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

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• 作者：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 Aub茅 ; Richard C. Larock ; Frank J. Schoenen ; Juan J. Marugan ; T. Jake Liang ; Kevin J. Frankowski
• 刊名：ACS Combinatorial Science
• 出版年：2015
• 出版时间：October 12, 2015
• 年：2015
• 卷：17
• 期：10
• 页码：641-652
• 全文大小：861K
• ISSN：2156-8944

文摘

Using a high-throughput, cell-based HCV luciferase reporter assay to screen a diverse small-molecule compound collection (鈭?00鈥?00 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 渭M), and excellent selectivity (selective index = CC₅₀/EC₅₀, > 371-fold). The structure鈥揳ctivity 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.