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化学学报
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化学学报 ›› 2006, Vol. 64 ›› Issue (11): 1151-1156. 上一篇    下一篇

研究论文

3-芳氧基-1-丙胺类HIV-1 Tat/PCAF BRD抑制剂的合成及生物活性

李家明1，汪志勇*,1，ZENG, Lei2，ZHOU, Ming-Ming*,2   

  1. (1中国科学技术大学化学系 合肥 230026)
    (2 Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York
    University, New York 10029-6574, U. S. A.)
  • 投稿日期:2005-08-26 修回日期:2006-02-14 发布日期:2006-06-15
  • 通讯作者: 汪志勇

Synthesis and Biological Acitivity of 3-Aryloxy-1-propylamineDerivatives as HIV-1 Tat/PCAF BRD Inhibitor

LI Jia-Ming1, WANG Zhi-Yong*,1, ZENG Lei2, ZHOU Ming-Ming*,2   

  1. (1 Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China)
    (2 Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York 10029-6574, U. S. A.)
  • Received:2005-08-26 Revised:2006-02-14 Published:2006-06-15
  • Contact: WANG Zhi-Yong

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被引次数

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为了研究HIV-1 Tat/PCAF BRD抑制剂的构效关系, 合成了6个3-芳氧基-1-丙胺类化合物. 以取代的2-硝基苯酚为起始原料, 在常规加热和微波辐射加热下与1,3-二溴丙烷反应合成3-(2-硝基芳氧基)-1-溴丙烷(3), 结果显示, 微波辐射加热比常规加热下的反应速度明显加快, 收率有所提高. 3和邻苯二甲酰亚胺钾进行N-烷基化反应合成了2-[3-(芳氧基)-丙基]二氢异吲哚-1,3-二酮, 再经肼解得到了目标化合物, 所有化合物的结构均经FTIR, 1H NMR, 13C NMR及HRMS确证. ELISA检测法测定了它们体外抑制HIV-1 Tat/PCAF BRD的活性, 并对影响活性的因素进行了讨论.

关键词: 3-芳氧基-1-丙胺盐酸盐, 微波辐射, 肼解, Gabriel反应, 抗HIV-1

Six 3-aryloxy-1-propylamines were synthesized for studying the SAR of HIV-1 Tat/PCAF BRD inhibitors. Substituted 2-nitrophenol reacted with 1,3-dibromopropane to give 3-(2-nitroaryloxy)-1-propylbromides (3) under common heating and microwave irradiation, the reaction rate was accelerated remarkably and the yields were increased under microwave irradiation in comparision with that under common heating. Compound 3 were treated with potassium phthalimide to produce 2-[3-(aryloxy)-propyl]isoindoline-1, 3-dione (4). Hydrazinolysis of compound 4 yielded target molecules. The structures of all compounds were characterized by FTIR, 1H NMR, 13C NMR and HRMS spectra. The inhibition of HIV-1 Tat/PCAF BRD interaction in vitro was determined by ELISA assay, and some influential factors of biological activity were discussed.

Key words: 3-aryloxy-1-propylamine hydrochloride, microwave irradiation, hydrazinolysis, Gabriel reaction, anti-HIV-1