Multifunctional quinoline derivatives as antineurodegenerative agents

FIELD: chemistry.

SUBSTANCE: invention relates to a hydroxy-derived quinoline of the formula (I)

or to a pharmaceutically acceptable salt thereof, (I) wherein R1 is hydrogen, (C1-C3)alkyl, (C1)alkylene(C3)cycloalkyl, (C1)haloalkyl or (C1)alkylene(C6)aryl; R2 is hydrogen or halogen; R3 is hydrogen, halogen, (C1)alkyl or (C1)alkoxy; R4 is hydrogen, halogen, (C1)alkyl, (C1)alkoxy or (C1)haloalkyl; R5 and R6 are hydrogen; and R7 is (C9-C15)alkanol, (C1)alkylenepiperazinyl(C1-C2)alkanol, (C1-C8)alkylenepiperazinyl (C1-C2)alkyl, (C10-C13)alkylene OCOCH3, (C1)alkylene(C1)alkylamino(C3)alkynyl, (C1)alkyleneamino(C8)alkanol or (C1)alkyleneamino(C6)alkanol(C1)alkylene(8-methoxyquinolin-2-yl); or (II), where R1, R2, R3, R4 and R6 each is as described in (I) above; R5 is (C11-C12)alkanol, and R7 is hydrogen. The invention also relates to a pharmaceutical composition based on the formula (I) compounds, a method for treatment of Alzheimer's disease, traumatic brain injury and/or damage to the spinal cord and a method for improvement of the ability of learning and/or memory in a patient suffering from Alzheimer's disease, based on the formula (I) compound.

EFFECT: new hydroxy derivatives of quinoline have been obtained that have useful biological properties.

13 cl, 13 dwg, 9 ex

 



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to benzimidazole-4-carboxamide derivatives of formula , wherein X means an alkenyl group C2-C7 substituted by two methyls, nitro-radical mono-substituted thienyl, unsubstituted quinolinyl, unsubstituted indolyl, unsubstituted pyridazinyl, unsubstituted piperazinyl, C1-C6-alkyl disubstituted piperazinyl, unsubstituted piperidinyl, unsubstituted pyrazinyl, unsubstituted imidazolyl, unsubstituted pyrimidinyl, phenyl monosubstituted pyrimidinyl, pyrimidinyl disubstituted by an amine radical and a radical specified in a group containing -F, -Cl, -Br or -I, hydroxyl trisubstituted phenyl, methoxy-radical trisubstituted phenyl, hydroxyl and methoxy-radical disubstituted phenyl, pyrazolyl disubstituted by a radical specified in a group containing a C1-C6-alkyl, and by a radical specified in a group containing -F, -C1, -Br or -I; Y means aminophenyl monosubstituted by a radical of -F, -O, -Br or -I phenyl, hydroxyethyl disubstituted by hydroxymethyl or C1-C6-alkyl and phenyl monosubstituted by a nitro group, an amino group or a halogen atom; Y also means unsubstituted piperazinyl, unsubstituted pyridyl, unsubstituted pyrazinyl, C1-C6-alkyl monosubstituted thiazol, unsubstituted pyrimidinyl, unsubstituted purinyl. The invention also refers to a pharmaceutical composition based on the compound of formula (I), using the compound of formula (I), a method for producing the compound of formula (I).

EFFECT: there are prepared new benzimidazol-4-carboxamide derivatives possessing antiviral activity.

