4-Methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic Acid. Peculiarities of Preparation, Structure, and Biological Properties
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-1H-2λ6,1-benzothiazine-3-carboxylic acid and some of its derivatives have been studied. Using nuclear magnet...
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MDPI AG
2018-03-01
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| Series: | Scientia Pharmaceutica |
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| Online Access: | http://www.mdpi.com/2218-0532/86/1/9 |
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| author | Igor V. Ukrainets Ganna M. Hamza Anna A. Burian Svitlana V. Shishkina Natali I. Voloshchuk Oxana V. Malchenko |
| author_facet | Igor V. Ukrainets Ganna M. Hamza Anna A. Burian Svitlana V. Shishkina Natali I. Voloshchuk Oxana V. Malchenko |
| author_sort | Igor V. Ukrainets |
| collection | DOAJ |
| description | 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-1H-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-1H-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-1H-2λ6,1-benzothiazine. The derivatographic study of the thermal stability of 4-methyl-2,2-dioxo-1H-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-1H-2λ6,1-benzothiazine is easily formed during the decarboxylation of not only 4-methyl-2,2-dioxo-1H-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-1H-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. |
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| issn | 2218-0532 |
| language | English |
| last_indexed | 2024-04-11T18:16:05Z |
| publishDate | 2018-03-01 |
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| spelling | doaj.art-39fdab6f4d7041c0900f2688dd3593db2022-12-22T04:09:52ZengMDPI AGScientia Pharmaceutica2218-05322018-03-01861910.3390/scipharm86010009scipharm860100094-Methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic Acid. Peculiarities of Preparation, Structure, and Biological PropertiesIgor V. Ukrainets0Ganna M. Hamza1Anna A. Burian2Svitlana V. Shishkina3Natali I. Voloshchuk4Oxana V. Malchenko5Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska st., 61002 Kharkiv, UkraineDepartment of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska st., 61002 Kharkiv, UkraineDepartment of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska st., 61002 Kharkiv, UkraineSTC “Institute for Single Crystals”, National Academy of Sciences of Ukraine, 60 Nauki ave., 61001 Kharkiv, UkraineDepartment of Pharmacology, N. I. Pirogov Vinnitsa National Medical University, 56 Pirogov st., 21018 Vinnitsa, UkraineDepartment of Pharmacology, N. I. Pirogov Vinnitsa National Medical University, 56 Pirogov st., 21018 Vinnitsa, UkraineIn 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-1H-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-1H-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-1H-2λ6,1-benzothiazine. The derivatographic study of the thermal stability of 4-methyl-2,2-dioxo-1H-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-1H-2λ6,1-benzothiazine is easily formed during the decarboxylation of not only 4-methyl-2,2-dioxo-1H-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-1H-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.http://www.mdpi.com/2218-0532/86/1/9estershydrolysis4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acid2,1-benzothiazinecrystal structureanti-inflammatory actionanalgesic activity |
| spellingShingle | Igor V. Ukrainets Ganna M. Hamza Anna A. Burian Svitlana V. Shishkina Natali I. Voloshchuk Oxana V. Malchenko 4-Methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic Acid. Peculiarities of Preparation, Structure, and Biological Properties Scientia Pharmaceutica esters hydrolysis 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acid 2,1-benzothiazine crystal structure anti-inflammatory action analgesic activity |
| title | 4-Methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic Acid. Peculiarities of Preparation, Structure, and Biological Properties |
| title_full | 4-Methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic Acid. Peculiarities of Preparation, Structure, and Biological Properties |
| title_fullStr | 4-Methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic Acid. Peculiarities of Preparation, Structure, and Biological Properties |
| title_full_unstemmed | 4-Methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic Acid. Peculiarities of Preparation, Structure, and Biological Properties |
| title_short | 4-Methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic Acid. Peculiarities of Preparation, Structure, and Biological Properties |
| title_sort | 4 methyl 2 2 dioxo 1h 2λ6 1 benzothiazine 3 carboxylic acid peculiarities of preparation structure and biological properties |
| topic | esters hydrolysis 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acid 2,1-benzothiazine crystal structure anti-inflammatory action analgesic activity |
| url | http://www.mdpi.com/2218-0532/86/1/9 |
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