DOS strategy, crystal structure, and in silico evaluation of the anti‐inflammatory activity of hydroxysulfanylazole derivatives.

We developed a DOS approach to the synthesis of hydroxysulfanylazole derivatives (12 examples) using diversification with various N,N‐ and N,O‐binucleophilic reagents of the carbonyl groups of hydroxysulfanyl diketones (6 examples) obtained by the piperidine‐catalyzed thiomethylation reaction involving the С(α)‐Н position of 2,4‐pentanedione with aromatic aldehydes and 2‐mercaptoethanol. X‐ray diffraction analysis was used to determine the structures and crystal packing for three hydroxysulfanylpyrazoles. The calculation of the intermolecular interactions in the crystals (analysis of Hirshfeld surfaces) demonstrated the influence of the substituent nature on the contribution of the H...O/O...H contacts. Using molecular docking studies, justified assumptions were made about the complementarity of the obtained series of compounds to the active sites of COX isoforms. [ABSTRACT FROM AUTHOR]