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新型2',3'-二脱氧-2'-α-氟-2'-β-甲基鸟苷磷酰胺酯前药的合成及其抗丙型肝炎病毒活性

Synthesis and Anti-HCV Activity of a Novel 2',3'-Dideoxy-2'-α-fluoro-2'-β--methyl Guanosine Phosphoramidate Prodrug.

作者信息

Yu Wenquan, Li Ertong, Lv Zhigang, Liu Ke, Guo Xiaohe, Liu Yuan, Chang Junbiao

机构信息

College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, Henan 450001, P. R. China.

High & New Technology Research Center of Henan Academy of Sciences, Zhengzhou, Henan 450002, P. R. China.

出版信息

ACS Med Chem Lett. 2017 May 1;8(6):682-684. doi: 10.1021/acsmedchemlett.7b00174. eCollection 2017 Jun 8.

DOI:10.1021/acsmedchemlett.7b00174
PMID:28626533
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5467188/
Abstract

A novel 2',3'-dideoxy-2'-α-fluoro-2'-β--methyl-6-methoxy guanosine () and its phosphoramidate prodrug () have been designed and synthesized. Their biological activity was evaluated in both cytotoxicity and cell-based HCV replicon assays. Neither compounds exhibited cytotoxicity up to the highest concentration tested (100 μM) in the Huh-7 cell line. The prodrug () displayed nanomolar level antiviral activity (EC = 0.39-1.1 μM) against the HCV genotype (GT) 1a, 1b, 2a, and 1b S282T replicons.

摘要

一种新型的2',3'-二脱氧-2'-α-氟-2'-β-甲基-6-甲氧基鸟苷（）及其磷酰胺酯前药（）已被设计并合成。在细胞毒性和基于细胞的丙型肝炎病毒（HCV）复制子测定中评估了它们的生物活性。在Huh-7细胞系中，直至测试的最高浓度（100μM），两种化合物均未表现出细胞毒性。前药（）对HCV基因型（GT）1a、1b、2a和1b S282T复制子显示出纳摩尔水平的抗病毒活性（EC = 0.39 - 1.1μM）。

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本文引用的文献

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Nucleoside Phosphate and Phosphonate Prodrug Clinical Candidates.核苷磷酸酯和膦酸酯前药临床候选药物。
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