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

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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

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Dopamine Plasma Membrane Transport Proteins
Serotonin Plasma Membrane Transport Proteins
Norepinephrine Plasma Membrane Transport Proteins
Derivatives
Tropanes
Muscarinic M1 Receptors
Cocaine
Isomers
Ligands

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Synthesis and Monoamine Transporter Binding of 2-(Diarylmethoxymethyl)-3β-aryltropane Derivatives. / Xu, Lifen; Kulkarni, Santosh S.; Izenwasser, Sari E; Katz, Jonathan L.; Kopajtic, Theresa; Lomenzo, Stacey A.; Newman, Amy Hauck; Trudell, Mark L.

In: Journal of Medicinal Chemistry, Vol. 47, No. 7, 25.03.2004, p. 1676-1682.

Research output: Contribution to journalArticle

Xu, L, Kulkarni, SS, Izenwasser, SE, Katz, JL, Kopajtic, T, Lomenzo, SA, Newman, AH & Trudell, ML 2004, 'Synthesis and Monoamine Transporter Binding of 2-(Diarylmethoxymethyl)-3β-aryltropane Derivatives', Journal of Medicinal Chemistry, vol. 47, no. 7, pp. 1676-1682. https://doi.org/10.1021/jm030430a
Xu, Lifen ; Kulkarni, Santosh S. ; Izenwasser, Sari E ; Katz, Jonathan L. ; Kopajtic, Theresa ; Lomenzo, Stacey A. ; Newman, Amy Hauck ; Trudell, Mark L. / Synthesis and Monoamine Transporter Binding of 2-(Diarylmethoxymethyl)-3β-aryltropane Derivatives. In: Journal of Medicinal Chemistry. 2004 ; Vol. 47, No. 7. pp. 1676-1682.
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