5(6)-nitro-1-(thietanyl-3)-2-ethoxybenzimidazole, inhibiting peroxidation of lipids

FIELD: chemistry.

SUBSTANCE: invention relates to field of organic chemistry, namely to novel compound - 5(6)-nitro-1-(thietanyl-3)-2-ethoxybenzimidazole, inhibiting peroxidation of lipids.

EFFECT: novel compound, possessing useful biological properties, has been obtained.

2 cl, 1 dwg, 2 ex


The present invention relates to organic chemistry and medicine, namely to a new connection - 5(6)-nitro-1-(titanyl-3)-2-ethoxybenzothiazole, inhibitory lipid peroxidation (LPO).

As the agents involved in the inhibition of PAUL, known drugs such as vitamin E (α-tocopherol), vitamin C (ascorbic acid), β-carotene, the enzyme superoxide dismutase, as well as BHT (2,6-di-tert-butyl-4-METHYLPHENOL) and Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) [the State register of medicines. Vol. 1, Wiley, 2004, pp. 103, 123, 142, 203, 290].

As a prototype and comparison drug taken Dibazol: 2-(Phenylmethyl)-1H-benzimidazol, as the closest analogue of the chemical structure used in medical practice [Register of medicines [Electronic resource]. - Access mode: http://www.reles.ru/cat/drugs/Bendazol/. Reference date: 07.05.2014].

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

The technical result - obtaining biologically active substances, inhibitory FLOOR.

Summary of the invention 5(6)-nitro-1-(titanyl-3)-2-ethoxy-benzimidazole of formula (I):

inhibits lipid peroxidation.

This compound and its properties are described in the literature.

Approx�R 1. The synthesis of the claimed compounds

Synthesis of 5(6)-Nitro-1-(titanyl-3)-2-ethoxybenzothiazole carried out by the method [Kataev, V. A., Khaliullin, A. N., Spirihin L. V., Gailunas I. A. Synthesis and isomerism of the products of the interaction 5(6)-nitro-2-chlorobenzimidazole with epimyocardium (article) //Russian Journal of organic chemistry 2002. - T. 38. - No. 10 - p. 1560-1562]. In 50 ml of anhydrous ethanol was dissolved 0.28 g (12 mmol) of metallic sodium. To the resulting solution was added 2.70 g (10 mmol) of 5(6)-nitro-1-(titanyl-3)-2-chlorobenzimidazole, boil for 5 hours. After cooling to 5-10°C, the solution was filtered, the filtrate neutralized with dilute acetic acid to pH 6-7 and evaporated. The rest is filled with water, the precipitate was filtered off, purified by crystallization from aqueous ethanol (1:1).

Yield 53%, Rf0,45. T a MP 182-184°C.

Found, % : 49,9 (C), And 4.2 (H), And 15.7 (N).

Calculated, %: 49,8 (C), And 4.2 (H) Of 15.8 (N).

Example 2

Assessment of the lower level FLOOR

The effect of the claimed compounds and product comparison on the processes of free radical oxidation (fro) in model systems in vitro was studied using a rapid method for determination of antioxidant activity, based on the detection of chemiluminescence (CHL) - the glow arising from the interaction of free radicals [Farkhutdinov R. R. research Methods chemiluminescence of biological material on chemilumi�the ETP CL-003. / R. R. Farkhutdinov, S. I. Tevdoradze // Methods for evaluation of antioxidant activity of biologically active substances of therapeutic and prophylactic purposes: Sat. Dokl. scientific. practical. of the seminar. M., 2005. - S. 147-154.].

Registration of luminescence was carried out on the device HL-003 (Russia). CL model systems were characterized by spontaneous glow, fast flash, and then a slow-paced flash. The most informative characteristics of CL were the sum of the luminescence is determined by the radiation intensity, and amplitude maximum luminescence.

To assess the impact on the processes of SRO in vivo studies were carried out on model systems in which the flow of the reaction FLOOR.

The influence of the studied compounds on PAUL studied in the chicken yolk lipids, similar in composition to the blood lipids. Lipids were obtained by homogenization of chicken yolk in phosphate buffer in the ratio 1:5 and then diluted 20-fold, were selected by Adding 10 ml. in 1 ml of 50 mm solution of Fe2+led to the initiation of the oxidation of unsaturated fatty acids, which was accompanied by chemiluminescence. The illumination intensity was judged on the process FLOOR.

Drugs were added to the model system at concentrations corresponding to therapeutic dose prescribed drugs - Dibazol. As control was used a model system, in �which is the test preparations were added to 0.9% saline in the same volume.

The invention is illustrated in the figure, which shows the effect of the claimed compounds and Dibazol on the SRO processes in the model system of lipid peroxidation, where To control, I - the claimed compound II - product comparison Dibazol.

In the model system of liposomes tested compound inhibited the spontaneous level of illumination, reduced flash and the CL light sum (figure). Thus, the antioxidant activity of compound (I) induced when the FLOOR is higher than the reference drug - Dibazol.

1. 5(6)-nitro-1-(titanyl-3)-2-ethoxybenzylidene formula:

2. A substance according to claim 1, inhibiting lipid peroxidation.


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8 cl, 1 tbl, 3 ex

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2 cl, 2 tbl, 4 ex

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2 ex

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30 cl, 3 tbl, 23 ex

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7 tbl, 5 ex

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