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

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 1 H-benzo[ de]isoquinoline-1,3(2 H)-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.