Abstract
Potent inhibition of Janus kinase 3 was found for a series of naphthyl(beta-aminoethyl)ketones (e.g. 7, pIC50 = 7.1+/-0.3). Further studies indicated that these compounds fragment in less than 1 h by retro-Michael reaction in the Jak3 in vitro ELISA assay procedure. The breakdown product of 7, 2-naphthylvinyl ketone (22, pIC50 = 6.8+/-0.3) showed very similar inhibitory activity to 7. Compounds 7 (in neutral buffer) and 22 will be useful pharmacological tools for the investigation of the Janus tyrosine kinase Jak3.
MeSH terms
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Enzyme-Linked Immunosorbent Assay
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Humans
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Indicators and Reagents
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Janus Kinase 3
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Ketones / chemical synthesis*
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Ketones / pharmacology
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Mannich Bases
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Naphthalenes / chemical synthesis*
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Naphthalenes / pharmacology
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Indicators and Reagents
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Ketones
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Mannich Bases
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Naphthalenes
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Protein-Tyrosine Kinases
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JAK3 protein, human
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Janus Kinase 3