P4 capped amides and lactams as HCV NS3 protease inhibitors with improved potency and DMPK profile.

Abstract SAR studies on the extension of P3 unit of Boceprevir ( 1 , SCH 503034) with amides and lactams and their synthesis is described. Extensive SAR studies resulted in the identification of 36 bearing 4, 4-dimethyl lactam as the new P4 cap unit with improved potency ( K i ∗ = 15 nM , EC 90 = 70 nM) and pharmacokinetic properties (Rat AUC (PO) = 3.52 μM h) compared to 1 .