Described herein is the development of a non-nucleoside, small molecule inhibitor of genotype 1 HCV NS5B Polymerase. We discovered a 23 uM analog that is active against HCV polymerase. This small fragment was elaborated into a potent single digit nanomolar inhibitor of HCV NS5B polymerase by manipulation of the R and R1 substituents. Subsequent modifications to improve physical properties were made in an attempt to achieve an acceptable pharmacokinetic profile. 

Discovery of a potent HCV NS5B polymerase inhibitor developed from an aryl-dihydro-uracil screening hit

244th National Meeting (2012)

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