Isonicotinohydrazide tarakanovas acid exhibiting hypoglycemic activity

 

(57) Abstract:

The invention relates to the class of hydrazides of dicarboxylic acids, namely to a new biologically active isonicotinohydrazide tarakanovas acid formula

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The compound obtained by the interaction of the hydrazide of isonicotinic acid with citramonum anhydride. The compound is a white crystalline substance, soluble in water, ethanol, DMF with TPL=103-104oC (R). The connection has hypoglycemic activity, reducing the level of sugar in the blood of healthy rats with intraperitoneal injection at a dose of 50 mg/kg 34,62,4% after 3 h and 29,96,9% after 5 h; when administered orally to rats with alloxan model of diabetes in a dose of 50 mg/kg reduces the level of glucose in the blood by 41,33,0% after 3 h and 37,73,2% after 5 h LD50intraperitoneal injection white mice equal to 410 (350-470) mg/kg 1 tab.

The claimed connection relates to the field of organic chemistry, class, hydrazides of dicarboxylic acids, namely to a new biologically active isonicotinohydrazide tarakanovas acid (I) formula

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which can find use as a hypoglycemic drug drug. The closest structural Ana is rmula

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used as anti-TB drug [Mashkovsky M. D. Medicines (manual for doctors), Kharkov, Torching", So 2, 332 S., (1997)]. The drug hypoglycemic activity is not.

Known and used in medical practice hypoglycemic drugs: gliclazide [Mashkovsky M. D. Medicines (manual for doctors), Kharkov, Torching", So 2, S. 24-25, (1997)] and Metformin [RLS-encyclopedia of medicine/ CH. editor Y. F. Krylov, M,, RLS - 2000", S. 573, (2000)], which were taken as standards of comparison hypoglycemic effect.

The aim of the invention is to obtain a new previously undescribed isonicotinohydrazide tarakanovas acid, having a hypoglycemic action. This goal is achieved by obtaining isonicotinohydrazide tarakanovas acid by acylation of the hydrazide of isonicotinic acid anhydride tarakanovas acid

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The method of obtaining isonicotinohydrazide tarakanovas acid. A solution of 1.12 g (0.01 mol) of anhydride tarakanovas acid in 50 ml of ethyl acetate and a solution of 1.37 g (0.01 mole) of the hydrazide of isonicotinic acid in 20 ml of water is poured while stirring at a temperature of 20oWith videris (R).

The inventive compound is a white crystalline substance, soluble in water, ethanol, DMF. The NMR spectrum1N ("OC-2310" (60 MHz) in DMSO-d6internal standard - GMDS) compounds are: a singlet of three protons of methyl group at 1,78 m D., singlet of one proton retinovoy group when 6,18 memorial plaques, two doublet of the four protons of the pyridine ring of 7.82 at M. D. and cent to 8.85 M. D., broadened signal of two protons hydrazide group at 10,85 m D.

The connection I investigated for the presence of hypoglycemic activity [II N. Century , Dolzhenko, A. C., Koterov C. P., Godin, A. T., Kozminykh C. O. Chem. -farmac. magazine, N12, S. 9-11, (1999)]. Experiments to study the hypoglycemic activity was carried out on healthy rats of both sexes and rats of both sexes with alloxan model of diabetes. The substance and the Comparators was administered to healthy animals at a dose of 50 mg/kg intraperitoneally and the animals with diabetes at a dose of 50 mg/kg orally. The control used equiano amount of 1% starch mucus. The concentration of glucose in the blood of animals was determined by glucose oxydase method before the introduction of substances through 3 and 5 hours after it. Animals were deprived of food for 14 hours before the experiment and at the time of the meeting, the water was not limited. In Icient The Student.

Acute toxicity intraperitoneal injection was determined by nonlinear white mice weighing from 17 to 25 g of the test substance and the Comparators were injected intraperitoneally in the form of an aqueous solution at a rate of 0.5 ml per 10 g in ascending doses. The results were processed by Prozorovsky calculation of the median lethal dose (LD50) at P=0.05 [Prozorovsky centuries, Prozorovsky M. P., Demchenko, C. M. Pharmacol. and toxicol., N4, S. 497-502, (1978)].

Compared the degree of hypoglycemic activity after 3 and 5 hours after administration of the compounds with standard compounds and their toxicity. The test results presented in the table.

For the studied compounds LD50410 (350-470) mg/kg According to the classification of the toxicity of preparations of compound I refers to the class of low-toxic drugs [Izmerov N. F., Sanotski I. C., Jones, K. K. Parameters toxicometric industrial poisons. M, "Medicine", S. 196-197, (1977)].

As can be seen from the table, studied the connection, showing excellent hypoglycemic activity, while not significantly different acute toxicity, superior drugs comparison on the speed of onset of effect and the severity of the action after 3 hours POS is the glycemic activity is low-toxic and very quick onset of effect. Therefore, the claimed connection I can find application in medicine as a hypoglycemic drugs.

Isonicotinohydrazide tarakanovas acid

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having hypoglycemic activity.

 

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