SYNTHESIS OF HALOGENATED ANALOGS OF -2,3-DIHYDRO-5-HYDROXY-5H-IMIDAZO[2,1-A]-ISOINDOLE OR MAZINDOL FOR EXPLORATION OF THE DOPAMINE TRANSPORTER

In order to study the presynaptic dopamine transporter in the human br ain by single photon emission tomography (SPET) or positron emission t omography (PET) we have developed new halogenated mazindol derivatives using a pathway involving a reaction between a dilithio derivative of 2-phenyl-2-imidazoline and appropriate methyl or ethyl halogenobenzoa tes. After HPLC purification and chemical characterization, the affini ty for the dopamine transporter was studied in vitro with [H-3]-GBR 12 935 and compared to mazindol and nomifensine. Affinity potencies were determined as follow:- mazindol > brominated derivatives > iodinated d erivatives > nomifensine > fluorinated derivatives. The properties wer e related tot eh structure of these compounds and showed the importanc e of the nature of the substituent on the primary phenyl ring of mazin dol for affinity to the dopamine transporter.