5 cl, 6 dwg, 4 tbl, 688 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel heterocyclic compounds of general formula (I) or enantiomers, diastereomers or pharmaceutically acceptable salts thereof, where Y is: phenyl or a heteroaryl selected from thiazolyl, pyridyl, pyrimidinyl, 1,3,5-triazinyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl and 1,3,4-thiadiazolyl; wherein the phenyl or heteroaryl is optionally substituted with one substitute selected from fluorine, chlorine, bromine, iodine, C1-4alkyl, trifluoromethyl, C1-4alkoxy, C1-4alkylthio, nitro and cyano; r=1-2; R2 is absent or is an oxo-group; Z is: (a) phenyl substituted with NRaRb; where Ra is: H or C1-4alkyl; where Rb is: C1-4alkyl, cycloalkyl, phenyl, furanylmethyl, or phenyl(C1-2alkyl); and wherein the phenyl or the furanyl are optionally substituted with iodine; alternatively, Ra and Rb are taken together with the nitrogen atom to which they are bonded to form a 5-8 member heterocyclyl, which is optionally condensed to a benzene ring; (b) biphenyl-3-yl or biphenyl-4-yl; where the interior phenyl ring, attached to the carbonyl in formula (I) is optionally substituted with a fluorine atom; and where the terminal phenyl ring is optionally substituted with a substitute selected from trifluoromethyl, C1-4alkoxy, chlorine, dichloro, fluorine, and iodine; (c) phenyl substituted with a substitute selected from C5-8cycloalkyl, -NHC(=O)cyclohexyl, phenyloxy, phenylcarbonyl, phenyl(C1-3)alkyl, phenyl(C1-3)alkoxy, pyrrolyl, pyrazolyl, imidazolyl, isoindol-2-yl-l,3-dione, 2,3-dihydro-isoindol-2-yl; l-(tert- butoxycarbonyl)piperidin-4-yloxy, and 1-(tert-butoxycarbonyl)piperidin-4-yl; (d) phenyl substituted with 1-2 substitutes independently selected from: C1-6alkyl, C1-4alkoxy, iodine, chlorine and nitro; (e) phenyl(C1-2)alkyl; where the phenyl is optionally substituted with 1 or 2 substitutes independently selected from iodine, fluorine, C1-6alkyl, phenyl and NRcRd; where Rc: H or C1-4alkyl; where Rd is: C1-4alkyl or C1-6cycloalkyl(C1-4)alkyl; and where the C1-2alkyl of phenyl(C1-2)alkyl is optionally substituted with phenyl; (f) phenyl(C2-4)alkenyl; where the phenyl is optionally substituted with a substitute selected from C1-4alkyl, C1-4alkoxy, trifluoromethyl, trifluoromethylthio and phenyl; (g) naphthyl; where the naphthyl is optionally substituted with one C1-4alkoxy substitute; (h) fluorenyl or xanthenyl; where the fluorenyl or xanthenyl is optionally substituted with an oxo group; (i) C5-8cycloalkyl; where the C5-8cycloalkyl is optionally substituted with one C1-6alkyl substitute; (j) benzene ring-condensed C5-8cycloalkyl or benzene ring-condensed C5-8cycloalkyl(C1-4)alkyl; where said C5-8cycloalkyl fragment is optionally substituted with 1-4 methyl groups; (k) bicyclo[2.2.2]octyl-1-yl; where the bicyclo[2.2.2]octyl-l-yl is optionally substituted with C1-6alkyl; (1) a heteroaryl or benzene ring-condensed heteroaryl selected from benzooxazolyl, quinolinyl, benzimidazolyl, pyridinyl, indolyl, thienyl, furanyl, pyrazolyl, oxazolyl, benzothienyl and benzofuranyl; where the heteroaryl or benzene ring-condensed heteroaryl is optionally substituted with 1 or 2 substitutes independently selected from C1-4alkyl, trifluoromethyl, C5-8cycloalkyl, phenyl, phenyl(C1-2)alkoxy, phenyl(C2-4)alkynyl and dichlorophenoxy; and where the phenyl substitute in the heteroaryl is further optionally substituted with C1-4alkyl, C1-4alkoxy or trifluoromethyl; (m) l,5-diphenyl-lH-pyrazol-3-yl; where the pyrazol-3-yl is optionally substituted with a methyl group; and where each of the phenyl groups of the 1,5-diphenyl substitutes is also optionally substituted with substitutes selected from chlorine, dichloro or aminosulphonyl; (n) 1,2,3,4-tetrahydroquinolin-6-yl; where the 1,2,3,4-tetrahydroquinolin-6-yl is optionally substituted with phenyl or trifluoromethyl-substituted phenyl; and (o) benzene ring-condensed heterocyclyl(C2-4)alkenyl; where the benzene ring-condensed heterocyclyl is attached to the C2-4alkenyl via the benzene ring; and where benzene ring-condensed heterocyclyl is further optionally substituted with C5-6cycloalkyl; taking into account constraining conditions indicated in claim 1. The invention also relates to a pharmaceutical composition based on the compound of formula (I), a method of producing said pharmaceutical composition, a method of treating said pathological conditions and use of the compound of formula (I).

