9-benzyl-2-biphenylimidazo[1,2-a]benzimidazole and pharmaceutically acceptable salts thereof that express properties of destroyers of transversal cross-links of glycosylated proteins

FIELD: pharmacology.

SUBSTANCE: invention relates to new 9-benzyl-2-biphenylimidazo[1,2-a]benzimidazole (I) and pharmaceutically acceptable salts thereof.

EFFECT: imidazobenzimidazole derivatives having the property of destroyers of transversal cross-links of glycosylated proteins.

3 cl, 2 dwg, 1 tbl, 1 ex

 



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to methods of obtaining heteroaryl compounds, represented by structural formulae (I) or (II): where R1-R4 have values, given in subcl. 1,14 of the formula.

EFFECT: compounds can be used for treatment or prevention of cancer, inflammatory states, immunological states, etc.

29 cl, 20 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound (I) or its pharmaceutically acceptable salt, which possess properties of selective phosphodiesterase inhibitors, and can be used for treating male erectile dysfunction. In compound (I) R1 represents C1-C6alkyl; R2 represents C1-6alkyl; R3 represents C1-C6alkyl; R4 represents C1-C6 alkyl; R5 means H. The above salt is formed by the compound of formula (I) and an acid specified in citric acid, oxalic acid, hydrochloric acid, sulphuric acid, phosphoric acid, maleic acid, fumaric acid, tartaric acid, hydroxysuccinic acid, succinic acid, methane sulphonic acid or n-toluene sulphonic acid. A preferential compound is 5-[2-ethoxy-5-(4-methyl-1-homopiperazinylsulphonyl)]phenyl-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one.

EFFECT: preparing the pharmaceutically acceptable salt that possesses the properties of selective phosphodiesterase inhibitors.

7 cl, 1 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula (I), possessing properties, making it possible to inhibit phosphorylation of AKT (proteinkinase B; PKB), to versions of method of their obtaining, as well as to intermediate products for their obtaining. In particular compounds can be applied in treatment of different tumours and/or metastases, as well as in case parasitic diseases such a malaria. In formula (I), R1 stands for -L-phenyl or -L-heteroaryl, with term "heteroaryl" standing for bicyclic radical, containing from 9 to 12 units, L stands for either linear or branched alkyl, containing 1-6 carbon atoms, optionally substituted with hydroxyl, or CO group, or group L'-X, where L' stands for linear or branched alkyl, containing 1-6 carbon atoms, and X stands for oxygen or sulphur atom; with phenyl and heteroaryl being optionally substituted with one or several radicals, similar or different, selected from halogen atoms, -NRxRy, alkoxy and alkyl; with said alkyl being optionally substituted with one or several halogen atoms; R2 stands for hydrogen atom or alkyl; R3 stands for alkyl, optionally substituted with one or several halogen atoms; R4 stands for hydrogen atom or halogen atom; with NRxRy being such that Rx and Ry form together with nitrogen atom, which they are bound to, cyclic radical, including 3-10 units, and optionally oxygen atom; and all alkyl or alkoxy radicals, mentioned above, are linear or branched and contain 1-6 carbon atoms.

EFFECT: compounds can be applied as active component for obtaining medications, intended for treatment or prevention of disease, characterised by deregulation of protein- or lipidkinase activity.

25 cl, 3 tbl, 43 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of structural formula

,

having Aβ42 secretion inhibiting activity. In formula I , hetaryl I is a five- or six-member heteroaryl group containing 1-3 heteroatoms selected from O, S or N, hetaryl II is a five- or six-member heteroaryl group containing 1-3 heteroatoms as defined above for hetaryl I, or is a bicyclic ring system containing 1-4 heteroatoms selected from S, O or N, where at least one ring is aromatic by nature, R1 is C1-7-alkyl, C1-7-alkoxy, C1-7-alkyl substituted with a halogen, or a halogen; R2 is a halogen, C1-7-alkyl, C1-7-alkoxy, hydroxy, C1-7-alkyl substituted with a halogen, C1-7-alkyl substituted with a hydroxy, or benzo[1,3]dioxolyl or is -(CHR)p-phenyl, optionally substituted with a halogen, C1-7-alkyl, C1-7-alkoxy, S(O)2-C1-7-alkyl, cyano, nitro, C1-7-alkoxy substituted with a halogen, dimethylamino, -(CH2)p-NHC(O)O-C1-7-alkyl or C1-7-alkyl, substituted with a halogen. The values of radicals R, R3, R4,p, n, m, o are given in the claim.

