Discovery of novel conformationally constrained tropane-based biaryl and arylacetylene ligands as potent and selective norepinephrine transporter inhibitors and potential antidepressants

Jia Zhou, Thomas Kläß, Kenneth M. Johnson, Kelly M. Giberson, Alan P. Kozikowski

Research output: Contribution to journalArticle

4 Scopus citations


To further explore the structure-activity relationships of conformationally constrained tropanes, a number of new biaryl and arylacetylene analogs were designed and synthesized. Some of these compounds such as 3a-b, 3d, 3f-h, 5b, and 7g were found to be highly potent and selective or mixed norepinephrine transporter (NET) inhibitors with Ki values of 0.8-9.4 nM. Moreover, all of these compounds display weak to extremely weak muscarinic receptor binding affinity, indicating that as potential antidepressants, they may overcome certain side effects that are of concern with other antidepressants, which are thought to be mediated by their anticholinergic properties.

Original languageEnglish (US)
Pages (from-to)2461-2465
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number10
StatePublished - May 16 2005
Externally publishedYes



  • Antidepressants
  • Biaryl and arylacetylene ligands
  • Conformationally constrained tropanes
  • Muscarinic receptor affinity
  • NET inhibitors

ASJC Scopus subject areas

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

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