Cystathionine-g-lyase (cse) inhibitors

FIELD: pharmacology.

SUBSTANCE: invention relates to compounds of the Formula (I) or their pharmaceutically acceptable salts inhibiting the activity of cystathionine-gamma-lyase (CSE). In Formula (I) A is

or -CONHSO2R4, where R4 is independently unsubstituted alkyl or unsubstituted aryl; X is CR1 or N; R1 is H; each R2 and R3 is H. The invention also relates to a pharmaceutical composition comprising the said compounds and a method for treatment or prevention of various diseases associated with CSE activity.

EFFECT: increased efficiency of the composition and treatment method.

13 cl, 11 dwg, 2 tbl, 17 ex

 



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to the following compounds: N-(1-{4-[2-(1-acetylamino-ethyl)-1-ethyl-1H-imidazol-4-yl]-benzyl}-3-hydroxy-propyl)-3-chloro-4-(2,2,2,-trofluoro-1-methyl-ethoxy)-benzamide, N-(1-{4-[2-(1-methyl-1-hydroxy-ethyl)-1-ethyl-1H-imidazole-4-yl}-benzyl}-3-hydroxy-propyl)-3-chloro-4-(,2,2,2-trifluoro-1-methyl-ethoxy)-benzamide, N-(1-{4-[2-(1-hydroxy-1-methyl-ethyl)-1-methyl-1H-imidazole-4-yl]-benzyl}-3-hydroxy-propyl)-3-chloro-4-(2,2,2,-trifluoro-1-methyl-ethoxy)-benzamide, 3-chloro-N-[2-[(N,N-dimethylglicyl)amino]-1-({4-[8-(1-hydroxyethyl)imidazo[1,2-a]pyridine-2-yl]phenyl}methyl)ethyl]-4-[(1-methylethyl)oxy]benzamide, 3-chloro-N-(1-(2-(dimethylamino)acetamido)-3-(4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl)propan-2-yl)-4-isopropoxybenzamide, 3-chloro-N-(2-[(2-methylalanyl)amino]-1-{[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}ethyl)-4-[(1-methylethyl)oxy]benzamide, 3-chloro-N-[(3-hydroxy)-1-({4-[8-(1-hydroxyethyl)imidazo[1,2-a]pyridine-2-yl]phenyl}methyl)propyl]-4-[(1-methylethyl)oxy]benzamide, as well as to their pharmaceutically acceptable salts.

EFFECT: obtained compounds and salts can be used for treatment cell proliferative diseases and disorders by modulating activity of mitotic kinesin CENP-E.

26 cl, 102 ex, 7 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of substituted 4-(benzimidazol-2-ylmethylamino)benzamidine of formula (I) or its physiologically compatible salt, in which R1 is a C1-C3alkyl group, R2 is a R21NR22 group, where R21 denotes a C1-C3alkyl group substituted with a C1-C3alkoxycarbonyl group, and R22 denotes a pyridinyl group, and R3 is a C1-C8alkoxycarbonyl group having thrombin inhibiting and thrombin clotting time prolonging activity. The method involves a step (a) where phenyldiamine of formula (II) in which R1 and R2 assume values given for formula (I), reacts with 2-[4-(1,2,4-oxadiazol-5-on-3-yl)phenylamino]acetic acid. At step (b), the obtained product of formula (III), in which R1 and R2 assume values given for formula (I), is hydrogenated and then at step (c), if necessary, the obtained product of formula (I), in which R3 is hydrogen, reacts with a compound of formula R3-X (IV), in which R3 assumes values given for formula (I), and X denotes an acceptable leaving group, and then converted to a physiologically compatible salt if necessary. The invention also relates to novel intermediate products - formula (III) compound, in which R1 and R2 assume values given for formula (I), as well as to 2-[4-(1,2,4-oxadiazol-5-on-3-yl)phenylamino]acetic acid, 4-(1,2,4-oxadiazol-5-on-3-yl)aniline and toluene sulphonate N-(2-pyridinyl)-N-(2-ethoxycarbonylethyl)amide 1-methyl-2-[N-[4-amidinophenyl]aminomethyl]benzimidazol-5-yl carboxylic acid.

