甲烷磺酰胺苯乙胺类化合物的合成及抗心律失常活性的研究(Ⅱ)

Synthesis and Antiarrhythmic Activity of Some Methyl sulfonamido phenylethylamino Derivatives

以Ⅲ类抗心律失常药ｄｏｆｅｔｉｌｉｄｅ为模板，以苯乙胺为原料，经酰化、硝化、还原得对硝基苯乙胺，再经取代、还原、甲烷磺酰化，设计合成了６个新的甲烷磺酰胺苯乙胺类化合物，其中化合物６ｃ是ｄｏｆｅｔｉｌｉｄｅ的代谢产物。初步药理研究结果表明：所合成的化合物对乌头碱诱发的心律失常大鼠有效，其中化合物６ａ，６ｂ，６ｃ在初步药理实验中显示与ｄｏｆｅｔｉｌｉｄｅ活性相当，有效剂量５μｇ／ｋｇ。

Selecting class Ⅲ antiarrhythmic compound dofetilide as lead compound, started from phenylethylamine, six novel N substituted methylsulfonamido phenylethylamino derivatives were designed and synthesized through seven step chemical reactions.Their chemical structures were determined by IR, 1HNMR and MS.The pharmacological study showed that these new compounds exhibit antiarrhythmic activities to varying degree in rats arrhythmia induced by aconitine.The antiarrhythmic activity of three compounds (6a,6b,6c) with an effective close of 5 mg/kg was similar to that of dofetilide.