Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 1. (+/-)-(3-pyridinylbicycloheptyl)alkanoic acids

J Med Chem. 1991 Jun;34(6):1790-7. doi: 10.1021/jm00110a006.


The design, synthesis, and in vitro pharmacology of a new class of compounds exerting both thromboxane receptor antagonist and thromboxane synthase inhibitory activities is described. [(3-Pyridinyl)bicycloheptyl] alkanoic acid 9 and its analogues, designed with the help of molecular modeling, were synthesized and found to be inhibitors of thromboxane A2 (TxA2) biosynthesis in a human platelet microsomal preparation. The compounds were also found to antagonize both platelet and vascular TxA2 receptors. The compounds inhibited the U 46619 induced aggregation of human washed platelets and platelet-rich plasma and the U 46619 induced contraction of the dog saphenous vein.

MeSH terms

  • Blood Platelets / drug effects
  • Bridged Bicyclo Compounds / chemical synthesis
  • Bridged Bicyclo Compounds / pharmacology*
  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / pharmacology*
  • Humans
  • In Vitro Techniques
  • Microsomes / drug effects
  • Models, Molecular
  • Pyridines / chemical synthesis
  • Pyridines / pharmacology*
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Receptors, Thromboxane
  • Thromboxane-A Synthase / antagonists & inhibitors*
  • Thromboxanes / metabolism*
  • X-Ray Diffraction


  • Bridged Bicyclo Compounds
  • Carboxylic Acids
  • Pyridines
  • Receptors, Prostaglandin
  • Receptors, Thromboxane
  • Thromboxanes
  • Thromboxane-A Synthase