DX 9065A, a novel, synthetic, selective and orally active inhibitor of factor Xa: In vitro and in vivo studies

Journal of Pharmacology and Experimental Therapeutics

Volumn 276, Issue 3, 1996, Pages 1030-1038

  Herbert, J M ^a   Bernat, A ^a   Dol, F ^a   Herault J P ^a   Crepon B ^a   Lormeau, J C ^a  

^a SANOFI   (France)

Author keywords

[No Author keywords available]

Indexed keywords

2 [4 [(1 ACETIMIDOYL 3 PYRROLIDINYL)OXY]PHENYL] 3 (7 AMIDINO 2 NAPHTHYL)PROPIONIC ACID; ANTICOAGULANT AGENT; BLOOD CLOTTING FACTOR 10A; NAPHTHALENE DERIVATIVE; PROPIONIC ACID DERIVATIVE; THROMBIN;

ANIMAL; ARTICLE; BLEEDING TIME; DOSE RESPONSE; DRUG EFFECT; HUMAN; IN VITRO STUDY; RABBIT;

ANIMALS; ANTICOAGULANTS; BLEEDING TIME; DOSE-RESPONSE RELATIONSHIP, DRUG; FACTOR XA; HUMANS; NAPHTHALENES; PROPIONIC ACIDS; RABBITS; THROMBIN;

EID: 0030097984     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (29)

