Quinoline derivatives

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to quinoline derivatives of formula I

, or to its pharmaceutically acceptable salts, wherein X1 represents O; p represents 0, 1 or 2; each group R1 which can be identical or different and which can be located only in positions of 6- and/or 7-quinoline ring, specified in halogen, cyano, carboxy, (1-6C)alkoxycarbonyl, carbamoyl, (1-6C)alkoxy, N-(1-6C)alkylcarbamoyl, N,N-di-[(1-6C)alkyl]carbamoyl, or in a group of formula: Q1-X2-, wherein X2 represents CO and Q1 represents pyrrolidine, q represents 0 or 1; R2 represents (1-6C)alkoxy; R3 represents hydrogen or (1-6C)alkyl; R4 represents hydrogen; R5 represents hydrogen, methyl, ethyl, propyl, allyl, 2-propynyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3-fluoropropyl, 3,3-difluoropropyl, 3,3,3-trifluoropropyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, 3-methoxypropyl, cyanomethyl, 2-cyanoethyl or 3-cyanopropyl; the ring A represents a 5-membor monocyclic heteroaryl ring with up to three ring heteroatoms specified in oxygen, nitrogen and sulphur; r represents 0, 1 or 2; and each group R6 which can be identical or different is specified in amino, (1-6C)alkyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, or in a group of formula: -X6-R15 wherein X6 represents a single link and R15 represents (1-6C)alkoxy-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl or in a group of formula: -X7-Q3 wherein X7 represents C(R17)2N(R17) wherein each R17 represents hydrogen and Q3 represents (3-8C)cycloalkyl, and wherein any CH2 group within the R6 group optionally carries a hydroxy group on each said group. Also, the invention refers to methods for making the compound of formula I, to a pharmaceutical composition on the basis of the compound of formula I, to applying the compound of formula I and the combinations on the basis of the compound of formula I and additional anticancer drugs.

EFFECT: there are produced new quinoline derivatives effective in treating diabetic retinopathy and disturbed cell proliferation.

15 cl, 6 tbl, 32 ex

 

The text descriptions are given in facsimile form.

1. A derivative of quinoline of the formula I

where X1represents About;
p represents 0, 1 or 2;
each group R1that may be the same or different and which may be located only in a positions 6 and/or 7-quinoline ring, selected from halogen, cyano, carboxy, (1-6C)alkoxycarbonyl, carbamoyl, (1-6C)alkoxy, N-(1-6C)allylcarbamate, N,N-di-[(1-6C)alkyl] carbamoyl, or from a group of the formula:
Q1-X2-,
where X2represents CO and Q1is pyrrolidin,
q represents 0 or 1;
R2represents (1-6C)alkoxy;
R3represents hydrogen or (1-6C)alkyl;
R4p is ecstasy a hydrogen;
R5represents hydrogen, methyl, ethyl, propyl, allyl, 2-PROPYNYL, 2-foretel, 2,2-dottorati, 2,2,2-triptorelin, 3-forproper, 3,3-direcror, 3,3,3-cryptochromes, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, 3-methoxypropyl, cyanomethyl, 2-cyanoethyl or 3-cyanopropyl,
ring a represents a 5-membered monocyclic heteroaryl ring with up to three ring heteroatoms selected from oxygen, nitrogen and sulfur;
r represents 0, 1 or 2; and
each group R6that may be the same or different, selected from amino, (1-6C)alkyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, or from a group of the formula:
-X6-R15,
where X6represents a simple bond, and R15represents (1-6C)alkoxy-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl or from a group of the formula:
-X7-Q3,
where X7represents C(R17)2N(R17), where each R17represents hydrogen and Q3represents a (3-8C)cycloalkyl,
and where any CH2group within R6group optionally bears on each specified group, hydroxy group;
or its pharmaceutically acceptable salt.

