Discovery of 4,5,6,7-Tetrahydropyrazolo[1.5-a]pyrizine Derivatives as Core Protein Allosteric Modulators (CpAMs) for the Inhibition of Hepatitis B Virus

作者：Buyu Kou, Zhisen Zhang, Xingchun Han, Zheng Zhou, Zhiheng Xu, Xue Zhou, Fang Shen, Yuan Zhou, Xiao‐Jun Tian, Guang Yang, John A. T. Young, Hong-Xia Qiu, Giorgio Ottaviani, A. Mayweg, Wei Zhu, Hong C. Shen, H Liu, Taishan Hu · 发表于：Journal of Medicinal Chemistry · 年份：2023 · DOI：10.1021/acs.jmedchem.3c01145 · 被引用次数：8 · 研究领域：Hepatitis B Virus Studies、Hepatitis C virus research、Viral Infections and Outbreaks Research

Hepatitis B Virus (HBV) core protein allosteric modulators (CpAMs) are an attractive class of potential anti-HBV therapeutic agents. Here we describe the efforts toward the discovery of a series of 4,5,6,7-tetrahydropyrazolo[1,5- a ]pyrazine (THPP) compounds as HBV CpAMs that effectively inhibit a broad range of nucleos(t)ide-resistant HBV variants. The lead compound 45 demonstrated inhibition of HBV DNA viral load in a HBV AAV mouse model by oral administration.