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目的设计合成阿齐利特类似物,并研究其体外抗心律失常活性。方法以1-氨基海因盐酸盐为原料,与一系列醛进行缩合反应得到关键中间体1-(取代甲叉基)氨基海因(2);2与1,4-二溴丁烷或1,3-二溴丙烷反应生成3,3与一系列仲胺反应,再经成盐得到盐酸阿齐利特衍生物。结果设计合成12个未见文献报道的目标化合物,所有化合物均经1H-NMR、MS谱确证结构。结论目标化合物5b、5h、5i、5j对离体心肌细胞具有Ⅲ类抗心律失常药物延长动作电位时程的特征,其中化合物5h活性最好。
Objective To design and synthesize azimilide analogs and study their in vitro antiarrhythmic activity. Methods The key intermediates 1- (substituted methylidene) hydantoin (2) was obtained by condensation reaction of a series of aldehydes with 1-aminohydantoin hydrochloride. The reaction of 2 with 1,4-dibromobutane or 1,3 - dibromopropane reaction of 3,3 with a series of secondary amine reaction, and then salt into the Azithromycin hydrochloride derivatives. Results Twelve novel target compounds were reported. All compounds were confirmed by 1H-NMR and MS spectra. Conclusion The target compounds 5b, 5h, 5i, 5j have the characteristic of prolonging the action potential duration of class Ⅲ antiarrhythmic drugs to isolated cardiomyocytes, and the compound 5h has the best activity.