Heterocyclic compounds and their application

FIELD: medicine.

SUBSTANCE: described are novel heterocyclic compounds of general formulae and (values of radicals are given in invention formula), pharmaceutical compositions containing them and application of said heterocyclic compounds for treatment disorders mediated with MAP kinase cascade.

EFFECT: increase of compound efficiency.

67 cl, 106 ex, 2 tbl, 2 dwg

 

The text descriptions are given in facsimile form.

1. The compound of formula (A) or its pharmaceutically acceptable salt:
,
where Y is absent or represents a residue selected from the group consisting of:
,and;
R1is a Deputy selected from the group consisting of
,and
R2represents hydrogen;
and
R3is a Deputy selected from the group consisting of:
,,,,,,,
,,,,,or

2. The compound according to claim 1, selected from the group of compounds having the structural formula (A1), (A2), (A3) and (A4):



3. The compound of claim 2 of structural formula (A1).

4. The compound according to claim 2 of formula (A1)selected from the group consisting of compounds having the formula (1):

5. The compound according to claim 2 of formula (A1)selected from the group consisting of compounds having the formula (3), (4) and (5):

6. The compound according to claim 2 of the formula (A2)selected from the group consisting of:



and.

7. The connection according to claim 6 of the formula:

8. The connection according to claim 6 of the formula:

9. The connection according to claim 6 of the formula:

10. The connection according to claim 6 of the formula:

11. The connection according to claim 6 of the formula:

12. The compound of the formula (2) or its pharmaceutically acceptable salt:
,
where Y is absent or represents a residue selected from the group consisting of:
,and;
R2represents hydrogen; and
R3is a Deputy selected from the group consisting of:
,,,,,,,,
,,,,or

13. The compound or its pharmaceutically acceptable salt, selected from:
,
,
,
,
.

14. The compound of formula (I) or its pharmaceutically acceptable salt:
,
where Z1and Z2represent N, Z3represents O or N-R4where R4represents hydrogen;
X is absent or represents NH; and
Y is absent or is selected from the group consisting of the following residues:
and;
R1selected from the group consisting of:
,,,,,
and;
R2represents hydrogen; and
R3selected from the group consisting of hydrogen and
,,,,, ,,
,,,,,,
and.

15. The connection 14 of the formula

or its pharmaceutically acceptable salt.

16. The connection 14, selected from the group consisting of:















and

17. Connection P16 formula:

18. Connection P16 formula:

19. Connection P16 formula:

20. Connection P16 formula:

21. Connection P16 formula:

22. Connection is about P16 formula:

23. Connection P16 formula:

24. Connection P16 formula:

25. Connection P16 formula:

26. Connection P16 formula:

27. Connection P16 formula:

28. Connection P16 formula:

29. Connection P16 formula:

30. Connection P16 formula:

31. Connection P16 formula:

32. Connection P16 formula:

33. Connection P16 formula:

34. The compound or its pharmaceutically acceptable salt, selected from:
and

35. The compound represented by the formula

or its pharmaceutically acceptable salt.

36. A method of treating disorders associated with a cascade of MAP kinases, including introduction to the subject in need, an effective amount of a compound according to claim 1, where the disorder is selected from the group consisting of cancer, eye disease, inflammation, psoriasis and viral infections.

37. The method according to p, where disorder is the th cancer.

38. The method according to clause 37, where the cancer is a cancer of the digestive/gastrointestinal tract cancer, colon cancer, liver cancer, skin cancer, breast cancer, ovarian cancer, prostate cancer, lymphoma, leukemia, kidney cancer, lung cancer, malignant tumor of the muscles, malignant bone tumor, bladder cancer or brain cancer.

39. A method of treating disorders associated with a cascade of MAP kinases, including introduction to the subject in need, an effective amount of a compound according to claim 2, where the disorder is selected from the group consisting of cancer, eye disease, inflammation, psoriasis and viral infections.

40. A method of treating disorders associated with a cascade of MAP kinases, including introduction to the subject in need, an effective amount of a compound according to claim 4, where the disorder is selected from the group consisting of cancer, eye disease, inflammation, psoriasis and viral infections.

