Discovery and optimization of benzenesulfonamides-based hepatitis B virus capsid modulators via contemporary medicinal chemistry strategies.

Yujie Ren, Yue Ma, Srinivasulu Cherukupalli, John E Tavis, Luis Menéndez-Arias, Xinyong Liu, Peng Zhan

Journal: European journal of medicinal chemistry 2021;206():112714

PMID: 32949990

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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.

Address: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, China.; 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.; Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid), Madrid, Spain. Electronic address: [email protected].; 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].; 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].

DOI: 10.1016/j.ejmech.2020.112714

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MeSH Terms: Capsid, Chemistry, Pharmaceutical, Drug Design, Hepatitis B virus, Humans, Sulfonamides, Benzenesulfonamides