DX-9065a, a new synthetic, potent anticoagulant and selective inhibitor for factor Xa

Thromb Haemost. 1994 Mar;71(3):314-9.

Abstract

DX-9065a is an orally active newly synthesized and specific inhibitor for factor Xa. We have examined the property of DX-9065a in vitro and ex vivo. DX-9065a prolonged human plasma recalcification time, APTT and PT. Its doubling concentrations for clotting times of each coagulation assay were 0.49, 0.97 and 0.52 microM, respectively. Kinetic study revealed that DX-9065a inhibited competitively human factor Xa (Ki value: 41 nM). Ki values (microM) for other human serine proteases were as follows; thrombin > 2000, trypsin 0.62, chymotrypsin > 2000, plasmin 23, t-PA 21, plasma kallikrein 2.3 and tissue kallikrein 1000. DX-9065a up to 100 microM had no effects on human platelet aggregation. After intravenous or oral administration, DX-9065a significantly prolonged APTT and PT with a dose dependent manner. These effects were well correlated with anti-Xa activity in plasma. These results suggest that DX-9065a may become an anticoagulant by means of the specific inhibition of factor Xa.

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Anticoagulants / chemical synthesis
  • Anticoagulants / pharmacology*
  • Blood Coagulation Tests
  • Chromogenic Compounds
  • Collagen / pharmacology
  • Epinephrine / antagonists & inhibitors
  • Epinephrine / pharmacology
  • Factor Xa Inhibitors*
  • Humans
  • Naphthalenes / chemical synthesis
  • Naphthalenes / pharmacology*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology
  • Propionates / chemical synthesis
  • Propionates / pharmacology*
  • Thrombin / pharmacology

Substances

  • (2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid
  • Anticoagulants
  • Chromogenic Compounds
  • Factor Xa Inhibitors
  • Naphthalenes
  • Platelet Aggregation Inhibitors
  • Propionates
  • Adenosine Diphosphate
  • Collagen
  • Thrombin
  • Epinephrine