The study of regularities of the structure – analgesic activity relationship in a series of 4-hydroxy-Nn-(pyridin-2-yl)-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides

Authors

  • I. V. Ukrainets National University of Pharmacy, Ukraine
  • L. A. Petrushova National University of Pharmacy, Ukraine
  • O. V. Gorokhova National University of Pharmacy, Ukraine
  • O. O. Davydenko National Pirogov Memorial Medical University, Ukraine

DOI:

https://doi.org/10.24959/ophcj.15.864

Keywords:

amidation, 2-aminopyridines, 4-hydroxy-2, 2-dioxo-1H-2λ6, 1-benzothiazine-3-carboxamides, synthesis, analgesic activity

Abstract

Continuing the search for new analgesics and with the purpose of revealing the structural-biological regularities, which are important for further studies, the synthesis of a series of 4-hydroxy-N-(pyridin-2-yl)-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides unsubstituted in position 1 has been carried out. The structure of all compounds synthesized has been confirmed by elemental analysis, 1H NMR spectra and mass spectra. Based on a detailed analysis of the mass spectra it has been concluded that 4-hydroxy-N-(pyridin-2-yl)-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides in crystals are inner salts – 3-{[(pyridinium-2-yl)amino]carbonyl}-2,2-dioxo-1H-2,1-benzothiazin-4-olates. It has been noted that spectroscopy of 1H NMR does not allow either to confirm or disprove that in DMSO solution the substances studied exist in the form of inner salts since the signals of the active protons of OH and NHgroups that are important do not appear. According to the results of the pharmacological screening the substances – for example, 3-{[(6-methylpyridinium-2-yl)amino]carbonyl}-2,2-dioxo-1H-2,1-benzothiazin-4-olate – exceeding Piroxicam by the analgesic activity have been found. It has been unequivocally determined that removal of the 1-N-methyl group from the structure of 4-hydroxy-1-methyl-N-(pyridin-2-yl)-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides in general leads to a marked decrease in analgesic properties and may be considered inappropriate.

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Published

2015-12-27

How to Cite

(1)
Ukrainets, I. V.; Petrushova, L. A.; Gorokhova, O. V.; Davydenko, O. O. The Study of Regularities of the Structure – Analgesic Activity Relationship in a Series of 4-Hydroxy-Nn-(pyridin-2-Yl)-2,2-Dioxo-1H-2λ6,1-Benzothiazine-3-Carboxamides. J. Org. Pharm. Chem. 2015, 13, 39-43.

Issue

Vol. 13 No. 4(52) (2015)

Section

Original Researches

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