Studies towards the identification of potent, selective and bioavailable thrombin inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 9; no. 5; pp. 737 - 742
• Main Authors: Ambler, John, Baker, Emma, Bentley, Dave, Brown, Lyndon, Butler, Keith, Butler, Paul, Farr, Dave, Dunnet, Karen, Grand, Darren Le, Hayler, Judy, Janus, Diana, Jones, Darryl, Menear, Keith, Mercer, Mark, Smith, Garrick, Talbot, Mark, Tweed, Morris
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 08.03.1999; Elsevier
• Subjects: Anticoagulants - isolation & purification; Anticoagulants - pharmacokinetics; Anticoagulants - pharmacology; Biological and medical sciences; Biological Availability; Blood. Blood coagulation. Reticuloendothelial system; Medical sciences; Pharmacology. Drug treatments; Structure-Activity Relationship; Thrombin - antagonists & inhibitors; Rat; Combinatorial chemistry; Cardiovascular disease; Non peptide compound; Thrombin; Anticoagulant; Pyridine derivatives; Vascular disease; Hydroxyether; Structure activity relation; Chemical compound library; Selection criterion; Intraduodenal administration; Sulfonamide; Serine endopeptidases; Enzyme; Rodentia; Oral administration; Enzyme inhibitor; Bioavailability; In vitro; Thrombosis; Peptidases; In vivo; Vertebrata; Experimental disease; Mammalia; Drug library; Animal; Hydrolases; Carboxamide; Pharmacokinetics
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(99)00061-X

The application of selection criteria, based on potency and physicochemical parameters, to a candidate library of thrombin inhibitors is described. The utility of the approach is exemplified by the discovery of a potent, selective and bioavailable thrombin inhibitor 62. The application of selection criteria, based on potency and physicochemical parameters, to a candidate library of thrombin inhibitors is described. The utility of the approach is exemplified by the discovery of a potent, selective and bioavailable thrombin inhibitor 1.