Structure-based design, synthesis, and biological evaluation of 1, 1-dioxoisothiazole and benzo [b] thiophene-1, 1-dioxide derivatives as novel inhibitors of hepatitis C …

…, AX Xiang, B Ayida, H McGuire, D Ellis, J Blazel…

Index: Kim, Sun Hee; Tran, Martin T.; Ruebsam, Frank; Xiang, Alan X.; Ayida, Benjamin; McGuire, Helen; Ellis, David; Blazel, Julie; Tran, Chinh V.; Murphy, Douglas E.; Webber, Stephen E.; Zhou, Yuefen; Shah, Amit M.; Tsan, Mei; Showalter, Richard E.; Patel, Rupal; Gobbi, Alberto; LeBrun, Laurie A.; Bartkowski, Darian M.; Nolan, Thomas G.; Norris, Daniel A.; Sergeeva, Maria V.; Kirkovsky, Leo; Zhao, Qiang; Han, Qing; Kissinger, Charles R. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 14 p. 4181 - 4185

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Citation Number: 21

Abstract

A novel series of HCV NS5B polymerase inhibitors comprising 1, 1-dioxoisothiazoles and benzo [b] thiophene-1, 1-dioxides were designed, synthesized, and evaluated. SAR studies guided by structure-based design led to the identification of a number of potent NS5B inhibitors with nanomolar IC50 values. The most potent compound exhibited IC50 less than 10nM against the genotype 1b HCV polymerase and EC50 of 70nM against a genotype ...