2. A derivative of quinoline of the formula I according to claim 1, in which:
X1represents About;
p represents 0 or p represents 1 or 2 and R1group fo the s in the 6th and/or 7th positions and are selected from fluorine, cyano, carbamoyl, methoxycarbonyl, methoxy, ethoxy, N-methylcarbamoyl and N,N-dimethylcarbamoyl,
q represents 1 and R2the group, which is located in the 2nd position (relative to C(R3R4) group), represents a methoxy group;
each of R3and R4represents hydrogen;
R5represents hydrogen;
ring a represents a 2-oxazolyl, 3-isoxazolyl, 5-isoxazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 1,2,4-oxadiazol-5-yl and 1,3,4-oxadiazol-5-yl; and
r represents 1 or 2 and each R6the group, which is selected from methyl, ethyl, propyl and isopropyl;
or its pharmaceutically acceptable salt.

3. A derivative of quinoline of the formula I according to claim 1, chosen from:
N-(1-ethyl-1H-pyrazole-4-yl)-2-(2-methoxy-4-quinoline-4-idoxifene)ndimethylacetamide,
N-(1-methyl-1H-pyrazole-4-yl)-2-[4-(6-ftorhinolon-4-yloxy)-2-methoxyphenyl]acetamide", she
N-(1-ethyl-1H-pyrazole-4-yl)-2-[4-(6-ftorhinolon-4-yloxy)-2-methoxyphenyl]acetamide", she
N-(1-ethyl-1H-pyrazole-4-yl)-2-[4-(7-ftorhinolon-4-yloxy)-2-methoxyphenyl]acetamide", she
N-(1-ethyl-1H-pyrazole-4-yl)-2-{2-methoxy-4-[6-methoxy-7-(N-methylcarbamoyl)quinoline-4-yloxy]phenyl}acetamide", she
N-(1-methyl-1H-pyrazole-4-yl)-2-[2-methoxy-4-(7-methoxyquinoline-4-yloxy)phenyl]acetamide", she
N-(1,3-dimethyl-1H-pyrazole-4-yl)-2-[2-methoxy-4-(7-methoxyquinoline-4-yloxy)phenyl]acetamide", she
N-(1,5-dimethyl-1H-Piras the l-4-yl)-2-[2-methoxy-4-(7-methoxyquinoline-4-yloxy)phenyl]acetamide", she
N-(1,3-dimethyl-1H-pyrazole-4-yl)-2-[4-(6,7-dimethoxyquinazolin-4-yloxy)-2-methoxyphenyl]acetamide", she
N-(4-methyl-1H-pyrazole-3-yl)-2-[4-(6,7-dimethoxyquinazolin-4-yloxy)-2-methoxyphenyl]acetamide", she
N-(4-ethyl-1H-pyrazole-3-yl)-2-[4-(6,7-dimethoxyquinazolin-4-yloxy)-2-methoxyphenyl]acetamide", she
N-(4,5-dimethyl-1H-pyrazole-3-yl)-2-[2-methoxy-4-(7-methoxyquinoline-4-yloxy)phenyl]acetamide", she
N-(5-methyl-1H-pyrazole-3-yl)-2-[4-(6-ftorhinolon-4-yloxy)-2-methoxyphenyl]acetamide", she
N-(4,5-dimethyl-1H-pyrazole-3-yl)-2-[4-(6-ftorhinolon-4-yloxy)-2-methoxyphenyl]acetamide", she
N-(4-methylisoxazol-3-yl)-2-[2-methoxy-4-(7-methoxyquinoline-4-yloxy)phenyl]acetamide", she
N-(4,5-dimethylisoxazol-3-yl)-2-(2-methoxy-4-quinoline-4-idoxifene)ndimethylacetamide,
N-(4,5-dimethylisoxazol-3-yl)-2-[2-methoxy-4-(7-methoxyquinoline-4-yloxy)phenyl]acetamide", she
N-(4,5-dimethylisoxazol-3-yl)-2-{2-methoxy-4-[7-methoxy-6-(N-methylcarbamoyl)quinoline-4-yloxy]phenyl}acetamide", she
N-(4,5-dimethylisoxazol-3-yl)-2-[4-(6-ftorhinolon-4-yloxy)-2-methoxyphenyl]acetamide", she
N-(4-methylthiazole-2-yl)-2-[2-methoxy-4-(6-ftorhinolon-4-yloxy)phenyl]ndimethylacetamide and
N-(4-methylthiazole-2-yl)-2-{2-methoxy-4-[6-methoxy-7-(N-methylcarbamoyl)quinoline-4-yloxy]phenyl}ndimethylacetamide;
or its pharmaceutically acceptable salt.

