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

Article abstract of DOI:10.1016/j.bmcl.2008.05.037

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 p38α MAPK over the related stress-activated kinase JNK.