AHPN衍生物的合成及其与RARγ的结合活性研究

Synthesis of AHPN Derivatives and Their Combining Activities with RARγ

目的本实验以6-{3'-(1-金刚烷基)-4'-羟基苯基}-2-萘甲酸(AHPN)母核为结构基础,设计、合成一系列AHPN衍生物,并对这些衍生物做初步的活性筛选,期望找到活性显著的衍生物。方法以对溴苯酚和1-金刚烷醇为原料经取代、缩合、氧化、还原等反应合成AHPN衍生物,经过^(1)H-NMR、^(13)C-NMR、HR-MS表征,并利用Biacore技术检测衍生物与蛋白质之间的结合能力。结果衍生物7c、6c、6e、6h显示出了显著优于先导化合物AHPN与视黄酸核受体γ(RARγ)的结合能力,亚磷酸二甲酯基与氮杂环的引入提高了该类化合物的活性。结论该类AHPN衍生物与RARγ结合能力显著,有进一步研究的价值。

OBJECTIVE To study the synthesis and activities of AHPN derivatives.METHODS Starting from p-bromophenol and 1-adamantanol,a series of AHPN derivatives were synthesized by substitution reaction,condensation reaction,oxidation reaction and reduction reaction.These new compounds were characterized by^(1)H-NMR,^(13)CNMR and HR-MS.Biacore technique was used to test the derivatives'combining activities with RARγ.RESULTS Four compounds,7c,6c,6e,and 6h,exhibited significant combining activities with RARγcompared with AHPN.The introduction of phosphoric acid groups and nitrogen heterocyclic ring increased the activities of these compounds.CONCLUSION Compounds 7c,6c,6e,and 6h show significant combining activities with RARγ,which are worthy of further study.