Cytotoxic benzodiazepine derivatives

Abstract

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

We claim: 
     
       1. A compound represented by the following structural formula: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       2. A method for preparing compound 3b represented by the following structural formula: 
       
         
           
           
               
               
           
         
         comprising reacting compound 3a represented by the following structural formula: 
       
       
         
           
           
               
               
           
         
         with hydrogen in the presence of a palladium catalyst, to form compound 3b. 
       
     
     
       3. The method of  claim 2 , wherein the palladium catalyst is palladium on carbon (Pd/C). 
     
     
       4. The method of  claim 2 , wherein the reaction is carried out in methanol. 
     
     
       5. The method of  claim 2 , wherein the reaction is carried out at room temperature. 
     
     
       6. The method of  claim 5 , wherein the reaction is carried out at room temperature overnight. 
     
     
       7. The method of  claim 2 , wherein the method further comprises purifying compound 3b by silica gel chromatography. 
     
     
       8. The method of  claim 3 , wherein the reaction is carried out at room temperature. 
     
     
       9. The method of  claim 8 , wherein the reaction is carried out at room temperature overnight. 
     
     
       10. The method of  claim 3 , wherein the method further comprises purifying compound 3b by silica gel chromatography. 
     
     
       11. The method of  claim 2 , wherein the palladium catalyst is palladium on carbon (Pd/C) and the reaction is carried out in methanol. 
     
     
       12. The method of  claim 11 , wherein the reaction is carried out at room temperature. 
     
     
       13. The method of  claim 12 , wherein the reaction is carried out at room temperature overnight. 
     
     
       14. The method of  claim 11 , wherein the method further comprises purifying compound 3b by silica gel chromatography.