Discovery and synthesis of a novel series of quinoline-based thrombin receptor (PAR-1) antagonists

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1544-8. doi: 10.1016/j.bmcl.2005.12.042. Epub 2005 Dec 27.

Abstract

The design, synthesis, and SAR studies of a structurally novel series of highly potent thrombin receptor (PAR-1) antagonists are described. Compound 30 is a highly potent thrombin receptor antagonist (IC(50)=6.3 nM), a related compound 36 showing efficacy in a monkey ex vivo study.

MeSH terms

  • Animals
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Fibrinolytic Agents / chemical synthesis*
  • Fibrinolytic Agents / chemistry
  • Fibrinolytic Agents / pharmacology
  • Heterocyclic Compounds, 3-Ring / chemical synthesis*
  • Heterocyclic Compounds, 3-Ring / chemistry
  • Heterocyclic Compounds, 3-Ring / pharmacology
  • Macaca fascicularis
  • Platelet Aggregation Inhibitors* / chemical synthesis
  • Platelet Aggregation Inhibitors* / chemistry
  • Platelet Aggregation Inhibitors* / pharmacology
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Quinolines / chemistry*
  • Receptors, Thrombin / metabolism
  • Structure-Activity Relationship

Substances

  • 4-(5-(3-trifluoromethylphenyl)pyridin-2-yl)ethenyl-3-methyldecahydronaphtho(2,3-c)furan-1(3H)-one
  • Fibrinolytic Agents
  • Heterocyclic Compounds, 3-Ring
  • Platelet Aggregation Inhibitors
  • Pyridines
  • Quinolines
  • Receptors, Thrombin
  • quinoline