VIF is one of the six accessory proteins of HTV-1,which plays an important role in surviving and remaining infectious in the body. VEC-5 is a novel HTV-1 VIF inhibitor. We made structural modifications on VEC-5 to improve the water solubility, and to explore the structure-activity relationships. Starting from isonicotinic acid via Friedel-Crafts reaction, 1,3-dipolar cycloaddition reaction and amidation,totally 30 ethyl 7-benzoylindolizine-l-carboxylate derivatives were synthesized and all of them were not reported yet, and their structures were confirmed by MS, 1H-NMR and 13C-NMR. The in vitro inhibitory activity of the synthesized compounds was evaluated via fluorescent screening method. All of the tested compounds show diverse inhibitory activity,among which the compounds 30,31,36 and 37 have the inhibitory activity equivalent to VEC-5. The distance between the indolizine and aromatic ring is very important. Three or four atomic length distance between indolizine and aromatic ring can produce the best inhibitory activity.%目的 设计合成7-苯甲酰基中氮茚-1-羧酸乙酯类化合物,并对其抗HIV-1活性进行初步研究.方法 以异烟酸、溴乙酸苄酯、丙炔酸乙酯为原料,经取代、Friedel-Crafts反应、1,3-偶极环加成反应、水解、缩合得到目标化合物；采用荧光筛选方法对目标化合物抗HIV-1病毒感染因子(viral infectivity factor,VIF)活性进行评价.结果 共合成30个未经文献报道的新化合物,其结构经1H-NMR、13 C-NMR、HRMS确证；活性结果表明,化合物30、31、36、37等4个化合物抗HIV-1活性与先导化合物相当.结论 7-苯甲酰基中氮茚-1-羧酸乙酯类化合物作为HIV-1 VIF复合物抑制剂,中氮茚环与取代芳环之间含3～4个原子长度为保持活性所必须,进一步的构效关系值得继续研究.
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