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

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 ?M), 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.

SUBMITTER: He S

PROVIDER: S-EPMC6015500 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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

He Shanshan S Jain Prashi P Lin Billy B Ferrer Marc M Hu Zongyi Z Southall Noel N Hu Xin X Zheng Wei W Neuenswander Benjamin B Cho Chul-Hee CH Chen Yu Y Worlikar Shilpa A SA Aubé Jeffrey J Larock Richard C RC Schoenen Frank J FJ Marugan Juan J JJ Liang T Jake TJ Frankowski Kevin J KJ

ACS combinatorial science 20150917 10

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 ...[more]

PMID: 26332742

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