Amido-(propyl and allyl)-hydroxybenzamidines: development of achiral inhibitors of factor Xa

Abstract The design, synthesis and SAR of amido-(propyl and allyl)-hydroxybenzamidine coagulation factor Xa inhibitors is described. These achiral inhibitors are selective for fXa vis a vis structurally related serine proteases and are readily prepared in 6–7 linear steps. The most potent member 9j (fXa K i =0.75 nM) is selective (>1000-fold) and an effective anticoagulant in mammalian plasma.