Synthesis and the biological activity of 4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazin-3-carboxylic acids trifluoromethyl-substituted anilides

L. A. Petrushova, I. V. Ukrainets, S. P. Dzyubenko, L. A. Grinevich


In order to reveal the regularities of the “structure – biological activity” relationship by interaction of esters of 1-R-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazin-3-carboxylic acids and trifluoromethyl substituted anilines in boiling xylene with good yields and purity the corresponding N-aryl-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazin-3-carboxamides have been synthesized. The structure of the compounds obtained has been confirmed by the data of elemental analysis and NMR 1Hspectroscopy. It has been shown that the presence of trifluoromethyl groups having the powerful electron-withdrawing properties affects the position of signals of the aniline moiety protons: comparing to the spectra of the model methyl derivatives they undergo a significant paramagnetic shift. According to the results of the pharmacological studies conducted it has been found that the replacement of methyl groups in the anilide moiety of 1-R-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazin-3-carboxamides to trifluoromethyl has a different effect on their analgesic activity, which can remain at the original level, be completely lost or significantly increase. However, N-aryl-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazin-3-carboxamides definitely lose the ability to influence in any way on the excretory renal function after this chemical modification.


anilides; 2,1-benzothiazines; synthesis; trifluoromethyl group; analgesic activity; diuretic properties

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