Design, Synthesis and Discovery of N,N'-Carbazoyl-aryl-urea Inhibitors of Zika NS5 Methyltransferase and Virus Replication.,ChemMedChem

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Design, Synthesis and Discovery of N,N'-Carbazoyl-aryl-urea Inhibitors of Zika NS5 Methyltransferase and Virus Replication.
ChemMedChem ( IF 3.6 ) Pub Date : 2020-01-07 , DOI: 10.1002/cmdc.201900533
Sharon Spizzichino _{1,

2} , Giulio Mattedi ₁ , Kate Lauder ₁ , Coralie Valle ₃ , Wahiba Aouadi ₃ , Bruno Canard ₃ , Etienne Decroly ₃ , Suzanne J F Kaptein ₄ , Johan Neyts ₄ , Carl Graham ₁ , Zakary Sule ₁ , David J Barlow ₁ , Romano Silvestri ₂ , Daniele Castagnolo ₁

Affiliation

The recent outbreaks of Zika virus (ZIKV) infection worldwide make the discovery of novel antivirals against flaviviruses a research priority. This work describes the identification of novel inhibitors of ZIKV through a structure-based virtual screening approach using the ZIKV NS5-MTase. A novel series of molecules with a carbazoyl-aryl-urea structure has been discovered and a library of analogues has been synthesized. The new compounds inhibit ZIKV MTase with IC50 between 23-48 μM. In addition, carbazoyl-aryl-ureas also proved to inhibit ZIKV replication activity at micromolar concentration.

中文翻译：

Zika NS5 甲基转移酶和病毒复制的 N,N'-咔唑酰基-芳基-脲抑制剂的设计、合成和发现。

最近在全球范围内爆发的寨卡病毒（ZIKV）感染使发现针对黄病毒的新型抗病毒药物成为研究重点。这项工作描述了使用 ZIKV NS5-MTase 通过基于结构的虚拟筛选方法鉴定新型 ZIKV 抑制剂。已经发现了一系列具有咔唑基-芳基-脲结构的新型分子，并合成了类似物库。新化合物抑制 ZIKV MTase，IC50 介于 23-48 μM 之间。此外，咔唑酰基芳基脲也被证明可以在微摩尔浓度下抑制 ZIKV 复制活性。

更新日期：2020-01-07

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