41. A method of treating disorders associated with a cascade of MAP kinases, including introduction to the subject in need, an effective amount of the compound according to clause 12, where the disorder is selected from the group consisting of cancer, eye disease, inflammation, psoriasis and viral infections.

42. A method of treating disorders associated with a cascade of MAP kinases, including introduction to the subject in need this, effectiveagainst connection according to claim 6, where the disorder is selected from the group consisting of cancer, eye disease, inflammation, psoriasis and viral infections.

43. A method of treating disorders associated with a cascade of MAP kinases, including introduction to the subject in need, an effective amount of the compound according to item 13, where the disorder is selected from the group consisting of cancer, eye disease, inflammation, psoriasis and viral infections.

44. A method of treating disorders associated with a cascade of MAP kinases, including introduction to the subject in need, an effective number of connections 14, where the disorder is selected from the group consisting of cancer, eye disease, inflammation, psoriasis and viral infections.

45. The method according to item 44, where the disorder is a cancer.

46. The method according to item 45, wherein the cancer is cancer of the digestive/gastrointestinal tract, colon cancer, liver cancer, skin cancer, breast cancer, ovarian cancer, prostate cancer, lymphoma, leukemia, kidney cancer, lung cancer, malignant tumor of the muscles, malignant bone tumor, bladder cancer or cancer of the brain.

47. A method of treating disorders associated with a cascade of MAP kinases, including introduction to the subject in need, an effective amount of the compound according to clause 15, where the disorder is selected from g is PI, consisting of cancer, eye disease, inflammation, psoriasis and viral infections.

48. A method of treating disorders associated with a cascade of MAP kinases, including introduction to the subject in need, an effective amount of the compound according to clause 16, where the disorder is selected from the group consisting of cancer, eye disease, inflammation, psoriasis and viral infections.

49. A method of treating disorders associated with a cascade of MAP kinases, including introduction to the subject in need, an effective amount of the compound according to clause 34, where the disorder is selected from the group consisting of cancer, eye disease, inflammation, psoriasis and viral infections.

50. A method of treating disorders associated with a cascade of MAP kinases, including introduction to the subject in need, an effective amount of a compound according p, where the disorder is selected from the group consisting of cancer, eye disease, inflammation, psoriasis and viral infections.

51. Pharmaceutical composition for use in treating disorders associated with a cascade of MAP kinases, where the disorder is selected from cancer, eye disease, inflammation, psoriasis and viral infections, containing at least one compound according to claim 1 or 14, or any combination thereof in a pharmaceutically acceptable carrier.

52. The finished product containing packaging material, and in it, f is rmaceuticals composition, moreover, the packaging material includes a label that indicates that the pharmaceutical composition can be used for treating disorders associated with a cascade of MAP kinases, where the disorder is selected from cancer, eye disease, inflammation, psoriasis and viral infections, and pharmaceutical composition contains at least one compound according to claim 1 or 14, or any combination thereof.

53. The finished product containing packaging material and its pharmaceutical composition and the packaging material includes a label that indicates that the pharmaceutical composition can be used for the treatment of cancer, the pharmaceutical composition contains at least one compound according to claim 1 or 14, or any combination thereof.

54. A method of treating disorders associated with a cascade of MAP kinases, including the introduction of a therapeutically effective amount of at least one compound according to claim 1 or 14, or any combination thereof, or their pharmaceutically acceptable salts entity that needs treatment, where the disorder is selected from the group consisting of cancer, eye disease, inflammation, psoriasis and viral infections.

55. The method according to item 54, wherein the disorder is a cancer.

56. The method according to § 55 where the cancer is cancer of the digestive/gastrointestinal tract, cancer of the m colon, liver cancer, skin cancer, breast cancer, ovarian cancer, prostate cancer, lymphoma, leukemia, kidney cancer, lung cancer, malignant tumor of the muscles, malignant bone tumor, bladder cancer or cancer of the brain.

57. The method of treatment of a subject suffering from a cancer associated with a cascade of MAP kinases, including introduction to the subject a therapeutically effective amount of a compound according to claim 1 or 14, or any combination thereof.

