Polymorphism and the analgesic activity of N-(3-pyridylmethyl)-4-hydroxy-2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxamide

I. V. Ukrainets, O. V. Mospanova, N. L. Bereznyakova, O. O. Davydenko


The advanced study of the analgesic activity of N-(3-pyridylmethyl)-4-hydroxy-2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxamide selected by the results of the primary pharmacological screening as the leading structure has revealed a significant change in anesthetic properties in different samples of this compound. Since the substance under study was not soluble in water, and animals received it orally as a thin aqueous suspension, the most likely cause of the effect observed was thought to be the changes in the crystalline structure of N-(3-pyridylmethyl)-4-hydroxy-2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxamide occurring in it under the influence of external factors. This assumption has been fully confirmed by the thorough microscopic investigation of righ – and low-active samples, as well as more objective data, the methods of powder and single crystal X-ray diffraction analysis. Thus, in particular, it has been found that with all the variety of crystalline and amorphous forms included in the samples studied their qualitative composition appeared to be quite similar. At the same time the quantitative content of some of the phases varies greatly, and obviously, it was the factor determining the size of the analgesic effect.


4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides; polymorphism; X-ray structural analysis; analgesic activity

Full Text:



Muresan-Pop M., Braga D., Pop M. M., Borodi G., Kacso I., Maini L. Journal of pharmaceutical sciences, 2014, Vol. 103, No.11, pp.3594-3601. DOI: 10.1002/jps.24151.

Nyström M., Roine J., Murtomaa M., Mohan Sankaran R., Santos H. A., Salonen J. European journal of pharmaceutics and biopharmaceutics, 2014, DOI: 10.1016/j.ejpb.2014.11.027.

Blandizzi C., Viscomi G. C., Scarpignato C. Drug design, development and therapy, 2015, Vol. 9, pp.1-11. DOI: 10.2147/DDDT.S72572.

Gana I., Barrio M., Do B., Tamarit J. L., Céolin R., Rietveld I. B. International journal of pharmaceutics, 2013, Vol. 456, No.2, pp.480-488. DOI: 10.1016/j. ijpharm.2013.08.031.

Patil S. S., Mahadik K. R., Paradkar A. R. European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences, 2015, Vol. 68, pp.43-50. DOI: 10.1016/j.ejps.2014.11.007.

Du Y., Zhang H., Xue J., Tang W., Fang H., Zhang Q., Li Y., Hong Z. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, 2015, Vol. 137, pp.1158-1163. DOI: 10.1016/j.saa.2014.08.128.

Marques M. P., Valero R., Parker S. F., Tomkinson J., Batista de Carvalho L. A. The journal of physical chemistry. B, 2013, Vol. 117, No.21, pp.6421-6429. DOI: 10.1021/jp403486z.

Sorrenti M., Catenacci L., Cruickshank D. L., Caira M. R. Journal of pharmaceutical sciences, 2013, Vol. 102, No.10, pp.3596-3603. DOI: 10.1002/jps.23660.

Russkiy khimicheskiy zhurnal – Russian chemical journal, 1997, Vol. XLI, No.5. The entire issue is devoted to the polymorphism of drugs and problems of a new generation of pharmacological agents.

Bernstein J. Polymorphism in Molecular Crystals. Oxford, Clarendon Press, 2002, 428 p.

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.

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.

Zefirov N. S., Palyulin V. A., Dashevskaya E. E. Journal of Physical Organic Chemistry, 1990, Vol. 3, No.3, pp.147-154. DOI: 10.1002/poc.610030304.

Burgi H.-B., Dunitz J. D. Structure Correlation. Weinheim, VCH, 1994, Vol. 2, pp.741-784.

Sheldrick G. M. Acta Crystallographica. Section A, 2008, Vol. 64, pp.112-122.

Vogel H. G. Drug Discovery and Evaluation: Pharmacological Assays, Berlin, Springer, 2008, pp.1030-1032.

Sigidin Ya. A., Shvarts G. Ya., Arzamastsev A. P., Liberman S. S. Drug Therapy of the Anti-inflammatory Process, Moscow, Meditsina, 1988, pp.60-63.

GOST Style Citations

DOI: https://doi.org/10.24959/ophcj.15.832

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

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