[3-cis-3,5-dimethyl-(1-piperazinyl)alkyl]-bis-(4 '-fluorophenyl)amine analogues as novel probes for the dopamine transporter

in a continuing effort to identify novel probes with which to study the dop amine transporter (DAT), we discovered that the a receptor antagonist, rimc azole, binds with moderate affinity (K-i=224 nM) to the DAT, The results fr om previous SAR studies suggested that substitution of the carbazole ring s ystem of rimcazole with bis-(4'-fluorophenyl)amine might improve binding af finity and selectivity for the DAT. Thus, a novel series of [3-cis-3.5-dime thyl-(1-piperazinyl)alkyl]bis-(4'-fluorophenyl)amines were synthesized. The most potent compound in this series (9b) displaced [H-3]WIN 35.428 binding in rat caudate-putamen (K-i = 17.6 nM) with comparable affinity to GBR 129 09. Despite high-affinity binding at DAT. and structural similarity to GBR 12909, preliminary studies suggest 9b behaves more like rimeazole than GBR 12909 and does not demonstrate cocaine-like psychostimulant behavior in mic e. (C) 2001 Published by Elsevier Science Ltd.