Method of producing substituted 4-hydroxy-3-oxo-3,4-dihydro-2h-1,4-benzoxazine-6,7-dicarbonitriles based on 4-bromo-5-nitrophthalonitrile

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6,7-dicarbonitriles of general formula: where R=H (a); CH3 (b); OCH3 (c); CI (d) which can be used as biologically active substances, fluorescent materials and for synthesis of phthalocyanines. The method involves synthesis of substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6,7-dicarbonitriles through a reaction which takes place in two steps, where at the first step 4-bromo-5-nitrophthalonitrile reacts with sodium salts of substituted 3-phenylpropanoates in molar ratio 1:2, respectively, at temperature 19…25°C for 12-20 hours in dimethyl formamide (DMF) solution, after which the reaction mass is diluted with tenfold excess water with T=0…25°C. The released resinous residue is extracted with dichloromethane, thoroughly washed with water and chromatographed on silica gel. The eluent (solvent) is evaporated. The residue of the intermediate product is filtered and re-crystallised from alcohol. At the second step of the method, tin dichloride solution in concentrated hydrochloric acid is mixed with the solution of the obtained intermediate product in ethyl alcohol in molar ratio 3.5-4.5:1, respectively, at temperature 30...50°C and reaction time of 1-2 hours, after which the reaction mixture is diluted with tenfold excess water with T=0…25°C, and the precipitate is filtered and re-crystallised from alcohol.

EFFECT: obtaining novel heterocyclic dicyano-derivatives of benzoxazines.

1 tbl, 5 ex

 

The invention relates to a method of obtaining new nitrogen - and oxygen-containing heterocyclic compounds, namely substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6,7-dicarbonitriles, which can be used as biologically active substances, fluorescent materials, and for the synthesis of phthalocyanines.

From the technical level we are not aware of ways to obtain these compounds, therefore, the object of the invention is to develop a method of producing substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6,7-dicarbonitriles the General structural formula:

where R=H(a); CH3(b); co3(C); Cl(d)

This object is achieved in that the method of synthesis of substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6,7-dicarbonitriles involves two steps. At the first stage synthesize intermediate products (3)obtained by a reaction between 4-bromo-5-nitrophthalonitrile (1) with the sodium salts of substituted 3-phenyl-propanoate (2). In the second stage the products (3) is subjected to reductive cyclization.

R=H(a); CH3(b); co3(C); Cl(d)

The interaction between the reagents (1) and (2) occurs at a temperature of 19...25°C and a molar ratio(1): (2)=1: 2, within 12-20 hours in a solution of DMF and does not require additional use of the catalysts of the RC. Then the reaction mass is diluted tenfold excess water from T=0...25°C. Released resinous residue is extracted with methylene chloride, washed thoroughly with water, chromatographic on silica gel. Eluent (solvent) is evaporated, the precipitation of the intermediate product (3) is filtered off, recrystallized from alcohol. Then to the solution douglasthe tin in concentrated hydrochloric acid at a temperature of 30...50°C under vigorous stirring was added a solution of the obtained intermediate product (3) in ethanol at a molar ratio of SnCl2:product (3)=3.5 to 4.5:1 and reaction time of 1-2 hours. Then the reaction mixture is diluted tenfold excess water from T=0...25°C, the precipitated product substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6,7-dicarbonitrile(4) is filtered off and recrystallized from alcohol.

The structure of the obtained compounds was confirmed by IR, NMR H1The NMR With13, NOESY spectroscopy and mass spectrometry, and x-ray diffraction analysis.

The invention is illustrated by the following examples.

