Structure-based Design of Novel Hepatitis B Virus Capsid Assembly Modulators

被引：4
|
作者：
Detta, Elena [1 ,2 ]
Corcuera, Angelica [1 ]
Urban, Andreas [1 ]
Goldner, Thomas [1 ]
Bonsmann, Susanne [1 ]
Engel, Florian [1 ]
May, Marina M. [1 ]
Buschmann, Helmut [1 ]
Fianchini, Mauro [2 ]
Alza, Esther [2 ]
Pericas, Miquel A.
Pushkarev, Pavel A. [3 ]
Varenyk, Anatolii O. [3 ]
Yakovyuk, Taras Y. [3 ]
Homon, Anton A. [3 ]
Sokoliuk, Pavlo A. [3 ]
Smaliy, Radomyr [3 ]
Donald, Alastair
机构：
[1] AiCuris Antiinfect Cures AG, Friedrich Ebert Str 475, D-42117 Wuppertal, Germany
[2] Inst Chem Res Catalonia ICIQ, Av Paisos Catalans 16, Tarragona 43007, Spain
[3] Enamine Ltd, Chervonotkatska St 78, UA-02094 Kiev, Ukraine
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2023年 / 93卷
关键词：
Hepatitis B; Capsid assembly; Small molecules; Virtual screening; Molecular docking; HBV; INFECTION; BIOLOGY;
D O I：
10.1016/j.bmcl.2023.129412
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Small-molecule capsid assembly modulators (CAMs) have been recently recognized as promising antiviral agents for curing chronic hepatitis B virus (HBV) infection. A target-based in silico screening study is described, aimed towards the discovery of novel HBV CAMs. Initial optimization of four weakly active screening hits was performed via focused library synthesis. Lead compound 42 and close analogues 56 and 57 exhibited in vitro potency in the sub- and micromolar range along with good physico-chemical properties and were further evaluated in molecular docking and mechanism of action studies.
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页数：8
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