Discovery and structure-activity relationship of coumarin derivatives as TNF-α inhibitors

被引：57

作者：

Cheng, JF

Chen, M

Wallace, D

Tith, S

Arrhenius, T

Kashiwagi, H

Ono, Y

Ishikawa, A

Sato, H

Kozono, T

Sato, H

Nadzan, AM

机构：

[1] Chugai Pharma USA LLC, Dept Chem, San Diego, CA 92121 USA

[2] Chugai Pharmaceut Co Ltd, Fuji Gotemba Res Labs, Shizuoka 412, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 10期

关键词：

coumarin; TNF-alpha;

D O I：

10.1016/j.bmcl.2004.03.022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery and structure-activity relationship of a novel series of coumarin-based TNF-alpha inhibitors is described. Starting from the initial lead la, various derivatives were prepared surrounding the coumarin core structure to optimize the in vitro inhibitory activity of TNF-alpha production by human peripheral blood mononuclear cells (hPBMC), stimulated by bacterial lipopolysaccharide (LPS). Selected compounds also demonstrated in vivo inhibition of TNF-alpha production in rats. (C) 2004 Elsevier Ltd. All rights reserved.

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页码：2411 / 2415

页数：5

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