期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 14, 期 20, 页码 5085-5088出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2004.07.075
关键词
hepatitis C virus; HCV; polymerase
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. (C) 2004 Elsevier Ltd. All rights reserved.
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