EFFECT: obtaining novel heterocyclic compounds having MGL inhibiting activity.

21 cl, 5 tbl, 11 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula A-I, where G1 stands for hydrogen atom or R'; G2 stands for halogen atom, CN, CF3, isopropyl or phenyl, where said isopropyl or phenyl is optionally substituted with up to three substituents, independently selected from WRW; G3 stands for isopropyl or (C3-C10)cycloaliphatic ring, where said G3 is optionally substituted with up to three substituents, independently selected from WRW; W stands for bond or (C1-C6)alkylidene chain, where up to two methylene groups of W residue are optionally and independently substituted for -CO2- or -O-; RW stands for R'; and R' is independently selected from hydrogen atom or (C1-C8)alkyl group. Invention also relates to method of obtaining compound of formula FF (stands for bromine atom, fluorine atom or tret-butyl; G3 stands for tret-butyl) by hydrogenation of respective nitrocompound in presence of palladium catalyst and to methods of obtaining C-9 and 433 compounds, which include stage of hydrogenation of respective nitrocompound in presence of palladium catalyst as intermediate stage.

EFFECT: formula A-I compounds, which are intermediate for synthesis of modulators of ATP-binding cassette ("ABC") transporters.

35 cl, 4 tbl, 80 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of pharmaceutics, namely, deals with compounds of formula , suitable for reduction of regulation of biological activity of melanocortin-5 receptor (MC5R). Such diseases and/or conditions include, but are not limited by, acne, seborrhoea, seborrheic dermatitis, cancer and inflammatory diseases.

EFFECT: compounds of claimed invention can be applied for treatment of diseases and/or conditions, in which reducing regulation of MC5R is favourable.

3 cl, 109 ex, 7 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

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.

SUBSTANCE: invention relates to a method of treatment or relieving the severity of cystic fibrosis in a patient, where the patient has the cystic fibrosis transmembrane receptor (CFTR) with R117H mutation, including a stage of introduction to the said patient of an effective quantity of N-(5-hydroxy-2,4-ditert-butyl-phenyl)-N-methyl-4-oxo-1H-quinoline-3-carboxamide.

EFFECT: elaborated is the method of treating cystic fibrosis, based on the application of N-(5-hydroxy-2,4-ditert-butyl-phenyl)-N-methyl-4-oxo-1H-quinoline-3-carboxamide.

3 cl, 4 tbl, 30 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing N-[4-(thi)oxo-1,3,5-triazinan-1-yl]arylamides of general formula (1), where R=m-C5H4N, o-MeOC6H4, m-MeOC6H4,X=O, S, which includes reacting N,N'-bis[dimethylaminomethyl](thio)urea of general formula (Me)2NCH2C(X)CH2N(Me)2, where X=S, O, with a hydrazide of general formula RC(O)NHNH2 in the presence of a samarium chloride crystalline hydrate catalyst SmCl3·6H2O with molar ratio N,N'-bis[dimethylaminomethyl](thio)urea:RC(O)NHNH2:SmCl3·6H2O=10:10:(0.8-1.2) in ethanol at 75-85°C and atmospheric pressure for 22-26 hours.

EFFECT: obtaining novel N-[4-(thi)oxo-1,3,5-triazinan-1-yl]arylamides.

