In this study, novel derivatives based on 6-methyluracil and condensed uracil were synthesized, namely, 2,4-quinazoline-2,4-dione with ω-(ortho-nitrilebenzylethylamino) alkyl chains at the N atoms of the pyrimidine ring. In this series of synthesized compounds, the polymethylene chains were varied from having tetra- to hexamethylene chains, and secondary NH, tertiary ethylamino, and quaternary ammonium groups were introduced into the chains. The molecular modeling of the compounds indicated that they could function as dual binding site acetylcholinesterase inhibitors, binding to both the peripheral anionic site and active site. The data from in vitro experiments show that the most active compounds exhibit affinity toward acetylcholinesterase within a nanomolar range, with selectivity for acetylcholinesterase over butyrylcholinesterase reaching four orders of magnitude. In vivo biological assays demonstrated the potency of these compounds in the treatment of memory impairment using an animal model of Alzheimer disease.

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Reactions of 1-(ω-bromoalkyl)-3,6-dimethyluracils and 1,3-bis(ω-bromoalkyl)-6-methyluracils with sodium azide gave the corresponding mono-and bis-azides. 1,3-Dipolar cycloaddition of the latter with prop-2-yn-1-ol, hex-1-yne, and dec-1-yne in the presence of copper(I) ions afforded acyclic and macrocyclic uracil derivatives containing 1,4-disubstituted 1,2,3-triazole fragments, which were subjected to quaternization with propyl iodide and methyl p-toluenesulfonate at the 1,2,3-triazole nitrogen atom.

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