Neumeyer J L, Perianayagam C, Ruchirawat S
J Med Chem. 1977 Jul;20(7):894-8. doi: 10.1021/jm00217a005.
The synthesis of a series of benzylisoquinolines 2-9 containing aminoacetamide side chains is described. The method involved reduction of the appropriately substituted nitrobenzylisoquinolines followed by acylation to the chloroacylamide derivatives. Amination with the appropriate amine yielded the desires secondary and tertiary amines. The primary amines were prepared via the phthalimides. Two acetanilides 14 and 15 are also described and compared with the benzylisoquinoline derivatives. All compounds were evaluated for their ability to protect against chloroform-induced ventricular fibrillation in mice. The active compounds 6 and 7 were tested for their effect against ventricular arrhythmias in dogs with myocardial infarction. All compounds with the exception of 5 and 12 exhibited some antiarrhythmic effect. The most potent compound, 1-[2-(2-ethylaminoacetyl)amino-3,4-dimethoxybenzyl]isoquinoline (7), showed greater antiarrhythmic potency, was considerably less toxic than lidocaine, and is a candidate for further evaluation.
本文描述了一系列含有氨基乙酰胺侧链的苄基异喹啉2-9的合成。该方法包括将适当取代的硝基苄基异喹啉还原，然后酰化为氯乙酰酰胺衍生物。用适当的胺进行胺化反应得到所需的仲胺和叔胺。伯胺通过邻苯二甲酰亚胺制备。还描述了两种乙酰苯胺14和15，并与苄基异喹啉衍生物进行了比较。评估了所有化合物对小鼠氯仿诱导的心室颤动的保护能力。对活性化合物6和7在心肌梗死犬中抗室性心律失常的作用进行了测试。除5和12外，所有化合物均表现出一定的抗心律失常作用。最有效的化合物1-[2-(2-乙氨基乙酰基)氨基-3,4-二甲氧基苄基]异喹啉(7)显示出更强的抗心律失常效力，毒性比利多卡因小得多，是进一步评估的候选药物。
