Synthesis and pharmacological evaluation of (Z)-9-(Heteroarylmethylene)-7-azatricyclo[4.3.1.03,7]decanes: Thiophene analogues as potent norepinephrine transporter inhibitors

Jia Zhou, Thomas Kläß, Ao Zhang, Kenneth M. Johnson, Cheng Z. Wang, Yanping Ye, Alan P. Kozikowski

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

To further explore the structure-activity relationships (SARs) of certain tropanes, and to gain insights into the structural features required for high activity and selectivity at norepinephrine transporters (NET), we have introduced both five- and six-membered heteroaromatic moieties such as substituted pyridyl, pyrazinyl, pyrimidyl, thiazolyl, and mono- or disubstituted thienyl groups into conformationally constrained, tricyclic tropane analogues. A number of (Z)-9-(heteroarylmethylene)-7-azatricyclo[4.3.1.03,7]decanes were synthesized, and their abilities to block dopamine, serotonin, and norepinephrine reuptake by their respective transporters were evaluated. It was found that the five- or six-membered N-containing aromatics are too basic to display high NET activity, while some of the thiophene analogues were identified as potent and selective NET inhibitors.

Original languageEnglish (US)
Pages (from-to)3565-3569
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume13
Issue number20
DOIs
StatePublished - Oct 20 2003

ASJC Scopus subject areas

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

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