The synthesis, anti-inflammatory, analgesic and antimicrobial activities of ethyl 2-amino-4-alkyl-4,6-dihydropyrano[3,2c][2,1]benzothiazin-3-carboxylate 5,5-dioxides and triethylammonium 3-[(4-hydroxy-1-ethyl-2,2-dioxido-1h-2,1-benzothiazin-3-yl)alkyl]-1-

D. A. Lega, N. I. Filimonova, I. A. Zupanets, S. K. Shebeko, V. P. Chernykh, L. A. Shemchuk

Abstract


The search for new groups of anti-inflammatory and analgesic drugs is a topical issue of the current medicinal chemistry. It is caused by numerous diseases that are accompanied by pain and inflammation, as well as by imperfection of the existing drugs aimed to provide treatment of these pathological conditions. Derivatives of 1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide are promising chemicals to search and develop drugs with the pharmacological properties required. This heterocyclic system is structurally close to 2H-1,2-benzothiazin-4-one 1,1-dioxide, which is the core of the famous non-steroidal anti-inflammatory drugs related to the “oxicam” group. Moreover, derivatives of 1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide are also considered to be promising structures for searching effective antimicrobial substances among them. The present article is devoted to the synthesis of new derivatives of 1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide, namely ethyl 2-amino-4-alkyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazin-3-carboxylate 5,5-dioxides and triethylammonium 3-[(4-hydroxy-1-ethyl-2,2-dioxido-1H-2,1-benzothiazin-3-yl)alkyl]-1-ethyl-1H-2,1-benzothiazin-5-olat 2,2-dioxides. Condensed 2-amino-4-alkyl-4H-pyran-3-carboxylates were synthesized via the three-component one-pot interaction of 1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide with ethyl cyanoacetate and aliphatic aldehydes. The abovementioned triethylammonium salts were obtained by the two component interaction of 1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide with aliphatic aldehydes in the presence of the equimolar amount of triethylamine. The study of the anti-inflammatory and analgesic activity has demonstrated high prospects of new effective drugs when searching among two classes of the compounds synthesized. The screening of the antimicrobial activity has shown that the compounds synthesized are the most active against the fungal strain of C. albicans.


Keywords


2,1-benzothiazine 2,2-dioxide; aliphatic aldehydes; ethyl cyanoacetate; 2-amino-4H-pyran;triethylammonium; enolate; antimicrobial activity; anti-inflammatory activity; analgesic activity

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DOI: https://doi.org/10.24959/ophcj.16.900

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

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