One-Pot Synthesis of 4,6-Diaryl-2-oxo(imino)-1,2-dihydropyridine-3-carbonitrile; a New Scaffold for p38α MAP Kinase Inhibition

Two series of new compounds with the general formula 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitriles and their isosteric 2-imino derivatives were synthesized by the multicomponent reaction of the appropriate acetophenone, aromatic aldehyde, ammonium acetate, and malononitrile or ethyl cyanoacetate. The products were obtained with excellent yields. The prepared compounds were evaluated for their in vitro ability to inhibit p38 α-MAP kinase. Several compounds showed p38 MAP kinase inhibitory properties with IC50 as low as 0.07 μM. This is the first time to report compounds with such scaffold as p38 α-MAP kinase inhibitors. This asserts the potentiality of multicomponent reactions in drug discovery.