N-Benzyl-1-(2-cyanoethyl)-4-hydroxy-2-oxo-1,2-dihydro-3-quinolinecarboxamides as promising analgesics

I. V. Ukrainets, O. V. Gorokhova, X. V. Andreeva, A. A. Davidenko


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.


benzyl amides; hetarylpropanoic acids; 4-hydroxy-2-oxo-1,2-dihydroquinolines; synthesis; analgesic activity


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Abbreviated key title: J. Org. Pharm. Chem.

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