Salts of 2-[2-(diethylamino)ethylthio] -5,6-dimethylbenzimidazole with anti-ischemic, hypoxic and anti-arrhythmic activity and 2-[2-(diethylamino)ethylthio] - 5,6-dimethylbenzimidazole as an intermediate product for the synthesis of salts of 2-[2-(diethylamino)ethylthio] -5,6 - dimethylbenzimidazole


(57) Abstract:

Usage: salt is used as a drug that has anti-ischemic, anti-toxic and anti-arrhythmic activity; 2-[2 - (diethylamino) ethylthio] -5,6-dimethylbenzimidazole - as an intermediate product for the synthesis dihydrochloride and succinate. The inventive product of General formula (I) , where I X = 2 HCl ; II X = 0,5(CH2COOH)2the product of General formula (II) Reagent I: 5,6 - dimethyl - 2 mercaptobenzimidazole. Reagent II: 2 - (diethylamino) ethylchloride in the environment introductory ethanol or dimethylformamide in the presence of a base. Reagent III: ethereal solution of hydrogen chloride or an alcoholic solution of succinic acid. 2 C. p. F.-ly, 3 ill., 9 table.

The invention relates to new chemical compounds of benzimidazole series, namely salts of 2-[2-(diethylamino)ethylthio]-5,6-dimethylbenzimidazole General formula

where I X = 2HCl;

II X = 0,5 (CH2COOH)2that have anti-ischemic, hypoxic and anti-arrhythmic activity and can find application in medicine for the treatment of ischemic heart disease, as well as to the intermediate product to obtain them.

The proposed compounds, their properties and the biological is II).

The literature describes a number of S-alkyl(dialkyl)aminoalkyl derivatives of 2-mercaptobenzimidazole with cardiotropic [1], antihistaminic [2-4] , antiallergic [2, 3], analgesic [4-6], anti-inflammatory [4, 7, 8], as well as antidepressant [7, 8], antimicrobial [9, 10] and radioprotective activity [11].

The proposed compounds exhibit anti-ischemic activity characteristic of a bradycardia selective drugs, and, in addition, antihypoxic and antiarrhythmic activity of broad-spectrum. In accordance with this as a prototype for anti-ischemic action selected verapamil, antihypoxic - piracetam, antiarrhythmic - quinidine, procainamide, lidocaine, propranolol, verapamil.

The aim of the invention is the creation of new connections in a series of derivatives of 2-mercaptobenzimidazole with anti-ischemic activity in combination with antihypoxic and antiarrhythmic activity.

The claimed compounds are synthesized according to standard techniques by alkylation of 5,6-dimethyl-2-mercaptobenzimidazole by 2-(diethylamino)ethylchloride in aqueous ethanol or dimethylcarbamate in Pris is thio]-5,6-dimethylbenzimidazole in ethanol ether solution of hydrogen chloride or alcoholic solution of succinic acid.

The invention is illustrated in the following examples.

P R I m e R 1. The dihydrochloride of 2-[2-(diethylamino)ethylthio]-5,6-dimethylbenzamide-ash (I).

To a solution of 1.4 g (0.035 mol) of sodium hydroxide in 2 ml of water and 20 ml of alcohol was added 2.67 g (0.015 mol) of 2-mercapto-5,6-dimethylbenzimidazole and 2.75 g (to 0.016 mol) of the hydrochloride of 2-(diethylamino)ethylchloride and boiled for 5 hours After cooling, the reaction mixture is diluted with water and extracted with chloroform. The extract was washed with 10% sodium hydroxide solution and water, dried with calcium chloride and evaporated. Obtain 3.7 g (84%) of the monohydrate of 2-[2-(diethylamino)ethylthio] -5,6-dimethylbenzamide-ash; so pl. 82-83about(From aq. SP.).

Found, %:60,76; N 8,20; N 14,22; S 10,97.


Calculated, %:C 60,98; N 8,53; N, 14.22; S 10,85.

UV-spectrum (ethanol),maxnm (lg): 293 (4,32); 301 (4,38).

