A series of multifunctional pyridine‐based derivatives was synthesized using optimized methodologies. These include N ‐, S ‐, and O ‐propargyl‐substituted compounds, achieved through tailored reaction conditions to exploit the inherent nucleophilicity of each functional group. C‐Alkylation with acetylacetone, mediated by mercury(II) acetate, produced C–H functionalized products: linear structures from N ‐ and O ‐propargyl substrates, and fused tricyclic thieno2,3‐ b :4,5‐ b’ dipyridine scaffolds from S‐propargyl analogs. All compounds were structurally confirmed by nuclear magnetic resonance (NMR), infrared spectroscopy, mass spectrometry, and single‐crystal x‐ray diffraction. Selected derivatives demonstrated significant anticonvulsant activity in both mice and rats using the pentylenetetrazole (PTZ)‐induced seizure model, with efficacy surpassing that of ethosuximide. Additionally, these compounds showed anxiolytic‐like effects in the elevated plus maze and increased exploratory behavior in the open‐field test. Monoamine oxidase (MAO) inhibition was also observed in rat brain homogenates, suggesting potential psychotropic activity. Overall, this study presents a versatile synthetic platform for the development of pyridine‐based compounds with combined anticonvulsant and neuropsychiatric properties.
Dashyan et al. (Thu,) studied this question.