发现RG7834：一流的选择性和口服可用的小分子乙型肝炎病毒

StephenW

J Med Chem. 2018 Oct 4. doi: 10.1021/acs.jmedchem.8b01245. [Epub ahead of print]
Discovery of RG7834: The First-in-Class Selective and Orally Available Small Molecule Hepatitis B Virus Expression Inhibitor with Novel Mechanism of Action.
Han X, Zhou C, Jiang M, Wang Y, Wang J, Cheng Z, Wang M, Liu Y, Liang C, Wang J, Wang Z, Weikert R, Lv W, Xie J, Yu X, Zhou X, Luangsay S, Shen HC, Mayweg AV, Javanbakht H, Yang S.
Abstract

Chronic hepatitis B virus (HBV) infection is a serious public health burden and current therapies cannot achieve satisfactory cure rate. There are high unmet medical needs of novel therapeutic agents with differentiated mechanism of action (MOA) from the current standard of care. RG7834, a compound from the dihydroquinolizinone (DHQ) chemical series, is a first-in-class highly selective and orally bioavailable HBV inhibitor which can reduce both viral antigens and viral DNA with a novel mechanism of action. Here we report the discovery of RG7834 from a phenotypic screening and the structure-activity relationship (SAR) of the DHQ chemical series. RG7834 can selectively inhibit HBV but not other DNA or RNA viruses in a virus panel screening. Both in vitro and in vivo profiles of RG7834 are described herein, and the data support further development of this compound as a chronic HBV therapy.

PMID:
    30286292
DOI:
    10.1021/acs.jmedchem.8b01245

StephenW

J Med Chem。 2018年10月4日doi：10.1021 / acs.jmedchem.8b01245。 [提前打印]
发现RG7834：一流的选择性和口服可用的小分子乙型肝炎病毒表达抑制剂具有新的作用机制。
Han X，Zhou C，Jiang M，Wang Y，Wang J，Cheng Z，Wang M，Liu Y，Liang C，Wang J，Wang Z，Weikert R，Lv W，Xie J，Yu X，Zhou X，Luangsay S ，Shen HC，Mayweg AV，Javanbakht H，Yang S.
抽象

慢性乙型肝炎病毒（HBV）感染是一种严重的公共卫生负担，目前的治疗方法无法达到令人满意的治愈率。从目前的护理标准来看，具有差异化作用机制（MOA）的新型治疗剂存在高度未满足的医疗需求。 RG7834是一种来自二氢喹嗪酮（DHQ）化学系列的化合物，是一流的高选择性和口服生物可利用的HBV抑制剂，可以通过新的作用机制减少病毒抗原和病毒DNA。在这里，我们报告了从表型筛选和DHQ化学系列的结构 - 活性关系（SAR）发现RG7834。 RG7834可以在病毒组筛选中选择性地抑制HBV，但不能抑制其他DNA或RNA病毒。本文描述了RG7834的体外和体内特征，并且该数据支持该化合物作为慢性HBV疗法的进一步开发。

结论：
    30286292
DOI：
    10.1021 / acs.jmedchem.8b01245

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