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

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 (Ki∗=15nM, EC 90 = 70 nM) and pharmacokinetic properties (Rat AUC (PO) = 3.52 μM h) compared to 1.

Graphical abstractSAR studies on the extension of P3 unit of Boceprevir (1, SCH 503034) with amides and lactams and their synthesis is described.Figure optionsDownload full-size imageDownload as PowerPoint slide