1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to compounds of formula (I), wherein R1 and R2 independently represent C6-C10 aryl optionally substituted by -OH, halogen, -OC1-C3 alkyl, -NO2, -CF3 or C1-C3 alkyl, or 5- or 6-merous heteroaryl containing one heteroatom specified in N, S and O; A and M independently represent a methylene group or a single bond; an adjacent aromatic cycle is attached directly to an amide group; the group Y=Z represents together and irregularly oxygen atom (-O-), cis-vinylidene group (-CH=CH-), iminogroup (-N=CH- or -CH=N-) or methylene group with sp2-hybridised carbon atom (=CH-); X irregularly represents methine group (=CH-), cis-vinylidene group (-CH=CH-) or carbon atom (=N-), and W represents hydroxyl group (-OH), C1-C6 alkyl optionally substituted by -SH, 5- or 6-merous heteroaryl containing 1 to 2 nitrogen heteroatoms, or C6-C10 aryl, optionally substituted by -SH, -NH2, and their pharmaceutically acceptable salts.

EFFECT: described are the methods for preparing the compounds, using as a drug for treating cancer and the based pharmaceutical composition.

14 cl, 6 tbl, 49 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula , wherein Y and Z are independently specified in a group of a) or b) so that one of Y or Z is specified in the group a), and another one - in the group b); the group a) represents i) substituted C6-10aryl; ii) C3-8cycloalkyl; iii) trifluoromethyl or iv) heteroaryl specified in a group consisting of thienyl, furanyl, thiazolyl, isothiazolyl, oxazolyl, pyrrolyl, pyridinyl, isoxazolyl, imidazolyl, furasan-3-yl, benzothienyl, thieno[3,2-b]thiophen-2-yl, pyrazolyl, triazolyl, tetrazolyl and [1,2,3]thiadiazolyl; the group b) represents i) C6-10aryl; ii) heteroaryl specified in a group consisting of thiazolyl, pyridinyl, indolyl, pyrrolyl, benzoxazolyl, benzothiazolyl, benzothienyl, benzofuranyl, imidazo[1,2-a]pyridin-2-yl, furo[2,3-b]pyridinyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, thieno[2,3-b]pyridinyl, quinolinyl, quinazolinyl, thienyl and benzimidazolyl; iii) benzofused heterocyclyl attached through a carbon atom, and when a heterocyclyl component contains a nitrogen atom, the carbon atom is optionally substituted by one substitute specified in a group consisting of C3-7cycloalkylcarbonyl; C3-7cycloalkylsulphonyl; phenyl; phenylcarbonyl; pyrrolylcarbonyl; phenylsulphonyl; phenyl(C1-4)alkyl; C1-6alkylcarbonyl; C1-6alkylsulphonyl; pyrimidinyl and pyridinyl; C3-7cycloalkylcarbonyl, phenyl, phenylcarbonyl, phenyl(C1-4)alkyl and phenylsulphonyl are optionally substituted by trifluoromethyl, or by one or two fluor-substitutes; iv) phenoxatiynyl; vi) fluoren-9-on-2-yl; vii) 9,9-dimethyl-9H-fluorenyl; viii) 1-chlornaphtho[2,1-b]thiophen-2-yl; ix) xanthen-9-on-3-yl; x) 9-methyl-9H-carbazol-3-yl; xi) 6,7,8,9-tetrahydro-5H-carbazol-3-yl; xiii) 3-methyl-2-phenyl-4-oxochromen-8-yl; or xiv) 1,3-dihydrobenzimidazol-2-on-5-yl optionally substituted by 1-phenyl, 1-(2,2,2-trifluoroethyl), 1-(3,3,3-trifluoropropyl) or 1-(4,4-difluorocyclohexyl); 1-phenyl is optionally substituted by one or more fluor-substitutes or trifluoromethyl; or xv) 4-(3-chlorophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl; R1 represents C6-10aryl, C1-3alkyl, benzyloxymethyl, hydroxy(C1-3)alkyl, aminocarbonyl, carboxy, trifluoromethyl, spirofused cyclopropyl, 3-oxo or aryl(C1-3)alkyl; or when s is equal to 2 and R1 represents C1-3alkyl, the substitutes C1-3akyl is taken with a piperazine ring to form 3,8-diazabicyclo[3.2.1]octanyl or 2,5-diazabicyclo[2.2.2]octanyl ring system, and its pharmaceutical compositions.

EFFECT: preparing the new pharmaceutical compositions.

