Anti-norovirus activity of C7-modified 4-amino-pyrrolo[2,1-f][1,2,4]triazine C-nucleosides.,European Journal of Medicinal Chemistry

当前位置： X-MOL 学术 › Eur. J. Med. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Anti-norovirus activity of C7-modified 4-amino-pyrrolo[2,1-f][1,2,4]triazine C-nucleosides.
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2020-03-07 , DOI: 10.1016/j.ejmech.2020.112198
Qingfeng Li ₁ , Elisabetta Groaz ₁ , Joana Rocha-Pereira ₂ , Johan Neyts ₂ , Piet Herdewijn ₁

Affiliation

Synthetic nucleoside analogues characterized by a C-C anomeric linkage form a family of promising therapeutics against infectious and malignant diseases. Herein, C-nucleosides comprising structural variations at the sugar and nucleobase moieties were examined for their ability to inhibit both murine and human norovirus RNA-dependent RNA polymerase (RdRp). We have found that the combination of 4-amino-pyrrolo[2,1-f][1,2,4]triazine and its 7-halogenated congeners with either a d-ribose or 2'-C-methyl-d-ribose unit resulted in analogues with good antiviral activity against murine norovirus (MNV), albeit coupled with a significant cytotoxicity. Among this series, 4-aza-7,9-dideazaadenosine notably retained a strong antiviral effect in a human norovirus (HuNoV) replicon assay with an EC50 = 0.015 μM. This study demonstrates that C-nucleosides can be used as viable starting scaffolds for further optimization towards the development of nucleoside-based inhibitors of norovirus replication.

中文翻译：

C7修饰的4-氨基-吡咯并[2,1-f] [1,2,4]三嗪C-核苷的抗诺如病毒活性。

以CC异头键为特征的合成核苷类似物形成了一个有前途的针对传染性和恶性疾病的疗法。本文中，检查了在糖和核碱基部分包含结构变异的C-核苷抑制鼠和人诺如病毒RNA依赖性RNA聚合酶（RdRp）的能力。我们发现4-氨基-吡咯并[2,1-f] [1,2,4]三嗪及其7-卤代同族与d-核糖或2'-C-甲基-d-核糖的组合该单元产生了对鼠诺如病毒（MNV）具有良好抗病毒活性的类似物，尽管其具有明显的细胞毒性。在该系列中，4-氮杂-7,9-二氮杂叠氮腺苷在人诺如病毒（HuNoV）复制子测定中的EC50 = 0.015μM时特别保留了强大的抗病毒作用。

更新日期：2020-03-09

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11