Conjugates for treating diseases caused by psma expressing cells

Abstract

The invention described herein pertains to the diagnosis, imaging, and/or treatment of pathogenic cell populations. In particular, the invention described herein pertains to the diagnosis, imaging, and/or treatment of diseases caused by PSMA expressing cells, such as prostate cancer cells, using compounds capable of targeting PSMA expressing cells.

1 .- 29 . (canceled) 
     
     
         30 . A conjugate having a formula B-L-D or a pharmaceutically acceptable salt thereof, wherein
 B is a radical of a PSMA binding ligand having the formula   
       
         
           
           
               
               
           
         
       
       wherein * is the point of attachment to L;
 L is a polyvalent linker optionally comprising an aminomethylphenyl acetic acid diradical and one or more portions selected from the group consisting of 
 
       
         
           
           
               
               
           
         
       
       and further comprising one or more amino acids in an unnatural configuration, and
 D is a radical of a therapeutic agent or a radioactive isotope of a metal coordinated to a radical of a chelating group. 
 
     
     
         31 . The conjugate of  claim 30 , comprising at least two amino acids in an unnatural configuration. 
     
     
         32 . The conjugate of  claim 30 , comprising at least three amino acids in an unnatural configuration. 
     
     
         33 . The conjugate of  claim 30 , wherein the at least one amino acid is in a D-configuration. 
     
     
         34 . The conjugate of  claim 31 , wherein the at least two amino acids are in a D-configuration. 
     
     
         35 . The conjugate of  claim 32 , wherein the at least three amino acids are in a D-configuration. 
     
     
         36 . The conjugate of  claim 30 , wherein the at least one amino acid is optionally substituted D-phenylalanine. 
     
     
         37 . The conjugate of  claim 30 , wherein the at least one amino acid is optionally substituted D-tyrosine. 
     
     
         38 . The conjugate of  claim 30 , wherein the at least one amino acid is D-lysine. 
     
     
         39 . The conjugate of  claim 30 , wherein the at least one amino acid is D-phenylalanine, D-tyrosine or D-lysine, wherein each hydrogen atom on the amino acid side chain is independently substituted with an amino, hydroxy, halo, thio, alkyl, haloalkyl, heteroalkyl, aryl, arylalkyl, arylheteroalkyl, heteroaryl, heteroarylalkyl, heteroarylheteroalkyl, nitro, or sulfonic acid group. 
     
     
         40 . The conjugate of  claim 30 , wherein the at least one amino acid is D-phenylalanine, wherein each hydrogen atom on the D-phenylalanine side chain is independently optionally substituted with an amino, hydroxy, halo, thio, alkyl, haloalkyl, heteroalkyl, aryl, arylalkyl, arylheteroalkyl, heteroaryl, heteroarylalkyl, heteroarylheteroalkyl, nitro, or sulfonic acid group. 
     
     
         41 . The conjugate of  claim 30 , wherein the at least one amino acid is D-tyrosine, wherein one or more hydrogen atoms on the D-tyrosine side chain is independently optionally substituted with an amino, hydroxy, halo, thio, alkyl, haloalkyl, heteroalkyl, aryl, arylalkyl, arylheteroalkyl, heteroaryl, heteroarylalkyl, heteroarylheteroalkyl, nitro, or sulfonic acid group. 
     
     
         42 . The conjugate of  claim 34 , wherein the at least two amino acids are each independently optionally substituted D-phenylalanine, optionally substituted D-tyrosine or optionally substituted D-lysine. 
     
     
         43 . The conjugate of  claim 35 , wherein the at least three amino acids are each independently optionally substituted D-phenylalanine, optionally substituted D-tyrosine or optionally substituted D-lysine. 
     
     
         44 . The conjugate of  claim 34 , wherein the at least two amino acids are each independently D-phenylalanine, D-tyrosine, or D-lysine, wherein each hydrogen atom on the amino acid side chain is independently optionally substituted with an amino, hydroxy, halo, thio, alkyl, haloalkyl, heteroalkyl, aryl, arylalkyl, arylheteroalkyl, heteroaryl, heteroarylalkyl, heteroarylheteroalkyl, nitro, or sulfonic acid group. 
     
     
         45 . The conjugate of  claim 35 , wherein the at least three amino acids are each independently D-phenylalanine, D-tyrosine, or D-lysine, wherein each hydrogen atom on the amino acid side chain is independently optionally substituted with an amino, hydroxy, halo, thio, alkyl, haloalkyl, heteroalkyl, aryl, arylalkyl, arylheteroalkyl, heteroaryl, heteroarylalkyl, heteroarylheteroalkyl, nitro, or sulfonic acid group. 
     
     
         46 . A pharmaceutical composition comprising a conjugate of  claim 30 , and at least one pharmaceutically acceptable carrier, excipient, or a combination thereof. 
     
     
         47 . A method of treating a disease in a patient caused by a pathogenic population of cells that express PSMA, comprising the step of administering to the patient a therapeutically effective amount of a conjugate of  claim 30 . 
     
     
         48 . The method of  claim 47 , wherein the disease is prostate cancer. 
     
     
         49 . A method of imaging a pathogenic population of cells that express PSMA in a patient comprising the step of administering to the patient a therapeutically effective amount of a conjugate of  claim 30 .