Novel 1,4-benzodiazepine-2,5-diones with therapeutic properties

Abstract

The present invention relates to novel chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides novel 1,4-benzodiazepine-2,5-dione compounds, and methods of using novel 1,4-benzodiazepine-2,5-dione compounds as therapeutic agents to treat a number of conditions associated with the faulty regulation of the processes of programmed cell death, autoimmunity, inflammation, hyperproliferation, and the like.

1 . A composition configured to induce apoptosis in a cell, said composition comprising a compound described by a formula selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       substituted and unsubstituted, including both R and S enantiomeric forms and racemic mixtures;
 wherein R1 is an electron rich heterocycle; 
 wherein R2 is selected from the group consisting of H, alkyl, substituted alkyl, and R 1 ; 
 wherein R 3  is selected from the group consisting of H, alkyl, and substituted alkyl; 
 wherein R 4  and R 4 ′ is independently selected from the group consisting of CH 3 , halogen, SO 2 R 4 ″, SO 2 N(R 4 ″) 2 , OR 4 ″, N(R 4 ″) 2 , CON(R 4 ″) 2 , NHCOR 4 ″, NHSO 2 R 4 ′, alkyl, mono-substituted alkyl, di-substituted alkyl, tri-substituted alkyl; wherein R 4 ″ is selected from the group consisting of halogen, H, alkyl, mono-substituted alkyl, di-substituted alkyl, tri-substituted alkyl, aryl, mono-substituted aryl, di-substituted aryl, tri-substituted aryl, cycloalipathic, mono-substituted cycloalipathic, di-substituted cycloalipathic, tri-substituted cycloalipathic; 
 wherein R 5  is selected from the group consisting of H, alkyl, mono-substituted aryl, di-substituted aryl, and tri-substituted aryl; and 
 wherein R6 is selected from the group consisting of C, N or S. 
 
     
     
         2 . The composition of  claim 1 , wherein said electron rich heterocycle contains 5 or more heterocyclic atoms. 
     
     
         3 . The composition of  claim 1 , wherein R 1  is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
       wherein R 1 ′ is selected from the group consisting of cycloalipathic, aryl, substituted aryl, heterocyclic, and substituted heterocyclic. 
     
     
         4 . The composition of  claim 1 , wherein R1 is selected from the group consisting of:
 In some embodiments, R1 is selected from the group consisting of:   
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and derivatives thereof. 
     
     
         5 . The composition of  claim 1 , wherein said compound is described by the following formula: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The composition of  claim 1 , wherein said compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         7 . The composition of  claim 1 , wherein said cells are selected from the group consisting of B cells, T cells, granulocytes, and proliferating cells. 
     
     
         8 . A method for regulating cell death, comprising
 a. providing:
 i. target cells;
 the position described in  claim 1 ; and 
 
   b. exposing said target cells to said composition under conditions such that said composition binds to said target cells so as to induce cellular apoptosis.   
     
     
         9 . The method of  claim 8 , wherein said target cells are in vitro cells. 
     
     
         10 . The method of  claim 8 , wherein said target cells are in vivo cells. 
     
     
         11 . The method of  claim 8 , wherein said target cells are ex vivo cells. 
     
     
         12 . The method of  claim 8 , wherein said target cells are cancer cells. 
     
     
         13 . The method of  claim 8 , wherein said target cells are selected from the group consisting of B cells, T cells, and granulocytes. 
     
     
         14 . The method of  claim 8 , wherein said target cells are proliferating cells. 
     
     
         15 . A method of treating autoimmune disorders, comprising:
 a) providing a subject and the composition described in  claim 1 , wherein said composition is capable of inducing cellular apoptosis, and wherein said composition demonstrates selective cytotoxicity against T cells as compared to B cells; and   b) administering said composition to said subject.