Example 1. 2-[cyano(phenyl)methylene]-4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6,7-dicarbonitrile (4A)

To a solution of 0.002 mole of 4-bromo-5-nitrophthalonitrile in 3 ml of DMF is added 0,004 mol of compound (2A) and stirred at a temperature of 19...25°C for 12-20 hours then poured into water (30 ml) with T=0...25°C. Released resinous residue is extracted with methylene chloride, washed thoroughly with water, chromatographic on silica gel. Eluent (solvent) is evaporated, precipitated precipitate is filtered off and recrystallized from alcohol. Then to a solution of 0.004 mol douglasthe tin in 2 ml of concentrated hydrochloric acid is poured 0.001 mol obtained intermediate product (3A) in 2 ml of ethanol and intensively stirred at a temperature of 30...50°C for 1-2 hours. Then the reaction mixture was diluted with water (30 ml) with T=0...25°C, the precipitation is filtered off and recrystallized from alcohol. Get 0,23 g (70% of theory) of 2-[cyano(phenyl)methylene]-4-hydroxy-3-oxo-3,4-di-hydro-2H-1,4-benzoxa-zine-6,7-dicarbonitrile - crystals of a bright yellow color, TPL>300°C.

Examples 2-5. Other substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6,7-dicarbonitrile get analogously to example 1. Physico-chemical characterization of substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6,7-dicarbonitriles are shown in table 1.

The method of obtaining substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6,7-dicarbonitriles General formula:

where R=H(a); CH3(b); co3(C); Cl(d),
namely, that the reaction proceeds in two stages, the first stage 4-bromo-5-nitrito iril subjected to interaction with the sodium salts of substituted 3-phenylpropanoate at a molar ratio of 1:2 respectively, at a temperature of 19...25°C for 12-20 hours in a solution of DMF, after which the reaction mass is diluted tenfold excess water from T=0...25°C, separated resinous residue is extracted with methylene chloride, washed thoroughly with water, chromatographic on silica gel, eluent (solvent) is evaporated, the precipitation of the intermediate product is filtered and recrystallized from alcohol, in the second step of the way to the solution douglasthe tin in concentrated hydrochloric acid added to the solution obtained intermediate product in ethanol at a molar ratio of 3.5 to 4.5:1, respectively, at a temperature of 30...50°C and the reaction time of 1-2 h, after which the reaction mixture is diluted tenfold excess water from T=0...25°C, the precipitated product is filtered and recrystallized from alcohol.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula

,

where R1 is selected from formulae

, and ,

n equals 0; R6 and R7 are independently selected from hydrogen, C1-C6alkyl, cyanoC1-C6alkyl, C3-C6cycloalkylC0-C4alkyl and C6arylC0-C4alkyl; or R6 and R7 together with a carbon atom to which they are bonded form a 6-member heterocycloalkyl with one nitrogen atom; wherein any alkyl in R6 and R7 can optionally contain a methylene group substituted with an O atom; wherein any aryl in R6 and R7 or formed by a combination of R6 and R7 can be optionally substituted with one radical independently selected from: halide, C1-C6alkyl, -XC(O)OR10; where X denotes a bond; R10 is independently selected from C1-C6alkyl; R8 is selected from C5-C9heteroarylC0-C4alkyl containing 2-3 heteroatoms independently selected from N, O and S; wherein any heteroaryl in R8 can be optionally substituted with one radical independently selected from: halide, C1-C6alkyl, C3-C6cycloalkyl; R2 denotes hydrogen; R3 and R4 are independently selected from hydrogen, C1-C6alkyl, C3-C6cycloalkylC0-C4alkyl and C6arylC0-C4alkyl; wherein any alkyl in R3 and R4 can optionally contain a methylene group substituted with a S(O)2 group; R5 is selected from C5-C6heterocycloalkyl with 1-2 heteroatoms selected from N and O, and NR12R13; where R12 and R13 are independently selected from C1-C6alkyl; as well as pharmaceutically acceptable salts and isomers thereof. The invention also relates to use of compounds of formula (I) in preparing a medicinal agent, and to a pharmaceutical composition having cathepsin S inhibiting properties, which contains a therapeutically effective amount of the compound of formula (I) in combination with a pharmaceutically acceptable filler.

EFFECT: obtaining compounds which can be used as cathepsin S inhibitors.

