The synthesis and the antitubercular activity of 1-benzyl-4-hydroxy-2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxamides

O. O. Davydenko


Unfortunately, tuberculosis still remains a cause of high mortality in humans and in modern conditions it has become a global health problem. Continuing the search for new antimycobacterial agents among the amidated derivatives of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids the corresponding group of 1-benzyl-4-hydroxy-2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxamides has been synthesized by the reaction of ethyl 1-benzyl-4-hydroxy-2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxylate and anilines or hetarylamines in DMF at 130°C. The chemical structure of the compounds obtained has been confirmed by the data of elemental analysis, NMR 1H spectroscopy and mass spectrometry. It has been noted that the 1H NMR spectra can reliably confirm the presence of the basic functional groups by their corresponding chemical shift, the integrated intensity and multiplicity of signals. It has been shown that under the influence of the electron impact the molecular ions of all the compounds studied undergo the primary fragmentation in two directions: with breaking the amide bond or the quinolone nucleus – the carbamide moiety bond. According to the data of microbiological tests among 1-benzyl-4-hydroxy-2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxamides synthesized the substances that are capable of inhibiting actively the growth of Mycobacterium tuberculosis H37Rv in low concentration have been identified, and therefore, they are of interest for further research.


amides; 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids; synthesis; thermolysis; antitubercular activity

Full Text:



Chiappini E., Sollai S., Bonsignori F., Galli L., de Martino M. Journal of chemotherapy (Florence, Italy), 2015, Vol. 27, No.3, p.127. DOI: 10.1179/1120 009X15Z.000000000321.

Prasad R., Gupta N., Singh M. The Indian journal of chest diseases & allied sciences, 2014, Vol. 56, No.4, pp.237-246.

Pai M., Schito M. The Journal of infectious diseases, 2015, Vol. 211, Suppl. 2, pp.21-28. DOI: 10.1093/infdis/jiu803.

Saybani M. R., Shamshirband S., Golzari Hormozi S., Wah T. Y., Aghabozorgi S., Pourhoseingholi M. A., Olariu T. Iranian Red Crescent medical journal, 2015, Vol. 17, No.4, pp.e24557. DOI: 10.5812/ircmj.17(4)2015.24557.

Shirani K., Talaei Z., Yaran M., Ataei B., Mehrabi-Koushki A., Khorvash F. Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences, 2015, Vol. 20, No.3, pp.224-227.

Engström A., Juréen P. Methods in molecular biology (Clifton, N.J.), 2015, Vol. 1315, pp.349-362. DOI: 10.1007/978-1-4939-2715-9_24.

Melak T., Gakkhar S. Clinical and translational medicine, 2015, Vol. 4, No.1, pp.61. DOI: 10.1186/s40169-015-0061-6.

Keri R. S., B S. S., Nagaraja B. M., Santos M. A. European journal of medicinal chemistry, 2015, Vol. 100, pp.257-269. DOI: 10.1016/j.ejmech.2015.06.017.

Ventura T. L., Calixto S. D., de Azevedo Abrahim-Vieira B., de Souza A. M., Mello M. V., Rodrigues C. R., Soter de Mariz e Miranda L., Alves de Souza R. O., Leal I. C., Lasunskaia E. B., Muzitano M. F. Molecules (Basel, Switzerland), 2015, Vol. 20, No.5, pp.8072-8093. DOI: 10.3390/molecules20058072.

Riordan S. W., Field J. J., Corkran H. M., Dasyam N., Stocker B. L., Timmer M. S., Harvey J. E., Teesdale-Spittle P. H. Bioorganic & medicinal chemistry letters, 2015, Vol. 25, No.10, pp.2152-2155. DOI: 10.1016/j.bmcl.2015.03.070.

Peng C. T., Gao C., Wang N. Y., You X. Y., Zhang L. D., Zhu Y. X., Xv Y., Zuo W. Q., Ran K., Deng H. X., Lei Q., Xiao K. J., Yu L. T. Bioorganic & medicinal chemistry letters, 2015, Vol. 25, No.7, pp.1373-1376. DOI: 10.1016/j.bmcl.2015.02.061.

Ukrainets I. V., Mospanova O. V., Golovchenko O. S., Abdel Naser Dakkah. Zhurnal Organichnoi ta Farmatsevtichnoi Khimii – Journal of Organic and Pharmaceutical Chemistry, 2011, Vol. 9, No.2(34), pp.38-43.

Ukrainets I. V., Kolesnik E. V., Sidorenko L. V., Gorokhova O. V., Turov A. V. Chemistry of Heterocyclic Compounds, 2006, Vol. 42, No.6, pp.765-775. DOI: 10.1007/s10593-006-0159-2.

Ukrainets I. V., Kolesnik E. V., Sidorenko L. V., Gorokhova O. V., Turov A. V. Chemistry of Heterocyclic Compounds, 2007, Vol. 43, No.3, pp.326-333. DOI:10.1007/s10593-007-0049-2.

Ukrainets I. V., Bereznyakova N. L., Kolesnik O. V., Turov A. V. Zhurnal Organichnoi ta Farmatsevtichnoi Khimii – Journal of Organic and Pharmaceutical Chemistry, 2007, Vol. 5, No.1(17), pp.32-38.

Li C., Ai J., Zhang D., Peng X., Chen X., Gao Z., Su Y., Zhu W., Ji Y., Chen X., Geng M., Liu H. ACS medicinal chemistry letters, 2015, Vol. 6, No.5, pp.507-512. DOI: 10.1021/ml5004876.

Al-Rashida M., Ejaz S. A., Ali S., Shaukat A., Hamayoun M., Ahmed M., Iqbal J. Bioorganic & medicinal chemistry, 2015, Vol. 23, No.10, pp.2435-2444. DOI: 10.1016/j.bmc.2015.03.054.

Tuyishime M., Danish M., Princiotto A., Mankowski M. K., Lawrence R., Lombart H. G., Esikov K., Berniac J., Liang K., Ji J., Ptak R. G., Madani N., Cocklin S. Bioorganic & medicinal chemistry letters, 2014, Vol. 24, No.23, pp.5439-5445.

Terent’ev P. B., Stankyavichyus A. P. Mass-spektrometricheskii analiz biologicheski aktivnyh azotistyh ocnovanii (Mass spectrometric analysis of bioactive nitrogen bases). Vilnyus, Mokslas, 1987; pp.239-255.

Inderleid C. B., Salfinger M. Antimycobacterial agents and susceptibility tests: mycobacteria. In: Manual of Clinical Microbiology, Ed. Murray P. R., Baron E. J., Pfaller M. A., Tenover F. C., Yolken R. H. Washington D. C., ASM Press; 1995, pp.1385-1404.

Inderleid C. B., Nash K. A. Antimycobacterial agents: in vitro susceptibility testing, spectra of activity, mechanisms of action and resistance, and assays for activity in biological fluids. In: Antibiotics in Laboratory Medicine, 4-th ed., Ed. Lorian V. Baltimore, Williams and Wilkins; 1996, pp.127-175.

GOST Style Citations

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

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

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