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目的寻找具有Ⅲ/Ⅱ复合作用的新型抗心律失常药物。方法拼合1-苄基-1,2,3,4-四氢异喹啉与具有Ⅲ/Ⅱ复合作用的sotalol结构片段,设计合成1-苄基-2-(4′-甲磺酰基-1-羟基-苯乙基)-1,2,3,4-四氢异喹啉类化合物,通过离体豚鼠心肌标本不应期测定法对所合成的目标化合物进行筛选。结果合成了18个未见文献报道的新化合物(1a-1r)。体外结果表明化合物1d、1e、1i、1j具有较好的延长动作电位时程的作用。结论化合物1d、1e、1i、1j表现出Ⅲ类抗心律失常药物延长动作电位时程的特征,有关Ⅲ/Ⅱ复合作用的药理实验有待进行。
Objective To find a new type of antiarrhythmic drug with the combined effect of Ⅲ / Ⅱ. Methods 1-benzyl-1,2,3,4-tetrahydroisoquinoline and sotalol structure fragment with Ⅲ / Ⅱ complex effect were synthesized and designed to synthesize 1-benzyl-2- (4’-methylsulfonyl- -hydroxy-phenethyl) -1,2,3,4-tetrahydroisoquinoline compounds were synthesized and their target compounds were screened by in vitro refractory assay of isolated guinea pig myocardium. Results A total of 18 new compounds (1a-1r) were synthesized. In vitro results show that the compounds 1d, 1e, 1i, 1j have better action potential duration action. Conclusions Compounds 1d, 1e, 1i, 1j exhibit characteristics of prolongation of action potentials of class Ⅲ antiarrhythmic agents. Pharmacological experiments on the combined effect of Ⅲ / Ⅱ are yet to be carried out.