【摘要】 为探索关附甲素药效基团，进行结构改造，设计合成了１３个（赤）苯丙二醇胺类化合物（Ｉ１～７，ＩＩ１～６）。用乌头碱诱发大鼠心律失常试验表明，多数化合物有一定的抗心律失常活性，其中Ｉ２的抗ＶＴ活性及Ｉ３的抗ＶＰ活性与关附甲素相近，苯环对位引入吸电性ＮＯ２基（Ｉ１～６）对活性不利。产物制备中发现，烯丙位Ｎ原子对Ｐｒｅｖｏｓｔ反应的立体选择性有较大影响，将胺基乙酰化后可排除干扰顺利进行反应。更多还原

【Abstract】 For the purpose of searching for new drug with high potency and simple chemical structure, the dominant conformation and structural parameters of Guan Fu base (GFA) molecule were modelled and calculated with a SGI 4D 25G computer. The propanediolamine chain in GFA might be considered to be a pharmacophore responsible for the bioactivity and the configuration of the chain seemed important. Thus, thirteen compounds of (erythro) p x PhCHOHCHOHCH 2NHR(x=H, I 1～7 ; X=NO 2, II 1～6 ) were prepared. Among them, 10 compounds showed antiarrhythmic effect on aconitine induced arrhythmia in rats. The ED 50(to stop VT) of I 2 and ED 50(to stop VP) of I 3 were shown to be comparable with those of GFA. In the synthesis, no stereoselectivity was found in the Prevost reaction with allylamine analogues (a 1～7 ). After a 1～7 were acetylated, the erythro type products(I 1～7 ) were obtained.更多还原