Potent and selective pyrazolo[1,5-a]pyrimidine based inhibitors of B-RafV600E kinase with favorable physicochemical and pharmacokinetic properties

被引：27

作者：

Ren, Li ^{[1
]}

Laird, Ellen R. ^{[1
]}

Buckmelter, Alex J. ^{[1
]}

Dinkel, Victoria ^{[1
]}

Gloor, Susan L. ^{[1
]}

Grina, Jonas ^{[1
]}

Newhouse, Brad ^{[1
]}

Rasor, Kevin ^{[1
]}

Hastings, Gregg ^{[1
]}

Gradl, Stefan N. ^{[2
]}

Rudolph, Joachim ^{[2
]}

机构：

[1] Array BioPharma Inc, Boulder, CO 80301 USA

[2] Genentech Inc, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 02期

关键词：

B-Rat; Kinase; Drug discovery; Cancer; METASTATIC MELANOMA; BRAF MUTATIONS; RAF; PATHWAY;

D O I：

10.1016/j.bmcl.2011.11.092

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein we describe a novel series of ATP competitive B-Rat inhibitors based on the pyrazolo[1,5-a]pyrimidine scaffold. These inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. Optimization led to the identification of compound 17, a potent, selective and orally available agent with improved physicochemical and pharmacokinetic properties. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1165 / 1168

页数：4

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