Application of soluble guanilate-cyclase activators for treatment

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to field of pharmaceutics and medicine and pharmaceutical composition for treatment of reperfusion disorders, which contains inert auxiliary substances and as active component compounds of general formula I-Iva.

EFFECT: obtaining pharmaceutical composition for treatment of reperfusion disorders.

3 ex

 

The present invention concerns the use of compounds for obtaining pharmaceutical drug/medicine for the prevention and/or treatment of reperfusion disorders.

Reperfusion disorders in General occur after prolonged ischemic period, for example, as a result of penetrating accumulated toxic metabolites after restoration of blood flow and/or massive selection of free calcium ions in excitable cells. These violations often occur after thrombosis, especially after acute arterial thrombosis, if there is no offsetting of collateral circulation (the so-called heart attacks). The most famous myocardial infarction and cerebral infarction (stroke). While early restoration of blood flow through thrombolyse after temporary ischemia can reduce the amount of cytopathic violations (scale heart attack) or to prevent them, the resumption of blood flow in spite of this can to some extent be called, for example, malfunction of the heart or the death of cells (postperfusion syndrome). Therefore, most clinical value are medicines that help to maintain normal functions, such as heart during reperfusion and in various forms of surgery.

It is known that ischemic reperfusion disorders and is knitted with this cellular damage is manifested, for example, in myocardial infarction, replacement, arterial coronary vessels of the heart, especially in cardiac surgery to open the chest, sore throat, diseases caused by thrombosis peripheral vascular, stroke, transplantation of organs and tissues (e.g. heart, liver, kidneys, lungs), General surgery, acute renal failure and insufficient blood flow to organs (e.g. lung, heart, liver, intestines, pancreas, kidneys, limbs or brain).

It is known that the mechanisms (for example, when the action of substances that emit NO), which lead to an increase in the intracellular transport of material to guanosine monophosphate (GMP), which may also lead to reduction of reperfusion disorders, if treatment with these drugs is started before the ischemic period or in some cases during it. The application before the ischemic period in General is known as prevention/protection and/or advance preparation and includes cellular protection, especially the protection of excitable cells (e.g., nerve and muscle cells). Treatment after ischemic period is called the respectively subsequent supportive treatment.

Elevated levels of GMF can lead to the protection of cells, tissues and organs from reperfusion disorders. Activate (agonists, agents, obladaushi and affinity to the receptor) of soluble guanylate cyclase leads to an increase in the transport of material for GMF. Surprisingly now found that the compounds according to the invention, the activators of soluble guanylate cyclase (compounds corresponding to formulas I to VI), especially suitable for the production of pharmaceuticals / medicines for the prevention and/or treatment and restrictions reperfusion disorders in mammals, especially in humans.

The compound (I) corresponds to the following formula:

The compound (I), its preparation and use as a medicinal product has already been published in the international patent WO 01/19780.

The compound (II) answers to the following formula:

The compound (II), its preparation and use as a medicinal product has already been published in the international patent WO 00/06569.

The compound (III) meet the following formula:

The compound (III), its preparation and use as a medicinal product has already been published in the international patent WO 00/06569 and WO 02/42301.

The compound (IV) meets the following formula:

The compound (IV), its preparation and use as a medicinal product has already been published in the international patent WO 00/06569 and WO 3/095451.

The compound (IVa) corresponds to the following formula:

The compound (IVa), its preparation and use as a medicinal product has already been published in the international patent WO 00/06569 and WO 03/095451.

The compound (V) corresponds to the following formula:

The compound (VI) corresponds to the following formula:

Compounds (V) and (VI), their preparation and use as pharmaceuticals have already been published in the international patent WO 00/02851.

The object of the present invention is the use of compounds corresponding to the formulas (I-VI), their salts, hydrates and hydrates of salts to obtain drugs for the treatment of circulatory problems.

An additional embodiment of the present invention includes a procedure for the prevention and/or treatment of disturbances of the blood supply using at least one of the compounds corresponding to formulae (I-VI).

The next subject of the present invention is a drug containing at least one compound according to the invention and at least one or more other biologically active substances, especially for the treatment and/or prophylaxis of the aforementioned diseases.

Compounds according to the invention can act systemically and/or locally. With this purpose, they can be applied in a suitable way, as for example: oralin is m, parenteral, intra-lungs, nazalnam, in the sublingual region (under the tongue), lingual (tongue), buccal (cheek area), rectal, and transdermal, subcutaneous, conjunctival (conjunctiva), inside ear (custom application) or as implant or stent (device for the reconstruction of the lumen of the body).

