Synthesis and structure-activity studies of benzyl ester meperidine and normeperidine derivatives as selective serotonin transporter ligands

A series of benzyl esters of meperidine and normeperidine were synthesized and evaluated for binding affinity at serotonin, dopamine and norepinephrine transporters. The 4-methoxybenzyl ester 8b and 4-nitrobenzyl ester 8c in the meperidine series and 4-methoxybenzyl ester 14a in the normeperidine series exhibited low nanomolar binding affinities at the SERT (Ki values <2 nM) and high SERT selectivity (DAT/SERT >1500 and NET/SERT >1500).