Comparative conventional and microwave assisted synthesis of heterocyclic oxadiazole analogues having enzymatic inhibition potential

• Published in: Journal of Heterocyclic Chemistry
• Main Author: Javid J.; Aziz-ur-Rehman; Abbasi M.A.; Siddiqui S.Z.; Iqbal J.; Virk N.A.; Rasool S.; Ali H.A.; Ashraf M.; Shahid W.; Hussain S.; Ali Shah S.A.
• Format: Article
• Language: English
• Published: HeteroCorporation 2021
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85091728084&doi=10.1002%2fjhet.4150&partnerID=40&md5=8f90331c9c17764aea946daec74fafed

A comparative microwave assisted and conventional synthetic strategies were applied to synthesize heterocyclic 1,3,4-oxadiazole analogues as active anti-enzymatic agents. Green synthesis of compound 1 was achieved by stirring 4-methoxybenzenesulfonyl chloride (a) and ethyl piperidine-4-carboxylate (b). Compound 1 was converted into respective hydrazide (2) by hydrazine and then into 1,3,4-oxadiazole (3) by CS2 on reflux. The electrophiles, N-alkyl/aralkyl/aryl-2-bromopropanamides (6a–p) were synthesized and converted to N-alkyl/aralkyl/aryl-2-propanamide derivatives (7a–p) by reaction with 3 under green chemistry. Microwave assisted method was found to be effective relative to conventional method. 13C-NMR, 1H-NMR and IR techniques were availed to corroborate structures of synthesized compounds and then subjected to screening against lipoxygenase (LOX), α-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. A number of compounds presented better potential against these enzymes. The most active compounds against LOX and α-glucosidase enzymes were subjected to molecular docking study to explore their interactions with the active sites of the enzymes. © 2020 Wiley Periodicals LLC.