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 . A compound of the formula: 
       
         
           
           
               
               
           
         
       
       wherein,
 Z 1  is NR 4 ; 
 R 4  and Z 2  part taken together forms a ring, where the compound (I) is represented by the following formula (I-11): 
 
       
         
           
           
               
               
           
         
       
       wherein,
 D ring is optionally substituted azepane; 
 R 1  is hydrogen or lower alkyl; 
 X is a single bond, a heteroatom group selected from O, S, SO, SO 2  and NH, or lower alkylene or lower alkenylene each may be intervened by the heteroatom group; 
 R 2  is optionally substituted aryl; and 
 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; 
 
       or a pharmaceutically acceptable salt, or solvate thereof. 
     
     
         2 . A compound according to  claim 1 , pharmaceutically acceptable salt, or solvate thereof, wherein R 1  is hydrogen. 
     
     
         3 . A compound according to  claim 1 , pharmaceutically acceptable salt, or solvate thereof, wherein X is lower alkylene; and R 2  is phenyl or phenyl substituted with at least halogen. 
     
     
         4 . A compound according to  claim 1 , pharmaceutically acceptable salt, or solvate thereof, wherein R 3  is hydrogen, halogen, hydroxy, lower alkyl, lower alkenyl, lower alkoxy, lower alkenyloxy or optionally substituted amino. 
     
     
         5 . A compound according to  claim 1 , pharmaceutically acceptable salt, or solvate thereof, wherein R 3  is hydrogen. 
     
     
         6 . A compound according to  claim 1 , pharmaceutically acceptable salt, or solvate thereof, wherein R 1  is hydrogen or lower alkyl; X is lower alkylene; R 2  is phenyl or phenyl substituted with at least halogen; and R 3  is hydrogen, halogen, hydroxy, lower alkyl, lower alkenyl, lower alkoxy, lower alkenyloxy or optionally substituted amino. 
     
     
         7 - 29 . (canceled) 
     
     
         30 . A compound of the formula: 
       
         
           
           
               
               
           
         
       
       wherein,
 D ring is optionally substituted azepane; 
 R 1  is hydrogen or lower alkyl; 
 X is a single bond, a heteroatom group selected from O, S, SO, SO 2  and NH, or lower alkylene or lower alkenylene each may be intervened by the heteroatom group; 
 R 2  is optionally substituted aryl; and 
 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; 
 
       or a pharmaceutically acceptable salt, or solvate thereof. 
     
     
         31 - 33 . (canceled) 
     
     
         34 . A pharmaceutical composition comprising a compound according to  claim 30 , or a pharmaceutically acceptable salt, or solvate thereof, together with a pharmaceutically acceptable carrier or diluent. 
     
     
         35 - 56 . (canceled)