Synthesis, activity, and pharmacokinetic properties of a series of conformationally-restricted thiourea analogs as novel hepatitis C virus inhibitors
| Autor: | Jing-Chyi Wang, Yu-Sheng Chao, Teng-Kuang Yeh, Sheng-Ju Hsu, Chung-Chi Lee, Yen-Chun Lee, Jyh-Haur Chern, Yen-Shian Wu, Andrew Yueh, Li-Wen Wang, Iou-Jiun Kang |
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| Rok vydání: | 2010 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Molecular Conformation Pharmaceutical Science Hepacivirus Fluorene Virus Replication Biochemistry Chemical synthesis Antiviral Agents chemistry.chemical_compound Structure-Activity Relationship In vivo Cell Line Tumor Drug Discovery Animals Humans Cytotoxicity Molecular Biology Subgenomic mRNA Fluorenes Organic Chemistry Thiourea In vitro Rats chemistry Fluorenone Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry. 18(17) |
| ISSN: | 1464-3391 |
| Popis: | A series of novel conformationally-restricted thiourea analogs were designed, synthesized, and evaluated for their anti-HCV activity. Herein we report the synthesis, structure–activity relationships (SARs), and pharmacokinetic properties of this new class of thiourea compounds that showed potent inhibitory activities against HCV in the cell-based subgenomic HCV replicon assay. Among compounds tested, the fluorene compound 4b was found to possess the most potent activity (EC 50 = 0.3 μM), lower cytotoxicity (CC 50 > 50 μM), and significantly better pharmacokinetic properties compared to its corresponding fluorenone compound 4c . |
| Databáze: | OpenAIRE |
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