Rational design, synthesis, and serine protease inhibitory activity of a novel P1-argininal derivative featuring a conformationally constrained P2-P3 bicyclic lactam moiety

Article abstract of DOI:10.1016/S0960-894X(97)00004-8

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.