Hit to lead optimization of pyrazolo[1,5-a]pyrimidines as B-Raf kinase inhibitors

被引：14

作者：

Gopalsamy, Ariamala ^{[1
]}

Ciszewski, Greg ^{[1
]}

Shi, Mengxiao ^{[1
]}

Berger, Dan ^{[1
]}

Hu, Yongbo ^{[1
]}

Lee, Frederick ^{[1
]}

Feldberg, Larry ^{[2
]}

Frommer, Eileen ^{[2
]}

Kim, Steven ^{[2
]}

Collins, Karen ^{[2
]}

Wojciechowicz, Donald ^{[2
]}

Mallon, Robert ^{[2
]}

机构：

[1] Wyeth Res, Chem & Screening Sci, Pearl River, NY 10965 USA

[2] Wyeth Res, Discovery Oncol, Pearl River, NY 10965 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 24期

关键词：

B-Raf inhibitor; Pyrazolo[1,5-a]pyrimidine;

D O I：

10.1016/j.bmcl.2009.10.074

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Our continued effort towards optimization of the pyrazolo[1,5-a]pyrimidine scaffold as B-Raf kinase inhibitors is described. Structure guided design was utilized to introduce kinase hinge region interacting groups in the 2-position of the scaffold. This strategy led to the identification of lead compound 9 with enhanced enzyme and cellular potency, while maintaining good selectivity over a number of kinases. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：6890 / 6892

页数：3

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