A method of obtaining a quinoline derivative

 

(57) Abstract:

The use of the invention as inhibitors acyltransferase cholesterol. The inventive product - quinoline derivative of f-crystals i where X is the group - NRC(O) or where R is H or lower alkyd R is lower alkyl or lower alkoxide And the phenyl ring, Manoli disubstituted by lower alkyl or chlorine, phenyl ring, unsubstituted, monosubstituted lower alkyl or chlorine or disubstituted by lower alkyl or hydroxyl group, With the phenyl ring, unsubstituted, monostereo lower alkyl, trifluoromethyl, chlorine or nitro-group, disubstituted by fluorine or lower akilam or tizamidine two lower alkoxy and one acetate groups. Reagent 1: the corresponding 3-Q quinoline, where Q is NH or NCO. Reagent 2: appropriate Q - substituted phenyl, where Q is NH or-NCO, and Q is not equal to Q . Reaction conditions: followed, if necessary , by turning the lower alkoxygroup in the o-ring Into hydroxyl group.

 

Same patents:

FIELD: organic chemistry, pharmacology.

SUBSTANCE: invention relates to compounds of formula I ,

where R(1), R(2), R(3), R(4), R(5), R(6), R(7), R(8), R(30), and R(31) are disclosed in claims. Compound of present invention are particularly useful as new antiarrythmia bioactive substances, in particular for treatment and prophylaxis of atrial arrhythmia (e.g., atrial fibrillation or auricular flutter).

EFFECT: higher efficiency.

13 cl, 18 ex, 1 tbl

FIELD: organic chemistry, chemical technology, pharmacy.

SUBSTANCE: invention relates to novel derivatives of urea of the general formula (I): and their pharmaceutically acceptable salts wherein A represents -CH- or nitrogen atom; R1 represents (C3-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkyl-(C1-C10)-alkyl, 6-membered nitrogen-containing heterocycle, 6-membered nitrogen-containing heterocyclyl-(C1-C10)-alkyl, phenyl, phenyl-(C1-C10)-alkyl, 5-10-membered heteroaryl or 5-10-membered heteroaryl-(C1-C10)-alkyl, and others; R2 represents hydrogen atom, (C1-C6)-alkyl, (C0-C2)-alkyl-(C3-C10)-cycloalkyl, (C0-C2)-alkylphenyl, (C3-C10)-cycloalkyl-(C0-C2)-alkyl or phenyl-(C0-C2)-alkyl; R5 represents (C1-C6)-alkyl, (C3-C10)-cycloalkyl, 6-membered nitrogen-containing heterocyclyl, and others; L1 represents -S-, -S(O)-, -S(O2)-, -C(O)-, -N(Rc)-, -CH2-, and others; L2 represents a covalent bond, -O-, -C(O)-, -OC(O)-, -N(Rc)-, and others; W represents oxygen (O) or sulfur (S) atom; Z represents -C(O)ORd wherein Rc, Rd and Re represents hydrogen atom or alkyl; Rb represents -ORe, -NO2, halogen atom, -CN, -CF, (C1-C6)-alkyl; p represents a whole number from 0 to 4. Compounds of the formula (I) and their salts possess antagonistic activity with respect to α4-integrin and can be used in medicine for inhibition or prophylaxis of cellular adhesion in patient body mediated by α4β1- and/or α4β7-integrins.

EFFECT: improved methods of synthesis, valuable medicinal properties of compounds and pharmaceutical composition.

17 cl, 2 tbl, 180 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of substituted urea of the formula (I) or their pharmaceutically acceptable salts possessing the retinoid activity, and to pharmaceutical composition and drug based on thereof. In the formula (I) n means a whole number from 0 to 2; X means oxygen atom (O); A-Y means compound of the formula ; R1 and R3 mean independently of one another hydrogen atom, (C1-C6)-alkyl, (C1-C4)-alkylene-(C1-C4)-alkoxy-group, (C1-C4)-alkylenephenyl optionally substituted with halogen atom, (C1-C4)-alkoxy-, (C1-C4)-alkylenebenzyloxy-, (C1-C4)-alkylenehydroxy-group, (C1-C4)-alkylene (monocyclic heteroaryl comprising 5 ring atoms and one or two heteroatoms chosen from atoms N, O or S) optionally substituted with (C1-C6)-alkyl in ring; R2 means hydrogen atom under condition that R1 doesn't mean hydrogen atom or (C1-C6)-alkyl) if R3 means hydrogen atom.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

