Synthesis, Characterization And Biological Activities Of Some Novel Oxadiazoles And Imidazo-thiadiazole Derivatives Containing Benzoxazolinon/Benzothiazolinon Moiety

1. Thirty novel target compounds TM-I-6a~6o' and eighteen novel target compounds TM-II-5a~5i', 2,5-disubstituted-1,3,4-oxadiazoles and 2,6-disubstituted -imidazo[2,1-b]-1,3,4-thiadiazoles containing benzoxazolinon/benzothiazolinon moiety, were synthesized by 2-aminophenol or 2-aminothiophenol and urea as starting materials via a series of reactions. Moreover, four novel related intermediate compounds, 5-[(benzoxazolinon/benzothiazolinon-3-yl)methyl]-2-mercapto-1,3,4-oxadiazoles and 2-amino-5-[(benzoxazolinon/benzothiazolinon-3-yl)methyl]-1,3,4-thiadiazoles, were also synthesized. The structures of the intermediates and target compounds were characterized by IR, 1D NMR, 2D NMR and elemental analysis.2. All the newly synthesized target compounds (TM-I-6a~6o' and TM-II-5a~5i') were screened for their anticancer, antiinflammatory and antivirus activity. The assay results of compounds TM-I-6a~6o' showed that some of target compounds possessed weak inhibitory activity to SHP1, and the inhibitory rate of TM-I-6o was higher than others with 36.51±1.67 % at 20μg/mL. This indicated that compounds TM-I-6a~6o' had weak inhibitory activity to prostate cancer. Most compounds displayed weak inhibitory activities to liver cancer, lung cancer and intestinal cancer, and TM-I-6o exhibited higher inhibitory activity to liver cancer (21.65 %), TM-I-6o' exhibited higher inhibitory activity to lung cancer (33.06 %), TM-I-6d showed higher inhibitory activity to intestinal cancer (17.11 %). Some of target compounds also showed weak inhibitory activity to T/B lymphocyte transformation, the inhibitory rate of TM-I-6e' was higher to T lymphocyte transformation(17.75 %), and TM-I-6l' was higher to B lymphocyte transformation (38.35 %). But all the newly synthesized target compounds TM-I-6a~6o' have no inhibitory activity to Cdc25B phosphatase and TNF-α.The assay results of compounds TM-II-5a~5i' showed good effect againstβ2-adrenergic receptor (β2-AR), and the antagonistic effect of TM-II-5c' was higher (70 %). Most compounds displayed weak activities against liver cancer, lung cancer and intestinal cancer, and TM-II-5h exhibited higher inhibitory activity to liver cancer (33.43 %), TM-II-5a exhibited higher inhibitory activity to lung cancer (16.60 %), TM-II-5g showed higher inhibitory activity to intestinal cancer (23.73 %). The target compounds also showed weak inhibitory activity to T/B lymphocyte transformation, the inhibitory rate of TM-II-5i' was higher to T lymphocyte transformation(16.04 %), and TM-II-5a' was higher to B lymphocyte transformation (12.46 %). Some of target compounds also showed weak activity against TNF-α, and TM-II-5h' was higher (18.85 %). But all the newly synthesized target compounds TM-II-5a~5i' 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 target compounds in TM-I-6a~6o' and TM-II-5a~5i' have weak anticancer and antiinflammatory activities. These preliminary results are promising and some of these compounds may be potential candidates for new anticancer (prostate cancer, lung cancer, liver cancer, lung cancer, intestinal cancer) and antiinflammatory agents.