Synthesis and analgesic activity of N-(benzothiazol-2-yl)-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides

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

Abstract


Continuing the search of new effective analgesics with improved properties the corresponding N-(benzothiazol- 2-yl)-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides have been synthesized in boiling xylene by the interaction of methyl ester of 4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acid with 2-aminobenzothiazoles. The structure of the substances synthesized has been confirmed by the data of elemental analysis, NMR 1H spectroscopy and mass-spectrometry. The peculiarities of the aromatic region interpretation in NMR 1H spectra of the structural class studied have been discussed. It has been shown that in ionization by electron impact the primary fragmentation of molecular ions of N-(benzothiazol-2-yl)-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides surprisingly occurs in a variety of ways. It starts with SO2 release in amide unsubstituted in the benzothiazole moiety of the molecule and its 6-methyl analogue, while for halogenated products the primary breaking of the terminal carbamide bond or the loss of halogen are characteristic. According to the results of the pharmacological research performed on the model of tail-flick procedure, N-(6-bromobenzothiazol-2-yl)-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide has been determined; it exhibits the analgesic effect at the level of Meloxicam.


Keywords


2-aminobenzothiazoles; 2,1-benzothiazines; hetarylamides; synthesis; analgesic activity

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DOI: https://doi.org/10.24959/ophcj.14.801

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

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)