Synthesis and Monoamine Transporter Binding of 2-(Diarylmethoxymethyl)-3β-aryltropane Derivatives

Lifen Xu, Santosh S. Kulkarni, Sari Izenwasser, Jonathan L. Katz, Theresa Kopajtic, Stacey A. Lomenzo, Amy Hauck Newman, Mark L. Trudell

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

3β-Aryltropane analogues wherein the 2-position was substituted with various diarylmethoxyalkyl groups were synthesized and evaluated for binding at the dopamine transporter (DAT), serotonin transporter (SERT), norepinephrine transporter (NET), and muscarinic (M1) receptors. The 2β-analogues 9a-i generally demonstrated high to moderate binding affinities (Ki = 34-112 nM) at the DAT with good selectivity over SERT, NET, and M, receptors. Alternatively, the 2α-isomers 10a-i were 10-fold less potent at the DAT with poor selectivity over SERT. These SAR studies provide further evidence for the varied binding requirements of structurally diverse tropane-based ligands and support future studies to elucidate DAT binding requirements in relation to cocaine-like behavioral endpoints.

Original languageEnglish (US)
Pages (from-to)1676-1682
Number of pages7
JournalJournal of Medicinal Chemistry
Volume47
Issue number7
DOIs
StatePublished - Mar 25 2004

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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