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

ABSTRACT: 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-α][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 = 0.017-0.159 μM) and low toxicity (CC50 > 25 μM). 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.

SUBMITTER: Wang H

PROVIDER: S-EPMC4569878 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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

Wang Huan H Wang Shuo S Cheng Lili L Chen Ligong L Wang Yongguang Y Qing Jie J Huang Shengdian S Wang Yuanhao Y Lei Xiaoqiang X Wu Yunfei Y Ma Zhilong Z Zhang Linqi L Tang Yefeng Y

ACS medicinal chemistry letters 20150727 9

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-α][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 = 0.017-0.159 μM) and low toxicity (CC50 > 25 μM). Moreover, it was revealed that these newly iden ...[more]

PMID: 26396683

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