2-[3-[2-(4,5-diphenyl-2-oxazolyl) ethyl] phenoxy] acetic acid (BMY 42393): 2). Oral activity and efficacy in animal models of arterial thrombosis

Thromb Res. 1994 Apr 15;74(2):125-33. doi: 10.1016/0049-3848(94)90005-1.

Abstract

The oral activity and antithrombotic efficacy of BMY 42393 was examined in ex vivo platelet aggregation studies and arterial thrombosis animal models. In a heterologous ex vivo platelet aggregation assay, ADP-induced human platelet aggregation was inhibited when washed human platelets were combined with rat platelet-poor plasma, taken from rats previously orally-dosed with BMY 42393. The IC50 for platelet aggregation inhibition was approximately 10 mg/kg. In a laser-induced thrombosis model, thrombus formation in a revascularized rabbit ear chamber was prevented in a dose-dependent fashion with an ED50 of about 2 mg/kg. A relatively long duration of anti-thrombotic activity was observed in the rabbit ear laser-induced thrombus study and the ex vivo platelet studies. Inhibition of thrombus formation was also demonstrated in a canine model of electrically-induced coronary artery thrombosis. BMY 42393 also prevented cyclic flow reductions in a monkey stenotic renal artery model. These studies indicate that BMY 42393 is orally active and capable of preventing laser and electric current-induced thrombus formation in animal models of arterial thrombosis.

MeSH terms

  • Administration, Oral
  • Animals
  • Chlorocebus aethiops
  • Coronary Thrombosis / drug therapy*
  • Disease Models, Animal
  • Dogs
  • Humans
  • Macaca fascicularis
  • Male
  • Oxazoles / therapeutic use*
  • Phenoxyacetates / therapeutic use*
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Renal Artery Obstruction / drug therapy

Substances

  • Oxazoles
  • Phenoxyacetates
  • BMY 42393