Heterocycle-peptide hybrid compounds. Aminotriazole-containing agonists of the thrombin receptor (PAR-1)

Bioorg Med Chem Lett. 1999 May 17;9(10):1423-8. doi: 10.1016/s0960-894x(99)00197-3.

Abstract

The thrombin receptor PAR-1 is activated by alpha-thrombin to stimulate cells, including platelets, through the tethered-ligand sequence SFLLRN. We have discovered a novel series of heterocycle-peptide hybrids comprised of a tripeptide segment, such as Cha-Arg-Phe, and an N-terminal heterocyclic group, many of which behave as full PAR-1 agonists. Certain compounds with an aminotriazole group, such as 4 and 16, are nearly as potent as SFLLRN-NH2 in inducing platelet aggregation. Also, some arylethenoyl "N-capped" compounds, such as 52 and 57, exhibit mixed PAR-1 agonist-antagonist activity.

MeSH terms

  • Cell Line
  • Heterocyclic Compounds / chemistry*
  • Humans
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Receptor, PAR-1
  • Receptors, Thrombin / agonists*
  • Receptors, Thrombin / antagonists & inhibitors
  • Structure-Activity Relationship
  • Triazoles / chemistry*

Substances

  • Heterocyclic Compounds
  • Oligopeptides
  • Receptor, PAR-1
  • Receptors, Thrombin
  • Triazoles