For these applications, the compounds according to the invention can be produced in easy to use forms.

For oral administration state of the art are suitable, such dosage forms that are fast and/or modify the dosage of the compounds according to the invention contained in the crystalline and/or amorphous and/or in the form of a solution, such as: tablets (uncoated or coated, for example with a coating resistant to gastric juice, or slowly soluble, or insoluble, which allows you to control the release of the compounds according to the invention), tablets quickly disintegrating in the oral cavity, or a wafer/drugs in the shell, lyophilizate / products obtained by sublimation method, capsules (for example, hard or soft gelatin capsules), tablets, granular products (pellets, powders, emulsions, suspensions, aerosols or solutions.

Parenteral administration can take place with the crawling stage Sasi the project (for example, when administered intravenously, intraarterially, intracardiac or in the lumbar spine, as well as in spinal / interspinales introduction) or with inclusion of an absorption (e.g., intramuscular, intradermal, transcutaneous, subcutaneous, or intraperitoneal injection). For parenteral use as dosage forms suitable including drugs for injection and infusion in the form of solutions, suspensions, emulsions, liofilizatow (products obtained by sublimation method) or sterile powders.

For other methods of application are suitable, for example, inhalation dosage forms (including powder inhalers, nebulizers for drugs), drops, solutions, sprays for the nose; the pills should be taken on the tongue, under the tongue or cheek; drugs in the shell/wafers or capsules, suppositories, ear or eye preparations, vaginal capsules, aqueous suspensions (lotions, shake mix), lyophilic suspensions, ointments, creams, transdermal therapeutic systems (e.g. patches), milk, pastes, foams, powders, implants or stents.

Compounds according to the invention can be converted in the above dosage forms. This can occur in a known manner by mixing with inert, non-toxic additives with appropriate pharmaceutical properties. So the mi auxiliary substances are considered including the media (for example, microcrystalline cellulose, lactose, mannitol), solvents (e.g. liquid polyethylene glycols), emulsifiers and dispersants or wetting agents (e.g. sodium dodecyl sulphate, polyoxyethylenesorbitan), binders (for example polyvinylpyrrolidone), synthetic and natural polymers (for example albumin), stabilizers (e.g. antioxidants like ascorbic acid), colorants (e.g. inorganic pigments such as iron oxide) and substances that improve the taste and/or smell of the medicine.

The next subject of the present invention are drugs that contain at least one compound according to the invention together with one or more inert, non-toxic additives with appropriate pharmaceutical properties, and their use for the aforementioned purposes.

In General, to achieve effective results, convenient (useful) was the daily dose of approximately 0.01 to 5000 mg/kg, preferably from 0.5 to 1000 mg/kg of body weight.

Despite this, if necessary, you may need to move away from these quantities, namely depending on the body weight, route of administration, individual characteristics in relation to biologically active substance, the type of preparation and time or interval at which accepted preparatin way in some cases, it may be sufficient to dispense smaller quantities (of the drug)than the above minimum, whereas in other cases it is necessary to exceed the specified upper limit. When using relatively large quantities (of the drug) I would recommend to divide the daily dose into several separate doses throughout the day.

However, in accordance with the nature of action of the drug formulation may contain from 0.1 to 99% active ingredient, in a favorable case, 25-95% for tablets and capsules and 1-50% for liquid formulations, i.e. the active substance shall be present in quantities sufficient to achieve the stated dosage range.

An additional embodiment of the present invention is the use of a combination of one or more compounds according to the invention together with one or more other substances. Suitable combinations of substances are, for example, substances which are used for prophylaxis and/or treatment of heart attacks and circulatory problems. The sample and the preferred option in this regard are substances that increase the amount of guanosine monophosphate (GMP), such as compounds that produce NO, phosphodiesterase inhibitors, thrombolytic drugs and substances with affinity to adenosine (adeno who unionista).

Experimental part

Limiting the level of the heart and further violations of the blood supply to the isolated heart with a dose of NO-independent activator of soluble guanylate cyclase

In determining the size of the infarct and the experiment followed the method described by Zhang et al. in J. Cardiovasc. Pharmacol., 42, 764-771, 2003.

