THE SYNTHESIS AND BIOLOGICAL PROPERTIES OF HYDROXY-(ALKOXY)SUBSTITUTED ANILIDES OF 4-HYDROXY-2,2-DIOXO-1H-2λ6,1-BENZOTHIAZINE-3-CARBOXYLIC ACIDS
Continuing the search for new biologically active substances of 2,1-benzothiazines a series of the corresponding anilides of 1-R-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acids has been synthesized by the re- action of alkyl-1-R-4- hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates and the equimolar quantities of hydroxy- and alkoxy-substituted anilines. Their structure has been confirmed by the data of elemental analysis, NMR 1Н 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 non-pedigree 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 the potent analgesics have been found. When administered orally in the dose of 20 mg/kg they several times exceed the reference medi- cines in their analgesic effect and are of interest for the profound research. The study of the effect of the com- pounds synthesized on the urinary function of the kidneys has shown that in this case transition from quinoline analogues to 2,1-benzothiazine ones is accompanied by some decrease in diuretic properties although some compounds increase diuresis at the level of hydrochlorothiazide in a much lower dose.