The synthesis and analgesic properties of N-(benzyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamides

I. V. Ukrainets, T. V. Alexeeva, O. O. Davydenko, V. V. Grinenko


Continuing the search for new analgesics among derivatives of azahetarylcaboxylic acids by the reaction of ethyl 2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate and benzylamines in boiling ethanol the corresponding group of N-(benzyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamides has been synthesized. The structure of the compounds obtained has been confirmed by the data of elemental analysis and NMR 1H spectroscopy. It is noted that the signals of aromatic protons of pyrido-pyrimidine nuclei are shifted downfield and generally for a typical AMX spin system. At the same time, the signals of aromatic protons of benzilamide fragments on the contrary are shifted upfield in all cases and focused on very narrow segments of the spectra, thereby undergoing strong distortion. According to the results of the primary pharmacological screening it has been found that using the standard model of “acetic acid writhings” all N-(benzyl)-2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamides without exception have analgesic properties to a greater or lesser  degree. Practically the same regularities of the benzylamide fragment structure –biological effect relationship as in the case of 4-hydroxyquinolin-2-ones analogues have been found. Based on it the conclusion about bioisosterism of 4-hydroxyquinolin-2-one and 2-hydroxy-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine nuclei has been made.


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

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