Synthesis, Characterization And Biological Activities Of Some Novel 2, 5-disubstituted-1, 3, 4-oxadiazoles And 3, 6-disubstituted-1, 2, 4-triazolo[3, 4-b]-1, 3, 4-thiadiazoles Containing Benzimidazole Moiety

1:Nine novel target compounds TM-Ⅰ-6a～6i,2,5-disubstituted-1,3,4-oxadiazoles containing benzimidazole moiety, were synthesized by the reaction of o-phenylenediamine with aryloxyacetic acids as the starting materials via multi-step reaction. Moreover, forty-five related intermediate compounds were also synthesized. Intermediate compounds, 2-aryloxymethylbenzimidazoles (2a-2i) were synthesized using a melting method firstly. This method has the advantages of simple operation, short reaction time, higher yield and easy purification. Target compounds TM-Ⅰ-6a～6i were obtained by the reaction of the sulfur alkylation reaction using the technique of the ultrasonic irradiation and phase transfer catalysis firstly. The structures of the intermediates and target compounds were characterized by IR, ID NMR and 2D NMR. The C, H chemical shifts of representative intermediate compounds 4e and 5e were assigned for the first time. The tautomers of intermediate compounds 4e and 5e were firstly determined and the tautomeric ratios of compounds 4 and 5 were first given in polar solvent. The target compounds were tested for their inhibitory activity to cell devision cycle 25B phosphatase and E. coli methionine aminopeptidase-1 (EcMetAP1). The preliminary biological activity results indicated that the compounds TM-Ⅰ-6g～6i had obvious inhibitory activity at 20μg/mL to the cell devision cycle 25B phosphatase and the inhibition rate was 31.75%,99.79% and 77.08% respectively. The inhibition rate of the compound TM-Ⅰ-6h was highest at 5μg/mL, up to 93.64%. But all the target compounds had not shown the inhibitory activity to E. coli methionine aminopeptidase-1 (EcMetAP1).2:Seventeen novel 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles (TM-Ⅱ-4a～4q) were synthesized by the condensation of 4-amino-5-[2-(4-chlorophenoxymethylbenzimidazole)-1-methylene]-3-mercapto-1,2, 4-triazole (3) with various aromatic acids in the presence of phosphorous oxychloride. The new intermediate 3 was synthesized by two-step reaction using 2-(4-chlorophenoxymethyl)-1H-benzimidazole acetic acid hydrazide (1)as raw material. The structures of the intermediate 3 and the target compounds TM-Ⅱ-4a～4q were characterized by IR,1H NMR,2D NMR and elemental analysis. The existence of the tautomer on intermediate compound 3 was proved by spectroscopy technology for the first time. The C, H chemical shifts of 3 were assigned, the coupling constant and the tautomeric ratios were also given out. The target compounds TM-Ⅱ-4a～4q were tested for their biological activities. The preliminary results indicated that the TM-Ⅱ-4a and TM-Ⅱ-4b exhibited higher inhibitory activity to EcMetAPl with the inhibition of 87.26% and 82.62% respectively, the compounds TM-Ⅱ-4f, TM-Ⅱ-4h and TM-Ⅱ-4I showed moderate activity at the concentration of 20μg/mL. The compounds TM-Ⅱ-4a～4q had obvious inhibition to the cell devision cycle 25B phosphatase at 20μg/mL and the compounds TM-Ⅱ-4b, TM-Ⅱ-4g and TM-Ⅱ-4i still had higher inhibition even at 5μg/mL with the inhibition of 98.76%,83.87% and 90.57% respectively. The results of the experiments on the antitumor in vitro showed that target compounds TM-Ⅱ-4a～4q possessed inhibiting activity to liver cancer, lung cancer, intestinal cancer, but lower than positive compound at 5μg/mL. The target compounds TM-Ⅱ-4a～4q had weak inhibitory activity at 4μg/mL to the influenza virus neuraminidase. Moreover, the results of screening for fungicidal, insecticidal, herbicidal and plant growth regulating activities indicated that the target compounds TM-Ⅱ-4a～4q showed no activities.In summary, these results in this paper are very important and significant to research further the synthesis, biological activity, drug designing and development containing condensed heterocyclic moieties.