4-monosubstituted thiazoline-quinolines

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I and their pharmaceutically acceptable salts. Disclosed compounds have inhibitory effect on CDK1 kinase and can be used to prepare medicinal agents for treating diseases associated with abnormal cell cycle development. In formula I , R1 is hydrogen, -C(O)OR9 or R2-(X)n-; X is (lower)alkylene, hydroxy(lower)alkylene, cyclised(lower)alkylne or mono- or dihalogen(lower)alkylene; R2 is a group, where denotes a phenyl or a 5-6-member heteroaromatic ring containing 1-2 heteroatoms selected from a group comprising oxygen, sulphur and nitrogen atoms; R5, R6 and R7 are independently selected from a group comprising hydroxy, hydrogen, (lower)alkyl, halogen and (lower)alkoxy; R4 is a halogen, , (O)k(CH2CH2O)y-R10, , -S-R12 or -O-(CH2)tR14, where denotes a phenyl, a cycloalkyl ring containing 3-6 carbon atoms, a 4-6-member heterocycloalkyl containing 3-5 carbon atoms and 1-2 heteroatoms selected from a group comprising oxygen, nitrogen and sulphur atoms; R9, R11, R15 and R16 independently denote (lower)alkyl; R10 and R12 denote (lower)alkyl; R14 denotes perfluoro(lower)alkyl or -NR15R16; R17 and R18 independently denote hydrogen, , F, OCH3 and -C(=O)CH3; n and k are equal to 0 or 1; m, w, y and z are equal an integer from 0 to 3; and t equals an integer from 0 to 6.

EFFECT: invention also relates to a pharmaceutical composition having antiproliferative activity, containing one or more of the disclosed compounds.

65 cl, 1 tbl, 49 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula

where R1means hydrogen, -C(O)OR9or R2(X)n-;
X means (ness.)alkylene, hydroxy(ness.)alkylen, sallisbury (ness.)alkylene or mono - or dihalogen(ness.)alkylen;
R2mean group
,
wheremeans phenyl or 5-6-membered heteroaromatic cycle-containing 1-2 heteroatoms selected from the group comprising atoms of oxygen, sulfur and nitrogen;
R5, R6and R7independently selected from the group comprising hydroxy, hydrogen, (ness.)alkyl, halogen and (ness.)alkoxy;
R4means halogen,
, (O)k(CH2CH2O)y-R10,
, -S-R12or-O-(CH2)tR14,
wheremeans phenyl, cycloalkyl cycle containing from 3 to 6 carbon atoms, a 4 to 6 membered heteroseksualci containing from 3 to 5 carbon atoms and 1-2 heteroatoms selected from the group comprising atoms of oxygen, nitrogen and sulfur;
R9, R11, R15and R16independent means (nor the sh.)alkyl;
R10and R12mean (ness.)alkyl;
R14means PERFLUORO(ness.)alkyl or-NR15R16;
R17and R18independently mean hydrogen,, F, och3and-C(=O)CH3;
n and k is an integer from 0 to 1;
m, w, y, and z is an integer from 0 to 3;
and t is an integer from 1 to 6;
or its pharmaceutically acceptable salt.

2. The compound according to claim 1 of formula I-A

where R1' means hydrogen, and
R4matter specified in claim 1,
or its pharmaceutically acceptable salt.

3. The compound according to claim 2, wheremeans phenyl.

4. The compound according to claim 2, where R4means -(O)k(CH2CH2O)y-R10and R10, k and y have the meanings indicated in claim 1.

5. The compound according to claim 4, where the specified connection selected from the group including
2-amino-5-(4-methoxyquinoline-6-elmet-(Z)-alidin)thiazole-4-one
2-amino-5-[4-(2-methoxyethoxy)quinoline-6-elmet-(Z)-ridin]thiazole-4-one and
2-amino-5-(4-butoxyaniline-6-elmet-(Z)-ridin]thiazole-4-one.