Rabbits breed "new Zealand white" of both sexes (body weight 2-3 kg) were anestesiologi using sodium-pentobarbital (Nembutal; 30 mg/kg intravenously) and connected to an artificial respirator. After surgery isolated heart quickly transferred to the installation of Langendorf. Isolated heart was taken with this to the root of the aorta and retrograde shock was filled with Krebs buffer consisting of (in mmol) from: to 118.5 NaCl; KCl 4,7; MgSO41,2; KH2PO41,2; NaHCO324,8; CaCl22.5 and glucose 10. The buffer was aziraphale with a mixture of 95% O2and 5% CO2with a pH 7,35-7,45 and a temperature of 38°C. All of the heart can lead to balance at least 30 minutes before the test.

The scale of infarction was determined at the end of the experiment, and the isolated heart was rapidly removed from the installation of Langendorf. After the stage of washing with saline coronary artery again pinched and heart were injected fluorescent microspheres, the button to submit the risk or ischemic area, in the form of fluorescent tissue. Thereafter, the heart was weighed and subjected to a deep freeze so that you can cut into plates with a thickness of 2 mm. These plates were incubated for 20 minutes at 37°C in a 1% solution of triphenyltetrazolium (TTX) in phosphate buffer. Viable tissue when it is painted in dark red color, nekrotizirovanne fabric, in contrast, is not painted and has brown (brown) color.

All hearts (n=6) were subjected to 30 minutes ischemia by applying the coronary ligature and 120-minute phase of blood flow (reperfusion). Control samples were subjected to only one ischemia and reperfusion. In the treatment group in the heart have introduced NO-independent activator of soluble generatrices. The results can be summed up in the conclusion that the activators of soluble guanylate cyclase useful in order to limit the scope of the heart and reduce blood circulation problems.

Pharmaceutical composition for treating reperfusion disorders, containing the active substance and an inert, non-toxic, pharmaceutically acceptable excipients, characterized in that the active substance it contains at least one substance from the group comprising compounds of formula (I-IVa)


their salts, hydrates and hydrates of salts.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel flavonoid compounds of formula 1 where R1-R5 assume values given in the description. The invention also relates to a pharmaceutical composition based on said compounds and a treatment and prevention method. Such compounds and corresponding pharmaceutically acceptable derivatives and/or salts are used in pharmaceutical, veterinary and nutraceutical fields.

EFFECT: compounds and compositions have antioxidant properties and are especially effective in treating ischemic and reperfusion injury.

39 cl, 19 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, and concerns an injection dosage form for treating an acute ischemic stroke and a craniocereberal injury characterised by the fact that as an active ingredient, it contains a therapeutically effective amount of heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro, and at least one substance chosen from a group of antioxidants.

EFFECT: invention provides high neuroprotective effect in acute severe CNS affections associating various models of the stroke and the craniocereberal injury, as well as high stability and prolonged use.

12 cl, 13 ex, 2 dwg, 5 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to an ester presented by formula [2] where R1' represents 1) C1-C6 alkyl which is optionally substituted by one or more identical or different halogens, or 2) -CO-C1-C6 alkoxy; R2' represents 1) hydrogen or 2) C1-C6 alkyl, R3', R4' and R5' are identical or different, and each represents 1) hydrogen, 2) halogen, 3) C1-C6 alkyl which is optionally substituted by one or more identical or different halogens, 4) C1-C6 alkoxy, 5) -COR13' where R13' represents (a) hydroxy, (b) C1-C6 alkyl, (c) C1-C6 alkoxy which is optionally substituted by one or more identical or different substitutes selected from (1) hydroxy, (2) C1-C6 alkoxy which is optionally substituted by phenyl, (3) -NR11'CO-C1-C6 alkyl where R11' represents hydrogen, (4) -CONR8'R9' where R8' and R9' are identical or different, and each represents C1-C6 alkyl, (5) -CO- C1-C6 alkoxy optionally substituted by phenyl, (6) phenyl optionally substituted by one or more identical or different substitutes selected from halogen, C1-C6 alkoxy and -CO-C1-C6 alkoxy, and (7) a heterocycle selected from pyridyl, thienyl and which all can be substituted by one or more identical or different C1-C6 alkyl groups, or (d) -OR19' where R19' represents a group or a group or piperidyl which is optionally substituted by -CO-C1-C6alkyl, 6) a heterocycle selected from oxadiazolyl and tetrazolyl, and said heterocycle is optionally substituted by C1-C6 alkyl optionally substituted by one or more identical or different substitutes selected from -CONR8'R9' (R8' and R9' have the same values as defined above) and -CO-aralkyloxy, or 7) nitrile; R6' and R7' are identical or different, and each represents 1) C1-C6 alkyl or 2) a nitrogen-containing 5 or 6-members saturated heterocycle containing a monocycle formed when R6', R7' and a neighbouring nitrogen atom are taken together, and optionally including oxygen as a heteroatom; Y1, Y2, Y3 are identical or different, and represent, 1) all carbon atoms, or 2) one of Y1, Y2, Y3 represent a nitrogen atom, and the others are carbon atoms; Y4 represent a carbon or nitrogen atom ;-X- represents 1) -(CH2)1 where 1 represents an integer 1 to 3, 2) -CH2-NR18'-CH2- where R18' represents C1-C6 alkyl, or 3) or to its pharmaceutically acceptable salt.

