title: Novel 2-alkylamino-1,4-benzoxazine derivatives as potent neuroprotective agents: structure-activity relationship studies.
abstract: 2-Alkylamino-substituted-1,4-benzoxazine derivatives, a new class of potential neuroprotective agents, were synthesized and examined for their intrinsic cytotoxicity and their capacity to inhibit oxidative stress-mediated neuronal degeneration in vitro. Through structure-activity relationship studies, the 3,3-diphenyl-substituted-1,4-benzoxazine derivative 3l was identified as the optimal candidate, owing to its potent neuroprotective activity, without the manifestation of intrinsic cytotoxicity. Accordingly, 3l proved to be effective in an animal model of excitotoxic lesions in newborn mice.
authors.affiliation: UMR 8638 CNRS - Université René Descartes, Synthèse et Structure de Molécules d'Intérêt Pharmacologique, Faculté des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l'Observatoire, 75270 Paris Cedex 06, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Blattes
authors.forename: Brian
authors.initials: B
authors.lastname: Lockhart
authors.forename: Pierre
authors.initials: P
authors.lastname: Lestage
authors.forename: Leslie
authors.initials: L
authors.lastname: Schwendimann
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.forename: Maurice-Bernard
authors.initials: MB
authors.lastname: Fleury
authors.forename: Martine
authors.initials: M
authors.lastname: Largeron
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D048588:Benzoxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002547:Cerebral Palsy / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D048588:Benzoxazines; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species