College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China.
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Mol Divers. 2017 Aug;21(3):565-576. doi: 10.1007/s11030-017-9740-0. Epub 2017 May 23.
Two series of novel 2-thiazolylhydrazone derivatives were designed and synthesized via one-pot reaction of benzaldehyde derivatives, [Formula: see text]-haloketones and thiosemicarbazide. The structures of compounds 1 and 2 were characterized by [Formula: see text] NMR and [Formula: see text] NMR, and compound 1g was further confirmed by X-ray crystallography. All of the target compounds were evaluated for their NA inhibitory activity against influenza viral neuraminidase (H1N1) in vitro, and the results showed that many compounds exhibited moderate to strong inhibitory activities against influenza viral neuraminidase (H1N1). Among them, compounds 1p, 1q and 2c showed the most potent inhibitory activities with [Formula: see text] values ranging from 10.50 to [Formula: see text]. Our structure-activity relationship analysis indicated that 2-thiazolylhydrazone is an effective scaffold for NA inhibitors and that introducing an ethoxycarbonyl group to the 5-position of thiazole ring could enhance inhibitory potency. Molecular docking was performed on the most active compounds 1p and 2c to provide more insight into their mechanism of interaction.
设计并合成了两个系列的新型 2-噻唑基腙衍生物，其通过一锅法反应由苯甲醛衍生物、[化学式：见正文] -卤代酮和氨基硫脲制备得到。化合物 1 和 2 的结构通过 [化学式：见正文] NMR 和 [化学式：见正文] NMR 进行了表征，化合物 1g 还通过 X 射线晶体学进行了进一步确认。所有目标化合物都进行了抗甲型流感病毒神经氨酸酶（H1N1）的体外抑制活性评估，结果表明，许多化合物对流感病毒神经氨酸酶（H1N1）表现出中等至较强的抑制活性。其中，化合物 1p、1q 和 2c 表现出最强的抑制活性，[化学式：见正文] 值范围为 10.50 至 [化学式：见正文]。我们的构效关系分析表明，2-噻唑基腙是神经氨酸酶抑制剂的有效骨架，在噻唑环的 5 位引入乙氧羰基可以增强抑制活性。对最活跃的化合物 1p 和 2c 进行了分子对接，以提供其相互作用机制的更多见解。
