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

Bioorg Med Chem. 2010 Dec 1;18(23):8356-64. doi: 10.1016/j.bmc.2010.09.060. Epub 2010 Sep 29.

Abstract

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 (K(i) values <2nM) and high SERT selectivity (DAT/SERT >1500 and NET/SERT >1500).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Esters
  • Ligands
  • Meperidine / analogs & derivatives*
  • Meperidine / chemical synthesis
  • Meperidine / chemistry
  • Meperidine / pharmacology
  • Selective Serotonin Reuptake Inhibitors / chemical synthesis*
  • Selective Serotonin Reuptake Inhibitors / chemistry
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin Plasma Membrane Transport Proteins / chemistry*
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Esters
  • Ligands
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Meperidine
  • normeperidine