10 cl, 12 dwg, 2 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to oxazolidinone derivatives covered by general graphic formula (I) and to their pharmaceutically acceptable salts. In formula (I) R1, R2, R3 and R4 are independently chosen from a group including -H and halogen; A is chosen from a group including R5 and R6 are independently chosen from a group including -H, -F, -CI, -Br, -OH, alkyl(C1-C6), haloalkyl(C1-C6), alkoxygroup(C1-C6); R7 is chosen from a group including -H, alkyl(C1-C6); either R7 and R5 or R6 taken together form a cycle of 2 carbon atoms and include 1 group chosen from O which in turn can be substituted by one substitute chosen from alkyl(C1-C6); R12 is chosen from a group including -H, -COR14, -CSR14, -COOR14; R14 is chosen from a group including alkyl (C1-C6), cycloalkyl(C3-C6), alkenyl(C2-C6), R16, R17 and R18 represent -H; R21 is chosen from a group including -H, alkyl(C1-C6); X is chosen from a group including O, S, and Y is chosen from a group including O, S, SO, SO2, and NR12; and optional substitutes of alkyl(C1-C6) groups can represent one or two groups chosen from the following: -OR21, -CN.

EFFECT: invention refers to methods for preparing the compounds of the invention, to application of oxazolidinone derivatives for preparing a drug for treating bacterial infections and to a pharmaceutical composition for treating bacterial infections, including a therapeutically effective amount of the compound of the invention.

36 cl, 10 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to (5H-pyrazolo[1,5-c][1,3]benzoxazin-5-yl)phenylmethanone derivatives (I), useful as HIV viral replication inhibitors, as well as pharmaceutical compositions, use thereof as medicinal agents.

EFFECT: disclosed compounds are meant for preventing or treating HIV infection and treating AIDS.

7 cl, 2 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula I and to their physiologically compatible salts. In general formula I , X denotes identical or different groups =C(-R)- or =N-, wherein at least one =C(-R-)- is substituted by =N-; Y is -O-; R denotes identical or different hydrogen, halogen, (C1-C6)-alkyl; R1 denoes (C4-C16-alkyl, (C1-C4)-alkylene-(C6-C10)-aryl, (C1-C4)-alkylene-(C3-C12)-cycloalkyl, (C9-C10)-bicyclic ring, wherein the aryl can be singly or multiply substituted with (C1-C6)-alkyl; R2 denotes hydrogen; or R1 and R2 together with the nitrogen atom which it is bonded form a monocyclic, saturated 6-member ring in which separate members of the ring system can be substituted with -CHR4-; R4 denotes (C1-C6)-alkyl. The invention also relates to a pharmaceutical composition having inhibiting action on endothelial lipase (EL) and containing one or more compounds of formula I, to use of the disclosed compounds to prepare a medicinal agent and to methods of producing compounds of formula I.

EFFECT: high effectiveness of derivatives.

11 cl, 20 ex

FIELD: chemistry.

SUBSTANCE: invention relates to azole derivatives of formula I , where: A denotes S, O; W denotes -(C=O)-; X are identical or different and denote =C(-R)- or =N-; Y denotes -O- or -NR1-; R denotes hydrogen, halogen, (C1-C6)-alkyl, nitro; R1 denotes hydrogen; R2 denotes (C5-C16)-alkyl, (C1-C4)alkyl-phenyl, where phenyl can be optionally mono- or poly-substituted with (C1-C6)-alkyl; R3 denotes hydrogen; or R2 and R3 together with the nitrogen atom bearing them can form a monocyclic saturated 6-member ring system, where separate members of this ring system can be substituted with 1 group selected from the following: -CHR5-, -NR5-; R5 denotes (C1-C6)-alkyl, trifluoromethyl; and physiologically acceptable salts thereof. The invention also pertains to methods of producing said compounds and a medicinal agent based on said compounds.

EFFECT: novel compounds and a medicinal agent based on said compounds are obtained, which can be used as hormone-sensitive lipase (HSL) or endothelial lipase (EL) inhibitors.