PMR-spectrum (deuterochloroform), , M. D.: 1,19 (6N, t, 2 N-C-CH3); 2,34 (6N, s, 2 CH3-Ar); 2,72 (4H, q, 2 N--CH3); to 2.99 (2H, m, S-CH2); the 3.11 (2H, m, N-CH2); from 7.24 (2H, s, Harene.).

The solution 4,43 g (0.015 mol) of monohydrate base in 10 ml of absolute alcohol and 50 ml of absolute ether is treated with ethereal solution of hydrogen chloride. Fallen UP>about(From a mix of see-EA).

Found, %: C 51,48; N 7,30; Cl 20,47; N 12,08; S 9,18.


Calculated, %: 51,42; N 7,19; CL 20,24; 12,00 N; S 9,15.

UV-spectrum (ethanol),maxnm (lg): 292 (4,30); 299 (4,30).

PMR-spectrum (deuterium oxide), , M. D.: 1,33 (6N, t, 2 N-C-CH3); 2.40 a (6N, s, 2 CH3-Ar) to 3.35 (4H, q, 2 N--CH3); of 3.57 (2H, m, S-CH2); 3,74 (2H, m, N-CH2); the 7.43 (2H, s, Harene.).

P R I m m e R 2. Succinate 2-[2-(diethylamino)ethylthio]-5,6-dimethylbenzimidazole (II).

To a solution of 1.78 g (0.01 mol) 2-mercapto-5,6-dimethylbenzimidazole and of 2.06 g (0.012 mol) of the hydrochloride of 2-(diethylamino)ethylchloride in 25 ml of dimethylformamide is added to 4.14 g (0.03 mol) of potash and stirred for 1 h at 80-90aboutC. After cooling, the reaction mixture is diluted with 250 ml of water. Separated oily product crystallized upon standing. The precipitate is filtered off, washed with water and dried in air. Obtain 2.24 g (76%) of the monohydrate of 2-[2-(diethylamino)ethylthio]-5,6-dimethylbenzimidazole; so pl. 82-83about(From aq. SP.).

The substance does not depression so plasma sample obtained above and is identical to him in the UV and IR spectrum.

To a solution 4,43 g (0.015 mol) of the monohydrate of the base in 30 ml of absolute alcohol portiamo the beginning of sedimentation, then add 50 ml of absolute ether. The precipitate is filtered off, washed with water and dried in air. Get to 4.33 g (87%) of compound (II); so pl. 180-181about(From the abs. SP.).

Found, %: C 60,94; N. Of 7.68; N 12,17; S 9,46.

WITH15H23N3S.0.5 C4H6O4.

Calculated, %: C 60,68; N 7,79; N 12,49; S At 9.53.

UV-spectrum (ethanol),maxnm (lg): 293 (4,44); 301 (4,44).

PMR-spectrum (deuterium oxide + 2 drops triperoxonane acid), M. D.: 1,45 (N, t, 4 N-C-CH3); 2,47 (N, s, 4 CH3Ar); 2,73 (4H, s, PRAS2CH2CO); 3,43 (8H, kV, 4 N--CH3); to 3.64 (8H, s, SCH2CH2N); 742 (4H, c, Harene.).

Pharmacological study of the claimed compounds was carried out on various models of ischemia, hypoxia and arrhythmia, in comparison with reference drugs.

1. Anti-ischemic activity.

For the evaluation of anti-ischemic properties of the claimed compounds were investigated for their influence on hemodynamics and activity of the intact heart cats. We also used two models of myocardial ischemia: a model of acute failure of coronary circulation and the model 20-minute occlusion and subsequent 30-min reperfusion of the coronary artery in cats. It was found that with the e 30 min after injection. However, other hemodynamic parameters and cardiac activity (mean arterial pressure, heart rate, average acceleration of blood flow in the aorta) was almost unchanged (see table. 1 and 2 of the act biological testing). Comparison drug verapamil also cause significant bradycardia. However, under his influence more significantly reduced systemic arterial pressure and decrease the average acceleration of blood flow in the aorta, which indicates the inhibition of the contractile function of cardiac muscle (see tab. 3).

