Thiourea and urea liquid-phase combinatorial libraries: synthesis and apoptosis induction

Abstract

This invention provides combinatorial chemistry libraries containing thiourea and urea compounds. In addition, the invention relates to methods for constructing combinatorial chemistry libraries containing thiourea and urea compounds. Furthermore, this invention relates to methods for the identification of bioactive thiourea and urea compounds as well as compositions and therapeutic methods for treating cancer.

1 . A process comprising: 
 reacting a compound of formula I:                          with an amine selected from:                                                              
     
     
         2 . A process comprising: 
 reacting a compound of formula I:                          with amines of formula:                                                              
     
     
         3 . A process comprising: 
 reacting a compound of formula I:                          with an amine selected from:                                                              
     
     
         4 . A process comprising: 
 reacting a compound of formula I:                          with amines of formula:                                                              
     
     
         5 . A product produced by the process of  claim 2 .  
     
     
         6 . The product of  claim 5 , wherein the product includes a library of 1830 members.  
     
     
         7 . A product produced by the process of  claim 4 .  
     
     
         8 . The product of  claim 7 , wherein the product includes a library of 1830 members.  
     
     
         9  A compound selected from the group of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         10 . A method of killing a cancer cell by contacting the cancer cell with the product of  claim 5 .  
     
     
         11 . A method of killing a cancer cell by contacting the cancer cell with the product of  claim 7 .  
     
     
         12 . A method comprising administering to a cancer patient an effective cancer cell killing amount of a compound of Formula I  
       
         
           
           
               
               
           
         
       
       wherein X is S or O; 
 R and R 1  are individually  
                     
 wherein Ar is aryl; R 2  is H or C 1  to C 6  alkyl; n is 0-3 and where the aryl moiety is optionally substituted from 1 to 7 times with any combination of H, halo, alkyl, haloalkyl, arylalkyl, alkoxy, haloalkoxy, and aralkoxy.  
 
     
     
         13 . The method of  claim 12 , wherein R and R 1  are individually selected from the group of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         14 . The method of  claim 12 , wherein the compound is:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         14 . The method of  claim 12 , wherein the cancer patient has leukemia.  
     
     
         15 . The method of  claim 10 , wherein the cancer cell is a leukemia cell.  
     
     
         16 . The method of  claim 11 , wherein the cancer cell is a leukemia cell.  
     
     
         17 . A kit for determining possible apoptosis induction agents for a biological substrate comprising the product of  claim 5 .  
     
     
         18 . A kit for determining possible apoptosis induction agents for a biological substrate comprising the product of  claim 7.