Virus therapeutic drug

Abstract

The object of the present invention is to provide a pharmaceutical composition for preventing or treating viral infectious diseases. The compounds of the present invention have extremely potent anti-HCV activity and HCV growth inhibitory effects, and since they also only demonstrate mild cytotoxicity in vivo, a pharmaceutical composition containing the compound of the present invention is extremely useful as an anti-HCV preventive/therapeutic agent.

1 . A pharmaceutical composition for preventing or treating viral infectious diseases comprising a compound represented by the following general formula (I): 
       
         
           
           
               
               
           
         
       
       (wherein
 A represents a phenyl group substituted with —OX, or a 3-indolyl group; 
 X represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, or a linear or branched alkynyl group having 2 to 8 carbon atoms; 
 B represents a hydrogen atom, a hydroxyl group, an oxo group, —N(R 4 )(R 5 ), ═N—OH, ═N—OR 6  or a halogen atom; 
 R 4  and R 5  may be the same or different, and each represent a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkenyl group having 2 to 6 carbon atoms, or a linear or branched alkynyl group having 2 to 6 carbon atoms, or R 4  and R 5  together represent a 3 to 8 membered ring; 
 R 6  represents a linear or branched alkyl group having 1 to 8 carbon atoms (which may be substituted with an amino group which may be mono- or di-substituted with a linear or branched alkyl group having 1 to 4 carbon atoms); 
 D represents a hydrogen atom or a hydroxyl group; 
 bond E represents a single bond or double bond; 
 R 1 , R 2  and R 3  may be the same or different, and each represent a hydrogen atom, a hydroxyl group, an amino group (which may be mono- or di-substituted with a linear or branched alkyl group having 1 to 4 carbon atoms), —OZ, a linear or branched alkyl group having 1 to 4 carbon atoms, a linear or branched alkenyl group having 2 to 4 carbon atoms, or a linear or branched alkynyl group having 2 to 4 carbon atoms; and, 
 Z represents a linear or branched alkyl group having 1 to 4 carbon atoms, a linear or branched alkenyl group having 2 to 4 carbon atoms, or a linear or branched alkynyl group having 2 to 4 carbon atoms) 
 
       a prodrug thereof or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The pharmaceutical composition according to  claim 1  comprising the compound of formula (I) according to  claim 1  represented by the following general formula (I′), a prodrug thereof or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       (wherein A, B, D, bond E, R 1 , R 2  and R 3  are the same as defined in  claim 1 ). 
     
     
         3 . The pharmaceutical composition according to  claim 1  comprising a compound of formula (I), a prodrug thereof or a pharmaceutically acceptable salt thereof wherein A represents a phenyl group substituted with —OX at position 4, X represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms, or a linear or branched alkynyl group having 2 to 8 carbon atoms. 
     
     
         4 . The pharmaceutical composition according to  claim 1  comprising a compound of formula (I), a prodrug thereof or a pharmaceutically acceptable salt thereof, wherein B represents an oxo group, a hydrogen atom, a hydroxyl group or ═N—OR 6 . 
     
     
         5 . The pharmaceutical composition according to  claim 1  comprising a compound of formula (I), a prodrug thereof or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2  and R 3  may be the same or different and each represent a hydroxyl group, an amino group, or —OZ (wherein Z represents a linear or branched alkyl group having 1 to 4 carbon atoms). 
     
     
         6 . The pharmaceutical composition according to  claim 1  comprising a compound of formula (I), a prodrug thereof or a pharmaceutically acceptable salt thereof, wherein A represents a phenyl group substituted with —OX at position 4, X represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms or a linear or branched alkynyl group having 2 to 8 carbon atoms, B represents an oxo group, a hydroxyl group or ═N—OR 6 , and R 1 , R 2  and R 3  may be the same or different and each represent a hydroxyl group or —OZ (wherein Z represents a linear or branched alkyl group having 1 to 4 carbon atoms). 
     
     
         7 . The pharmaceutical composition according to  claim 6  comprising a compound of formula (I), a prodrug thereof or a pharmaceutically acceptable salt thereof, wherein X represents a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkenyl group having 2 to 8 carbon atoms or a linear or branched alkynyl group having 2 to 8 carbon atoms, B represents an oxo group or a hydroxyl group, and R 1 , R 2  and R 3  each represent a hydroxyl group. 
     
     
         8 . The pharmaceutical composition according to  claim 1  comprising a compound of formula (I), a prodrug thereof or a pharmaceutically acceptable salt thereof, wherein A represents a 3-indolyl group. 
     
     
         9 . The pharmaceutical composition according to  claim 8  comprising a compound of formula (I), a prodrug thereof or a pharmaceutically acceptable salt thereof, wherein B represents an oxo group or a hydroxyl group, and R 1 , R 2  and R 3  each represent a hydroxyl group. 
     
     
         10 . The pharmaceutical composition according to  claim 1  comprising a compound of formula (I), a prodrug thereof of a pharmaceutically acceptable salt thereof, selected from the compounds indicated below. 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         11 . The pharmaceutical composition according to  claim 1  comprising a compound of formula (I), a prodrug thereof or a pharmaceutically acceptable salt thereof, selected from the compounds indicated below. 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         12 . The pharmaceutical composition according to  claim 1  comprising a compound of formula (I), a prodrug thereof or a pharmaceutically acceptable salt thereof, selected from the compounds indicated below. 
       
         
           
           
               
               
           
         
       
     
     
         13 . The pharmaceutical composition according to  claim 1 , wherein the viral infectious disease is HCV infection. 
     
     
         14 . The pharmaceutical composition according to  claim 13 , wherein the HCV infection is hepatitis C.