Abstract
This paper presents the synthesis of some unique bi-heterocyclic hybrid molecules with a thiazole and an oxadiazole ring. The synthesis was initiated by the conversion of ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (1) to the corresponding 2-(2-amino-1,3-thiazol-4-yl)acetohydrazide (2) by the reaction with hydrazine hydrate in methanol. The treatment of the acid hydrazide, 2, with carbon disulfide gave the bi-heterocyclic nucleophile, 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazole-2-thiol (3). Finally, the target compounds, 5a-o, were synthesized by stirring the nucleophile 3 with different electrophiles, 4a-o, in DMF using LiH as a base and an activator. The structures of the newly synthesized molecules were confirmed through spectroscopic techniques, such as IR, EI-MS, H-1-NMR and C-13-NMR. The structure-activity relationship of all these bi-heterocycles was established by evaluating them against four enzymes, namely, acetylcholinesterase, butyrylcholinesterase, urease and alpha-glucosidase, followed by their in silico study. Moreover, their cytotoxicity was also profiled by killing data of brine shrimps at various concentrations.