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.
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Authors | S Ono, T Yamafuji, H Chaki, H Morita, Y Todo, N Okada, M Maekawa, K Kitamura, M Tai, H Narita |
Journal | Chemical & pharmaceutical bulletin
(Chem Pharm Bull (Tokyo))
Vol. 43
Issue 9
Pg. 1492-6
(Sep 1995)
ISSN: 0009-2363 [Print] Japan |
PMID | 7586072
(Publication Type: Journal Article)
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Chemical References |
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Topics |
- Amnesia
(drug therapy)
- Animals
- Avoidance Learning
(drug effects)
- Blood-Brain Barrier
- Crystallization
- Electroshock
- Ethanol
(chemical synthesis, pharmacology, toxicity)
- Hypoxia, Brain
(drug therapy)
- Lethal Dose 50
- Male
- Mice
- Mice, Inbred Strains
- Nootropic Agents
(chemical synthesis, pharmacology, toxicity)
- Rats
- Rats, Wistar
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