The traditional crystal packing study based on the analysis of geometrical characteristics of intermolecular interactions is found to be not informative enough. The application of quantum-chemical calculations for the evaluation of pairwise interaction energies between molecules allows to get much more information about supramolecular architecture. The staking interactions between π-systems of neighboring molecules form the building unit of the crystal packing in the absence of any strong interactions as well as in the presence of the N–H…O classical hydrogen bond. Unexpectedly the hydrogen bonds play the secondary role in the crystal packing formation as compared to stacking. Analysis of the total interaction energy of the basic molecule with all the molecules of its first coordination sphere and the pairwise interaction energies allows to evaluate the extent of crystal isotropy from point of view of interaction energies.

In continuing the search for new analgesics among derivatives of 2,1-benzothiazines, a series of corresponding toluidides and xylidides of 4-hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylic acid has been synthesized by the reaction of ethyl 4-hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylate with equimolar amounts of mono- and dimethyl-substituted anilides in boiling dry xylene. Their structure has been confirmed by the data of elemental analysis, nuclear magnetic resonance (NMR) spectroscopy (¹Н and ¹³С), as well as mass spectrometry. All compounds obtained were subjected to pharmacological screening to identify their analgesic properties. Testing was carried out in male rats using the standard model of the thermal tail-flick (tail immersion test) in parallel and in comparison with the structurally related drugs meloxicam and piroxicam. Among the substances studied, highly active oral painkillers have been found; they exceed the analgesic effect of the reference drugs using the same dose. Interesting structural and biological regularities have been described; they will be useful in further research on creating promising new analgesics based on 4-hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxamides.