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Sci. Pharm. 2016, 84(4), 705-714; doi:10.3390/scipharm84040705

Synthesis, Spatial Structure and Analgesic Activity of Sodium 3-Benzylaminocarbonyl-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazin-4-olate Solvates

1
Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska St., 61002 Kharkiv, Ukraine
2
SSI “Institute for Single Crystal” National Academy of Sciences of Ukraine, 60 Nauki ave., 61001 Kharkiv, Ukraine
3
Department of Inorganic Chemistry, V. N. Karazin Kharkiv National University, 4 Svobody sq., 61077 Kharkiv, Ukraine
4
Department of Pharmaceutical Chemistry, Far Eastern State Medical University, 35 Murav’eva-Amurskogo St., 680000 Khabarovsk, Russia
*
Author to whom correspondence should be addressed.
Academic Editor: Thomas Erker
Received: 5 August 2016 / Accepted: 19 September 2016 / Published: 19 October 2016
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Abstract

In order to obtain and then test pharmocologically any possible conformers of the new feasible analgesic N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide, its 4-O-sodium salt was synthesized using two methods. X-ray diffraction study made possible to determine that, depending on the chosen synthesis conditions, the above-mentioned compound forms either monosolvate with methanol or monohydrate, where organic anion exists in the form of three different conformers. Pharmacological testing of the two known pseudo-enantiomeric forms of the original N-benzylamide and of the two solvates of its sodium salt was performed simultaneously under the same conditions and in equimolar doses. Comparison of the results obtained while studying the peculiarities of the synthesized compounds spatial structure and biological properties revealed an important structure-action relationship. In particular, it was shown that the intensity of analgesic effect of different conformational isomers of N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide may change considerably: while low active conformers are comparable with piroxicam, highly active conformers are more than twice as effective as meloxicam. View Full-Text
Keywords: analgesic activity; conformation; conformer; crystal structure; 4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide; solvate analgesic activity; conformation; conformer; crystal structure; 4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide; solvate
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Ukrainets, I.V.; Petrushova, L.A.; Shishkina, S.V.; Grinevich, L.A.; Sim, G. Synthesis, Spatial Structure and Analgesic Activity of Sodium 3-Benzylaminocarbonyl-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazin-4-olate Solvates. Sci. Pharm. 2016, 84, 705-714.

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