EFFECT: invention relates to a method of producing said compounds, a medicinal agent containing said compounds and a method of treating Alzheimer's disease, cerebral amyloid angiopathy, Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), vascular dementia, dementia pugilistica or Down syndrome, associated with β amyloid activity.

21 cl, 283 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to 5,5-condensed heteroarylene compounds IIIB, where U2, V1, V2 and W1 are selected from O, N, NH, S or CR3a; U1, W2, X1 and X2 represent C or N; R1 and R2 represents hydrogen, -C(O)CH(NR1bR1c)R1a, -C(O)CH(N(R1c)C(O)OR1b)R1a or -C(O)OR1a; R3a represents hydrogen or R3; R3 represents halogen or -C(O)OR1a; L1 and L2 are such as given in invention formula, each Z1 and Z2 represents bond or -O-; each Rla, R1b and R1c represents hydrogen, C1-6 alkyl or C6-14 aryl; or Rlb and Rlc together with N atom, which they are bound to, form 5-6-membered heterocyclyl; q, r, s, t and u equal 1. Invention also relates to pharmaceutical compositions, containing 5,5-condensed heteroarylene compounds, and methods of treating or preventing HCV infection.

EFFECT: 5,5-condensed heteroarylene derivatives, possessing inhibiting activity with respect to hepatitis C virus.

43 cl, 42 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of obtaining a formula compound. The method includes a stage of binding a formula compound with a formula compound in the presence of a base with the formation of the formula (I) compound. In formula (I) stereochemical configurations in the positions, marked with asterisks, are relative; Rb represents hydrogen; R00 represents a C1-10 aliphatic group or a C6-14 aryl group, including one-three rings; Rd, Re, Re', Rf, Rh, Rh', Rk represent hydrogen; Rg represents chlorine, fluorine, iodine or bromine; Rm represents a protective hydroxyl group; values of radicals Ra, R*, Rc are given in the invention formula. In formulas (II) and (III) Ra, Rb, Rc, Rd, Re, Re', Rf, Rg, Rh, Rh', Rj, Rk and Rm are such as determined in formula (I) and R1 represents -CH2CHO. The invention also relates to methods of obtaining compounds of formulae (V), (VI), (VId) and to a compound of the structural formula (IIa). Structural formulae of compounds (V), (VI), (VId), (IIa) are given in the invention formula.

EFFECT: method makes it possible to carry out synthesis in a regioselective way and use the obtained product without purification.

15 cl, 1 tbl, 26 ex

Ethinyl derivatives // 2553461

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to ethinyl derivatives of formula I, where X represents N or C-R1; Y represents N or C-R2; Z represents CH or N; R4 represents 6-membered ring, containing 0, 1 or 2 nitrogen atoms, possibly substituted with 1-2 groups, selected from halogen, lower alkyl, lower alkoxy or NRR'; R1 represents hydrogen, lower alkyl, lower hydroxyalkyl, lower cycloalkyl or represents 5-6-membered heterocycloalkyl, containing 1-2 heteroatoms, selected from O and N; R2 represents hydrogen, CN; R and R' independently on each other represent hydrogen; or their pharmaceutically acceptable salts or acid-addition salts. Invention also relates to pharmaceutical composition, possessing activity of positive allosteric modulator of mGluR5 receptor, including effective quantity of at least one invention compound, and to application of invention compounds for manufacturing medication for treatment or prevention of diseases, associated with positive allosteric modulators of mGluR5 receptor.

EFFECT: obtained are novel compounds, which can be applied as positive allosteric modulator of mGluR5 receptor.

14 cl, 51 ex

FIELD: chemistry.

