Lipid peroxidation inhibiting 6-(thietanyl-3)aminopyrimidine-2,4(1h, 3h)-dione

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and medicine and specifically to a novel compound - 6-(thietanyl-3)aminopyrimidine-2,4(1H,3H)-dione of formula (1), which inhibits lipid peroxidation.

EFFECT: obtaining a compound which inhibits lipid peroxidation.

2 cl, 1 dwg, 2 ex

 

The present invention relates to organic chemistry and medicine, in particular to a new connection - 6-(titanyl-3)aminopyrimidine-2,4(1H, 3H)-dione, the inhibitory lipid peroxidation (LPO).

As funds involved in the inhibition FLOOR, well known drugs such as vitamin E (α-tocopherol), vitamin C (ascorbic acid), β-carotene, the precursor of vitamin a, the enzyme superoxide dismutase, as well as BHT (2,6-Di-tert-butyl-4-METHYLPHENOL) and Mexidol (2-ethyl-6-methyl-3-oksipiridina succinate) [the State register of medicines, vol. 1, M., 2004, s, 123, 142, 203, 290].

As a prototype, and the comparison drug taken methyluracil (6-methylpyrimidin-2,4(1H, 3H)-dione) as the closest analogue to the chemical structure, used in medical practice [Mashkovsky PPM Medicines. // M OOO "New wave", 2004 - Vol.2, p.160-161; P. Taran, L.N. Shishkina. The influence of 6-methyluracil on some indicators of the system of regulation of lipid peroxidation in the body. // Issues of honey. chemistry, 1993. - T. - Issue 1. - p.37-41].

The objective of the invention is to expand the Arsenal of biologically active substances, including having the property of inhibiting the FLOOR.

The technical result - obtaining biologically active substance that inhibits the FLOOR.

The inventive 6-(titanyl-3)aminopyrimidine-2,4(1H, 3H)-dione form is s (I):

inhibiting lipid peroxidation.

The specified connection and its properties are not described in literature.

The claimed compound synthesized by the interaction of 6-aminopyrimidine-2,4(1H, 3H)-dione with epimyocardium in the presence of potassium hydroxide in aqueous medium in tiirn-titanoboa rearrangement.

Example 1.

The synthesis of the claimed compounds.

To the solution was 4.02 g (72 mmol) of potassium hydroxide in 90 ml of water, add a 7.62 g (60 mmol) of 6-aminopyrimidine-2,4(1H, 3H)-dione and heated to 50-60°C. Then add to 6.9 g (66 mmol) of aetiocholanolone and stirred for 1 hour at 50-55°C. the Precipitate is filtered from the hot reaction mixture, washed with water until neutral pH of the leachate, treated with ethyl acetate, hot water, dried at 60°C. MP.=204-206°C. Gain of 8.25 g (69%) of 6-(titanyl-3)aminopyrimidine-2,4(1H, 3H)-dione, purify by crystallization from a mixture of dimethylformamide - water (volume ratio 1:1).

IR spectrum, ν, cm-1: 717 (S(CH2)2), 1384 (C-N), 1746 (C2=O), 1608 (C4=O, C=C), 2952,3344 (N-H).

An NMR spectrum1N (DMCO-d6), δ, ppm: 2,74 (1H, s, 6-NH); 2,82-2,89 (2H, m, S(CH)2); 3,98-4,07 (2H, m, S(CH)2); 4,35-4,43 (1H, m, NCH); of 6.20 (1H, s, 5-H); OF 9.89 (1H, ush. s, 1-NH); 10,27 (1H, ush. C, 3-NH).

Elemental analysis.

Found, %: C 42,36; N Br4.61; N 21,30 - C7H9N3O2S.

Calculated, %: C 42,21; N To 4.52; N 21,11.

Declare the giving is a white crystalline powder, insoluble in water, ethanol, acetone, chloroform, soluble in alkaline solution, in dimethylformamide and dimethylsulfoxide when heated.

Example 2.

Assessment of the lower level FLOOR.

The effect of the claimed compounds and drug comparisons on the processes of free radical oxidation in model systems in vitro was studied using a rapid method for determination of antioxidant activity based on detection of chemiluminescence (CHL) fluorescence arising from the interaction of free radicals (Baimatov V.N., Farkhutdinov P.P., Bagautdinov A.M. // Chemiluminescent methods for the study of free radical oxidation in agriculture, veterinary medicine and animal husbandry. - Ufa, Izd-vo "Health of Bashkortostan", 2009. - 104 S.).

The chemiluminescence was detected on the installation HLM-003 (Russia). Chlorophyll model systems were characterized by spontaneous light emission, quick flash and then developing a slow flash. The main most informative characteristics of CHL serve sutasoma glow determined by the intensity of the radiation, and the maximum amplitude of the glow.

To assess the impact on the processes of SRO in vitro studies were carried out on model systems in which reactions proceed the FLOOR.

The influence of the studied compounds on the FLOOR studied in lipids chickens the aqueous egg yolk, similar in composition to blood lipids. Lipids were obtained by homogenization of chicken yolk in phosphate buffer in the ratio 1:5 and subsequent dilution in 20 times, was selected 10 ml Add in 1 ml of 50 mm solution of Fe2+led to the initiation of oxidation of unsaturated fatty acids, which was accompanied by chemiluminescence. On light intensity is judged processes the FLOOR.

The drugs were added in model systems in concentrations appropriate therapeutic dose of a prescribed drug methyluracil. As control was used a model system in which instead of the investigated drugs were added to 0.9% saline in the same volume.

The invention is illustrated in the figure, which shows the influence of the proposed connection and methyluracil on the processes SRO in the model system of lipid peroxidation, where To control, I declare the connection II is a drug comparison methyluracil.

In the model system of liposomes the compounds inhibited the level of spontaneous luminescence, reduced flash and sutasoma CHL (figure). Thus, the antioxidant activity of compound (I) when induced by a FLOOR higher than the comparison drug - methyluracil.

1. 6-(Titanyl-3)aminopyrimidine-2,4(1H,3H)-dione of the formula:

2. The substance according to claim 1, inhibiting peroxide oxidized the e lipids.



 

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