The Studies On Synthesis,antimicrobial Activity And Structure-activity Relationship Of 3-aroyl-1,5-benzodiazepine Compounds

Benzodiazepines are a pharmacologically important class of chemical compounds with various biological activities,various members of the benzodiazepine family are used as commercially available anxiolytic,antipsychotic,or antiepileptic drugs.Such as clozapine and olanzapine,which are effective drugs for the treatment of schizophrenia and have already been used in clinical treatment.In recent years,many studies have reported that 1,5-benzodiazepines also have the properties of inhibition of bacteria and fungi.So the design and synthesis of 1,5-benzodiazepines are attracting more and more attention.Our group has been devoted to the design and synthesis of novel1,5-benzodiazepine compounds with high bioactivity.Successfully synthesized series of 1,5-benzodiazepines with high antibacterial activity by introducing active groups on heterocyclic rings such as ester groups,acyl groups,carboxyl groups,and so on.Studies have showed that the introduction of ester groups or acyl groups can effectively enhance the antibacterial activity of the compounds.So we designed and synthesized series of 3-ester-1,5-benzodiazepines.In the course of our research on the development of efficient methods for synthesis of 1,5-benzodiazepines with high bioactivity,we designed a new synthetic route and successfully synthesized series of3-aroyl-1,5-benzodiazepine.Additionally,the antimicrobial activity of the compounds was also tested and the structure-activity relationship of these compounds was summarized.The main work of this paper is as follows:1.A simple protocol for the synthesis of 3-ester-1,5-benzodiazepines is achieved viacatalyst-freecondensationofo-phenylenediamineorsubstituted ortho-phenylenediamine,dicarbonyl ester and 4-Hydroxybenzaldehyde as raw materials in ethanol at ambient temperature,the method is applicable to both glyoxylic acid and propionaldehyde in good yields.Seven compounds were characterized by ¹H NMR,¹³C NMR,IR,MS and elemental analysis confirmed to be structurally correct.The possible reaction mechanism was also proposed.The antibacterial activity results showed that the compounds showed selectivity to the tested strains,that is,only showed a certain inhibitory effect on antifungal activity?C.neoformans,C.neoformans clinical isolates and C.albicans?.And its structure-activity relationship was studied.2.An environmentally benign method has been developed for the synthesis of2-substituted-3-Aroyl-1,5-benzodiazepines via the reaction of N,N-dimethyl formamide dimethyl acetal,aromatic ketone,o-phenylenediamine or substituted ortho-phenylenediamine and a series of aldehydes under catalyst-free conditions.The key benefits of this new method include high yields,the use of green solvent,short reaction times,the reaction of raw materials cheap and readily available.Twenty-two compounds were characterized by ¹H NMR,¹³C NMR,IR,MS and elemental analysis confirmed to be structurally correct.A possible mechanism for the formation of products was also proposed.We also assayed for their antibacterial activity and the results show selectivity to the tested strains,that is,only showed a certain inhibitory effect on C.albicans.3.The structure-activity relationship of different groups and antibacterial activity of the compounds was analyzed by using of DFT method on B3LYP/6-31G level which obtain the related structural parameters.