Synthesis Characterization And Biological Activity Of Containing 1,2,4-triazole And 1,3,4-oxadiazole Bis-heterocyclic Derivatives

In recent years,enhanced and mutation pathogen resistance,resulting in the inactivation of existing drugs,in order to find a broad spectrum and low toxicity antibacterial agent.5-?4-substituted benzyl?amino-5-methyl-4H-1,2,4-triazole-3-sulfanyl)-1,3,4-oxadiazole-2-thiol and 5-?4-?2-hydroxy-5-substituted benzyl?amino-5-methyl-4H-1,2,4-triazole-3-sulfanyl?-1,3,4-oxadiazole-2-thiol,13compounds were reasonably designed and synthesized according to the superposition principle of bioactive substructures by the combination of"ortho-hydroxyphenyl,""1,2,4-triazole,""1,3,4-oxadiazole"and"Schiff base".The structures of thirteen new products were characterized by means of IR,¹H NMR,¹³C NMR and HRMS techniques.Compound 5-?4-amino-5-methyl-4H-1,2,4-triazole-3-sulfanyl?-1,3,4-oxadiazole-2-thiol by the reactions of cyclization,substitution,hydrazinolysis and ring-closure starting from hydrazine hydrate and carbon disulfide.Then compounds?6a-6m?were obtained by a refluence of compound 5 with substituted aromatic aldehydes.This paper discusses the influence of reaction temperature,medium and the amount of alkali on the yield of the compounds 3and 5.The best process was screened out,and the target compound?6a-6m?was finally obtained by the total yield of 11%-16%.Multi-target data with E.coli indicated that the target compound binding free energy score on the E.coli FabI target was closest to that of the reference triclosan,indicating that these compounds have the highest binding capacity for ecFabI and may be a class of targets for ecFabI Inhibitor?The binding mode action are consistent with triclosan.In particular,compounds 6g and 6k have the most stable binding conformation.The preliminary bioassay was carried out based on U.S.National Clinical Laboratory Standards Committee?NCCLS?Minimal Inhibitory Concentration regulation.The in vitro antimicrobial activity data show that all target compounds possess efficient antibacterial activities against four bacterial strains.Compound 6g and 6k show strong antibacterial activity and great development potential.