Identification of anthranilic acid derivatives as a novel class of allosteric inhibitors of hepatitis C NS5B polymerase

…, K Wheless, B Feld, J O'Connell…

Index: Nittoli, Thomas; Curran, Kevin; Insaf, Shabana; DiGrandi, Martin; Orlowski, Mark; Chopra, Rajiv; Agarwal, Atul; Howe, Anita Y. M.; Prashad, Amar; Floyd, M. Brawner; Johnson, Bernard; Sutherland, Alan; Wheless, Karen; Feld, Boris; O'Connell, John; Mansour, Tarek S.; Bloom, Jonathan Journal of Medicinal Chemistry, 2007 , vol. 50, # 9 p. 2108 - 2116

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Citation Number: 52

Abstract

A series of potent anthranilic acid-based inhibitors of the hepatitis C NS5B polymerase has been identified. The inhibitors bind to a site on NS5B between the thumb and palm regions adjacent to the active site as determined by X-ray crystallography of the enzyme-inhibitor complex. Guided by both molecular modeling and traditional SAR, the enzyme activity of the initial hit was improved by approximately 100-fold, yielding a series of potent and selective ...