6. The compound according to claim 2, where
R4means;
w, k, ®, R17and R18have the meanings indicated in claim 1.

7. The connection according to claim 6, where w is equal to 0.

8. The connection according to claim 7, where the specified connection selected from the group including
2-amino-5-(4-phenoxyphenol-6-elmet-(Z)-or is in)thiazole-4-one and
2-amino-5-[1-[4-(piperidine-4-yloxy)quinoline-6-yl]meth-(Z)-ilidene]thiazole-4-one.

9. The connection according to claim 6, where w is an integer from 1 to 3.

10. The connection according to claim 9, where the specified connection selected from the group including
2-amino-5-{4-[2-(3-methoxyphenyl)ethoxy]quinoline-6-elmet-(Z)-ridin}thiazole-4-one and
2-amino-5-{4-[2-(4-forfinal)ethoxy]quinoline-6-elmet-(Z)-ridin}thiazole-4-one.

11. The compound according to claim 2, where R4means-S-R12and R12matter specified in claim 1.

12. Connection claim 11, where the connection specified is a
2-amino-5-(4-ethylsulfanyl-6-elmet-(Z)-alidin)thiazole-4-one.

13. The compound according to claim 2, where R4means-O-(CH2)t-R14.

14. The connection indicated in paragraph 13, where R14means PERFLUORO(ness.)alkyl.

15. The connection 14, where R14means trifluoromethyl.

16. The connection indicated in paragraph 15, where the connection specified is a
2-amino-5-[4-(2,2,2-triptoreline)quinoline-6-elmet-(Z)-ridin]thiazole-4-one.

17. The compound according to claim 1 of formula I-B

where R1means R'2-(X')n-;
n and R4have the meanings specified in claim 2; and
X' means (ness.)alkylene, hydroxy(ness.)alkylen, sallisbury (ness.)alkylene, mono - or dihalogen(ness.)alkylen;
R2' shall mean a group
;
wheremeans phenyl or 5-6-h is i.i.d. heteroaromatic cycle, containing 1-2 heteroatoms selected from the group comprising atoms of oxygen, sulfur and nitrogen;
R5' and R6' are independently selected from the group comprising hydroxy, hydrogen, (ness.)alkyl, halogen and (ness.)alkoxy;
or its pharmaceutically acceptable salt.

18. The connection 17, where n is equal to 1.

19. Connection p, where X' means sallisbury (ness.)alkylen.

20. The connection according to claim 19, where the specified sallisbury (ness.)alkylen means cyclopropyl.

21. Connection claim 20, where R2' means phenyl or phenyl substituted by halogen.

22. Connection item 21, where R4means -(O)k(CH2CH2O)y-R10and y, k and R10have the meanings indicated in claim 1.

23. Connection p.22, where the specified connection selected from the group including
5-(4-methoxyquinoline-6-elmet-(Z)-alidin)-2-((1R,2S)-2-phenylcyclopropane)thiazole-4-one,
5-(4-ethoxyquinoline-6-elmet-(Z)-alidin)-2-((1R,2S)-2-phenylcyclopropane)thiazole-4-one,
5-[1-(4-ethoxyquinoline-6-yl)-meth-(Z)-ilidene]-2-[2-(4-forfinal)cyclopropylamino]thiazole-4-one,
5-[4-(2-methoxyethoxy)quinoline-6-elmet-(Z)-ridin]-2-((1R,2S)-2-phenylcyclopropane)thiazole-4-one and
5-(4-butoxyaniline-6-elmet-(Z)-alidin)-2-((1R,2S)-2-phenylcyclopropane)thiazole-4-one.

24. Connection claim 20, where R4means halogen.

25. The connection point 24, where the specified connection is a 5-(4-chlor the nolin-6-elmet-(Z)-alidin)-2-((1R,2S)-2-phenylcyclopropane)thiazole-4-one.

