Trithiazacrown Ethers Containing Piperidine Heterocycle: Synthesis, Structural Characterization and Evaluation Of α-Glucosidase Inhibitory Activity

New derivatives of crown compounds were successfully prepared via multicomponent reactions of a thia-podand, an β-keto ester and ammonium acetate based on modifications of the Petrenko-Kritschenko reaction. The structure of the synthesized compounds was identified by physical-chemical methods of analysis including IR, NMR, HRMS, and single-crystal X-ray diffraction. In addition, an in vitro assay against the α-glucosidase of synthetic compounds was first evaluated and showed positive results. The most active compound exhibited an IC50 value of 5.69±0.27 μM, which is 37 fold more potent than the standard drug of acarbose (IC50 208.42±4.68 μM). Furthermore, prediction of ADMET parameters revealed that almost all synthesized trithiacrown ether derivatives expressed drug-like characteristics. Our results provide useful evidence that crown ether compounds are not only good chelators with metal ions but also scaffolds for developing lead candidates in the treatment of diabetic disease. © 2024 Wiley-VCH GmbH.