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    Bioorg Med Chem Lett. 2009 Oct 1;19(19):5648-51. Epub 2009 Aug 8.

    Non-nucleoside inhibitors of HCV polymerase NS5B. Part 3: synthesis and optimization studies of benzothiazine-substituted tetramic acids.

    de Vicente J, Hendricks RT, Smith DB, Fell JB, Fischer J, Spencer SR, Stengel PJ, Mohr P, Robinson JE, Blake JF, Hilgenkamp RK, Yee C, Zhao J, Elworthy TR, Tracy J, Chin E, Li J, Lui A, Wang B, Oshiro C, Harris SF, Ghate M, Leveque VJ, Najera I, Le Pogam S, Rajyaguru S, Ao-Ieong G, Alexandrova L, Fitch B, Brandl M, Masjedizadeh M, Wu SY, de Keczer S, Voronin T.

    Source

    Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. javier.devicente@roche.com

    Abstract

    Benzothiazine-substituted tetramic acids were discovered as highly potent non-nucleoside inhibitors of HCV NS5B polymerase. X-ray crystallography studies confirmed the binding mode of these inhibitors with HCV NS5B polymerase. Rational optimization of time dependent inactivation of CYP 3A4 and clearance was accomplished by incorporation of electron-withdrawing groups to the benzothiazine core.

    PMID:
    19700319
    [PubMed - indexed for MEDLINE]

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      Cited by 1 PubMed Central article

      • 2-(3-Oxo-3,4-dihydro-2H-1,4-benzothia-zin-4-yl)acetohydrazide. [Acta Crystallogr Sect E Struct Rep Online. ...]
        2-(3-Oxo-3,4-dihydro-2H-1,4-benzothia-zin-4-yl)acetohydrazide.
        Saeed A, Mahmood Z, Yang S, Ahmad S, Salim M. Acta Crystallogr Sect E Struct Rep Online. 2010 Aug 11; 66(Pt 9):o2289-90. Epub 2010 Aug 11.

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