As shown by experiments on a model of acute failure of coronary circulation have shot cats, compounds I and II (1.0 mg/kg bolus + 50 µg/kg/min during the intravenous experience) significantly reduce the average ST segment elevation in multiple leads epicardial electrogram during the 5-minute occlusion of the coronary artery. This is reflected in Fig. 1 and 2. On the y - axis the average rise in segment SI mV; the abscissa shows the time of occlusion and reperfusion of the coronary artery, min. Curve 1 - control occlusion; curve 2 - occlusion immediately after the introduction of the connection; curve 3 - 20 minutes and the comparator Drug verapamil on this model operates in a similar manner.

In the control series of experiments in animals during occlusion and reperfusion frequently encountered arrhythmia various severity. Compound I under these conditions reduces the incidence of arrhythmias, the time of occurrence of arrhythmia shifted by a period of reperfusion (see tab. 4).

Thus, compounds I and II have a pronounced anti-ischemic action which, apparently, is associated with reduced need of the heart for oxygen during emergent bradycardia. The advantage over the comparison drug verapamil is that the claimed compounds causing bradycardia does not inhibit the contractile function of the heart and not have a practical impact on other hemodynamic parameters.

Recently in the clinic coronary heart disease has greatly increased the interest in the new class antianginal funds - a bradycardia selective agents type alinidine and valiamala. From lechitel is even reduce the need of the heart for oxygen, without significant impact on other hemodynamic parameters. In this respect they differ from other drugs classes used for treatment of myocardial infarction-blockers, which inhibit the contractile function of the heart muscle and reduce cardiac output, and calcium antagonists, reduces systemic blood pressure and decreasing the contractility of the myocardium.

On the basis of obtained results it can be assumed that the proposed compounds belong to this class antianginal funds type valiamala (similar to verapamil) and can find application in medicine for the treatment of ischemic heart disease.

2. Antihypoxic activity.

To assess antihypoxic effect of the claimed compounds, in comparison with piracetam, conducted experiments on different hypoxic conditions: acute hypobaric hypoxia (AGBG), hypoxia in the containment, acute Himicheskaya hypoxia (Ageg), acute histologically hypoxia (AGTG), apoxia in mice.

The effect of compound I on portability AGBG was studied in the pressure chamber when the "rise" over 1 min to a height of 11000 feet was Estimated life expectancy (TJ) animal who's rats-males, pre-divided according to their sensitivity to AGBG to highly resistant (WU) and discostick (WELL). The proposed connection I and the comparator drug was administered intraperitoneally in saline solution for 30 minutes before experienced climb to 11000 m experimental Data (see tab. 5) show that in terms AGBG the inventive compound in a dose of 40 mg/kg increases the life expectancy of WELL and WU animals, respectively, 1.5 and 1.7 times. Piracetam has a similar antihypoxic effect on the animals WELL and does not affect the resistance to AGBG WU animals. Therefore, in conditions of simulated hypoxia connection I has a wider range than piracetam.

The effect of compound I on the lifespan of animals in terms of containment was studied in outbred mice, which were put in glass jars with a volume of 200 ml; cans tightly closed. Register the lifetime of the mice before the onset of their death from lack of oxygen. The data obtained (see tab. 6) indicate that compound I, as well as piracetam, does not significantly impact on the duration of life of the animals on this model of hypoxia.

It was also studied the influence soedinen the males of sodium nitrite at a dose of 300 mg/kg Compound I was administered intraperitoneally 30 min before the injection of sodium nitrite. Control served as saline solution, administered 30 min prior to hypoxia. Estimated lifespan of mice from the moment of introduction of the sodium nitrate to the death of the animal. The results of this series of experiments show that the claimed compound I in a dose of 40 mg/kg, as well as piracetam, not having antihypoxic action, and at a dose of 80 mg/kg is superior in efficacy of the drug in comparison to 1.4 times (see tab. 7).

