Use of conformationally restricted benzamidines as arginine surrogates in the design of platelet GPIIb-IIIa receptor antagonists

J Med Chem. 1997 Aug 29;40(18):2843-57. doi: 10.1021/jm970020k.

Abstract

The use of 5,6-bicyclic amidines as arginine surrogates in the design of a novel class of potent platelet glycoprotein IIb-IIIa receptor (GPIIb-IIIa) antagonists is described. The additional conformational restriction offered by the bicyclic nucleus results in 20-400-fold increases in potency compared to the freely flexible, acyclic benzamidine counterpart. The design, synthesis, structure-activity relationships (SAR), and in vitro activity of this novel class of GPIIb-IIIa antagonists are presented.

Publication types

  • Comparative Study

MeSH terms

  • Arginine*
  • Benzamidines / chemical synthesis*
  • Benzamidines / chemistry
  • Benzamidines / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Fibrinogen / metabolism
  • Humans
  • Indicators and Reagents
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Benzamidines
  • Indicators and Reagents
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Fibrinogen
  • Arginine