Zeng Debin, Zhang Rui, Nie Quandeng, Cao Lin, Shang Luqing, Yin Zheng
State Key Laboratory of Elemento-Organic Chemistry, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University , Haihe Education Park, 38 Tongyan Road, Tianjin 300353, PR China.
ACS Med Chem Lett. 2016 Oct 19;7(12):1197-1201. doi: 10.1021/acsmedchemlett.6b00270. eCollection 2016 Dec 8.
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 , , and exhibit potent activities against HCV, with EC 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 to form the in-line conformation necessary for its incorporation into the viral RNA chain.
合成了2'-α-C-甲基-2'-β-C-氟尿苷及其磷酰胺酯前药，并评估了它们对丙型肝炎病毒（HCV）的抑制活性。对磷酰胺部分的构效关系分析发现，[具体化合物名称未给出]、[具体化合物名称未给出]和[具体化合物名称未给出]对HCV表现出强效活性，其半数有效浓度（EC）值分别为1.82±0.19、0.88±0.12和2.24±0.22μM。对接研究表明，精氨酸158对2'-β-氟的识别、天冬酰胺291对3'-羟基的识别以及与模板的沃森-克里克配对使得[具体化合物名称未给出]能够形成将其掺入病毒RNA链所必需的直线构象。
