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Peer-reviewed veterinary case report

Design and Synthesis of Selurampanel, a Novel Orally Active and Competitive AMPA Receptor Antagonist.

Journal:
ChemMedChem
Year:
2017
Authors:
Orain, David et al.
Affiliation:
Novartis Institute for Biomedical Research

Abstract

A series of potent quinazolinedione sulfonamide antagonists of the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor were designed and synthesized. The structure-activity relationships (SAR) and in vivo activity of the series were investigated. In particular, compound 1 S (selurampanel; N-[7-isopropyl-6-(2-methylpyrazol-3-yl)-2,4-dioxo-1H-quinazolin-3-yl]methanesulfonamide) has shown excellent oral potency against maximal electroshock seizure (MES)-induced generalized tonic-clonic seizures in rodents as well as significant activity in patients suffering from various forms of epilepsy. The X-ray crystal structure of selurampanel bound to the AMPA receptor hGluA was also obtained.

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Original publication: https://pubmed.ncbi.nlm.nih.gov/27863026/