Synthesis and activity studies of conformationally restricted α-ketoamide factor Xa inhibitors

Conformationally restricted borolysine compounds containing a 2-(2-cyanophenylthio) benzoyl in the P3 position unexpectedly led to enhanced factor Xa inhibition. In an effort to improve both the potency and selectivity of this series by extending into the S′ domain, we have replaced the boronic acid with α-ketoamides, utilizing a novel process that was developed in our labs.