Derivatives of tetrahydroisoquinoline: synthesis and initial evaluation of novel non-peptide antagonists of the alpha(IIb)beta(3)-integrin

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4444-6. doi: 10.1016/j.bmcl.2010.06.051. Epub 2010 Jun 15.

Abstract

The novel RGDF mimetics were synthesized with the use of 4-(1,2,3,4-tetrahydroisoquinoline-7-yl)amino-4-oxobutyric or 5-(1,2,3,4-tetrahydroisoquinoline-7-yl)amino-5-oxopentanoic acids as a surrogate of Arg-Gly motif. The synthesized compounds have demonstrated a high potency to inhibit platelet aggregation in vitro and to block FITC-Fg binding to alpha(IIb)beta(3) on washed human platelets.

MeSH terms

  • Fibrinogen / chemistry
  • Fluorescein-5-isothiocyanate / chemistry
  • Humans
  • Oligopeptides / chemistry
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Protein Binding
  • Tetrahydroisoquinolines / chemical synthesis
  • Tetrahydroisoquinolines / chemistry*
  • Tetrahydroisoquinolines / pharmacology

Substances

  • Oligopeptides
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Tetrahydroisoquinolines
  • arginyl-glycyl-aspartyl-phenylalanine
  • 1,2,3,4-tetrahydroisoquinoline
  • Fibrinogen
  • Fluorescein-5-isothiocyanate