2,4,6-trimethyl-3-oxypyridine nitrosuccinate and method for production thereof

FIELD: new 2,4,6-trimethyl-3-oxypyridine nitrosuccinate and method for production thereof.

SUBSTANCE: claimed compound is useful in medicine as future antiishemic agent with vasodilatation effect and has potent protective action in barotraumatic damages and ballistic wounds due to inhibition of secondary necrosis creation and progress. Compound of present invention is obtained by nitration of malic acid with mixture of sulfuric and nitric acids, separation of nitrohydroxymalic acid and treatment thereof with 2,4,6-trimethyl-3-oxypyridine in alcohol media with subsequent isolation of target product.

EFFECT: new antiishemic agent.

2 cl, 1 ex

 

The invention relates to a new derivative of 2,4,6-trimethyl-3-oksipiridina, specifically to nitroresorcinol 2,4,6-trimethyl-3-oksipiridina formulas (1)

The compound (1) is a hybrid molecule that combines two antiradical fragment. The function of inhibitors of radical chain reactions of oxidation performs 2,4,6-trimethyl-3-oxypyridine.

The compound (1) can be used in pharmacology as the anti-ischemic agent with vasodilator effect.

Known for high cardiac activity nitroglycerin [Ginevich, A.I., Gorehalova N.A. Cardiac glykosides. The positive and negotive aspectsof applikation nitroglyzerin., J.Chim. Pharmakol, 1989, 31, 247], which, treating of polynuclear alcohols, widely used in practice for unloading of the heart and improve coronary circulation. However, it has a high toxicity in relation to caloric animals, LD50for it is 108 mg/kg of the closest in chemical structure and therapeutic use of the present compound is N-(2-nitroxyethyl)nicotinamide commercial name nicorandil, which is currently considered as the most effective drug for the treatment of angina and congestive heart failure [K. Sakai, Am. J. Cardiology, 1989, 63, 2j-10j]. However, nicorandil has insufficient activity and, in addition,does not provide high efficiency when barotraumatic damage to exclude secondary necrosis.

The present invention is the synthesis of new anti-ischemic tools, specifically a new connection with a hybrid structure - nitroresorcinol 2,4,6-trimethyl-3-oksipiridina-based antioxidant - 2,4,6-trimethyl-3-oksipiridina and mitroxantrone acid, a source of nitrogen monoxide and designing method thereof.

This object is achieved by the method lies in the fact that malic acid nitrous mixture of sulfuric acid and nitric acid, then separated microcentro acid and process it 2,4,6-trimethyl-3-oxypyridine, followed by separation of the target product.

The invention is characterized by the following example.

Example. Nitroresorcinol 2,4,6-trimethyl-3-oksipiridina.

To a mixture of 30 ml of HNO3and 10 ml of N2SO4at 10-12°and With vigorous stirring was added 20 g of malic acid, then the reaction mixture was stirred for 30-60 min at 0-10°and poured into ice-cold water, and then neutralizing the mixture with soda to pH 3-4 and extracted target product by ethyl acetate (5×20 ml), the extract was dried over CaCl2the solvent was removed in vacuum. Output mitroxantrone acid 16 g, TPL 133-135°C (With decomp.).

NMR1H (DMSO-d6): 2.87 (DD, J1=17.0 Hz, J2=7.2 Hz, CH), 3.0 (DD, J1=17.0 Hz, J2=4.6 Hz, CH), 5.62 (DD, J1=7.2 Hz, J2=4.6 Hz, CHONO ), 13,30 (USS, noos).

NMR13(DMSO-d6): 37.8 (CH2), 80.3 (CHONO2), 172.5, 173.9 (C=O). Found (%): 27.21; N, 3.05; N, 7.61. C4H5NO7. Calculated (%): at 26.83; N, 2.81; N, 7.82.

A mixture of 1 g (0.0056 mol) mitroxantrone acid and 0.765 g (0.0056 mol) of 2,4,6-trimethyl-3-hydroxypyridine in 10 ml of methanol is boiled for 10 minutes the Solvent is removed in vacuum, the residue is triturated in 5 ml of dry isopropanol, oil crystallizes, a white crystalline precipitate was separated by filtration and dried. Obtain 1.35 g (76.5%) of salt. T square 132-133°C (With decomp.).

NMR1H (DMSO-d6): 2.21(C), 2.36 (C), 2.39 (s, SN3-PY), 2.74 (DD, J1=17.0 Hz, J2=7.8 Hz, CH), 2.95 (DD, J1=17.0 Hz, J2=4.9 Hz, CH), 5.48 (DD, J1=7.8 Hz, J2=4.9 Hz, CH), 7.05 (s, CH-PY), 11.80 (USS, noos). NMR13(DMSO-d6): 20.3, 20.5, 23.9 (CH3), 38.4 (CH2), 80.3 (CH2ONO2), 128.6 (CH-PY), 143.4, 146.3, 148.3, 153.1 (Ru), 173.0, 174.4 (C=O).

Found (%): 45.92; N, 5.30; N, 8.50. With12H16N2O8. Calculated (%): at 45.53; H 5.06; N, 8.83.

Thus, the proposed method for obtaining compounds of formula (1) allows to solve the problem of the invention and to obtain the unknown nitroresorcinol 2,4,6-trimethyl-3-oksipiridina, which, according to VSC BAS, has a high antianginal activity (the ratio of the area of necrosis of the ischemic area is 11±3.4%) and can be used in medicine in cachestatistics active compounds, with anti-ischemic activity.

According to the laboratory of physical chemistry of Biosystems, Institute of chemical physics RAS, prior the introduction of the drug as a medicine before mechanical acoustic effects on rabbits and rats allows you to fully protect the lungs of experimental animals from hemorrhage.

1. Nitroresorcinol 2,4,6-trimethyl-3-oksipiridina formulas (1)

2. The method of producing nitroresorcinol 2,4,6-trimethyl-3-oksipiridina, namely, that malic acid nitrous mixture of sulfuric acid and nitric acid, then separated microcentro acid and process it 2,4,6-trimethyl-3-oxypyridine, followed by separation of the target product.



 

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< / BR>
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< / BR>
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FIELD: medicine.

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