Aminoisoquinolines: Design and synthesis of an orally active benzamidine isostere for the inhibition of factor Xa.

Article abstract of DOI:10.1016/S0960-894X(99)00421-7

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 proteasesof interest (>600 fold).