4. A method of obtaining a quinoline derivative of the formula I or its pharmaceutically acceptable salt as defined in claim 1, including interaction quinoline of the formula II

where L represents a displaced group, and p and R1have any of the values specified in claim 1 except that any functional group is optionally protected, with phenylacetamido formula III

where X1, q, R2, R3, R4, R5, ring A, r and R6have any of the values specified in claim 1 except that any functional group is optionally protected, then any existing protective group is removed, and then, if necessary, to form a pharmaceutically acceptable salt of a derivative of quinoline of formula I.

5. A method of obtaining a quinoline derivative of the formula I or its pharmaceutically acceptable salt as defined in claim 1, including the combination of a quinoline of the formula VII

or its reactive derivative, in which p, R1X1, q, R2, R3and R4have any of the values specified in claim 1 except that any functional group is optionally protected, with an amine of the formula VI

where R5, ring A, r and R6have any of the values specified in claim 1 except that any functional group is optionally protected, then any existing protective group is removed, and then, if necessary, to form a pharmaceutically who ramlau salt quinoline derivative of the formula I.

6. The way to obtain those compounds of formula I in which R represents carboxypropyl, including the splitting of the compounds of formula I in which R1represents (1-6C)alkoxycarbonyl group; then, if necessary, to form a pharmaceutically acceptable salt of a derivative of quinoline of formula I.

7. Pharmaceutical composition having inhibitory activity against-DERIVED tyrosine kinase, containing a quinoline derivative of the formula I or its pharmaceutically acceptable salt as defined in claim 1, in combination with a pharmaceutically acceptable diluent or carrier.

8. The application of a quinoline derivative of the formula I or its pharmaceutically acceptable salt as defined in claim 1, for preparing a medicinal product for use in the treatment of diabetic retinopathy.

9. The combination is suitable for use for the treatment of disorders of cell proliferation, which contains a quinoline derivative of the formula I or its pharmaceutically acceptable salt as defined in claim 1, and an additional anticancer agent.

10. A derivative of quinoline of the formula I according to claim 1, which is 2-{4-[(6,7-dimethoxyquinazolin-4-yl)oxy]phenyl}-N-[1-(propane-2-yl)-1H-pyrazole-4-yl)]ndimethylacetamide or its pharmaceutically acceptable salt.

11. A derivative of quinoline of the formula I according to claim 1, which is 2-{4[(6,7-dimethoxyquinazolin-4-yl)oxy]phenyl}-N-(5-ethyl-1H-pyrazole-3-yl)ndimethylacetamide or its pharmaceutically acceptable salt.

12. A derivative of quinoline of the formula I according to claim 1, which is 2-{4-[(6,7-dimethoxyquinazolin-4-yl)oxy]phenyl}-N-(5-ethyl-1,2-oxazol-3-yl)-ndimethylacetamide or its pharmaceutically acceptable salt.

13. A derivative of quinoline of the formula I according to claim 1, which is 4-(4-{2-[(5-ethyl-1,2-oxazol-3-yl)amino-2-oxoethyl}phenoxy)-7-methoxyquinoline-6-carboxamide or its pharmaceutically acceptable salt.

14. A derivative of quinoline of the formula I according to claim 1, which is 4-(4-{2-[(5-ethyl-1,2-oxazol-3-yl)amino-2-oxoethyl}-3-methoxyphenoxy)-7-methoxy-N-methylinosine-6-carboxamide or its pharmaceutically acceptable salt.

15. A derivative of quinoline of the formula I according to claim 1, which is 4-(4-{2-[(5-ethyl-1H-pyrazole-3-yl)amino]-2-oxoethyl}-3-methoxyphenoxy)-N-methylinosine-7-carboxamide or its pharmaceutically acceptable salt.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1 or pharmaceutically acceptable derivatives thereof, where values of radicals X, W, R4, Ar1, Ar2, R3, R4, R20 are as described in paragraph 1 of the claim. The invention also describes a composition for treating or preventing pain, UI, ulcers, inflammatory bowel disease or irritable bowel syndrome.

