Psma-targeted nir dyes and their uses

Abstract

The present disclosure relates to prostate specific membrane antigen (PSMA) targeted compounds conjugated to near-infra red (NIR) dyes and methods for their therapeutic and diagnostic use. More specifically, this disclosure provides compounds and methods for diagnosing and treating diseases associated with cells and/or vasculature expressing prostate specific membrane antigen (PSMA), such as prostate cancer and related diseases. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds.

1 - 22 . (canceled) 
     
     
         23 . A compound having the structural formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         each R 1  represents a hydrogen or SO 3 H; 
         each R 2  represents a hydrogen, CH 3 , C 3 H 6 SO 3   − , C 3 H 6 SO 3 H or C 4 H 8 SO 3   − , or C 4 H 8 SO 3 H or C 3 H 6 N + (CH 3 ) 3 H; 
         R 3  and R 5  each represents a carbon, optionally one or more sharing bonds, 
         R 4  represents a carbon with optionally one or more sharing bonds; 
         R 6  represents nitrogen, oxygen, sulfur or nothing; 
         R 7  is optional and, when present, represents an aromatic substitution group that enhances the spectral properties of the compound; 
         R 8  represents linkers with aromatic amino acids or derivatives of them, cationic amino acids or derivatives of them, anionic amino acids or derivatives of them, or unnatural amino acids of aromatic/cationic/anionic acids or derivatives of them; 
         R 9  represents a C 7 -linear carbon chain or a derivative thereof or a polyethylene glycol linker or a derivative thereof; 
         R 10  represents a CO 2 H, PO 3 H 2 , SO 3 H, CH 2 SO 3 H, CH 2 CONHCH 2 SO 3 H, or CH 2 CONHCH 2 CH 2 SO 3 H; 
         each R 1 , represents a CO 2 H, SO 3 H, CH 2 CONHCH 2 SO 3 H, or CH 2 CONHCH 2 CH 2 SO 3 H; and 
         each R 12  represents a hydrogen. 
       
     
     
         24 . The compound of  claim 23 , or a pharmaceutically acceptable salt thereof, wherein R 9  represents: 
       
         
           
           
               
               
           
         
       
     
     
         25 . The compound of  claim 23 , or a pharmaceutically acceptable salt thereof, wherein R 10  and R 11  each represents a CO 2 H group and each R 12  represents a hydrogen. 
     
     
         26 . The compound of  claim 23 , or a pharmaceutically acceptable salt thereof, wherein [—N(H)—R 8 —] represents an aromatic amino acid. 
     
     
         27 . The compound of  claim 26 , or a pharmaceutically acceptable salt thereof, wherein R 8  forms a peptide bond with another amino acid. 
     
     
         28 . The compound of  claim 27 , or a pharmaceutically acceptable salt thereof, wherein [—N(H)—R 8 —] is phenylalanyl and phenylalanyl forms a peptide bond with another phenylalanyl. 
     
     
         29 . The compound of  claim 23 , or a pharmaceutically acceptable salt thereof, wherein R 6  represents oxygen. 
     
     
         30 . The compound of  claim 23 , or a pharmaceutically acceptable salt thereof, wherein each R 1  represents SO 3 H. 
     
     
         31 . The compound of  claim 23 , or a pharmaceutically acceptable salt thereof, wherein each R 2  represents C 3 H 6 SO 3   −  or C 3 H 6 SO 3 H. 
     
     
         32 . The compound of  claim 23 , or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of the formula: