Transition metal complexes of a bis[thiohydrazide amide] compound

Abstract

The present invention is directed to a compound comprising a bis[thiohydrazide amide] or a deprotonated form thereof, complexed to a transition metal cation, wherein the bis[thiohydrazide amide] is represented by Structural Formula (I): or a prodrug, isomer, ester, salt, hydrate, solvate, polymorph or a deprotonated form thereof. The present invention also provides a pharmaceutical composition comprising a compound of the invention and method of use thereof.

1 - 20 . (canceled) 
     
     
         21 . A method of treating a subject with cancer, said method comprising administering to the subject an effective amount of a bis[thiohydrazide amide] or a deprotonated form thereof complexed to a transition metal cation, wherein the bis[thiohydrazide amide] is represented by the following Structural Formula: 
       
         
           
           
               
               
           
         
       
     
     
         22 - 24 . (canceled) 
     
     
         25 . The method of  claim 21 , further comprising administering to the subject an effective amount of paclitaxel or a paclitaxel analog. 
     
     
         26 . The method of  claim 21 , wherein the compound is greater than 90% pure by weight. 
     
     
         27 . The method of  claim 21 , wherein the transition metal cation has a charge of +2. 
     
     
         28 . The method of  claim 27 , wherein the transition metal cation is Ni 2+ , Cu 2+ , Co 2+ , Fe 2+ , Zn 2+ , Pt 2+  or Pd 2+ . 
     
     
         29 . The method of  claim 28 , wherein the transition metal cation is Cu 2+ . 
     
     
         30 . The method of  claim 21 , wherein the molar ratio of bis[thiohydrazide amide] or deprotonated form thereof to transition metal cation is equal to or greater than 0.5 and equal to or less than 2.0. 
     
     
         31 . The method of  claim 30 , wherein the molar ratio of bis[thiohydrazide amide] or deprotonated form thereof to transition metal cation is 1:1. 
     
     
         32 . A method of treating a subject with cancer, said method comprising administering to the subject an effective amount of a compound represented by the following structural formula: 
       
         
           
           
               
               
           
         
         wherein X is a transition metal cation with a +2 charge. 
       
     
     
         33 . The method of  claim 32 , wherein the compound is greater than 90% pure by weight. 
     
     
         34 . The method of  claim 33 , wherein X is Ni 2+ , Cu 2+ , Co 2+ , Fe 2+ , Zn 2+ , Pt 2+  or Pd 2+ . 
     
     
         35 . The method of  claim 34 , wherein X is Cu 2+ . 
     
     
         36 . The method of  claim 32 , further comprising administering to the subject an effective amount of paclitaxel or a paclitaxel analog.