58. Pharmaceutical composition for use in treating disorders associated with a cascade of MAP kinases, where the disorder is selected from cancer, eye disease, inflammation, psoriasis and viral infections, containing a compound according to claim 3 in a pharmaceutically acceptable carrier.

59. Pharmaceutical composition for use in treating disorders associated with a cascade of MAP kinases, where the disorder is selected from cancer, eye disease, inflammation, psoriasis and viral infections, containing a compound according to claim 4 in a pharmaceutically acceptable carrier.

60. Pharmaceutical composition for use in treating disorders associated with a cascade of MAP kinases, where the disorder is selected from cancer, eye disease, inflammation, psoriasis and viral infections, containing a compound according to claim 6 in a pharmaceutically acceptable carrier.

61. The pharmaceutical composition d which I use for the treatment of disorders associated with a cascade of MAP kinases, where the disorder is selected from cancer, eye disease, inflammation, psoriasis and viral infections that contains the connection section 12 in a pharmaceutically acceptable carrier.

62. Pharmaceutical composition for use in treating disorders associated with a cascade of MAP kinases, where the disorder is selected from cancer, eye disease, inflammation, psoriasis and viral infections containing compound according to item 13 in a pharmaceutically acceptable carrier.

63. Pharmaceutical composition for use in treating disorders associated with a cascade of MAP kinases, where the disorder is selected from cancer, eye disease, inflammation, psoriasis and viral infections that contains the connection 14 in a pharmaceutically acceptable carrier.

64. Pharmaceutical composition for use in treating disorders associated with a cascade of MAP kinases, where the disorder is selected from cancer, eye disease, inflammation, psoriasis and viral infections that contains the connection 15 in a pharmaceutically acceptable carrier.

65. Pharmaceutical composition for use in treating disorders associated with a cascade of MAP kinases, where the disorder is selected from cancer, eye disease, inflammation, psoriasis and viral infections that contains the connection P16 in pharmaceutically acceptable carrier.

66. Pharmaceutical to notice for use for the treatment of disorders associated with a cascade of MAP kinases, where the disorder is selected from cancer, eye disease, inflammation, psoriasis and viral infections that contains the connection 34 in a pharmaceutically acceptable carrier.

67. Pharmaceutical composition for use in treating disorders associated with a cascade of MAP kinases, where the disorder is selected from cancer, eye disease, inflammation, psoriasis and viral infections that contains the connection p in a pharmaceutically acceptable carrier.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compound of formula , where A, Q, R1, R2, R3, R4, R5' are represented in i.1 of the formula, as well as to its hydrates, solvates and pharmaceutically acceptable salts, Also described are application of said compound and pharmaceutical composition, including such compound, for treatment of disease condition in mammals, which is sensitive to action of antagonists of vasopressin V1a, V1b or V2 receptors.

EFFECT: increase efficiency of compound application.

20 cl, 13 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a quinazoline derivative of general formula [1], or a pharmaceutically acceptable salt thereof [1], where R1-R6 assume values given claim 1, except compounds in which R5 is hydrogen and R6 is -NH2. The invention also relates to a pharmaceutical composition having the activity of an antipruritic agent, containing as an active ingredient said quinazoline derivative or pharmaceutically acceptable salt thereof.

EFFECT: obtaining a novel quinazoline derivative with low irritant action on skin and excellent action of significant suppression of scratching behaviour, as well as an antipruritic agent containing such a quinazoline derivative as an active ingredient.

9 cl, 250 ex, 7 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to di(arylamino)aryl derivatives presented in the patent claim. The compounds show an inhibitory effect on protein EML4-ALK v1 and protein EGFR kinase activity. Also the invention refers to a pharmaceutical composition containing said compounds, the hybrid protein EML4-ALK and mutant protein EGFR kinase activity inhibitor, the use of said compounds for preparing the pharmaceutical composition, and to a method of preventing or treating non-small-cell lung cancer or EML4-ALK hybrid polynucleotide-positive and/or mutant EGFR polynucleotide-positive non-small-cell lung cancer.

