title: 4,10-Dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-carboxylic acid derivatives: highly potent and selective AMPA receptors antagonists with in vivo activity.
abstract: A novel series of 2-substituted-4,5-dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2-e]pyrazine derivatives was synthesised. One of them, 4e-a highly water soluble compound exhibited a nanomolar affinity and demonstrated competitive antagonist properties at the ionotropic AMPA receptors. This compound also displayed potent anticonvulsant properties against electrically or sound-induced convulsions in mice after systemic administration, thus suggesting adequate brain penetration.
authors.affiliation: Aventis Pharma S.A., Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Stutzmann
authors.forename: G A
authors.initials: GA
authors.lastname: Bohme
authors.forename: A
authors.initials: A
authors.lastname: Boireau
authors.forename: D
authors.initials: D
authors.lastname: Damour
authors.forename: M W
authors.initials: MW
authors.lastname: Debono
authors.forename: A
authors.initials: A
authors.lastname: Genevois-Borella
authors.forename: A
authors.initials: A
authors.lastname: Imperato
authors.forename: P
authors.initials: P
authors.lastname: Jimonet
authors.forename: J
authors.initials: J
authors.lastname: Pratt
authors.forename: J C
authors.initials: JC
authors.lastname: Randle
authors.forename: Y
authors.initials: Y
authors.lastname: Ribeill
authors.forename: M
authors.initials: M
authors.lastname: Vuilhorgne
authors.forename: S
authors.initials: S
authors.lastname: Mignani
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008811:Mice, Inbred DBA; D011719:Pyrazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011810:Quinoxalines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
chemical_list: C413746:8-methylureido-4,10-dihydro-4-oxo-4H-imidazo(1,2-a)indeno(1,2-e)pyrazin-2-carboxylic acid; D000927:Anticonvulsants; D007546:Isoquinolines; D011719:Pyrazines; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D013777:Tetrazoles; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C086162:6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione; C082309:tezampanel; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D014508:Urea