Novel, Potent And Selective Chimeric Fxa Inhibitors Featuring Hydrophobic P-1-Ketoamide Moieties

Judicious combination of P-region sequences of highly potent anticoagulant proteins including NAPS, NAP6, Ecotin, and Antistasin with SAR from small molecule FXa inhibitors led to a series of chimeric inhibitors of formula 1a-j. We report herein the design, synthesis, and biological activity of this novel family of FXa inhibitors that express both high in vitro potency and superb selectivity against related serine proteases. (C) 2000 Elsevier Science Ltd. All rights reserved.