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    • 2. 发明申请
    • PHARMACEUTICAL COMPOSITIONS FOR TREATMENT OR PREVENTION OF HBV INFECTION
    • 用于治疗或预防HBV感染的药物组合物
    • US20110160252A1
    • 2011-06-30
    • US12999055
    • 2009-06-18
    • Masashi MizokamiYasuhito TanakaMasaya SugiyamaMasayuki Sudoh
    • Masashi MizokamiYasuhito TanakaMasaya SugiyamaMasayuki Sudoh
    • A61K31/44C07C229/34A61K31/195C07D213/55A61P31/12
    • A61K31/13A61K31/165A61K31/201A61K31/381A61K31/405A61K31/4406A61K31/4418
    • First, the present inventors assessed the effect of the compound represented by formula (III) below on Huh-7 cells infected with HBV, and demonstrated that the compound alone had an anti-HBV effect in vitro.Formula (III) Then, the present inventors revealed that the HBV replication-suppressing effect of PEG-IFN is enhanced in chimeric mice having a human liver infected with genotype C or A HBV when PEG-IFN is used in combination with the compound represented by formula (III) above. The present inventors also revealed that the HBV replication-suppressing effect of Entecavir is enhanced in chimeric mice having a human liver infected with genotype C HBV (wild-type and Entecavir-resistant strains) when Entecavir is used in combination with the compound represented by formula (III) above. In addition, the present inventors revealed that the compound represented by formula (III) above exerts the anti-HBV effect not only against wild-type HBV strains but also against Entecavir- and/or Lamivudine-resistant HBV strains.
    • 首先,本发明人评估了下述式(III)表示的化合物对HBV感染的Huh-7细胞的作用,并证明该化合物在体外具有抗HBV作用。 式(III)然后,本发明人揭示了当将PEG-IFN与由下列化合物组合使用时,将具有基因型C或A HBV感染的人肝的嵌合小鼠中的PEG-IFN的HBV复制抑制作用增强 上述式(III)。 本发明人还发现,当恩替卡韦与式(I)表示的化合物组合使用时,恩替卡韦的HBV复制抑制作用在具有感染基因型C HBV(野生型和恩替卡韦抗性菌株)的人肝脏的嵌合小鼠中得到增强 (三)。 此外,本发明人发现,上述式(III)表示的化合物不仅对抗野生型HBV株而且对依替卡韦和/或拉米夫定耐药的HBV株产生抗HBV作用。