Methylation of position 8 in the pyridine moiety of the N-(benzyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamide molecule as an attempt to enhance their analgesic properties

Authors

  • I. V. Ukrainets National University of Pharmacy, Ukraine
  • O. V. Gorokhova National University of Pharmacy, Ukraine
  • L. V. Sydorenko National University of Pharmacy, Ukraine
  • S. G. Taran National University of Pharmacy, Ukraine

DOI:

https://doi.org/10.24959/ophcj.15.858

Keywords:

amidation, tricarbonylmethane heterocyclic derivatives, 2-hydroxy-4-oxo-4H-pyrido[1, 2-a] pyrimidine-3-carboxamides, synthesis, chemical modification, analgesic activity

Abstract

The chemical modification of the pyridine moiety of the molecule – displacement of the methyl group in position 8 of pyrido[1,2-a]pyrimidine nucleus has been considered as one of the possible versions to optimize the biological properties of N-(benzyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamides. The synthesis of the research targets was carried out by the reaction of the corresponding benzylamines and ethyl 2-hydroxy-8-methyl-4-oxo-4H-pyrido[1,2-a] pyrimidine-3-carboxylate, in its turn obtained by condensation of 2-amino-4-methylpyridine (i.e. the product with the methyl group in the intentionally required position) and triethyl methanetricarboxylate. The structure of the compounds obtained has been confirmed by the data of elemental analysis and NMR 1H spectroscopy, and in the case of optically active 1-phenylethylamides additionally by polarimetry. The study of the analgesic properties of all N-(benzyl)-2-hydroxy-8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamides was performed on the standard experimental “acetic acid writhing” model. At the same time, it has been found that our modification is accompanied with the increased biological activity of exclusively para-substituted derivatives. For profound research 4-fluorobenzylamide exceeding Piroxicam and Nabumetone by the level of the specific effect has been recommended as a potential new analgesic.

Downloads

Download data is not yet available.

