title: Enantiomerically pure tetrahydroquinoline derivatives as in vivo potent antagonists of the glycine binding site associated to the NMDA receptor.
abstract: To identify neuroprotective agents after stroke, new substituted tetrahydroquinoline derivatives were designed as antagonists of the glycine binding site associated to the NMDA receptor, satisfying the key pharmacophoric requirements. In particular, the racemate 3c exhibited outstanding in vivo activity in the MCAo model in rats, when given iv both pre- and post-ischemia. Pure enantiomers 3c-(+) and 3c-(-) have been prepared following an original synthetic route. Despite the significant difference of activity observed in vitro, they shown similar neuroprotective profile in the MCAo model in rats.
authors.affiliation: Medicines Research Centre, GlaxoSmithKline S.p.A, Via Fleming 4, 37135 Verona, Italy. rdf26781@gsk.com
authors.forename: Romano
authors.initials: R
authors.lastname: Di Fabio
authors.forename: Elvira
authors.initials: E
authors.lastname: Tranquillini
authors.forename: Barbara
authors.initials: B
authors.lastname: Bertani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Alvaro
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Micheli
authors.forename: Fabio
authors.initials: F
authors.lastname: Sabbatini
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Pizzi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pentassuglia
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pasquarello
authors.forename: Tommaso
authors.initials: T
authors.lastname: Messeri
authors.forename: Daniele
authors.initials: D
authors.lastname: Donati
authors.forename: Emiliangelo
authors.initials: E
authors.lastname: Ratti
authors.forename: Roberto
authors.initials: R
authors.lastname: Arban
authors.forename: Giovanna
authors.initials: G
authors.lastname: Dal Forno
authors.forename: Angelo
authors.initials: A
authors.lastname: Reggiani
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Barnaby
mesh_terms: D000818:Animals; D001665:Binding Sites; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D020768:Middle Cerebral Artery; D008968:Molecular Conformation; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
chemical_list: D018696:Neuroprotective Agents; D011804:Quinolines; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate