Identification of isothiazole-4-carboxamidines derivatives as a novel class of allosteric MEK1 inhibitors
详细信息 查看全文
- 作者：Hassan El Abdellaoui ; Chamakura V.N.S. Varaprasad ; Dinesh Barawkar ; Subrata Chakravarty ; Andreas Maderna ; Robert Tam ; Huanming Chen ; Matt Allan ; Jim Z. Wu ; Todd Appleby et al.
- 关键词：MEK inhibitor ; MEK-1 ; MEK-2 ; Isothiazole carboxamidine ; Allosteric inhibitors
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2006
- 出版时间：1 November 2006
- 年：2006
- 卷：16
- 期：21
- 页码：5561-5566
- 全文大小：160 K
文摘
The development of potent, orally bioavailable, and selective series of 5-amino-3-hydroxy-N(1-hydroxypropane-2-yl)isothiazole-4-carboxamidine inhibitors of MEK1 and MEK-2 kinase is described. Optimization of the carboxamidine and the phenoxyaniline group led to the identification of 55 which gave good potency as in vitro MEK1 inhibitors, and good oral exposure in rat.