EFFECT: compound which can be used in medicine is obtained and described.

46 cl, 10 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention refers to a compound which represents a biphenyl derivative of formula . What is also described is a pharmaceutical composition for treating or relieving HCV on the basis of said compound.

EFFECT: higher efficacy of the composition.

3 cl, 265 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to N-(2-thiazolyl)amide derivatives of formula wherein R1 and R2 are independently selected from H, -NO2, fluorine, chlorine and iodine, provided at least one of R1 and R2 is different from H; m is equal to 1 or 2, or to its pharmaceutically acceptable salts.

EFFECT: invention refers to a method for preparing said compounds, based pharmaceutical composition and applying them for preparing a drug for treating or preventing GSK-3 mediated diseases or conditions, especially neurodegenerative diseases, such as Alzheimer's disease or insulin-independent diabetes.

24 cl, 3 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 5-amino-3-(2-aminopropyl)-[1,2,4]thiadiazole derivatives of general formula wherein R1, R2, R3 can be identical or different independently means hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, heteroaralkyl (wherein 5- or 6-member N-, O- or S-heteroaromatic cycle), cycloalkyl, 2,2,6,6-tetramethyl-piperidin-4-yl, and also R1+R2 can mean heterocycle specified in optionally substituted pyrrolidine, piperidine, azepane, piperazine, morpholine wherein optional substitutes can be hydroxyl, cyanogroup, halogens, alkyls, lower alkoxy groups, lower alkothio groups, trihalogen methyl, sulphamide, optionally substituted amino groups (amino, dimethyl amino, diethyl amino) provided R1=H, R2 is different from hydrogen or methyl.

EFFECT: there are produced new compounds which can find application in medicine as the substances possessing neuromodulatory activity.

2 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) and pharmaceutically acceptable salts thereof, where Ar denotes a phenyl group substituted with piperazine or benzo[d]thiazole, with a phenyl part bonded to B, where the piperazine or benzo[d]thiazole can be unsubstituted or substituted with substitutes selected from alkyl or acetyl; B denotes -O-; R1 denotes hydrogen; R2 denotes S(O)2R4 or C(O)(CH2)n-C(O)OR5; R3 denotes halogen; R4 denotes an aryl which can be unsubstituted or substituted with substitutes selected from a group comprising halogen, alkyl, fluoroalkyl, alkoxy and trifluoromethoxy; R5 denotes hydrogen; n is a whole number from 1 to 3. The invention also relates to a method of producing said compounds and a pharmaceutical composition for treating metabolic disorders associated with insulin resistance or hyperglycaemia, based on said compounds.

EFFECT: novel compounds are obtained, which can be used in medicine to treat type 2 diabetes, obesity, glucose intolerance, dyslipidaemia, hyperinsulinaemia, atherosclerotic disease, polycystic ovary syndrome, coronary artery disease, hypertension or non-alcoholic fatty liver disease.

28 cl, 3 dwg, 4 tbl, 22 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing amide-containing 1,3,5-dithiazinanes of general formula , where R=H (Ia), CH3 (Ib). The method is realised by reacting hydrogen sulphide-saturated aldehyde (formal or acetic) with a mixture of isonicotinic acid hydrazide - BuONa (1:3, pH>11.5). The process is carried out at ratio hydrazide: aldehyde: H2S equal to 1:3:2, at temperature 40°C while stirring constantly for 4 hours, followed by neutralisation with a calculated quantity of dilute HCl and purification via column chromatography on SiO2. The substances obtained using the disclosed method can be used as radiation protection, antitumour and diuretic agents, as well as selective sorbents and extractants of noble and precious metals.

EFFECT: obtaining amide-containing 1,3,5-dithiazinanes of general formula (I).

