The design, synthesis and SAR of sulfonamidopyrrolidinone fXA inhibitors incorporating a new benzamidine isostere, namely aminoisoquinolines, is described. These inhibitors have higher Caco-2 cell permeability than comparable benzamidines and attain higher levels of exposure upon oral dosing. The most potent member 14b (fXa Ki= 6 nM) is selective against other serine proteases of interest (> 600 fold).
