衣壳
化学
CYP3A4型
乙型肝炎病毒
病毒学
病毒
生物化学
基因
生物
新陈代谢
细胞色素P450
作者
Xianfeng Lin,Shi Houguang,Weixing Zhang,Zongxing Qiu,Zheng Zhou,Fabian Dey,Sheng Zhong,Hong-Xia Qiu,Jianxun Xie,Xue Song Zhou,Guang Yang,Guozhi Tang,Hong Shen,Wei Zhu
标识
DOI:10.1021/acs.jmedchem.9b01421
摘要
Described herein is a new approach to mitigate CYP3A4 induction. In this unconventional approach, a fine-tuning of the dihedral angle between the C4 phenyl and the dihydropyrimidine core of the heteroaryldihydropyrimidine (HAP) class of capsid inhibitors successfully altered the structure-activity-relationships (SARs) of the unwanted CYP3A4 induction and the desired HBV capsid inhibition to more favorable values. This eventually led to the discovery of a new capsid inhibitor with significantly reduced CYP3A4 induction, excellent anti-HBV activity, favorable preclinical PK/PD profiles, and no early safety flags.
科研通智能强力驱动
Strongly Powered by AbleSci AI