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  • Title: Derivatives of bis-aldonic acid amides and their anticoagulant and antithrombotic properties.
    Author: Raake W, Klauser RJ, Elling H, Zeiller P, Meinetsberger E.
    Journal: Semin Thromb Hemost; 1994; 20(2):176-81. PubMed ID: 7997889.
    Abstract:
    Aprosulate sodium was the first representative of a new class of synthetic polyanions showing antithrombotic efficacy in different animal models. In several clinical trails (Phase I) in human volunteers aprosulate demonstrated anticoagulant properties, too. Searching for other active substances of similar structure, a series of bis-aldonic acid amides were synthesized. These compounds exhibited interesting antithrombotic and anticoagulant activities. The pharmacodynamic activities of the compounds LW 10121, LW 10125, LW 10114, 10244, and LW 10168 are summarized in this article. These substances prolonged the APTT to 150% of the blank values at concentrations of 1.5 to 13.5 micrograms/mL. The thrombin time and anti-Xa test were only slightly influenced by concentrations up to 100 micrograms/mL. All compounds were investigated in a jugular vein hemostasis model in rats to examine their antithrombotic potential. They all had an antithrombotic activity lower than aprosulate, except compound LW 10121, which seemed to be a little more active. The subcutaneous injection of 10 mg/kg LW 10121 resulted in a longer duration of action than aprosulate and heparin. On the basis of the chemical structure and the profile of action, it is assumed that the new compounds may possess the same mode of action as aprosulate, but the mechanism of action may be different from heparin and low molecular weight heparins.
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