rpr-120844 and Thrombosis

rpr-120844 has been researched along with Thrombosis* in 3 studies

Reviews

1 review(s) available for rpr-120844 and Thrombosis

ArticleYear
Factor Xa inhibitors: next-generation antithrombotic agents.
    Journal of medicinal chemistry, 2010, Sep-09, Volume: 53, Issue:17

    Topics: Administration, Oral; Animals; Anticoagulants; Biological Availability; Clinical Trials as Topic; Drug Design; Drug Evaluation, Preclinical; Factor Xa Inhibitors; Hemostasis; Humans; Models, Molecular; Protein Conformation; Structure-Activity Relationship; Thrombosis

2010

Other Studies

2 other study(ies) available for rpr-120844 and Thrombosis

ArticleYear
Design and structure-activity relationships of potent and selective inhibitors of blood coagulation factor Xa.
    Journal of medicinal chemistry, 1999, Sep-09, Volume: 42, Issue:18

    The discovery of a series of non-peptide factor Xa (FXa) inhibitors incorporating 3-(S)-amino-2-pyrrolidinone as a central template is described. After identifying compound 4, improvements in in vitro potency involved modifications of the liphophilic group and optimizing the angle of presentation of the amidine group to the S1 pocket of FXa. These studies ultimately led to compound RPR120844, a potent inhibitor of FXa (K(i) = 7 nM) which shows selectivity for FXa over trypsin, thrombin, and several fibrinolytic serine proteinases. RPR120844 is an effective anticoagulant in both the rat model of FeCl(2)-induced carotid artery thrombosis and the rabbit model of jugular vein thrombus formation.

    Topics: Animals; Anticoagulants; Crystallography, X-Ray; Factor Xa Inhibitors; Humans; Models, Molecular; Molecular Structure; Pyrrolidinones; Rabbits; Rats; Serine Proteinase Inhibitors; Stereoisomerism; Structure-Activity Relationship; Sulfonamides; Thiophenes; Thrombosis

1999
Sulfonamidopyrrolidinone factor Xa inhibitors: potency and selectivity enhancements via P-1 and P-4 optimization.
    Journal of medicinal chemistry, 1999, Sep-09, Volume: 42, Issue:18

    Sulfonamidopyrrolidinones were previously disclosed as a selective class of factor Xa (fXa) inhibitors, culminating in the identification of RPR120844 as a potent member with efficacy in vivo. Recognizing the usefulness of the central pyrrolidinone template for the presentation of ligands to the S-1 and S-4 subsites of fXa, studies to optimize the P-1 and P-4 groups were initiated. Sulfonamidopyrrolidinones containing 4-hydroxy- and 4-aminobenzamidines were discovered to be effective inhibitors of fXa. X-ray crystallographic experiments in trypsin and molecular modeling studies suggest that our inhibitors bind by insertion of the 4-hydroxybenzamidine moiety into the S-1 subsite of the fXa active site. Of the P-4 groups examined, the pyridylthienyl sulfonamides were found to confer excellent potency and selectivity especially in combination with 4-hydroxybenzamidine. Compound 20b (RPR130737) was shown to be a potent fXa inhibitor (K(i) = 2 nM) with selectivity against structurally related serine proteinases (>1000 times). Preliminary biological evaluation demonstrates the effectiveness of this inhibitor in common assays of thrombosis in vitro (e.g. activated partial thromboplastin time) and in vivo (e.g. rat FeCl(2)-induced carotid artery thrombosis model).

    Topics: Amidines; Animals; Anticoagulants; Binding Sites; Factor Xa Inhibitors; Humans; Models, Molecular; Protein Binding; Pyrrolidinones; Rats; Rats, Sprague-Dawley; Serine Proteinase Inhibitors; Sulfonamides; Sulfones; Thrombosis

1999
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