In terms OGTG connection I, like piracetam, none of the investigated doses does not show antihypoxic properties (see tab. 8).

It was also investigated antihypoxic action of the compounds I and II on the model of apoxie caused by compression of the trachea in mice. On the protective effect of substances judged by the duration of preservation of the bioelectric activity of the heart. Experiments showed that control the duration of the bioelectric activity of the heart in conditions of simulated hypoxia was 453 43,8 C. the Compounds I and II in a dose of 80 mg/kg (intraperitoneally) increased this figure to 980,4103,2 with and 775,889,9 s, respectively. The claimed compounds increased the number of animals living in conditions of apoxie more than 1 compounds I and II are distinct antihypoxic protective effect on different models of hypoxia. Compound I shows antihypoxic activity in acute hypobaric and acute himicheskoi hypoxia and exceeds piracetam on spectrum use in hypoxia of different etiology; AGBG shows antihypoxic effect, regardless of individual resistance of the animal to it, unlike piracetam, increasing life expectancy only discostick animals and, in addition, is effective in smaller doses than piracetam used in the clinic at a dose of 400 mg/kg and above.

All this allows us to consider the connection I more promising antihypoxic drug compared with piracetam used in the clinic.

3. Antiarrhythmic activity.

Pharmacological study of the claimed compounds I spent on experimental models of arrhythmias: chloralkali - in awake rats, adrenaline - in awake rabbits and arabanoo in anesthetized Guinea pigs.

The results of the experiment showed that the model adrenaline arrhythmia connection I has a pronounced antiarrhythmic effect. The effect was more significant than antiaritmikov class I - quinidine, procainamide hydrochloride and lidocaine, and almost no witeska tests).

A significant antiarrhythmic effect of compound I showed on the model chloralkali arrhythmia: it's at a dose of 1.75 mg/kg prevented the death of rats from lethal fibrillatio ventricles. This model comparison I several times was more procainamide hydrochloride or lidocaine, but was slightly less than the propranolol and verapamil (see tab. 9).

It is important to note that arabanoo models of arrhythmias in Guinea pigs connection I 2-3 times increased the survival time of the animals (see table. 9).

As the experiments showed, the claimed compound I has a relatively low toxicity (LD5048 mg/kg when administered intravenously to rats), and, most importantly, it has high anti-arrhythmic index, i.e., a greater breadth of therapeutic action. By this measure, the compound I is superior also widely known antiaritmiki as quinidine, procainamide, lidocaine, verapamil and propranolol.

Thus, on the basis of obtained data we can conclude that the claimed compound I is an antiarrhythmic agent that combines the properties of antiaritmikov I, II and IV classes. In comparison with the known means of complications, taken as Comparators, soedineniya I is the unlike most antiaritmikov, as shown by experiments on models of ischemia, does not cause inhibition of contractility.

These data suggest that the proposed connection I may be promising for the creation of new antiarrythmia with a wide spectrum of action.


1. Salts of 2-[2-(diethylamino)ethylthio]-5,6-dimethylbenzimidazole General formula

< / BR>
where I X - 2HCl;

II X - 0,5 (CH2COOH)2,

with anti-ischemic, hypoxic and anti-arrhythmic activity.

2. 2-[2-(Diethylamino)ethylthio]-5,6-dimethylbenzimidazole

< / BR>
as an intermediate product for the synthesis of salts of 2-[2-(diethylamino)ethylthio]-5,6-dimethylbenzimidazole.


Same patents:

The invention relates to new derivatives of benzimidazole, method of production thereof and their use as medicines

The invention relates to tetrahydropyrimidine derivative of formula (1) or their pharmaceutically acceptable salts, suitable as 3-HT3-capetronic antagonists:

(1) where Неt is a heterocyclic group, possibly substituted by 1-3 substituents selected from lower alkyl, lower alkenyl, lower quinil, group cycloalkyl-lower alkyl, arylalkyl, lower alkoxycarbonyl, halogen atom;

