| 贾镇,张关丽,李毅,李永,汤磊,樊玲玲.化学通报,2024,87(1):110-117. |
| 丁苯酞-哒嗪酮衍生物的设计、合成及其抗凝活性研究 |
| Design,SynthesisandAnticoagulantActivityofButylphthalide-PyridazinoneDerivatives |
| 投稿时间：2023-07-06 修订日期：2023-07-26 |
| DOI： |
| 中文关键词: 丁苯酞衍生物 哒嗪酮 设计 合成 抗血小板凝集活性 |
| 英文关键词:Butylphthalide derivative Pyridazinone Design Synthesis Anti-platelet aggregation activity |
| 基金项目:国家自然科学基金项目(32060627)、贵州省科技计划项目(黔科合基础-ZK[2023]一般309)、贵州省普通高等学校青年科技人才成长计划项目(黔教合KY字[2022]246号)和贵州省2021年大学生创新创业训练计划项目(S202110660026)资助 |
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| 中文摘要: |
| 为了提高丁苯酞的抗血小板凝集活性,以6-氨基丁苯酞为起始原料,经重氮化/还原、环化、水解、脱氯、醚化和磺酰化反应合成了20个新型的丁苯酞-哒嗪酮衍生物,其结构经1H-NMR、13C-NMR和HRMS确证。体外抗血小板凝集活性测试结果表明:化合物6a、6b和6k对二磷酸腺苷(ADP)诱导的血小板凝集的抑制活性(IC50 = 44.9-180.0 μmol/L)优于先导化合物丁苯酞(IC50 = 1252 μmol/L)和阳性对照阿司匹林(IC50 = 1140 μmol/L)；同时化合物 6b(IC50 = 63.6 μmol/L)和6k(IC50 = 191.9 μmol/L)对花生四烯酸(AA)诱导的血小板凝集也表现出显著的抑制活性。本研究为丁苯酞-哒嗪酮骨架在治疗缺血性脑卒中方面的研究提供了理论参考。 |
| 英文摘要: |
| In order to improve the antiplatelet agglutination activity of butylphthalide, 6-aminobutylphthalide was used as the starting material, twenty novel butylphthalide-pyridazinone derivatives were synthesized by diazotization/reduction, cyclization, hydrolysis, dechlorination, etherification and sulfonation acylation. Their structures were confirmed by 1H-NMR, 13C-NMR and HRMS. The results of antiplatelet agglutination activity test in vitro showed that compounds 6a, 6b and 6k exhibited better inhibitory activity (IC50 = 44.9-180.0 μmol/L) against ADP-induced platelet aggregation than the lead compound butylphthalide (IC50 = 1252 μmol/L) and positive control aspirin (IC50 = 1140 μmol/L). Meanwhile, compound 6b (IC50 = 63.6 μmol/L) and 6k (IC50 = 191.9 μmol/L) also possessed significant inhibitory activity against AA-induced platelet aggregation. This study provides a theoretical reference for the study of butylphthalide-pyridazinone skeleton in the treatment of ischemic stroke. |
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