期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 24, 期 17, 页码 4276-4280出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2014.07.019
关键词
Hepatitis C virus; HCV RNA replication; Anti-HCV agent; Full genome length; ORL8
资金
- Drug Discovery for Intractable Infectious Diseases Project, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University from the Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Grants-in-Aid for Scientific Research [25293110] Funding Source: KAKEN
Using our recently developed assay system for full-genome-length hepatitis C virus (HCV) RNA replication in human hepatoma-derived Li23 cells (ORL8), we identified 4-(1,1,1,3,3,3-hexafluoro-2-hydroxy-2-propyl)aniline analog la as a novel HCV inhibitor. Structural modifications of la provided a series of sulfonamides 7 with much more potent HCV RNA replication-inhibitory activity than ribavirin. Compound 7a showed an additive anti-HCV effect in combination with standard anti-HCV therapy (IFN-alpha plus ribavirin). Since 7a generated reactive oxygen species (ROS) in the ORL8 system and its anti-HCV activity was blocked by vitamin E, its anti-HCV activity may be mediated at least in part by ROS. (C) 2014 Elsevier Ltd. All rights reserved.
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