中国药科大学学报2026，Vol.57Issue(2)：196-205,10.DOI:10.11665/j.issn.1000-5048.2025100902
Asundexian衍生物的设计、合成及活性评价
Design,synthesis and biological evaluation of Asundexian derivatives
吴杰 1朱华超 1王鑫浩 1宫平2
作者信息
- 1. 齐鲁医药学院药学院,淄博 255213
- 2. 沈阳药科大学制药工程学院,沈阳 110016
- 折叠
摘要
Abstract
Coagulation factor XIa(FXIa)plays a crucial role in thrombus formation;therefore,the development of potent and safe FXIa inhibitors is of great significance.In this study,compound F22,previously discovered by our group,was selected as the lead compound.Based on the principles of bioisosterism and fragment-based drug design,four series comprising 14 novel Asundexian derivatives not previously reported in the literature were designed and synthesized.The structures of the target compounds were confirmed by 1H NMR and HRMS,and their inhibitory activities against FXIa were evaluated using chromogenic substrate assay.Results showed that compound FD-1 exhibited the most potent activity,with an IC50 value of 2.8 nmol/L,which was superior to that of the lead compound F22(IC50=4.5 nmol/L)and the reference drug Asundexian(IC50=5.0 nmol/L).Furthermore,in the activated partial thromboplastin time(aPTT)assay,compound FD-1 demonstrated excellent anticoagulant activity,outperforming Asundexian,showing no significant effect on prothrombin time(PT).These findings provide valuable insights for further structural optimization and rational design of small-molecule FXIa inhibitors.关键词
FXIa抑制剂/Asundexian/生物电子等排/活性研究Key words
FXIa inhibitors/Asundexian/bioisosterism/biological activity分类
医药卫生引用本文复制引用
吴杰,朱华超,王鑫浩,宫平..Asundexian衍生物的设计、合成及活性评价[J].中国药科大学学报,2026,57(2):196-205,10.
