Synthesis and evaluation of a new series of substituted acyl(thio)urea and thiadiazolo [2,3-a] pyrimidine derivatives as potent inhibitors of influenza virus neuraminidase
Synthesis and evaluation of a new series of substituted acyl(thio)urea and thiadiazolo [2,3-a] pyrimidine derivatives as potent inhibitors of influenza virus neuraminidase
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DOI：
10.1016/j.bmc.2006.08.034
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发表时间：
2006-12-15
影响因子：
3.5
通讯作者：
Zhou, Pei
中科院分区：
文献类型：
--
作者：
Sun, Chuanwen;Zhang, Xiaodong;Zhou, Pei
制备了一系列取代酰基（硫代）尿素和2h -1,2,4-噻二唑[2,3- A]嘧啶衍生物，并对其细胞培养和对流感病毒的酶活性进行了测试。体外神经氨酸酶抑制活性与体外培养细胞活性一致，是有效的神经氨酸酶抑制剂。在IC(50)s < 0.1 μ M的类似物中，16和60作为最有潜力的候选物被进一步研究。本文描述了代表性化合物的分子对接工作，以提供对其作用机制的更多见解，并进一步使本文新系列的观察结果合理化，该系列代表了一类新型高效选择性流感病毒抑制剂。(c) 2006 Elsevier Ltd.版权所有。
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 < 0.1 mu M, 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. (c) 2006 Elsevier Ltd. All rights reserved.