2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to derivatives of 1,3,4-thiadiazolines (I), thiadiazinones (II) and thiadiazepines (III), obtained based on thiohydrazides of oxamic acids, which can be used to inhibit pathogenic bacteria, and can particularly affect type III secretion system in pathogens, having general formula:

, , ,

where R denotes H; R1 denotes H, pyridinyl; phenyl, substituted with alkyl C1-C5, Hal, CF3; a group , where X denotes S, substituted with alkyl C1-C5, COOR4; R2, R3 denotes alkyl C1-C5, pyridinyl, phenyl, substituted Hal, OH, OR4, a R4 denotes unsubstituted alkyl C1-C4.

EFFECT: obtaining compounds which can be used to inhibit pathogenic bacteria.

2 cl, 2 dwg, 6 tbl, 21 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula I wherein the substitutes A, B, B', Q and R1-R5 in formula I are specified as follows: A and B' are one of the following groups: (i) (R6)N(CH2)n, wherein n is 0 or 1; (ii) (CH2)n, wherein n is 0, 1 or 2; (iii) C(O)(CH2)n, wherein n is 0 or 1; or provided each of A and B' represents nitrogen, together they can form a bivalent radical of formula: -(CH2)s-X1-(CH2)t- (a), wherein each s and t is independently 1 or 2, and X1 represents (CH2)n, wherein n is 0 or 1; B is one of the following groups: (i) (R6)N; (ii) oxygen; (iii) C=δ, wherein δ represents oxygen or sulphur; (iv) C(R6)=C(R7); each R6 and R7 independently represent hydrogen, C1-4-alkyl; R1 is specified in the following groups: (i) phenyl group substituted by one or more substitute such as: - halogen specified in F, CI, Br or I, or alkyl1 group; aryl1 or heteroaryl group1; cyano, NH-alkyl1, N(alkyl1)(alkyl1) and amino; - NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl group, or (ii) pyridinyl group which can be substituted by one substitute, such as halogen specified in I, F, Cl or Br; alkyl1 group; aryl1 group; cyano, NH-alkyl1, N(alkyl1)(alkyl1), and amino; -NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl1 group; each R2, R3, R4 and R5 are independently specified in hydrogen or linear or branched alkyl group containing 1 to 10 carbon atoms; Q is specified in the following groups: (i) alkyl1; (ii) aryl1; (iii) heteroaryl1. The compounds of formula (I) are used for preparing a drug showing the c-kit inhibitor properties and aiming at treating a disease specified in neoplastic, allergic, inflammatory and autoimmune diseases.

EFFECT: use of oxazole derivatives as tyrosine kinase inhibitors.

13 cl, 1 tbl, 31 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula

and ,

where the ring X represents benzole or pyridine; R1 represents substituted alkyl; R2 represents optionally substituted aryl or optionally substituted 4-7-member monocyclic heterocyclic group or optionally substituted condensed group of heterocyclic group with the benzole ring where the substitutes of optionally substituted aryl, optionally substituted 4-7-member monocyclic heterocyclic group and optionally substituted condensed group of heterocyclic group with the benzole ring are selected from a group consisting of; (1) alkyl optionally substituted by a group selected from halogen and alkoxycarbonyl, (2) alkoxy optionally substituted by halogen, (3) halogen, (4) 4-7-member monocyclic heterocyclic group or (5) amino, optionally mono- or disubstituted alkyl, and (6) hydroxyl, R3 represents hydrogen or alkyl: R4 represents hydrogen, halogen or alkyl; R5 represents hydrogen or alkyl; R6 and R7 are identical or different, and each represents hydrogen or halogen; or pharmaceutically acceptable salt. Also, the invention refers to a IKur blocker containing the compounds described above as an active ingredient, and also to a preventive and therapeutic agent for cardiac arrhythmia and atrial fibrillation.

EFFECT: there are produced and described new compounds applicable as a IKur blocker effective for preventing or treating cardiac arrhythmia, such as atrial fibrillation.

