Discovery of functionalized bisimidazoles bearing cyclic aliphatic-phenyl motifs as HCV NS5A inhibitors

This Letter describes the discovery of a number of functionalized bisimidazoles bearing a cyclohexylphenyl, piperidylphenyl, or bicyclo[2,2,2]octylphenyl motif as HCV NS5A inhibitors. Compounds 2c, 4b and 6 have shown low single-digit nM potency in gt-1a replicon and double-digital pM potency in gt-1b replicon, respectively. Moreover, both 4b and 6 have exhibited good oral bioavailability in rats with a favorable liver/plasma ratio of the drug concentration.109