3-取代二碘苯甲酰吲哚衍生物的合成

Synthesis of 3-Substituted Diiodo Benzoylindole Derivatives

为了寻找活性高,毒副作用小的抗心律失常药物,设计并合成了3-[3,5-二碘-4-(烷胺基烷氧基)苯甲酰]吲哚和2-甲基-3-[3,5-二碘-4-(烷胺基烷氧基)苯甲酰]吲哚类等12个化合物。初步药理试验表明,它们都有不同程度的抗心律失常活性,其中2-甲基-3-[3,5-二碘-4-(N-吗啡啉乙氧基)苯甲酰]吲哚对氯仿诱发的小鼠心律失常具有明显的保护作用。

In order to search for novel antiarrhythmic drugs possessing higher activities and less side effects, twelve derivatives of 3-[3,5-diiodo-4-(alkylaminoalkoxy) benzoyl] indole (Ⅰ) and 2-methyl-3-[3,5-diiodo-4-(alkylaminoalkoxy) benzoyl] indole (Ⅱ) were designed and synthesized. On basis of the Structureactivity relattionship of antiarrhythmic drugs and the structural features of indole compounds and amiodarone, indole reacts with ethylmagnesium bromide to give indole magnesium bromide, which then undergoes acylation, hydrolysis, iodination and etherification to yield compound Ⅰ and Ⅱ. Preliminary pharmacological tests show that compound Ⅱ_1 has significant protective effect on arrhythmias induced by chloroform in rats.