4-Methyl-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylic Acid. Peculiarities of Preparation, Structure, and Biological Properties.

Autor: Ukrainets IV; Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska st., 61002 Kharkiv, Ukraine. igor.v.ukrainets@gmail.com., Hamza GM; Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska st., 61002 Kharkiv, Ukraine. annahamza@ukr.net., Burian AA; Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska st., 61002 Kharkiv, Ukraine. anna_chem@ukr.net., Shishkina SV; STC 'Institute for Single Crystals', National Academy of Sciences of Ukraine, 60 Nauki ave., 61001 Kharkiv, Ukraine. sveta@xray.isc.kharkov.com.; Department of Inorganic Chemistry, V. N. Karazin Kharkiv National University, 4 Svobody sq., 61077 Kharkiv, Ukraine. sveta@xray.isc.kharkov.com., Voloshchuk NI; Department of Pharmacology, N. I. Pirogov Vinnitsa National Medical University, 56 Pirogov st., 21018 Vinnitsa, Ukraine. voloshchuknatali@gmail.com., Malchenko OV; Department of Pharmacology, N. I. Pirogov Vinnitsa National Medical University, 56 Pirogov st., 21018 Vinnitsa, Ukraine. malchenko2576@gmail.com.
Jazyk: angličtina
Zdroj: Scientia pharmaceutica [Sci Pharm] 2018 Mar 08; Vol. 86 (1). Date of Electronic Publication: 2018 Mar 08.
DOI: 10.3390/scipharm86010009
Abstrakt: In order to determine the regularities of the structure-analgesic activity relationship, the peculiarities of obtaining, the spatial structure, and biological properties of 4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylic acid and some of its derivatives have been studied. Using nuclear magnetic resonance (NMR) spectroscopy and X-ray diffraction analysis, it has been proven that varying the reaction conditions using alkaline hydrolysis of methyl 4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylate makes it possible to successfully synthesize a monohydrate of the target acid, its sodium salt, or 4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine. The derivatographic study of the thermal stability of 4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylic acid monohydrate has been carried out; based on this study, the optimal conditions completely eliminating the possibility of unwanted decomposition have been proposed for obtaining its anhydrous form. It has been shown that 4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine is easily formed during the decarboxylation of not only 4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylic acid, but also its sodium salt, which is capable of losing СО₂ both in rather soft conditions of boiling in an aqueous solution, and in more rigid conditions of dry heating. The NMR spectra of the compounds synthesized are given; their spatial structure is discussed. To study the biological properties of 4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylic acid and its sodium salt, the experimental model of inflammation caused by subplantar introduction of the carrageenan solution in one of the hind limbs of white rats was used. The anti-inflammatory activity and analgesic effect were assessed by the degree of edema reduction and the ability to affect the pain response compared to the animals of control groups. According to the results of the tests performed, it has been found that after intraperitoneal injection, the substances synthesized demonstrate a moderate anti-inflammatory action and simultaneously increase the pain threshold of the experimental animals very effectively, exceeding Lornoxicam and Diclofenac in a similar dose by their analgesic activity.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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