26. Connection claim 20, where
R4means,
and R15, R16and m have the meanings indicated in claim 1.

27. Connection p, where the specified connection is a 5-(4-diethylaminophenol-6-elmet-(Z)-alidin)-2-((1R,2S)-2-phenylcyclopropane)thiazole-4-one.

28. Connection claim 20, where R4means-S-R12.

29. Connection p, where the specified connection is a 5-(4-ethylsulfanyl-6-elmet-(Z)-alidin)-2-((1R,2S)-2-phenylcyclopropane)thiazole-4-one.

30. Connection claim 20, where
R4means,
and R17, R18, k and w have the meanings indicated in claim 1,

31. Connection item 30, where k is 1.

32. Connection p, where the specified connection selected from the group including
5-(4-cyclohexylmethoxy-6-elmet-(Z)-alidin)-2-((1R,2S)-2-phenylcyclopropane)thiazole-4-one and
5-(4-phenoxyphenol-6-elmet-(Z)-alidin)-2-((1R,2S)-2-phenylcyclopropane)thiazole-4-one.

33. Connection item 30, where k is equal to 0.

34. Connection p, where the specified connection is a 5-(4-(morpholine-4-rhinolin-6-elmet-(Z)-alidin)-2-((1R,2S)-2-phenylcyclopropane)thiazole-4-one.

35. The connection 17, where X' means (ness.)alkylen.

36. Connection p, wheremeans phenyl.

37. Connection p, where R4means -(O)k(CH2CH2 y-R10and R10, k and y have the meanings indicated in claim 1.

38. The connection clause 37, where the specified connection selected from the group including
2-[2-(2-ethoxyphenyl)ethylamino]-5-[1-(4-ethoxyquinoline-6-yl)-meth-(Z)-ilidene]thiazole-4-one,
2-(2-chlorobenzylamino)-5-(4-ethoxyquinoline-6-elmet-(Z)-alidin)thiazole-4-one and
2-(2-chloro-6-methylbenzylamino)-5-(4-ethoxyquinoline-6-elmet-(Z)-alidin)thiazole-4-one.

39. Connection p, where R4means-O-(CH2)tR14, a R14and t have the meanings indicated in claim 1.

40. Connection § 39, where the specified connection selected from the group including
2-[2-(3-forfinal)ethylamino]-5-[4-(2,2,2-triptoreline)quinoline-6-elmet-(Z)-ridin]thiazole-4-one, and
5-[4-(2-dimethylaminoethoxy)quinoline-6-elmet-(Z)-ridin]-2-[2-(3-forfinal)ethylamino]thiazole-4-one.

41. The connection 17, where R4means-S-R12and R12matter specified in claim 1.

42. The connection at paragraph 41, where the specified connection is a 5-(4-ethylsulfanyl-6-elmet-(Z)-alidin)-2-[2-(3-forfinal)ethylamino]thiazole-4-one.

43. Connection p, where ® denotes heteroaromatic cycle.

44. Connection p.43, where R4means -(O)k(CH2CH2O)y-R10and R10, k and y have the meanings indicated in claim 1.

45. Connection item 44, where the specified connection selected from the group including
5-(4-methoxyquinoline-6-elmet-(Z)-ylides is h)-2-[(thiophene-2-ylmethyl)amino]thiazol-4-one,
5-(4-ethoxyquinoline-6-elmet-(Z)-alidin)-2-[(thiophene-2-ylmethyl)amino]thiazol-4-one,
5-[4-(2-methoxyethoxy)quinoline-6-elmet-(Z)-ridin]-2-[(thiophene-2-ylmethyl)amino]thiazol-4-one and
2-[(3-methylthiophene-2-ylmethyl)amino]-5-(4-ethoxyquinoline-6-elmet-(Z)-alidin)thiazole-4-one.

46. Connection p.43, where R4means halogen.

47. Connection p.46, where the specified connection is a 5-(4-chlorhydrin-6-elmet-(Z)-alidin)-2-[(thiophene-2-ylmethyl)amino]thiazol-4-one.

