High-Throughput Screening, Discovery, and Optimization to Develop a Benzofuran Class of Hepatitis C Virus Inhibitors
Issue Date
2015-09-02Author
He, Shanshan
Jain, Prashi
Lin, Billy
Ferrer, Mark
Hu, Zongyi
Southall, Noel
Hu, Xin
Zheng, Wei
Neuenswander, Benjamin
Cho, Chul-Hee
Chen, Yu
Worlikar, Shilpa A.
Aubé, Jeffrey
Larock, Richard C.
Schoenen, Frank J.
Marugan, Juan J.
Liang, T. Jake
Frankowski, Kevin J.
Publisher
American Chemical Society
Type
Article
Article Version
Scholarly/refereed, publisher version
Metadata
Show full item recordAbstract
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.
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Citation
Shanshan He, Prashi Jain, Billy Lin, Marc Ferrer, Zongyi Hu, Noel Southall, Xin Hu, Wei Zheng, Benjamin Neuenswander, Chul-Hee Cho, Yu Chen, Shilpa A. Worlikar, Jeffrey Aubé, Richard C. Larock, Frank J. Schoenen, Juan J. Marugan, T. Jake Liang, Kevin J. Frankowski
ACS Comb Sci. 2015 Oct 12; 17(10): 641–652. Published online 2015 Sep 17. doi: 10.1021/acscombsci.5b00101
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