Structure-Based Design of a Benzodiazepine Scaffold Yields a Potent Allosteric Inhibitor of Hepatitis C NS5B RNA Polymerase

详细信息    查看全文

• 作者：Koen Vandyck ; Maxwell D. Cummings ; Origne Nyanguile ; Carlo W. Boutton ; Sandrine Vendeville ; David McGowan ; Benoit Devogelaere ; Katie Amssoms ; Stefaan Last ; Klara Rombauts ; Abdellah Tahri ; Pedro Lory
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：July 23, 2009
• 年：2009
• 卷：52
• 期：14
• 页码：4099-4102
• 全文大小：718K
• 年卷期：v.52,no.14(July 23, 2009)
• ISSN：1520-4804

文摘

HCV NS5B polymerase, an essential and virus-specific enzyme, is an important target for drug discovery. Using structure-based design, we optimized a 1,5-benzodiazepine NS5B polymerase inhibitor chemotype into a new sulfone-containing scaffold. The design yielded potent inhibitor (S)-4c (K_D = 0.79 nM), which has 20-fold greater affinity for NS5B than its carbonyl analogue (R)-2c.