通過當代藥物化學策略發現和優化基於苯磺酰胺的乙型肝炎

StephenW

Discovery and optimization of benzenesulfonamides-based hepatitis B virus capsid modulators via contemporary medicinal chemistry strategies
Yujie Ren  1 , Yue Ma  1 , Srinivasulu Cherukupalli  1 , John E Tavis  2 , Luis Menéndez-Arias  3 , Xinyong Liu  4 , Peng Zhan  5
Affiliations
Affiliations

    1
    Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China.
    2
    Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA; Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, MO, USA.
    3
    Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid), Madrid, Spain. Electronic address: [email protected].
    4
    Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China. Electronic address: [email protected].
    5
    Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China. Electronic address: [email protected].

    PMID: 32949990 DOI: 10.1016/j.ejmech.2020.112714

Abstract

Hepatitis B is a vaccine-preventable, but potentially life-threatening liver infection caused by the Hepatitis B virus (HBV). It represents an important health burden, with 257 million active cases globally. Current HBV treatments using nucleos(t)ide analogs and pegylated interferons cannot alleviate the situation completely since they are unable to cure the infection or reduce the amount of viral covalently closed circular DNA (cccDNA). The HBV core protein is a small protein of 183 amino acids that participates in multiple essential functions in the HBV replicative cycle. Capsid assembly modulators that target the core protein are being developed. Sulfonamides are synthetic functional groups, found in several drugs. Herein, we provide a concise report focusing on the sulfamoylbenzamides as HBV capsid modulators, and medicinal chemistry strategies used in their design and development.

Keywords: CAMs; Drug design; HBV; Small molecule; Sulfonyl group.

Copyright © 2020 Elsevier Masson SAS. All rights reserved.

StephenW

通過當代藥物化學策略發現和優化基於苯磺酰胺的乙型肝炎病毒衣殼調節劑
任玉杰1，馬​​躍1，斯里尼瓦蘇魯·庫魯庫帕利1，約翰·塔維斯2，路易斯·梅嫩德斯-阿里亞斯3，劉新勇4，彭展5
隸屬關係
隸屬關係

    1個
    山東大學藥學院，藥物化學系，化學生物學教育部重點實驗室，濟南250012
    2
    聖路易斯大學醫學院分子微生物學和免疫學系，美國密蘇里州聖路易斯；美國密蘇里州聖路易斯市聖路易斯大學醫學院聖路易斯大學肝臟中心。
    3
    分子生物學中心“ Severo Ochoa”（西班牙體育研究中心和馬德里自治大學），馬德里，西班牙。電子地址：[email protected]。
    4
    山東大學藥學院，藥物化學系，化學生物學教育部重點實驗室，濟南250012電子地址：[email protected]。
    5
    山東大學藥學院，藥物化學系，化學生物學教育部重點實驗室，濟南250012電子地址：[email protected]。

    PMID：32949990 DOI：10.1016 / j.ejmech.2020.112714

抽象

乙型肝炎是可以預防的疫苗，但可能由乙型肝炎病毒（HBV）引起威脅生命的肝臟感染。它代表著重要的健康負擔，全球有2.57億活躍病例。當前使用核苷（核苷酸）類似物和聚乙二醇化干擾素的HBV治療無法完全緩解這種情況，因為它們無法治愈感染或減少病毒共價閉合環狀DNA（cccDNA）的量。 HBV核心蛋白是一種183個氨基酸的小蛋白，在HBV複製週期中參與多種基本功能。正在開發靶向核心蛋白的衣殼裝配調節劑。磺酰胺是合成的官能團，存在於幾種藥物中。在此，我們提供一份簡明的報告，重點介紹作為HBV衣殼調節劑的氨磺酰苯甲酰胺，以及在其設計和開發中使用的藥物化學策略。

關鍵字：CAM；藥物設計；乙肝病毒小分子；磺酰基。

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