Microwave-assisted synthesis of 5-aminopyrazol-4-yl ketones and the p38^MAPK inhibitor RO3201195 for study in Werner syndrome cells

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• 作者：Mark C. Bagley ; Terence Davis ; Matthew C. Dix ; Paola G.S. Murziani ; Michal J. Rokicki ; David Kipling
• 关键词：p38 MAPK ; Werner syndrome ; RO3201195 ; Microwaves ; Heterocycles
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2008
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：1 July 2008
• 卷：18
• 期：13
• 页码：3745-3748
• 文件大小：357 K

摘要

5-Aminopyrazol-4-yl ketones are prepared rapidly and efficiently using microwave dielectric heating from β-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 MAPK over the related stress-activated kinase JNK.