12 cl, 11 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of tetrahydrobenzoxazines

in which substitute R1 denotes a hydrocarbyl residue having 1-3000 carbon atoms, and substitutes R2, R3, R4 and R5 independently denote hydrogen atoms, hydroxyl groups or hydrocarbyl residues, having 1-3000 carbon atoms, respectively, and in which substitutes R3 and R4 or R4 and R5 with a partial structure -O-CH2-NR7-CH2-, bonded to the benzene ring, can also form a second tetrahydrooxazine ring, where R7 denotes hydrocarbyl residues having 1-3000 carbon atoms, provided that at least one of substitutes R1, R2, R3, R4, R5 or R7 are polyisobutenyl, having 3000 carbon atoms and the rest of the substitutes from the group R1, R2, R3, R4, R5 or R7, if they denote hydrocarbyl residues, have 1-20 carbon atoms, respectively, as anti-oxidants for stabilising mineral oil and fuel products against the effect of light, oxygen and heat. The invention also describes jet fuel and jet fuel additive concentrate containing tetrahydrobenzoxazine of formula (I).

EFFECT: preparation of stabilisers having improved stabilisation of nonliving organic material, particularly jet fuel against the effect of light, oxygen and heat.

9 cl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula [I-D1] or pharmaceutically acceptable salt thereof,

,

where each symbol is defined in the claim. The invention also relates to pharmaceutical compositions containing said compound and having HCV polymerase inhibiting activity.

EFFECT: disclosed compound exhibits anti-HCV activity, based on HCV polymerase inhibiting activity and is useful as an agent for preventing and treating hepatitis C.

32 cl, 497 tbl, 1129 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to methods for synthesis of compounds of formula (A), where R1 denotes halogen, C1-C6halogenalkyl, C1-C6alkoxy(C1-C6)alkyloxy or C1-C6alkoxy(C1-C6)alkyl; R2 denotes halogen, C1-C4alkyl or C1-C4alkoxy; R3 and R4 independently denote a branched C3-C6alkyl; and R5 denotes C3-C12cycloalkyl, C1-C6alkyl, C1-C6hydroxyalkyl, C1-C6alkoxy(C1-C6)alkyl, C1-C6alkanoyloxy(C1-C6)alkyl, C1-C6aminoalkyl, C1-C6alkylamino(C1-C6)alkyl, C1-C6dialkylamino(C1-C6)alkyl, C1-C6alkanoylamino(C1-C6)alkyl, HO(O)C-(C1-C6)alkyl, C1-C6alkyl-O-(O)C-(C1-C6)alkyl, H2N-C(O)-(C1-C6)alkyl, C1-C6alkyl-HNC(O)-(C1-C6)alkyl or (C1-C6alkyl)2N-C(O)-(C1-C6)alkyl, or their pharmaceutically acceptable salts which have renin inhibiting activity, as well as to basic intermediate compounds obtained during steps for synthesis of the desired compounds and to methods for synthesis of said intermediate compounds.

EFFECT: alternative synthesis method.

