Abstract:
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.