12 cl, 10 tbl, 3 sch, 27 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to derivatives of tetrahydronaphthalene and their salts, which have antagonistic properties towards the vanilloid receptor, to their use and medicinal preparation based on them. The compounds can be used for curing and preventing diseases, related to the activity of VR1, particularly for treating acute uroclepsia, hyperactive urinary bladder, chronic pain etc. In general formula (I) X represents an alkyl with 1-6 carbon atoms, or , Y represents a single bond, or , R1, R2 and R3 independently represent hydrogen, halogen, hydroxyq, nitro, carboxyl, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, (C3-8cycloalkyl)amino, (C1-6alkoxy)carbonyl, sulfonamide, C1-6alkyl, optionally substituted with a cyano group or mono-, di-, or tri-halogen, C1-6alkoxy group, optionally substituted with a halogen or C1-6alkyl group, or (C1-6alkyl)thio-group, optionally substituted mono-, di- or tri-halogen; R4, R5, R6 and R7 independently represent hydrogen, alkyl with 1-6 carbon atoms or phenyl; Z1 represents hydrogen or alkyl with 1-6 carbon atoms; and Z2 represents hydrogen, halogen or alkyl with 1-6 carbon atoms.

EFFECT: obtaining tetrahydronaphthalene derivatives and its salts, with antagonistic properties towards the vanilloid receptor.

10 cl, 3 tbl, 123 ex

FIELD: chemistry.

SUBSTANCE: invention relates to aldimines used to produce a polymer precursor, obtained via reaction of at least one sterically hindered aliphatic aldehyde A of formula with an aliphatic amine B, where all values of substitutes are given in the claim, via a condensation reaction with splitting of water, a product containing an aldimine-containing compound, and use thereof as a protected cross-linking agent for the polymer precursor and as a source of amines [H2N]m-R4-[XH]y (B).

EFFECT: obtaining polymer precursors containing isocyanate groups, which are characterised by high stability during storage.

15 cl, 51 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to a novel method for synthesis of (Z)-3-[2-butoxy-3'-(3-heptyl-1-methylureido)biphenyl-4-yl]-2-methoxyacrylic acid of formula (I) and intermediate compounds (XII), (XIII) and (XIV). The disclosed method involves reaction of a sulphonate of formula (XII), where R2 denotes methyl, trifluoromethyl, phenyl or tolyl, with 3-heptyl-1-methyl-1-[3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]urea of formula (IIIb) or with a corresponding boronic acid of formula (IIIa).

EFFECT: easier synthesis owing to fewer steps.

8 cl, 1 ex, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to method of obtaining novel bis[3-methyl(adamant-1-yl)]urea of general formula: , where . Obtained products can be applied in chemical-pharmaceutical industry. Method consists in interaction of 1-aminomethyladamantane with diisocyanates selected from line hexamethylene-1, 6 or 4,4'-diphenylmethane diisocyanate, at temperature 15-25 °C, for 2-4 hours in dimethylformamide with molar ratio diisocyanate: amine: dimethylformamide (1:2.04-2.12:87-129) and separation of target product.

EFFECT: compounds are obtained with 93-94% product output.

2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to detergent containing dye transfer inhibitor in the form of a urea derivative with general formula I, where M denotes H or alkaline metal, A and B independently from each other denote an aromatic part of the molecule, which is a benzol or naphthalene group, optionally containing up to 3 alkyl substitutes with 1-4 carbon atoms, a and b independently from each other denote 0, 1, 2 or 3 and a+b≥1, and c denotes 1, 2 or 3, in addition to traditional components compatible with the above ingredient, where said detergent contains from 0.1 WT% to 10 WT%, preferably from 0.2 WT% to 5 WT%, of urea derivative which inhibits transfer of colouring agent of general formula. Present invention relates to use of urea derivatives of general formula I (versions) and to a method of washing textile products.

EFFECT: technical result of this invention is creation of a detergent composition with urea derivatives inhibiting dye transfer.

9 cl, 6 ex

FIELD: pharmacology.

SUBSTANCE: invention relates to a compound of formula

, where R1 and R2 together with the carbon atom to which they are attached form C3-C10-cycloalkyl; R3 is H or C1-C12-alkyl; R4 is H; W is a bond; A is phenyl substituted by R8, R9 and R10; B is phenyl substituted by R11, R12 and R13; R8 R9 R10 are independently selected from H, halogen-C1-C12-alkyl, halogen; R11, R12 and R13 are independently selected from H, halogen; or pharmaceutically acceptable salts thereof. A pharmaceutical composition, application of a compound of formula (I) and a method for treatment and preventingon of type 2 diabetes, atherosclerosis, cancer, chronic renal failure and non-alcoholic steatohepatitis are also provided.