EFFECT: compounds presented by formula are effective as agents for treatment or prevention hyperlipidemia, arteriosclerosis, coronary artery disease, obesity, diabetes and hypertension or similar diseases since they are withdrawn very quickly and exhibit excellent MTP inhibitory activity.

23 cl, 32 tbl, 137 ex

FIELD: chemistry.

SUBSTANCE: invention relates to aminophosphate derivatives of general formula (1a), pharmaceutically acceptable salts or hydrates thereof, which can be used in medicine as S1P (sphingosine-1-phosphate) receptor modulators,

where R3 is a straight alkyl group containing 1-3 carbon atoms; X is an oxygen or sulphur atom and n equals 2 or 3.

EFFECT: obtaining novel biologically active compounds with high S1P receptor modulating action.

9 cl, 59 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

, where R and R1 independently denote a link selected from: i) hydrogen; ii) substituted or unsubstituted phenyl and iii) substituted or unsubstituted 5- or 6-member heteroaryl in which heteroatoms are selected from nitrogen, oxygen, sulphur or combinations thereof; said substitutes are selected from: i) C1-C4 linear, C3-C4 branched or C3-C4 cyclic alkyl; ii) C1-C4 linear, C3-C4 branched or C3-C4 cyclic alkoxy; iii) C1-C4 linear, C3-C4 branched or C3-C4 cyclic halogenalkyl; iv) halogen; v) -CN; vi) -NHC(O)R4 vii) -C(O)NR5aR5b; viii) 5- or 6-member heteroaryl in which heteroatoms are selected from nitrogen, oxygen, sulphur or combinations thereof; or ix) two substitutes may be taken together to form a condensed ring containing 5-7 atoms; R4 is C1-C4 linear, C3-C4 branched or C3-C4 cyclic alkyl; R5a and R5b each independently denotes: 1) hydrogen; ii) C1-C4 linear, C3-C4 branched or C3-C4 cyclic alkyl; or iii) R5a and R5b can be taken together to form a ring containing 3-7 atoms; R2 is selected from: i) -OR6; or ii) -NR7aR7b; R6 is hydrogen or C1-C4 linear, C3-C4 branched or C3-C4 cyclic alkyl; R7a and R7b each independently denotes: i) hydrogen; ii) C1-C4 linear, C3-C4 branched or C3-C4 cyclic alkyl; or iii) R7a and R7b may be taken together to form a ring containing 3-7 atoms; R3 is hydrogen, methyl or ethyl; L is a binding link of formula -[C(R8aR8b)]n -R8a and R8b each independently denotes hydrogen, methyl or ethyl; n ranges from 1 to 3; R9 is hydrogen or methyl; or pharmaceutically acceptable salt thereof; provided that R and R1 both denote hydrogen. The invention also relates to compositions based on the described compounds for treating anaemia or assisting wound healing and use of said compounds to prepare a composition for treating anaemia or wounds.

EFFECT: novel compounds which are HIF-16 prolyl hydroxylase inhibitors are obtained.

14 cl, 18 ex, 15 tbl, 2 dwg

FIELD: medicine.

SUBSTANCE: for treatment of patients with ischemic heart disease in addition to basic therapy introduced is cudesan in dose 25 drops simultaneously with preductal MB 35 mg 2 times per day during meal for 3 months, with further parenteral introduction of essentiale H in dose 0.5-1 g for 10 days, after that, enterally in dose 1 capsule 3 times per day for 20 days. Course of treatment is repeated 3 times per year.

EFFECT: expressed anti-ischemic effect and normalisation of processes of lipid peroxidation, including in patients with severe affection of coronary channel and expressed diastolic dysfunction of left ventricle.

