SYNTHESIS, CHARACTERIZATION, AND BIOLOGICAL EVALUATION OF SOME NOVEL GLYCOSYL 1,3,4-THIADIAZOLE DERIVATIVES AS ACETYLCHOLINESTERASE INHIBITORS

The corresponding 4-substituted glycosyl thiosemicarbazide derivatives (6a-61) were obtained by the reaction of glycosyl isothiocyanate 4 with various hydrazides. Further cyclization with the system of p-TsCl/TEA led to the formation of N-glycosyl-5-substituted 1,3,4-thiadiazole-2-amine (7a-71). Subsequent removal of the acetyl groups were conducted using the system of NaOMe/MeOH. The chemical structures of all new products were confirmed by JR. H-1 NMR and ESI-HRMS. The acetylcholinesterase (AChE) inhibitory activities of those compounds were tested by Ellman's method. Among them, the compound 8h possessed the best acetylcholinesterase-inhibition activity with IC50 of 18.38 +/- 0.89 mu M.