References

  1. Kubinyi H. Rossiiskii Khimicheskii Zhurnal – Russian Chemical Journal, 2006, Vol. L, No.2, pp.5-17.
  2. Xiong W., Ma X., Wu Y., Chen Y., Zeng L., Liu J., Sun W., Wang D., Hu Y. BMC Veterinary Research, 2015, No.11, pp.205. DOI: 10.1186/s12917-015-0459-9.
  3. Kang Y. G., Park C. Y., Shin H., Singh R., Arora G., Yu C. M., Lee I. Y. Bioorganic & Medicinal Chemistry Letters, 2015, Vol. 25, No.17, pp.3650-3653. DOI: 10.1016/j.bmcl.2015.06.060.
  4. Weng X., Baez J. E., Khiterer M., Hoe M. Y., Bao Z., Shea K. J. Angewandte Chemie (International ed. in English), 2015, Vol. 54, No.38, pp.11214-11218. DOI: 10.1002/anie.201504934.
  5. Murakami T., Okamoto H., Kim H. Biomaterials Science, 2015, Vol. 3, No.5, pp.712-715. DOI: 10.1039/c4bm00402g.
  6. Uchida S., Kataoka K., Itaka K. Pharmaceutics, 2015, Vol. 7, No.3, pp.137-151. DOI: 10.3390/pharmaceutics7030137.
  7. Ahmed S. A., El-Shayeb N. M., Hashem A. G., Saleh S. A., Abdel-Fattah A. F. Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology], 2015, Vol. 46, No.1, pp.23-28. DOI: 10.1590/S1517-838246120120462.
  8. Kirdponpattara S., Khamkeaw A., Sanchavanakit N., Pavasant P., Phisalaphong M. Carbohydrate Polymers, 2015, No.132, pp.146-155. DOI: 10.1016/j. carbpol.2015.06.059.
  9. Du H., Liu M., Yang X., Zhai G. Journal of Colloid and Interface Science, 2015, No.460, pp.87-96. DOI: 10.1016/j.jcis.2015.08.049.
  10. Sureshbabu A. R., Kurapati R., Russier J., Ménard-Moyon C., Bartolini I., Meneghetti M., Kostarelos K., Bianco A. Biomaterials, 2015, No.72, pp.20-28. DOI: 10.1016/j.biomaterials.2015.08.046.
  11. Kuznetsov S. G., Chigareva S. M., Ramsh S. M. Itogi nauki i tekhniki. Organicheskaya Khimiya (The results of science and technology. Organic chemistry). Moscow, VINITI; 1991, Vol. 19, pp.25-54.
  12. Fijałkowski K., Żywicka A., Drozd R., Niemczyk A., Junka A. F., Peitler D., Kordas M., Konopacki M., Szymczyk P., Fray M. E., Rakoczy R. Carbohydrate Polymers, 2015, No.133, pp.52-60. DOI: 10.1016/j.carbpol.2015.07.011.
  13. Guilini C., Baehr C., Schaeffer E., Gizzi P., Rufi F., Haiech J., Weiss E., Bonnet D, Galzi J. L. Analytical Chemistry, 2015, Vol. 87, No.17, pp.8858-8866. DOI: 10.1021/acs.analchem.5b02100.
  14. Morrison P. M., Foley P. J., Warriner S. L., Webb M. E. Chemical Communications (Cambridge, England), 2015, Vol. 51, No.70, pp.13470-13473. DOI: 10.1039/c5cc05469a.
  15. Nilsen T. W. Cold Spring Harbor protocols, 2015, Vol. 2015, No.6, pp.599-603. DOI: 10.1101/pdb.prot081059.
  16. Ukrainets I. V., Gorokhova O. V., Nidal Amin Jaradat, Petrushova L. A., Mospanova E. V., Savchenkova L. V., Kuz’min V. E., Lyahovsky A. V. 4-Hydroxyquinolin-2-ones and their Close Structural Analogues as a New Source of Highly Effective Pain-killers. In book: Pain and Treatment, Racz G.B. and Noe C.E.(Ed.), Rijeka: InTech, 2014, pp.21-73. DOI: 10.5772/57402.
  17. Ukrainets I. V., Petrushova L. A., Dzyubenko S. P., Sim G. Chemistry of Heterocyclic Compounds, 2014, Vol. 50, No.1, pp.103-110. doi:10.1007/s10593-014-1452-0.
  18. Ukrainets I. V., Petrushova L. A., Dzyubenko S. P., Liu Yangyang. Chemistry of Heterocyclic Compounds, 2014, Vol. 50, No.4, pp.564-572. DOI:10.1007/ s10593-014-1508-1.
  19. Ukrainets I. V., Alexeeva T. V., Davidenko A. A., Grinenko V. V. Zhurnal Organichnoi ta Farmatsevtichnoi Khimii – Journal of Organic and Pharmaceutical Chemistry, 2015, Vol. 13, No.3(51), pp.9-14.
  20. Ukrainets I. V., Tugaibei I. A., Bereznyakova N. L., Kravchenko V. N., Turov A. V. Chemistry of Heterocyclic Compounds, 2008, Vol. 44, No.5, pp.565-575. DOI: 10.1007/s10593-008-0076-7.
  21. Potapov V. M. Stereokhimiya (Stereochemistry). Moscow, Khimiya, 1988, 464 p.
  22. Günther H. NMR Spectroscopy: Basic Principles, Concepts, and Applications in Chemistry. Weinheim, Wiley-VCH, 2013, 734 p.
  23. Ukrainets I. V., Taran S. G., Likhanova N. V., Rybakov V. B., Gorokhova O. V., Jaradat Nidal Amin. Chemistry of Heterocyclic Compounds, 2000, Vol. 36, No.1, pp.49-56. DOI: 10.1007/BF02256844.
  24. Vogel H. G. Drug Discovery and Evaluation: Pharmacological Assays. Berlin, Springer; 2008, pp.1030-1032.
  25. Sigidin Ya. A., Shvarts G. Ya., Arzamastsev A. P., Liberman S. S. Lekarstvennaya terapiya vospalitel’nogo protsessa (Drug Therapy of the Anti-inflammatory Process). Moscow, Meditsina; 1988, pp.60-63.
  26. Sernov L. N., Gatsura V. V. Elementy experimentalnoi pharmakologii (Elements of Experimental Pharmacology). Moscow, Nauka, 2000, pp.308-316.

Downloads

Published

2015-12-27

How to Cite

(1)
Ukrainets, I. V.; Gorokhova, O. V.; Sydorenko, L. V.; Taran, S. G. Methylation of Position 8 in the Pyridine Moiety of the N-(benzyl)-2-Hydroxy-4-Oxo-4H-pyrido[1,2-a]pyrimidine-3-Carboxamide Molecule As an Attempt to Enhance Their Analgesic Properties. J. Org. Pharm. Chem. 2015, 13, 6-11.

Issue

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

Section

Original Researches

License

Copyright (c) 2015 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).