中国药科大学学报2024，Vol.55Issue(3)：367-374,8.DOI:10.11665/j.issn.1000-5048.2023072901
3-乙酰基-7-羟基香豆素衍生物的设计、合成及抗血小板聚集活性
Design,synthesis and antiplatelet aggregation activity of 3-acetyl-7-hydroxycoumarin derivatives
摘要
Abstract
In order to search for coumarin-based anti-platelet aggregation compounds with high efficacy and good druggability,twenty-five 3-acetyl-7-hydroxy-coumarin oxime derivatives(6a-6y)were synthesized via Vilsmeier-Haack reaction,Knoevenagel reaction,Williamson reaction,electrophilic substitution reaction and oximation reaction from resorcinol.Their structures were confirmed by HRMS and 1H NMR spectra.The anti-platelet aggregation activity of the target compounds was evaluated using Born's turbidimetric method.The results revealed that most of them could significantly inhibit platelet aggregation induced by adenosine diphosphate(ADP),collagen,arachidonic acid(AA)and thrombin.Among them,the target compounds 6a and 6b not only had strong inhibitory activity on platelet aggregation induced by the four inducers,but also exhibited good water solubility(3.46 mg/mL and 3.85 mg/mL,respectively)and lipid-water partition coefficient(2.56 and 2.85,respectively)and were expected to become a preclinical candidate compound with multi-target action against platelet aggregation.关键词
3-乙酰基-7-羟基-香豆素/肟/水溶性/抗血小板聚集Key words
3-acetyl-7-hydroxy-coumarin/oxime/aqueous solubility/anti-platelet aggregation分类
医药卫生引用本文复制引用
尚飞扬,刘成波,谭鸿舟,何冰,何黎琴..3-乙酰基-7-羟基香豆素衍生物的设计、合成及抗血小板聚集活性[J].中国药科大学学报,2024,55(3):367-374,8.基金项目
This study was supported by the Natural Science Foundation of Department of Education of Anhui Province(No.KJ2020A0957,No.KJ2021B003) 安徽省教育厅自然科学科研项目(No.KJ2020A0957,No.KJ2021B003) （No.KJ2020A0957,No.KJ2021B003）
