Novel polyamine analog conjugates and quinone conjugates as therapies for cancers and prostate diseases

Abstract

Peptide conjugates in which cytocidal and cytostatic agents, such as polyamine analogs or naphthoquinones, are conjugated to a polypeptide recognized and cleaved by enzymes such as prostate-specific antigen (PSA) and cathepsin B are provided, as well as compositions comprising these conjugates. Methods of using these conjugates in the treatment of prostate diseases are also provided.

1 - 46 . (canceled) 
     
     
         47 . A compound selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and all pharmaceutically-suitable salts and stereoisomers thereof. 
     
     
         48 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         49 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         50 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         51 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         52 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         53 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         54 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         55 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         56 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         57 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         58 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         59 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         60 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         61 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         62 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         63 . A compound of  claim 47  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-suitable salt or a stereoisomer thereof. 
     
     
         64 . A method of treating cancer, comprising administering to an individual a therapeutic amount of one or more of the compounds of  claim 47 , or a pharmaceutically-suitable salt or stereoisomer thereof. 
     
     
         65 . The method of  claim 64 , wherein the cancer is prostate cancer. 
     
     
         66 . The method of  claim 64 , wherein the cancer is breast cancer. 
     
     
         67 . The method of  claim 64 , wherein the cancer is brain cancer. 
     
     
         68 . The method of  claim 64 , wherein the cancer is colon cancer. 
     
     
         69 . The method of  claim 64 , wherein the cancer is lung cancer.