Microwave-assisted synthesis of 5-aminopyrazol-4-yl ketones and the p38MAPK inhibitor RO3201195 for study in Werner syndrome cells

被引：28

作者：

Bagley, Mark C. ^{[1
]}

Davis, Terence ^{[2
]}

Dix, Matthew C. ^{[1
]}

Murziani, Paola G. S. ^{[1
]}

Rokicki, Michal J. ^{[2
]}

Kipling, David ^{[2
]}

机构：

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

[2] Cardiff Univ, Sch Chem, Dept Pathol, Cardiff CF14 4XN, S Glam, Wales

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 13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; RO3201195; microwaves; heterocycles;

D O I：

10.1016/j.bmcl.2008.05.037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

5-Aminopyrazol-4-yl ketones are prepared rapidly and efficiently using microwave dielectric heating from beta-ketonitriles by treatment with N, N'-diphenylformamidine followed by heterocyclocondensation by irradiation with a hydrazine. The inhibitory activity of RO3201195 prepared by this methodology was confirmed in hTERT-immortalized HCA2 and WS dermal fibroblasts at 200 nM concentration, both by ELISA and immunoblot assay, and displays excellent kinase selectivity for p38 alpha MAPK over the related stress-activated kinase JNK. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：3745 / 3748

页数：4

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