43 cl, 8 dwg, 11 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula pharmaceutically acceptable salts thereof, where ---- independently denotes a single or double bond; ring Q is imidazole, triazole (for example 1,2,3-triazole or 1,3,4-triazole), tetrazole or oxadiazole; B denotes C(R7)(R8) or C(R7), where if the bond between B and Y is a single bond, B denotes C(R7)(R8), and when the bond between B and Y is a double bond, B denotes C(R7); Y denotes C(R7), C(R7)(R8) or O, where if the bond between B and Y is a single bond, Y denotes C(R7)(R8) or O, and when the bond between B and Y is a double bond, B denotes C(R7); Z1 denotes -CH2-, -(CH2)2-, -CH2CH-CH3-, where Z1 is bonded on the left side to a nitrogen atom or -(CH2)3-; X denotes C(R1) or N; A denotes quinolyl, quinazolinyl or benzofuranyl, any of which is optionally substituted with 1-4 substitutes, which can be identical or different and are selected from a group comprising halogen, cyano, C1-6-alkyl, halogen-C1-6-alkyl, C(O)N(R3)(R4), 5-member heterocyclic ring containing 1-3 heteroatoms selected from N or O. The heterocyclic ring is optionally substituted with C1-6-alkyl; when R is present, each independently denotes halogen, C1-6-alkyl; each R1 denotes hydrogen or methyl; each R2 denotes cyano, C1-6-alkyl, C1-6-alkoxy, halogen-C1-6-alkyl, =O, -C(O)N(R3)(R4), -C(O)N(R3)-C1-6-alkoxy, -C(NOR5)R6, -C(O)R6, -C(O)OR7, -C(O)NHNHC(O)R6, 5-member heterocyclic ring containing 1-3 heteroatoms selected from N or O. The heterocyclic ring is optionally substituted with C1-6-alkyl; R3 and R4 independently denote hydrogen; C1-6-alkyl; C3-7-cycloalkyl; C3-7-cycloalkyl-C1-6-alkyl; or when R3 and R4 are bonded to the same nitrogen atom, they, together with the nitrogen atom, they form a 4-, 5- or 6-member ring which optionally contains one extra O atom in the ring; R5 denotes C1-4-alkyl; R6 denotes C3-7-cycloalkyl or C1-6-alkyl; R7 and R8 independently denote hydrogen or C1-6-alkyl; p equals 0, 1 or 2; r equals 0, 1, 2 or 3; s equals 0, 1, 2 or 3. The invention also relates to 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazin-3-carboxamide, 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperidinyl]ethyl}imidazo-[1,5-a]quinoline-3-carboxamide, dihydrochloride 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperidinyl]ethyl}[1,2,3]triazolo[1,5-a]quinoline-3-carboxamide, 7-methyl-6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4,5-dihydroimidazo[1,5-a]quinoline-3-carboxamide, to use of the compound in any of claims 1-16, as well as a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds, having 5-HT1 receptor mediated activity.

23 cl, 195 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of a compound of formula , where R1 is an alkyl or aryl group, or a pharmaceutically acceptable salt or solvate thereof, including hydrate, involving reaction of a compound of formula with a Grignard reagent of formula , where X is a halogen selected from Cl, Br and I, and R1 is an alkyl or aryl group; and optional conversion of the obtained free base compound of formula (I) to a pharmaceutically acceptable salt. The invention also relates to a compound of formula II; a compound of formula , where X is a halogen selected from O, Br and I and to use of formula II and IIIA compounds in synthesis of delmopinol and a derivative of the formula I compound.

EFFECT: novel method for synthesis of a compound of formula I using novel intermediate compounds of formulae II and IIIA.

18 cl, 11 ex

FIELD: organic chemistry, chemical technology, herbicides.

SUBSTANCE: invention describes a method for preparing compounds of the formula (I):

wherein each R1, R2, R3 means independently of one another (C-C6)-alkyl; R can represent also pyridyl; R4 and R5 in common with nitrogen atoms to which they are joined form unsaturated 5-8-membered heterocyclic ring that can be broken by oxygen atom; G means hydrogen atom. Method involves interaction of compound of the formula (II):

wherein R1, R2 and R3 have above given values; R6 is a group RR9N-; R7 is a group R10R11N-; each among R8, R, R10 and R11 means independently of one another hydrogen atom or (C1-C6)-alkyl in inert organic solvent being optionally with the presence of a base with compound of the formula (IV) ,

(IVa)

or (IVb) ,

wherein R4 and R have above given values; H x Hal means hydrogen halide. The prepared compound of the formula (I) wherein G represents ammonium cation is converted to the corresponding compound of the formula (I) by treatment with Brensted's acid wherein G represents hydrogen atom. Also, invention describes compound of the formula (II) wherein R1, R2, R3, R6 and R7 have above indicated values.

EFFECT: improved preparing method.

9 cl, 12 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to oxazolo- and thiazolo-[4,5-c]-quinoline-4-amines of the general formula (I)

wherein R1 is taken among group consisting of oxygen and sulfur atoms; R2 is taken among hydrogen atom, alkyl, alkyl-OH (hydroxyalkyl), alkyl-X-alkyl, alkyl-O-C(O)-N(R5)2, morpholinyl, pyrrolidinyl, alkyl-X-aryl radical, alkenyl-X-aryl radical; each substitute R3 and R4 represents hydrogen atom or substitutes R3 and R4 taken in common form the condensed aromatic or [1,5]-naphthiridine system; X represents -O- or a single bond; R5 represents hydrogen atom. Also, invention describes intermediate compounds, pharmaceutical composition and a method for stimulating biosynthesis of cytokinins (cytokines) based on these compounds. Invention provides preparing new compounds eliciting valuable biological properties.

