Structure-based design of a benzodiazepine scaffold yields a potent allosteric inhibitor of hepatitis C NS5B RNA polymerase

…, D McGowan, B Devogelaere, K Amssoms…

文献索引：Vandyck, Koen; Cummings, Maxwell D.; Nyanguile, Origene; Boutton, Carlo W.; Vendeville, Sandrine; McGowan, David; Devogelaere, Benoit; Amssoms, Katie; Last, Stefaan; Rombauts, Klara; Tahri, Abdellah; Lory, Pedro; Hu, Lili; Beauchamp, Derek A.; Simmen, Kenny; Raboisson, Pierre Journal of Medicinal Chemistry, 2009 , vol. 52, # 14 p. 4099 - 4102

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被引用次数: 34

摘要

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 (KD= 0.79 nM), which has∼ 20-fold greater affinity for NS5B than its carbonyl analogue (R)-2c.