ADME Study, Molecular Docking, Elucidating the Selectivities and the Mechanism of [4 + 2] Cycloaddition Reaction Between (E)-N ((dimethylamino)methylene)benzothioamide and (S)-3-acryloyl-4-phenyloxazolidin-2-one

The molecular electron density theory (MEDT) was employed to examine the [4 + 2] cycloaddition reaction between (E)-N-((dimethylamino)methylene)benzothioamide (1) and (S)-3-acryloyl-4-phenyloxazolidin-2-one (2) at the B3LYP/6-311++G(d,p) design level. Parr functions and energy studies clearly show that this reaction is regio- and stereoselective, in perfect agreement with experimental results. By evaluating the chemical mechanism in terms of bond evolution theory (BET) and electron localization function (ELF), which divulges a variety of variations in the electron density along the reaction path, a single-step mechanism with highly asynchronous transition states structures was revealed. Additionally, we conducted a docking study on compounds P1, P2, P3, and P4 in the SARS-CoV-2 main protease (6LU7) in comparison to Nirmatrelvir. Our findings provide confirmation that product P4 may serve as a potent antiviral drug.