Format

Send to

Choose Destination
ACS Comb Sci. 2015 Oct 12;17(10):641-52. doi: 10.1021/acscombsci.5b00101. Epub 2015 Sep 17.

High-Throughput Screening, Discovery, and Optimization To Develop a Benzofuran Class of Hepatitis C Virus Inhibitors.

Author information

1
Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , 10 Center Drive, Bethesda, Maryland 20892, United States.
2
NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health , 9800 Medical Center Drive, Rockville, Maryland 20850, United States.

Abstract

Using a high-throughput, cell-based HCV luciferase reporter assay to screen a diverse small-molecule compound collection (∼ 300,000 compounds), we identified a benzofuran compound class of HCV inhibitors. The optimization of the benzofuran scaffold led to the identification of several exemplars with potent inhibition (EC50 < 100 nM) of HCV, low cytotoxicity (CC50 > 25 μM), and excellent selectivity (selective index = CC50/EC50, > 371-fold). The structure-activity studies culminated in the design and synthesis of a 45-compound library to comprehensively explore the anti-HCV activity. The identification, design, synthesis, and biological characterization for this benzofuran series is discussed.

KEYWORDS:

HCV inhibitor; HCV replication; antiviral; benzofuran; hepatitis C

PMID:
26332742
PMCID:
PMC6015500
DOI:
10.1021/acscombsci.5b00101
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center