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在临床观察中,发现常咯啉(Ⅰ)对多种病因引起的室性早搏,房性早搏及短阵室速效果显著。惟该药尚存在一些副作用。为了寻找优于常咯啉的抗心律失常药物,我们合成了若干类似物及其有关化合物(Ⅱ～Ⅵ)。这些化合物的合成,除(Ⅴ)是以对酰胺苯酚为原料外,化合物(Ⅱ)～(Ⅳ)是以相应的氯化物与对氨基苯酚缩合,所得产物再按常法分别进行Mannich反应,便生成预期的化合物。化合物(Ⅵ)系将4-氯代喹唑啉与各种胺在适当溶液中,按不同条件反应而制备。 药理试验结果表明,其中化合物1、5、7、8、14、15、17等均能对抗乌头碱引起的实验性心律失常,其中化合物14、15、17疗效显著。化合物14对抗由氯化乙酰胆碱对狗引起的房颤,其疗效可能超过常咯啉。常咯啉结构改造的进一步工作,尚在继续进行中。
In the clinical observation, we found that regular pyrroline (Ⅰ) on a variety of causes of ventricular premature beats, atrial premature beats and short-term ventricular tachycardia effect is significant. However, the drug still has some side effects. In order to find anti-arrhythmic drugs superior to those of statin, we synthesized several analogs and their related compounds (Ⅱ ~ Ⅵ). The compounds (II) and (IV) are obtained by condensing the corresponding chlorides with p-aminophenol except that the p-aminophenol is used as the starting material for the synthesis of these compounds. The resulting products are subjected to the Mannich reaction according to a conventional method The expected compound is produced. The compound (VI) is prepared by reacting 4-chloroquinazoline with various amines in a suitable solution under different conditions. Pharmacological test results show that compounds 1, 5, 7, 8, 14, 15, 17 and so on are able to fight aconitine induced experimental arrhythmia, of which compound 14,15,17 significant effect. Compound 14 counteracts atrial fibrillation induced by acetylcholine chloride in dogs, which may outweigh the efficacy of the regular statins. The further work on the structural modification of pyrroloquinoline is still under way.