Design and construction of novel thrombin inhibitors featuring P3-P4 quaternary lactam dipeptide surrogates

Article abstract of DOI:10.1016/S0960-894X(98)00448-X

Potent serine protease inhibitor la featuring a hybrid P₃-P₄ quaternary lactam dipeptide surrogate was prepared based upon SAR and molecular modeling investigations and in order to further probe the S₂/S₃ thrombin and FXa subsites. An efficient and concise synthetic route to the key aminolactam intermediate 4 was developed. The design, synthesis, and biological activity of this target and its P₃-P₄ diastereomer 1b is presented.