EFFECT: valuable properties of compounds.

21 cl, 2 tbl, 64 ex

FIELD: organic chemistry, madicine.

SUBSTANCE: tricyclic benzodiazepines of formula I as well as their pharmaceutical acceptable salts, pharmaceutical composition containing the same and methods for hypertension treatment are disclosed. In formula A is -C(O)-; Y is CH2 or CH as olefinic site; X is CH2 or CH as olefinic site S, O or NR3 (R3 is C1-C8-alkyl) with the proviso that when Y is CH, X also is CH; Z is N or CH; R1 is hydrogen, C1-C8-alkyl, C1-C8-alkoxy or halogen; R2 is NR4COAr (R4 is hydrogen; Ar is phenyl optionally substituted with 1-3 substitutes independently selected from C1-C8-alkyl, halogen, hydroxyl, fluorinated C1-C8-alkylthio and another phenyl optionally substituted with substitute selected from C1-C4-alkyl, halogen, and hydroxyl); R5 is hydrogen, C1-C4-alkyl, C1-C4-alkoxy, fluorine, chlorine, hydroxyl or di-(C1-C4)-alkylamino.

EFFECT: improved pharmaceutical composition for hypertension treatment.

12 cl, 5 tbl, 52 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compounds of the general formula (1)

wherein A represents bicyclic or tricyclic azepine derivative; V1 and V2 both represent hydrogen atom (H) or one among V1 and V2 represents hydrogen atom (H), OMe, OBn, OPh, O-acyl, Br, Cl, F, N3, NH2, NHBn and another represents hydrogen atom (H); or V1 and V2 represent in common =O or -O(CH2)pO-; W1 represents oxygen (O) or sulfur (S) atom; X1 and X2 both represent hydrogen atom (H) or in common represent =O or =S; Y represents OR5 or NR6R7; R1 means hydrogen atom (H), lower alkyl, F, Cl and Br; R2 means lower alkoxy-group or values given for R1; R3 and R5 are taken independently among hydrogen atom (H) and lower alkyl; R4 means hydrogen atom (H); R6 and R7 are taken independently among hydrogen atom (H) and lower alkyl, or they in common mean -(CH2)n-; n = 3, 4, 5 or 6; p = 2 or 3. These compounds are agonists of vasopressin V2 receptors and useful as antidiuretic and procoagulants, and also to pharmaceutical compositions comprising these vasopressin agonists. These compositions are useful especially in treatment of diabetes insipidus of the central origin and night enuresis.

EFFECT: valuable medicinal properties of compounds, improved method for treatment.

26 cl, 1 tbl, 119 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacology.

SUBSTANCE: invention relates to gyrase inhibitors that reduce amount of microorganisms in biological sample by contacting the indicated sample with compound of the formula (I): , to a method for treatment of bacterial infection by using compounds of the formula (I), compounds of the formula (I) and a pharmaceutical composition comprising compounds of the formula (I). Invention provides the enhanced effectiveness of treatment.

EFFECT: valuable medicinal properties of gyrase.

54 cl, 5 tbl, 13 ex

FIELD: organic chemistry, medicine, hematology.

SUBSTANCE: invention elates to new compounds that inhibit activated blood coagulating factor X (Fxa factor) eliciting the strong anti-coagulating effect. Invention proposes compound of the formula (1): Q1-Q2-C(=C)-N-(R1)-Q3-N(R2)-T1-Q4(1) wherein R1, R2, Q1, Q2, Q4 and T1 have corresponding values, and Q2 represents the group of the formula: wherein R9, R10 and Q5 have corresponding values also, or its salt, solvate or N-oxide. Invention provides the development of a novel compound possessing strong Fxa-inhibiting effect and showing the rapid, significant and stable anti-thrombosis effectin oral administration.

EFFECT: valuable medicinal properties of compounds.

