川芎嗪衍生物的设计、合成及抗血小板凝集活性研究
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摘要
分别以川芎嗪(TMP)和邻苯二胺为起始原料,经KMn O4氧化、酯缩合、环化、还原等步骤合成了7个新型的川芎嗪衍生物,其结构经1H NMR、13C NMR及HRMS确证。并采用Born比浊法初步测试了化合物的体外抗血小板凝集活性。结果表明,化合物3和7对二磷酸腺苷(ADP)诱导的血小板凝集抑制率IC50分别为0.23mmol/L和0.27mmol/L,优于母体化合物川芎嗪(0.42mmol/L)。
Using ligustrazine( TMP) and o-phenylenediamine as raw materials, seven derivatives were synthesized via KMn O4 oxidation,esterification,cyclization and reduction. The structures were confirmed by1 H NMR,13 C NMR and HRMS. The in vitro anti-platelet aggregation activities of the target compounds have been preliminarily tested by the Born turbidimetric method,and the experimental results showed that compounds 3( IC50=0. 23 mmol/L) and 7( IC50= 0. 27 mmol/L) have significant inhibitory activity for adenosine diphosphate( ADP)induced platelet aggregation,higher than that of ligustrazine( IC50= 0. 42 mmol/L).
Using ligustrazine( TMP) and o-phenylenediamine as raw materials, seven derivatives were synthesized via KMn O4 oxidation,esterification,cyclization and reduction. The structures were confirmed by1 H NMR,13 C NMR and HRMS. The in vitro anti-platelet aggregation activities of the target compounds have been preliminarily tested by the Born turbidimetric method,and the experimental results showed that compounds 3( IC50=0. 23 mmol/L) and 7( IC50= 0. 27 mmol/L) have significant inhibitory activity for adenosine diphosphate( ADP)induced platelet aggregation,higher than that of ligustrazine( IC50= 0. 42 mmol/L).
引文
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[3]张昌林,倪小佳,李春花等.中药新药与临床药理,2017,28(4):549~556.
[4]彭晓云,曲韵智,李素芬等.中药药理与临床,2005,21(1):19~20.
[5]汪林,王鹏龙,绪扩等.中草药,2013,44(19):2766~2771.
[6]李国梁,王鹏龙,徐昕等.中国中药杂志,2014,39(14):2679~2683.
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[13]朱桃,李毅,樊玲玲等.化学试剂,2017,39(4):353~356.