Modified PSMA ligands and uses related thereto

Abstract

The instant invention provides reagents and methods for diagnosis, detection and treatment of cancers (for example, prostate cancers). In particular, the invention provides methods to generate various functionalized PSMA ligands, and their uses in diagnosis, detection, imaging, and treatment of prostate cancers, especially those overexpressing PSMA.

1 - 3 . (canceled)  
     
     
         4 . A compound represented in the general formula (Ie):  
       
         
           
           
               
               
           
         
         wherein:  
         X represents O or S;  
         Y represents:  
         
           
             
             
                 
                 
             
           
         
         R represents a chelate ligand, a fluorescence tag, or a cytotoxic moiety;  
         R1 and R3, independently for each occurrence, represents an alkyl, an alkenyl, a cycloalkyl, a cycloalkenyl, an aryl, —(CH 2 ) m -aryl, -alkyl-CO 2 R4, -alkenyl-CO 2 R4, -cycloalkyl-CO 2 R4, -cycloalkenyl-CO 2 R4 or -aryl-CO 2 R4;  
         R2 and R4, independently for each occurrence, represent hydrogen, a lower alkyl, or a pharmaceutically acceptable salt;  
         D 1  represents O or S;  
         D 2  represents N 3 , SH 2 , NH 2 , or NO 2 ;  
         m is 1, 2, 3 or 4; and,  
         n is 0, 1, 2 or 3.  
       
     
     
         5 - 66 . (canceled)  
     
     
         67 . A compound represented by the formula VI, or a pharmaceutically acceptable salt thereof:  
       
         
           
           
               
               
           
         
         wherein R represents a chelate ligand, a fluorescence tag, or a cytotoxic moiety, and n is 0, 1, 2 or 3.  
       
     
     
         68 . The compound of  claim 67 , wherein the fluorescence tag is IRDye78, and the compound is represented by the formula VI(a):  
       
         
           
           
               
               
           
         
       
     
     
         69 . The compound of  claim 67 , wherein the chelate ligand is a radioscintigraphic probe.  
     
     
         70 . The compound of  claim 69 , wherein the compound is represented by the formula VI(b):  
       
         
           
           
               
               
           
         
       
     
     
         71 . The compound of  claim 67 , wherein the cytotoxic moiety is a cytotoxic drug for prostate cancer treatment.  
     
     
         72 . The compound of  claim 71 , wherein the compound is represented by the formula VI(c):  
       
         
           
           
               
               
           
         
       
     
     
         73 . A pharmaceutical composition comprising the compound or salt thereof of  claim 67 , and a pharmaceutically acceptable carrier.  
     
     
         74 . The pharmaceutical composition of  claim 67 , wherein the fluorescence tag is IRDye78, and the compound is represented by the formula VI(a).  
     
     
         75 . The pharmaceutical composition of  claim 67 , wherein the chelate ligand is a radioscintigraphic probe.  
     
     
         76 . The pharmaceutical composition of  claim 67 , wherein the chelate ligand is a radioscintigraphic probe, and the compound is represented by the formula VI(b).  
     
     
         77 . The pharmaceutical composition of  claim 68 , wherein the cytotoxic moiety is a cytotoxic drug for prostate cancer treatment.  
     
     
         78 . The pharmaceutical composition of  claim 68 , wherein the cytotoxic moiety is a cytotoxic drug for prostate cancer treatment, and the compound is represented by the formula VI(c).  
     
     
         79 . A method to treat a patient suffering from a disease condition associated with PSMA-overexpression, comprising administering to the patient an effective amount of the compound or salt of  claim 67 , or pharmaceutical composition thereof.  
     
     
         80 . The method of  claim 79 , wherein the disease condition is prostatic hyperplasia or prostate cancer.  
     
     
         81 . The method of  claim 79 , wherein the chelate ligand is a radioscintigraphic probe, and the compound is represented by the formula VI(b).  
     
     
         82 . The method of  claim 79 , wherein the cytotoxic moiety is a cytotoxic drug for prostate cancer treatment, and the compound is represented by the formula VI(c).