13 cl, 1 tbl, 195 ex

FIELD: biochemistry, medicine, in particular new bioactive compounds having peptide hormone vasopressin agonistic activity.

SUBSTANCE: disclosed are compounds of general formula 1 or 2 or tautomers, or pharmaceutically acceptable salts thereof, wherein W represents N or C-R4; R1-R4 are independently H, F, Cl, Br, alkyl, O-alkyl, NH2, NH-alkyl, N(alkyl)2, NO2 or R2 and R3 together may form -CH=CH-CH=CH-; G1 represents bicyclic or tricyclic condensed azepine derivatives selected from general formulae 3-8 wherein A1, A4, A7, and A10 are independently CH3, O, and NR5; A2, A3, A9, A11, A12, A14, and A15 are independently CH and N; or A5 represents covalent bond and A6 represents S; or A5 represents N=CN and A6 represents covalent bond; A8 and A12 are independently NH, N-CH3 and S; A16 and A17 both represent CH2 or one of A16 and A17 represents CH2 and the other represents CH(OH), CF2, O, SOa, and NR5; R5 represents H, alkyl, CO-alkyl, and (CH2)bR6; R6 represents phenyl, pyridyl, OH, CO2H; a = 0-2; b = 1-4; Y represents CH or N; Z represents CH=CH or S; and G2 represents group selected from groups of formulae 9-11 wherein Ar represents phenyl, pyridyl, naphthyl, and mono- or polysubstituted phenyl, pyridyl, wherein substituents are selected from F, Cl, Br, alkyl, NO2; D represents covalent bond or NH; E1 and E2 both are H, OMe, F, or one of E1 and E2 represents OH, O-alkyl, OBn, OPh, OAc, F, Cl, Br, N2, NH2, NHBn or NHAc and the other represents H; or E1 and E2 together form =O, -O(CH2)gO- or -S(CN2)gS-; F1 and F2 both represent H or together form =O or =R; L represents OH, O-alkyl, NH2, NH-alkyl, and NR9R10; R7 represents COR8; R8 represents OH, O-alkyl, NH2, NH-alkyl, N(alkyl)2, pyrolidinyl, and piperidinyl; R9 and R10 both are alkyl or together form -(CH2)h-; V represents O, N-CN or S; c = 0 or 1; d = 0 or 1, e = 0 or 1; f = 0-4; g = 2 or 3; h = 3-5, with the proviso, that both d and e are not 0. Also disclosed are pharmaceutical composition having agonistic activity in relate to V2 receptor, method for treatment one or more diseases (e.g., enuresis, nycturia, diabetes insipidus, hemorrhage disorders, urinary incontinence.

EFFECT: new compounds with value biological characteristics.

41 cl, 19 tbl, 193 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new amide derivatives of carboxylic acid that are antagonists of NMDA receptors of the formula (I): , wherein one radical among R1, R2, R3 and R4 represents -OH or NH2-group and others are hydrogen atoms; or two adjacent groups R1, R2, R3 and R4 in this case in common with one or more similar or different additional heteroatoms and -CH= and/or -CH2-groups form 5-6-membvered homo- or heterocyclic ring but preferably pyrrole, pyrazole, imidazole, oxazole, oxooxazolidine or 3-oxo-1,4-oxazine ring; two other groups among R1, R2, R3 and R4 radicals represent hydrogen atoms; R5 and R6 in common with nitrogen atom between them form saturated or unsaturated 4-6-membered heterocyclic ring that is substituted with phenoxy-, phenyl-[(C1-C4)-alkoxy]-, phenoxy-[(C1-C4)-alkyl]-, benzoyl-group optionally substituted in aromatic ring with one or more halogen atoms, (C1-C4)-alkyl or (C1-C4)-alkoxy-group; X and Y mean independently oxygen, nitrogen atom or group -CH=, and to their salts formed with acids and bases. Also, invention relates to a method for preparing compounds of the formula (I) and pharmaceutical compositions showing activity as selective antagonists of NR2B receptor based on these compounds. Invention provides preparing new compounds and pharmaceutical compositions based on thereof for aims in treatment of the following diseases: chronic neurodegenerative diseases, chronic painful states, bacterial and viral infections.

