Chemokine receptor binding compounds

Abstract

The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR5. These compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

1 . A compound having the formula 2 
       
         
           
           
               
               
           
         
         and pharmaceutically acceptable salts thereof; 
         wherein W is oxygen, sulfur, NR 2 , NOR 2 , NCN, NSO 2 R 2 , NAc, NNO 2 , CRNO 2 , NCOR 2 , C(CN) 2  or CRCN; 
         V is O, S, N-L-R 3 , or CR-L-R 3 ; 
         L is a bond or a (CR 2 ) m  linker optionally having one carbon of (CR 2 ) m  replaced by a group selected from O, S, and NR, and m is 1-3; 
         R 1  is an optionally substituted aryl or heteroaryl; 
         R 2  is H, an optionally substituted alkyl, a carbocyclic ring, a heterocyclic ring, an aryl, or a heteroaryl; 
         R 3  is H; an optionally substituted alkyl, alkenyl or alkynyl; hydroxy, alkoxy, cyano, amino, amido, COR 2 , CO 2 R 2 , S═(O) p R 2 , CR═N—OR, O(CR 2 )CN, NR—COR 2 , SR 2 ; a carbocyclic ring, a heterocyclic ring, an aryl, or a heteroaryl; and 
         R is H, C 1-6  alkyl, or C 3-6  cycloalkyl; 
         wherein in each said optionally substituted alkyl, alkenyl or alkynyl, a carbon may be optionally substituted with halo, N, O, or S, and/or replaced with N, O or S; and 
         each carbocyclic ring, heterocyclic ring, aryl or heteroaryl may be optionally substituted and/or fused with a carbocyclic, aryl, heterocyclic, or heteroaryl ring. 
       
     
     
         2 . The compound of  claim 1 , wherein R 1  is phenyl, pyrimidinyl or pyridinyl, each optionally substituted with halo, cyano, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, or N-oxide. 
     
     
         3 . The compound of  claim 1 , wherein R 2  is phenyl, thienyl, or imidazolyl each optionally substituted with halo, cyano, alkoxy, heterocyclyl, aryl, heteroaryl, or N-oxide; or alkyl or cycloalkyl, each of which may be optionally substituted with halo, cyano, OR, SR, or N(R) m , or in which one carbon may be optionally replaced with N, O, or S. 
     
     
         4 . The compound of  claim 1 , wherein R 3  is H, C 1-10  straight or branched alkyl; or R 3  is a C 3-7  cycloalkyl, a 5-6 membered aryl, heteroaryl or heterocyclic ring, each optionally substituted with halo, cyano, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, or fused with a carbocyclic or heterocyclic ring. 
     
     
         5 . The compound of  claim 4 , wherein R 3  is H, cyclopentyl, cyclohexyl, cycloheptyl, tetrahydropyran, morpholine, phenyl optionally fused to a 5-6 membered heterocyclic ring, pyridinyl, imidazole, furan, pyrimidine, thienyl, C 1-6  straight or branched alkyl, or bicyclo[4.2.0]octa-1,3,5-triene. 
     
     
         6 . The compound of  claim 1 , wherein said compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         including the pharmaceutically acceptable salts thereof. 
       
     
     
         7 . A pharmaceutical composition comprising the compound of  claim 1  or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.