New antiarrhythmic agents. 5. .alpha.-Aminoaceto-2,6-xylidides with functionalized amide alkyl substituents
作者:Paul D. McMaster、Eugene W. Byrnes、Alan J. Block、Paul A. Tenthorey
DOI:10.1021/jm00133a012
日期:1981.1
The synthesis of aminoaceto-2',6'-xylidides substituted on the amide nitrogen with 2-(diethylamino)ethyl, 2-aminoethyl, 2-hydroxyethyl, and 2-ethoxyethyl groups is described. The 2-aminoethyl derivatives were prepared by treatment of N-(2-phthalimidoethyl)-2',6'-xylidine with chloroacetyl chloride, followed by treatment with either potassium phthalmide or diethylamine. Hydrazinolysis of the phthalimides
描述了在酰胺氮上被2-(二乙基氨基)乙基,2-氨基乙基,2-羟基乙基和2-乙氧基乙基取代的氨基乙酰基2′,6′-二甲苯基的合成。通过用氯乙酰氯处理N-(2-邻苯二甲酰亚胺基乙基)-2',6'-二甲基吡啶,然后用邻苯二甲酰亚胺钾或二乙胺处理来制备2-氨基乙基衍生物。邻苯二甲酰亚胺的肼解作用释放出游离胺。剩余的目标化合物是通过利多卡因或2-phthalimidoaceto-2',6'-二甲苯基与适当的卤化物和氢化钠烷基化,然后在必要时进行肼解反应制得的。评估了所有目标化合物对氯仿诱导的室性心动过速的抗心律失常功效,以及对小鼠的急性中枢神经系统毒性。大多数目标化合物比相应的仲酰胺更有效,并且对中枢神经系统毒性具有更好的治疗效果。二胺N-(2-氨基乙基)-2-氨基乙酰基2',6'-木糖苷(13)和N-(2-氨基乙基)-2-(二乙基氨基)乙酰基-2',6'-木糖苷(29 )在这方面特别有前途。测试了几种化合物作为脊髓麻醉剂。