EFFECT: agents are highly effective.

12 cl, 2 dwg, 6 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to the obtaining of the new derivatives of benzamide of the formulas (I), which possess the activating influence on glucokinase, which can be used for treating of diabetes and obesity: where X1 and X2 represent oxygen, R1 represents alkylsufonyl, alkaneyl, halogen or hydroxyl; R2 represents alkyl or alkenyl, R3 represents alkyl or hydroxyalkyl, ring A represents phenyl or pyridyl, the ring B represents thiazolyl, thiadiazolil, isoxazoleyl, pyridothiazolyl or pyrazolyl, in which the atom of carbon of ring B, which is connected with the atom of nitrogen of the amide group of the formula(I), forms C=N bond with ring B.

EFFECT: obtaining new bioactive benzamides.

12 cl, 166 ex, 4 tbl

FIELD: organic chemistry, medicine, pharmacology.

SUBSTANCE: invention relates to new derivatives of carbamic acid esters of the general formula (I):

and their pharmaceutically acceptable salts eliciting activity with respect to metabotropic glutamate receptors mGlu of group I that can be used for treatment of acute and/or chronic neurological disorders. In the general formula (I) R1 means hydrogen atom or (C1-C7)-alkyl; R2 and R2' mean independently of one another hydrogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-group, halogen atom or trifluoromethyl; X means oxygen (O), sulfur (S) atom or two hydrogen atoms not forming a bridge; A1/A2 mean independently of one another phenyl or 6-membered heterocycle comprising 1 or 2 nitrogen atom; B represents group of the formula:

wherein R3 means (C1-C7)-alkyl and others; Y means -O-, -S- or a bond; Z means -O- or -S-; or B means 5-membered heterocyclic group of formulae: (a) , (b) , (c) or (d) . Also, invention relates to methods for preparing compounds and to a medicinal agent based on thereof.

EFFECT: improved preparing methods, valuable medicinal properties of compounds.

22 cl, 1 tbl, 2 sch, 78 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing (R)-1-aryl-2-tetrazolylethyl ether of carbamic acid of chemical formula 1 which involves asymmetric reduction of aryl ketone and carbamation of alcohol.

EFFECT: improved method.

15 cl, 8 tbl, 50 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to a method of producing N-nitromethyl azoles of formula

where R= , , , , , which can be used as biologically active substances and intermediates during synthesis of other azole derivatives. The method of producing N-nitromethyl azole derivatives is realised by treating a ketone with a corresponding azole acetic acid and nitric acid mixture at 50-60°C in the presence of 0.05-0.25 mole sodium nitrite per mole of the initial ketone. The volume ratio of nitric acid (58-70% concentration) to glacial acetic acid is equal to 1:6.

EFFECT: novel method of producing N-nitromethyl azole derivatives and synthesis of novel N-nitromethyl derivatives of 3-nitro-1,2,4-triazole.

1 cl, 5 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to derivatives of adamantine, in particular, to a new method for preparing adamant-1-yl-containing azoles of the general formula I-VIII: wherein R1 means ; R2 means ; R3 means ; R4 means ; R5 means ; R6 means ; R7 means , and R8 means . Indicated derivatives of adamantine are semifinished products used in synthesis of biologically active substances. Proposed method for preparing these compounds involves using a new method for synthesis of adamant-1-yl-containing azoles that includes the addition reaction of azoles: 2-methylimidazole, 3(5)-methylpyrazole and 4-methylpyrazole, 3,4-dinitropyrazole, 1,2,4-triazole, 3-methylpyrazole, 3-nitro-1,2,4-triazole and 5-methyltetrazole to 1,3-dehydroadamantane in the mole ratio of 1,3-dehydroadamantane to azole = 1:1 in diethyl ether medium at temperature 100°C for 4-5 h.

EFFECT: improved preparing method.

