Bioorganic & Medicinal Chemistry 2010-04-15

Allosteric inhibitors of hepatitis C virus NS5B polymerase thumb domain site II: structure-based design and synthesis of new templates.

Savina Malancona, Monica Donghi, Marco Ferrara, Josè I Martin Hernando, Marco Pompei, Silvia Pesci, Jesus M Ontoria, Uwe Koch, Michael Rowley, Vincenzo Summa

Index: Bioorg. Med. Chem. 18 , 2836-48, (2010)

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Abstract

Chronic hepatitis C virus (HCV) infections are a significant medical problem worldwide. The NS5B Polymerase of HCV plays a central role in virus replication and is a prime target for the discovery of new treatment options. We recently disclosed 1H-benzo[de]isoquinoline-1,3(2H)-diones as allosteric inhibitors of NS5B Polymerase. Structural and SAR information guided us in the modification of the core structure leading to new templates with improved activity and toxicity/activity window.Copyright 2010 Elsevier Ltd. All rights reserved.