Synthesis And Preliminary Anti-microbial Activity Of Bis-1,3,4-Oxadiazoles/Thiadiazoles Derivatives

For the studies of antibacterial drugs,1,3,4-oxadiazoles/thiadiazoles derivatives are two important classes of nitrogen-containing heterocyclic compounds due to their superior selectivity,low toxicity and broad-spectrum antimicrobial activities,which have become one of the hot research directions of antibacterial drugs.That 1,3,4-oxadiazoles/thiadiazoles compounds containing heterocyclic ring are superior to not containing heterocyclic ring was found by comparing antimicrobial activities of 1,3,4-oxadiazoles/thiadiazoles derivatives containing different substituent groups.In order to find new compounds with higher antibacterial activities,benzodiimidazole or diimidazopyridine moieties were introduced into 1,3,4-oxadiazole/thiadiazole matrix structures firstly.Four new bis-1,3,4-oxadiazoles/thiadiazoles derivatives were designed and synthesized,namely,5,5'-(1,5-dihydro-benzo[1,2-d:4,5-d']diimidazole-1,5-diyldimethylene)bis(1,3,4-oxadiazoles-2-thiol)? a 5,5'-(1,5-dihydro-benzo[1,2-d:4,5-d']diimidazole-1,5-diyl dimethylene)bis(1,3,4-thiadiazoles-2-thiol)? b,5,5'-(1,5-dihydro-diimidazo[4,5-b:4',5'-e]pyridine-diyldimethylene)bis(1,3,4-oxadiazoles-2-thiol)? a,5,5'-(1,5-dihydro-diimidazo-[4,5-b:4',5'-e]pyridine-diyldimethylene)bis(1,3,4-thiadiazole-2-thiol)?b.1,2,4,5-tetraaminobenzene hydrochloride was synthesized from m-dichlorobenzene via nitration,ammonolysis and reduction reaction;2,3,5,6-tetraaminopyridine hydrochloride were synthesized from 2,6-diaminopyridine via nitration and reduction reaction;The targeted compounds were synthesized via dehydration condensation,nucleophilic substitution,hydrazinolysis,cyclization reaction from the intermediates respectively.All compounds were determined by NMR and ESI-MS and the related spectrums were simply analyzed.The preliminary antimicrobial activity tests of the targeted compounds against E.coli(gram-positive bacteria)and S.aureus(gram-negative bacteria)were determined by double dilution method,and the Log P values of the targeted compounds are calculated via ChemBio3D Ultra 14.0 for investigating the hydrophobic performances of them.The results showed that all targeted compounds had different degrees of antibacterial activity,especially the MIC of 5,5'-(1,5-dihydro-diimidazo[4,5-b:4',5'-e]pyridine-diyldimethylene)bis(1,3,4-thiadiazoles-2-thiol)?b against S.aureus is 0.1 mg/mL,and its log P value is 4.762.