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  • Title: Design and synthesis of lactam-thiophene carboxylic acids as potent hepatitis C virus polymerase inhibitors.
    Author: Barnes-Seeman D, Boiselle C, Capacci-Daniel C, Chopra R, Hoffmaster K, Jones CT, Kato M, Lin K, Ma S, Pan G, Shu L, Wang J, Whiteman L, Xu M, Zheng R, Fu J.
    Journal: Bioorg Med Chem Lett; 2014 Aug 15; 24(16):3979-85. PubMed ID: 24986660.
    Abstract:
    Herein we report the successful incorporation of a lactam as an amide replacement in the design of hepatitis C virus NS5B Site II thiophene carboxylic acid inhibitors. Optimizing potency in a replicon assay and minimizing potential risk for CYP3A4 induction led to the discovery of inhibitor 22a. This lead compound has a favorable pharmacokinetic profile in rats and dogs.
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