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  • Title: Inhibitors of hepatitis C virus NS3.4A protease. Effect of P4 capping groups on inhibitory potency and pharmacokinetics.
    Author: Perni RB, Chandorkar G, Cottrell KM, Gates CA, Lin C, Lin K, Luong YP, Maxwell JP, Murcko MA, Pitlik J, Rao G, Schairer WC, Van Drie J, Wei Y.
    Journal: Bioorg Med Chem Lett; 2007 Jun 15; 17(12):3406-11. PubMed ID: 17482818.
    Abstract:
    Reversible tetrapeptide-based compounds have been shown to effectively inhibit the hepatitis C virus NS3.4A protease. Inhibition of viral replicon RNA production in Huh-7 cells has also been demonstrated. We show herein that the inclusion of hydrogen bond donors on the P4 capping group of tetrapeptide-based inhibitors result in increased binding potency to the NS3.4A protease. The capping groups also impart significant effects on the pharmacokinetic profile of these inhibitors.
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