title: Studies on cognitive enhancing agents. III. Antiamnestic and antihypoxic activities of a series of 1-bicycloaryl-2-(omega-aminoalkoxy)ethanols.
abstract: 2-(2-Aminoethoxy)-1-hydroxyethyl derivatives of bicyclic arenes (naphthalene, thianaphthene, benzofuran, and indole) were prepared and screened for antiamnestic (AA) and antihypoxic (AH) activities which were evaluated by measuring the reversing potency in electroconvulsion-induced amnesia and the protective effect against hypoxia, respectively, in mice. Compound 3o, 1-(benzo[b]thiophen-5-yl)-2- (2-diethylaminoethoxy)ethanol, showed the best AA and AH activity profile, being superior to our prototype compound, 2-(2-dimethylaminoethoxy)-1-phenylethanol (1). Elongation of the ethylene linkage in the side chain of 3o to 3- and 4-carbon moieties brought about a significant decrease in AH activity. Compound 3o was further investigated for its protective effect against CO2-induced memory impairment and for acute toxicity in mice. It is ten-fold more potent than tacrine in the amnesia-reversal assay and is considerably less toxic than tacrine.
authors.affiliation: Research Laboratories, Toyama Chemical Co., Ltd., Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ono
authors.forename: T
authors.initials: T
authors.lastname: Yamafuji
authors.forename: H
authors.initials: H
authors.lastname: Chaki
authors.forename: H
authors.initials: H
authors.lastname: Morita
authors.forename: Y
authors.initials: Y
authors.lastname: Todo
authors.forename: N
authors.initials: N
authors.lastname: Okada
authors.forename: M
authors.initials: M
authors.lastname: Maekawa
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
authors.forename: M
authors.initials: M
authors.lastname: Tai
authors.forename: H
authors.initials: H
authors.lastname: Narita
mesh_terms: D000647:Amnesia / Q000188:drug therapy*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001812:Blood-Brain Barrier; D003460:Crystallization; D004597:Electroshock; D000431:Ethanol / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002534:Hypoxia, Brain / Q000188:drug therapy*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018697:Nootropic Agents; D000431:Ethanol