Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with biaryl P4 motifs

Abstract

Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating biaryl P4 groups, producing highly potent inhibitors with encouraging oral pharmacokinetic profiles and significant but sub-optimal anticoagulant activities.