Synthesis, Glucosidase Inhibition, and In Silico Modeling Analysis of Highly Fluorinated 2-Imino-1,3-thiazolines in Search of Potent Antidiabetic Agents.

In the present work, 2-imino-1,3-thiazolines featuring highly fluorinated fragments were synthesized through a straightforward cyclization of diversely substituted thioureas with 2-bromo-1-(4-fluorophenyl)ethan-1-one. The target compounds were obtained in good yields, and structures were established by FTIR and 1 H- and 13 C NMR spectroscopic methods. The in vitro biological assay revealed that all the compounds significantly obstruct the α-glucosidase. Compound 6d (3-fluoro- N -(3-(2-fluorophenyl)-4-(4-fluorophenyl)thiazol-2(3 H )-ylidene)benzamide) showed the highest antidiabetic potential with an IC 50 value of 1.47 ± 0.05 μM. In addition, computational analysis revealed the binding energy of -11.1 kcal/mol for 6d which was lower than the positive standard, acarbose (-7.9 kcal/mol). Several intermolecular interactions between the active site residues and 6d highlight the significance of 2-imino-1,3-thiazoline core in attaining the potent efficacy and making these compounds a valuable pharmacophore in drug discovery.