Potent bicyclic lactam inhibitors of thrombin: Part I: P3 modifications.

Abstract Peptidomimetic inhibitors of general structure 1 have been prepared. Optimization of the binding affinities of these compounds through variation of the P3 hydrophobic residue is described. Selected substituted bicylic lactams displayed interesting pharmacological profiles both in vitro and in vivo. Design, synthesis, and SAR of low molecular weight peptidomimetic inhibitors of thrombin are described.