12 cl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound of general formula I

,

and a pharmaceutically acceptable salt thereof, where X denotes CH2, CHF or S, Y denotes CN, R1, R2, R3 and R4 denotes hydrogen, n equals 1, m equals 0 or 1, R denotes R11, R12 or R13, where R11 includes at least one group selected from the following b) or c), where optionally substituted heterocyclic and heteroaryl groups are bonded with a noradamantyl part either directly or through a methylene adjacent group or a C-C bond or C-N bond; b) the substituted 5-member heteroaryl group, in which the heteroaryl ring is a monocyclic aromatic ring system, includes two or more heteroatoms selected from nitrogen and oxygen; c) the heterocyclic group is optionally substituted with a C1-C3 alkyl or oxo group, where the heterocyclic ring system is a 5-9-member mono- or bicyclic ring system with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where heteroatoms can also be present as functional groups, where the heterocyclic ring system can contain one or two double bonds, and where the monocyclic heterocyclic ring can be condensed with a phenyl ring, R12 is selected from hydrogen, halogen, hydroxy, amino and C1-C4 alkoxy; R13 is a substituted phenyl, where the substitutes, which can be identical or different, include at least one group selected from a) hydrogen; b) nitro, amino; c) the saturated or unsaturated monocyclic heterocyclic ring system is optionally substituted with one or more groups selected from C1-C3 alkyl and oxo, where the heterocyclic ring system is a 5-member ring with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where the heteroatoms can also be present as functional groups. The present invention also relates to a pharmaceutical composition having dipeptidyl peptidase IV inhibiting activity, methods of obtaining the novel compound of formula I and use in treating type II diabetes and diabetic complications as well as for treating dyslipidaemia, hypercholesteremia, obesity and hyperglycaemia.

EFFECT: novel dipeptidyl peptidase IV inhibitors.

10 cl, 1 tbl, 43 ex

FIELD: chemistry.

SUBSTANCE: invention describes isoxazolines of formula (I), in which A denotes C or N; R denotes C1-4 haloalkyl; X denotes identical or different halogens or C1-4 haloalkyl; l equals 0, 1 or 2; Y denotes halogen or C1-4 alkyl, C1-4alkoxy, C1-4haloalkyl, cyano, nitro, amino, C1-4 alkylcarbonylamino, benzoylamino or C1-4 alkoxycarbonylamino; m equals 1 or 1; and G denotes any group selected from heterocyclic groups given in the description, and a method of producing said compounds and use as insecticides for controlling the population of harmful insects or arthropods.

EFFECT: high efficiency of using said compounds.

11 cl, 28 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to use of 1,2,4-triazole derivatives of formula I:

, where R1, R2 and R3 independently denote hydrogen or halogen; R4 denotes C1-C6 alkyl; R5 and R6 independently denote C1-C6 alkyl or, together with a nitrogen atom to which they are bonded, form a 5-7-member heterocyclyl group, in which the 6-member heterocyclyl can further contain one oxygen or nitrogen atom and can be substituted with acetyl, C1-C6 alkyl or phyenyl; X-S-, -SO-, -SO2- or O; and n is a whole number selected from 1-8; or pharmaceutically acceptable salts, stereoisomers or solvates thereof, when producing a drug for treating or preventing sigma-1 receptor-mediated diseases or conditions, methods of producing said compounds, intermediate compounds and pharmaceutical compositions which contain compounds of formula 1.

EFFECT: improved compounds.

19 cl, 49 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds specified in cl. 1, and also to a pharmaceutical composition possessing binding activity with respect to Bcl proteins, to applying the declared compounds for preparing a drug for treating cancer and for treating a bcl-mediated disorder.

EFFECT: use of the compounds as Bcl protein inhibitors.

18 cl, 2 tbl, 41 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed compound relates to novel biaryl-meta-pyrimidine, corresponding to structure (A) and their pharmaceutically acceptable salts. In structure (A): X is selected from group consisting of bond O, and CH2, and Y represents bond; or X and Y together can represent bond; each R1 and R2 independent on each other are selected from group consisting of H and unsubstituted C1-C6alkyl; each of p, q, r, n, m independent on each other represents integer number 0 or 1; G0 is selected from group consisting from N and CH; each G represents independently CH, N, CR6 or C, when bound with X, on condition that not more than two groups of G represent N, and each R6 does not depend on another R6; R5 represents methyl, Values of other radicals are given in the invention formula.

