Optimization of the β-Aminoester class of factor Xa inhibitors. part 1: P4 and side-Chain modifications for improved In vitro potency

Abstract A systematic modification of the C 3 side-chain of the β-aminoester class of factor Xa inhibitors and a survey of P 4 variations is described. These changes have resulted in the identification of sub-nanomolar inhibitors with improved selectivity versus related proteases. Coagulation parameters (i.e., APTT doubling concentrations) are also improved.