Design, synthesis, and biological activity of novel factor Xa inhibitors: Improving metabolic stability by S1 and S4 ligand modification

Serine protease factor xa (fXa) inhibitor 1 showed good ex vivo anti-fXa activity upon oral administration in rats. However, it has been revealed that 1 had low metabolic stability against human liver microsomes. To improve the metabolic stability, we attempted to modify the S1 and S4 ligands of 1. These modifications resulted in compound 34b, which exhibited selective anti-fXa activity and excellent anti-coagulation activity.

A novel fXa inhibitor 34b was reported. Compound 34b exhibited selective anti-fXa activity, excellent anti-coagulation activity, and good anti-thrombotic effect in an in vivo model after oral administration.Figure optionsDownload as PowerPoint slide