To find novel butyrylcholinesterase inhibitors, three novel 2-phenylthiazole derivatives were synthesised. The synthesised compounds were characterised by NMR and single-crystal X-ray diffraction analysis. Hirshfeld surface analysis and two-dimensional fingerprint plots of the compounds were used as a theoretical approach to assess the driving force for crystal structure formation via the intermolecular interactions in the crystal lattices of the synthesised compounds. Among the three compounds, N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro- 1H-pyrazol-4-yl)-2-(4-methoxyphenyl)thiazole-4-carboxamide showed the best butyrylcholinesterase-inhibition activity with an IC50 value of 75.12 μM. A docking study demonstrated that this compound interacts with the peripheral anionic site of butyrylcholinesterase.

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Two new similar zinc(II) complexes, [ZnCl 2 L1 2 ] and [ZnCl 2 L2 2 ] derived from the 2-amino-1,3,4-thiadiazole derivatives, were prepared and structurally characterized by X-ray diffraction. The Zn atom in each complex has a tetrahedral coordination and is coordinated by two N atoms of the ligands and two Cl atoms. The urease inhibitory activities of the complexes and the ligands were evaluated.

Three novel 5-benzyl-1,3,4-thiadiazole derivatives were synthesised starting from phenylacetic acid derivatives. These compounds were characterised by NMR, HRMS and single-crystal X-ray diffraction analysis. 2-Pyrrolidyl-5-[2-(4-bromophenyl)methyl]-1,3,4-thiadiazole showed moderate acetylcholinesterase-inhibition activity with a 50% inhibitory concentration value of 33.16 μM. 2-Pyrrolidyl-5-[2-(4-bromophenyl)methyl]-1,3,4-thiadiazole and acetylcholinesterase docking was demonstrated using the Molecular Operating Environment program.

A new series of 2‐phenylthiazole derivatives were designed, synthesized, characterized and evaluated as potential candidates to treat Alzheimer's disease. Most of these compounds exhibited significant acetylcholinesterase inhibitory activities. Among them, compound ethyl 2‐[4‐(4‐{[2‐(pyrrolidin‐1‐yl)ethyl]amino}butoxy)phenyl]thiazole‐4‐carboxylate (5 b–8) exhibited the best acetylcholinesterase inhibition activity with IC50 values of 4.8 μM. Moreover, the compound ethyl 2‐(4‐{[5‐(cyclohexylamino)pentyl]oxy}phenyl)thiazole‐4‐carboxylate (5 c–6) had the best butyrylcholinesterase inhibitory activity, with an IC50 value of 0.16 μM. The docking studies demonstrated that compound 5 b–8 could interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of acetylcholinesterase. Compound 5 b–8 also showed biometal chelating abilities. These attributes highlight 5 b–8 as a promising candidate for further studies directed to the development of novel drugs against Alzheimer's disease.