Hepatitis C virus (HCV) afflicts an estimated 170 million people worldwide, including 4 million people in the US.  People infected are at risk of developing chronic liver disease, cirrhosis, and cancer.  The current standard of care includes injectable interferon combined with oral agents, and is limited by negative side effects, modest efficacy, and numerous contraindications. HCV polymerase is an enzyme essential for viral RNA replication and proliferation and is an attractive target.   A series of chiral compounds were prepared by a highly diasteroselective Evan's Aldol reaction.  This series has been shown to be potent inhibitors of HCV-RNA dependent RNA Polymerase.

Synthesis of chiral inhibitors of the HCV-RNA dependent RNA polymerase: Discovery of a clinical candidate

245th National Meeting (2013)

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