B-Raf kinase inhibitors: Hit enrichment through scaffold hopping

被引：18

作者：

Gopalsamy, Ariamala ^{[1
]}

Shi, Mengxiao ^{[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 Sci, Pearl River, NY 10965 USA

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 08期

关键词：

B-Raf kinase; Thienopyrimidine;

D O I：

10.1016/j.bmcl.2010.03.030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In continuation of our efforts toward hit identification and optimization for a B-Raf kinase project, we have employed a scaffold hopping strategy. The original HTS hit scaffold pyrazolo[1,5-a]pyrimidine was replaced with different thienopyrimidine and thienopyridine scaffolds to append the optimal pharmacophore moieties in order to generate novel B-raf kinase inhibitors with desirable potency and properties. This strategy led to the identification of additional lead compound 11b which had good enzyme and cell potency, while maintaining selectivity over a number of kinases. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：2431 / 2434

页数：4

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