EFFECT: improved preparing method, valuable medicinal properties of compounds and compositions.

11 cl, 2 tbl, 27 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of benzoxazepine and describes derivative of benzoxazepine of the general formula (I): wherein X represents -CO or -SO2; R1, R2, R3 and R4 are chosen independently from hydrogen atom (H), (C1-C4)-alkyl, (C1-C4)-alkoxy-group, (C1-C4)-alkyloxy-(C1-C4)-alkyl, -CF3, halogen atom, nitro-group, cyano-group, -NR8R9, -NR8COR10 and -CONR8R9; R5, R6 and R7 represent independently hydrogen atom (H) or (C1-C4)-alkyl; R8 and R9 represent independently hydrogen atom (H) or (C1-C4)-alkyl; or R8 and R9 in common with nitrogen atom to which they are bound form 5- or 6-membered saturated heterocyclic ring comprising optionally the additional heteroatom chosen from oxygen atom (O), sulfur atom (S) or the group -NR11; R10 represents (C1-C4)-alkyl; R11 represents (C1-C4)-alkyl; A represents residue of 4-7-membered saturated heterocyclic ring comprising optionally oxygen atom wherein ring is substituted optionally with 1-3 substitutes chosen from (C1-C4)-alkyl, (C1-C4)-alkoxy-, hydroxy-group, halogen atom and oxo-group, or to its pharmaceutically acceptable salt under condition that compounds of the formula (I) are excluded wherein X represents -CO, and each among R1-R7 represents hydrogen atom (H), and A represents -(CH2)3 or -(CH2)4; compounds of the formula (I) wherein X represents -CO; R1 represents hydrogen atom (H); R2 represents methyl (CH3); each among R3-R7 represents hydrogen atom (H), and A represents -(CH2)3; compounds of the formula (I) wherein X represents -CO; R1 and R2 represent hydrogen atom (H); R3 represents methyl; each among R4-R7 represents hydrogen atom (H), and A represents -(CH2)3; compounds of the formula (I) wherein X represents -CO; each among R1-R3 represents hydrogen atom (H); R4 represents methyl; each among R5-R7 represents hydrogen atom (H), and A represents -(CH2)3, and compounds of the formula (I) wherein X represents -CO; each among R1-R4 represents hydrogen atom (H); R5 represents methyl; R6 and R7 represent hydrogen atom (H), and A represents -(CH2)3. Also, invention describes pharmaceutical compositions comprising indicated derivatives and using these benzoxazepine derivatives in treatment of neurological diseases and psychotic disorders sensitive to enhancing responses mediated by AMPA receptors in the central nervous system. Invention provides preparing new compounds possessing the useful biological properties.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

8 cl, 1 tbl, 31 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel anellated carbamoylazaheterocycles of the general formula (1) that possess inhibitory property of kinase activity and eliciting, for example, an anticancer activity. Also, compounds can be used as agonists, antagonists, receptor modulating agents, antiparasitic and antibacterial agents. Also, invention relates to a method for synthesis of compounds of the formula (1), a pharmaceutical composition based on thereof and a focused library for assay of leader-compounds. In compounds of the general formula (1) W represents 6-oxopiperazine, [1,4]-thiazepane, [1,4]-oxazepane or [1,4]-diazepane cycle anellated with at least one optionally substituted and optionally condensed heterocycle or carbocycle Q; Q represents optionally substituted thiophene, optionally substituted pyrrole, optionally substituted imidazole, optionally substituted thiazole, optionally substituted pyrrolidine, optionally substituted indole, optionally substituted benzofuran, optionally substituted pyridine, optionally substituted quinoline, optionally substituted benzene or optionally substituted naphthalene cycle; R1, R2 and R represent independently of each another hydrogen atom, inert substitute, optionally substituted (C1-C6)-alkyl, optionally substituted (C3-C8)-cycloalkyl, optionally substituted phenyl, optionally substituted aryl, optionally substituted heterocyclyl.

EFFECT: improved preparing method, valuable biological and medicinal properties of compounds and pharmaceutical composition.

15 cl, 5 tbl, 6 ex

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