EFFECT: formula compound inhibits the activity of FABP4 and FABP5 proteins and can be used to treat and prevent the aforementioned diseases.

17 cl, 17 ex

FIELD: organic chemistry.

SUBSTANCE: invention describes novel substituted benzoylcyclohexenones of the general formula (I): wherein values Q, Y, Z, R1-R5 and their possible tautomeric forms and their possible salts given in the invention claim. Invention proposes substituted benzoylcyclohexenones of the general formula (I) that possess the herbicide activity.

EFFECT: valuable property of compounds.

2 cl, 10 tbl, 6 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of 3-aminomethylquinolone-2 of the general formula (1)

(2)

or (3) wherein R1 means hydrogen atom (H) or Alk; R2 is taken among Alk; -OAlk, -SCH3, -Hal, -CF3, 3,4-OCH2CH2O-, 3,4-OCH2O-, 4-OCF3, 2-Ph, -OPh, -NHCOR, 2-OCH3, 5-Ph, 4-Obzk, 3-NO2, 2-CH3, 5-iPr, di-OAlk, di-Hal; or R2 represents halogen atom and alkyl group, or halogen atom and alkoxy-group taken simultaneously and independently of one another; or R2 represents the group -CONR4R5 wherein each R4 and R5 means independently of one another the group Alk, or they form the group -(CH2)n- wherein n = 2-6. R means -CH3; R3 means hydrogen atom (H); X is taken among hydrogen atom (H), 6-(C1-C3)-Alk, 6-iPr, 6-iBu; 7-(C1-C2)-Alk, 8-(C1-C2)-Alk, 6-(C1-C2)-OAlk, 6-OCF3, 7-(C1-C2)-Alk, 7-SCH3, 6,7-OCH2O-, 6,7-OCH2CH2O-, 5,6,7-OCH3, 6-F; X and Y are similar or different and taken among 7,8-CH3, 6,8-CH3, 5,8-CH3, 5,7-CH3, 6,7-CH3, 6,7-OCH3, 6-CH3, 7-Cl. Also, invention relates to a method for preparing indicated compounds and to pharmaceutical composition inhibiting activity of NO-synthetase based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof for aims preparing medicinal agents for treatment diseases associated with hyperactivity of phagocytizing cells, for example, rheumatic arthritis, asthma and others.

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

19 cl, 1 tbl, 95 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel amino- and hydroxy-derivatives of phenyl-3-aminomethylquinolone-2 of the general formula (1):

wherein R1, R2, R3 and R4 are independently similar or different and R1 is chosen from hydrogen atom (H), Alk, OAlk; R2 is chosen from H, Alk, OAlk, -OCF3; R3 is chosen from H, Alk, OAlk, -SCH3; R4 is chosen from H. Alk, OAlk, or R2 and R3 are chosen from -(CH2)3, -OCH2O-, -OCH2CH2O-; R5 means H or Alk; R6, R7 and R9 mean H; R8 is chosen independently from the following substitutes:

wherein n = 1, 2, 3; Het represents furan; R represents hydrogen atom or alkyl. In case of hydroxy-derivatives at least one among R6, R7, R8 or R9 is -OH and other represent H. Also, invention relates to methods for synthesis of these compounds and to a pharmaceutical composition based on these compounds inhibiting activity of NO-synthase. Invention provides preparing novel compounds and pharmaceutical compositions based on thereof in aims for treatment of diseases associated with hyperactivity of phagocytizing cells, for example, rheumatic arthritis, asthma and others.

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

32 cl, 1 tbl, 132 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to a method for synthesis of 1-propyl-2-oxo-4-hydroxyquinoline 3-carboxylic acid diethylaminoethylamide hydrochloride (chinoxycaine) that can elicit anesthetic, anti-arrhythmic, anti-oxidative, antibacterial and fungicide effect. Invention describes a method for synthesis of 1-propyl-2-oxo-4-hydroxyquinoline 3-carboxylic acid diethylaminoethylamide hydrochloride of the formula:

