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

Therapeutic Approaches


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.


He, Shanshan; Jain, Prashi; Lin, Billy; Ferrer-Alegre, Marc; 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; Liang, T Jake; Frankowski, Kevin J;


  • Antiviral Agents/ chemical synthesis
  • Antiviral Agents/ pharmacology
  • Antiviral Agents/ toxicity
  • Benzofurans/ chemical synthesis
  • Benzofurans/ pharmacology
  • Benzofurans/ toxicity
  • Cell Line
  • Drug Discovery
  • Hepacivirus/ drug effects
  • Hepatitis C/ drug therapy
  • Hepatitis C/ virology
  • High-Throughput Screening Assays
  • Humans
  • Small Molecule Libraries
  • Structure-Activity Relationship
  • Virus Replication/ drug effects

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