Potent and selective bicyclic lactam inhibitors of thrombin. Part 4: transition state inhibitors

Bioorg Med Chem Lett. 2001 Feb 12;11(3):287-90. doi: 10.1016/s0960-894x(00)00636-3.

Abstract

Bicyclic piperazinone based thrombin inhibitors of general structure 2 were prepared and evaluated in vitro and in vivo. These inhibitors, having in common an electrophilic basic trans-cyclohexylamine P1 residue, displayed high thrombin affinity, high selectivity against trypsin and good in vivo efficacy in the rat arterial thrombosis model.

MeSH terms

  • Animals
  • Blood Coagulation Tests
  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Combinatorial Chemistry Techniques
  • Crystallography, X-Ray
  • Disease Models, Animal
  • Fibrinolytic Agents / chemical synthesis*
  • Fibrinolytic Agents / pharmacology
  • Lactams / chemical synthesis
  • Lactams / pharmacology*
  • Models, Molecular
  • Rats
  • Structure-Activity Relationship
  • Thrombin / antagonists & inhibitors*
  • Thrombosis / drug therapy
  • Trypsin Inhibitors / pharmacology

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Fibrinolytic Agents
  • Lactams
  • Trypsin Inhibitors
  • Thrombin