Following the discovery of a new series of benzimidazole derivatives bearing a diarylmethyl group as inhibitors of hepatitis C virus NS5B RNA-dependent RNA polymerase (HCV NS5B RdRp),1,2 we extended the structure-activity relationship (SAR) study to analogues bearing a substituted biphenyl group and succeeded in a significant advancement of activity. Starting from compound 1, optimization of the A, B, and C rings afforded potent inhibitors with low nanomolar potency against genotype 1b NS5B. The compounds, which have a substituent with a carbonyl function at the 4-position of the B-ring, efficiently blocked subgenomic viral RNA replication in the replicon cell assay at low submicromolar concentrations. Among the new compounds, compound 10n (JTK-109) exhibited favorable pharmacokinetic profiles, high selectivity for NS5B, and good safety profiles, suggesting the potential for a clinical candidate in the treatment of hepatitis C.

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Curvularin, 8-dehydrocurvularin, and 8-hydroxycurvularin as well as a minor newmetabolite, 8-methoxycurvularin, wereisolated as fungal metabolites having cytotoxic activity toward sea urchin embryogenesis. Curvularin induced barrel-shaped mitotic spindles and 8-dehydrocurvularin caused miniature spindles. They were shownto act on componentsof the mitotic apparatus and to effectively inhibit cell division. Cell cleavage has great physiological significance for cell biologists. Many chemicals

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