Methyl-substituted anilides of 4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carb-oxylic acid. Synthesis, spectral characteristics and biological properties

I. V. Ukrainets, L. O. Petrushova, S. P. Dzyubenko


The synthesis of a series of methyl-substituted anilides of 4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine- 3-carboxylic acid has been carried out by the reaction of methyl 4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate and the corresponding anilines in boiling xylene. To confirm their structure elemental analysis and NMR 1H spectroscopy have been used. The central component in the mechanism of analgesic properties of the compounds obtained has been studied in non-pedigree rats on the standard model of the thermal tail-flick in parallel and in comparison with the structurally related drugs – Meloxicam and Piroxicam. Furthermore, among the substances studied the potent analgesics have been found. When administered orally in the dose of 20 mg/kg they significantly exceed the reference medicines in their analgesic effect. Being sulfo analogues of quinolone diuretics all the anilides obtained have been subjected to the pharmacological screening to reveal the diuretic properties. Some of these substances stimulate diuresis at the level of Hydrochlorothiazide in much lesser dose. According to the results of biological tests the structural and biological regularities that are important for further research have been revealed. In fact, they appeared to be practically identical for analgesic and diuretic properties: 2 - and 2,4-dimethylsubstituted derivatives exhibit the highest effect, and 3-methyl group inactivates the molecule.


anilides; 2,1-benzothiazines; synthesis; analgesic activity


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Abbreviated key title: Ž. org. farm. hìm.

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