Methylation of position 8 in the pyridine moiety of the N-(benzyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamide molecule as an attempt to enhance their analgesic properties

I. V. Ukrainets, O. V. Gorokhova, L. V. Sydorenko, S. G. Taran

Abstract


The chemical modification of the pyridine moiety of the molecule – displacement of the methyl group in position 8 of pyrido[1,2-a]pyrimidine nucleus has been considered as one of the possible versions to optimize the biological properties of N-(benzyl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamides. The synthesis of the research targets was carried out by the reaction of the corresponding benzylamines and ethyl 2-hydroxy-8-methyl-4-oxo-4H-pyrido[1,2-a] pyrimidine-3-carboxylate, in its turn obtained by condensation of 2-amino-4-methylpyridine (i.e. the product with the methyl group in the intentionally required position) and triethyl methanetricarboxylate. The structure of the compounds obtained has been confirmed by the data of elemental analysis and NMR 1H spectroscopy, and in the case of optically active 1-phenylethylamides additionally by polarimetry. The study of the analgesic properties of all N-(benzyl)-2-hydroxy-8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamides was performed on the standard experimental “acetic acid writhing” model. At the same time, it has been found that our modification is accompanied with the increased biological activity of exclusively para-substituted derivatives. For profound research 4-fluorobenzylamide exceeding Piroxicam and Nabumetone by the level of the specific effect has been recommended as a potential new analgesic.


Keywords


amidation; tricarbonylmethane heterocyclic derivatives; 2-hydroxy-4-oxo-4H-pyrido[1,2-a] pyrimidine-3-carboxamides; synthesis; chemical modification; analgesic activity

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References


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DOI: https://doi.org/10.24959/ophcj.15.858

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

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