RGD mimetics containing phthalimidine fragment as novel ligands of fibrinogen receptor

Bioorg Med Chem Lett. 2011 Oct 1;21(19):5971-4. doi: 10.1016/j.bmcl.2011.07.063. Epub 2011 Jul 26.

Abstract

The novel RGD mimetics with phthalimidine central fragment were synthesized with the use of 4-piperidine-4-yl-butyric, 4-piperidine-4-yl-benzoic, 4-piperazine-4-yl-benzoic and 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acids as surrogates of Arg motif. The synthesized compounds potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to α(IIb)β(3) integrin in a suspension of washed human platelets. The key α(IIb)β(3) protein-ligand interactions were determined in docking experiments.

MeSH terms

  • Arginine / analogs & derivatives
  • Arginine / metabolism
  • Blood Platelets / metabolism
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Fibrinogen / metabolism
  • Fluorescein-5-isothiocyanate / metabolism
  • Humans
  • Isoquinolines / chemistry
  • Isoquinolines / metabolism
  • Ligands
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism
  • Phthalimides / chemical synthesis*
  • 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
  • Receptors, Fibrinogen / antagonists & inhibitors*
  • Receptors, Fibrinogen / metabolism
  • Software
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tirofiban
  • Tyrosine / analogs & derivatives
  • Tyrosine / chemistry
  • Tyrosine / metabolism

Substances

  • Isoquinolines
  • Ligands
  • Oligopeptides
  • Phthalimides
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Receptors, Fibrinogen
  • Tyrosine
  • arginyl-glycyl-aspartic acid
  • Fibrinogen
  • Arginine
  • Tirofiban
  • Fluorescein-5-isothiocyanate
  • isoquinoline