Structure–activity relationship and in silico study of unique bi-heterocycles: 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazole-2-thiol derivatives

• Published in: Journal of the Serbian Chemical Society
• Main Author: Abbasi M.A.; Ramzan M.S.; Aziz-Ur-Rehman; Siddiqui S.Z.; Hassan M.; Raza H.; Shah S.A.A.; Mirza B.; Seo S.-Y.
• Format: Article
• Language: English
• Published: Serbian Chemical Society 2019
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85071284618&doi=10.2298%2fJSC180203019A&partnerID=40&md5=579ade91e32eb71c0f380e66e793bf5f

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, 1H-NMR and 13C-NMR. The structure––activity relationship of all these bi-heterocycles was established by evaluating them against four enzymes, namely, acetylcholinesterase, butyrylcholinesterase, urease and α-glucosidase, followed by their in silico study. Moreover, their cytotoxicity was also profiled by killing data of brine shrimps at various concentrations. © 2019 Serbian Chemical Society. All rights reserved.