Selective 3-Amino-2-pyridinone acetamide thrombin inhibitors incorporating weakly basic partially saturated heterobicyclic P1-Arginine mimetics

Novel, highly selective and potent thrombin inhibitors were identified as a result of combing the 3-benzylsulfonylamino-2-pyridinone acetamide P2–P3 surrogate with weakly basic partially saturated heterobicyclic P1-arginine mimetics 1–8. The design, synthesis, biological activity, and the binding modes of non-covalent thrombin inhibitors featuring P1-4,5,6,7-tetrahydroindazole, 5,6,7,8-tetrahydroquinazoline, and 4,5,6,7-tetrahydrobenzothiazole moieties are described.