Synthesis, X-Ray Diffraction, Spectroscopic Characterization, Hirshfeld Surface Analysis, Molecular Docking Studies, and DFT Calculation of New Pyrazolone Derivatives

Pyrazolones derivatives are known for their pharmaceutical and therapeutic activities. In this regard, some new pyrazolone derivatives have been synthesized using cyclocondensation, nucleophilic substitution, and alkylation reactions. Their corresponding structures were elucidated using X-ray diffraction and NMR spectroscopic techniques. The experimental spectral data were compared with the predicted ones obtained at the B3LYP/6-311++G(d,p) level of theory. Geometrical parameters and chemical shifts are relatively well reproduced with correlation coefficients higher than 90%. The intercontacts in crystal units were investigated by the analysis of their corresponding Hirshfeld surfaces and fingerprint maps, which reveal that the major contacts are found for H…H intercontacts. Finally, the inhibition efficiency of the novel pyrazolone derivatives as SARS-CoV-2 Mpro is estimated by determining their binding affinities into the binding site of SARS-CoV-2 M^pro. The docking results reveal that the current pyrazolone derivatives may act as potent inhibitors of SARS-CoV-2 M^pro and that their inhibition efficiency may be strongly influenced by the substituted functional groups of pyrazolone moiety.