Synthesis and antiplatelet effects of an isoxazole series of glycoprotein IIb/IIIa antagonists

Bioorg Med Chem Lett. 1998 Dec 15;8(24):3499-504. doi: 10.1016/s0960-894x(98)00637-4.

Abstract

Despite the excellent in vitro potency of a series of benzamide glycoprotein IIb/IIIa antagonists, which have been reported previously, poor in vivo potency in the inhibition of platelet aggregation was observed when the most potent inhibitor XU057 was dosed intravenously to dogs. In this communication, we report that replacement of the benzamide in XU057 with an isoxazolecarboxamide resulted in significant improvement in in vivo potency. More importantly, the analogue XU065 showed an excellent oral antiplatelet effect in dogs.

MeSH terms

  • Animals
  • Dogs
  • Humans
  • Isoxazoles / chemical synthesis*
  • Isoxazoles / chemistry
  • Isoxazoles / pharmacology*
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*

Substances

  • Isoxazoles
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex