McMaster P D, Byrnes E W, Feldman H S, Takman B H, Tenthorey P A
J Med Chem. 1979 Oct;22(10):1177-82. doi: 10.1021/jm00196a006.
The synthesis of a series of N-alkyl 2-amino 2',6'-xylidides is described. The method involved coupling of the N-alkyl-2',6'-xylidine with the appropriate 2-haloacyl halide, followed by ammonolysis. Alternatively, alkylation of the 2-phthalimido 2',6'-xylidide with NaH and the alkyl halide followed by hydrazinolysis was used. All compounds were evaluated for their ability to protect mice against chloroform-induced ventricular fibrillation. The compounds were generally more potent antifibrillatory agents than the corresponding secondary amides. All were more potent than tocainide and several showed less CNS toxicity. Five compounds were further evaluated in dogs with ventricular arrhythmias resulting from myocardial infarction. N-Ethyl-2-aminoaceto-4'-propoxy-2',6'-xylidide was as potent as lidocaine and produced less CNS toxicity.
描述了一系列N-烷基-2-氨基-2',6'-二甲基苯胺的合成。该方法包括将N-烷基-2',6'-二甲基苯胺与适当的2-卤代酰卤偶联，然后进行氨解。另外，使用2-邻苯二甲酰亚氨基-2',6'-二甲基苯胺与氢化钠和卤代烃进行烷基化反应，随后进行肼解。评估了所有化合物保护小鼠免受氯仿诱导的心室颤动的能力。这些化合物通常比相应的仲酰胺更有效的抗纤颤剂。所有化合物都比妥卡胺更有效，并且几种化合物显示出较低的中枢神经系统毒性。对五种化合物在患有心肌梗死引起的室性心律失常的犬中进行了进一步评估。N-乙基-2-氨基乙酰基-4'-丙氧基-2',6'-二甲基苯胺与利多卡因效力相当，并且产生的中枢神经系统毒性较小。
