Structure-activity studies of 3′-4′-dichloro-meperidine analogues at dopamine and serotonin transporters

Jill B. Rhoden, Maud Bouvet, Sari Izenwasser, Dean Wade, Stacey A. Lomenzo, Mark L. Trudell

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The structure-activity relationships of 3′,4′-dichloro- meperidine were investigated at dopamine (DAT) and serotonin transporters (SERT). Large ester substituents and lipophilic groups at the 4-position favored molecular recognition at the SERT. The benzyl ester of 3′,4′- dichloro-meperidine exhibited high potency and high selectivity for the SERT (DAT/SERT = 760). Chemical modification of the ester group and N-substitution generally led to compounds with decreased DAT affinity. Only small esters and alkyl groups were tolerated at the 4-position of the meperidine ring system by the DAT. Overall, the meperidine analogues were generally more selective for the SERT than for the DAT.

Original languageEnglish (US)
Pages (from-to)5623-5634
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume13
Issue number19
DOIs
StatePublished - Oct 1 2005

Keywords

  • Dopamine transporter
  • Meperidine
  • Serotonin transporter

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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