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

被引：74
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.
引用
收藏
页码：2277 / 2281
页数：5
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