Hepatitis C virus (HCV) infections continue to be a major worldwide medical issue whereby current treatments are of limited efficacy and have with significant side effects. Therefore, a therapeutic need exists for a treatment regimen with improved efficacy and tolerability.  Towards the discovery of anti-HCV therapeutics, we have focused our efforts on the inhibition of the HCV NS3-4A protease an essential enzyme for viral replication. The N3-4A protease as a target has been previously validated. The first proof of concept in man for the HCV NS3-4A protease target was achieved with BILN 2061. In our search for a new generation of HCV protease inhibitors, we have focused on diverse acyclic tripeptide inhibitors which led to the discovery of novel acyclic P-2 substituted proline inhibitors. These inhibitors are characterized by a substituted-1-triazole moiety at the 4-proline.  Details of the SAR and NMR binding mode studies will be presented, as well as the synthetic sequence for the preparation of these compounds.