EFFECT: compounds possess inhibiting activity with respect to family of JAK kinases, in particular JAK2 kinases, and can be used in treatment of myeloproliferative disease, which results from genetic or protein fusions, as a result of increase of function of kinase from family of JAK kinases in cell signal transmission, as well as in treatment of true polycythemia, primary thrombocytopenia, myeloid fibrosis with myeloid metaplasia, proliferative diabetic retinopathy, cancer or eye diseases.

66 cl, 2 tbl, 246 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula where R1, R2 and R3 are independently selected from a group consisting of hydrogen, halogen and lower alkyl containing 1-6 carbon atoms; R4 denotes a residue given in the claim; R5 denotes hydrogen or methyl; R10 is selected from a group consisting of: (i) hydrogen; (ii) (C1-C10) alkyl; (iii) (C1-C10)alkyl, substituted with one or more substitutes independently selected from a group consisting of -N(CH3)2, morpholinyl, (C1-C4) alkoxy, hydroxyl, -CON(CH3)2 and halogen; (iv) monocyclic (C3-C8) cycloalkyl containing one N heteroatom; (v) 9-methyl-9-azabicyclo[3.3.1]nonane; (vi) phenyl; (vii) phenyl substituted with one or more (C1-C4)alkoxy; R11 is selected from a group consisting of hydrogen and (C1-C10)alkyl; or R10, R11 and a nitrogen atom with which they are bonded, together, form a nitric heterocycle or a substituted nitric heterocycle, such as given in the claim. The invention also relates to a pharmaceutical composition, having serotonin type 3 receptor modulating capacity and a method of treating a disorder which depends on serotonin type 3 receptor modulation.

EFFECT: compounds of formula II as serotonin type 3 receptor modulators.

18 cl, 1 tbl, 159 ex

FIELD: chemistry.

SUBSTANCE: invention relates to specific derivatives of bicyclic amides disclosed in the claim, as well as a pharmaceutical composition.

EFFECT: compounds having protein kinase inhibiting activity, meant for use in treating protein kinase-dependant diseases, preferably proliferative diseases such as tumorous diseases.

13 cl, 115 ex

FIELD: chemistry.

SUBSTANCE: described are novel 7-member heterocyclic compounds of general formula (values of radicals are given in the claim) or salts thereof or solvates thereof having chymase inhibiting activity and suitable for preventing or treating different diseases in which chymase is involved, a method of producing said compounds, intermediate compounds and a pharmaceutical composition for preventing or treating diseases in which chymase is involved, including compounds of formula (I) or pharmaceutically acceptable salts or solvates thereof.

EFFECT: improved properties of the compound.

23 cl, 12 tbl, 308 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula I wherein the substitutes A, B, B', Q and R1-R5 in formula I are specified as follows: A and B' are one of the following groups: (i) (R6)N(CH2)n, wherein n is 0 or 1; (ii) (CH2)n, wherein n is 0, 1 or 2; (iii) C(O)(CH2)n, wherein n is 0 or 1; or provided each of A and B' represents nitrogen, together they can form a bivalent radical of formula: -(CH2)s-X1-(CH2)t- (a), wherein each s and t is independently 1 or 2, and X1 represents (CH2)n, wherein n is 0 or 1; B is one of the following groups: (i) (R6)N; (ii) oxygen; (iii) C=δ, wherein δ represents oxygen or sulphur; (iv) C(R6)=C(R7); each R6 and R7 independently represent hydrogen, C1-4-alkyl; R1 is specified in the following groups: (i) phenyl group substituted by one or more substitute such as: - halogen specified in F, CI, Br or I, or alkyl1 group; aryl1 or heteroaryl group1; cyano, NH-alkyl1, N(alkyl1)(alkyl1) and amino; - NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl group, or (ii) pyridinyl group which can be substituted by one substitute, such as halogen specified in I, F, Cl or Br; alkyl1 group; aryl1 group; cyano, NH-alkyl1, N(alkyl1)(alkyl1), and amino; -NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl1 group; each R2, R3, R4 and R5 are independently specified in hydrogen or linear or branched alkyl group containing 1 to 10 carbon atoms; Q is specified in the following groups: (i) alkyl1; (ii) aryl1; (iii) heteroaryl1. The compounds of formula (I) are used for preparing a drug showing the c-kit inhibitor properties and aiming at treating a disease specified in neoplastic, allergic, inflammatory and autoimmune diseases.