20 cl, 7 tbl, 72 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of pharmaceutics, namely, deals with compounds of formula , suitable for reduction of regulation of biological activity of melanocortin-5 receptor (MC5R). Such diseases and/or conditions include, but are not limited by, acne, seborrhoea, seborrheic dermatitis, cancer and inflammatory diseases.

EFFECT: compounds of claimed invention can be applied for treatment of diseases and/or conditions, in which reducing regulation of MC5R is favourable.

3 cl, 109 ex, 7 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to 2-pyridone compounds, represented by general formula [1], , where A represents benzene ring or pyridine ring, X represents structure, represented by general formula [3], V represents single bond or lower alkylene, W represents single bond, ether bond or lower alkylene, which can include ether bond, or their tautomers or stereoisomers.

EFFECT: obtaining pharmaceutically acceptable salts, which possess excellent activating activity with respect to GK and can be applied as medications.

27 cl, 23 tbl, 371 ex

FIELD: chemistry.

SUBSTANCE: invention refers to a method for producing 5,6-disubstituted 3-pyridylmethyl ammonium bromides , wherein Q represents a tertiary aliphatic or cyclic, saturated, partially unsaturated or aromatic amine; Z represents hydrogen or halogen; Z1 represents hydrogen, halogen cyano or nitro; each Y and Y1 independently represents OR1, NR1R2, or wherein YY1 together represent -O-, -S- or NR3-; each R1 and R2 independently represents hydrogen, C1-C4 alkyl optionally substituted by C1-C4 alkoxy or phenyl optionally substituted by one-three C1-C4 alkyl groups, C1-C4 alkoxy groups or halogen atoms, or a phenyl optionally substituted by one-three C1-C4 alkyl groups, C1-C4 alkoxy groups or halogen atoms; R3 represents hydrogen or C1-C4 alkyl, which involves the stages of (i) interaction of a compound of formula , wherein the symbols have values specified for formula (I) with bromine in the presence a radical initiator in the mixture of solvents containing an aqueous phase and an organic phase, wherein the organic phase contains a solvent specified in 1,2-dichloroethane, chlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene and tetrachloromethane, and wherein pH of the aqueous phase makes from 3 to <8 to produce 3-bromomethyl-5,6-disubstituted pyridine compound , wherein Y, Y1, Z and Z1 have values specified for formula (I), and (ii) interaction of the bromine compound of formula (III) with tertiary amine base Q in the solvent at a temperature falling within the range of 0°C to 100°C.

EFFECT: higher effectiveness of the method.

14 cl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to new quinolin-4-one derivatives of formula (1) or to its pharmaceutically acceptable salt, wherein R1 represents: (1) hydrogen, (2) C1-C6 alkyl, (35) carbamoyl-C1-C6 alkyl optionally containing morpholinyl-C1-C6 alkyl, or (36) phosphonoxy-C1-C6 alkyl optionally containing one or two C1-C6 alkyl groups on a phosphonoxy group; R2 represents: (1) hydrogen or (2) C1-C6 alkyl; R3 represents phenyl, thienyl or furyl, wherein a phenyl ring presented by R3, can be substituted by one C1-C6 alkoxy group; R4 and R5 are bound to form a group presented by any of the following formulas: , , , , , , or a group presented by the following formula: a group optionally containing one or more substitutes specified in a group consisting of C1-C6 alkyl groups and oxogroups; R6 represents hydrogen; and R7 represents C1-C6 alkoxy group. The invention also refers to a pharmaceutical composition based on the compound of formula , to a preventive and/or therapeutic agent based on the compound of formula (1), using the compound of formula (1), a method for preparing the compound of formula , as well as to specific compounds.

EFFECT: there are prepared new quinolin-4-one derivatives effective in treating neurodegenerative diseases, diseases caused by neurological dysfunction, or diseases caused by mitochondrial dysfunction.

18 cl, 1 tbl, 257 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing a compound of formula (I) which includes reacting a compound of formula (IV) with an oxalic acid diether of formula (V) . The invention also relates to intermediate compounds and methods for production thereof.

EFFECT: novel method of producing a compound having useful biological properties.

