Psma-targeting compounds and uses thereof

Abstract

Compositions and methods for visualizing tissue under illumination with near-infrared radiation, including compounds comprising near-infrared, closed chain, sulfo-cyanine dyes and prostate specific membrane antigen ligands are disclosed.

1 . A compound having the structure 
       
         
           
           
               
               
           
         
         wherein the subunits associated with elements p, q, r, and s may be in any order; 
         Z is tetrazole or CO 2 Q; each Q is independently selected from hydrogen or a protecting group, a is 1, 2, 3, or 4; 
         R is each independently H or C 1 -C 4  alkyl; 
         r is 0 or 1; 
         Tz is a triazole group selected from the group consisting of 
       
       
         
           
           
               
               
           
         
         L 1  is 
       
       
         
           
           
               
               
           
         
         L 2  is 
       
       
         
           
           
               
               
           
         
         X 1  is —NRC(O)—, —NRC(O)NR—, —NRC(S)NR—, or —NRC(O)O—; 
         X 2  is —C(O)NR—, —NRC(O)NR—, —NRC(S)NR—, or —OC(O)NR—; 
         R 5  is H, CO 2 H, or CO 2 R 6 , where R 6  is a C 1 -C 6  alkyl, C 2 -C 12  aryl, or C 4 -C 16  alkylaryl; 
         b is 1, 2, 3, or 4; 
         d is 1, 2, 3, or 4; 
         q is 0 or 1; 
         W is —NRC(O)—, —NRC(O)NR—, NRC(S)NR—, —NRC(O)O—, —OC(O)NR—, —OC(O)—, —C(O)NR—, or —C(O)O— 
         R 2  and R 3  are independently H, CO 2 H, or CO 2 R 4 , where R 4  is a C 1 -C 6  alkyl, C 2 -C 12  aryl, or C 4 -C 16  alkylaryl, wherein if one of R 2  and R 3  is CO 2 H or CO 2 R 2 , then the other is H; 
         n is 1, 2, 3, 4, 5 or 6; 
         s is 0 or 1, 
         Y is —C(O)—, —NRC(O)—, —NRC(S)—, —OC(O)—; 
         m is 1, 2, 3, 4, 5, or 6; 
         p is 0, 1, 2, or 3, and when p is 2 or 3, each R 1  may be the same or different; 
         R 1  is H, C 1 -C 6  alkyl, C 2 -C 12  aryl, or C 4 -C 16  alkylaryl; 
         G is a moiety selected from the group consisting of 
       
       
         
           
           
               
               
           
         
         where Ch is a metal chelating moiety, optionally including a chelated metal; FG is a fluorescent dye moiety which emits in the visible or near infrared spectrum; one of A and A 1  is Ch and the other is FG; V and V are independently —C(O)—, —NRC(O)—, —NRC(S)—, or —OC(O)—; and g is 1, 2, 3, 4, 5, or 6; 
         with the condition that: 
         when G is 
       
       
         
           
           
               
               
           
         
          and r is 0, then q and s are both 1; 
         when G is 
       
       
         
           
           
               
               
           
         
          and r is 0, then q and s are both 0 or both 1; 
         when G is 
       
       
         
           
           
               
               
           
         
          then p is 0 and R 2  is H, and the structure optionally includes a chelated metal ion; 
         when G is 
       
       
         
           
           
               
               
           
         
          and r is 0, then if p is 0, then one of R 2  and R 3  is CO 2 R 2 , and the other is H; and 
         when g is 
       
       
         
           
           
               
               
           
         
          then r is 0. 
       
     
     
         2 .- 150 . (canceled)