Synthesis and evaluation of anthranilamide-based derivatives as FXa inhibitors

Huang, Changjiang; Wang, Wenzhi; Li, Yao; Zhang, Shijun; Meng, Fancui; Xu, Weifeng; Yuan, Jing; Chen, Ligong

doi:10.18632/oncotarget.16427

Cited by 4 publications

(1 citation statement)

References 10 publications

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“…Although the inhibitory effect of compound 7 on FXa (IC 50 = 25.0 nM) did not improve much, the anticoagulant effect in vitro was enhanced (2 × PT (Human) = 12.8 μM), but it was still weaker than that of Rivaroxaban (2 × PT (Human) = 0.2 μM). Based on compound 7, Huang et al (2017) replaced the chlorine in the P1 moiety with bromine, resulting in a stronger Br-p interaction in the S1 pocket, resulting in compound 8. Compared with compound 7, compound 8 showed increased FXa inhibitory (IC 50 = 13.4 nM) and anticoagulant activity [2 × PT (Human) = 4.2 μM], suggesting a stronger interaction of bromo at the S1 pocket.…”

Section: Anthranilate Derivativesmentioning

confidence: 99%

Discovery and development of Factor Xa inhibitors (2015–2022)

Zheng

Dai

et al. 2023

Front. Pharmacol.

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As a pathological coagulation process, thrombus can lead to many serious diseases, including ischemic stroke, acute myocardial infarction (AMI), acute coronary syndrome (ACS), and deep venous thrombosis (DVT). And anticoagulant drugs are one of the most effective ways to prevent and treat these diseases. Although macromolecular anticoagulant drugs such as low molecular weight heparins (LMWHs) are widely used in the clinic, their characteristics of requiring injectable use hinder their further promotion in the clinic, and the disadvantages of oral anticoagulant drugs, such as warfarin and dabigatran etexilate, which can easily cause bleeding adverse effects, are also not addressed. Factor Xa (FXa) has gained attention because it lies at the intersection of the coagulation cascade pathways, whereas subsequently introduced Factor Xa inhibitors such as rivaroxaban and apixaban, among others, have gained market popularity because of their high potency for anticoagulation and high specificity for Factor Xa when administered orally. But some of the drawbacks that these Factor Xa inhibitors have simultaneously such as fewer indications and the lack of an effective reversal drug when bleeding occurs are urgently addressed. The development of new Factor Xa inhibitors therefore becomes one means of addressing these questions. This article summarizes the small molecule Factor Xainhibitors developed from 2015 to 2022, classifies them according to their scaffolds, focuses on the analysis of their structure-activity relationships, and provides a brief assessment of them.

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Section: Anthranilate Derivativesmentioning

confidence: 99%