8 ex

The invention relates to new derivatives of aryl - and heteroarylboronic General formula I, where R1denotes a substituted phenyl or pyridyl, R2denotes a substituted phenyl, R3denotes hydrogen, (lower)alkyl, cyano, carboxy, esterified carboxylate, phenyl, 1H-tetrazolyl or the group,- CONR5R6, R5denotes hydrogen or the radical R7, R6represents -(CH2)mR7or R5and R6together with the nitrogen atom to which they are attached, denote morpholino, 2,6-dimethylmorpholine, piperidino, 4-(lower)alkylpiperazine, 4-(lower)alkoxyimino, 4-(lower)alkoxycarbonylmethyl or 4 formylpiperazine,7denotes phenyl, substituted phenyl, pyridyl, 1H-tetrazolyl, (lower)alkyl, cyano(lower)alkyl, hydroxy(lower)alkyl, di(lower)alkylamino(lower)alkyl, carboxy(lower)alkyl, (lower)alkoxycarbonyl(lower)alkyl, (lower)alkoxycarbonyl(lower)alkyl or phenyl(lower)alkoxycarbonyl, Radenotes hydrogen or hydroxy, Rbrepresents hydrogen, Z represents hydroxy or the group-OR8or-OC(O)NR8, R8denotes pyridyl or pyrimidinyl, X represents nitrogen or CH, m is 0, 1 or 2, n is 0, 1 or 2, and

The invention relates to new derivatives of formula (I), where R1- R4- hydrogen atoms; X - alkylene with 1 to 6 carbon atoms; Y is lower alkyl; B is - NR5R11where R5is a hydrogen atom, R11selected from 5 - to 6-membered heterocyclic radical, in which one ring member is a carbon and 1 to 4 members of the heteroatoms nitrogen, or sulfur, or their pharmaceutically acceptable salts, are useful as inhibitors of the synthesis of nitric oxide

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing (R)-1-aryl-2-tetrazolylethyl ether of carbamic acid, which includes enantioselective enzymatic reduction of an aryl ketone in a reaction mixture containing oxidoreductase and carbamination of the obtained alcohol.

EFFECT: obtaining (R)-1-aryl-2-tetrazolylethyl ether of carbamic acid.

19 cl, 1 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: described is an improved method of obtaining 2-(1-adamantyl)-5R-tetrazoles of general formula 1 , where: R=H, CH3, C2H5, or phenyl, possibly substituted with NO2 orF, consisting in the fact, that a reaction mixture, which consists of carbon acid nitrile (RCN), ammonium azide (NH4+N3) in a ratio of 1.2-1.8 mol of ammonium azide per 1 mol of nitrile in dimethylformamide, is heated at a temperature of 90-110°C by means of electromagnetic radiation with a frequency of 2450 MHz for not more than 2 hours, with the following processing of obtained 5R-tetrazole with 1-adamantanol in sulphuric acid with the concentration not less than 98 wt %.

EFFECT: method is safe, makes it possible to selectively obtain the target product with the high output due to reduction of a probability of a side process of thermal decomposition of 5R tetrazol and exclusion of a probability of ammonium azide sublimation, the target product is active against the virus of type A.

1 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: described are novel compounds of general formula ,

where X equals 1 or 2; Y equals 0 1, 2, or 3; R1 is hydrogen, C1-2alkyl or C1-2alkoxy; A denotes 2,6,-dimethylphenyl, a pharmaceutical composition containing same, a method of reducing concentration of uric acid in blood or increasing release of uric acid in a mammalian subject, and use the novel compounds to obtain a medicinal agent for treating, particularly, gout and hyperuricemia.

EFFECT: obtaining a medicinal agent for treating gout and hyperuricemia.

