Synthesis and monoamine transporter affinity of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position

Fanxing Zeng, Nachwa Jarkas, Michael J. Owens, Clinton D. Kilts, Charles B. Nemeroff, Mark M. Goodman

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

A series of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position was synthesized, and their binding affinities were determined in cells transfected to express human norepinephrine transporter (NET), serotonin transporter (SERT), and dopamine transporter (DAT) via competition binding assays. All compounds studied in this series exhibit a moderate to high potency at all three transporters with SERT or DAT selectivity. 3β-(4′-iodo)phenyltropane bearing methylene on the bridge to the 2β-position (24) presents a particularly attractive pharmacological profile, with very high SERT affinity (Ki = 0.09 nM) and selectivity versus NET (65-fold) and DAT (94-fold).

Original languageEnglish (US)
Pages (from-to)4661-4663
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number17
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

Keywords

  • Carbon-11
  • NET
  • PET
  • SERT
  • Tropane

ASJC Scopus subject areas

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

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