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1,3,4-Oxadiazole moiety is a crucial pharmacophore in many biologically active compounds. In a typical synthesis, probenecid was subjected to a sequence of reactions to obtain a 1,3,4-oxadiazole–phthalimide hybrid (PESMP) in high yields. The NMR (1H and 13C) spectroscopic analysis initially confirmed the structure of PESMP. Further spectral aspects were validated based on a single-crystal XRD analysis. Experimental findings were confirmed afterwards by executing a Hirshfeld surface (HS) analysis and quantum mechanical computations. The HS analysis showed the role of the π⋯π stacking interactions in PESMP. PESMP was found to have a high stability and lower reactivity in terms of global reactivity parameters. α-Amylase inhibition studies revealed that the PESMP was a good inhibitor of α-amylase with an s value of 10.60 ± 0.16 μg/mL compared with that of standard acarbose (IC50 = 8.80 ± 0.21 μg/mL). Molecular docking was also utilized to reveal the binding pose and features of PESMP against the α-amylase enzyme. Via docking computations, the high potency of PESMP and acarbose towards the α-amylase enzyme was unveiled and confirmed by docking scores of −7.4 and −9.4 kcal/mol, respectively. These findings shine a new light on the potential of PESMP compounds as α-amylase inhibitors. [ABSTRACT FROM AUTHOR]

New S-alkyl phthalimide 5a–f and S-benzyl 6a–d analogs of 5-(2-phenylquinolin-4-yl)-1,3,4-oxadiazole-2-thiol (4) were prepared by reacting 4 with N-bromoalkylphthalimide and CF3-substituted benzyl bromides in excellent yields. Spectroscopic techniques were employed to elucidate the structures of the synthesized molecules. The inhibition activity of newly synthesized molecules toward MAO-A, MAO-B, and AChE enzymes, was also assessed. All these compounds showed activity in the submicromolar range against all enzymes. Compounds 5a and 5f were found to be the most potent compounds against MAO-A (IC50 = 0.91 ± 0.15 nM) and MAO-B (IC50 = 0.84 ± 0.06 nM), while compound 5c showed the most efficient acetylcholinesterase inhibition (IC50 = 1.02± 0.65 μM). Docking predictions disclosed the docking poses of the synthesized molecules with all enzymes and demonstrated the outstanding potency of compounds 5a, 5f, and 5c (docking scores = −11.6, −15.3, and −14.0 kcal/mol against MAO-A, MAO-B, and AChE, respectively). These newly synthesized analogs act as up-and-coming candidates for the creation of safer curative use against Alzheimer's illness. [ABSTRACT FROM AUTHOR]