Exploration of 4,4-disubstituted pyrrolidine-1,2-dicarboxamides as potent, orally active Factor Xa inhibitors with extended duration of action

With the intent to improve upon the projected human half-life of the previously disclosed Factor Xa inhibitor 5, a series of 4,4-disubstituted pyrrolidine-1,2-dicarboxamides were explored. This work led to the discovery of 26, a selective, orally bioavailable, and efficacious Factor Xa inhibitor.