9 cl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds, represented by formula 1, where m stands for an integer number from 1 to 5; and Q represents a heteroaromatic ring or phenyl, where the heteroaromatic ring is selected from the group, consisting of triazole, tetrazole, indole, imidazole, pyridine and pyrrole, and is independently substituted with 0, 1, 2 or 3 substituents, selected from C1-C4alkyl, C1-C4alkoxy, hydroxy and halogen, and where phenyl is independently substituted with 1, 2 or 3 substituents, selected from hydroxy and fluorine; a method of obtaining them and a 5-HT4 receptor agonist, which contains them as an active ingredient.

EFFECT: obtaining the novel compounds.

17 cl, 4 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: group of inventions relates to an imine derivative, represented by formula , where "Ar" stands for pyridine, containing a chlorine atom on a ring or thiazole, which can contain the chlorine atom on a ring; "X" stands for a sulphur atom or CH2; when "Y" represents COR1, "R1" stands for a hydrogen atom or a C1-C5alkyl group, halogenated methyl group, except trifluoromethyl group, halogenated C2-C5alkyl group, C2-C5alkenyl group, halogenated C2-C5alkenyl group, C3-C5alkinyl group, non-substituted or substituted with an atom of chlorine, fluorine, methyl group or acetamide phenyl group, non-substituted (C6) aryl(C1-C3)alkyl group, (C1-C4)alkoxy (C1-C5)alkyl group, C1-C3alkoxycarbonyl group, (C1-C3) alkylsulphonyl (C1-C3)alkyl group, (C1-C3)alkylthio (C1-C3)alkyl group, non-substituted or substituted with a methyl group or a fluorine atom C3-C7cycloalkyl group, cyano(C1-C3) alkyl group, non-substituted phenoxy(C1-C3) alkyl group, non-substituted pyridylmethyl group, non-substituted imidazolylmethyl group, furanyl group, morpholine group, adamantly group, isothiocyanate group or a heterocyclic ring selected from quinoline, indole, pyridine, pyrazine, pyridazine or tetrahydrofurane, substituted with one, two or five substituents, selected from chlorine, bromine, trifluoromethane or fluorine, and a non-substituted heterocyclic ring, selected from quinoline, indole, pyridine, pyrazine, pyridazine or tetrahydrofurane, when "Y" represents CONR3R4 "R3" and "R4" stands for a hydrogen atom or C1-C5alkyl group, C1-C3alkoxygroup, non-substituted phenyl group, (C1-C3)alkoxy(C1-C3)alkyl group, C1-C3alkoxycarbonylmethyl group, non-substituted C3-C7cycloalkyl group, non-substituted benzenesulphonyl group; except the cases, when "R3" and "R4" simultaneously stand for hydrogen; when "Y" represents CONHCOR5, "R5" stands for a halogenated C1-C5alkyl group, non-substituted phenyl group; when "Y" represents CO2R9, "R9" stands for C1-C7alkyl group, halogenated C1-C5alkyl group, C2-C5alkenyl group, halogenated C2-C5alkenyl group, C3-C5alkinyl group, non-substituted or substituted with chlorine, fluorine or a nitro group naphthyl or a phenyl group, non-substituted (C6)aryl(C1-C3)alkyl group, (C1-C3)alkoxy (C1-C3) alkyl group, (C1-C3)alkylthio (C1-C3)alkyl group, tri(C1-C3alkyl)silyl(C1-C3)alkyl group, non-substituted C3-C7cycloalkyl group, 3-6-membered non-substituted heterocycloalkyl group, containing an oxygen atom as the heteroatom, non-substituted or substituted with methoxygroup phenylmethyl group, non-substituted furanylmethyl group, non-substituted thienylmethyl group, non-substituted pyridylmethyl group, succinimide group. The group of inventions also relates to methods of obtaining imine derivative of formula (1) (versions). The compound by the invention can be obtained from compounds, selected from the group, consisting of compounds, represented by formulas ACO-B (5), ACOOCOA (6), ACOOH (7), D-N=C=O (8) or HCO2Et(10) in the interaction with the compound of formula .

