- PROCESS FOR THE PREPARATION OF PERAMPANEL
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The present invention provides intermediates useful for the synthesis of Perampanel and processes employing said intermediates for preparing Perampanel. The invention also provides processes for making the intermediates, crystalline forms of the intermediates and the use of the crystalline forms for preparing Perampanel.
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- 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
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Dysfunction of glutamatergic neurotransmission has been implicated in the pathogenesis of epilepsy and numerous other neurological diseases. Here we 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, 6), 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 (minimum effective dose of 2 mg/kg po). Perampanel is currently in regulatory submission for partial-onset seizures associated with epilepsy.
- Hibi, Shigeki,Ueno, Koshi,Nagato, Satoshi,Kawano, Koki,Ito, Koichi,Norimine, Yoshihiko,Takenaka, Osamu,Hanada, Takahisa,Yonaga, Masahiro
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p. 10584 - 10600
(2013/02/23)
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- 1,2-DIHYDROPYRIDINE COMPOUNDS, PROCESS FOR PREPARATION OF THE SAME AND USE THEREOF
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The present invention provides a novel compound having an excellent AMPA receptor inhibitory action and/or kainate inhibitory action. A compound represented by the following formula, a salt thereof or hydrates thereof. In the formula, Q indicates NH, O or S; and R1, R2, R3, R4 and R5 are the same as or different from each other and each indicates hydrogen atom, a halogen atom, a C1-6 alkyl group or a group represented by the formula -X-A (wherein X indicates a single bond, an optionally sbutituted C1-6 alkylene group etc.; and A indicates an optionally substituted C6-14 aromatic hydrocarbocyclic group or 5- to 14-membered aromatic heterocyclic group etc.).
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