摘要：As a coagulation factor in the intrinsic coagulation pathway,factor XIa(FXIa)is an effective and safe target for the development of antithrombotic *** small-molecule FXIa inhibitors have been discovered,some of which are being evaluated in clinical ***,none of them have been *** the present study,a highly selective potent FXIa inhibitor with poor solubility reported in our previous work was selected as a lead compound to be further modified to improve FXIa potency and physicochemical *** structure-based drug design and structure-activity relationship study led to the discovery of LY8,LY17,and LY25,which demonstrated enhanced FXIa potency and maintained excellent *** addition,LY8 exhibited significantly improved aqueous solubility,suggesting that it could be a promising compound to be further evaluated.