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

Xiaobo Gu, Sari E Izenwasser, Dean Wade, Amy Housman, Gerard Gulasey, Jill B. Rhoden, Christopher D. Savoie, David L. Mobley, Stacey A. Lomenzo, Mark L. Trudell

Research output: Contribution to journalArticle

2 Citations (Scopus)

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

Original languageEnglish
Pages (from-to)8356-8364
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number23
DOIs
StatePublished - Dec 1 2010

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Meperidine
Esters
Ligands
Derivatives
Norepinephrine Plasma Membrane Transport Proteins
Dopamine Plasma Membrane Transport Proteins
normeperidine

Keywords

  • Depression
  • Dopamine transporters
  • Meperidine
  • Norepinephrine transporters
  • Normeperidine
  • Serotonin transporter

ASJC Scopus subject areas

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

Cite this

Synthesis and structure-activity studies of benzyl ester meperidine and normeperidine derivatives as selective serotonin transporter ligands. / Gu, Xiaobo; Izenwasser, Sari E; Wade, Dean; Housman, Amy; Gulasey, Gerard; Rhoden, Jill B.; Savoie, Christopher D.; Mobley, David L.; Lomenzo, Stacey A.; Trudell, Mark L.

In: Bioorganic and Medicinal Chemistry, Vol. 18, No. 23, 01.12.2010, p. 8356-8364.

Research output: Contribution to journalArticle

Gu, Xiaobo ; Izenwasser, Sari E ; Wade, Dean ; Housman, Amy ; Gulasey, Gerard ; Rhoden, Jill B. ; Savoie, Christopher D. ; Mobley, David L. ; Lomenzo, Stacey A. ; Trudell, Mark L. / Synthesis and structure-activity studies of benzyl ester meperidine and normeperidine derivatives as selective serotonin transporter ligands. In: Bioorganic and Medicinal Chemistry. 2010 ; Vol. 18, No. 23. pp. 8356-8364.
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AU - Wade, Dean

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AU - Gulasey, Gerard

AU - Rhoden, Jill B.

AU - Savoie, Christopher D.

AU - Mobley, David L.

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AU - Trudell, Mark L.

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