Synthesis and biological activity of P 2–P 4 azapeptidomimetic P 1-argininal and P 1-ketoargininamide derivatives: a novel class of serine protease inhibitors

Abstract

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 P 2–P 4-azapeptidomimetic P 1-argininal and P 1-ketoargininamide derivatives ( 3a-j). The synthesis and biological activity of these potential serine protease inhibitors are presented.