. Method involves acylation of N-propylanthranilic acid ethyl ester with ethoxymalonyl chloride in water-insoluble organic solvent medium in the presence of sodium carbonate as acceptor of evolving hydrogen chloride, amidation reaction of synthesized substance with diethylaminoethylamine in alcoholic medium, extraction of formed 1-propyl-2-oxo-4-hydroxyquinoline 3-carboxylic acid diethylaminoethylamide base from the reaction mixture by extraction with organic solvent and its conversion to hydrochloride. Then N-propyl-N-(1-malonoyl-3-ethoxy)-anthranilic acid ethyl ester formed in the acylation reaction without its isolation is subjected directly for condensation and amidation reaction simultaneously with diethylaminoethylamine by boiling the reaction mixture in ethanol for 5-7 h followed by extraction of 1-propyl-2-oxo-4-hydroxyquinoline 3-carboxylic acid diethylaminoethylamide base by the known method and its conversion to monohydrate hydrochloride by treatment with hydrochloric acid (HCl) aqueous solution to pH value 3-3.5. Invention provides simplifying method in synthesis of the end substance and its enhancing yield and quality.

EFFECT: improved method of synthesis.

4 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the new phenethanolamine derivatives having selective stimulant action at β2-adrenoreceptors and can be used for the treatment of respiratory diseases. In formula (I) m is an integer from 2 to 8, n is an integer from 3 to 11 with the proviso that the sum total of m and n is from 5 to 19, R1 represents SOR6 or SO2R6, where R6 represents a C3-7cycloalkyl group or a C3-7cycloalkelene group, R2 and R3 are independently derived from hydrogen and C1-6alkyl, each of R4 and R5 represents hydrogen, Ar represents a group selected from (a) and (b) where R8 represents hydrogen, halogen, -(CH2)qOR11, -NR11C(O)R12 or -NR11SO2R12, and R7 represents hydrogen, or R8 represents -NR11C(O)R12 and forms with R7 5- or 6-membered heterocyclic ring, R9 represents -OR11, R10 represents hydrogen, each of R11 and R12 independently represents hydrogen or C1-4alky, q is zero or an integer from 1 to 4. The invention also relates to the methods of compounds production and their application in pharmaceuticals production.

EFFECT: production of the new phenethanolamine derivatives having a selective stimulant action can be used for the treatment of respiratory disease.

16 cl, 5 dwg, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel atropoisomers of formula , in which R and R1 each independently represents hydrogen or methyl; R2, R3 and R4 each independently represents hydrogen or trifluoromethyl, on condition that R2, R3 and R4 all do not represent hydrogen; and R5 represents bromine, chlorine; or to its non-toxic pharmaceutically acceptable salt, solvate. Invention also relates to pharmaceutical composition, as well as to method of treatment.

EFFECT: obtaining novel biologically active compounds, possessing properties which open calcium-activated potassium channels of high conductivity.

12 cl, 6 ex, 2 tbl, 7 dwg

FIELD: pharmacology.

SUBSTANCE: invention concerns novel compounds of formula (I): , where each of R1, R2, R3 and R4 is independently selected out of hydrogen, hydroxy, and -NHCHO, or R1 and R2 together are selected out of -NHC(=O)CH=CH- and -CH=CHC(=O)NH-; R1 can also be -CH2OH; one of R5 and R6 is -[X-C1-6alkylenyl]n-NR10R11 or C1-6alkylenyl-NR12R13, and the other of R5 and R6 is selected out of hydrogen, C1-4alkoxy and C1-4alkyl, where C1-4alkylis optionally substituted by halogen, where each X is -O-; each of R10, R11, R12 and R13 is independently hydrogen or C1-4alkyl; or R10 and R11 together with nitrogen atom linking them, or R10 together with nitrogen atom linking it and carbon atom from neighbour C1-6alkylenyl form heterocyclic or heteroaryl ring with 5 to 7 atoms in ring and optionally with additional heteroatom selected out of oxygen and nitrogen, where nitrogen atom is optionally substituted by -S(O)2-C1-4alkyl; and n is 1 or 2; and each of R7, R8 and R9 is independently hydrogen; and pharmaceutically acceptable salt or solvate or stereoisomer of claimed compounds. Also invention claims application and pharmaceutical composition based on the compounds and having agonistic effect on β2 adrenergetic receptor.

EFFECT: obtaining novel compounds for application in therapy of asthma or chronic obstructive lung disease.

25 cl, 1 tbl, 6 dwg, 17 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a salt of amine with carbostyril derivative, formed from carbostyril derivative, with formula , R is a halogen atom, substitution position in the side chain is the 3rd or 4th position in the carbostyril skeleton, and the bond between the 3rd and 4th positions on the carbostyril skeleton is a single or double bond, and amine, chosen from: amino acid; C1-6alkyl-substituted amine, which can have a substituted chosen from a group which contains a hydroxy group and an amino group; and amino sugar, which dissolves in water very well. The invention also relates to a pharmaceutical composition which contains a salt of amine with carbostyril derivative of formula (I) as an active ingredient.

