ChemInform Abstract: Rational Design, Synthesis, and Serine Protease Inhibitory Activity of a Novel P1-Argininal Derivative Featuring a Conformationally Constrained P2-P3 Bicyclic Lactam Moiety.

Based on molecular modeling and judicious combination of the salient topographic features of the recently discovered P3-lactam derivative 1 with the P2-prolyl derivatives 2a, b, the novel thrombin inhibitor 3a was designed. Inhibitor 3a incorporates a fused bicyclic lactam as a novel type of P2–P3 dipeptide surrogate. The synthesis and biological activity of this potent serine protease inhibitor is presented.