SUBSTITUTED 3-PHENYLTROPANE ANALOGS OF COCAINE - SYNTHESIS, INHIBITION OF BINDING AT COCAINE RECOGNITION SITES, AND POSITRON EMISSION TOMOGRAPHY IMAGING

It is now accepted that (-)-cocaine binds to specific recognition sites associated with monoamine transporters in the mammalian brain. In this study, several analogs of 3beta-phenyltropane-2beta-carboxylic acid methyl ester were prepared and their potency for inhibiting the binding of [H-3]-3beta-(4-fluorophenyl)tropane-2beta-carboxylic acid methyl ester to primate caudate-putamen was evaluated. The synthesis and binding affinity of 3beta-(3,4-dichlorophenyl)tropane-2beta-carboxylic acid methyl ester, one of the most potent cocaine congeners yet reported, is presented. The feasibility of synthesizing high-affinity ligands for cocaine recognition sites and their suitability as PET imaging ligands for cocaine receptors in vivo is demonstrated.