UA127071U - N- [2- (5,7-DIMETHYL-2-OXOTIAZOLO [4,5-b] PYRIDIN-3-YL) -ACETYL] -BUTORATIC ACID HYDRAID EXPRESSING ANTIOXIDANT ACTION - Google Patents

Abstract

N- [2- (5,7-dimethyl-2-oxothiazolo [4,5-b] pyridin-3-yl) -acetyl] -hydrazide butyric acid of the general formula EMBED ISISServer, which has an antioxidant effect.

Description

A useful model belongs to new chemical compounds and pharmacy, in particular, the production of biologically active substances, namely M-(2-(5,7-dimethyl-2-oxothiazolo|4,5-B|Ipyridin-3-yl)-acetyl|- butyric acid hydrazide, which exhibits an antioxidant effect, and can be used in clinical medicine as an antioxidant drug.

One of the important problems of modern medicine and pharmacy is the chemical regulation of numerous pathological conditions caused by the development of oxidative stress in the body, as well as research into the mechanisms of inhibition of biochemical free radical processes. Oxidative stress is an important link in the pathogenesis of many diseases, resulting in the activation of lipid peroxidation (LPO) and the accumulation of free radicals, which is accompanied by an imbalance of enzymatic and non-enzymatic components of the body's antioxidant defense system. Increased interest in the creation of prophylactic and therapeutic antioxidant agents of synthetic origin determines the urgency of developing and improving methods for the assessment of antioxidant activity.

Thiazolidone derivatives annelized with a pyridine ring, in particular thiazolo|4,5-b|Ipyridines, are the object of increased interest of researchers, since these compounds show different types of biological activity. Therefore, of course, the synthesis of thiazolidines fused with a pyridine ring is an interesting and relevant direction.

The molecule of the claimed object contains a pyridine cycle, therefore a derivative of pyridine is similar in composition and structure to the claimed compound - an antioxidant drug - mexidol |Mashkovsky M.D. Medicines. In two volumes. T.1. - Ed. 13th, new. -

Kharkiv: Torsing, 1998. - 560 p.| formulas: on

Uh SHO

Not M dream,

However, this medicine has a number of disadvantages, in particular, when using it, nausea, dryness of the oral mucosa, and skin-allergic reactions are observed. In this context, the search for organic compounds capable of exhibiting high antioxidant activity and the development of new medicines based on them is relevant.

The basis of a useful model is the task of creating new antioxidant drugs that have improved properties and do not cause side effects.

The task is solved by the synthesis of M-(2-(5,7-dimethyl-2-oxothiazolo|4,5-b|pyridine-

From 3-yl)y-acetyl|-hydrazide of butyric acid of the general formula:

M-- iv a

Sound di o o - no

Because it has an antioxidant effect.

The synthesized compound has the appearance of a creamy crystalline powder, well soluble in

DMFA, DMSO, little - in benzene, toluene, alcohols; bad - in other organic solvents and water.

To prove the composition and structure of the synthesized compound, well-known physicochemical methods were used, in particular PMR spectroscopy and elemental analysis. The obtained results indicate the conformity of the synthesized compound with the claimed one.

The declared M-(2-(5,7-dimethyl-2-oxothiazolo|4,5-B|Ipyridin-3-yl)-acetyl|-hydrazide of butyric acid is obtained by the reaction of hydrazide (5,7-dimethyl-2-oxothiazolo |4,5-b|pyridin-3Z-yl)-acetic acid with butyric acid chloride.The reaction takes place in anhydrous dioxane in the presence of an equimolar amount of triethylamine.