30 cl, 9 dwg, 17 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of general formula (I) or pharmaceutically acceptable salts thereof, where Alk is an C1-C6alkyl group; G is C=O and Q is CR51R52 or NR51, where R51 and R52, being identical or different, independently denote H, C1-C6alkyl, optionally substituted with a substitute selected from a group comprising carboxy, phenoxy, benzyloxy, C1-C6alkoxy or hydroxy; C3-C6cycloalkylC1-C6alkyl; phenylC1-C6alkyl, optionally substituted with a halogen; phenylamidoC1-C6alkyl; phenylC1-C6alkylamidoC1-C6alkyl, optionally substituted with a C1-C6alkoxy group; or R51 and R52, together with a carbon atom with which they are bonded form a C=O or C2-C6alkenyl group, optionally substituted with a phenyl; M1 is CR49, where R49 is H; M2 is CR50, where R50 is H; R38 is H, C1-C6alkyl, substituted with a phenoxy group; C3-C6cycloalkylC1-C6alkyl; arylC1-C6alkyl, optionally substituted with 1 or 2 substitutes selected from a group comprising C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxycarbonyl, carboxyl, N-methylamido, hydroxy, C1-C6alkoxyC1-C6alkoxy, C1-C6alkylthio, C1-C6alkylsulphanyl, cyano, halogen, perfluoroC1-C6alkyl, nitro, formyl, hydroxyC1-C6alkyl and amino, wherein the aryl moiety is a phenyl or naphthyl; and heteroarylC1-C6alkyl, where the heteroaryl moiety is pyridinyl, optionally substituted with 1 or 2 groups selected from C1-C6alkoxy or hydroxyC1-C6alkyl, pyrazolyl or isoxazolyl, substitute with 1 or 2 C1-C6alkyl groups; R47 and R48 is C1-C6alkyl. The invention also relates to specific compounds, a method of reducing or weakening bitter taste, a composition of a food/non-food product or beverage or drug for reducing or lightening bitter taste and a method of producing a compound of formula (I).

EFFECT: obtaining novel compounds which are useful as bitter taste inhibitors or taste modulators.

37 cl, 6 dwg, 12 tbl, 186 ex

FIELD: chemistry.

SUBSTANCE: described is a method of producing compounds of general formula, or , where R=C6H5 (Ia, IIa), 4-CH3C6H4 (Ib, IIb), C6H5CH2 (Ic, IIc), 4-CH3OC6H4 (Id, IId), 4-ClC6H4 (Ie, IIe), 4-NO2C6H4 (If, IIf), CH3 (Ig, IIg), by mixing corresponding isomeric 3-methyl-5-trinitromethyltetrazoles with an equimolar amount of hydrazine of formula (R)2NNH2, where R has values given above, in dry ethoxyethane at 0°C and then holding the reaction mixture at 25°C for 2 hours.

EFFECT: high efficiency of the method.

14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compound, which contains pyridine ring, represented by formula (1) , where R0 represents C1-6alkoxygroup, C1-6alkoxy-C1-6alkoxygroup, C1-6alkoxy-C1-6alkyl group, 1,3-dioxan-2-yl-C1-6alkyl group or group CR01C(=NOR02) (where each of R01 and R02 independently represents C1-6alkyl group), R1 represents C1-2 alkoxycarbonyl group, acetyl group or benzoyl group, which can be substituted with nitrogroup, X represents halogen atom, and n represents quantity of X substituents and equals integer number from 0 to 3, and when n equals 2 or more, X substituents can be similar or different from each other, which can be synthesised in industrially profitable way and used as intermediate compound for obtaining tetrazolyloxime derivatives which demonstrate fungicidal activity.

EFFECT: industrially profitable methods of obtaining tetrazolyloxime derivatives are described.

10 cl, 3 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a dual action compound which is characterised by general formula [((S)-N-valeryl-N-{[2'-(lH-tetrazol-5-yl)biphenyl-4-uyl]methyl}valine) ethyl ether (2R,4S)-5-biphenyl-4-yl-4-(3-carboxypropionylamino)-2-methylpentanoic acid]Na1-3·xH2O, in solid form, where x equals 0-3, which is an angiotensin receptor inhibitor and a NEP inhibitor, and can be used to treat hypertension.

EFFECT: high efficiency of using the compound.

