Studies on Cognitive Enhancing Agents. III. Antiamnestic and Antihypoxic Activities of a Series of l-Bicycloaryl-2-(.OMEGA.-aminoalkoxy)ethanols.
作者:Satoshi ONO、Tetsuo YAMAFUJI、Hisaaki CHAKI、Hajime MORITA、Yozo TODO、Naomi OKADA、Mutsuko MAEKAWA、Kazunori KITAMURA、Masaru TAI、Hirokazu NARITA
DOI:10.1248/cpb.43.1492
日期:——
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 moiethies 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.
双环芳烃(萘、噻吊、苯并呋喃和吲哚)的2-(2-氨基乙氧基)-1-羟乙基衍生物被制备并筛选出具有抗遗忘(AA)和抗缺氧(AH)活性的化合物。这些活性通过测定逆转电休克诱导的遗忘和保护小鼠免受缺氧影响的效力来评估。化合物3o,1-(苯并[b]噻吩-5-基)-2-(2-二乙基氨基乙氧基)乙醇,显示出最佳的AA和AH活性特征,优于我们的原型化合物,2-(2-二甲基氨基乙氧基)-1-苯乙醇(1)。在3o的侧链中延长乙烯链接到3-和4-碳单元,显著降低了AH活性。化合物3o进一步研究了其对Co2诱导记忆障碍的保护作用和在小鼠中的急性毒性。在逆转遗忘试验中,其效力是他克林的十倍,并且毒性远低于他克林。