2 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: claimed are method of reducing in circulating blood of LDL-cholesterol, triglycerides, total cholesterol and their mixtures, including introduction of efficient amount of one or more phosphate derivatives of one or more electron-transfer agents, which represent monotocopheryl phosphate, dotocopheryl phosphate, monotocotrienyl phosphate, ditocotrienyl phosphate and their mixtures, their application for relief of symptoms, treatment and/or prevention of disease, selected from group which consists of chronic renal failure, primary and secondary hyperemias and dislipemia, retinopathy, enlargement of liver and spleen, xanthomas and their combinations by reduction of lipid content in circulating blood.

EFFECT: reduction under action of claimed tocopherylphosphates of levels of total cholesterol, LDL in mice and reduction in them of atherosclerotic lesions, in people - improvement of dislipidemia state and increase of HDL cholesterol in comparison with tocopherol acetate.

5 cl, 3 dwg, 5 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) given below or pharmaceutically acceptable salts thereof:

[where: each of X, Y, Z and W independently denotes a methane group which optionally contains substitutes selected from a group of substitutes α, or a nitrogen atom (except when all elements X, Y, Z and W denote a methane group which optionally contain substitutes selected from the group of substitutes α); A denotes -(C(R3)(R4))m1-; B denotes -O-; D denotes -C(O)-; m1 equals 0; Q denotes a methane group or a nitrogen atom; R denotes a group of formula (II)

, where R6 denotes a lower alkyl group; R7 and R8, together with the nitrogen atom with which they are bonded, form a 5-6-member nitrogen-containing aliphatic heterocyclic group; and where the group of substitutes α includes the following substitutes. Group of substitutes α: halogen atom, hydroxyl group, lower alkyl group, alkoxyl group (said group can be substituted with a cycloalkyl group), amino group, mono- or disubstituted lower alkylamino group, aryl group (said group can be substituted with a halogen atom, a -SO2CH3 group), aryloxy group (said group can be substituted with a halogen atom), heteroaryl group, where 'heteroaryl group' denotes a 5- or 6-member monocyclic saturated or unsaturated group containing 1-2 heteroatoms selected from an oxygen atom or a nitrogen atom (said group can be substituted with an alkoxyl group, alkyl group). The invention also relates to a histamine 3 receptor antagonist, histamine 3 receptor inverse agonist, a prophylactic or medicinal agent, as well as a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds having histamine H3 receptor antagonist or inverse agonist action.

15 cl, 57 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, particularly to an agent for treating cardiovascular and cerebrovascular diseases. A method of preparing a therapeutic composition for treating cardiovascular and cerebrovascular diseases that involves selection of scorpion, centipede, eupolyphaga or steleophaga, leech, cicadas, ginseng root, prepared incense, peony root, sweet and white sandal wood, boras camphor and Ziziphi spinosae seeds according to the preset amounts, preparation of crude therapeutic extracts of said initial materials, agitation of the prepared extracts. A product of the therapeutic composition for treating cardiovascular and cerebrovascular diseases. A method of preparing the therapeutic insect extracts for treating cardiovascular and cerebrovascular diseases. The therapeutic insect extracts for treating cardiovascular and cerebrovascular diseases.

EFFECT: agents are effective for treating cardiovascular and cerebrovascular diseases.

11 cl, 2 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmacology and medicine, namely to obtaining orally decomposing powder of cilostazol. For this purpose into pharmaceutical preparation included are from 10% wt to 20% wt of cilostazol and from 70% to 79.5% wt of mannitol.

EFFECT: creation of cilostazol preparation, easily decomposing in oral cavity and not requiring taking water with it.

13 cl, 3 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to hematology and cardiology, and can be used for reduction of spontaneous erythrocyte aggregation in case of arterial hypertension with abdominal obesity. For this purpose at the background of hypocaloric diet, dosed static and dynamic physical exercise and daily swimming for not less than 30 minutes per day in the middle of the day lisinopril and metformin are introduced. Physical exercise includes morning hygienic gymnastics, therapeutic and preventive gymnastics, dosed physical exercised throughout the day. Lisinopril is introduced in dose 10 mg 1 time per day in the morning. Metformin is introduced in dose 500 mg 2 times per day. Treatment is carried out for 2 months.