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12 cl, 95 tbl, 55 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted sulphamide derivatives of formula I: , in which n, m, R1, R2a-c, R3, R4, R5 and R6 are as described in claim 1, in form of a racemate, enantiomers, diastereomers, mixtures of enantiomers or diastereomers or a separate enantiomer or diastereomer, bases and/or salts of physiologically compatible acids. The invention also relates to a method of producing said compounds, a medicinal agent having antagonist action on bradykinin receptor 1 (B1R), containing such compounds, use of such compounds to produce medicinal agents, as well as sulphamide-substituted derivatives selected from a group of compounds given in claim 8.

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13 cl, 581 ex

FIELD: chemistry.

SUBSTANCE: invention is a 6-10-member aryl selected from phenyl, naphthyl, tetrahydronaphthalenyl, indanyl or a 6-member heteroaryl containing 1-2 N atoms, selected from pyridyl or pyrimidinyl, where the aryl and heteroaryl groups can be unsubstituted or substituted with 1-3 substitutes selected from a group consisting of C3-6-cycloalkyl, phenyl, phenyloxy, benzyl, benzyloxy, halogen atom, C1-7-alkyl, C1-7-alkoxy, oxazolyl, piperidin-1-yl, or C1-7-alkyl, substituted with a halogen atom, or represents phenyl, where at least one hydrogen atom is substituted with deuterium or tritium; R2 is a hydrogen atom, C1-7-alkyl or is benzyl, unsubstituted or substituted C1-7-alkoxy or halogen atom; or R1 and R2 together with a N atom with which they are bonded form 2,3-dihydroindol-1-yl or 3,4-dihydro-1quinolin-1-yl. The invention also relates to a method of producing compounds of formula and to a pharmaceutical composition having high affinity for the TAAR1 receptor.

EFFECT: compounds of formula (I), having high affinity for the TAAR1 receptor.

29 cl, 4 dwg, 1 tbl, 183 ex

FIELD: medicine, pharmaceutics.

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13 cl, 1 tbl

FIELD: chemistry.

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EFFECT: obtaining novel cyanoisoquinoline compounds having useful biological properties.

42 cl, 1 tbl, 54 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula (I): wherein n means 1 or 2, X means an oxygen atom, a sulphur atom or NH, R1 means a side group of natural α-amino acid or its homologues or isomers specified in hydrogen, methyl, propan-2-yl, propan-1-yl, 2-methyl-propan-1-yl, imidazol-4-ylmethyl, hydroxymethyl, 1-hydroxy-ethyl, carboxymethyl, 2-carboxyethyl, carbamoyl-methyl, 2-carbamoyl ethyl a, 4-aminobutan-1-yl, 3-aminopropan-1-yl, 3-guanidinopropan-1-yl, benzyl or 4-hydroxybenzyl, R2 means hydrogen or methyl, R3 means hydrogen, or R1 and R3 are coupled together by the group (CH2)3- or (CH2)4- and together with nitrogen and carbon atoms whereto attached form a five- or six-member ring, as well to their salts, solvates and salt solvates.

EFFECT: preparing compounds for treating and/or preventing the diseases, first of all thromboembolic diseases.

2 cl, 2 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing optionally substituted 4-(benzimidazo-2-yl methylamino)benzamidine of formula (I) in which R1 denotes a methyl group, R2 denotes a R21NR22 group, where R21 denotes an ethyl group which is substituted with an ethoxycarbonyl group, and R22 denotes a pyridin-2-yl group, R3 denotes an n-hexyloxycarbonyl group, where at step (a) phenyldiamine of formula (II) where R1 and R2 assume values given for formula (I), which reacts with 2-[4-(1,2,4-oxadiazol-5-on-3-yl)phenylamino]acetic acid, to obtain a product of formula (III) where R1 and R2 assume values given for formula (I), which is hydrogenated at temperature from 30 to 60°C at hydrogen pressure from 1 to 10 bar, over palladium on activated charcoal (Pd/C) in a mixture of tetrahydrofuran and water, and then, without any preliminary extraction of the hydrogenation product, the obtained compound of formula (I), in which R3 denotes hydrogen, in the presence of potassium carbonate reacts with a compound of formula (IV) R3-X (IV), where R3 assumes values given for formula (I), and X denotes a suitable splitting group.

