Discovery of SHR5133, a Highly Potent and Novel HBV Capsid Assembly Modulator

被引：8

作者：

Li, Xin ^{[1
]}

Zhang, Zhigao ^{[1
]}

Chen, Yang ^{[1
]}

Wang, Bin ^{[1
]}

Yang, Guimei ^{[1
]}

Xu, Xiangbin ^{[1
]}

Yechao, Baihui ^{[1
]}

Bai, Dongdong ^{[1
]}

Feng, Binqiang ^{[1
]}

Mao, Yuchang ^{[1
]}

Feng, Jun ^{[1
]}

Bai, Chang ^{[1
]}

He, Feng ^{[1
]}

Tao, Weikang ^{[1
]}

机构：

[1] Shanghai Hengrui Pharmaceut Co Ltd, Shanghai 200245, Peoples R China

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2022年 / 13卷 / 03期

关键词：

HBV; capsid assembly; antiviral; SHR5133; modulator; INHIBITORS;

D O I：

10.1021/acsmedchemlett.2c00002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Capsid assembly modulators (CpAMs) represent a new class of antivirals targeting hepatitis B virus (HBV) core protein to disrupt the assembly process. In this work, a novel chemotype featuring a fused heterocycle amide was discovered through pharmacophore exploration. Lead optimization resulted in compound 8 with an EC50 value of 511 nM, and then methyl substitution on the piperazine was found to improve the in vitro potency remarkably. Further SAR studies established the key compound SHR5133, which showed high in vitro antiviral potency, favorable pharmacokinetic profiles across species, and robust in vivo efficacy.

引用

页码：507 / 512

页数：6

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