title: Discovery of 2'-α-C-Methyl-2'-β-C-fluorouridine Phosphoramidate Prodrugs as Inhibitors of Hepatitis C Virus.
abstract: 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 that17m,17q, and17rexhibit potent activities against HCV, with EC50values 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 allowed23to form the in-line conformation necessary for its incorporation into the viral RNA chain.
authors.affiliation: 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.
authors.forename: Debin
authors.initials: D
authors.lastname: Zeng
authors.affiliation: 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.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Quandeng
authors.initials: Q
authors.lastname: Nie
authors.affiliation: 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.
authors.forename: Lin
authors.initials: L
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Luqing
authors.initials: L
authors.lastname: Shang
authors.affiliation: 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.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yin
keywords: Hint 1; docking; hepatitis C virus; inhibitor; phosphoramidate prodrugs