川芎嗪的结构改造及修饰

Structural Modification of Ligustrazine

综述了在川芎嗪结构改造及活性研究方面的进展。由于川芎嗪具有代谢快、半衰期短等不利于临床应用的药动学特性,人们根据前药原理,分别以川芎嗪及其体内活性代谢产物2-羟甲基-3,5,6-三甲基吡嗪为先导化合物,设计合成了川芎嗪酯类、醇类、醚类、胺类、烃类及氘代等衍生物,并通过筛选发现了一些具有较好心脑血管药理活性和良好药动学性质的化合物。

The recent advances in structural modification of Ligustrazine and bioactivities of Ligustrazine derivatives were reviewed in this article. In view of the rapid metabolism and short half-life, Ligustrazine is not suitable to be applicated in clinical practice. Some leading drugs of Ligustrazine were designed and synthesized, such as the ether, amine, hydrocarbon and deuterated derivatives from Ligustrazine and the ester and alcohol derivatives from 2-hydroxymethyl-3,5,6-trimethyl pyrazine, one active metabolite of Ligustrazine. Some of them present better cerebrocardiac vascular activities and favorable pharmacokinetic properties than Ligustrazine.