Design and Structure−Activity Relationships of Potent and Selective Inhibitors of Blood Coagulation Factor Xa
| العنوان: | Design and Structure−Activity Relationships of Potent and Selective Inhibitors of Blood Coagulation Factor Xa |
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| المؤلفون: | Alfred P. Spada, Robert J. Leadley, Jonathan S. Mason, Dennis J. Colussi, Ewing William R, Mark H. Perrone, Karen D. Brown, Michael R. Becker, Don D. Cha, Daniel M. Green, Ross Bentley, Henry W. Pauls, Christopher T. Dunwiddie, Jean-Pierre Guilloteau, Y.M. Choi-Sledeski, Sebastien Maignan, Mason Helen J, Vincent E. Manetta, Charles Kasiewski, Valeria Chu, Roderick S. Davis, Suzanne Morgan, Daniel L. Cheney, Jeff Bostwick |
| المصدر: | Journal of Medicinal Chemistry. 42:3557-3571 |
| بيانات النشر: | American Chemical Society (ACS), 1999. |
| سنة النشر: | 1999 |
| مصطلحات موضوعية: | Models, Molecular, Serine Proteinase Inhibitors, medicine.drug_mechanism_of_action, medicine.drug_class, Factor Xa Inhibitor, Thiophenes, Crystallography, X-Ray, Amidine, Structure-Activity Relationship, chemistry.chemical_compound, Thrombin, In vivo, Drug Discovery, medicine, Animals, Humans, Structure–activity relationship, Sulfonamides, Molecular Structure, biology, Chemistry, Anticoagulant, Anticoagulants, Stereoisomerism, Thrombosis, Trypsin, Pyrrolidinones, Rats, Biochemistry, Enzyme inhibitor, biology.protein, Molecular Medicine, Rabbits, Factor Xa Inhibitors, medicine.drug |
| الوصف: | 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. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2009f497bb352b54bc0c7e881834e15b https://doi.org/10.1021/jm990040h |
| رقم الأكسشن: | edsair.doi.dedup.....2009f497bb352b54bc0c7e881834e15b |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204804 00222623 |
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