Cyclohexenyl-ethyl-thiourea compounds and use

Abstract

Novel CycloHexenyl-Ethyl-Thiourea (CHET) compounds as inhibitors of reverse transcriptase and effective agents for the treatment of HIV infection, including mutant, drug-sensitive, drug-resistant, and multi-drug resistant strains of HIV.

We claim:  
     
         1 . A method for treating drug-resistant HIV in a subject comprising administering to said subject an effective amount of at least one compound of the formula  
       
         
           
           
               
               
           
         
       
       wherein 
 n is 0 to 6;  
 R is H, halogen, (C 1 -C 12 ) alkyl, (C 1 -C 12 ) alkoxy, amino, cyano, nitro, or hydroxy; and  
 R 1  comprises cyclo(C 3 -C 12 ) alkyl, cyclo(C 3 -C 12 ) alkenyl, isothiazolyl, tetrazolyl, triazolyl, pyridyl, imidazolyl, phenyl, napthyl, benzoxazolyl, benzimidazolyl, thiazolyl, oxazolyl, benzothiazolyl, pyrazinyl, pyridazinyl, thiadiazolyl, benzotriazolyl, pyrolyl, indolyl, benzothienyl, thienyl, benzofuryl, quinolyl, isoquinolyl, or pyrazolyl; or a pharmaceutically acceptable addition salt thereof:  
 
     
     
         2 . The method of  claim 1 , wherein R 1  is substituted with one or more of (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, halo, or hydroxy.  
     
     
         3 . The method of  claim 1 , wherein R 1  is pyridyl.  
     
     
         4 . The method of  claim 1 , wherein R 1  is pyridyl substituted with halogen.  
     
     
         5 . The method of  claim 1 , wherein R 1  is pyridyl substituted with bromine or chlorine.  
     
     
         6 . The method of  claim 1 , wherein n is 1 and R is halogen.  
     
     
         7 . The method of  claim 1 , wherein n is 0.  
     
     
         8 . The method of  claim 1 , wherein the compound is: 
 N-[2-(1-cyclohexenyl) ethyl]-N 1   -[2 -(5-bromopyridyl)]-thiourea (HI-346);    N-[2-(1-cyclohexenyl) ethyl]-N 1   -[2 -(5-chloropyridyl)]-thiourea (HI-445); or a pharmaceutically acceptable addition salt thereof.