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本文设计了一系列新型结构的肟及肟醚化合物,通过分子对接进行虚拟筛选。以苯、甲苯、甲氧基苯、氯苯为初始原料合成12个新化合物,其中肟类4个、肟醚类8个,并对其结构进行了~1H NMR、~(13)C NMR和MS确认。体外活性测试结果表明,部分目标化合物具有一定的抗乙肝病毒活性且毒性较小。其中化合物4B-2抑制活性最好,其对表面抗原(HBsAg)与e抗原(HBeAg)的抑制活性IC_(50)和治疗指数分别为IC_(50 HBsAg)=81.15μmol·L~(-1)、SI_(HBsAg)=9.20;IC_(50 HBeAg)=90.66μmol·L~(-1)、SI_(HBeAg)=8.24。初步的构效关系显示甲基肟醚类化合物活性较好,为新抗乙肝药物的研究提供参考。
In this paper, a series of novel oxime and oxime ether compounds have been designed and screened by molecular docking. Twelve new compounds were synthesized from benzene, toluene, methoxybenzene and chlorobenzene, including 4 oximes and 8 oxime ethers. Their structures were analyzed by 1H NMR, 13 C NMR and MS confirmed. In vitro activity test results show that some of the target compounds have a certain anti-hepatitis B virus activity and less toxicity. Among them, compound 4B-2 showed the best inhibitory activity against IC50 (50) and therapeutic index (IC 50 HBsAg) of 81.15 μmol·L -1 for HBsAg and HBeAg, respectively , SI_ (HBsAg) = 9.20; IC_ (50 HBeAg) = 90.66μmol·L -1, SI_ (HBeAg) = 8.24. The preliminary structure-activity relationship shows that the activity of methyloxime ether compounds is good, which provides a reference for the new anti-hepatitis B drug research.