Naphthyl ketones: a new class of Janus kinase 3 inhibitors.

Abstract Potent inhibition of Janus kinase 3 was found for a series of naphthyl(β-aminoethyl)ketones (e.g. 7 , pIC 50 =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 , pIC 50 =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.