【摘要】 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。更多还原

【Abstract】 Thirty three 1, 2-disubstituted-l, 2, 3, 4-tetrahydroisoquinolines of two types, alkylaminoaoetamide( )and alkylaminoethylamine(Ⅳ), were synthesized and their antiarrhythmio activities assessed. Compounds (Ⅲ) were produced from N-pheneihyl-p-substituted-benzamide by the Biseher-Napieralski reaction, reduction with KBH4, chlo roaoetylation., and amination. Compounds (Ⅳ) were derived from (Ⅲ) by reduction with LiAlH4, Most of them exhibited high an tiarrhythmic effects against aconitine arrhythmia in rats. 1-p-methylphenyltetra-hydroisoquinoline derivatives show the most potent antiarrhythmio effects and weaker cardiotoxic effects. They have a markedly higher antiarrhythmic potency and a lower acute toxicity than aprindine.更多还原