The synthesis and evaluation of the bactericidal activity of 4-(4-chloro-1H-imidazol-5-yl)-2-oxo-1,2-dihydropyridin-3-carbonitriles

Authors

  • O. Ya. Mel’nyk SHHE «Ivano-Frankivsk National Medical University», Ukraine
  • V. O. Chornous Bukovinian State Medical University, Ukraine
  • N. D. Yakovychuk Bukovinian State Medical University, Ukraine
  • N. V. Mel’nichenko Institute of Organic Chemistry of the NAS of Ukraine, Ukraine
  • M. V. Vovk Institute of Organic Chemistry of the NAS of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/ophcj.15.860

Keywords:

5-formyl-4-chloroimidazoles, acetophenones, ethyl cyanoacetate, ammonium acetate, 4-(4-chloroimidazol- 5-yl)pyridin-3-carbonitriles, cyclocondensation, antimicrobial and fungicidal activity

Abstract

The synthetic approach to preparation of some new 4-imidazolyl substituted derivatives of pyridine-3-carboxylic acid nitriles has been proposed, and their antimicrobial and antifungal properties have been studied in the article. It has been found that 4-(4-chloro-1H-imidazol-5-yl)-2-oxo-1,2-dihydropyridin-3-carbonitriles are prepared with 41-51% yields by four component cyclocondensation of 4-chloroimidazol-5-carbaldehydes with acetophenones and ethyl cyanoacetate in the presence of the 10-fold excess of ammonium acetate when boiling in ethanol for 15-30 h. A detailed monitoring of the reaction by liquid chromatography–mass spectrometry has shown that the reaction is accompanied with the by-process forming the corresponding chalcones that do not tend to undergo cyclization to the target products. The structure of the compounds synthesized has been proven by the complex of physical and chemical methods: IR, 1H and 13C NMR spectroscopy and liquid chromatography–mass spectrometry. The most evidential among them are 13C NMR spectra with characteristic signals for the pyridоne system in such ranges as C3 (90-92 ppm), C5 (115-116 ppm), C4 (127-129 ppm), C6 (144-146 ppm) and C2 (159-161 ppm). The results of the bactericidal activity study of a number of the compounds synthesized have convincingly confirmed their high antimicrobial and antifungal action. They inhibit the growth of microorganism vegetative forms in the concentrations of 7.8-125 mg/ml.

Downloads

Download data is not yet available.

References

  1. Mekillor A., Boulton A. J. Comprehensive Heterocyclic Chemistry. Eds A. R. Katrizky, C. W. Rees, Pergamon, Oxford, 1984, Vol. 2, pp.67-98.
  2. Ismail M. M. F., Noaman E. Medicinal Chemistry Research, 2005, Vol. 14, No.7, pp.382-403.
  3. Abadi A. H., Abouel-Ella D. A., Lehmann J., Tinsley H. N., Gary B. D., Piazza G. A., Abdel Fattah M. A. O. European Journal of Medicinal Chemistry, 2010, Vol. 45, pp.90-97.
  4. Cheney I. W., Yan S., Applely T., Walker H., Vo T., Yao N., Hamatake R., Hong Z., Wu J. Z. Bioorganic and Medicinal Chemistry Letters, 2007, Vol. 17, pp.1679-1683.
  5. Bekhit A. A., Hymete A., Damtew A., Mohamed A. M. I., Bekhit A. E. A. Journal of Enzyme Inhibition and Medicinal Chemistry, 2012, Vol. 27, pp.69-77.
  6. Bekhit A. A., Baraca A. M. European Journal of Medicinal Chemistry, 2005, Vol. 40, pp.69-77.
  7. Abd El Salam H. A., Shaker N. O., Wl-Telbani E. H., Nawwar G. A. M. Journal of Chemical Reserch, 2009, Vol. 6, pp.400-404.
  8. El-Emary T. I., Bakhite E. A. Pharmazie, 1999, Vol. 54, No.2, pp.106-111.
  9. Al-Issa S. A. R. Molecules, 2012, Vol. 17, pp.10902-10915.
  10. Atmekur K., Emmadi N. R., Balasubramanian S. Journal of Heterocyclic Chemistry, 2013, Vol. 50, pp.513-518.
  11. Chavva K., Pillalamarri S., Banda V., Gautham S., Gaddamedi J., Yedla P., Kumar C. G., Banda N. Bioorganic and Medicinal Chemistry Letters, 2013, Vol. 23, pp.5893-5895.
  12. Abdou J. M., Rateb N. M., Eldead H. A. Heterocyclic Communications, 2012, Vol. 18, pp.135-141.
  13. Raju K., Chandra S. A., Sathaiah G., Ravi K. A., Narsaiah B., Shanthan R. P., Srujana R., Srigiridhar K. Letters in Organic Chemistry, 2014, Vol. 11, No.4, pp.293-302.
  14. Rong L., Han H., Jiang H., Shi D., Tu.s Synthetic Communications, 2008, Vol. 38, pp.217-224.
  15. Zayed S. M. A. D., Attia A. Journal of Heterocyclic Chemistry, 1983, Vol. 20, pp.129-131.
  16. Michael M. A., Becher J., Winckelmann I. Journal of Heterocyclic Chemistry, 1983, Vol. 20, pp.1651-1656.
  17. El-Sayed H. A., Ouf N. H., Moustafa A. H. Research of Chemical Intermediates, 2014, Vol. 40, pp.407-412.
  18. Nalage S. V., Nikum A. P., Kalyankar M. B., Patil V. S., Patil U. D., Desale K. R., Patil S. L., Bhosale S. V. Letters in Organic Chemistry, 2010, Vol. 7, pp.406-410.
  19. Rostom S. A. F., Bekhit A. A. European Journal of Medicinal Chemistry, 2015, Vol. 92, pp.712-722.
  20. Chornous V. O., Grozav A. M., Vovk M. V. Khimiya i biologicheskaya aktivnost azolov. Eds. V. Brovarets, V. Zyabrev. LAP Lambert Acad. Publ., 2014, pp.75-101.
  21. Chornous V. A., Bratenko M. K., Vovk M.V. Russian Journal of Organic Chemistry, 2009, Vol. 45, pp.1210-1213.
  22. Chornous V. A., Grozav A. M., Rusanov E. B., Nesterenko A. M., Vovk M. V. Russian Journal of Organic Chemistry, 2011, Vol. 47, pp.702-709.
  23. Chornous V. O., Melnyk O. Ya, Kutsyk R. V., Vovk M. V. Naukovyy Visnyk Chernivets’kogo universytetu, Khimiya, 2014, Vol. 683, pp.90-96.
  24. Labinskaya A. S., Blinkova L. P., Eshhina A. S. Obshchaya i sanitarnaya microbiologiya s tekhnikoj mikrobiologicheskikh issledovanij. Moskow, Meditsina, 2010.

Downloads

Published

2015-12-27

How to Cite

(1)
Mel’nyk, O. Y.; Chornous, V. O.; Yakovychuk, N. D.; Mel’nichenko, N. V.; Vovk, M. V. The Synthesis and Evaluation of the Bactericidal Activity of 4-(4-Chloro-1H-Imidazol-5-Yl)-2-Oxo-1,2-Dihydropyridin-3-Carbonitriles. J. Org. Pharm. Chem. 2015, 13, 57-61.

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).