Design and Synthesis of Non-peptide RGD Mimics for Evaluation of Their Utility as Anti-platelet Agents

Chem Pharm Bull (Tokyo). 2016;64(12):1726-1738. doi: 10.1248/cpb.c16-00594.

Abstract

Arg-Gly-Asp (RGD) mimics were synthesized and their anti-platelet activity was evaluated. A concise method was developed for the synthesis of the target compounds from dehydroepiandrosterone and Wieland-Miescher and Hajos-Parrish ketones, which are suitable for readily available platform. Among the synthesized compounds, the perhydronaphthalene framework with a 3-(4-piperidinyl)propoxyl structure 3e possessed the highest anti-aggregative activity. The IC50 values of 3e were 0.91 mM (ADP initiation) and 0.54 mM (collagen initiation).

MeSH terms

  • Blood Platelets / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Molecular Conformation
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / chemical synthesis
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Oligopeptides
  • Platelet Aggregation Inhibitors
  • arginyl-glycyl-aspartic acid