Novel pyridyl ring C5 substituted analogues of epibatidine and 3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine (A-84543) as highly selective agents for neuronal nicotinic acetylcholine receptors containing β2 subunits

Zhi Liang Wei, Yingxian Xiao, Hongbin Yuan, Maryna Baydyuk, Pavel A. Petukhov, John L. Musachio, Kenneth J. Kellar, Alan P. Kozikowski

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction of a hydrophobic or hydrogen-bonding alkynyl group into the C5 position of the pyridyl ring of epibatidine and A-84543 significantly increased the selectivity for neuronal nicotinic acetylcholine receptors (nAChRs) containing β2 subunits over nAChRs containing β4 subunits (K i ratio up to 92000-fold). Our data indicate that the extracellular domains of the nAChRs are sufficiently different to allow for the design of novel ligands with high affinity and selectivity for the nAChR subtypes.

Original languageEnglish (US)
Pages (from-to)1721-1724
Number of pages4
JournalJournal of medicinal chemistry
Volume48
Issue number6
DOIs
StatePublished - Mar 24 2005

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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