Design, synthesis and structure-activity relationship of oxazolidinone derivatives containing novel S4 ligand as FXa inhibitors

作者：Zhao, Yanfang; Jiang, Mingyan; Zhou, Shunguang; Wu, Shasha; Zhang, Xiaolong; Ma, Longsheng; Zhang, Kai; Gong, Ping^*

来源：European Journal of Medicinal Chemistry, 2015, 96: 369-380.

DOI：10.1016/j.ejmech.2015.04.025

• Factor Xa inhibitors
• Oxazolidinone derivatives
• Anticoagulant activity
• Synthesis

A novel series of potent and efficacious factor Xa inhibitors which possesses pyrrole/indole/thiazole moieties as S4 binding element was identified. Compound 7b showed strong human factor Xa inhibitory activity (IC50 = 2.01 nM) and anticoagulant activities in both human (PTCT2 = 0.15 mu M, APPTCT(2) = 0.30 mu M) and rabbit plasma (PTCT2 = 0.46 mu M, APPTCT(2) = 0.75 mu M). The SARs analyses indicated that the size and water solubility of different alkylamino group at the position of S4 ligand were responsible for the anticoagulant activity.

• 出版日期2015-5-26
• 单位沈阳药科大学