One-pot synthesis of 4,6-diaryl-2-oxo(imino)-1,2-dihydropyridine-3-carbonitrile; a New Scaffold for p38alpha 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 alpha-MAP kinase. Several compounds showed p38 MAP kinase inhibitory properties with IC(50) as low as 0.07 microM. This is the first time to report compounds with such scaffold as p38 alpha-MAP kinase inhibitors. This asserts the potentiality of multicomponent reactions in drug discovery.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt.
Aya M
AM
Serry
Sabine
S
Luik
Stefan
S
Laufer
Ashraf H
AH
Abadi
D020650:Combinatorial Chemistry Techniques; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D004095:Dihydropyridines; D009570:Nitriles; D054852:Small Molecule Libraries; D048051:p38 Mitogen-Activated Protein Kinases