青藤碱衍生物的合成及其镇痛抗炎作用定量构效关系  

Synthesis of Sinomenine's Derivatives and Their Analgesic and Anti-Inflammatory Quantitative Structure-Activity Relationships

作　　者：杨健[1] 罗烈[1] 赵巍[1] 罗顺德[1] 

机构地区：[1]武汉大学人民医院药学部,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2009年第1期29-32,共4页Medical Journal of Wuhan University

基　　金：湖北省自然科学基金资助项目(编号:2001ABB156)

摘　　要：目的:研究青藤碱衍生物镇痛抗炎作用的定量构效关系。方法:以青藤碱为先导化合物,在其A环4位酚羟基进行酰化、醚化合成了七种青藤碱衍生物;通过小鼠扭体和大鼠足跖肿胀模型分别考察这些衍生物的镇痛和抗炎作用,并用Logit法计算ED50;采用Hansch模型对实验结果进行数学处理,拟合QSAR方程。结果:青藤碱衍生物的结构经红外、质谱及氢谱得以证实;所得镇痛作用定量构效关系方程为lg1/ED50=0.152+0.832π(n=8,R2=0.692,F=13.502);而青藤碱衍生物抗炎活性与取代基的疏水参数和范德华体积均无显著的相关性。结论:在青藤碱的酚羟基上引入亲脂性基团时有利于增强其镇痛活性,但对其抗炎活性无显著影响。Objective. To study the analgesic and anti-inflammatory quantitative structure-activity relationship （QSAR） Of sinomenine＇s derivatives. Methods. On the basis of sinomenine as lead-compound, seven derivatives were synthesized via acylation and alkylation on the 4-phenol hydroxyl groups. Through the analgesic model of writhing response induced by acetic acid in mouse and anti-inflammatory model of the rat＇s hind paw edema induced by carrageenan, the analgesic and anti inflammatory effects of these derivatives were evaluated, and their ED50 were also calculated. Hansch＇s model was adopted to deal with experimental result mathematically. Results： The basic structures of these compounds were proven by IR, MS and ^1H-NMR method. The established QSAR equation was lgl/ED50 =0. 152＋0. 832π（Analgesic, n=8, R^2 =0. 692, F= 13. 502）; π and Vw of sinomenine＇s derivatives replacement groups had no significant correlation with their anti-inflammatory activity. Conclusion： An incveased analgesic activity was showed when the phenol groups of sinomenine were replaced by the lipophilic groups, but the anti-inflammatory activity did not change significantly.

关 键 词：青藤碱衍生物 合成 镇痛 抗炎 定量构效关系 

分 类 号：R284[医药卫生—中药学]