Atropisomeric quinazolin-4-one derivatives are potent noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists

被引：135

作者：

Welch, WM ^{[1
]}

Ewing, FE ^{[1
]}

Huang, J ^{[1
]}

Menniti, FS ^{[1
]}

Pagnozzi, MJ ^{[1
]}

Kelly, K ^{[1
]}

Seymour, PA ^{[1
]}

Guanowsky, V ^{[1
]}

Guhan, S ^{[1
]}

Guinn, MR ^{[1
]}

Critchett, D ^{[1
]}

Lazzaro, J ^{[1
]}

Ganong, AH ^{[1
]}

DeVries, KM ^{[1
]}

Staigers, TL ^{[1
]}

Chenard, BL ^{[1
]}

机构：

[1] Pfizer Inc, Groton Labs, Global Res & Dev, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 02期

关键词：

D O I：

10.1016/S0960-894X(00)00622-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Piriqualone (1) was found to be an antagonist of AMPA receptors. Structure-activity optimization was conducted on each of the three rings in 1 to afford a series of potent and selective antagonists. The sterically crowded environment surrounding the N-3 aryl group provided sufficient thermal stability for atropisomers to be isolated. Separation of these atropisomers resulted in the identification of (+)-38 (CP-465,022), a compound that binds to the AMPA receptor with high affinity (IC50 = 36 nM) and displays potent anticonvulsant activity. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：177 / 181

页数：5

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