48. Connection p.43, where
R4means,
and R17, R18, k and w have the meanings indicated in claim 1.

49. Connection p, where the specified connection selected from the group including
5-(4-phenoxyphenol-6-elmet-(Z)-alidin)-2-[(thiophene-2-ylmethyl)amino]thiazol-4-one,
5-(4-cyclohexylmethoxy-6-elmet-(Z)-alidin)-2-[(thiophene-2-ylmethyl)amino]thiazol-4-one and
5-(4-(morpholine-4-rhinolin-6-elmet-(Z)-alidin)-2-[(thiophene-2-ylmethyl)amino]thiazol-4-one.

50. Connection p, where X' is hydroxy(ness.)alkylen.

51. Connection item 50, where R4means -(O)k(CH2CH2O)y-R10and R10, k and y have the meanings indicated in claim 1.

52. Connection § 51, where the specified connection selected from the group including
5-(4-ethoxyquinoline-6-elmet-(Z)-alidin)-2-(2-hydroxy-1-(R)-phenylethylamine)thiazole-4-one,
2-(2-hydroxy-1-(R)-phenylethylamine)-5-(4-methoxyquinoline-6-elmet-(Z)-is lidin)thiazole-4-one and
5-[4-(2-methoxyethoxy)quinoline-6-elmet-(Z)-ridin]-2-(2-hydroxy-1-(R)-phenylethylamine)thiazole-4-one.

53. Connection item 50, where
R4means,
a R17, R18, k and w have the meanings indicated in claim 1.

54. Connection item 53, where the specified connection selected from the group including
5-(4-cyclohexylmethoxy-6-elmet-(R)-alidin)-2-(2-hydroxy-1-(R)-phenylethylamine)thiazole-4-one and
5-(4-(morpholine-4-rhinolin-6-elmet-(R)-alidin)-2-(2-hydroxy-1-(R)-phenylethylamine)thiazole-4-one.

55. Connection p, where X' denotes dihalogen(ness.)alkylen.

56. Connection § 55, where R1' means heteroaromatic cycle.

57. Connection p, where R4means -(O)k(CH2CH2O)y-R10and R10, k and y have the meanings indicated in claim 1.

58. Connection § 57, where the connection specified is a
methanesulfonate of 2-(2,2-debtor-2-pyridine-2-ylethylamine)-5-[1-(4-ethoxyquinoline-6-yl)-meth-(Z)-ilidene]thiazole-4-it.

59. The compound of formula I according to claim 1, where
R1means(X)-R2;
X means C1-C6alkylene, hydroxy(C1-C6)alkylen or debtor(C1-C6)alkylen;
R2means thiophenyl, unsubstituted or monosubstituted C1-C6alkyl group; pyrazinyl, unsubstituted or mono - or disonesty C1-C6alkyl group; phenyl, which zamesheny or mono-, di - or tizamidine Deputy independently selected from the group comprising halogen, hydroxy, -O-(C1-C6)alkyl or C1-C6alkyl; and pyridinyl;
R4means halogen, morpholino, phenoxy or-O-(C1-C6)alkyl, where the alkyl is unsubstituted or mono-, di - or trisemester Deputy independently selected from the group comprising cyclohexyl, methoxy, trifluoromethyl, -N(C1-C6alkyl)2,
and its pharmaceutically acceptable salts.

60. The compound of formula I according to claim 1, where
R1means hydrogen;
R4means phenoxy; piperidines, unsubstituted or N-substituted groups,- C(O)-CH3, -S-(C1-C6)alkyl or-O-(C1-C6)alkyl, where the alkyl is unsubstituted or monosubstituted by a Deputy selected from the group comprising 4-forfinal, 3-methoxyphenyl, trifluoromethyl or methoxy,
and its pharmaceutically acceptable salts.

61. The compound of formula I according to claim 1, where
R1means(X)-R2;
X means cyclopropyl;
R2means phenyl or 4-forfinal;
R4means halogen, morpholino, phenoxy, -S-(C1-C6)alkyl, N-(C1-C6alkyl)2, -O-(C1-C6)alkyl, where the alkyl is unsubstituted or mono - or disamament Deputy independently selected groups including methoxy, cyclohexyl is;
and its pharmaceutically acceptable salts.

