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ID: ALA1147967
Journal: Bioorg Med Chem
Title: Prodrug-based design, synthesis, and biological evaluation of N-benzenesulfonylpiperidine derivatives as novel, orally active factor Xa inhibitors.
Authors: Ishihara T, Seki N, Hirayama F, Orita M, Koshio H, Taniuchi Y, Sakai-Moritani Y, Iwatsuki Y, Kaku S, Kawasaki T, Matsumoto Y, Tsukamoto S.
Abstract: We describe here our investigation of a new series of orally active fXa inhibitors based on a prodrug strategy. Solid-phase parallel synthesis identified a unique series of fXa inhibitors with a substituted benzenesulfonyl group as a novel S4 binding element. This series resulted in compound 39, which exhibited potent inhibitory activity against fXa (IC50 = 13 nM) and excellent selectivity over thrombin (>7000-fold). The masking of its highly hydrophilic groups led to the creation of related prodrug 28, which demonstrated an anticoagulant effect after oral dosing.
CiteXplore: 17416533