“慢心率”(mexiletine)类似物的合成
SYNTHESIS OF MEXILETINE ANALOGUES
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摘要: 本文以2,6-二甲基苯氧乙叉(Ⅱ)为母体,设计合成了苯氧烷胺类(Ⅲ~V),苯氧羟基烷胺类(Ⅵ),N-酰化苯氧烷胺类(Ⅶ),苯甲酸苯氧烷酯类(Ⅷ),苯氧烷胺盐类(Ⅸ)等不同类型的2,6-二甲基苯氧乙叉衍生物。药理试验表明,部分化合物对蟾蜍离体心脏的心跳频率有明显的减慢作用,其中化合物Ⅲa~c和Ⅵa~b,减慢心律作用比“慢心律”(mexiletine)强,部分化合物具有抗惊厥活性。Abstract: Five types of derivatives related to 1-(2,6-dimethylphenoxy)amino-propane have been synthesized. They are phenoxy-aminopropane (Ⅲ,Ⅴ), phenoxy-hydroxy-aminopropane (Ⅵ), N-acyl-phenoxy-aminoisopropane (Ⅶ), phenoxy-isopropyl ester of benzoic acid (Ⅷ) and phenoxy-isopropyl-ammonium salts (Ⅸ).In preliminary pharmacological assay, some of these compounds exhibited obvious effect of decreasing heart rate on the isolated toad heart. Ⅲ a~c were shown to be more active than mexiletine.In addition, some of the compounds Ⅲa~b, Ⅳa~b, and VIb were found to possess anticonvulsant activity.
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