EFFECT: method makes it possible to normalise spontaneous erythrocyte aggregation during 2 months, bringing it to the level close to that of healthy people, thus favouring prevention of vascular complications in patients with arterial hypertension with abdominal obesity.

2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, specifically to complexes exhibiting improved bioavailability. Complexes of an olive leaf or fruit extract with phospholipids exhibiting improved bioavailability, with the certain phospholipid to olive leaf or fruit extract relation. A method of producing the complexes. Pharmaceutical compositions for increasing bioavailability of the active ingredients. Application of the complexes for producing drug exhibiting chemopreventive, antioxidant and preventive properties with respect to cardiovascular diseases.

EFFECT: complexes and compositions exhibit improved bioavailability.

9 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel flavonoid compounds of formula 1 where R1-R5 assume values given in the description. The invention also relates to a pharmaceutical composition based on said compounds and a treatment and prevention method. Such compounds and corresponding pharmaceutically acceptable derivatives and/or salts are used in pharmaceutical, veterinary and nutraceutical fields.

EFFECT: compounds and compositions have antioxidant properties and are especially effective in treating ischemic and reperfusion injury.

39 cl, 19 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are offered compounds for injections in local lipopexia regions, containing a prolonged selective beta-2-adrenergic receptor agonist selected from salmeterol, formoterol, their salts and their solvates; a compound for decreasing fatty tissue desensitisation to the beta-adrenergic receptor agonist (or a compound for decreasing target tissue desensitisation to the beta-adrenergic receptor agonist - a version); and a liquid carrier, a related method of local treatment of lipopexia regions (versions), a method of decreasing fatty tissue. It is shown that combined use of the ingredients surpasses an effect (e.g., waist size) as compared with intake of only one of them.

EFFECT: development of the method of decreasing fatty tissue.

30 cl, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, and concerns an injection dosage form for treating an acute ischemic stroke and a craniocereberal injury characterised by the fact that as an active ingredient, it contains a therapeutically effective amount of heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro, and at least one substance chosen from a group of antioxidants.

EFFECT: invention provides high neuroprotective effect in acute severe CNS affections associating various models of the stroke and the craniocereberal injury, as well as high stability and prolonged use.

12 cl, 13 ex, 2 dwg, 5 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to an ester presented by formula [2] where R1' represents 1) C1-C6 alkyl which is optionally substituted by one or more identical or different halogens, or 2) -CO-C1-C6 alkoxy; R2' represents 1) hydrogen or 2) C1-C6 alkyl, R3', R4' and R5' are identical or different, and each represents 1) hydrogen, 2) halogen, 3) C1-C6 alkyl which is optionally substituted by one or more identical or different halogens, 4) C1-C6 alkoxy, 5) -COR13' where R13' represents (a) hydroxy, (b) C1-C6 alkyl, (c) C1-C6 alkoxy which is optionally substituted by one or more identical or different substitutes selected from (1) hydroxy, (2) C1-C6 alkoxy which is optionally substituted by phenyl, (3) -NR11'CO-C1-C6 alkyl where R11' represents hydrogen, (4) -CONR8'R9' where R8' and R9' are identical or different, and each represents C1-C6 alkyl, (5) -CO- C1-C6 alkoxy optionally substituted by phenyl, (6) phenyl optionally substituted by one or more identical or different substitutes selected from halogen, C1-C6 alkoxy and -CO-C1-C6 alkoxy, and (7) a heterocycle selected from pyridyl, thienyl and which all can be substituted by one or more identical or different C1-C6 alkyl groups, or (d) -OR19' where R19' represents a group or a group or piperidyl which is optionally substituted by -CO-C1-C6alkyl, 6) a heterocycle selected from oxadiazolyl and tetrazolyl, and said heterocycle is optionally substituted by C1-C6 alkyl optionally substituted by one or more identical or different substitutes selected from -CONR8'R9' (R8' and R9' have the same values as defined above) and -CO-aralkyloxy, or 7) nitrile; R6' and R7' are identical or different, and each represents 1) C1-C6 alkyl or 2) a nitrogen-containing 5 or 6-members saturated heterocycle containing a monocycle formed when R6', R7' and a neighbouring nitrogen atom are taken together, and optionally including oxygen as a heteroatom; Y1, Y2, Y3 are identical or different, and represent, 1) all carbon atoms, or 2) one of Y1, Y2, Y3 represent a nitrogen atom, and the others are carbon atoms; Y4 represent a carbon or nitrogen atom ;-X- represents 1) -(CH2)1 where 1 represents an integer 1 to 3, 2) -CH2-NR18'-CH2- where R18' represents C1-C6 alkyl, or 3) or to its pharmaceutically acceptable salt.

