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从Morgan和Mathison等所综述的抗心律失常药构效关系出发,以利多卡因和安搏律定(Aprindine)的结构作为先导化合物,设计并合成了33个1,2-二取代四氢异喹啉的酰胺类和烷胺类衍生物。经乌头碱致大鼠心律失常模型初步试验结果,发现绝大多数化合物均具有很强的抗心律失常作用。并对其构效关系作了初步小结。其中1-对甲苯基四氢异喹啉衍生物的抗心律失常作用最强,对心脏毒性小,并与安搏律定作了比较,其最小中毒量/最小有效量和最小致死量/最小有效量之值大大超过安搏律定。
Based on the structure-activity relationship of antiarrhythmic drugs reviewed by Morgan and Mathison et al., The structures of lidocaine and Aprindine were used as the lead compounds to design and synthesize 33 1,2-disubstituted tetrahydroisogens Quinoline amides and alkylamine derivatives. The preliminary results of rat model of arrhythmia induced by aconitine found that most of the compounds have strong anti-arrhythmic effect. And made a preliminary summary of its structure-activity relationship. Among them, 1-p-tolyltetrahydroisoquinoline derivatives have the strongest anti-arrhythmic effect and little cardiotoxicity and are compared with ambroxol at the minimum to the minimum effective dose and the minimum lethal dose / The effective amount of the value greatly exceeds the ambush set.