Discovery and structure -: Activity relationship of quinuclidine benzamides as agonists of α7 nicotinic acetylcholine receptors

被引：191

作者：

Bodnar, AL ^{[1
]}

Cortes-Burgos, LA ^{[1
]}

Cook, KK ^{[1
]}

Dinh, DM ^{[1
]}

Groppi, VE ^{[1
]}

Hajos, M ^{[1
]}

Higdon, NR ^{[1
]}

Hoffmann, WE ^{[1
]}

Hurst, RS ^{[1
]}

Myers, JK ^{[1
]}

Rogers, BN ^{[1
]}

Wall, TM ^{[1
]}

Wolfe, ML ^{[1
]}

Wong, E ^{[1
]}

机构：

[1] Pfizer Inc, Dept Neurosci, Global Res & Dev, Groton, CT USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 04期

关键词：

D O I：

10.1021/jm049363q

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A library of benzamides was tested for alpha7 nicotinic acetylcholine receptor (nAChR) agonist activity using a chimeric receptor in a functional, cell-based, high-throughput assay. From this library, quinuclidine benzamides were found to have alpha7 nAChR agonist activity. The SAR diverged from the activity of this compound class verses the 5-HT3 receptor, a structural homologue of the alpha7 nAChR. PNU-282987, the most potent compound from this series, was also shown to open native alpha7 nAChRs in cultured rat neurons and to reverse an amphetamine-induced gating deficit in rats.

引用

页码：905 / 908

页数：4

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