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 method of treating HIV comprising administering to a patient infected with HIV a compound of the Formula (I-1-1): 
       
         
           
           
               
               
           
         
         wherein the stereochemistry of an asymmetric carbon represented by * is in the R-configuration or S-configuration, or is a mixture thereof; 
         R X  is hydrogen; 
         R 14  is hydrogen; 
         R 3  is hydrogen; 
         R 1  is hydrogen; 
         each R is halogen; 
         m is 2 or 3; 
         ring A is an unsubstituted bicyclic ring residue having a chemical formula C 6 H 9 NO; and 
         the carbon represented by * is directly bonded to an oxygen. 
       
     
     
         58 . The method according to  claim 57 , wherein the unsubstituted bicyclic ring of ring A includes two carbon-nitrogen single bonds, two carbon-oxygen single bonds, five carbon-carbon single bonds, and nine carbon-hydrogen single bonds. 
     
     
         59 . The method according to  claim 58 , wherein one of the rings of the unsubstituted bicyclic ring of ring A is 
       
         
           
           
               
               
           
         
       
       wherein Z is oxygen. 
     
     
         60 . The method according to  claim 59 , wherein m is 2. 
     
     
         61 . The method according to  claim 60 , wherein each R is fluorine. 
     
     
         62 . The method according to  claim 61 , wherein one R is at the 4-position of the ring. 
     
     
         63 . The method according to  claim 62 , wherein one R is located at the 4-position, and one R is located at the 2-position. 
     
     
         64 . The method according to  claim 63 , wherein the asymmetric carbon represented by * is in the R-configuration. 
     
     
         65 . The method according to  claim 64 , wherein the pharmaceutically acceptable salt is a sodium salt. 
     
     
         66 . The method according to  claim 59 , wherein m is 3. 
     
     
         67 . The method according to  claim 66 , wherein each R is fluorine. 
     
     
         68 . The method according to  claim 67 , wherein one R is at the 4-position of the ring. 
     
     
         69 . The method according to  claim 68 , wherein one R is located at the 4-position, and one R is located at the 2-position. 
     
     
         70 . The method according to  claim 69 , wherein the asymmetric carbon represented by * is in the R-configuration. 
     
     
         71 . The method according to  claim 70 , wherein the pharmaceutically acceptable salt is a sodium salt.