62. The compound of formula I according to claim 1, having inhibitory activity against CDK1 kinase.

63. Pharmaceutical composition having anti-proliferative activity containing one or more compounds of the formula I according to claim 1 in a mixture with pharmaceutically acceptable adjuvants.

64. The compound of formula I according to claim 1 for obtaining a drug intended for treatment of diseases associated with the development of impaired cell cycle.

65. The compound of formula I according to claim 1 for obtaining a drug intended for the treatment of cancer, particularly solid tumors.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I): wherein dashed lines present single or double bonds, and the values of radicals R1, R2, R3, R4 are described in cl. 1 of the patent claim. Besides the invention refers to application and a based pharmaceutical composition for prevention and treatment of neurodegenerative diseases and other diseases wherein cell dystrophy and/or cell loss (apoptosis) caused by free radicals act the main part.

EFFECT: production of new compounds and the based pharmaceutical composition which can find application in medicine for prevention and treatment of neurodegenerative diseases.

6 cl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of general formula I and to their pharmaceutically acceptable acid addition salts. The compounds of the present invention exhibit the properties of glycine carrier 1 (GlyT-1) inhibitors. In formula I , R1 represents -OR1', -SR1' or morpholinyl; R1' represents lower alkyl, halogen-substituted lower alkyl, or represents -(CH2)n-lower cycloalkyl; R2 represents -S(O)2-lower alkyl, -S(O)2NH-lower alkyl, NO2 or CN; X1 represents CR3 or N; X2 represents CR3' or N; R3/R3' independently represent hydrogen, halogen, lower alkyl, CN, NO2, -S(O)2-phenyl, -S(O)2-lower alkyl, -S(O)2-pyridine-2, 3 or 4-yl, phenyl optionally substituted with one or two substitutes specified from the group consisting of NO2 or halogen, or represent halogen-substituted lower alkyl, or represent -C(O)-lower alkyl; n has a value of 0, 1 or 2. The invention also concerns a drug containing one or more compounds of the invention and pharmaceutically appropriate excipients.

EFFECT: preparation of the compounds exhibiting the properties of glycine carrier inhibitors.

20 cl, 1 tbl, 133 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) , where R1 is selected from group, including: phenyl, unsubstituted or mono-, di- or tri-substituted independently with lower alkyl, lower alkoxy group, halogen or lower halogenalkyl; naphtyl; tetrahydronaphtyl; C3-7cycloalkyl; -(CHR3)m-phenyl, where m stands for 1, 2, or 3; and phenyl is unsubstituted or mono-, di- or tri-substituted with lower alkoxy group, and where R3 is independently selected from hydrogen and lower alkyl; -(CH2)n-heteroaryl, where n stands for 1, 2 or 3; term "heteroaryl" relates to aromatic 5- or 6- member ring or bicyclic 9-member aromatic groups, which can include 1, 2 or 3 atoms, selected from nitrogen and/or sulphur; -(CH2)n-heteroaryl, where n stands for 1, 2 or 3; term "heteroaryl" relates to aromatic 5- or 6- member ring or bicyclic 9-member aromatic groups, which can include 1, 2 or 3 atoms, selected from nitrogen and/or sulphur, and heteroaryl is mono-, di- or tri-substituted independently with lower alkoxy group; and R2 is selected from group including: n-butyl; phenyl, unsubstituted or mono-, di- or tri-substituted independently with lower alkyl, halogen or lower alkoxy group; heteroaryl, where term "heteroaryl" relates to aromatic 5-member ring, which can include 1, 2 or 3 atoms, selected from nitrogen and/or sulphur; unsubstituted or mono-, di- or tri-substituted independently with lower alkoxy group; -C(O)-NR4R5; where R4 and R5 stand for lower alkyl or together with nitrogen atom, to which they are bound, form 5-member heterocycle, which can additionally contain heteroatom, selected from N or S, and to their pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds, able to inhibit DPP-IV.

