Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1367826 | Bioorganic & Medicinal Chemistry Letters | 2005 | 6 Pages |
Abstract
Thrombin-inhibitor X-ray crystal structures, in combination with the installation of binding elements optimized within the pyrazinone series of thrombin inhibitors, were utilized to transform a weak triazolopyrimidine lead into a series of potent oxazolopyridines. A modification intended to attenuate plasma protein binding (i.e., conversion of the P3 pyridine to a piperidine) conferred significant factor Xa activity to this series. Ultimately, these dual thrombin/factor Xa inhibitors demonstrated excellent in vitro and in vivo anticoagulant efficacy.
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Related Topics
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Authors
James Z. Deng, Daniel R. McMasters, Philippe M.A. Rabbat, Peter D. Williams, Craig A. Coburn, Youwei Yan, Lawrence C. Kuo, S. Dale Lewis, Bobby J. Lucas, Julie A. Krueger, Berta Strulovici, Joseph P. Vacca, Terry A. Lyle, Christopher S. Burgey,