Banitt E H, Bronn W R, Coyne W E, Schmid J R
J Med Chem. 1977 Jun;20(6):821-6. doi: 10.1021/jm00216a016.
Benzamides characterized by one or more 2,2,2-trifluoroethoxy ring substituents and a heterocyclic amide side chain have been prepared and evaluated for oral antiarrhythmic activity in mice. The most potent compounds are derived from 2,5-bis(2,2,2-trifluoroethoxy)benzamide, and, within this group, both tertiary as well as secondary benzamides are active. Considerable variation in the heterocyclic ring is permissible, but antiarrhythmic activity is strongly influenced by the basicity of the amine nitrogen and the nature of the link between heterocycle and amide nitrogen. One of these compounds, N-(2-piperidylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide acetate (flecainide acetate, USAN), was studied extensively in animals and selected for clinical trial as an antiarrhythmic.
已制备出具有一个或多个2,2,2 - 三氟乙氧基环取代基和杂环酰胺侧链的苯甲酰胺，并在小鼠中评估了其口服抗心律失常活性。最有效的化合物衍生自2,5 - 双（2,2,2 - 三氟乙氧基）苯甲酰胺，在该组化合物中，叔苯甲酰胺和仲苯甲酰胺均具有活性。杂环允许有相当大的变化，但抗心律失常活性受胺氮的碱性以及杂环与酰胺氮之间连接性质的强烈影响。其中一种化合物，N - （2 - 哌啶基甲基）-2,5 - 双（2,2,2 - 三氟乙氧基）苯甲酰胺乙酸盐（氟卡尼乙酸盐，美国采用名称），在动物中进行了广泛研究，并被选作抗心律失常药物进行临床试验。
