Sun Chuanwen, Zhang Xiaodong, Huang Hai, Zhou Pei
Department of Biosynthetic Drugs, School of Pharmacy, Fudan University, Shanghai 200032, China.
Bioorg Med Chem. 2006 Dec 15;14(24):8574-81. doi: 10.1016/j.bmc.2006.08.034. Epub 2006 Sep 18.
A series of substituted acyl(thio)urea and 2H-1,2,4-thiadiazolo [2,3-a] pyrimidine derivatives were prepared and both of their cell culture and enzymatic activity toward influenza virus were tested. Their in vitro neuraminidase inhibitory activities were in good agreement with the corresponding activities in cultured cells and they were evaluated as potent neuraminidase inhibitors. Of the analogues that demonstrated IC(50)s<0.1microM, 16 and 60 were further investigated as candidates with the most potential for future development. The molecular docking work of the representative compound was described to provide more insight into their mechanism of action and further rationalize the observations of this new series herein, which represents a novel class of highly potent and selective inhibitors of influenza virus.
制备了一系列取代的酰基（硫代）脲和2H-1,2,4-噻二唑并[2,3-a]嘧啶衍生物，并测试了它们的细胞培养情况以及对流感病毒的酶活性。它们的体外神经氨酸酶抑制活性与在培养细胞中的相应活性高度一致，并且被评估为有效的神经氨酸酶抑制剂。在表现出IC(50)s<0.1微摩尔的类似物中，16号和60号作为最具未来开发潜力的候选物被进一步研究。描述了代表性化合物的分子对接工作，以便更深入地了解其作用机制，并进一步合理化本新系列化合物的观察结果，该系列代表了一类新型的高效且选择性的流感病毒抑制剂。
