1578156-21-4Relevant articles and documents
DIHYDROPYRIMIDINE DERIVATIVES AND USES THEREOF IN THE TREATMENT OF HBV INFECTION OR OF HBV-INDUCED DISEASES
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Page/Page column 39; 132-133, (2020/01/24)
The application describes dihydropyrimidine derivatives which are useful in the treatment or prevention of HBV infection or of HBV-induced diseases, more particularly of HBV chronic infection or of diseases induced by HBV chronic infection, as well as pharmaceutical or medical applications thereof.
Discovery and Pre-Clinical Characterization of Third-Generation 4-H Heteroaryldihydropyrimidine (HAP) Analogues as Hepatitis B Virus (HBV) Capsid Inhibitors
Qiu, Zongxing,Lin, Xianfeng,Zhang, Weixing,Zhou, Mingwei,Guo, Lei,Kocer, Buelent,Wu, Guolong,Zhang, Zhisen,Liu, Haixia,Shi, Houguang,Kou, Buyu,Hu, Taishan,Hu, Yimin,Huang, Mengwei,Yan, S. Frank,Xu, Zhiheng,Zhou, Zheng,Qin, Ning,Wang, Yue Fen,Ren, Shuang,Qiu, Hongxia,Zhang, Yuxia,Zhang, Yi,Wu, Xiaoyue,Sun, Kai,Zhong, Sheng,Xie, Jianxun,Ottaviani, Giorgio,Zhou, Yuan,Zhu, Lina,Tian, Xiaojun,Shi, Liping,Shen, Fang,Mao, Yi,Zhou, Xue,Gao, Lu,Young, John A. T.,Wu, Jim Zhen,Yang, Guang,Mayweg, Alexander V.,Shen, Hong C.,Tang, Guozhi,Zhu, Wei
, p. 3352 - 3371 (2017/05/05)
Described herein are the discovery and structure-activity relationship (SAR) studies of the third-generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the first- and second-generation 4-H HAPs. X-ray crystallographic study of analogue 12 (HAP_R01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen bonding interactions with capsid protein and coordinated waters. The representative analogue 10 (HAP_R10) was extensively characterized in vitro (ADMET) and in vivo (mouse PK and PD) and subsequently selected for further development as oral anti-HBV infection agent.
6-AMINO ACID HETEROARYLDIHYDROPYRIMIDINES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
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, (2014/03/26)
The invention provides novel compounds having the general formula:, wherein R1, R2, R3, R4 and A are as described herein, compositions including the compounds and methods of using the compounds.