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

被引：42
作者：
Wei, ZL
Xiao, YX
Yuan, HB
Baydyuk, M
Petukhov, PA
Musachio, JL
Kellar, KJ
Kozikowski, AP
机构：
[1] Univ Illinois, Coll Pharm, Dept Med Chem, Chicago, IL 60612 USA
[2] Georgetown Univ, Dept Pharmacol, Washington, DC 20057 USA
[3] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD USA
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 06期
关键词：
D O I：
10.1021/jm0492406
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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 beta 2 subunits over nACbRs containing beta 4 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.
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页码：1721 / 1724
页数：4
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