Shape-based virtual screening, synthesis and evaluation of novel pyrrolone derivatives as antiviral agents against HCV

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• 作者：Marcella Bassetto^a ; ^{bassettom@cardiff.ac.uk} ; Pieter Leyssen^b ; Johan Neyts^b ; Mark M. Yerukhimovich^c ; David N. Frick^c ; Andrea Brancale^a
• 关键词：Ligand-based virtual screening ; Shape-similarity search ; Novel pyrrolones ; Anti-HCV activity
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：27
• 期：4
• 页码：936-940
• 全文大小：715 K
• 卷排序：27

文摘

A ligand-based approach was applied to screen in silico a library of commercially available compounds, with the aim to find novel inhibitors of the HCV replication starting from the study of the viral NS3 helicase. Six structures were selected for evaluation in the HCV subgenomic replicon assay and one hit was found to inhibit the HCV replicon replication in the low micromolar range. A small series of new pyrrolone compounds was designed and synthesised, and novel structures were identified with improved antiviral activity.