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

ACS Combinatorial Science
Shanshan HeKevin J Frankowski

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.

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Citations

May 26, 2016·The Journal of Organic Chemistry·Yilong ZhaoJingping Qu
Mar 25, 2018·Chemistry : a European Journal·Shintaro YamaneTetsuya Satoh
Jan 3, 2018·Organic & Biomolecular Chemistry·Kohei WatanabeMasami Sakamoto
Sep 29, 2019·Expert Opinion on Therapeutic Patents·Kamal M Dawood
Jun 27, 2020·Current Organic Synthesis·Dau Xuan Duc
Sep 23, 2021·Chemical Biology & Drug Design·Shivali Sharma, Divya Utreja

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