Green Synthesis, Molecular Modelling, and ADME Evaluation of Functionalized Pyridine Derivatives as Potential SARS-CoV-2 Inhibitors

Abstract A series of highly functionalized pyridine derivatives were synthesized using an efficient, eco-friendly, and rapid microwave-assisted one-pot, four-component reaction involving aldehydes, ketones, malononitrile, and ammonium acetate in ethanol, catalysed by uranyl nitrate hexahydrate. The reaction proceeds under mild conditions and utilizes readily available starting materials, offering a sustainable route to structurally diverse pyridine scaffolds. The structures of the synthesized compounds were confirmed through 1H NMR, 13C NMR, IR, and mass spectrometry analyses. Molecular docking studies were conducted against key SARS-CoV-2 target proteins to assess their antiviral potential. Notably, compound 4j demonstrated favourable binding affinity along with promising in silico ADMET properties, including high solubility, good intestinal absorption, and minimal predicted toxicity. These findings suggest that the synthesized pyridine scaffolds hold potential as lead candidates for further antiviral drug development.