SUBSTANCE: invention describes a method of producing and a method of purifying dialkyl pemetrexed of formula (I) , having antifolate action. The compound can be used to treat non-small-cell cancer and, coupled with cisplatin, to treat malignant pleural mesothelioma of the lungs. The method includes reacting a carboxylic acid of formula (II) with a diester of glutamic acid of formula (III) or an acid-addition salt thereof. The process is carried out in the presence of a substituted triphenyl phosphate of formula (IV) , a base and a solvent. In formulae (I) and (III) each R1 and R2 independently represents alkyl groups. In formula (IV) X, Y and Z assume values given in the claim.

EFFECT: use of safe, mild, cheap, non-oxidising and easy to handle triphenyl phosphate simplifies the process and enables to obtain, for example, diethyl pemetrexed with purity higher than 99%.

14 cl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of organic chemistry, namely to novel heterocyclic compounds of formula (1) and/or to their pharmaceutically acceptable salts, where A1 represents CH; A4and A5 independently represent CR2 or N; A2 and A3 together with ring B represent 5-membered heteroaryl or heterocycle, with said 5-membered heteroaryl or heterocycle being selected from where t represents 1 or 2; and R3 is independently selected from H, C1-C6 alkyl, C6-aryl, C3-C6-membered cycloalkyl, C(O)NRcRd, -ORb, heteroaryl, representing pyridine, and heterocycle, representing piperidine and tetrahydropyran; and each of said alkyl, aryl, cycloalkyl, heteroaryl and heterocycle can be substituted with one group, independently selected from C1-C6 alkyl, possibly substituted with one substituent, selected from -CONMe2, C3-membered cycloalkyl, -CN, -OMe, -pyridine, tetrahydropyran, -CO-morpholine, -CO-pyrrolidine, (3-methyl)oxetane; -OH; -C(O)Ra; -CN; -C(O)NRcRd; -NRcRd; -ORb; -S(O)nRe; halogen, and substituted with one group -COMe heterocycle, representing piperidine, on condition that when A4 represents CR2, A2 and A3 together with ring B are selected from structure (3), (5) or (6); represents single bond or double bond; R1 represents heteroaryl, representing 6-membered or 9-10-membered aromatic mono- or bicyclic ring, containing 1-3 heteroatoms, selected from nitrogen, oxygen and sulphur; possibly substituted with one or two groups, independently selected from C1alkyl, C2alkinyl, -NRcRd, -NRcS(O)nRe, -ORb, halogen, halogenalkyl; R2 is independently selected from H; each Ra, Rb, Rc, Rd, and Re is independently selected from H; C1-C4alkyl, possibly substituted with one substituent, selected from -OH, -OMe, -CN, -NH2, -NMe2, C3-cycloalkyl; C2-C3alkenyl; C3alkinyl; C6aryl, possibly substituted with one or more substituents, selected from fluorine or methyl group; C3-membered cycloalkyl, possibly substituted with one substituent, selected from -OH and -CN; halogenalkyl; heteroaryl, representing pyridine; and substituted with one methyl group heterocycle, representing piperidine, or Rc and Rd together with atom (atoms) which they are bound to form 5-6-membered heterocyclic ring, representing pyrrolidine or morpholine; and in each case n is independently equal 2. Invention also relates to particular compounds, pharmaceutical composition, based on claimed compounds; method of inhibiting PI3K and/or mTOR activity and to application of claimed compounds.

EFFECT: novel compounds, useful for inhibiting PI3K and/or mTOR activity have been obtained.

15 cl, 16 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to a method of obtaining methyl ether of 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]propionic acid and benzosulphonate of methyl ether of 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]propionic acid, which includes the interaction of methyl ether of 3-[(S)-7-bromo-2-((R and/or S)-2-hydroxypropylamino)-5-pyridin-2-yl-3H-benzo[e][1,4]diazepin-3-yl]propionic acid with an oxidiser and, optionally, processing the reaction product in acidic conditions, as well as to intermediate compounds and .

EFFECT: simplification and reduction of the price of the obtaining method due to the reduction of the number of stages.