The antioxidant activity of the compounds was studied by mit, determining the decrease in free radical concentration (Moiupeikh R. Te ize oi oiye o5iabie ipee gadisa! dirpepuirisguIpuagagu! (ORRN) og eziitaiiipod apiyohidapi asiimiu // U. si. Tesppoi. - 2004. - Moi. 26. -

R. 211-219). For this, the relatively stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) was used. Intensely purple DFPG in ethanol solution is characterized by a light absorption maximum at 517 nm. In the presence of antioxidants, the free radical center is quenched

DFPG, as a result of which the solution gradually loses its purple color. Comparing the optical density of the solution containing the substance under study and an excess of the radical with the optical density of the solution of the radical itself makes it possible to determine the radical-absorbing activity (RPA) of the compounds.

Solutions of the compounds in ethanol (0.3 ml, 20 nmol/l) were added to an alcoholic solution of DFPG (2.7 ml, 150 rmol/l). The mixture was intensively stirred and left for 2 hours. After that, the solution was introduced into the cuvette of the spectrophotometer and its optical density was determined. Calculate the radical-absorbing part of the body according to the following formula:

And dopg where "DPPH - optical density of a solution of the free radical DPPH (135 cmol/l), Av - optical density of a solution of DPPH with the tested substance.

Ascorbic acid (RPA-21.5 95) was used as a standard. Measurements were performed three times with independent aliquots.

Toxicometric studies of the synthesized compound were studied according to known methods

IStefanov O.V. Preclinical studies of medicinal products / Methodological recommendations. - Kyiv:

Avicenna, 2001. - 527 pp. The substance was administered in doses of 500, 800, 1000, 1500 mg/kg of animal weight, with a single parenteral administration of the suspension of the substance under study to white mice of both sexes. A group of animals that were injected with purified water was used as a control. The animals were observed for 14 days.

As a result of the conducted toxicometric studies, it was established that the value of IYuvo allows to attribute the synthesized compound to M safety class, that is, according to the degree of toxicity and danger, it meets the requirements for medicinal products.

The results of the conducted research are presented in the Table.

Table

Antioxidant activity and acute toxicity of the studied compound and the reference drug

Compound or reference drug RPA, 95 24.68 below

M -

M - M

Shk r oo 3427 320 pcs (in)

WITH

Therefore, the claimed compound exhibits a high antioxidant effect, and in terms of the degree of toxicity and danger it meets the requirements for medicinal products, therefore it can be a promising antioxidant medicinal product.

To understand the useful model, below is an example of obtaining a synthesized compound.

Synthesis of M-(2-(5,7-dimethyl-2-oxothiazolo|4,5-b|Ipyridin-3-yl)y-acetyl|-hydrazide of butyric acid. In a flat-bottomed flask, dissolve 0.01 mol of hydrazide (5 ,7-dimethyl-2-oxothiazolo|4,5-

From VIpyridin-3-yl)-acetic acid in 10 ml of anhydrous dioxane. A solution consisting of 0.01 mol of butyric acid chloride and 0.01 mol of triethylamine in 10 ml of dioxane is added to the resulting solution. Keep for 15 minutes. in a drying cabinet at a temperature of 100 "C and poured into water. The filtered precipitate is recrystallized from acetic acid. Yield - 74 95, Ttopl. 165-167 "C. Gross formula C14NivMa45.

Found, du: M-17,16; 5-9,74.

Deducted, 905: M-17.38; 5-9.95.

NMR spectrum "H: 0.86 t (311, 9U-7.4 Н7, СН»АСНе-СнНвз), 1.51-1.55 m (2Н, СНо-СНе-СнНЗ), 2.09 t (2Н, 9У-7.2 Н7, СНо-СН» e -CH"), 2.34 s (ZN, CH), 2.44 s (ZN, CH"), 4.64 s (2H, M-CH"), 7.02 s (1H,

RU.), 9.87 s (2H, SOMN), 10.24 s (2H, MNSO).

Claims (1)

FORMULA OF A USEFUL MODEL M-(2-(5,7-dimethyl-2-oxothiazolo|4,5-b|pyridin-3-yl)-acetyl-hydrazide of butyric acid of the general formula: Mchat tur r go -- about Z that exhibits an antioxidant effect.