Novel Anthranilamide-Based FXa Inhibitors: Drug Design, Synthesis and Biological Evaluation

被引：12

作者：

Wang, Wenzhi ^{[1
,2
]}

Yuan, Jing ^{[2
]}

Fu, Xiaoli ^{[2
]}

Meng, Fancui ^{[2
]}

Zhang, Shijun ^{[2
]}

Xu, Weiren ^{[2
]}

Xu, Yongnan ^{[1
]}

Huang, Changjiang ^{[2
]}

机构：

[1] Shenyang Pharmaceut Univ, Sch Pharmaceut Engn, Shenyang 110016, Peoples R China

[2] Tianjin Inst Pharmaceut Res, Tianjin Key Lab Mol Design & Drug Discovery, Tianjin 300193, Peoples R China

来源：

MOLECULES | 2016年 / 21卷 / 04期

关键词：

thrombosis; FXa inhibitor; anthranilamide-based FXa inhibitors; docking simulation; FACTOR XA INHIBITORS; COAGULATION-FACTOR XA; DISCOVERY; POTENT; ANTICOAGULANT; PHARMACOLOGY;

D O I：

10.3390/molecules21040491

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Factor Xa (FXa) plays a significant role in the blood coagulation cascade and it has become a promising target for anticoagulation drugs. Three oral direct FXa inhibitors have been approved by the FDA for treating thrombotic diseases. By structure-activity relationship (SAR) analysis upon these FXa inhibitors, a series of novel anthranilamide-based FXa inhibitors were designed and synthesized. According to our study, compounds 1a, 1g and 1s displayed evident FXa inhibitory activity and excellent selectivity over thrombin in in vitro inhibition activities studies. Compounds 1g and 1s also exhibited pronounced anticoagulant activities in in vitro anticoagulant activity studies.

引用

页数：16

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