13 cl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical composition, containing compound of formula or for prevention or treatment of diseases, associated with oxidative stress, selected from group, consisting of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke episodes), MERRF syndrome (myoclonic epilepsy with ragged red fibres) or Kearns-Sayre syndrome, arrhythmia, cardioplegia or myocardium infarction. in formula (1) na stands for 1 or 2, Aa represents 5-membered heteroaryl or heterocycle, each of which has 2 heteroatoms, selected from N, O and S, Rla represents R5a-Xa-Ba-X′a-, Ba represents direct bond, Xa and X′a independently on each other represent direct bond or -OC(O)-, R5a represents hydrogen or 6-9-membered monocyclic or condensed cyclic heterocycle or heteroaryl, each of which has from 1 to 3 heteroatoms, selected from N, O and S, and is optionally substituted with oxo or C1-C6-alkyl, R2a represents -(CR8aR9a)pa-Ya-R7a, pa stands for number from 0 or 1, Ya represents direct bond or -O-, R7a represents hydrogen or phenyl, R3a, R8a, R9a, R10a represent hydrogen, R4a represents -(CH2)pa-Da-R10a-, Da represents C5-cycloalkyl or 6-membered heterocycle, which has 1 heteroatom, selected from N, S and O. Radical values for formula (2) are give in invention formula.

EFFECT: obtaining compositions for prevention or treatment of diseases, associated with oxidative stress.

19 dwg, 5 tbl, 3 ex

Crystals // 2556206

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention describes crystals of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulphonyl)acetamide ("compound A"), as a form I of the compound A crystal, which shows diffraction peaks at 9.4 degrees, 9.8 degrees, 17.2 degrees and 19.4 degrees in its power X-ray diffraction spectrum, as a form II of the compound A crystal, which shows diffraction peaks at 9.0 degrees, 12.9 degrees, 20.7 degrees and 22.6 degrees in its power X-ray diffraction spectrum, as a form III of the compound A crystal, which shows diffraction peaks at 9.3 degrees, 9.7 degrees, 16.8 degrees, 20.6 degrees and 23.5 degrees in its power X-ray diffraction spectrum. There are also described methods for producing the forms I, II and III of the compound A crystal, based pharmaceutical composition and PGI2 receptor agonist agent, an accelerating agent for angiogenic therapy, gene engineering or autoimmune bone marrow transplantation, and an accelerating agent for angiogenesis for peripheral artery recovery or angiogenic therapy on the basis thereof; there are also described a preventive or therapeutic agent for a wide range of diseases and conditions.

EFFECT: preparing the new therapeutic agent for the wide range of diseases and conditions.

11 cl, 6 dwg, 6 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention represents a mixture of two structural isomers: 2,6-di(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)-4-methylphenol and its diastereomers, and 2-(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)-6-(2,2,1-trimethylbicyclo[2.2.1]hept-5-yl)-4-methylphenol, and their diastereomers with the ratio of the first and second structural isomer isomers from 60:40 wt % to 95:5 wt %.

EFFECT: extension of the arsenal of means, possessing simultaneously haemorheological, anti-aggregate, anti-thrombogenic, retinoprotecting, endothelium-protecting, neuroprotecting, anti-arrhythmia and anti-ischemic activity, enhancing the cerebral blood flow.

4 dwg, 20 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to synthetic biologically active heterocyclic substances having antagonist activity on purinoreceptors and which are products of modifying pyridoxin, particularly n-(1,5-dihydro-3-R-8-methyl-9-hydroxy-[1,3]dioxepino[5,6-c]pyridinyl-6-azo)phenyl sulphonic acid and salt forms thereof of general formula I , where is selected from: a hydrogen atom, ethyl, heptyl or octyl.

EFFECT: compounds of the given formula have high antagonist activity on purinoreceptors and can be used in medicine and veterinary.

2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of synthetic biologically active heterocyclic substances as purinoreceptor antagonists, said substances having antagonist activity on purinoreceptors and being a product of modifying pyridoxin, particularly n-(1,5-dihydro-3-R1-3-R2-8-methyl-9-hydroxy-[1,3]dioxepino[5,6-c]pyridinyl-6-azo)phenyl sulphonic acid and salt forms thereof of general formula I , where R1 is a hydrogen atom or methyl, R2 is methyl, isopropyl.

EFFECT: compounds of the given formula have high antagonist activity on purinoreceptors and can be used in medicine and veterinary.

