Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: potential positron emission tomography (PET) imaging agents for the dopamine transporter

Abstract

A series of novel fluoroalkyl-containing tropane derivatives was synthesized, and their binding affinities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) were determined via competitive binding assays. Among these derivatives, the fluoropropyl ester of β-CIT ( 19), the fluoroethyl ester of β-CIT ( 20), the N-fluoropropyl derivative of β-CBT ( 12), and the fluoropropyl ester of β-CMT ( 18) displayed higher affinity and greater selectivity for the DAT versus SERT and NET than FP-CIT, which indicates that they are attractive candidates for the development of 18F-labeled PET imaging agents for the DAT.