Synthesis of dopamine transporter selective 3-{2-(Diarylmethoxyethylidene)}-8-alkylaryl-8-azabicyclo[3.2.1]octanes

A series of 3-{2-(diarylmethoxyethylidene)}-8-alkylaryl-8-azabicyclo[3.2.1]octanes was synthesized and the binding affinities of the compounds were determined at the dopamine and serotonin transporters. The 8-phenylpropyl analogues 8a (Ki=4.1 nM) and 8b (Ki=3.7 nM) were the most potent compounds of the series with binding affinities 3 times greater than GBR-12909. In addition, 8a (SERT/DAT=327) was over 300-fold more selective for the dopamine transporter than the serotonin transporter.