Synthesis, Crystal Structure and Biological Evaluation of Novel 2-Phenylthiazole Derivatives as Multi-Targeting Agents to Treat Alzheimer's Disease

Three novel 2-phenylthiazole derivatives were synthesised and characterised by spectroscopic techniques. The structure of the synthesised compounds was unambiguously confirmed by a single-crystal X-ray diffraction analysis of ethyl 2-(4-{[5-(4-benzylpiperidin-1-yl)pentyl]oxy}phenyl)thiazole-4-carboxylate. All of the compounds presented good cholinesterase-inhibition activities and ethyl 2-(4-{[5-(4-benzylpiperidin-1-yl)pentyl]oxy}phenyl)thiazole-4-carboxylate showed the best acetylcholinesterase-inhibition and butyrylcholinesterase-inhibition abilities with IC50 values of 5.19 μM and 5.83 μM. The docking study demonstrated that it could interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of acetylcholinesterase and could chelate with metal ions like Cu2+ and Zn2+.