Article
Discovery of novel P3-oxo inhibitor of hepatitis C virus NS3/4A serine protease.
Bioorganic & medicinal chemistry letters - 15 Apr 2012
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, Baker Stephen J
Abstract excerpt
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...
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