Identification of amidoheteroaryls as potent inhibitors of mutant (V600E) B-Raf kinase with in vivo activity

被引：10

作者：

Lyne, Paul D. ^{[1
]}

Aquila, Brian ^{[1
]}

Cook, Donald J. ^{[1
]}

Dakin, Les A. ^{[1
]}

Ezhuthachan, Jay ^{[1
]}

Ioannidis, Stephanos ^{[1
]}

Pontz, Timothy ^{[1
]}

Su, Mei ^{[1
]}

Ye, Qing ^{[1
]}

Zheng, Xiaolan ^{[1
]}

Block, Michael H. ^{[1
]}

Cowen, Scott ^{[1
]}

Deegan, Tracy L. ^{[1
]}

Lee, John W. ^{[1
]}

Scott, David A. ^{[1
]}

Custeau, Dominique ^{[1
]}

Drew, Lisa ^{[1
]}

Poondru, Srinivasu ^{[1
]}

Shen, Minhui ^{[1
]}

Wu, Allan ^{[1
]}

机构：

[1] AstraZeneca R&D Boston, Canc Res, Waltham, MA 02451 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 03期

关键词：

B-Raf; V600E; Amidoheteroaryl; P38 MAP KINASE; ACTIVATION; MUTATIONS; CANCER; PATHWAY;

D O I：

10.1016/j.bmcl.2008.10.053

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of amidoheteroaryl compounds were designed and synthesized as inhibitors of B-Raf kinase. Several compounds from the series show excellent potency in biochemical, phenotypic and mode of action cellular assays. Potent examples from the series have also demonstrated good plasma exposure following an oral dose in rodents and activity against the Ras-Raf pathway in tumor bearing mice. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1026 / 1029

页数：4

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