2－烃基－3－（3′，5′－双胺甲基－4′－羟基）－苯甲酰吲哚衍生物的合成及其心血管活性

SYNTHESIS AND CARDIOVASCULAR ACTIVITIES OF 2-ARYL-3-(3',5'- DIAMINOETHYL-4'-HYDROXY)-BENZFOYL INDOLE DERIVATIVES

本文以具有心血管活性的２－取代－３－对羟基苯甲酰吲哚为母核引入常咯啉双胺甲基结构合成了一系列衍生物。对部分化合物进行了抗哇巴因所致心律失常试验，受试化合物具有不同程度的抗心律失常活性，其中化合物（Ⅱ１）为常咯啉的２．４倍，并略高于慢心律，该化合物抗胆碱能的副作用较小，约为常咯啉的１／２。本文还初步探讨了构效关系。

Indole compounds have wide bioactivities and aminomethyl compounds,such as changrolin,possess antiarrythmic action。 In order to search for novel antiarrythmic drugs with higher activities and less side effects, fourteen derivatives of 2-aryl-3-(3',5'-diaminomethyl-4'-hydroxy)-benzoyl indole were designed and synthesized on the basis of the SAR of antiarrythmic drugs and the structural features of some indole compounds。 Indole and 2-substituted indole reacted with ethyl magnesium bromide to obtain indolemagnesium bromide,which under went acylation ,demethylation or hydrolysis ,and Mannish reaction to give compounds Ⅰ,Ⅱ,Ⅲ.Six compounds(Ⅱ1～3,Ⅲ1～3)were submitted to antiarrythmic tests,The results indicated that the tested compounds showed various degrees of antiarrythmic activity by restoration of sinus rhythm from oubain-induced tachcardia in guinea pigs。 The antiarrytmic activity of compound (Ⅱ1)was more potent then that of changrolin,but its anti-cholinergic activity was only half of that of latter. Primarily SAR of these compounds was discussed in this paper.