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 process for preparing an HIV integrase inhibitor comprising a step of cyclizing a compound of Formula XXIX: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  and R 3  are each H; 
         R 2  is phenyl substituted by 1-3 fluorines; 
         P 1  is selected from the group comprising hydrogen and a hydroxy protecting group; 
         X is methylene; 
         n is an integer selected from the group consisting of 1, 2, and 3; 
         R 16  and R 18  are joined to form an unsubstituted 5- or 6-membered carbocycle; and 
         R 15  and R 17  are each hydrogen. 
       
     
     
         58 . The process of  claim 57 , wherein the hydroxyl protecting group is selected from the group consisting of acyl, aralkyl, lower alkyl, alkoxyalkyl, lower alkylsulfinyl, arylsulfonyl, and alkoxycarbonyl. 
     
     
         59 . The process of  claim 57 , wherein the cyclized compound is a compound of Formula XXX: 
       
         
           
           
               
               
           
         
       
     
     
         60 . The process of  claim 59 , further comprising a step of deprotecting the compound of Formula XXX to yield a compound of Formula XXXI: