Discovery of Imidazo[1,2-伪][1,8]naphthyridine Derivatives as Potential HCV Entry Inhibitor

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• 作者：Huan Wang ; Shuo Wang ; Lili Cheng ; Ligong Chen ; Yongguang Wang ; Jie Qing ; Shengdian Huang ; Yuanhao Wang ; Xiaoqiang Lei ; Yunfei Wu ; Zhilong Ma ; Linqi Zhang ; Yefeng Tang
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：September 10, 2015
• 年：2015
• 卷：6
• 期：9
• 页码：977-981
• 全文大小：313K
• ISSN：1948-5875

文摘

RO8191 represents a newly discovered small-molecule IFN-like agent that displays potent anti-HCV activity. With it as lead, a series of compounds bearing an imidazo[1,2-伪][1,8]naphthyridine core and an amide bond-linked side chain were designed and synthesized. These compounds were evaluated on HCV cell culture system (HCVcc-hRluc-JFH1), and some of them exhibited remarkable anti-HCV activity (EC₅₀ = 0.017鈥?.159 渭M) and low toxicity (CC₅₀ > 25 渭M). Moreover, it was revealed that these newly identified anti-HCV agents exert their antiviral effect through a distinct mechanism of action from that of RO8191 by targeting the viral entry process. Thus, our study provides a starting point for the development of potential HCV entry inhibitor.