2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

possessing properties of binding with delta opioid receptors. In formula I R1 is selected from the group, consisting of phenyl, pyridinyl and thiazolyl, with R1 being optionally substituted with one or two substituents, independently selected from the group, consisting of C1-4alkoxy, fluorine atom, chlorine atom, bromine atom and cyanogroup; in addition, R1 is optionally substituted with di(C1-4alkyl)aminocarbonyl; Y represents O, S, H3, vinyl, ethinyl or S(O); R2 represents a substituent, selected from the group, consisting of hydrogen, C1-4alkyl, C1-4alkoxy, C1-4alkylthio, fluorine atom, chlorine atom, bromine atom and hydroxy; Ra represents hydrogen or methyl; R3 is selected from the group, consisting of pyrrolidin-2-ylmethyl; pyrrolidin-3-ylmethyl; piperidin-2-ylmethyl, piperidin-3-ylmethyl, piperidin-4-ylmethyl, piperidin-2-ylethyl, piperidin-3-ylethyl, piperidin-4-ylethyl, pyridine-4-yl-(C1-2)alkyl, azetidin-3-ylmethyl; morpholin-2-ylmethyl, morpholin-3-ylmethyl, imidazolylmethyl, thiazolylmethyl, (amino)-C3-6cycloalkyl, 3-hydroxy-2-aminopropyl, 8-azabicyclo[3.2.1]octanyl, 1-azabicyclo[2.2.2]octanyl, guanidinylethyl, 4-(imidazol-1-yl)phenylmethyl, 2-(methylamino)ethyl, 2-diethylaminoethyl, 4-diethylaminobut-2-yl, piperidin-3-yl, piperidin-4-yl and pyrrolidin-3-yl; with piperidin-3-yl being optionally substituted on a carbon atom with phenyl; with pyrrolidin-2-yl in pyrrolidin-2-yl-methyl, pyrrolidin-3-yl, piperidin-3-yl and piperidin-4-yl being optionally substituted on a nitrogen atom with methyl, phenylmethyl, phenethyl or methylcarbonyl.

EFFECT: compounds can be used in the treatment of pain, induced by diseases or conditions, such as osteoarthritis, rheumatoid arthritis, migraine, burn, fibromyalgia, cystitis, rhinitis, neuropathic pain, idiopathic neuralgia, toothache, etc.

24 cl, 3 tbl, 19 ex

Hypotensive means // 2554815

FIELD: medicine.

SUBSTANCE: invention represents a hypotensive means, which contains felodipinum as an active component, as well as target additional components: mesoporous silicon dioxide, lactose, hypromeloza. Realisation of the invention ensures the high technological efficiency of the claimed medical means production with the provision of a prolonged release of an active substance with the application of available components. Felodipinum is included into spherical particles with a highly developed mesoporous structure of silicon oxide.

EFFECT: increase of stability in storage and protection from unfavorable environmental factors.

4 cl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of structural formula I

which can be used for protecting cardiomyocytes or for preventing or treating a disease or a disorder related to cardiomyocyte apoptosis. In formula I A represents =S, -SR4 or =O, X represents F, Cl, Br or I, R1 represents phenyl, R2 and R3 are connected to form morpholine, and R4 represents C1-C6-alkyl.

EFFECT: invention refers to using the compound for producing the therapeutic agent for protecting cardiomyocytes or for preventing or treating a disease or a disorder related to cardiomyocyte apoptosis, and to the method for producing the above compounds.

