A novel five‐step synthetic route to 1,3,4‐oxadiazole derivatives with potent α‐glucosidase inhibitory potential and their in silico studies

A series of new N-aryl/aralkyl derivatives of 2-methyl-2-{5-(4-chlorophenyl)-1,3,4-oxadiazole-2ylthiol}acetamide were synthesized by successive conversions of 4-chlorobenzoic acid (a) into ethyl 4-chlorobenzoate (1), 4-chlorobenzoylhydrazide (2) and 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-thiol (3), respectively. The required array of compounds (6a-n) was obtained by the reaction of 1,3,4-oxadiazole (3) with various electrophiles (5a-n) in the presence of DMF (N,N-dimethylformamide) and sodium hydroxide at room temperature. The structural determination of these compounds was done by infrared, (1) H-NMR (nuclear magnetic resonance), (13) C-NMR, electron ionization mass spectrometry, and high-resolution electron ionization mass spectrometry analyses. All compounds were evaluated for their alpha-glucosidase inhibitory potential. Compounds 6a, 6c-e, 6g, and 6i were found to be promising inhibitors of alpha-glucosidase with IC50 values of 81.72 +/- 1.18, 52.73 +/- 1.16, 62.62 +/- 1.15, 56.34 +/- 1.17, 86.35 +/- 1.17, 52.63 +/- 1.16 microM, respectively. Molecular modeling and ADME (absorption, distribution, metabolism, excretion) predictions supported the findings. The current synthesized library of compounds was achieved by utilizing very common raw materials in such a way that the synthesized compounds may prove to be promising drug leads.