Rapid synthesis of VX-745: p38 MAP kinase inhibition in Werner syndrome cells

被引：46

作者：

Bagley, Mark C.

Davis, Terence

Dix, Matthew C.

Rokicki, Michal J.

Kipling, David

机构：

[1] Univ Cardiff Wales, Sch Chem, Cardiff CF10 3AT, Wales

[2] Univ Cardiff Wales, Sch Med, Dept Pathol, Cardiff CF14 4XN, Wales

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 18期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

p38; MAPK; Werner syndrome; VX-745; microwaves; heterocycles; ullmann coupling; palladium;

D O I：

10.1016/j.bmcl.2007.07.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The p38 mitogen-activated protein kinase inhibitor VX-745 is prepared rapidly and efficiently in a four-step sequence using a combination of conductive heating and microwave-niediated steps. Its inhibitory activity was confirmed in hTERT immortalized HCA2 and WS dermal fibroblasts at 0.5-1.0 mu M concentration by ELISA and immunoblot assay, and displays excellent kinase selectivity over the related stress-activated kinase JNK. (c) 2007 Elsevier Ltd. All rights reserved.

引用

收藏

页码：5107 / 5110

页数：4

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