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

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 metho...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2008-07, Vol.18 (13), p.3745-3748
Main Authors: Bagley, Mark C, Davis, Terence, Dix, Matthew C, Murziani, Paola GS, Rokicki, Michal J, Kipling, David
Format: Article
Language:English
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Summary: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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmcl.2008.05.037