Discovery of 2-(2-Oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile (Perampanel): A Novel, Noncompetitive α-Amino-3-hydroxy-5-methyl-4-isoxazolepropanoic Acid (AMPA) Receptor Antagonist was written by Hibi, Shigeki;Ueno, Koshi;Nagato, Satoshi;Kawano, Koki;Ito, Koichi;Norimine, Yoshihiko;Takenaka, Osamu;Hanada, Takahisa;Yonaga, Masahiro. And the article was included in Journal of Medicinal Chemistry in 2012.Formula: C11H9NO This article mentions the following:
Dysfunction of glutamatergic neurotransmission has been implicated in the pathogenesis of epilepsy and numerous other neurol. diseases. Here the authors describe the discovery of a series of 1,3,5-triaryl-1H-pyridin-2-one derivatives as noncompetitive antagonists of AMPA-type ionotropic glutamate receptors. The structure-activity relationships for this series of compounds were investigated by manipulating individual aromatic rings located at positions 1, 3, and 5 of the pyridone ring. This culminated in the discovery of 2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile (perampanel), a novel, noncompetitive AMPA receptor antagonist that showed potent activity in an in vitro AMPA-induced Ca2+ influx assay (IC50 = 60 nM) and in an in vivo AMPA-induced seizure model (min. ED of 2 mg/kg po). Perampanel is currently in regulatory submission for partial-onset seizures associated with epilepsy. In the experiment, the researchers used many compounds, for example, 5-Phenylpyridin-2-ol (cas: 76053-45-7Formula: C11H9NO).
5-Phenylpyridin-2-ol (cas: 76053-45-7) belongs to pyridine derivatives. The ring atoms in the pyridine molecule are sp2-hybridized. The nitrogen is involved in the π-bonding aromatic system using its unhybridized p orbital. The lone pair is in an sp2 orbital, projecting outward from the ring in the same plane as the σ bonds. Pyridine derivatives are also useful as small-molecule α-helix mimetics that inhibit protein-protein interactions, as well as functionally selective GABA ligands.Formula: C11H9NO