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1H-NMR、13C-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。
Abstract
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 1H-NMR, 13CNMR 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 RARγ compared 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.
关键词
视黄酸核受体γ /
6-{3′-(1-金刚烷基)-4′-羟基苯基}-2-萘甲酸 /
靶向结合 /
化学合成
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Key words
RARγ /
AHPN /
targeted binding /
synthesis
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中图分类号：
R962
R914.5
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参考文献
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脚注
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基金
扬州市邗江区科技计划项目资助;福建省基金项目资助(2014Y0044);国家海洋局第三海洋研究所基本科研业务费专项资金资助项目(海三科2016044)
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