【摘要】 为了研究HIV-1Tat/PCAFBRD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,1HNMR,13CNMR及HRMS确证.ELISA检测法测定了它们体外抑制HIV-1Tat/PCAFBRD的活性,并对影响活性的因素进行了讨论.更多还原

【Abstract】 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-propyl-bromides(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.更多还原