Synthesis and biological evaluation of antiplatelet 2-aminochromones

J Med Chem. 1993 Jul 9;36(14):2026-32. doi: 10.1021/jm00066a012.

Abstract

The synthesis and biological evaluation of a series of antiplatelet 2-morpholinylchromones has been described. Modification of the C-7 phenylmethoxy group of 8-methyl-7-(phenylmethoxy)-2-(4-morpholinyl)-4H-1-benzopyran-4-one (2) has led to the discovery of a series of 7-[(amino-ethyl)oxy]-8-methyl derivatives which are potent inhibitors of ADP-induced platelet aggregation. Several members of this class proved active in preventing platelet-dependent thrombus formation in the dog, including 8-methyl-7-[2-(4-methyl-1-piperazinyl)ethoxy]-2-(4- morpholinyl)-4H-1-benzopyran-4-one (39) which was devoid of hemodynamic effects at the effective antithrombotic dose.

MeSH terms

  • Adenosine Diphosphate / antagonists & inhibitors
  • Animals
  • Chromones / chemical synthesis*
  • Chromones / chemistry
  • Chromones / pharmacology*
  • Dogs
  • Female
  • Humans
  • Male
  • Morpholines / chemical synthesis*
  • Morpholines / chemistry
  • Morpholines / pharmacology*
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Structure-Activity Relationship

Substances

  • Chromones
  • Morpholines
  • Piperazines
  • Platelet Aggregation Inhibitors
  • 8-methyl-7-(2-(4-methyl-1-piperazinyl)ethoxy)-2-(4-morpholinyl)-4H-1-benzopyran-4-one
  • Adenosine Diphosphate