Document Report Card

ID: ALA1139456

Journal: J Med Chem

Title: Discovery of alpha,gamma-diketo acids as potent selective and reversible inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase.

Authors: Summa V, Petrocchi A, Pace P, Matassa VG, De Francesco R, Altamura S, Tomei L, Koch U, Neuner P.

Abstract: alpha,gamma-Diketo acids (DKA) were discovered from screening as selective and reversible inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase. The diketo acid moiety proved essential for activity, while substitution on the gamma position was necessary for selectivity and potency. Optimization led to the identification of a DKA inhibitor of NS5b polymerase with IC(50) = 45 nM, one of the most potent HCV NS5b polymerase inhibitors reported.

CiteXplore: 14695815

DOI: 10.1021/jm0342109