X represents a single bond attached to the carbon atom of the heterocyclic group

The invention relates to new chemical compound - complex 1-ethylimidazole with ascorbate zinc (eskazole) formula

enhance the body's resistance to the action of nitrogen dioxide and has cytoprotective and antihypoxant activity (N state of registration 10191991)

The invention relates to new imidazole derivative of General formula I

where R1-COOH or the group< / BR>
R2=H-C3H7or n-C4H9;

R3-Cl, CF3C2F5C6H5or COOH;

R4-COOH, CHO, or CH2HE, provided that

a) when R4-CH2OH, R3-C2F5and R2-n-C3H7,

b) when R3-COOH, R4also is COOH,

b) when R2-n-C3H7, R3-C2F5and R4-COOH, R1is the groupwhich inhibit the action of the hormone angiotensin and can be used in medicine

The invention relates to 7-examinerlawrence heterocyclic Amida - analogues of prostaglandins, which are receptor antagonists AND thromboxane a2(THA2or combined receptor antagonists AND thromboxane a2(thromboxane synthetase inhibitors, and are used, for example, in the treatment of thrombotic disease and/or vascular spasm: have a long duration of action

The invention relates to new chemical compounds in a series of benzimidazole, namely periodical benzimidazole General formula 1

where R is H, CH3; R1= CH3H

provided that 1A R - H, R1- H (N 65 in the work log); 1B, R = CH3, R1= H (N 66 in the work log); 1B, R = CH3, R1= CH3(N 71 in the work log);

possessing antibacterial action

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with treating patients with uterine cervix cancer with relapses in parametral fiber and in case of no possibility for radical operative interference and effect of previous radiation therapy. During the 1st d of therapy one should intravenously inject 30 mg platidiam incubated for 1 h at 37 C with 150 ml autoblood, during the next 3 d comes external irradiation per 2.6 G-r. During the 5th d of therapy one should introduce the following composition into presacral space: 60 ml 0.5%-novocaine solution, 1 ml hydrocortisone suspension, 2 ml 50%-analgin solution, 1 ml 0.01%-vitamin B12 solution, 1.6 g gentamycine, 800 mg cyclophosphan, 10 mg metothrexate. These curative impacts should be repeated at mentioned sequence four times. The method enables to decrease radiation loading and toxic manifestations of anti-tumor therapy at achieving increased percent of tumor regression.

EFFECT: higher efficiency of therapy.

1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a group of new derivatives of 4,5-dihydro-1H-pyrazole of the general formula (I):

wherein R means phenyl, thienyl or pyridyl and these indicated groups can be substituted with (C1-C3)-alkoxy-group or halogen atom; R1 means phenyl that can be substituted with (C1-C3)-alkoxy-group or pyridyl group; R2 means hydrogen atom or hydroxy-group; Aa means one group among the following groups: (i) , (ii) , (iii) , (iv) or (v) ; R4 and R5 mean independently from one another hydrogen atom or (C1-C8)-branched or unbranched alkyl; or R4 means acetamido- or dimethylamino-group or 2,2,2-trifluoroethyl, or phenyl, or pyridyl under condition that R5 means hydrogen atom; R6 means hydrogen atom at (C1-C3)-unbranched alkyl; Bb means sulfonyl or carbonyl; R3 means benzyl, phenyl or pyridyl that can be substituted with 1, 2 or 3 substitutes Y that can be similar or different and taken among the group including (C1-C3)-alkyl or (C1-C3)-alkoxy-group, halogen atom, trifluoromethyl; or R3 means naphthyl, and its racemates, mixtures of diastereomers and individual stereoisomers and as well as E-isomers, Z-isomers and mixture of E/Z-compounds of the formula (I) wherein A has values (i) or (ii), and its salt. These compounds are power antagonists of Cannbis-1 (CB1) receptor and can be used for treatment of psychiatric and neurological diseases. Except for, invention relates to a pharmaceutical composition used for treatment of some diseases mediated by CB1-receptor, to a method for preparing this composition, a method for preparing representatives of compounds of the formula (I) wherein Aa means group of the formulae (i) or (ii), intermediate compounds used for preparing compounds of the formula (I) and to a method for treatment of some diseases mediated by CB1-receptor.

