A novel β-D-2′-deoxy-2′-α-fluoro-2′-β-C-(fluoromethyl)uridine phosphoramidate prodrug (1) has been synthesized. This compound exhibits submicromolar-level antiviral activity in vitro against HCV genotypes 1b, 1a, 2a, and S282T replicons (EC₅₀ = 0.18–1.13 μM) with low cytotoxicity (CC₅₀ > 1000 μM). Administered orally, prodrug 1 is well tolerated at doses of up to 4 g/kg in mice, and produces a high level of the corresponding triphosphate in rat liver.

中文翻译：

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用于治疗丙型肝炎病毒感染的新型β-D-2'-脱氧-2'-α-氟-2'-β- C-（氟甲基）尿苷氨基磷酸酯前药的合成及生物学评价

合成了新型的β-D-2'-脱氧-2'-α-氟-2'-β- C-（氟甲基）尿苷氨基磷酸酯前药（1）。该化合物在体外对HCV基因型1b，1a，2a和S282T复制子（EC ₅₀  = 0.18-1.13μM）表现出亚微摩尔水平的抗病毒活性，且具有低细胞毒性（CC ₅₀  > 1000μM）。口服给药，前药1在小鼠中的剂量高达4 g / kg时具有良好的耐受性，并在大鼠肝脏中产生高水平的相应三磷酸酯。