S-triazolyl alpha-mercapto acetanilides as inhibitors of hiv reverse transcriptase

Abstract

A series of S-triazolyl α-mercaptoacetanilides having general structure (1) are provided, where Q is CO 2 H, CONR 2 , SO 3 H, or SO 2 NR 2 . The compounds inhibit several variants of the reverse transcriptase of HIV, and are useful in the treatment of HIV infections.

1 . A compound of formula A 
       
         
           
           
               
               
           
         
       
       wherein:
 Q is CONR′R″; 
 P is selected from the group consisting of (a), (b), (c) and (d): 
 
       
         
           
           
               
               
           
         
         R 1  is selected from the group consisting of Cl, Br, I, CH 3 , CF 3 , CHF 2 , and CH 2 F; 
         R 3  is H or CH 3 ; 
         R′ and R″ are independently selected from the group consisting of H, lower alkyl, and lower alkyl substituted with one or more OR, CO 2 R, NHR, NR 2 , or CF 3  groups wherein R is H or lower alkyl, or R′ and R″ together with the nitrogen atom to which they are attached form a 4-, 5-, or 6-membered heterocyclic ring; 
         R 0  is selected from the group consisting of Cl, Br, CF 3  and methyl; 
         R P  is selected from the group consisting of halogen, methyl, ethyl, propyl, isopropyl, cyclopropylmethyl, and C 3 -C 6  cycloalkyl; 
         R 4 , R 5  and R 6  are independently selected from the group consisting of H, F, Cl, Br, CH 3 , CF 3 , CFH 2 , CF 2 H, isopropyl, cyclopropyl, OCH 3 , OH, OCF 3 , NH 2  and NHCH 3 ; 
         U and U′ are independently selected from N and CH; 
         R 7  is selected from the group consisting of Cl, Br, I, CH 3 , CF 3 , OCH 3 , isopropyl, cyclopropyl, tert-butyl, and cyclobutyl; and 
         R 8 , R 9 , R 10  and R 11  are independently H or CH 3 . 
       
     
     
         2 . The compound of  claim 1 , wherein none of R 4 , R 5 , and R 6  are OH, NH 2  or NHCH 3 . 
     
     
         3 . The compound of  claim 1 , wherein P is not substituted phenyl and at least one of R 4 , R 5 , and R 6  is other than H or CH 3 . 
     
     
         4 . The compound of  claim 1 , wherein P is a substituted phenyl and R 6  is not methyl. 
     
     
         5 . The compound of  claim 2 , wherein P is not substituted phenyl and at least one of R 4 , R 5 , and R 6  is other than H or CH 3 . 
     
     
         6 . (canceled) 
     
     
         7 . The compound of  claim 2 , wherein P is a substituted naphthyl and R 1  is selected from the group consisting of Br, CF 3 , CFH 2 , and CF 2 H. 
     
     
         8 . The compound of  claim 7 , wherein each of R 4 , R 5 , and R 6  is H. 
     
     
         9 . The compound of  claim 7 , wherein R P  is cyclopropyl. 
     
     
         10 . The compound of  claim 7 , wherein R 1  is Br and R 0  is Cl. 
     
     
         11 . The compound of  claim 2 , wherein P is a substituted quinoline or isoquinoline and R 1  is selected from the group consisting of Br, CF 3 , CFH 2 , and CF 2 H. 
     
     
         12 . The compound of  claim 11 , wherein each of R 4 , R 5 , and R 6  is H. 
     
     
         13 . The compound of  claim 11 , wherein R P  is cyclopropyl. 
     
     
         14 . The compound of  claim 11 , wherein R 1  is Br and R 0  is Cl. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . A pharmaceutical composition comprising a compound of  claim 1  in combination with one or more pharmaceutically acceptable carriers. 
     
     
         19 . A compound of Formula A 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is C 1-3  alkyl, —CF 3 , —CHF 2 , —CH 2 F, —Cl, —Br, —NH 2 , or hydrogen; 
 R 2  is an aryl or heteroaryl moiety containing a cycloalkyl or heterocyclic group which can be further substituted with alkyl, cycloalkyl, aryl or heteroaryl moieties; 
 Q is a C 3-5  cycloalkyl; 
 W is S, O, or an optionally substituted amine; 
 R 3  is C 1-3  alkyl, —CF 3 , —CHF 2 , —CH 2 F, —Cl, —Br; and 
 R 4  is —COR′, wherein R′ is —NH 2  or —NH(alkyl). 
 
     
     
         20 . A compound of Formula 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is C 1-3  alkyl, —CF 3 , —CHF 2 , —CH 2 F, —Cl, —Br, —NH 2 , or hydrogen; 
 R 2  is an 4-Q-naphth-1-yl or 4-Q-phen-1-yl-; 
 Q is C 2-5  alkyl; 
 W is S, O or an optionally substituted amine; 
 R 3  is C 1-3  alkyl, —CF 3 , —CHF 2 , —CH 2 F, —Cl, —Br; and 
 R 4  is —COR′, wherein R′ is —NH 2  or —NH(alkyl).