19 cl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of the following general formula [1a], wherein R1 represents (1) a hydrogen atom, (2) C1-C6alkyl group, (3) C2-C6alkenyl group, (4) C2-C6alkynyl group, (5) C1-C6alkoxygroup, (6) hydroxyC1-C6alkyl group, (7) C1-C6alkoxy(C1-C6)alkyl group, (8) -CONR11R12, wherein R11 and R12 are identical or different, and each represents a hydrogen atom or C1-C6alkyl group, (9) phenyl group or (10) a five-member heteroaryl group which contains at least one heteroatom specified in a group consisting of a nitrogen atom and oxygen atom, and which may be substituted by C1-C6alkyl group; R2 represents (1) a halogen atom, (2) C1-C6alkyl group, (3) hydroxy group or (4) C1-C6alkoxy group; p is equal to 0, 1, 2 or 3; X represents a carbon atom or nitrogen atom; m1 is equal to 0, 1 or 2; m2 is equal to 0 or 1; the spiro ring AB may be substituted by 1-5 identical or different, specified in a group consisting of (1) hydroxy group, (2) C1-C6alkyl group, (3) C1-C6alkoxygroup and (4) oxo group; n1 is equal to 0, 1, 2, 3 or 4; n2 is equal to 1, 2, 3 or 4; n3 is equal to 0, 1 or 2, provided n2+n3 is equal to 2, 3 or 4; and a bond presented by the symbol means a single bond or a double bond, provided the three adjoining carbon atoms forms no allene bond presented by formula: C=C=C, or a pharmaceutically acceptable salt thereof.

EFFECT: invention refers to a pharmaceutical composition possessing GPR40 agonist activity, to a GPR40 agonist drugs; to a hypoglycemic agent stimulating insulin secretion on the basis of the above compounds.

45 cl, 42 tbl, 120 ex

Indanyl compounds // 2474572

FIELD: chemistry.

SUBSTANCE: in formula (I): , A is a single bond or a phenylene group which is substituted with R1; R1 is a methyl group; D is a single bond; R2a and R2b are identical or different and denote a hydrogen atom, a fluorine atom, a chlorine atom, a methyl group, a methoxy group, an ethoxy group or a trifluoromethyl group; R3a and R3b denote a hydrogen atom; R4 and R5 denote methyl groups, or R4 and R5 are bonded to each other to form an ethylene group; R6 is a methyl group or an ethyl group; m is an integer from 0 to 4; Z is a carboxy group. The invention also relates to a pharmaceutical composition containing said compounds, use of said compounds to produce a medicinal agent for treating or preventing disorders associated with abnormal bone or mineral homeossatis, such as hypoparathyroidism and osteoporosis, and a method of improving bone metabolism.

EFFECT: high activity of the calcium receptor antagonist.

15 cl, 78 tbl, 85 ex

FIELD: chemistry.

SUBSTANCE: described is a method of producing 1-C1-6alkyl- and 1-phenyl-5-iodotetrazoles by reacting C1-6alkyl- and 1-phenyl-mercaptotetrazoles with hydrogen peroxide in the presence of free iodine, hydroiodic acid or hydroiodic acid salt in a solvent medium in form of acetic acid or mixture thereof with water, when the reaction is carried out using convection heating or microwave activation.

EFFECT: method is safe and environmentally friendly, and enables to significantly cut reaction time and reduce reaction temperature, which increases output of the end product, overall.

4 cl, 20 ex

FIELD: chemistry.

SUBSTANCE: described is an improved method of producing 5-amino-3-aminomethyl-1,2,4-triazole dihydrochloride, which can be used in producing medicinal and biologically active substances and chemicals. The described method involves successively mixing aminoguanidine bicarbonate, hydrochloric acid and phthalimidoglycine of formula (II) in molar ratio 1.0:(1.0÷1.1):1.0 and the obtained mixture is heated with gradual distillation of water at atmospheric pressure and stirring until achieving temperature of 160-185°C; the reaction mixture is then heated at that temperature for 1-5 hours, after which a solution of sodium carbonate in water is added until achieving pH 10-11; the obtained solution is boiled and the compound of formula (III) formed is separated and subjected to hydrolysis with hydrochloric acid.

EFFECT: improved method of producing 5-amino-3-aminomethyl-1,2,4-triazole dihydrochloride.

1 cl, 6 ex

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