Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Chemistry, Pharmaceutical / methods
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Enzyme Activation
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Humans
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Inhibitory Concentration 50
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Ketones / chemistry*
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MAP Kinase Kinase 4 / metabolism
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Microwaves*
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Models, Chemical
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Naphthalenes / chemistry
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Nitriles / chemistry
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Protein Isoforms
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Pyrazoles / chemical synthesis*
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Pyrazoles / chemistry
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Pyrazoles / pharmacology
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p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
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5-amino-1-(4-fluorophenyl)-4-(3-(2,3-dihydroxypropoxy)benzoyl)pyrazole
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Enzyme Inhibitors
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Ketones
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Naphthalenes
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Nitriles
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Protein Isoforms
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Pyrazoles
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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doramapimod