【作者】 胡丰；

【导师】 宫平；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2007， 硕士

【摘要】 本文简要介绍了乙肝病毒的生物学特征，阐述了抗乙肝病毒药物的研究进展概况。重点对5-羟基-1H-苯并咪唑类化合物进行了设计与合成研究。在本实验室前期构效关系研究工作的基础上，以阿比朵尔为先导化合物，将吲哚环替换为可发挥抗病毒活性的苯并咪唑环，设计得到5-羟基-1H-苯并咪唑类化合物，并在母环的1位、2位、4位和6位分别进行结构修饰和改造，以考察化合物分子的立体效应、电性效应、疏水性等对抗病毒活性的影响。通过大量的实验摸索，确立了目标化合物的合成路线，分别以对硝基苯酚和2-氟-4-硝基苯酚为起始原料，通过两条路线进行合成。此外，对中间体的合成方法进行了考察，找到了操作简便、收率较高的合成方法。共设计并合成了30个未见文献报道的目标化合物，其化学结构经MS、~1H-NMR确证。目标化合物的药理活性测试正在进行中。更多还原

【Abstract】 In this paper, the biological characteristics of the hepatitis B virus, and the development of the anti-HBV drugs were introduced briefly. The design and synthesis of 1H-benzo[d]imidazol-5-ol derivatives were introduced in details.Based on the structure-activity relationship studies of the former research, Arbidol was took as lead compound, and the indole ring was replaced with the benzimidazole ring, which had been reported to have antiviral activities in many literatures. Thus 1H-benzo[d]imidazol-5-ol derivatives were designed, and modifications and optimizations were made at 1-position 2-position 4-position and 6-position, in order to investigate the effects of the steric effect the electronic effect and the hydrophobicity on antiviral activities.The synthetic route was confirmed in the experiments. Starting from 4-nitrophenol or 2-fluoro-4-nitrophenol, the target compounds were synthesized through two different routs. Also, the reaction conditions were optimized during the experiments.Total 30 target compounds that had never been reported in literatures were designed and synthesized, their structures were confirmed by MS and ~1H-NMR. The pharmacological evaluation of the target compounds is underway.更多还原