Discovery of 2′-α-C-Methyl-2′-β-C-fluorouridine Phosphoramidate Prodrugs as Inhibitors of Hepatitis C Virus

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• 作者：Debin Zeng ; Rui Zhang ; Quandeng Nie ; Lin Cao ; Luqing Shang ; Zheng Yin
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：December 8, 2016
• 年：2016
• 卷：7
• 期：12
• 页码：1197-1201
• 全文大小：379K
• ISSN：1948-5875

文摘

2′-α-C-Methyl-2′-β-C-fluorouridine and its phosphoramidate prodrugs were synthesized and evaluated for their inhibitory activity against HCV. The structure–activity relationship analysis of the phosphoramidate moiety found that 17m, 17q, and 17r exhibit potent activities against HCV, with EC₅₀ values of 1.82 ± 0.19, 0.88 ± 0.12, and 2.24 ± 0.22 μM, respectively. The docking study revealed that the recognition of the 2′-β-F by Arg158, 3′-OH by N291, and the Watson–Crick pairing with the template allowed 23 to form the in-line conformation necessary for its incorporation into the viral RNA chain.