四环素AD环类似物的合成及其趋骨性探讨  

Synthesis of tetracycline AD ring analogs and their bone-affinity

作　　者：黄文才[1] 林钢[1] 翁玲玲[1] 

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《中国药物化学杂志》2003年第3期138-141,共4页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金资助项目 (30 0 70 883)

摘　　要：目的以四环素AD环为模板 ,设计并合成其类似物 ,检测它们的趋骨性。方法以苯并吡喃 4 酮为核心 ,根据四环素的结构在其 2、3、5、6位进行衍生化 ,用羟基磷灰石吸附实验检测目标物的趋骨性。结果所合成的 6个目标化合物中 ,有 2个化合物的趋骨性好于四环素 ,其余 4个化合物比四环素差。结论四环素A环的三羰基甲烷系统可能是其趋骨活性的主要贡献部分 ,经简化的四环素AD环类似物可以保持趋骨活性 ,甚至优于四环素。Aim With the AD ring of tetracycline as the model,to design and synthesize its analogs and test their bone affinities.Methods Derivatization was conducted at C-2,C-3,C-5 and C-6 positions with benzopyran-4-one as the core.The adsorption abilities on hydroxyapatite of the target compounds were tested.Results Among all the target compounds synthesized,two have higher bone affinities than tetracycline and the others have poorer bone affinities.Conclusion The tricarbonyl methane region in ring A of tetracycline may be the key region involved in bone affinity,and the AD ring analogs synthesized may keep or even have better bone affinities than tetracycline.

关 键 词：药物化学 制备 衍生化 四环素 羧基磷灰石 趋骨性 

分 类 号：R914[医药卫生—药物化学]