EFFECT: imine derivative, used as an insecticide, possessing the prolonged effect and wide spectrum of action.

5 cl, 22 tbl, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula

,

where values A, R1-R6 are given in i.1 of the invention formula. Methods of obtaining the formula (I) compound are described.

EFFECT: compounds demonstrate an inhibiting activity of the cathepsin enzyme, which makes it possible to use them for the preparation of a pharmaceutical composition and for the preparation of a medication.

38 cl, 12 dwg, 495 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new phenylamide or pyridylamide derivatives of formula

or their acceptable salts, wherein A1 is CR12 or N; A2 is CR13 or N; R1 and R2 are independently specified in hydrogen, C1-7-alkyl, halogen and C1-7-alkoxygroup; R12 and R13 are independently specified in hydrogen, C1-7-alkyl, halogen, C1-7-alkoxygroup, amino group and C1-7-alkylsulphanyl; R3 is specified in hydrogen, C1-7-alkyl, halogen, C1-7-alkoxygroup, cyano group, C3-7-cycloalkyl, five-merous heteroaryl and phenyl; R4 is specified in methyl and ethyl; or R3 and R4 together represent -X-(CR14R15)n- and form a part of the ring, wherein X is specified in -CR16R17-, O, S, C=O; R14 and R15 are independently specified in hydrogen or C1-7-alkyl; R16 and R17 are independently specified in hydrogen, C1-7-alkoxycarbonyl, heterocyclyl substituted by two groups specified in a halogen, or R16 and R17 together with an atom C, which they are attached to, form =CH2 group; or X is specified in a group NR18; R14 and R15 are hydrogen; R18 is specified in hydrogen, C1-7-alkyl, halogen-C1-7-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-7-alkyl, heterocyclyl, heteroaryl-C1-7-alkyl, carboxyl-C1-7-alkyl, C1-7-alkoxycarbonyl-C1-7-alkyl, C1-7-alkylcarbonyloxy-C1-7-alkyl, phenyl, wherein phenyl is unsubstituted, phenylcarbonyl, wherein phenyl is substituted by C1-7-alkoxycarbonyl, and phenylsulphonyl, wherein phenyl is substituted by carboxyl-C1-7-alkyl, or R18 and R14 together represent -(CH2)3- and form a part of the ring, or R18 together with R14 and R15 represent -CH=CH-CH= and form a part of the ring; and n has the value of 1, 2 or 3; B1 represents N or CR19 and B2 represents N or CR20, provided no more than one of B1 and B2 represents N; and R19 and R20 are independently specified in a group consisting of hydrogen and halogen-C1-7-alkyl; R5 and R6 are independently specified in a group consisting of hydrogen, halogen and cyano group; and one-three, provided R4 represents methyl or ethyl, two of the residues R7, R8, R9, R10 and R11 are specified in C1-7-alkyl, halogen, halogen-C1-7-alkyl, halogen-C1-7-alkoxygroup, cyano group, C1-7-alkoxycarbonyl, hydroxy-C3-7-alkynyl, carboxyl-C1-7-alkyl, carboxyl-C2-7-alkenyl, C1-7-alkoxycarbonyl-C2-7-alkenyl, C1-7-alkoxycarbonyl-C2-7-alkynyl, C1-7-alkoxycarbonyl-C1-7-alkylaminocarbonyl, carboxyl-C1-7-alkylaminocarbonyl-C1-7-alkyl, carboxyl-C1-7-alkyl-(C1-7-alkylamino)-carbonyl-C1-7-alkyl, phenyl-carbonyl, wherein phenyl is unsubstituted, phenyl-C1-7-alkyl, wherein phenyl is substituted by 1-2 groups specified in a halogen, C1-7-alkoxygroup, carboxyl, phenyl-C2-7-alkynyl, wherein phenyl is substituted by 2 groups specified in halogen, carboxyl or C1-7-alkoxycarbonyl, and pyrrolidine carbonyl-C1-7-alkyl, wherein pyrrolidinyl is substituted by carboxyl, and the other R7, R8, R9, R10 and R11 represent hydrogen; the term 'heteroaryl' means an aromatic 5-merous ring containing one or two atoms specified in nitrogen or oxygen; the term 'heterocyclyl' means a saturated 4-merous ring, which can contain one atom specified in nitrogen or oxygen. Besides, the invention refers to a pharmaceutical composition based on the compound of formula I.

