Acetylcholinesterase (AChE) is the enzyme that catalyzes the hydrolysis of the neurotransmitter acetylcholine (ACh) into acetic acid and choline, a crucial mechanism for regulation of neurotransmission at synapses in all nervous systems. According to the cholinergic hypothesis, depleted levels of ACh are associated with Alzheimer's disease. As part of a program aimed at preparing new bioactive heterocycles with kinase and AChE inhibition properties, we designed and synthesized a series of (Z)-2-arylidene- and 2-aminomethylene derivatives of thiazolo[3,2-a]pyrimidine by a convenient multicomponent method. The products were fully characterized by 1D- and 2D-NMR, high resolution ESI-MS/MS and single crystal X-ray diffraction analysis, which indicated a consistent Z configuration at the arylidene and amino methylene double bond. Additionally, molecular docking simulations of the series of 2-arylidene/aminomethylene-thiazolo[3,2-a]pyrimidine derivatives to human AChE (PDB ID: 4m0f, chain A) were conducted to investigate the binding mode of those compounds in comparison to Territrem B, used as positive control. The results indicate that some of the test compounds have binding energies to AChE that are comparable, or better, than the positive control, Territrem B. Biological activity studies are underway to assess the activities of the new compounds [1-4].
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