European Journal of Medicinal Chemistry p. 107 - 113 (2018)
Update date:2022-08-11
Topics:
Li, Ertong
Wang, Yafeng
Yu, Wenquan
Lv, Zhigang
Peng, Youmei
Liu, Bingjie
Li, Shiliang
Ho, Wenzhe
Wang, Qingduan
Li, Honglin
Chang, Junbiao
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.
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Doi:10.3184/174751914X13932618023986
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