EFFECT: there are prepared new compounds possessing the GPBAR1 agonist activity.

21 cl, 1 tbl, 190 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to a compound of Formula

,

where Y represents a group of formula -(CR9R10)-; X is selected from the group, consisting of -C(=O)-, -OC(=O)-, -NHC(=O)-, -(CR11R12)- and -S(-O)2-; Z represents a group of formula -(CR13R14)q-; R1 is selected from the group, consisting of C1-C12alkyl, optionally substituted with one substituent, selected from naphthyl, indole and biphenyl; C2-C12alkenyl, substituted with a substituent, selected from thienyl, naphthyl and phenyl, with the said phenyl being optionally substituted with 1-2 substituents; selected from halogen, trifluoroalkyl, C1-C6alkyl, methoxy and hydroxy; C3-C6cycloalkyl; C6-C10aryl, optionally substituted with 1-2 substituents, selected from halogen, phenyl, amino, phenoxy, C1-C6alkyl, methoxy, hydroxyl and carboxy; and C4-C9heteroaryl, selected from indole, quinoline, quinoxaline, benzofuranyl, benzothiophene, benzimidazole, benzotriazole, benzodioxin, benzothiasole, pyrazole, furyl and isoxazole, optionally substituted with a substituent, selected from C1-C6alkyl and phenyl; R2 and R3 each is independently selected from the group, consisting of H and C1-C12alkyl; R4a is selected from the group, consisting of H, C1-C12alkyl, optionally substituted with phenyl; C2-C12alkenyl, C3-C6cycloalkyl, C6aryl, C(=O)R15, C(=O)NR15R16, C(=O)OR15, SO2R15 and -C(=NR15)-NR16R17; R4d represents hydrogen or R4a and R4b, taken together with a nitrogen atom, which they are bound to, form an optionally substituted heterocyclic fragment, selected from piperidine, morpholine, pyrrolidine and azetidine, where the substituent is selected from C1-C12alkyl, hydroxy, halogen, carboxy and oxo; each R5a and R5b represents H, or R6, R7 and R8 each is independently selected from the group, consisting of H, C1-C12alkyl, C3-C6cycloalkyl, C6-C10aryl, optionally substituted with halogen, or taken together with a carbon atom, which they are bound to, two or more of R6, R7 and R8 form a fragment, selected from the group, consisting of C2-C12alkenyl; C3-C6cycloalkyl, optionally substituted with C1-C6alkyl; C6aryl, optionally substituted with 2 substituents, selected from halogen; each R9 and R10 represents H or C1-C12alkyl, substituted with naphthyl; each R11 and R12 represents H; R13 and R14 represent H, or each R15, R16 and R17 is independently selected from the group, consisting of H, C1-C12alkyl, C3-C6cycloalkyl, C6aryl, substituted with one substituent, selected from C1-C6alkyl; and C5-heteroaryl, additionally containing one nitrogen atom, with the said heteroaryl representing pyridyl; q represents an integer number, selected from the group, consisting of 2, 3 and 4; r represents 1; or its pharmaceutically acceptable salt. The invention also relates to particular compounds of 1,4-diazepan-2-one derivatives.

EFFECT: obtaining 3-aminoalkyl-1,4-diazepan-2-one melanocortin-5 receptor antagonists.

21 cl, 7 tbl, 110 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one heminapadisylate of formula (I) wherein n is equal to 2, and to pharmaceutically acceptable solvates thereof. Also, the invention refers to a pharmaceutical composition of the salt of formula (I), to a method of treating the above pathological conditions and to using the salt of formula (I) and to the pharmaceutical composition thereof.

EFFECT: what is prepared is the new salt of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one effective in treating the pathological pulmonary conditions, particularly asthma or chronic obstructive pulmonary disease.

11 cl, 3 dwg, 6 ex

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