Active site inhibitors of HCV NS5B polymerase. The development and pharmacophore of 2-thienyl-5,6-dihydroxypyrimidine-4-carboxylic acid

Bioorganic & Medicinal Chemistry Letters
Ian StansfieldSteven Harper

Abstract

5,6-Dihydroxypyrimidine-4-carboxylic acids are a promising series of hepatitis C virus (HCV) NS5B polymerase inhibitors that bind at the active site of the enzyme. Here we report a simple 2-thienyl substituted analogue that shows 10-fold improved activity over the original lead, and which allowed us to further delineate the key elements of the pharmacophore of this class of inhibitor. This work led to the identification of a trifluoromethyl acylsulfonamide group as a viable replacement for the C4 carboxylic acid in this series.

References

Sep 27, 2002·Current Opinion in Pharmacology·Michelle P Walker, Zhi Hong
Nov 30, 2002·The Journal of Biological Chemistry·Isabelle BougieMartin Bisaillon

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Citations

Apr 24, 2013·Bioorganic & Medicinal Chemistry·Iwona E WeidlichIan F Thorpe
Dec 22, 2011·Journal of Medicinal Chemistry·Michael J SofiaBruce S Ross
Nov 29, 2013·SAR and QSAR in Environmental Research·M WangC Yu
Jan 1, 2008·Angewandte Chemie·Joyce Wei Wei Chang, Philip Wai Hong Chan
May 20, 2009·Chemical Reviews·Sarah Van der Jeught, Christian V Stevens

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