Design of novel quinazoline derivatives and related analogues as potent and selective ALK5 inhibitors

被引：75

作者：

Gellibert, F. ^{[1
]}

Fouchet, M. -H. ^{[1
]}

Nguyen, V. -L. ^{[1
]}

Wang, R. ^{[2
]}

Krysa, G. ^{[1
]}

de Gouville, A. -C. ^{[1
]}

Huet, S. ^{[1
]}

Dodic, N. ^{[1
]}

机构：

[1] GlaxoSmithKline Inc, F-91951 Les Ulis, France

[2] GlaxoSmithKline Inc, Res Triangle Pk, NC 27703 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 08期

关键词：

Transforming growth factor-beta; ALK5; P38MAP Kinase; Liver fibrosis; I RECEPTOR KINASE; TGF-BETA; FIBROSIS; CANCER;

D O I：

10.1016/j.bmcl.2009.02.087

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Starting from quinazoline 3a, we designed potent and selective ALK5 inhibitors over p38MAP kinase from a rational drug design approach based on co-crystal structures in the human ALK5 kinase domain. The quinazoline 3d exhibited also in vivo activity in an acute rat model of DMN-induced liver fibrosis when administered orally at 5 mg/kg (bid). (c) 2009 Elsevier Ltd. All rights reserved.

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页码：2277 / 2281

页数：5

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