Substituted phenylamide-3-(4`-oxo - 4h-1`-benzopyranyl-3`)- propen-2-carboxylic acid, which has anti-allergic activity

 

(57) Abstract:

Usage: in medicine to create a drug that has anti-allergic activity. The invention productsmany phenylamide 3-( 4-oxo 4 1 benzopyranyl - 3 )-propen-2-carboxylic acid f-ly I, where R is 1. COCH32. SO2NH23. COOC2H4N(C2H5)2. So pl. 232-233°C, 273-275°C, 211-213°C. compounds of f-crystals I inhibit the reaction of passive cutaneous anaphylaxis by 57.3 76,1% and surpass Intal. Connection structure f-ly I

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 replaced phenylamide 3-(4'-oxo-4H-1'-benzopyranyl-3')-propen-2-CT - oil acid formula

where I R is COCH3< / BR>
II R-SO2NH2< / BR>
III R-COOC2H5N(C2H5)2< / BR>
The claimed compounds, their properties and biological activity not described in literature.

The closest analogue to the structure and action of the claimed compounds are drug cu is logical activity [1]

< / BR>
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

where I R is COCH3< / BR>
II R-SO2NH2< / BR>
III R-COOC2H4N(C2H5)2that obtained by the interaction of the acid chloride of 3-(4'-oxo-4H-1'-benzopyranyl-3')-propan-2-carboxylic acid and substituted aromatic amine.

P R I m e R 1. p-Acetylenic 3-(6'-methoxy-4'-oxo-4H-1'-benzopyranyl-3')-propen - 2-carboxylic acid (substance 1).

To a solution of 1.35 g (0.01 mol) p-aminoacetophenone in 10 ml of dry pyridine was added with stirring 2.7 g of acid chloride of the appropriate acid. The reaction mixture was stirred at room temperature for 4 h and left for the day. After decomposition of the reaction mixture is cooled, acidified water, the precipitate is filtered off, dried and periostat of DMF. Yield 2.25 g (62% of theoretical). So pl. 232-233aboutC.

Found, C 68,92; H A 4.53; N To 3.92.

Calculated C 69,4; H To 4.68; N 3,86.

The infrared spectrum, vaseline oil; 3360, 1685, 1650, 980 (cm-1)

A similar technique is acid (substance 2). The output is 3.08 g (76% of theoretical). So pl. 273-275aboutC.

Found, C 56,72; H Of 3.85; N 7,18.

Calculated C 57,00; H 4,00; N 7,00.

IR spectrum (liquid paraffin) and p-carditimmediately 3-(6'-methoxy-4'-oxo-4H-1'-benzopyranyl-3')-Pro-pen-2-carboxylic acid (substance 3). Output 2,69 g (58% of theoretical). So pl. 211-213aboutC.

Found, C 67,80; H 5,72; N 6,15.

Calculated C And 67.2; H 6,03; N 6,03.

IR spectrum (liquid paraffin) 1726, 1675, 1620, 1270 (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 antibody class NgE [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 an amount of 50 μl. After 24 h, rats intravenously injected resolving dose of ovalbumin (1 mg/mouse) in 1 ml of 0.5% solution dyed orcival, 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.

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 in action) [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 prior to injection of antigen. Diasorin was administered at a dose of 10 mg/kg intraperitoneally for 90 min prior to injection of antigen. Control rats were injected intraperitoneally with saline. The percentage of inhibition of the reaction was calculated by the formula:

A= 100 where a percentage of inhibition of the Russian perfumery-cosmetic Association,

With mcg Evans blue in the skin of rats that received 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.

The definition of acute toxico ml suspension of the investigated substances, prepared with addition of 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.

The results of these studies show that the claimed compounds 1, 2 and 3 has a pronounced anti-allergic action, exceeding the activity of drugs cromolyn sodium and diazoline. This indicates the feasibility of further research of these substances with the aim of creating effective medicines.

Substituted phenylamine 3-(4'-oxo-4H-1'-benzopyranyl-3')-propen-2-carboxylic acid of General formula

< / BR>
where R is COCH3, SO2NH2or COOC2H4N(C2H5)2group,

having antiallergic activity.

 

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