Synthesis, Characterization And Biological Activities Of Some Novel Oxadiazoles And Triazolo-thiadiazines Derivatives Containing Benzimidazole Moiety

1. Twenty novel 2,5-disubstituted-1,3,4-oxadiazoles (TM-I-8a~8r and TM-I-9a~9b) and nine novel [1,2,4]triazolo[3,4-b]-1,3,4-thiadiazines (TM-II-4a~4i) containing benzimidazole moiety were synthesized by o-phenylenediamine and aryloxyacetic acids as the starting materials via multi-step reactions. Moreover, seven novel related intermediate compounds were also synthesized. The structures of the intermediates and target compoundswere characterized by IR, 1D NMR, 2D NMR, MS and elemental analysis.2. The newly synthesized target compounds (TM-I-8a~8r and TM-II-4a~4i) were screened for their antidiabetic, anticancer, antiinflammatory and antivirus activity.The assay results of compounds TM-I-8a~8r showed that some of them showed a potent activity against PTP1B for potential antidiabetic effect, and the inhibitory rate of TM-I-8o~8q were highest (90%~95%) at 20μg/mL, TM-I-8g and TM-I-8r were higher (73%~79%), TM-I-8m~8n were moderate (42%~43%). The target compounds TM-I-8o and TM-I-8q displayed higher activities against Cdc25B phosphatase at 20μg/mL with the inhibitory rate of 86% and 96%. Most compounds displayed weak inhibitory activities to liver cancer, lung cancer and intestinal cancer at 5μg/mL, and TM-I-8f exhibited higher inhibitory activity to lung cancer (37.23 %), TM-I-8b exhibited higher inhibitory activity to liver cancer (22.26 %), TM-I-8o showed higher inhibitory activity to intestinal cancer (19.37 %). The target compounds also showed weak inhibitory activity to T/B lymphocyte transformation at 5μg/mL, the inhibitory rate of TM-I-8m was higher to T lymphocyte transformation (19.41 %), and TM-I-8c was higher to B lymphocyte transformation (15.31 %). But all the newly synthesized target compounds TM-I-8a~8r have no inhibitory activity to TNF-α.The assay results of compounds TM-II-4a~4i showed that TM-II-4d~4f and TM-II-4h~4i displayed a potent activity against Cdc25B phosphatase at 20μg/mL with the inhibitory rate of 82.6%~95.1%, and the TM-II-4d was highest up to 95.1%, the TM-II-4g was moderate (40.4%). Most compounds displayed weak activities against liver cancer, lung cancer and intestinal cancer, and TM-II-4h exhibited higher inhibitory activity to liver cancer (35.36 %), TM-II-4a exhibited higher inhibitory activity to lung cancer (27.76 %), TM-II-4g showed higher inhibitory activity to intestinal cancer (26.21 %). But all the newly synthesized target compounds TM-II-4a~4i have no inhibitory activity to C-C chemokine receptor 2 (CCR2) and influenza virus neuraminidase.3. In conclusion, the assay results of biological activity show that some of target compounds (TM-I-8a~8r and TM-II-4a~4i) have potent anticancer activity, some of target compounds TM-I-8a~8r possess potent antidiabetic activity, all the newly synthesized target compounds (TM-I-8a~8r and TM-II-4a~4i) exhibited weak antiinflammatory activity. These preliminary results are promising and some of these compounds may be potential candidates for new antidiabetic, anticancer and antiinflammatory agents.