8 cl, 2 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula I, possessing ability of binding with delta-opioid receptors. In formula R1 is selected from the group, consisting of i) phenyl, optionally substituted with one-two substituents, independently selected from the group, consisting of C1-4alkyl, C1-4alcoxy, C1-4alkylthio, hydroxyl, di(C1-4alkyl), aminocarbonyl, chlorine and fluorine, in such a way that only one di(C1-4alkyl)aminocarbonyl is present; ii) naphthyl; iii) pyridinyl, optionally substituted with one substituent, selected from the group, consisting of C1-4alkyl, C1-4alcoxy, C1-4alkylthio, hydroxy, fluorine, chlorine and cyano; iv) pyrimidin-5-yl; v) furanyl; vi) thienyl; vii) 5-oxo-4,5-dihydro-[1,2,4]oxodiazol-3-yl; and viii) di(C1-2alkyl)aminocarbonyl; Y represents ethyl, vinyl or bond; or Y represents O, when R1 represents optionally substituted phenyl, where substituent represents C1-4alcoxy; R2 represents phenyl, optionally substituted with one-two substituents, independently selected from the group, consisting of C1-4alkyl, C1-4alcoxy, fluorine, chlorine and cyano, trifluoromethoxy and hydroxy; or R2 represents phenyl, substituted with one aminocarbonyl, di(C1-4alkyl)aminocarbonyl, C1-4alcoxycarbonyl or carboxysubstituent; R3 is selected from the group, consisting of i) 3-aminocyclohexyl; ii) 4-aminocyclohexyl; iii) piperidin-3-yl; iv) piperidin-4-yl; v) pyrrolodin-2-yl-methyl, in which pyrrolodin-2-yl is optionally substituted by 3-rd or 4-th position with one or two fluorine-substituents; vi) azetidin-3-yl; vii) 2-(N-methylamino)ethyl; viii) 3-hydroxy-2-aminopropyl; ix) piperidin-3-yl-methyl; x) 1-azabicyclo[2.2.2]octan-3-yl; and xi) 8-azabicyclo[3.2.1]octan-3-yl; or R3 together with Ra and nitrogen atom, which they both are bound to, form piperazinyl, optionally substituted with 4-C1-4alkyl; Ra represents hydrogen, 2-(N-methylamino)ethyl or C1-2alkyl, optionally substituted with azetidin-3-yl.

EFFECT: compounds can be used in treatment of pain in the range from medium to strong, caused by diseases or conditions, such as osteoarthritis, migraine, burn, fibromyalgia, cystitis, rhenite, neuropathic pain, idiopathic neuralgia, toothache, etc.

21 cl, 4 tbl, 26 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 3-phenylpropionic acid derivatives of formula

wherein R1A represents hydrogen, methyl, ethyl, cyclopropyl or cyclobutyl, R1B is hydrogen or methyl, R2A represents hydrogen, methyl, trifluoromethyl, ethyl or n-propyl, R2B is hydrogen or methyl or R1A and R2A are combined together, and in a combination to carbon atoms to which they are attached, form a cyclopropyl ring of formula

wherein R1B and R2B have the values as specified above, or R2A and R2B are combined together, and in a combination to a carbon atom, to which they are attached, form a cyclic group of formula or

wherein n means a number 1 or 2, R3 is hydrogen, fluorine or methyl, R4 represents hydrogen, fluorine, chlorine or a cyanogroup, R5A represents methyl, R5B is trifluoromethyl or R5A and R5B are combined together, and in a combination to a carbon atom, to which they are attached, form a difluorosubstituted cycloalkyl ring of formula or

R6 represents chlorine, alkyl with 1-4 carbon atoms, alkenyl with 2-4 carbon atoms, cyclopropyl or cyclobutyl; alkyl with 1-4 carbon atoms and alkenyl with 2-4 carbon atoms can contain up to three fluorine atoms, cyclopropyl and cyclobutyl up to three fluorine atoms as substitutes, and R7 represents hydrogen, fluorine, chlorine, methyl or a methoxy group. The invention also refers to a therapeutic agent containing the above compounds and to a method for producing the compounds of formula (I).

EFFECT: compounds of formula (I) activate the form of soluble haem-free guanylate cyclase and are applicable in the method of treating and/or preventing cardiac failure, angina, hypertension, pulmonary hypertension, ischemia, vascular diseases, disturbed microcirculation, thromboembolic diseases and arterial sclerosis.

6 cl, 4 tbl, 113 ex

FIELD: veterinary medicine.

SUBSTANCE: treatment is carried out with an aqueous solution of the preparation "Biopag-D" at a concentration of 4-2% by drifting animals through the baths with the solution having the immersion depth up to the carpal joint.

EFFECT: invention enables to treat efficiently and stress-free and prevent treatment of diseases of hooves and dew claws of animals.

3 cl, 5 dwg, 4 tbl, 1 ex

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