EFFECT: simple method of producing optionally substituted 4-(benzimidazo-2-yl methylamino)benzamidine.

3 cl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new piperazine amide derivatives of formula wherein X represents N or CH; Y represents N or CH; R1 represents lower alkyl, phenyl, phenyl-lower alkyl wherein phenyl can be optionally substituted by 1-2 substitutes independently specified in a group consisting of halogen, lower alkyl; R2 represents lower alkyl, phenyl, naphthyl or heteroaryl specified in dimethylisoxazolyl, quinolinyl, thiophenyl or pyridinyl wherein phenyl or heteroaryl are optionally substituted by 1 substitute optionally specified in a group consisting of halogen, lower alkoxy group, fluor-lower alkyl, lower alkoxy-carbonyl and phenyl; R3 represents phenyl, pyridinyl or pyrazinyl wherein phenyl, pyridinyl or pyrazinyl are substituted by 1-2 substituted optionally specified in a group consisting of halogen, lower alkyl and fluor-lower alkyl; R4, R5, R6, R7, R8, R9, R10 and R11 independently represent hydrogen, as well as to their physiologically acceptable salts. These compounds are bound with LXR alpha and LXR beta, and are applicable as therapeutic agents for treatment and/or prevention of high lipid levels, high cholesterol levels, low HDL cholesterol, high LDL cholesterol, atherosclerotic diseases, diabetes, non insulin dependent diabetes mellitus, metabolic syndrome, dislipidemia, sepsis, inflammatory diseases, infectious diseases, skin diseases, colitis, pancreatitis, cholestasis, liver fibrosis, psoriasis, Alzheimer's disease, etc.

EFFECT: preparing new piperazine amide derivatives.

15 cl, 88 ex

FIELD: medicine.

SUBSTANCE: in claimed invention described is compound of general formula 1, or its pharmaceutically acceptable salt, where in each case independently on each other m equals 0, 1; p equals 1 or 2; R1 is selected from group, including -OH, -OC(O)NHMe, -OC(O)NMe2, -OC(O)NH(CH2)2Ph and OC(O)NH(CH2)2NMe2; R2 stands for -OH, -OC(O)Me, -OCH2CO2H, -OCH2CO2Et, -N3, -N=C(NMe2)2, -NH2, -NMe2, -NHC(O)Me, -NHC(O)CF3, - NHC(O)Ph, -NHC(O)NHPh, -NHC(O)CH2CH2CO2H, -NHC(O)CH2CH2CO2Me, - NHCH2Ph, -NHCH2(4-pyridyl), -NHCH2(2-pyridyl), -NHCH2(4-(CO2H)Ph), - NHCH2(3-(CO2H)Ph), -NHEt, -NHCHMe2, -NHCH2CHMe2, -N(CH2CHMe2)2, - NHCH2(cyclopropyl) or -NHC(O)CH2CH2NMe2; R3 stands for -OMe, -OEt, - OCH2(cyclopropyl), F, -O(CH2)2NMe2 or -O(CH2)2(4-morpholino); R4 stands for -NMe2, -NEt2, -NHEt, -NHCH2CHMe2, -N(Me)CH2CHMe2, - N(Me)CH2CH2NHS(O)2Me, -N(Me)CH2CH2NHS(O)2CF3, -NHCH2CH2OH, - N(Me)CH2CH2OH, -N(Me)CH2CO2H, -N(Me)CH2C(O)NH2, N(Me)CH2C(O)NHMe, -N(Me)CH2C(O)NMe2, -NHC(O)Me, 1-piperidinyl, 4-morpholino, (R)-2-(hydroxymethyl)-1-pyrrolidinyl, -NH2, -NO2, Br, CI, F, -C(O)Me or -CH2NH2; R5 stands for -OH or -N(R17)(R18); R17 and R18 independently in each case stand for H, (C1-C6)-alkyl, (C5-C7)-aryl-(C1-C6)-alkyl, where said aryl contains from zero to two heteroatoms, (C1-C6)-alkoxy or -[C(R19)(R20)]P-R21 R19 and R20 independently in each case represent H, (C1-C6)-alkyl, (C1-C6)-alkoxy, amino-(C1-C6)-alkyl, acylamino, sulfonylamino, (C5-C7)-aryl, (C5-C7)-aryl-(C1-C6)-alkyl or 3-10-membered heterocyclyl-(C1-C6)-alkyl, containing in ring from one to two heteroatoms; R21 independently in each case represents H, 3-10-membered heterocyclyl, containing in ring one heteroatom, (C1-C6)-alkylsulfonyl, (C1-C6)-alkylsulfonamido or amido; R22 stands for halogen; R23 stands for methyl; R24 stands for methyl and R25 stands for methyl, where said aryl stands for 5-7-membered ring, containing from zero to two heteroatoms, and said aryl or said heterocyclyl can be non-substituted or substituted halogen, (C1-C6)-alkyl or amino. Also described is pharmaceutical composition, possessing inhibiting activity with respect to Bcl-2 and/or Bcl-XL proteins, which includes said compound, also described is method of treating disorder, mediated by Bcl-2 and/or Bcl-XL proteins, which lies in introduction of said compound to patient, who needs such treatment, in therapeutically efficient amount.

