Design, Synthesis And Antimicrobial Activities Of New N-sulfonyl Azoles And Sulfonamides

Sulfonamide compounds exhibit extensive biological activities and as medicinal agents are becoming more and more active. Based on the current situation of sulfonamides as antimicrobial agents, this thesis designed and synthesized a series of N-sulfonyl azoles and novel sulfonamides, and evaluated their antimicrobial activities. It was also discussed the structure-activity relationships. The main contents are as follows:(1) A series of N-sulfonyl azole compounds were designed and synthesized starting from substituted benzyl chlorides or bromides. The intermediates 42a-g were obtained by the reaction of substituted benzyl halides with sodium sulfite, and the chlorination of compounds 42a-g with POCl3 afforded sulfonyl chlorides 43a-g, then the N-alkylation of the later with a series of azoles including 1,2,4-triazole, imidazole,4-nitroimidazole, 2-methyl-5-nitroimidazole to give the desired N-sulfonyl azoles 48-49.(2) A series of novel sulfonamides 44-46 were prepared by the reaction of substituted benzyl sulfochlorides respectively with a series of hydrazine or amine compounds.(3) The reaction conditions, including the reaction of substituted benzyl halides with Na2SO3 for the preparation of sodium salt of (halogeno-)methanesulfonic acid 42a-g, and chlorination of compounds 42a-g with POCl3 were investigated. The optimum reaction condition for sulfonylation and chlorination were obtained.(4) The synthesized compounds were confirmed by UV-Vis, IR,1H-NMR and MS spectra. (5) The antifungal activities in vitro showed that novel sulfonamides and N-sulfonyl azoles containing 1,2,4-triazole, imidazole,4-nitroimidazole and 2-methyl-5-nirtoimidazole moiety displayed good activities against A. fumifatus, and they gave gave stronger biological activities than antifungal Fluconazole in clinic. These compounds as potential drugs against A. fumifatus are necessary to further research and develop. No obvious activities against C. albicans, C. mycoderma were observed.(6) The antibacterial assays in vitro showed that most compounds gave significant antibacterial activies. All the compounds possessed significant antibacterial activity against P.aerufinosa and B.subtilis. Compound 44f showed more effective against B.subtilis, and it MIC value 192μM, Compound 49u exhibited remarkable antibacterial activity against P.aerufinosa with the lowest MIC values 201μM. All these compounds displayed weak activities against E. coli, S. aureus, S. dysenteriae, E. typhosa, MRSA. However, compounds 44d and 44g displayed almost same activities as Chloramphenicol against E. coli and E. typhosa, their MIC values being both 54μM. Compound 49u showed the same activity as Chloramphenicol against S. aureus.The structure-activity relationships showed that the structure of azole rings, the type of substitutents, the number and location of the halogen atom in the aryl ring and the length of alkyl chain in the new compounds are responsible for the variation of the antibacterial and antifungal activities against tested strains. Moreover, the water-solubility of the tested compounds has effect on their biological atcivities to some extent.In this thesis, sixty-three target compounds including six N-sulfonyl triazoles, seven N-sulfonyl imidazoles, seven N-sulfonyl nitroimidazoles, seven N-sulfonyl 2-methyl-5-nitroimidazoles, thirty-nine novel sulfamides were synthesized. Among them, fifty compounds are new.