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

O. Ya. Mel’nyk, V. O. Chornous, N. D. Yakovychuk, N. V. Mel’nichenko, M. V. Vovk

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.


Keywords


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

References


Mekillor A., Boulton A. J. Comprehensive Heterocyclic Chemistry. Eds A. R. Katrizky, C. W. Rees, Pergamon, Oxford, 1984, Vol. 2, pp.67-98.

Ismail M. M. F., Noaman E. Medicinal Chemistry Research, 2005, Vol. 14, No.7, pp.382-403.

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.

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.

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.

Bekhit A. A., Baraca A. M. European Journal of Medicinal Chemistry, 2005, Vol. 40, pp.69-77.

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.

El-Emary T. I., Bakhite E. A. Pharmazie, 1999, Vol. 54, No.2, pp.106-111.

Al-Issa S. A. R. Molecules, 2012, Vol. 17, pp.10902-10915.

Atmekur K., Emmadi N. R., Balasubramanian S. Journal of Heterocyclic Chemistry, 2013, Vol. 50, pp.513-518.

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.

Abdou J. M., Rateb N. M., Eldead H. A. Heterocyclic Communications, 2012, Vol. 18, pp.135-141.

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.

Rong L., Han H., Jiang H., Shi D., Tu.s Synthetic Communications, 2008, Vol. 38, pp.217-224.

Zayed S. M. A. D., Attia A. Journal of Heterocyclic Chemistry, 1983, Vol. 20, pp.129-131.

Michael M. A., Becher J., Winckelmann I. Journal of Heterocyclic Chemistry, 1983, Vol. 20, pp.1651-1656.

El-Sayed H. A., Ouf N. H., Moustafa A. H. Research of Chemical Intermediates, 2014, Vol. 40, pp.407-412.

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.

Rostom S. A. F., Bekhit A. A. European Journal of Medicinal Chemistry, 2015, Vol. 92, pp.712-722.

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.

Chornous V. A., Bratenko M. K., Vovk M.V. Russian Journal of Organic Chemistry, 2009, Vol. 45, pp.1210-1213.

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.

Chornous V. O., Melnyk O. Ya, Kutsyk R. V., Vovk M. V. Naukovyy Visnyk Chernivets’kogo universytetu, Khimiya, 2014, Vol. 683, pp.90-96.

Labinskaya A. S., Blinkova L. P., Eshhina A. S. Obshchaya i sanitarnaya microbiologiya s tekhnikoj mikrobiologicheskikh issledovanij. Moskow, Meditsina, 2010.


GOST Style Citations






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

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)