四环素BCD环类似物的合成及其趋骨性探讨  

Study on the synthesis of the tetracycline BCD ring analogs and their bone-affinity

作　　者：黄文才[1] 翁玲玲[1] 郑虎[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》2004年第2期65-70,共6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BCD环为模板 ,设计并合成其类似物 ,检测它们的趋骨性。方法以α 苯甲酰基取代的四氢萘酮、苯并吡喃 4 酮或蒽醌为母核 ,根据四环素BCD环中可能与其趋骨性有关的结构 ,合成其简化类似物 ,用羟基磷灰石吸附实验检测各目标物的趋骨性。结果部分所合成的化合物具有优于四环素的趋骨性。结论四环素CD环中酚羟基 酮结构可能是该类化合物趋骨活性的贡献部分 ,它们保持在一个平面内的构象是其具有较高趋骨性的必备条件。Aim Taking the phenol-β-diketone structure in the BCD ring of the tetracycline as the model,to design and synthesize its analogs and test their bone affinities.Methods With α-benzoyl-tetrahydronaphthalenone,benzopyran-4-one,or anthrone as the core,the simplified tetracycline BCD ring analogs were synthesized.The adsorption abilities in the hydroxyapatite of the target compounds were tested.Results Some synthesized target compounds have higher bone affinities than that of tetracycline.Conclusion The phenol-ketone structure in the CD ring may be responsible for the tetracycline′s bone affinity.The conformation that the structure keeps almost in one plane is necessary for its bone affinity.

关 键 词：药物化学 制备 化学合成 四环素 类似物 羟基磷灰石 趋骨性 

分 类 号：R914[医药卫生—药物化学]