EFFECT: increased efficiency of compound application.

41 cl, 6 dwg, 125 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a quinazoline derivative of general formula [1], or a pharmaceutically acceptable salt thereof [1], where R1-R6 assume values given claim 1, except compounds in which R5 is hydrogen and R6 is -NH2. The invention also relates to a pharmaceutical composition having the activity of an antipruritic agent, containing as an active ingredient said quinazoline derivative or pharmaceutically acceptable salt thereof.

EFFECT: obtaining a novel quinazoline derivative with low irritant action on skin and excellent action of significant suppression of scratching behaviour, as well as an antipruritic agent containing such a quinazoline derivative as an active ingredient.

9 cl, 250 ex, 7 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted pyrimidine derivatives having PGDS inhibiting properties. In formula (I): (I), R1 denotes phenyl or a 5- or 6-member heteroaryl containing 1-3 heteroatoms selected from N, O and S, each optionally having one or more of the following independent substitutes: halogen, (C1-C6)-alkyl, or (C1-C4)-haloalkyl; R2 denotes hydrogen or (C1-C6)-alkyl, which is optionally substituted with one or more halogens; R3 denotes hydrogen, (C1-C6)-alkyl or phenyl; R4 denotes C6-cycloalkyl, phenyl, a 6-member heterocyclyl containing one N heteroatom, a 6-member heteroaryl containing one N heteroatom, -C(=O)-NY1Y2, -C(=S)-NY1Y2, or -C(=O)-R5, where the phenyl, 6-member heteroaryl or 6-member heterocyclyl group optionally has one or more independent substitutes R6, or R3 and R4 together with a nitrogen atom with which they are bonded form a 5- or 6-member heterocyclyl containing one or two heteroatoms selected from N, O and S, a 6-member heterocyclenyl containing two or three N heteroatoms, a 5-member monocyclic or 9-member bicyclic heteroaryl containing one to three N heteroatoms, phenylheterocyclyl, where the heterocyclyl is 5- or 6-membered and contains one or two heteroatoms selected from N and O, each optionally having one or more independent substitutes R6. Values of R5, R6, Y1, Y2 are given in the claim. The invention also relates to a pharmaceutical composition containing said compounds.

EFFECT: improved method.

15 cl, 227 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to di(arylamino)aryl derivatives presented in the patent claim. The compounds show an inhibitory effect on protein EML4-ALK v1 and protein EGFR kinase activity. Also the invention refers to a pharmaceutical composition containing said compounds, the hybrid protein EML4-ALK and mutant protein EGFR kinase activity inhibitor, the use of said compounds for preparing the pharmaceutical composition, and to a method of preventing or treating non-small-cell lung cancer or EML4-ALK hybrid polynucleotide-positive and/or mutant EGFR polynucleotide-positive non-small-cell lung cancer.

