Synthesis and biological evaluation at nicotinic acetylcholine receptors of N-arylalkyl- and N-aryl-7-azabicyclo[2.2.1]heptanes

Jie Cheng, Chunming Zhang, Edwin D. Stevens, Sari Izenwasser, Dean Wade, Shaoyi Chen, Dennis Paul, Mark L. Trudell

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

A new series of N-arylalkyl-substituted 7-azabicyclo[2.2.1]heptanes and N-aryl-substituted 7-azabicyclo[2.2.1]heptanes were synthesized and evaluated as potential ligands for neuronal nicotinic acetylcholine receptors. The in vitro binding affinities (Ki) of the 7-azabicyclo[2.2.1]heptane derivatives were measured by inhibition of [3H]cytisine binding to rat brain tissue, The most potent ligand of the series was found to be N-(3-pyridylmethyl)-7-azabicyclo[2.2.1]heptane (5b, Ki = 98 nM). The chloro analogue (5a, Ki = 245 nM) 5a and epibatidine (1) produced dose-dependent analgesia in both hotplate and tail-flick tests when administered subcutaneously. However, when compounds 1 and 5a,b were administered intrathecally, all produced analgesia in the tail-flick test but only 5a produced analgesia in the hotplate test.

Original languageEnglish (US)
Pages (from-to)3041-3047
Number of pages7
JournalJournal of Medicinal Chemistry
Volume45
Issue number14
DOIs
StatePublished - Jul 4 2002

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'Synthesis and biological evaluation at nicotinic acetylcholine receptors of N-arylalkyl- and N-aryl-7-azabicyclo[2.2.1]heptanes'. Together they form a unique fingerprint.

Cite this