Synthesis and biological activity of P2–P4 azapeptidomimetic P1-argininal and P1-ketoargininamide derivatives: a novel class of serine protease inhibitors

Molecular modeling and topographic considerations of the thrombin-specific sequences Boc-Asp-Pro-Arg-TS or Ac-d-Phe-Pro-Arg-TS (TS = transition state analog electrophilic center) and related scaffolds led to the design of novel P2–P4-azapeptidomimetic P1-argininal and P1-ketoargininamide derivatives (3a-j). The synthesis and biological activity of these potential serine protease inhibitors are presented.