川芎嗪仲醇类衍生物的合成及其正性肌力活性研究  

Synthesis and Positive Inotropic Effects of the Secondary Alcohol Derivatives of Ligustrazine

作　　者：陈磊[1] 李伟[1] 陈龙[1] 刘峥[1] 

机构地区：[1]南京中医药大学,南京210046

出　　处：《中国药学杂志》2013年第13期1118-1122,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(81072542);江苏省自然科学基金资助项目(BK2011077)

摘　　要：目的设计合成川芎嗪仲醇衍生物,观察化合物对正常大鼠离体心脏的正性肌力作用。方法 2,5-二羟甲基-3,6-二甲基吡嗪被氧化成3,6-二甲基-2,5-吡嗪二甲醛,然后与格氏试剂反应得仲醇化合物;采用Langendorff离体灌流装置观察化合物对大鼠离体心脏心功能的影响。结果 中间体和目标化合物经氢谱(1H-NMR)、碳谱(13C-NMR)、红外(IR)、质谱(MS)确证结构;正性肌力活性实验结果显示,川芎嗪衍生物对正常大鼠离体心脏产生正性肌力作用,对心率无影响。结论 川芎嗪仲醇衍生物具有正性肌力作用,且随着取代烷基的增长,其正性肌力活性减弱。Objective To design and synthesize the secondary alcohol derivatives of ligustrazine and to investigate their inotropic effects in normal isolated rat hearts. Methods 3,6-Dimethyl-2,5-pyrazine formaldehyde was obtained from oxidizing 2,5-dihydroxymethyl-3,6-dimethylpyrazine, and then reacted with Grignard reagent in tetrahydrofuran, to get the secondary alcohol derivatives. Normal isolated rat hearts were perfused by the Langendorff technique and observed for the effects of these compounds on left ventricular inotropic effects. Results These compounds were verified by1H-NMR,13C-NMR, IR and MS spectra, and they induced positive inotropic effects in normal isolated rat hearts without affecting heart rate. Conclusion Series of ligustrazine secondary alcohol derivatives produced positive inotropic effect in normal isolated rat hearts. The derivatives with longer alkyl substituents showed less positive inotropic effect.

关 键 词：川芎嗪 结构修饰 仲醇衍生物 正性肌力活性 

分 类 号：R282[医药卫生—中药学]