Synthesis, SAR studies, and evaluation of 1,4-benzoxazepine derivatives as selective 5-HT1A receptor agonists with neuroprotective effect:: Discovery of Piclozotan

被引：64

作者：

Kamei, K ^{[1
]}

Maeda, N ^{[1
]}

Nomura, K ^{[1
]}

Shibata, M ^{[1
]}

Katsuragi-Ogino, R ^{[1
]}

Koyama, M ^{[1
]}

Nakajima, M ^{[1
]}

Inoue, T ^{[1
]}

Ohno, T ^{[1
]}

Tatsuoka, T ^{[1
]}

机构：

[1] Daiichi Asubio Pharma Co Ltd, Osaka 6188513, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2006年 / 14卷 / 06期

关键词：

1,4-benzoxazepine; 5-HT1A; neuroprotective; anti-ischemia; piclozotan; SUNN4057;

D O I：

10.1016/j.bmc.2005.10.046

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A new series of 1,4-benzoxazepine derivatives was designed, synthesized, and evaluated for binding to 5-HT1A receptor and cerebral anti-ischemic effect. A lot of compounds exhibited nanomolar affinity for 5-HT1A receptor with good selectivity over both dopamine D, and alpha(1)-adrenergic receptors. Among these compounds, 3-chloro-4-[4-[4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-y]butyl]-1, 4-benzoxazepin-5(4H)-one (50: SUN N4057 (Piclozotan) as 2HCl salt) showed remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：1978 / 1992

页数：15

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