Synthesis of pyrrolo[3,2-d]pyrimidineone derivatives as novel FXa inhibitors

被引：0

作者：

Yang, Jiabin ^{[1
]}

Su, Bolang ^{[1
]}

Liao, Ruizhu ^{[1
]}

Wang, Jinrui ^{[3
]}

Bo, Shuyu ^{[2
]}

机构：

[1] Nanjing Zhongrui Pharmaceut Co Ltd, Nanjing 211100, Jiangsu, Peoples R China

[2] Nanjing Univ, Nanjing Drum Tower Hosp, Dept Geriatr, Affiliated Hosp,Med Sch, Nanjing 210008, Peoples R China

[3] Xuchang Univ, Sch Med, Xuchang 461000, Henan, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2023年 / 80卷

关键词：

FXa inhibitor; Pyrrolo[3; 2-d]pyrimidineone; Antithrombotic activity; FACTOR XA INHIBITORS; 3,4-DIAMINOBENZOYL DERIVATIVES; VENOUS THROMBOEMBOLISM; DESIGN; POTENT; DISCOVERY;

D O I：

10.1016/j.bmcl.2023.129127

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of pyrrolo[3,2-d]pyrimidineone compounds have been designed and synthesized as novel FXa inhibitors. Bioassay of the tested compounds showed moderate to excellent anticoagulant potency in vitro. Further FXa inhibitory and bioactivity evaluation in rats, the FeCl3-induced venous thrombosis model, showed that the compound 17a has good FXa inhibitory activity (IC50 = 1.57 nM) and in vivo antithrombotic potency. The anticoagulant effects of compound 17a were dose dependent whether in vitro or in vivo. The results further confirmed our hypothesis that the large conjugated structure is an ideal skeleton binding FXa.

引用

页数：5

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