EFFECT: use of di(arylamino)aryl as the protein EML4-ALK v1 and protein EGFR kinase activity inhibitors.

12 cl, 95 tbl, 55 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: it has been confirmed that the new azolcarboxamide compound or its pharmaceutically acceptable salt wherein a thiazole ring or an oxazole ring is bound to a benzene ring, a pyridine ring, a pyridazine ring, a thiophen ring, a pyrazole ring or a pyrrol ring through carboxamide or its ring possess high activity of receptor trkA inhibition; it has been found that they may be used as a therapeutic and/or preventive agent which is different in the fact concerning the effectiveness and safety for repeated urination, frequent micturate urge and urine incontinence associated with various urogenital diseases, including higher bladder activity, various lower bladder diseases accompanied with urogenital pain, such as interstitial cystitis, chronic prostatitis and others, and various diseases accompanied by pain; thereby the present invention has been created.

EFFECT: provided therapeutic and/or preventive agent for repeated urination, frequent micturate urge and urine incontinence associated with various urogenital diseases, including higher bladder activity, various lower bladder diseases accompanied with urogenital pain, such as interstitial cystitis, chronic prostatitis and others, and various diseases accompanied by pain on the basis of excellent inhibitory action on the receptor trkA.

24 cl, 1195 ex, 215 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (1), where R1 denotes a C1-C4 halogenalkyl group, R2 denotes a halogen atom, R3 denotes a C1-C6alkyl group, C1-C6alkoxy group or a halogen atom, m equals an integer from 0 to 5, n equals an integer from 0 to 4, M denotes an oxygen or sulphur atom, R4 is as defined in the claim. The invention also relates to a insect control method, use of compounds of formula (1) and a composition containing compounds of formula (1) for insect control.

EFFECT: obtaining compounds of formula (1) for insect control.

20 cl, 119 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel xinafoate salt of N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-on)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonyl methyleneoxy)phenyl]-2,4-pyrimidine diamine, having the structural formula given below. The invention also relates to a method of producing a salt, use of the latter, a pharmaceutical composition and a treatment method. The method of producing a xinafoate salt involves dissolving N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-on)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonyl methyleneoxy)phenyl]-2,4-pyrimidine diamine and 1-1.1 molar equivalents of 1-hydroxy-2-naphthoic acid in a minimum amount of a suitable organic solvent such as acetone, acetonitrile or methyl ethyl ketone, each optionally containing a small amount of water, and subsequent slow cooling of the solution with optional stirring until precipitation of the salt from the solution.

EFFECT: obtained salt has Syk-kinase inhibiting properties and can be used in treating an inflammatory condition such as asthma (I).

12 cl, 6 tbl, 1 ex

New compounds // 2458920

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula or to its pharmaceutically acceptable salts wherein -A-(R1)a means a group; -B-(R2)b means a group specified in the patent claim 1, R3 means hydrogen; X means CH2 or O; and Y means CH2. Also, the invention refers to a pharmaceutical composition exhibiting FGFR inhibitor activity on the basis of the declared compound.

EFFECT: there are produced new compounds and based pharmaceutical composition which can find application in medicine for preparing a cancer drug.

