任勇, 华维一, 彭司勋, 朱东亚, 郭寅龙. (赤)-苯丙二醇胺类化合物的合成及抗心律失常活性J. 药学学报, 1997, 32(4): 264-270.
引用本文: 任勇, 华维一, 彭司勋, 朱东亚, 郭寅龙. (赤)-苯丙二醇胺类化合物的合成及抗心律失常活性J. 药学学报, 1997, 32(4): 264-270.
Y Ren, WY Hua, SX Peng, DY Zhu , YL Guo, . SYNTHESIS AND ANTIARRHYTHMIC ACTIVITY OF SOME (ERYTHRO)-PHENYLPROPANEDIOLAMINE COMPOUNDSJ. Acta Pharmaceutica Sinica, 1997, 32(4): 264-270.
Citation: Y Ren, WY Hua, SX Peng, DY Zhu , YL Guo, . SYNTHESIS AND ANTIARRHYTHMIC ACTIVITY OF SOME (ERYTHRO)-PHENYLPROPANEDIOLAMINE COMPOUNDSJ. Acta Pharmaceutica Sinica, 1997, 32(4): 264-270.

(赤)-苯丙二醇胺类化合物的合成及抗心律失常活性

SYNTHESIS AND ANTIARRHYTHMIC ACTIVITY OF SOME (ERYTHRO)-PHENYLPROPANEDIOLAMINE COMPOUNDS

  • 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。

     

    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-PhCHOHCHOHCH2NHR(x=H,I1~7; X=NO 2, II1~6) were prepared. Among them, 10 compounds showed antiarrhythmic effect on aconitine induced arrhythmia in rats. The ED50(to stop VT) of I2 and ED50(to stop VP) of I3 were shown to be comparable with those of GFA. In the synthesis, no stereoselectivity was found in the Prevost reaction with allylamine analogues (a1~7). After a1~7 were acetylated, the erythro type products(I1~7) were obtained.

     

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