EFFECT: use of oxazole derivatives as tyrosine kinase inhibitors.

13 cl, 1 tbl, 31 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula

and ,

where the ring X represents benzole or pyridine; R1 represents substituted alkyl; R2 represents optionally substituted aryl or optionally substituted 4-7-member monocyclic heterocyclic group or optionally substituted condensed group of heterocyclic group with the benzole ring where the substitutes of optionally substituted aryl, optionally substituted 4-7-member monocyclic heterocyclic group and optionally substituted condensed group of heterocyclic group with the benzole ring are selected from a group consisting of; (1) alkyl optionally substituted by a group selected from halogen and alkoxycarbonyl, (2) alkoxy optionally substituted by halogen, (3) halogen, (4) 4-7-member monocyclic heterocyclic group or (5) amino, optionally mono- or disubstituted alkyl, and (6) hydroxyl, R3 represents hydrogen or alkyl: R4 represents hydrogen, halogen or alkyl; R5 represents hydrogen or alkyl; R6 and R7 are identical or different, and each represents hydrogen or halogen; or pharmaceutically acceptable salt. Also, the invention refers to a IKur blocker containing the compounds described above as an active ingredient, and also to a preventive and therapeutic agent for cardiac arrhythmia and atrial fibrillation.

EFFECT: there are produced and described new compounds applicable as a IKur blocker effective for preventing or treating cardiac arrhythmia, such as atrial fibrillation.

12 cl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

,

and pharmaceutically acceptable salts and solvates thereof, in which R1 is an optionally substituted alkyl or similar, R2 is a group of formula: -Y-R5, where Y is -O- or S; R5 is a substituted alkyl (the substitute is an optionally substituted cycloalkyl or similar), a branched alkyl or similar; R4 is hydrogen or C1-10 alkyl; R3 is a group of formula: -C(=O)-Z-R6, where Z is -NR7- or -NR7-W-; R6 is an optionally substituted cycloalkyl or similar; R7 is hydrogen or C1-10 alkyl, W is C1-10 alkylene; X is =N- provided that a compound in which R2 is 2-(4-morpholino)ethoxy, 2-, 3- or 4-pyridylmethoxy, 1-methylpiperidinyl-2-methoxy, benzyloxy or 4-substituted benzyloxy is excluded; and R3 is N-(1-adamantyl)carbamoyl, N-(2-adamantyl)carbamoyl and N-(3-noradamantyl)carbamoyl. Said compound is an 11β-hydroxysteroid dehydrogenase type 1 inhibitor. The invention also relates to a pharmaceutical composition containing said compound as an active ingredient.

EFFECT: improved properties of the compound.

23 cl, 72 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing piperazinophenols, involving reaction of piperazine, N-(β-aminoethyl)piperazine, N-(β-benzylaminoethyl)piperazine or N,N1-bis-(piperazinoethyl)ethylenediamine with a Mannich base in an aqueous medium at temperature 90-110°C in molar ratio of piperazine, N-(β-aminoethyl)piperazine, N-(β-benzylaminoethyl)piperzine:Mannich base equal to 1:0,8-2, N,N1-bis-(piperazinoethyl)ethylenediamine:Mannich base equal to 1:2 or 1:4 until release of dimethylamine stops; as well as aminomethylation of piperazine or N-(β-aminoethyl) piperazine with diphenylol propane (DPP) in the presence of formaldehyde (FA) in an aqueous medium with molar ratio piperazine: FA: DPP equal to 1:1:1 or 1:2:2 at temperature 50-90°C for 4-10 hours. Reactants react in the presence of a surfactant in amount of 2-6% of the weight of the starting piperazine, and the surfactant used is neonol, OP-7, OP-10.

EFFECT: ensuring fire safety of the process, high output of the end product which can be used as antioxidant phenol stabilisers.

1 cl, 13 ex

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