8 cl, 1 tbl, 180 ex

New compounds // 2456273

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula: wherein B is specified in a group consisting of pyridine, pyridazine, pyrimidine and oxazole which can be optionally substituted by halogen, C1-7-alkyl or a C1-7-alkoxy group; L1 is specified in a group consisting of -NH-, -C(O)NH- and -NHC(O)-, A means C3-C12-cycloalkyl, C6-C12-aryl, a 4-7-member monocyclic heterocyclic group consisting of 1-3 heteroatoms optionally specified in O N and S, or a bicyclic heterocyclyl specified in a group consisting of benzimidazolyl, benzoxazolyl, benzothiazolyl, wherein cycloalkyl, aryl, mono- or bicyclic heterocyclyl can be optionally substituted by one or more substitutes optionally specified in a group consisting of a cyano group, halogen, an oxo group, C1-7-alkyl, C1-7-halogenalkyl, a C1-7-alkoxy group, C1-7-halogenalkoxy group, an amino group, a di-C1-7-alkylamino group, a C1-7-alkylthio group and C3-8-cycloalkyl, 1-2- means a bivalent residue specified in a group consisting of: - a bivalent alkyl group consisting of 1 to 4 carbon atoms, a bivalent alkenyl group consisting of 2 to 3 carbon atoms, - -C(O)-, - -C(O)-[R4]c-R5- wherein c is equal to 0, and R5 is specified in a group consisting of a bivalent C1-C4-alkyl group optionally substituted by another C1-4-alkyl, a C4-C8-cycloalkyl group, a phenyl group and a 5- or 6-member heterocyclyl group consisting of N heteroatoms, - -C(O)-NH-, - -(CH2)1-3-C(O)-NH-(CH2)1-3-, - -C(O)-NH-R4- wherein R4 is specified in a group consisting of a bivalent C1-C7-alkyl group optionally substituted by another C1-4-alkyl, a cyclohexyl group and a cyclopentyl group, and E is specified in a group consisting of: - COOH, - a ester group of carboxylic acid, or to its pharmaceutically acceptable salts. What is also described is a pharmaceutical composition exhibiting DGAT1 modulatory activity, on the basis of the presented compounds, and also a method of treating pathological conditions or disorders associated with DGAT1 activity.

EFFECT: there are prepared and described new compounds applicable for treating or preventing the pathological conditions or disorders associated with DGAT1 activity.

22 cl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: in formula (1): R1 means haloalkyl containing 1-6 fluorine atoms; R2 means C1-C6alkyl or halogen; R3 means -L-NR4R5, -X-NR-C(O)R8 or -X-NR-C(O)NR4R5 wherein L means -X-C(O), -(CR2)j, -O(CR2)1-4 or and X means (CR2)j or [C(R)(CR2OR)]; R4 and R5 independently mean H, C1-C6alkyl, halogen-substituted C1-C6alkyl, hydroxy group-substituted C1-C6alkyl, or (CR2)k-R6; R8 independently means (CR2)k-R6 or C1-C6alkyl, or halogen-substituted C1-C6alkyl; R7 means H; alternatively, R4 and R5 together with N atom in each NR4 R5 form a 4-7-member heterocyclic ring containing 1 -2 heteroatoms independently specified in N and O substituted by 0-3 groups R11; R11 means R8, (CR2)k-OR7, CO2R7, (CR2)k-C(O)-(CR2)k-R8, (CR2)kC(O)NR7R7 or (CR2)kS(O)1-2R8; each R means H or C1-C6alkyl; each k is equal to 0-6; and j and m are independently equal to 0-4; provided R1 does not mean trifluoromethoxygroup, provided R3 means C(O)NH2, C(O)NR12R13; wherein R12 and R13 together form piperazinyl; the values of the radical R6 are presented in the patent claim. The invention also refers to the pharmaceutical composition containing said compounds.

EFFECT: producing new 5-(4-(halogenalkoxy)phenyl)pyrimidin-2-amine derivatives showing c-kit, PDGFRα, PDGFRβ kinase inhibitory activity, optionally in the form of isomers or pharmaceutically acceptable salts.

12 cl, 77 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to substituted sulphamide derivatives of formula I: , in which n, m, R1, R2a-c, R3, R4, R5 and R6 are as described in claim 1, in form of a racemate, enantiomers, diastereomers, mixtures of enantiomers or diastereomers or a separate enantiomer or diastereomer, bases and/or salts of physiologically compatible acids. The invention also relates to a method of producing said compounds, a medicinal agent having antagonist action on bradykinin receptor 1 (B1R), containing such compounds, use of such compounds to produce medicinal agents, as well as sulphamide-substituted derivatives selected from a group of compounds given in claim 8.

EFFECT: providing novel compounds which are suitable as pharmacologically active substances in medicinal agents for treating disorders or diseases which are at least partially transmitted through B1R receptors.

13 cl, 581 ex

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