according to  claim 1 , wherein R 1  is a 5- to 10-membered monocyclic or bicyclic cyclic group which may have a substituent(s), a salt thereof, an N-oxide thereof, a quaternary ammonium salt thereof or a solvate thereof, or a prodrug thereof. 
     
     
         9 . The spiro-piperidine compound according to  claim 1 , wherein R 1  is alkyl having from 1 to 6 carbon atoms susbtituted with a 3- to 10-membered monocyclic or bicyclic cyclic group which may have a substituent(s), a salt thereof, an N-oxide thereof, a quaternary ammonium salt thereof or a solvate thereof, or a prodrug thereof. 
     
     
         10 . A pharmaceutical composition which comprises the spiro-piperidine compound according to  claim 1 , a salt thereof, an N-oxide thereof, a quaternary ammonium salt thereof or a solvate thereof, or a prodrug thereof, and a pharmaceutically acceptable carrier or diluent. 
     
     
         11 . The pharmaceutical composition according to  claim 10 , which is a chemokine receptor antagonist. 
     
     
         12 . The pharmaceutical composition according to  claim 11 , wherein the chemokine receptor is CCR5. 
     
     
         13 . The pharmaceutical composition according to  claim 10 , which is a preventive and/or therapeutic agent for human immunodeficiency virus infection. 
     
     
         14 . The pharmaceutical composition according to  claim 10 , which is a preventive and/or therapeutic agent for acquired immunodeficiency syndrome. 
     
     
         15 . The pharmaceutical composition according to  claim 10 , which is a morbid state progress inhibitor for acquired immunodeficiency syndrome. 
     
     
         16 . The pharmaceutical composition according to  claim 11 , wherein the chemokine receptor is CCR2. 
     
     
         17 . The pharmaceutical composition according to  claim 10 , which is a preventive and/or therapeutic agent for arteriosclerosis or nephropathy. 
     
     
         18 . A medicament which comprises a combination of the spiro-piperidine compound according to  claim 1 , a salt thereof, an N-oxide thereof, a quaternary ammonium salt thereof or a solvate thereof, or a prodrug thereof with one or at least two of agents selected from protease inhibitors, reverse transcriptase inhibitors, integrase inhibitors, fusion inhibitors and/or chemokine inhibitors. 
     
     
         19 . A method for preventing and/or treating diseases caused by CCR5 or CCR2 in a mammal, which comprises administering to a mammal an effective amount of the spiro-piperidine compound according to  claim 1 , a salt thereof, an N-oxide thereof, a quaternary ammonium salt thereof or a solvate thereof, or a prodrug thereof.