1. Discovery of novel P3-oxo inhibitor of hepatitis C virus NS3/4A serine protease
- Author
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Duan, Maosheng, Kazmierski, Wieslaw, Crosby, Renae, Gartland, Margaret, Ji, Jinjing, Tallant, Matt, Wang, Amy, Hamatake, Robert, Wright, Lois, Wu, Min, Zhang, Yong-Kang, Ding, Charles Z., Li, Xianfeng, Liu, Yang, Zhang, Suoming, Zhou, Yasheen, Plattner, Jacob J., and Baker, Stephen J.
- Subjects
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SERINE proteinase inhibitors , *HEPATITIS C virus , *MACROCYCLIC compounds , *REPLICONS , *CARBONATES , *CHEMICAL synthesis , *ENZYMES - Abstract
Abstract: A novel series of P3 oxo-modified macrocyclic hepatitis C virus NS3/4A serine protease inhibitor was designed, synthesized and biologically evaluated. The hydroxy-substituted inhibitor 10 demonstrated high potency in genotype 1a and 1b replicon and in the panel of HCV protease mutants. Interestingly, the t-butyl carbonate analog 9c, while not the most potent one in this series, exhibited a virtually flat potency profile in the panel of HCV protease mutants, thus providing opportunity for further optimization. [Copyright &y& Elsevier]
- Published
- 2012
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