EFFECT: new salts are obtained, with useful biological properties.

25 cl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) , where Ar denotes each of R2, R3, R4, R5, R4' and R5' denote hydrogen; A denotes C(O); D denotes oxygen or NR8; E denotes CR63R64CR65R66; R63 and R64 denote hydrogen; R65 and R66 independently denote hydrogen or C1-4alkyl; k equals 0; m equals 1; R6 denotes a group -(X)p-Y-(Z)q-R10, or R6 denotes α- or β-branched C3-6alkyl (optionally substituted with C6cycloalkyl); X and Z independently denotes a C1-4alkylene group; p and q are independently equal to 0 or 1; Y denotes a bond; R8 denotes hydrogen; R10 denotes hydrogen or a saturated 5-7-member ring system; R7 denotes a 6-member aromatic ring, optionally substituted with a halogen, carboxyl, C1-6alkyl, C1-2alkoxy or a 5-member heteroaromatic ring (which is optionally substituted with C1-6alkyl); or a pharmaceutically acceptable salt thereof. Compounds of formula (I) or a pharmaceutically acceptable salt thereof are used to produce a medicinal agent for treating respiratory distress syndrome (ARDS), pulmonary emphysema, bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD), asthma or rhinitis.

EFFECT: high efficiency of using said compounds.

7 cl, 1 tbl, 102 ex

FIELD: chemistry.

SUBSTANCE: invention is related to organic chemistry and specifically to novel quinoline derivatives of general formula I or pharmaceutically acceptable salts, stereoisomers or N-oxides, where m = 0 and 1; R1 is independently selected from a group consisting of chlorine, fluorine and bromine; R2b and R2 c are independently selected from a group, consisting of hydrogen, halogen, C1-C3 alkyl, fluorinated C1-C3alkyl, cyano and N (CH3)2; X is selected from a group consisting of n is selected from a group consisting of 0 and 1; R3 is independently selected from a group consisting of halogen, C1-C3 alkyl, fluorinated with1-C3 alkyl, cyano, C1-C3alkoxy and NR4R4′, where R4 and R4′ are independently selected from a group consisting of C1-C3 alkyl; and a is selected from a group consisting of .Invention is also related to the use of formula I, pharmaceutical composition based on the compound of formula I, method of treating pulmonary disorders and inflammatory diseases based on use of the compound of formula I, and a method of producing a pharmaceutical composition based on the compound of formula I.

EFFECT: technical result is obtaining novel quinoline derivatives, useful as inhibitors of S-nitrozoglutation reductase (GSNOR).

17 cl, 64 ex

FIELD: biotechnology.

SUBSTANCE: invention relates to a compound of formula 1

that is a new rebamipide prodrug, and to the pharmaceutical composition thereof.

EFFECT: new rebamipide prodrug with absorption rate 25 times higher than that of rebamipide, which can be used for prevention or treatment of gastric ulcer, acute gastritis, chronic gastritis, xerophthalmia, cancer, osteoarthritis, rheumatoid arthritis, or obesity.

7 cl, 3 tbl, 204 ex, 1 dwg

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to R-2-aminoarylpropionic acid amides and pharmaceutical composition comprising thereof that can be used for prophylaxis and inhibition of recruiting and activation of leukocytes, and in treatment of pathologies directly dependent on indicated activation. Invention proposes compound of the general formula (1): wherein A, q, Ph and R have corresponding values, or its pharmaceutically acceptable salt. Also, invention describes a method for preparing amide of the formula (1) and pharmaceutical composition used in prophylaxis of leukocytes activation. Invention provides the development of pharmaceutical composition that can be used for prophylaxis and treatment of damaged tissues caused by enhancing activation of neutrophile granulocytes (polymorphonuclear leukocytes) in inflammation foci. Also, the invention relates to R-enantiomers 2-(aminoaryl)-propionylamides of the formula (1) that can be used for suppression of neutrophyles hemotaxis caused by IL-8. Also, compounds of this invention can be sued in treatment of psoriasis, ulcerous colitis, glomerulonephritis, acute respiratory insufficiency and rheumatic arthritis.

EFFECT: valuable medicinal properties of compounds.

8 cl, 16 ex

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