Derivatives of 6-methoxy chromosol-3-acrylamide having antiallergic activity

 

(57) Abstract:

Usage: in medicine as anti-allergic drugs. The inventive product 6-methoxypropanol-3-acrylic - 4-carboethoxy and 6-methoxypropanol-3-acryl-2-carboxy 1300 mg/kg, %. inhibition of Russian perfumery-cosmetic Association-59,1 - 63,8. Antiallergic activity 5 times more than diazoline. Reagent 1: the acid chloride 6-methoxypropan-3-acrylic acid. Reagent 2: the corresponding substituted aromatic amine. 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, 6-methoxypropanol-3-acrylanmido formula:

where I R1-H; R2-COOC2H5< / BR>
II R1-COOH; R2-H.

The claimed compounds, their properties and biological activity not described in literature.

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 of DOS is 2-H. which is obtained by the interaction of the acid chloride of 6-methoxypropan-3-acrylic acid with the corresponding substituted aromatic amines.

P R I m e R 1. of 1.23 g (0.005 M) 6-methoxypropan-3-acrylic acid dissolved in 10 ml of dry 1,4 dioxane, add 0.4 ml of pyridine and 0.36 ml (0.005 M) chloride tiomila and left for 2 h at room temperature. Then to the reaction mixture was added a solution of 0,825 g (0.005 M) ethyl ester of n-aminobenzoic acid in pyridine. The mixture is heated on a water bath for 15 min, cooled and filtered loose sediment. After recrystallization from isopropyl alcohol yield is 1.3 g (68%).

So pl. 255-256about< / BR>
Found, 68,17; N. Of 4.83; N 3,55; 24,42.

Calculated From 67,50; N. Of 4.90; N 3,30; 24,30.

IR spectrum (liquid paraffin): 1710 cm-1(R);

1680 cm-1(C=C-C=0).

1620 cm-1(ONR); 995 cm-1(C=C).

The second substance 6-methoxypropan-3-acrylic-on-carboxanilide obtained according to a similar method with a total yield of 59%

So pl. 208-209aboutC.

Found, C 65,75; H 4,11; N 3,84; O 26,3.

Calculated With 66,2; N 4,15; N 3,65; O 26,0.

IR spectrum (liquid paraffin): 1685 cm-1(COOH);

1660 cm-1.

1530 cm-1(C reaction 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 (6,7).

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) (8). The resulting serum at a dilution of 1: 200 was injected intradermally in 6 clipped skin of the back of Wistar rats male Wistar (160-180 g) in an amount of 50 μl. 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 anesthesia was decapotable, the skin turned inside out, discolored areas were cut out and extracted the dye formamide at 37aboutC for 4 days. The amount of dye in extravasate was determined spectrophotometrically at 600 nm on a calibration curve (9).

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 f is e substances, because the dose of 10 mg/kg expressed anti-allergic actions, he has not shown) intraperitoneally for 90 min prior to injection of antigen. Diasorin was administered at a dose of 10 mg/kg 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 where As the 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 statistically processed (3) and listed 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 investigated substances prepared by adding 1-2 drops of Tween-80. At each dose in the experience took 6 mice. Found that LD50the investigated substances is more than 1300 mg/kg, therefore, these substances belong to the class of practically non-toxic substances (5).

The results of these studies show that the claimed compounds 1 and 2 have a pronounced anti-allergic action, exceeding the activity of drugs CROs the x substances with the aim of creating effective medicines.

Derivatives of 6-methoxypropanol-3-acrylamide General formula

< / BR>
where R1is hydrogen, R2- COOC2H5or

R1- COOH, R2is hydrogen,

having antiallergic activity.

 

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