RU2763728C1 - Application of 3-(2-(4-nitrophenyl)-2-oxoethylidene)morpholin-2-one as antimicrobial agent - Google Patents

Abstract

FIELD: pharmacology.

SUBSTANCE: invention relates to the field of pharmacology, in particular to the use of 3-(2-(4-nitrophenyl)-2-oxoethylidene)morpholin-2-one of the following formula, as an agent with antimicrobial activity.

EFFECT: antimicrobial activity of 3 (2-(4-nitrophenyl)-2-oxoethylidene)morpholin-2-one, which can also be used as starting products for the synthesis of new heterocyclic systems.

1 cl, 1 tbl, 2 ex

Description

The invention relates to the field of organic chemistry, namely the use of individual compounds of the class 3-(2-aryl-2-oxoethylidene)morpholin-2-ones as agents with antimicrobial activity, which can be used as starting products for the synthesis of new heterocyclic systems and in pharmacology.

The claimed compound 3-(2-(4-nitrophenyl)-2-oxoethylidene)morpholin-2-one and the method for the synthesis of its derivatives are known from the prior art. The claimed compound is a product of the interaction of aroylpyruvic acids with ethanolamine or propan-2olamine (“Synthesis of pyrrolo[2,1-c][1,4]oxazine-1,6,7-triones by the interaction of 3-methylenemorpholin-2-ones with oxalyl chloride”, Tretyakov N.A., Dmitriev M.V., Maslivets A.N., ZHORH, 2020, 56, No. 8, 1203 -triones by the Reaction of 3-Methylenemorpholin-2-ones with Oxalyl Chloride Tretyakov NA, Dmitriev MV, Maslivets AN Russ JOC, 2020, 56(8), 1367-1373 doi: 10.1134/S1070428020080060]), is formed by the following scheme:

where: 1 Ar \u003d Ph (a), 4-ClC ₆ H ₄ (b), 4-BrC ₆ H ₄ (c), 4-MeC ₆ H ₄ (d), 4-MeOC ₆ H ₄ (e), 4-NO ₂ C ₆ H ₄ (e);

2 R=H (a), Me (b); 3 R=H, Ar=Ph (a), 4-СlС ₆ Н ₄ (b), 4-BrC ₆ H ₄ (c), 4-MeC ₆ H ₄ (d), 4-MeOC ₆ Н ₄ (e ), 4-NO ₂ C ₆ H ₄ (e), R=Me, Ar=Ph (g), 4-СlС ₆ Н ₄ (h), 4-BrC ₆ H ₄ (i),

4-MeC ₆ H ₄ (d), 4-MeOS ₆ H ₄ (j).

The antimicrobial activity of 3-(2-aryl-2-oxoethylidene)morpholin-2-one has not been previously investigated.

The objective of the invention is to find new compounds with antimicrobial activity, and to expand the arsenal of means of influencing a living organism.

The problem is solved by the fact that the compound 3-(2-(4-nitrophenyl)-2-oxoethylidene)morpholin-2-one exhibits high antimicrobial activity at a concentration of 1000 μg/ml.

The claimed compound is synthesized by reacting (4-nitrobenzoyl)pyruvic acid with ethanolamine in a solvent medium, followed by isolation of the target product, according to the following scheme:

The process is carried out at a temperature of 108-110°C with a Dean-Stark nozzle to separate water, and toluene is used as a solvent.

The invention is illustrated by the following examples.

Example 1 3-(2-(4-Nitrophenyl)-2-oxoethylidene)morpholin-2-one (4a).

To a solution of 130.1 mmol (4-nitrobenzoyl)pyruvic acid in 300 ml of toluene was added 130.1 mmol of acetic acid and 130.1 mmol of monoethanolamine, refluxed for 6 h with a Dean-Stark trap (until the evolution of water ceased), the solvent was removed, recrystallized in ethyl acetate, and the precipitate was filtered off. Yield 75%, m.p. 267-269°C (EyuAc).

Compound (4a) C ₁₂ H ₁₀ N ₂ O ₅ .

Found, %: С 55.21; H 3.69; N 10.54

Calculated, %: С 54.97; H 3.84; N 10.68.

Compound (4a) is a dark yellow crystalline substance, readily soluble in DMSO and DMF, sparingly soluble in less polar organic solvents, and insoluble in water and alkanes. Stable under normal storage conditions.

In the IR spectrum of compound (4a), recorded as a paste in vaseline oil, there are bands of NH stretching vibrations in the form of a broad peak at 3202 cm ^-1 , a narrow peak of the nitro group NO ₂ 3074 cm ^-1 , ketone carbonyl group at 1730 cm ^-1 and an aroyl carbonyl group at 1623 cm ^-1 .

The ¹ H NMR spectrum of the compound (4a) recorded in solution in DMSO-d _6, except the proton signals of the aromatic rings, there is a group of 4 methylene protons of the ethoxy substituent at 3.65 ppm (dd, 2H, C ⁴ H ₂ , J 8.3, 5.4 Hz), 4.60 ppm (dd, 2Н, С ³ H ₂ , J 5.8, 4.7 Hz), respectively, the singlet of the methane proton of the enamine fragment at 6.56 ppm. (1H, CH=), and a singlet of the proton of the NH group at 10.53 ppm.

Example 2 Pharmacological study of compound (4a) for antimicrobial activity.

For research, the generally accepted method of two-fold serial dilutions in a liquid nutrient medium by the micromethod was used [Guidelines for the experimental (preclinical) study of new pharmacological substances - M.: I-vo Medicine, 2005]. Initial dilutions of microorganisms in physiological saline were prepared from daily agar culture according to the optical turbidity standard (OCO) for 5 ME using a densitometer. After a series of dilutions, the final concentration of cells in the experiment was 2.5×10 ⁵ cells/ml.

The antimicrobial properties of the chemical were studied on 3 collection opportunistic strains of microorganisms: Staphylococcus aureus (strain 906), Escherichia coli (strain 1257), Candida albicans, 1353.

Compound (4a) inhibits the growth of S. aureus at a concentration of 500.0 μg/ml, culture death occurs from a concentration of 1000 μg/ml.

The proposed substance 3-(2-(4-nitrophenyl)-2-oxoethylidene)morpholin-2-one (4a) has pharmacological activity, namely antimicrobial activity, and can be used in pharmacology as a potential drug.

Claims (3)

Application of 3-(2-(4-Nitrophenyl)-2-oxoethylidene)morpholin-2-one

as an agent with antimicrobial activity.