Discovery of α,γ-diketo acids as potent selective and reversible inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase

被引：133

作者：

Summa, V

Petrocchi, A

Pace, P

Matassa, VG

De Francesco, R

Altamura, S

Tomei, L

Koch, U

Neuner, P

机构：

[1] IRBM, MRL Rome, Dept Med Chem, I-00040 Rome, Italy

[2] IRBM, MRL Rome, Dept Biochem, I-00040 Rome, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 01期

关键词：

D O I：

10.1021/jm0342109

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 IC50 = 45 nM, one of the most potent HCV NS5b polymerase inhibitors reported.

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页码：14 / 17

页数：4

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