Synthesis and factor Xa inhibitory activity of rivaroxaban derivatives

Rivaroxaban is the first launched drug as a potent factor Xa inhibitor.Based on current SAR study results of rivaroxaban and its derivatives,we designed and synthesized a series of new oxazolidinone derivatives,and tested their anti-factor Xa activity.Rivaroxaban derivatives were synthesized starting from 2-phenylaminoethanol via acylation,nitrification,reduction,and then cyclization to afford (S)-4-(4-(5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl)phenyl)morpholin-3-one,which was condensed with 5-chlorothiophene-2-carbonyl chloride or thiazole carboxylic acid to afford the target compounds.Ten novel rivaroxaban derivatives（ 11a-11j ) were synthesized,and their structures were identified by IR,¹H NMR,¹³C NMR and MS.Preliminary results of factor Xa inhibition assays showed that most of the test compounds exhibited factor Xa inhibitory activity,yet with less potency than rivaroxaban.