The Research On Synthesis And Structure-activity Relationship Of Potential Biological Evaluation1,5-benzodiazepines

1,5-benzodiazepines are a kind of seven-membered heterocycle compounds andhave both important physiological activities and biological activities. Manyderivatives of them are nowadays widely used as medications which have the curativeeffect of treatment nervous system and cardiovascular system diseases. In additionthis kind of compounds also has antifungal, antimicrobial, antivirus and antagonistactivities. So far1,5-benzodiazepines has got a huge applications in medicaltreatment and the effect is good. Therefore the research of its unique chemical structureand special physiological activity has been getting people’s attention.The research showed that1,5-benzodiazepine derivatives have antibacterialactivity, and the introduction of the ester group in the1,5-benzodiazepineseven-membered ring, can be increased in animalsthe liposoluble thus effectivelyenhance its pharmacological activity.In order to find new1,5-benzodiazepinecompounds which have efficient antibacterial activity, this paper has designed andsynthesized twenty-two2-aryl-3-ester groups-4-methyl-1,5–benzodiazepines.and we have tested the antibacterial activities of the compounds mentioned above. Inaddition,we also have done a detailed study of the method of synthesis of the targetcompounds. Ultimately, we found the best synthetic route of the target compound andthe desired synthesis conditions.We made a theoretical study on the factors ofaffecting antibacterial activity of1,5–benzodiazepine compounds by the Gaussian03quantum chemistry package, density functional theory (DFT) at the B3LYP method,in the6-31G basis set level.This thesis includes the following parts:Firstly, three routes were designed to synthesis the target compound2-phenyl-3-ester base-4-methyl-1,5-benzodiazepines where ethyl acetoacetate,benzaldehyde, o-phenylenediamine are the starting material. Besides the experimentalstudy of the conditions on the synthesis reaction was done and the optimal reactionconditions of the target product was obtained.Secondly, twenty-two novel kinds of2-aryl-3-ester base-4-methyl-1,5-benzodiazepines were synthesized by a two-step reaction when ethyl acetoacetate,substituted benzaldehyde and substituted o-phenylenediamine are the starting material.The structures of these new compounds are determined by IR、MS、1H NMR、elemental analysis and13C NMR. Thirdly, antimicrobial activities of twenty-two novel compounds are researchedby filter paper method. On the foundation of these results, the originalstructure-activity relationship is studied.Lastly, We made a theoretical study on the factors of affecting antibacterialactivity of1,5–benzodiazepine compounds by the Gaussian03quantum chemistrypackage, density functional theory (DFT) at the B3LYP method, in the6-31G basis setlevel. We found that Seven-membered ring is the center of its biological activity andN7atoms are the efficacy of the compound groups.