Rational design and synthesis of a novel, selective class of thrombin inhibitors: P1-argininal derivatives incorporating P3---P4 quaternary lactam dipeptide surrogates

SAR and molecular modeling investigations on the potent and selective thrombin inhibitor 1b (CVS 1578) and related serine protease inhibitors led to the design of series 2a–g, featuring quaternary α-amino-α-benzyl-lactam scaffolds that serve as novel P3---P4 dipeptide mimics. The design, synthesis, and biological activity of these targets are presented.