Synthesis and biological evaluation of 2β,3α-(substituted phenyl)nortropanes as potential norepinephrine transporter imaging agents

A series of 2β,3α-(substituted phenyl)nortropanes was synthesized and evaluated in vitro for human monoamine transporters. All compounds studied in this series exhibited nanomolar potency for the norepinephrine transporter (NET). Radiolabeling and nonhuman primate microPET brain imaging studies were performed with the most promising compound, [11C]1, to determine its utility as a NET imaging agent. Despite high in vitro affinity for the human NET, the high uptake of [11C]1 in the caudate and putamen excludes its use as an in vivo PET imaging agent for the NET.