Polycyclic carbamoylpyridone derivative having hiv integrase inhibitory activity

Abstract

The present invention is to provide a novel compound (I) shown below, having the anti-virus activity; particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. (wherein Z 1 is NR 4 ; R 1 is hydrogen or lower alkyl; X is a single bond, a hetero atom group selected from O, S, SO, SO 2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R 2 is optionally substituted aryl; R 3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R 4 and Z 2 part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.

1 - 56 . (canceled) 
     
     
         57 . A compound of the formula: 
       
         
           
           
               
               
           
         
         wherein, 
         ring A is 
       
       
         
           
           
               
               
           
         
         Z═NH; 
         R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , R 38 , and R 39  are independently hydrogen C 1 -C 8 alkyl, C 6 -C 14 arylC 1 -C 8 alkyl, C 6 -C 14 aryl, or alkoxy, and wherein any two groups of R 32-39  together may form a cycloalkyl; 
         the stereochemistry of an asymmetric carbon represented by * shows R- or S-configuration, or a mixture thereof; 
         R is halogen; 
         m is an integer from 0 to 3; 
         R X  is hydrogen; 
         R 1  is hydrogen or lower alkyl; 
         R 3  is hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted lower alkenyl, optionally substituted lower alkoxy, optionally substituted lower alkenyloxy, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heterocyclic group, optionally substituted heterocycleoxy or optionally substituted amino; 
         R 14  is hydrogen; and, 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         58 . A pharmaceutical composition comprising the compound of  claim 57  or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or diluent. 
     
     
         59 . A compound of the formula: 
       
         
           
           
               
               
           
         
         wherein, 
         ring A is 
       
       
         
           
           
               
               
           
         
         R 20 , R 21 , R 22 , R 23 , R 24 , and R 25 a are independently hydrogen or C 1 -C 8 alkyl; 
         the stereochemistry of an asymmetric carbon represented by * shows R- or S-configuration, or a mixture thereof; 
         R is halogen; 
         m is an integer from 0 to 3; 
         R X  is hydrogen; 
         R 1  is hydrogen or lower alkyl; 
         R 3  is hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted lower alkenyl, optionally substituted lower alkoxy, optionally substituted lower alkenyloxy, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heterocyclic group, optionally substituted heterocycleoxy or optionally substituted amino; 
         R 14  is hydrogen; and, 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         60 . A pharmaceutical composition comprising the compound of  claim 59  or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or diluent. 
     
     
         61 . A compound of the formula: 
       
         
           
           
               
               
           
         
         wherein, 
         ring A is 
       
       
         
           
           
               
               
           
         
         Z═O; 
         R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , R 38 , and R 39  are independently hydrogen, C 1 -C 8 alkyl, C 6 -C 14 arylC 1 -C 8 alkyl, C 6 -C 14 aryl, or alkoxy, and wherein any two groups of R 32-39  together may form a cycloalkyl; 
         the stereochemistry of an asymmetric carbon represented by * shows R- or S-configuration, or a mixture thereof; 
         R is halogen; 
         m is an integer from 0 to 3; 
         R X  is hydrogen; 
         R 1  is hydrogen or lower alkyl; 
         R 3  is hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted lower alkenyl, optionally substituted lower alkoxy, optionally substituted lower alkenyloxy, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heterocyclic group, optionally substituted heterocycleoxy or optionally substituted amino; 
         R 14  is hydrogen; and, 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         62 . A pharmaceutical composition comprising the compound of  claim 61  or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or diluent.