N-Benzyl-1-(2-cyanoethyl)-4-hydroxy-2-oxo-1,2-dihydro-3-quinolinecarboxamides as promising analgesics
Based on the regularities of the “structure – analgesic activity” relationship revealed earlier in the complex study of the biological properties of numerous N-substituted amides of 1-R-4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids the target chemical modification of the structurally related N-alkyl-1-(2-cyanoethyl)-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides has been conducted. These changes concerned only the amide fragment of the given compounds, and they are actually the replacement of one of the hydrogen atoms of the methyl group in N-methyl-1-(2-cyanoethyl)-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamide by the aromatic ring. It has been shown that in the synthesis of the target compounds various variants of amidation of 4-hydroxy-2-oxo-1-(2-cyanoethyl)-1,2-dihydroquinoline-3-carboxylic acid ethyl ester with the benzyl amines can be successfully used: by thermolysis of the ester and amine without a solvent at 140°C or by interaction of the ester with the excess of amine in boiling alcohol. The peripheral component in the mechanism of analgesic properties of N-benzyl-1-(2-cyanoethyl)-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides has been studied on the standard model of “acetic acid-induced writhing” in white mice concomitantly and in comparison with diclofenac. It has been found that some of the substances synthesized exceed notably the reference drug as for the analgesic effect when administered orally in the dose of 5 mg/kg, and they can be recommended for more profound research as potential analgesics.
Full Text:PDF (Русский)
Roouf Bhat A., Arshad M., Ju Lee E., Pokharel S., Choi I., Athar F. Chemistry & biodiversity, 2013, Vol. 10, No.12, pp.2267-2277.
Shi J.F., Wu P., Jiang Z.H., Wei X.Y. European Journal of Medicinal Chemistry, 2014, Vol. 71, pp.219-228.
Singh K.D., Muthusamy K. Acta pharmacologica Sinica, 2013, Vol. 34, No.12, pp.1592-606.
Rami C., Patel L., Patel C.N., Parmar J.P. Journal of pharmacy & bioallied sciences, 2013, Vol. 5, No.4, pp.277-289.
Sun G.X., Sun Z.H., Yang M.Y., Liu X.H., Ma Y., Wei Y.X. Molecules, 2013, Vol. 18, No.12, pp.14876-14891.
Lim C.J., Choi J.Y., Lee B.H., Oh K.S., Yi K.Y. Chemical & pharmaceutical bulletin (Tokyo), 2013, Vol. 61, No.12, pp.1239-1247.
Mospanova Ye.V., Ukrainets I.V., Bevz O.V., Savchenkova L.V., Yankovich S.I. Zhurnal organichnoi ta farmatsevtichnoi khimii – Journal of organic and pharmaceutical chemistry, 2012, Vol. 10, 2(38), pp.50-53.
Ukrainets I.V., Mospanova E.V., Jaradat N.A., Bevz O.V., Turov A.V. Chemistry of Heterocyclic Compounds, 2012, Vol. 48, No.9, pp.1347-1356.
Ukrainets I.V., Andreeva K.V., Gorokhova O.V., Kravchenko V.N. Chemistry of Heterocyclic Compounds, 2012, Vol. 48, No.12, pp.1809-1816.
Ukrainets I.V., Gorokhova O.V., Andreeva X.V., Sim G. International Journal of Pharmacy and Pharmacology, 2012, Vol. 1, No.3, pp.33-40, available at: http://www.internationalscholarsjournals.org/journal/ijpp/articles?index=3
Ukrainets I.V., Gorokhova O.V., Andreeva X.V., Golik N.Yu. Zhurnal organichnoi ta farmatsevtichnoi khimii – Journal of organic and pharmaceutical chemistry, 2013, Vol. 11, 3 (43), pp.32-35.
Ukrainets I.V., Gorokhova O.V., Andreeva X.V. Zhurnal organichnoi ta farmatsevtichnoi khimii – Journal of organic and pharmaceutical chemistry, 2013, Vol. 11, 4(44), pp.61-66.
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. Lekarstvennaya terapiya vospalitelnogo protsessa (experimentalnaya i klinicheskaya farmakologiya protivovospalitelnyh preparatov) – Drug Therapy of the Anti-inflammatory Process (Experimental and Clinical Pharmacology of Anti-inflammatory Medications). Moscow, Meditsina, 1988, pp.60-63.
Ukrainets I.V., Gorokhova O.V., Andreeva K.V. Russian Journal of Organic Chemistry, 2013, Vol. 49, No.6, pp.867-871.
GOST Style Citations
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)