Derivatives of 3-(6`-methoxypropanol-3`)-2-acetylfuran-2 - carboxylic acid, which has anti-allergic activity

 

(57) Abstract:

Use in medicine to create a drug that has anti-allergic activity. The inventive product: derivatives of 3-( 6-methoxypropanol - 3 ) -2-acetylfuran-2-carboxylic acid, namely ethyl ester of 3-(6 - methoxypropanol-3) -2-acetylfuran-2-carboxylic acid. C17H16O6. So pl. 206°C and about-anized 3-(6 - methoxypropanol-3) -2-acetylfuran-2 - carboxylic acid. C22H19NO6. So pl. 263°C. Inhibit the reaction of passive cutaneous anaphylaxis 32.2 52.9 per cent of Reagent 1: 6-methoxypropan-3-aldehyde. Reagent 2: acetoacetic ester or o-anisidin acetoacetic acid. The process conditions in the environment of pyridine under heating. table 1.

The invention relates to chemical-pharmaceutical industry, namely to new biologically active substances on the basis of which can be created drugs that have anti-allergic activity.

The claimed compounds are new derivative chromone, namely Amida and esters of 3-(chromosol-3l)-2-acetylfuran-2-carboxylic acid formula

< / BR>
where I R OS2H5< / BR>
II R=-

The claimed compounds, their properties and biological aktivnost are drug sodium cromoglycate (Intal) disodium salt of 1,3-bis-(2-carboxyphenyl-5-oxy)-2-oxoprop, having antiallergic activity [1]

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The purpose of the invention to provide new derivatives of chromone with more pronounced in comparison with the prototype of the INTA, antiallergic activity.

The goal has been achieved by the synthesis of compounds of the formula

< / BR>
where I R COC2H5< / BR>
II R is obtained by condensation of 6-methoxypropan-3-aldehyde with ethyl ether or o-methylaniline acetoacetic acid.

P R I m e R 1. Ethyl ester of 3-(6l-methoxypropanol-3l)-2-acetylfuran-2-Carbo - new acid.

To a solution 2,04 g 6-methoxypropan-3-aldehyde in 15 ml of dry pyridine are added dropwise of 1.26 ml (0.01 mol) of fresh acetoacetic ester. The mixture is heated on a water bath at a temperature of 60aboutC for 2.5 h, then cooled and poured into ice water, acidified with hydrochloric acid. The precipitate is filtered off and, after recrystallization from toluene obtain 2.15 g of white crystalline powder. Exit 68% of theoretical. So pl. 206aboutC.

Found, 64,12; N 4,82;

Calculated With 64,56; N 5,06; 30,38.

The IR-spectrum, liquid paraffin, 1740, 1700, 1635 (cm-1).

P R I m m e R 2. o-Anisidin 3-(6lIDA and 1,91 g o anisidine acetoacetic acid are dissolved in 20 ml of dry pyridine and heated on water bath for 4 hours After cooling, the reaction mixture is poured into ice water, acidified with hydrochloric acid, the precipitated precipitate is filtered off. After recrystallization from isopropyl alcohol get 2,75 g yellow powder. The yield was 73% of theoretical. So pl. 263aboutC.

Found, 69,62; H 5,15; N A 3.87

Calculated With 70,03; N 5,04; N 3,71.

The IR-spectrum, liquid paraffin, 3300, 1700, 1675, 1645 (cm-1)

Research anti-allergic effects of the substances was carried out on the model reaction of passive cutaneous anaphylaxis (Russian perfumery-cosmetic Association), mediated by antibodies of class IgE [2] which is one of the most frequently used methods for the evaluation of anti-allergic activity of the compounds.

Serum containing specific homotaurine antibodies, received the third week after sensitization of mice CBA with ovalbumin (0.5 μg) with aluminum hydroxide (2.5 mg/mouse). The resulting serum at a dilution of 1: 200 was injected intradermally in 6 clipped skin of the back of white rats-males line Wisar (160-180 g) in the amount of 590 mm. After 24 h, rats intravenously injected resolving dose of ovalbumin (1 mg/kg) in 1 ml of 0.5% solution of the dye Evans blue in saline. After 30 min the rats under ether Nadom at 37aboutC for 4 days. The amount of dye in extravasate was determined spectrophotometrically at 600 nm on a calibration curve.

The analyte was injected at a dose of 10 mg/kg over 90 min to a resolution of the dose of antigen. As a comparison object used antiallergic drug sodium cromoglycate (Intal), which are similar in structure (derived chromone) and action, and diasorin (similar compared [1] sodium cromoglycate was administered at a dose of 50 mg/kg (5 times greater than the analyte, as in the dose of 10 mg/kg expressed anti-allergic actions, he has not shown) intraperitoneally for 90 min to resolving dose. Control rats were injected intraperitoneally with saline. The percentage of inhibition of the reaction was calculated by the formula a 100 A 100 a percentage of inhibition of the Russian perfumery-cosmetic Association,

With mcg Evans blue in the skin of rats treated with the drug,

In mcg Evans blue in the skin of control rats.

The results of the experiments are processed statistically [3] and is shown in the table.

Determination of acute toxicity and calculations LD50carried out according to the method of Cerberus [4] White mice weighing 18-20 g were injected intraperitoneally 0.5 ml of the suspension of the substances under study, prepared the x substances is more than 1300 mg/kg, therefore, these compounds belong to the class of practically non-toxic substances.

The results of these studies show that the claimed compounds 1 and 2 have a pronounced anti-allergic action, exceeding the activity of a drug cromolyn sodium introduced at a dose 5 times higher compared to the doses of the compounds under study. The substance 2 is superior in activity diasorin.

This indicates the feasibility of further research of these substances with the aim of creating effective medicines.

Derivatives of 3-( 6-methoxypropanol - 3)-2-acetylfuran-2-carboxylic acid formula

< / BR>
where R OC2H5or

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having antiallergic activity.

 

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