EFFECT: valuable medicinal properties of compounds.

16 cl, 9 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new 1-(p-thienylbenzyl)-imidazoles of the formula (I): , wherein indicated residues represent the following values: R(1) means halogen atom, (C1-C4)-alkoxyl, (C1-C8)-alkoxyl wherein one carbon atom can be replaced with heteroatom oxygen atom (O); R(2) means CHO; R(3) means aryl; R(4) means hydrogen halogen atom; X means oxygen atom; Y means oxygen atom or -NH-; R(5) means (C1-C6)-alkyl; R(6) means (C1-C5)-alkyl in their any stereoisomeric forms and their mixtures taken in any ratios, and their physiologically acceptable salts. Compounds are strong agonists of angiotensin-(1-7) receptors and therefore they can be used as a drug for treatment and prophylaxis of arterial hypertension, heart hypertrophy, cardiac insufficiency, coronary diseases such as stenocardia, heart infarction, vascular restenosis after angioplasty, cardiomyopathy, endothelial dysfunction or endothelial injures, for example, as result of atherosclerosis processes, or in diabetes mellitus, and arterial and venous thrombosis also. Invention describes a pharmaceutical composition based on above said compounds and a method for their applying also.

EFFECT: valuable medicinal properties of compounds and composition.

10 cl, 19 ex

FIELD: organic chemistry and pharmaceutical compositions.

SUBSTANCE: invention relates to new 3-(5)-heteroaryl-substituted pyrazoles of formula I , tautomers or pharmaceutically acceptable salt of compounds and tautomers. In formula R1 is hydride, piperidinyl substituted with methyl, lower alkyl optionally substituted with halogen, hydroxyl, lower alkylanimo or morpholino; R2 is hydride, lower alkyl, amino, aminocarbonylamino, lower alkylaminocarbonylamino, lower alkylsulfonylamino, aminosulfonylamino, lower alkylaminosulfonylamino; Ar1 is phenyl optionally substituted with one or more independently selected halogen; HetAr2 is pyridinyl with the proviso that R2 is not amino or n-propyl when HetAr2 is pyridinyl; and HetAr2 is not 2-pyriridinyl when R2 is hydrogen or lower alkyl. Compounds of formula I have kinase p38 inhibitor activity and are useful in pharmaceutical compositions for treatment of various diseases.

EFFECT: new effective kinase p38 inhibitors.

23 cl, 6 dwg, 1 tbl, 1 ex

FIELD: veterinary science.

SUBSTANCE: a dog should be introduced with 4-[3-(difluoromethyl)-5-(3-fluoro-4-methoxyphenyl)-1H-pyrazole-1-il]benzene sulfonamide or its pharmaceutically acceptable salt at daily dosage ranged about 0.1-10 mg/kg body weight.

EFFECT: higher efficiency of therapy.

4 cl,262 ex, 12 tbl

FIELD: medicine, gynecology, anesthesiology.

SUBSTANCE: invention concerns to a method for carrying out the anesthesiology assistance for woman in childbirth with accompanying bronchial asthma. Method involves administration of atropine, dimedrol, analgin and clophelin. Method involves additional intravenous administration of transamine for 5-7 min. Transamine is administrated in doses 12-14 and 15-17 mg/kg in woman in childbirth with body mass 75 kg and above and 74 kg and less, respectively. Method provides enhancing quality and safety of anesthesia in this class of woman in childbirth.

EFFECT: improved assistance method.

7 tbl, 4 ex

FIELD: medicine, dermatology, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to an antifungal gel pharmaceutical composition based on ketoconazole and clotrimazole that are derivatives of imidazole. The composition comprises ketoconazole or clotrimazole as an active component, polyethylene glycol-400 (PEG-400) as a solvent, carboxyvinyl polymer as a gel-forming agent, polyethylene glycol as a gel stabilizing agent, organic amine or inorganic bas as a regulator of pH and water taken in the definite ratio of components. The composition is prepared by dissolving active component in PEG-400, dispersing carboxyvinyl polymer in water, successive addition to dispersion propylene glycol as a stabilizing agent and regulator of pH and combination of prepared solution and gel followed by stirring the mixture up to preparing the gel composition with pH 5-7. Invention provides preparing antifungal composition with reduced adverse effect.

