Synthesis and monoamine transporter affinity of new 2β-carbomethoxy-3β-[aryl or heteroaryl]phenyltropanes

A series of 16 new 2β-carbomethoxy-3β-[aryl or heteroaryl]phenyltropane derivatives was synthesized and evaluated for binding to monoamine transporters. Most of the compounds exhibited nanomolar affinity for the serotonin transporter (SERT). Four compounds (29, 14, 11, and 10) presented a particularly attractive pharmacological profile, with very high SERT affinity (Ki 0.15–0.5 nM) and selectivity versus the dopamine transporter of 25- to 77-fold.

Graphical abstractA series of 16 new 2β-carbomethoxy-3β-[aryl or heteroaryl]phenyltropane derivatives was synthesized and evaluated for binding to monoamine transporters. Most of the compounds exhibited subnanomolar affinity for the serotonin transporter (SERT).Figure optionsDownload full-size imageDownload as PowerPoint slide