Synthesis and analgesic activity of N-(benzothiazol-2-yl)-4-hydroxy-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
  • S. P. Dzyubenko National Pirogov Memorial Medical University, Ukraine
  • L. O. Grinevich National Pirogov Memorial Medical University, Ukraine

DOI:

https://doi.org/10.24959/ophcj.14.801

Keywords:

2-aminobenzothiazoles, 2, 1-benzothiazines, hetarylamides, synthesis, analgesic activity

Abstract

Continuing the search of new effective analgesics with improved properties the corresponding N-(benzothiazol- 2-yl)-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides have been synthesized in boiling xylene by the interaction of methyl ester of 4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acid with 2-aminobenzothiazoles. The structure of the substances synthesized has been confirmed by the data of elemental analysis, NMR 1H spectroscopy and mass-spectrometry. The peculiarities of the aromatic region interpretation in NMR 1H spectra of the structural class studied have been discussed. It has been shown that in ionization by electron impact the primary fragmentation of molecular ions of N-(benzothiazol-2-yl)-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides surprisingly occurs in a variety of ways. It starts with SO2 release in amide unsubstituted in the benzothiazole moiety of the molecule and its 6-methyl analogue, while for halogenated products the primary breaking of the terminal carbamide bond or the loss of halogen are characteristic. According to the results of the pharmacological research performed on the model of tail-flick procedure, N-(6-bromobenzothiazol-2-yl)-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide has been determined; it exhibits the analgesic effect at the level of Meloxicam.

Downloads

Download data is not yet available.

