Byrnes E W, McMaster P D, Smith E R, Blair M R, Boyes R N, Duce B R, Feldman H S, Kronberg G H, Takman B H, Tenthorey P A
J Med Chem. 1979 Oct;22(10):1171-6. doi: 10.1021/jm00196a005.
Thirty-two alpha-amino anilides with various substituents in the aromatic ring and in the alpha position are described. Their abilities to protect mice against chloroform-induced fibrillation and to elicit toxicity were determined. Substitution of an alkyl or aryl group in the alpha position enhanced the antifibrillatory activity. In most cases, increased potency was accompanied by increased toxicity. Eleven compounds were tested in dogs with surgically induced myocardial infarction; most showed antiarrhythmic activity. 2-Aminopropiono-2',6'-xylidide, tocainide, was chosen for clinical investigation.
本文描述了32种在芳环和α位带有不同取代基的α-氨基苯胺。测定了它们保护小鼠免受氯仿诱导的纤颤以及引发毒性的能力。在α位取代烷基或芳基可增强抗纤颤活性。在大多数情况下，效力增加伴随着毒性增加。对11种化合物在手术诱导心肌梗死的犬中进行了测试；大多数显示出抗心律失常活性。选择2-氨基丙酸-2',6'-二甲基苯胺（妥卡尼）进行临床研究。
