Synthesis and amine transporter affinities of novel phenyltropane derivatives as potential positron emission tomography (PET) imaging agents

A series of novel fluoroalkyl-containing tropane derivatives (6–8, 10–14, 17, and 18) were synthesized from cocaine. Novel compounds were evaluated for affinity and selectivity in competitive radioligand binding assays selective for cerebral serotonin (5-HT), dopamine (DA), and norepinephrine (NE) transporters (SERT, DAT, and NET). The nortropane-fluoroalkyl esters (7, 10, 11) were most potent for SERT (Ki: 0.18, 0.24, and 0.30 nM, respectively). Tosylate esters 17 and 18, synthesized as precursors for [18F]-labeled, Positron Emission Tomography (PET) imaging agents, also showed high affinity for DAT.