References

  1. Xie X., Yan Y., Zhu N., Liu G. European Journal of Medicinal Chemistry, 2014, Vol. 76, pp.67-78. Doi: 10.1016/j.ejmech.2014.02.007.
  2. Netalkar P. P., Netalkar S. P., Budagumpi S., Revankar V. K. European Journal of Medicinal Chemistry, 2014, Vol. 79, pp.47-56. Doi: 10.1016/j.ejmech.2014.03.083.
  3. Seenaiah D., Reddy P. R., Reddy G. M., Padmaja A., Padmavathi V., Krishna N. S. European Journal of Medicinal Chemistry, 2014, Vol. 77, pp.1-7. Doi: 10.1016/j.ejmech.2014.02.050.
  4. Stokes N. R., Thomaides-Brears H. B., Barker S., Bennett J. M., Berry J., Collins I., Czaplewski L. G., Gamble V., Lancett P., Logan A., Lunniss C. J., Peasley H., Pommier S., Price D., Smee C., Haydon D. J. Antimicrobial Agents and Chemotherapy, 2013, Vol. 57, No.12, pp.5977-5986. Doi: 10.1128/AAC.00719-13.
  5. Santhoshi A., Mahendar B., Mattapally S., Sadhu P. S., Banerjee S. K., Jayathirtha Rao V. Bioorganic & Medicinal Chemistry Letters, 2014, Vol. 24, No.8, pp.1952-1957. Doi: 10.1016/j.bmcl.2014.02.073.
  6. Wang S., Chen Y., Zhao S., Xu X., Liu X., Liu B. F., Zhang G. Bioorganic & Medicinal Chemistry Letters, 2014, Vol. 24, No.7, pp.1766-1770. Doi: 10.1016/j. bmcl.2014.02.031.
  7. Komiya M., Asano S., Koike N., Koga E., Igarashi J., Nakatani S., Isobe Y. Chemical & Pharmaceutical Bulletin (Tokyo), 2013, Vol. 61, No.10, pp.1094-1097.
  8. Liu D. C., Deng X. Q., Wang S. B., Quan Z. S. Archiv der Pharmazie, 2014, Vol. 347, No.4, pp.268-275.
  9. Bandyopadhyay P., Sathe M., Tikar S. N., Yadav R., Sharma P., Kumar A., Kaushik M. P. Bioorganic & Medicinal Chemistry Letters, 2014, Vol. 24, No.13, pp.2934-2939. Doi: 10.1016/j.bmcl.2014.04.082.
  10. Amir M., Hassan M. Z. Mini Reviews in Medicinal Chemistry, 2013, Vol. 13, No.14, pp.2060-2075.
  11. Song J. M., DiBattista A. M., Sung Y. M., Ahn J. M., Turner R. S., Yang J., Pak D. T., Lee H. K., Hoe H. S. Experimental Neurology, 2014, Vol. 252, pp.105-13. Doi: 10.1016/j.expneurol.2013.11.023.
  12. Irifune M., Kikuchi N., Saida T., Takarada T., Shimizu Y., Endo C., Morita K., Dohi T., Sato T., Kawahara M. Anesthesia and Analgesia, 2007, Vol. 104, No.6, pp.1415-1421.
  13. Shafi S., Alam M. M., Mulakayala N., Mulakayala C., Vanaja G., Kalle A. M., Pallu R., Alam M. S. European Journal of Medicinal Chemistry, 2012, Vol. 49, pp.324-333. Doi: 10.1016/j.ejmech.2012.01.032.
  14. Sharma P. C., Sinhmar A., Sharma A., Rajak H., Pathak D. P. Journal of Enzyme Inhibition and Medicinal Chemistry, 2013, Vol. 28, No.2, pp.240-266. Doi: 10.3109/14756366.2012.720572.
  15. Azam M. A., Dharanya L., Mehta C. C., Sachdeva S. Acta Pharmaceutica (Zagreb, Croatia), 2013, Vol. 63, No.1, pp.19-30. Doi: 10.2478/acph-2013-0001.
  16. Kaplancikli Z. A., Altintop M. D., Turan-Zitouni G., Ozdemir A., Can O. D. Journal of Enzyme Inhibition and Medicinal Chemistry, 2012, Vol. 27, No.2, pp.274-280. Doi: 10.3109/14756366.2011.587417.
  17. Gurupadayya B. M., Gopal M., Padmashali B., Manohara Y. N. Indian Journal of Pharmaceutical Sciences, 2008, Vol. 70, No.5, pp.572-577. Doi: 10.4103/0250-474X.45393.
  18. Jeong C. Y., Choi J. I., Yoon M. H. European Journal of Pharmacology, 2004, Vol. 502, No.3, pp.205-211.
  19. Yous S., Poupaert J. H., Chavatte P., Espiard J. G., Caignard D. H., Lesieur D. Drug Design and Discovery, 2001, Vol. 17, No.4, pp.331-336.
  20. Ferreira S. H., Lorenzetti B. B., Devissaguet M., Lesieur D., Tsouderos Y. British Journal of Pharmacology, 1995, Vol. 114, No.2, pp.303-308.
  21. Palagiano F., Arenare L., De Caprariis P., Grandolini G., Ambrogi V., Perioli L., Filippelli W., Falcone G., Rossi F. Farmaco (Società Chimica Italiana), 1996, Vol. 51, No.7, pp.483-491.
  22. Ukrainets I. V., Petrushova L. A., Dzyubenko S. P. Chemistry of Heterocyclic Compounds, 2013, Vol. 49, No.9, pp.1378-1383.
  23. Ukrainets I. V., Petrushova L. A., Dzyubenko S. P., Sim G. Chemistry of Heterocyclic Compounds, 2014, Vol. 50, No.1, pp.103-110.
  24. Ukrainets I. V., Petrushova L. A., Dzyubenko S. P., Liu Yangyang. Chemistry of Heterocyclic Compounds, 2014, Vol. 50, No.4, pp.564-572.
  25. Gunther H. NMR Spectroscopy: basic principles, concepts, and applications in chemistry, Weinheim: Wiley-VCH, 2013, 718 p.
  26. Vogel H. G. Drug Discovery and Evaluation: Pharmacological Assays. Berlin, Springer; 2008, pp. 1011-1013.

Downloads

Published

2014-12-10

How to Cite

(1)
Ukrainets, I. V.; Petrushova, L. A.; Dzyubenko, S. P.; Grinevich, L. O. Synthesis and Analgesic Activity of N-(benzothiazol-2-Yl)-4-Hydroxy-2,2-Dioxo-1H-2λ6,1-Benzothiazine-3-Carboxamides. J. Org. Pharm. Chem. 2014, 12, 38-43.

Issue

Vol. 12 No. 4(48) (2014)

Section

Original Researches

License

Copyright (c) 2014 National University of Pharmacy

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors publishing their works in the Journal of Organic and Pharmaceutical Chemistry agree with the following terms:

1. Authors retain copyright and grant the journal the right of the first publication of the work under Creative Commons Attribution License allowing everyone to distribute and re-use the published material if proper citation of the original publication is given.

2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal’s published version of the work (e.g., post it to an institutional repository or publish it in a book) providing proper citation of the original publication.

3. Authors are permitted and encouraged to post their work online (e.g. in institutional repositories or on authors’ personal websites) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (see The Effect of Open Access).