EFFECT: improved preparing method, valuable medicinal properties of composition.

2 cl, 1 tbl, 11 ex

FIELD: veterinary science.

SUBSTANCE: the present innovation deals with applying selector as a selenium-containing organic preparation to be introduced for cows and calves monthly intramuscularly at the dosage of 10 mcg/kg body weight. The method provides decreased fodder expenses for the synthesis of the production obtained.

EFFECT: higher productivity in cattle.

2 ex, 7 tbl

FIELD: organic chemistry, medicine, allergology, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a method for treatment of patient suffering with allergic disease. Method involves administration to patient the therapeutically effective dose of pharmaceutical composition comprising compound of the formula (I)

. The compound elicits high effectiveness in treatment of allergy and shows low toxicity also.

EFFECT: improved method for treatment.

9 cl, 2 tbl, 2 dwg, 40 ex

FIELD: veterinary science.

SUBSTANCE: one should apply a selenium-containing preparation named selecor: it should be introduced on the 80-90th d of swine gestation twice at 10-15-d-long interval parenterally at the dosage of 20 mg/kg animal body weight. Application of low-toxic antioxidant as selecor enables to improve functional properties of cell membranes of placental system and endometrium and increase inspecific immune resistance in sows. It, also, enables to increase fertility in sows, values of uncomplicated deliveries and puerperal period.

EFFECT: higher viability of off-spring.

2 ex, 3 tbl

FIELD: organic chemistry, biochemistry, pharmacy.

SUBSTANCE: invention relates to new heterocyclylsulfonyl alkylcarboxylic acids and their derivatives of the general formula (1): or their pharmaceutically acceptable salts, N-oxides or hydrates possessing the inhibitory effect on kinase activity and to the focused library for search of active leader-compounds comprising at least abovementioned compound. In the general formula 91) W represents optionally substituted heterocyclic radical, among them: pyrrole-3-yl, thiophene-2-yl, isooxazole-4-yl, pyrazole-4-yl, imidazole-4-yl, pyridine-3-yl, 1H-2,4-dioxopyrimidine-5-yl, 2,3-dihydro-1H-indole-5-yl, 2,3-dihydro-1H-indole-7-yl, 1,3-dihydro-2-oxoindole-5-yl, 2,3-dioxo-1H-indole-5-yl, 2-oxo-3H-benzoxazole-6-yl, benzothiazole-6-yl, 1H-benzimidazole-5-yl, benzo[1,2,5]oxadiazole-4-yl, benzo[1,2,5]thiadiazole-4-yl, 1,2,3,4-tetrahydroquinoline-6-yl, 3,4-dihydro-2-oxo-1H-quinoline-6-yl, quinoline-8-yl, 1,4-dihydro-2,3-dioxoquinoxaline-6-yl, 3-oxo-4H-benzo[1,4]oxazine-7-yl, 3-oxo-4H-benzo[1,4]thiazine-7-yl, 2,4-dioxo-1H-quinazoline-6-yl, 2,4-dioxo-1,5-dihydrobenzo[b][1,4]diazepine-7-yl or 2,5-dioxo-3,4-dihydrobenzo[b][1,4]diazepine-7-yl; Y represents optionally substituted methylene group; R1 represents chlorine atom, optionally substituted hydroxyl group, optionally substituted amino-group, optionally substituted azaheterocyclyl; n = 1, 2 or 3; or Yn represents carbon atom of optionally substituted (C3-C7)-cycloalkyl or optionally substituted (C4-C7)-heterocyclyl. Also, invention relates to a pharmaceutical composition in form of tablets, capsules or injections placed into pharmaceutically acceptable package.

EFFECT: valuable properties of compounds.

5 cl, 3 sch, 5 tbl, 6 ex