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;
 wherein B is a radical of a prostate-specific membrane antigen (PSMA) binding ligand having the formula   
       
         
           
           
               
               
           
         
       
       wherein * is the point of attachment to L;
 L is a polyvalent linker comprising an alkylenecarbonyl substituted with one or more substituents X 1  selected from the group consisting of aryl, substituted aryl, arylalkyl, and substituted arylalkyl; and one or more cyclic structures selected from the group consisting of a cyclic ether, a cyclic amine, a heterocycle, an arylene, and a heteroarylene; and 
 wherein D is a therapeutic agent or a positron emission tomography (PET) imaging agent; 
 
       or a pharmaceutically acceptable salt thereof. 
     
     
         31 . The conjugate of  claim 30 , or a pharmaceutically acceptable salt thereof, wherein X 1  is arylalkyl. 
     
     
         32 . The conjugate of  claim 31 , or a pharmaceutically acceptable salt thereof, wherein X 1  is 
       
         
           
           
               
               
           
         
       
     
     
         33 . The conjugate of  claim 30 , or a pharmaceutically acceptable salt thereof, wherein the linker further comprises two or more amino acids selected from the group consisting of asparagine, aspartic acid, cysteine, glutamic acid, lysine, glutamine, arginine, serine, ornithine, and threonine. 
     
     
         34 . The conjugate of  claim 33 , or a pharmaceutically acceptable salt thereof, wherein the linker further comprises two or more amino acids selected from the group consisting of aspartic acid, and glutamic acid. 
     
     
         35 . The conjugate of  claim 31 , or a pharmaceutically acceptable salt thereof, wherein the linker further comprises two or more amino acids selected from the group consisting of asparagine, aspartic acid, cysteine, glutamic acid, lysine, glutamine, arginine, serine, ornithine, and threonine. 
     
     
         36 . The conjugate of  claim 35 , or a pharmaceutically acceptable salt thereof, wherein the linker further comprises two or more amino acids selected from the group consisting of aspartic acid, and glutamic acid. 
     
     
         37 . The conjugate of  claim 32 , or a pharmaceutically acceptable salt thereof, wherein the linker further comprises two or more amino acids selected from the group consisting of asparagine, aspartic acid, cysteine, glutamic acid, lysine, glutamine, arginine, serine, ornithine, and threonine. 
     
     
         38 . The conjugate of  claim 37 , or a pharmaceutically acceptable salt thereof, wherein the linker further comprises two or more amino acids selected from the group consisting of aspartic acid, and glutamic acid. 
     
     
         39 . The conjugate of  claim 30 , or a pharmaceutically acceptable salt thereof, wherein the positron emission tomography (PET) imaging agent is an  18 F group covalently attached to the polyvalent linker. 
     
     
         40 . The conjugate of  claim 31 , or a pharmaceutically acceptable salt thereof, wherein the positron emission tomography (PET) imaging agent is an  18 F group covalently attached to the polyvalent linker. 
     
     
         41 . The conjugate of  claim 32 , or a pharmaceutically acceptable salt thereof, wherein the positron emission tomography (PET) imaging agent is an  18 F group covalently attached to the polyvalent linker. 
     
     
         42 . The conjugate of  claim 33 , or a pharmaceutically acceptable salt thereof, wherein the positron emission tomography (PET) imaging agent is an  18 F group covalently attached to the polyvalent linker. 
     
     
         43 . The conjugate of  claim 34 , or a pharmaceutically acceptable salt thereof, wherein the positron emission tomography (PET) imaging agent is an  18 F group covalently attached to the polyvalent linker. 
     
     
         44 . The conjugate of  claim 35 , or a pharmaceutically acceptable salt thereof, wherein the positron emission tomography (PET) imaging agent is an  18 F group covalently attached to the polyvalent linker. 
     
     
         45 . The conjugate of  claim 36 , or a pharmaceutically acceptable salt thereof, wherein the positron emission tomography (PET) imaging agent is an  18 F group covalently attached to the polyvalent linker. 
     
     
         46 . The conjugate of  claim 37 , or a pharmaceutically acceptable salt thereof, wherein the positron emission tomography (PET) imaging agent is an  18 F group covalently attached to the polyvalent linker. 
     
     
         47 . The conjugate of  claim 38 , or a pharmaceutically acceptable salt thereof, wherein the positron emission tomography (PET) imaging agent is an  18 F group covalently attached to the polyvalent linker. 
     
     
         48 . A pharmaceutical composition comprising a conjugate of  claim 30 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier, excipient, or a combination thereof. 
     
     
         49 . A method of imaging comprising administering a subject a conjugate of  claim 30 , or a pharmaceutically acceptable salt thereof, and imaging by positron emission tomography (PET).