SUBSTITUTED SPIROPYRIDO[1,2-a]PYRAZINE DERIVATIVE AND PHARMACEUTICAL USE OF SAME AS HIV INTEGRASE INHIBITOR

Abstract

[Problem] Provided is a substituted spiropyrido[1,2-a]pyrazine derivative or a pharmaceutically acceptable salt thereof, which is useful as an anti-HIV agent. [Solving Means] The present invention relates to a compound represented by the following formula [I] or [II] or a pharmaceutically acceptable salt thereof: wherein each symbol is as defined in the specification.

1 . A compound represented by the following formula [I] or [II], or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is halogen atom, 
         R 2  is hydrogen atom, halogen atom or trifluoromethyl group, 
         each R 3  is the same or different and is
 (1) halogen atom, 
 (2) C 1-6  alkoxy group, or 
 (3) 2-oxopyrrolidinyl group, 
 
         R 4  is C 1-6  alkyl group or cyclopropyl group, 
         R 5  is
 (1) hydroxy group, 
 (2) C 1-6  alkoxy group, 
 (3) benzyloxy group, 
 (4) C 1-6  alkoxy C 2-6  alkyleneoxy group, 
 (5) carboxy group, 
 (6) —CO—NR 6a R 6b  
 wherein R 6a  and R 6b  are the same or different and each is 
 (i) hydrogen atom, or 
 (ii) C 1-6  alkyl group, 
 
 (7) —NR 7a COR 7b  
 wherein R 7a  and R 7b  are the same or different and each is 
 (i) hydrogen atom, or 
 (ii) C 1-6  alkyl group, 
 
 (8) methanesulfonyl group, or 
 (9) methanesulfonyloxy group, 
 
         p is an integer of 0 to 3, 
         q is 0 or 1, and 
         r is 0 or 1. 
       
     
     
         2 . The compound according to  claim 1 , wherein q is 1 or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The compound according to  claim 1 , wherein q is 0 or a pharmaceutically acceptable salt thereof. 
     
     
         4 . The compound according to  claim 1 , wherein p is 0 or 1, or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The compound according to  claim 1 , wherein r is 1, or a pharmaceutically acceptable salt thereof. 
     
     
         6 . The compound according to  claim 1 , wherein r is 0, or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The compound according to  claim 1 , wherein R 2  is halogen atom, or a pharmaceutically acceptable salt thereof. 
     
     
         8 . The compound according to  claim 1 , wherein R 4  is C 1-6  alkyl group, or a pharmaceutically acceptable salt thereof. 
     
     
         9 . The compound according to  claim 1 , wherein R 5  is
 (1) hydroxy group,   (2) C 1-6  alkoxy group,   (3) benzyloxy group,   (4) C 1-6  alkoxy C 2-6  alkyleneoxy group,   (5) carboxy group, or   (6) —CO—NR 6a R 6b  
 wherein R 6a  and R 6b  are the same or different and each is 
 (i) hydrogen atom, or 
 (ii) C 1-6  alkyl group, 
   
       or a pharmaceutically acceptable salt thereof. 
     
     
         10 . The compound according to  claim 9 , wherein R 5  is
 (1) hydroxy group,   (2) C 1-6  alkoxy group, or   (3) —CO—NR 6a R 6b      wherein R 6a  and R 6b  are the same or different and each is   (i) hydrogen atom, or   (ii) C 1-6  alkyl group,   
       or a pharmaceutically acceptable salt thereof. 
     
     
         11 . A pharmaceutical composition comprising the compound according to  claim 1  or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         12 . An anti-HIV agent comprising the compound according to  claim 1  or a pharmaceutically acceptable salt thereof, as an active ingredient. 
     
     
         13 . An HIV integrase inhibitor comprising the compound according to  claim 1  or a pharmaceutically acceptable salt thereof, as an active ingredient. 
     
     
         14 . An anti-HIV agent comprising the compound according to  claim 1  or a pharmaceutically acceptable salt thereof, in combination with one or more other kinds of anti-HIV active substances. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . A method for the prophylaxis or treatment of an HIV infection in a mammal, comprising administering an effective amount of the compound according to  claim 1  or a pharmaceutically acceptable salt thereof, to the mammal. 
     
     
         18 . The method according to  claim 17 , further comprising administering an effective amount of one or more other kinds of anti-HIV active substances to the mammal. 
     
     
         19 . A method for inhibiting HIV integrase in a mammal, comprising administering an effective amount of the compound according to  claim 1  or a pharmaceutically acceptable salt thereof, to the mammal.