Novel, potent phenethylamide inhibitors of the hepatitis C virus (HCV) NS3 protease: probing the role of P2 aryloxyprolines with hybrid structures

Synthesis of hybrid HCV NS3 protease/NS4A inhibitors having the 4,4-difluoroaminobutyric acid (difluoroAbu) phenethylamides as P1–P1′ and quinolyloxyprolines as P2 fragments led to 7 (IC50 54 nM). Molecular modelling suggests that this potent tripeptide inhibitor utilizes interactions in the S1′, S1, S2, S3 and S4 sites of the protease.