Design, synthesis, and evaluation of novel heteroaryldihydropyrimidine derivatives as non‐nucleoside hepatitis B virus inhibitors by exploring the solvent‐exposed region
| Autor: | Xiao Ding, Yu Ji, Xiaowei Guo, Xiaohong Liang, Haiyong Jia, Samuel Desta, Xinyong Liu, Peng Zhan, Zhang Shuo, Jian Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
Hepatitis B virus
Protein Conformation Drug design Virus Replication medicine.disease_cause Antiviral Agents 01 natural sciences Biochemistry Structure-Activity Relationship chemistry.chemical_compound Morpholine Drug Discovery medicine Humans Enzyme Inhibitors IC50 Pharmacology Sulfonamides 010405 organic chemistry Chemistry Organic Chemistry DNA replication Lamivudine DNA-Directed RNA Polymerases Triazoles In vitro 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Pyrimidines Drug Design Solvents Molecular Medicine Nucleoside Protein Binding medicine.drug |
| Zdroj: | Chemical Biology & Drug Design. 95:567-583 |
| ISSN: | 1747-0285 1747-0277 |
| DOI: | 10.1111/cbdd.13512 |
| Popis: | In continuation of our efforts toward the discovery of potent non-nucleoside hepatitis B virus (HBV) inhibitors with novel structures, we have explored the solvent-exposed protein region of heteroaryldihydropyrimidine derivatives. Herein, the morpholine ring of GLS4 was replaced with substituted sulfonamides and triazoles to generate novel non-nucleoside HBV inhibitors with desirable potency. In in vitro biological evaluation, several derivatives showed good anti-HBV DNA replication activity compared to lamivudine. In particular, compound II-1 displayed the most potent activity against HBV DNA replication (IC50 = 0.35 ± 0.04 μM). The preliminary structure-activity relationships of the new compounds were summarized, which may help in discovering more potent anti-HBV agents via rational drug design. |
| Databáze: | OpenAIRE |
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