Radiometal complexes of 2-pyrrolylthiones and their use as radiopharmaceuticals for imaging and therapy

Abstract

Novel 2-pyrrolylthione derived metal chelate compounds are disclosed as imaging and therapeutic agents. Compositions and methods for their preparation and use as diagnostic imaging and therapeutic agents are also disclosed.

We claim:  
     
         1 . A diagnostic imaging or therapeutic agent precursor having the formula:  
       
         
           
           
               
               
           
         
         wherein 
 each of R 1 , R 2 , and R 3  is independently hydrogen, alkyl, OH or its derivative, halogen, NO 2 , NH 2 , N + R 3 , NHCOR, CN, an alkyl carboxylic acid or acid ester group or its derivative, keto, SO 3 H or its derivative, or a group that, when taken together with another ring, ring substituent, forms a fused 5 or 6 membered ring, wherein R is independently hydrogen, alkyl, OH or its derivative, halogen, CN, an alkyl carboxylic acid or acid ester group or its derivative, keto, or SO 3 H or its derivative;  
 X is independently selected from the group consisting of unsubstituted or substituted alkyl or heteroalkyl, unsubstituted or substituted carbocycle, including aryl, unsubstituted or substituted heterocycle, AOH, ACOOH, ACOOR, AHal, CN, ANO 2 , ANH 2 , ANR 2 , AN + R 3 , and ANHCOR wherein A is alkyl, heteroalkyl, carbocycle, including aryl or heterocycle, and  
 R is alkyl or aryl and Hal is a halogen, preferably F, Cl, Br, or I.  
 
       
     
     
         2 . The agent of  claim 1  wherein R 3  is SO 3 H or the salt thereof.  
     
     
         3 . The agent of  claim 2  wherein said salt is Na.  
     
     
         4 . The agent of  claim 1  wherein X is a pyrrole group.  
     
     
         5 . The agent of  claim 1  wherein X is a substituted or unsubstituted phenyl group.  
     
     
         6 . The agent of  claim 5  wherein X is a carboxymethyl substituted phenyl group.  
     
     
         7 . The agent of  claim 1  wherein said carbocycle is aryl or heterocycle.  
     
     
         8 . The agent of  claim 1  wherein Hal is F, Cl, Br, or I.  
     
     
         9 . A composition comprising an agent of  claim 1 .  
     
     
         10 . A method comprising sulfonating an agent of  claim 1  with 1,4-dioxane-sulfotrioxide in the presence of 1,4-dioxane as solvent.  
     
     
         11 . A method of inhibiting a metalloenzyme or chelating a metal comprising contacting said metalloenzyme or metal with an agent according to  claim 1 .  
     
     
         12 . A method of inhibiting a metalloenzyme or chelating a metal comprising contacting said metalloenzyme or metal with an agent according to  claim 2 .  
     
     
         13 . A method of inhibiting a metalloenzyme or chelating a metal comprising contacting said metalloenzyme or metal with an agent according to  claim 3 .  
     
     
         14 . A method of inhibiting a metalloenzyme or chelating a metal comprising contacting said metalloenzyme or metal with an agent according to  claim 4 .  
     
     
         15 . A method of inhibiting a metalloenzyme or chelating a metal comprising contacting said metalloenzyme or metal with an agent according to  claim 5 .  
     
     
         16 . A method of inhibiting a metalloenzyme or chelating a metal comprising contacting said metalloenzyme or metal with an agent according to  claim 6 .  
     
     
         17 . A method of inhibiting a metalloenzyme or chelating a metal comprising contacting said metalloenzyme or metal with an agent according to  claim 7 .  
     
     
         18 . A method of inhibiting a metalloenzyme or chelating a metal comprising contacting said metalloenzyme or metal with an agent according to  claim 8 .  
     
     
         19 . The method of  claim 11  wherein said metal is selected from Tc, Re, Cd, Pb, Zn, Ag, Au, Ga, Pt, Pd, Rh, Cr, Cu, V.