Hepatitis C virus (HCV) is a major disease that infects over 170 million people world wide. HCV NS3 protease is essential for cleavage of the viral polypeptide during the viral replication process. In our efforts to identify small molecule inhibitors of HCV NS3 protease, we discovered a novel series of compounds with tetrazoyl P* groups. Systematic SAR study on both acyclic and P1-P3 macrocyclic compounds led to the discovery of EA-084 with excellent potency in both enzyme (IC50 = 0.1 nM) and replicon assays (EC50 = 0.8 nM). This compound also has very good bioavailability in rat PK studies. The details of synthetic methods, SAR and PK profile of EA-084 will be presented.

Novel HCV NS3/4A protease inhibitors with tetrazoyl P* groups

243rd National Meeting (2012)

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