Design, synthesis and antiplatelet aggregation activity of 3-acetyl-7-hydroxycoumarin derivatives

SHANG Feiyang; LIU Chengbo; TAN Hongzhou; HE Bing; HE Liqin

doi:10.11665/j.issn.1000-5048.2023072901

Journal of China Pharmaceutical University > 2024 > 55(3): 367-374. > DOI: 10.11665/j.issn.1000-5048.2023072901

SHANG Feiyang, LIU Chengbo, TAN Hongzhou, et al. Design, synthesis and antiplatelet aggregation activity of 3-acetyl-7-hydroxycoumarin derivatives[J]. J China Pharm Univ, 2024, 55(3): 367 − 374. DOI: 10.11665/j.issn.1000-5048.2023072901

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Design, synthesis and antiplatelet aggregation activity of 3-acetyl-7-hydroxycoumarin derivatives

College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038, China

Funds: This study was supported by the Natural Science Foundation of Department of Education of Anhui Province（No. KJ2020A0957, No.KJ2021B003）

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Received Date: July 28, 2023
Available Online: June 24, 2024

Graphical Abstract

Abstract

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.
- 3-acetyl-7-hydroxy-coumarin,
- oxime,
- aqueous solubility,
- anti-platelet aggregation

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References (17)

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