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 journalArticle

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

Fingerprint Dive into the research topics of 'Synthesis and Monoamine Transporter Binding of 2-(Diarylmethoxymethyl)-3β-aryltropane Derivatives'. Together they form a unique fingerprint.

  • Cite this

    Xu, L., Kulkarni, S. S., Izenwasser, S., Katz, J. L., Kopajtic, T., Lomenzo, S. A., Newman, A. H., & Trudell, M. L. (2004). Synthesis and Monoamine Transporter Binding of 2-(Diarylmethoxymethyl)-3β-aryltropane Derivatives. Journal of Medicinal Chemistry, 47(7), 1676-1682. https://doi.org/10.1021/jm030430a