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 . A conjugate of the formula 
       or a pharmaceutically acceptable salt thereof, wherein B comprises a urea of lysine and an amino acid selected from the group consisting of aspartic acid, glutamic acid, and homoglutamic acid, L is a polyvalent linker comprising (i) an alkylene or an alkylenecarbonyl, each of which is substituted with a guanidinoalkyl, an alkyl carboxylate or an arylalkyl, and (ii) an alkylene, a cycloalkylene, an alkylenecycloalkyl, or a cycloalkylenecarbonyl, and D is a radioactive isotope of a metal coordinated to a chelating group, wherein the chelating group is covalently attached to L. 
     
     
         2 - 29 . (canceled) 
     
     
         30 . The conjugate of  claim 1 , or the pharmaceutically acceptable salt thereof, wherein B is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         31 . The conjugate of  claim 30 , or the pharmaceutically acceptable salt thereof, wherein B 
       
         
           
           
               
               
           
         
       
     
     
         32 . The conjugate of  claim 1 , or the pharmaceutically acceptable salt thereof, wherein L forms an amide, a thioamide, a urea, or a thiourea with the lysine. 
     
     
         33 . The conjugate of  claim 32 , or the pharmaceutically acceptable salt thereof, wherein L forms an amide or a urea with the lysine. 
     
     
         34 . The conjugate of  claim 33 , or the pharmaceutically acceptable salt thereof, wherein L forms an amide with the lysine. 
     
     
         35 . The conjugate of  claim 1 , or the pharmaceutically acceptable salt thereof, wherein L is not a releasable linker. 
     
     
         36 . The conjugate of  claim 1 , or the pharmaceutically acceptable salt thereof, wherein the amino acid is glutamic acid. 
     
     
         37 . The conjugate of  claim 31 , or the pharmaceutically acceptable salt thereof, wherein the linker comprises an alkylene substituted with an arylalkyl or an alkylenecarbonyl substituted with an arylalkyl. 
     
     
         38 . The conjugate of  claim 37 , or the pharmaceutically acceptable salt thereof, wherein the arylalkyl comprises a naphthyl. 
     
     
         39 . The conjugate of  claim 38 , or the pharmaceutically acceptable salt thereof, wherein the naphthyl comprises a 2-naphthyl. 
     
     
         40 . The conjugate of  claim 38 , or the pharmaceutically acceptable salt thereof, wherein the arylalkyl is of the formula 
       
         
           
           
               
               
           
         
       
       wherein * represents a point of covalent attachment to the alkylene or the alkylenecarbonyl. 
     
     
         41 . The conjugate of  claim 1 , or the pharmaceutically acceptable salt thereof, wherein the cycloalkylene, alkylenecycloalkyl, or cycloalkylenecarbonyl comprises a cyclohexyl group. 
     
     
         42 . The conjugate of  claim 31 , or the pharmaceutically acceptable salt thereof, wherein the cycloalkylene, alkylenecycloalkyl, or cycloalkylenecarbonyl comprises a cyclohexyl group. 
     
     
         43 . The conjugate of  claim 37 , or the pharmaceutically acceptable salt thereof, wherein the cycloalkylene, alkylenecycloalkyl, or cycloalkylenecarbonyl comprises a cyclohexyl group. 
     
     
         44 . The conjugate of  claim 39 , or the pharmaceutically acceptable salt thereof, wherein the cycloalkylene, alkylenecycloalkyl, or cycloalkylenecarbonyl comprises a cyclohexyl group. 
     
     
         45 . The conjugate of  claim 40 , or the pharmaceutically acceptable salt thereof, wherein the cycloalkylene, alkylenecycloalkyl, or cycloalkylenecarbonyl comprises a cyclohexyl group. 
     
     
         46 . The conjugate of  claim 1 , or the pharmaceutically acceptable salt thereof, wherein L comprises a chain of at least about 8 atoms. 
     
     
         47 . The conjugate of  claim 1 , or the pharmaceutically acceptable salt thereof, wherein L comprises a chain of at least about 9 atoms. 
     
     
         48 . The conjugate of  claim 44 , or the pharmaceutically acceptable salt thereof, wherein L comprises a chain of at least about 9 atoms.