Bioorganic & Medicinal Chemistry Letters 2008-07-01

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

Mark C Bagley, Terence Davis, Matthew C Dix, Paola G S Murziani, Michal J Rokicki, David Kipling

文献索引：Bioorg. Med. Chem. Lett. 18(13) , 3745-8, (2008)

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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 200nM concentration, both by ELISA and immunoblot assay, and displays excellent kinase selectivity for p38alpha MAPK over the related stress-activated kinase JNK.