Abstract

The macrocyclic urea <b>2</b>, a byproduct in the synthesis of benzoxaborole <b>1</b>, was identified to be a novel and potent HCV protease inhibitor. We further explored this motif by synthesizing additional urea-based inhibitors and by characterizing them in replicase HCV protease-resistant mutants assay. Several compounds, exemplified by <b>12</b>, were found to be more potent in HCV replicon assays than leading second generation inhibitors such as danoprevir and TMC-435350. Additionally, following oral administration, inhibitor <b>12</b> was found in rat liver in significantly higher concentrations than those reported for both danoprevir and TMC-435350, suggesting that inhibitor <b>12</b> has the combination of anti-HCV and pharmacokinetic properties that warrants further development of this series

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oai:figshare.com:article/2531143Last time updated on 2/12/2018

This paper was published in FigShare.

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