1. AGNELLI, G., PASCUCCI, C., COSNI, B. AND NENCI, G. G.: The comparative effects of recombinant hirudin (Cgp 39393) and standard heparin on thrombus growth in rabbits. Thromb. Haemost. 63: 204-207, 1990.
2. BARROWCLIFFE, T. W., HAVERCROFT, S. J , KEMBALL-COOK, G. AND LINDAHL, U.: The effect of calcium, phospholipids and factor V. on the anti-factor Xa activity of heparin and its high affinity oligosaccharides. Biochem. J. 243: 31-37, 1987.
3. BERRY, C., GIRARDOT, C , LECOFFRE, C. AND LUNVEN, C.: Effects of the synthetic thrombin inhibitor argatroban on fibrin- or clot-incorporated thrombin: Comparison with heparin and recombinant hirudin. Thromb. Haemost. 72: 381-386, 1994.
4. DEJANA, E., VILLA, S AND DE GAETANO, G.: Bleeding time in rats; a comparison of different experimental conditions. Thromb. Haemost. 48: 108-111, 1982.
5. EISENBERG, P. R., JEFFREY, E. S., ABENDSCHEIN, D. R. AND MILETICH, J. P.: Importance of factor Xa in determining the procoagulant activity of whole-blood clots. J. Clin. Invest. 91: 1877-1883, 1993.
6. FREUND, M., CAZENAVE, J. P., COURTNEY, M., DEGRYSE, E., ROITSCH, C., BERNAT, A., DELEBASSEE, D., DEFREYN, G. AND MAFFRAND, J. P.: Inhibition by recombinant hirudins of experimental venous thrombosis and disseminated intravascular coagulation induced by tissue factor in rats. Thromb. Haemost. 63: 187-192, 1990.
7. HARA, T., KUNITADA, S. AND IWAMOTO, M.: DX-9065a, a synthetic and selective factor Xa inhibitor; species difference in its anticoagulant activity Thromb. Haemost. 69: 890-899, 1993.
8. HARA, T., YOKOYAMA, A., ISHIHARA, H., YOKOYAMA, Y., NAGAHARA, T. AND IWAMOTO, M.: DX-9065a, a new synthetic, potent anticoagulant and selective inhibitor for factor Xa. Thromb. Haemost. 71: 314-319, 1994.
9. HARA, T., YOKOYAMA, A., TANABE, K, ISHIHARA, H., AND IWAMOTO, M.: DX-9065a, an orally active, specific inhibitor of factor Xa, inhibits thrombosis without affecting bleeding time in rats. Thromb. Haemost., 74: 635-639, 1995.
10. HEMKER, H. C., WILLEMS, G. M. AND BÉGUIN, S.: A computer assisted method to obtain the prothrombin activation velocity in whole plasma independent of thrombin decay processes. Thromb. Haemost. 56: 9-17, 1986.
11. HERBERT, J. M., BERNAT, A., SAINTE MARIE, M., ROQUE, C., INGELAERE, V. AND MAFFRAND, J. P.: Low doses of endotoxin potentiate venous thrombosis in the rabbit. Haemostasis 34: 209-218, 1094.
12. HOBBELEM, P. M. J., VAN DINTHER, T. G., VOGEL, G. M. T., VAN BOECKEL, C. A. A., MOELKER, H. C. T. AND MEULEMAN, D. G.: Pharmacological profile of the chemically synthetized antithrombin III binding fragment of heparin (pentasaccharide) in rats. Thromb. Haemost. 63: 265-272, 1990.
13. JACKSON, C. V., CROWE, G., FRANK, J. D., WILSON, H. C., COFFMAN, W. J., UTTERBACK, B. G., JAKUBOWSHI, J. A. AND SMITH, G. F.: Pharmacological assessment of antithrombotic activity of the peptide inhibitor, D-methylphenylalanyl-prolyl-arginal (GYKI-14766), in a canine model of coronary artery thrombosis. J. Pharmacol. Exp. Ther. 261: 546-552, 1992.
14. JUST, M., TRIPIER, D. AND SEIFFGE, D.: Antithrombotic effects of recombinant hirudin in different animal models. Haemostasis 21: 80-87, 1991.
15. KATAKURA, S., NAGAHARA, T., HARA, T. AND IWAMOTO, M.: A novel factor Xa inhibitor: Structure-activity relationships and selectivity between factor Xa and thrombin. Biochem. Biophys. Res. Commun. 197: 965-972, 1993.
16. LAWSON, J. H., BUTENAS, S., RIBARIK, N. AND MANN, K. G.: Complex-dependent inhibition of factor Vila by antithrombin III and heparin. J. Biol. Chem. 268: 767-773, 1993.
17. LORMEAU, J. C. AND HERAULT, J. P.: Comparative inhibition of extrinsic and intrinsic thrombin generation by standard heparin, a low molecular weight heparin and the synthetic ATIII-binding pentasaccharide. Thromb. Haemost. 69: 152-156, 1993.
18. MAFFRAND, J. P.: Direct thrombin inhibitors Nouv. Rev. Fr. Hematol. 34: 405-419, 1992.
19. OLSON, S. T., BJÖRK, I., SHEFFER, R., CRAIG, P. A., SHORE, J. D. AND CHOAY, J.: Role of the antithrombin-binding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions. J. Biol. Chem. 267: 12528-12538, 1992.
20. PAQUES, E. P. AND RÖMISCH, J.: Comparative study on the in vivo effectiveness of antithrombotic agents. Thromb. Res. 64: 11-21, 1991.
21. REYERS, I., MUSSONI, L., DONATI, M. B. AND DE GAETANO, G.: Failure of aspirin at different doses to modify experimental thrombosis in rats. Thromb. Res. 18: 669-674, 1980.
22. STÜRZEBECHER, J., MARKWARDT, F. AND WALSMANN, P.: Synthetic inhibitors of serine proteases: Inhibition of factor Xa by derivatives of benzamidine. Thromb. Res. 9: 637-646, 1976.
23. TALBOT, M. D., AMBLER, J., BUTLER, K. D., FINDLAY, V. S., MITCHELI, K. A., PETERS, R. F., TWEED, M. F. AND WALLIS, R. B.: Recombinant desulphatohirudin (CGP 39393). Anticoagulant and antithrombotic properties in vivo. Thromb. Haemost. 61: 77-80, 1989.
24. TEIEN, A. N. AND LIE, M.: Evaluation of an amidolytic heparin assay method: Increased sensitivity by adding purified antithrombin III. Thromb. Res. 13: 285-288, 1978.
25. UMETSU, T. AND SANAI, K.: Effect of KC-6141, an anti-aggregating compound, on experimental thrombosis in rats. Thromb. Haemost. 39: 74-83, 1978.
26. VOGEL, G. M., MEULEMAN, D. G., BOURGONDIEU, F. G. AND HOBBELEM, M.: Comparison of two experimental thrombosis models in rats: Effect of four glycosaminoglycans. Thromb. Res. 54: 399-410, 1989.
27. WALLIS, R. B.: Inhibitors of coagulation factor Xa: From macromolecular beginnings to small molecules. Curr. Opin. Ther. Patents 32: 1173-1179, 1993.
28. WEITZ, J. I., HUDOBA, M., MASSEL, D., MARAGANORE, J. AND HIRSH, J.: Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. J. Clin. Invest. 86: 385-391, 1990.
29. YOKOYAMA, T. AND FUJII, S.: New synthetic inhibitors of chymotrypsin, trypsin, thrombin, plasmin, urokinase, tissue plasminogen activator, factor Xa, tissue fcallikrein and plasma kallikrein. Jpn. J. Clin. Chem. 15:338-344, 1986.