EFFECT: compounds presented by formula are effective as agents for treatment or prevention hyperlipidemia, arteriosclerosis, coronary artery disease, obesity, diabetes and hypertension or similar diseases since they are withdrawn very quickly and exhibit excellent MTP inhibitory activity.

23 cl, 32 tbl, 137 ex

FIELD: chemistry.

SUBSTANCE: invention relates to aminophosphate derivatives of general formula (1a), pharmaceutically acceptable salts or hydrates thereof, which can be used in medicine as S1P (sphingosine-1-phosphate) receptor modulators,

where R3 is a straight alkyl group containing 1-3 carbon atoms; X is an oxygen or sulphur atom and n equals 2 or 3.

EFFECT: obtaining novel biologically active compounds with high S1P receptor modulating action.

9 cl, 59 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention describes novel bicyclic derivatives of general formula (I)

(values of radicals are given in the description) and a pharmaceutical composition containing said derivatives, as well as use of said novel compounds to treat or inhibit symptomatic diseases where CEPT is involved, and a method of treating said diseases.

EFFECT: high efficiency of using compounds when treating diseases.

14 cl, 34 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to cardiology and angiologia, and can be used for optimising vascular wall activity in patients with degree I-II arterial hypertension (AH) associating metabolic syndrome (MS) suffered eye vessel thrombosis. That is ensured by introduction of the preparations pioglitazone and amlodipine with underlying an individually prescribed hypocaloric diet and graduated physical exercises. The hypocaloric diet is calculated in kcal by formula: for women of 18-30 years old - (0.0621 × body weight, kg + 2.0357) × 240, of 31-60 years old - (0.342 × body weight, kg + 3.5377) × 240, over 60 years old - (0.0377 × body weight, kg + 2.7545) × 240, for men of 18-30 years old - (0.0630 × body weight, kg + 2.8957) × 240, of 31-60 years old - (0.0484 × body weight, kg + 3.6534) × 240; over 60 years old - (0.0491 × body weight, kg + 2.4587) × 240. The graduated physical exercises represent morning hygienic gymnastics, therapeutic exercises and graduated physical exercises throughout a day. The preparations pioglitazone 30 mg and amlodipine 10 mg are introduced once a day in the same time. The therapy is performed for 4 months.

EFFECT: method provides correction of reduced vascular wall function in the patients with degree I-II AH associating MS suffered eye vessel thrombosis for 4 months and allows avoiding vascular complications in such patients.

1 dwg, 1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: for correction of hyperhomocysteine-induced endothelial dysfunction in white rat males of Wistar line modeled is endothelial dysfunction by intragastric introduction of methionine in dose 3 g/kg daily during 7 days. Degree of dysfunction development is estimated by ratio of indices of endothelium-independent and endothelium-dependent vasodilatation, as well as by increase of homocysteine concentration. Correction of endothelial dysfunction is carried out by intragastric introduction of medication "Phosphogliv" capsules in dose 2.2 g/kg once per day an hour after methionine introduction.

EFFECT: method insures study of correction of hyperhomocysteine-induced endothelial dysfunction by means of phosphogliv with creation of definite model of said pathology.

2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel carbostyril compounds of general formula (1) or salts thereof with common pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds, having activity on promotion of TFF2 production, a pharmaceutical composition based on said compounds, an agent based on disclosed compounds used in case of a disorder where up-regulation of TFF has a prophylactic and/or therapeutic effect, use of disclosed compounds to prepare said agent and a method of producing disclosed compounds. The invention also relates to novel specific carbostyril compounds or salts thereof with common pharmaceutically acceptable acids or pharmaceutically acceptable basic compounds. In structural formula (1), A is a direct bond, a lower alkylene group or lower alkylidene group, X is an oxygen or sulphur atom, the bond between positions 3 and 4 of the carbostyril backbone is a single bond or a double bond, R4 and R5 each denotes a hydrogen atom provided that, when the bond between positions 3 and 4 of the carbostyril backbone is a double bond, R4 and R5 can instead be bonded to each other in form of a -CH=CH-CH=CH- group, and R1, R2 and R3 assume values given in the claims.

EFFECT: high efficiency of compositions based on said compounds.

32 cl, 23 dwg, 184 tbl, 1535 ex

Up!