Synthesis and biological activity of 5-aryl-4-acyl-3-hydroxy-1-[2-(diethylamino)ethyl]-3-pyrrolin-2-ones

Abstract

A series of 4,5-disubstituted 3-hydroxy-1-(2-diethylaminoethyl)-3-pyrrolin-2-ones were synthesized via reactions of methyl esters of acylpyruvic acid with a mixture of an aromatic aldehyde and 2-(diethylamino)ethylamine. The synthesized compounds were characterized with respect to antiinflammatory, antidepressant, and antibacterial properties and acute toxicity.Previously, we demonstrated [1] that reactions of methyl esters of acylpyruvic acid with a mixture of an aromatic aldehyde and 2-(dimethylamino)ethylamine yield 4,5-disubstituted 1-[2-(dimethylamino)ethyl]-3-hydroxy-3-pyrrolin-2-ones possessing antimicrobial properteis. Taking into account that, depending on the structure of substituents in position 1 of the heterocycle, the resulting 3-hydroxy-3-pyrrolin-2-ones also exhibit antiinflammatory [2], analgesic [3], antiviral [4], and nootropic [5] effects, it was of intrest to continue the search for biologically active compounds in the series of 4,5-disubstituted 1-[(dialkylamino)alkyl]-3-hydroxy-3-pyrrolin-2-ones.In this context, we have studied the interaction of methyl esters of acylpyruvic acids with a mixture of an aromatic aldehyde and 2-(diethylamino) ethylamine. It was established that the reactions between equimolar amounts of these initial compounds in 1,4-dioxane lead to a good yield of 5-aryl-4-acyl-3-hydroxy-1-[2-(diethylamino)ethyl]-3-pyrrolin-2-ones (I -XIV). The synthesized compounds appear as colorless or light-yellowish crystalline substances poorly soluble in alcohols, DMSO, and DMF (Table 1).The proposed structures of the synthesized compounds were confirmed by the results of IR and NMR spectroscopic measurements ( Table 2). The IR spectra of compounds I -XIV display the absorption bands related to stretching vibrations of the lactam carbonyl group (1676 -1698 cm -1 ) and ketone carbonyl groups (1603 -1622 cm -1 ). The spectra of compounds III, IV, VI, VII, and XIII also contain a broad band due to the enol hydroxy group (3322 -3398 cm -1 ); this band is absent in the spectra of other compounds, which is probably caused by exchange processes. R 1 = Me, R 2 = H; II: R 1 = Me, R 2