13 cl, 43 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I)

, pharmaceutical compositions based on the said compounds, as well as methods of using said compounds in preparing medicinal agents.

EFFECT: obtaining compounds and a composition which can inhibit phosphatase cdc25, particularly phosphatase cdc25-C and can be particularly used for treating cancer.

12 cl, 56 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I and their pharmaceutically acceptable salts. The disclosed compounds have inhibitory effect on CDK1 kinase. In formula I , R1 is hydrogen or R2-(X)n-; X is a lower alkylene or cyclic lower alkylene; R2 denotes ; where denotes phenyl; cycloalkyl containing 3-6 carbon atoms; 4-6-member heterocycloalkyl ring having 3-5 carbon atoms and 1-2 oxygen atoms; R5, R6 and R7 are independently selected from a group containing hydrogen or halide; R4 is hydrogen or -(O)k(CH2CH2O)y-R10; R19 is hydrogen; R20 is hydrogen or -C(O)-R11; R10 and R11 is a lower alkyl; n and k are equal to 0 or 1; y is an integer from 0 to 3.

EFFECT: obtaining a pharmaceutical composition with inhibitory effect on CDK1 kinase, containing one or more of the disclosed compounds.

15 cl, 10 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to compounds of formula I or to pharmaceutically acceptable salts thereof, where Ar is imidazole or pyrazole, where the said Ar can be substituted with substitute(s) selected from a group consisting of a C1-C6 alkyl group, a phenyl group and a halogen atom, each of Y1, Y2 and Y3 is a carbon ot nitrogen atom, A is an oxygen atom, a sulphur atom or a group of formula -SO2-, R1 is a hydrogen atom, a C1-C6 alkyl group which can be substituted with one phenyl group (where the said phenyl group can be substituted with one substitute selected from a group consisting of a halogen atom and a C1-C6 alkyl group), or a phenyl group, R2 is a C1-C6 alkyl group, R3 is (i) a C1-C18 alkyl group, (ii) C2-C8 alkenyl group, (iii) C2-C8 alkynyl group, (iv) C3-C8 cycloalkyl group, (v) C1-C6 alkyl group substituted with 1-3 substitutes selected from a group given in paragraph 1 of the formula of invention, or (vi) a phenyl group, a naphthyl group, a pyrazolyl group, a pyridyl group, an indolyl group, a quinolinyl group or an isoquinolinyl group, where each of the said groups can be substituted with 1-3 substitutes selected from a group given in paragraph 1, R4 is a hydrogen atom or a C1-C6 alkyl group, and R5 is (i) C1-C10 alkyl group, (ii) C1-C10 alkyl group which is substituted with one or two substitutes selected from a group given in paragraph 1, (iii) C2-C8 alkenyl group which can be substituted with a phenyl group, or (iv) phenyl group, naphthyl group, thienyl group, pyrrolyl group, pyrazolyl group, pyridyl group, furanyl group, benzothienyl group, isoquinolinyl group, isoxazolyl group, thiazolyl group, benzothiadiazolyl group, benzoxadiazolyl group, phenyl group, condensed with a 5-7-member saturated hydrocarbon ring which can contain one or two oxygen atoms as ring members, uracyl group or tetrahydroisoquinolinyl group, where each of the said groups can be substituted with 1-5 substitutes selected from a group given in paragraph 1, provided that when Ar is a group of formula 5, which can be substituted with a C1-C6 alkyl group, R5 is not a C1-C10 alkyl group, and the formula (I) compound is not 5-(3,5-dichlorophenylthio)-4-isopropyl-2-methane-sulfonylaminomethyl-1-methyl-1H-imidazole or 5-(3,5-dichlorophenylthio)-4-isopropyl-1-methyl-2-p-toluene-sulfonylaminomethyl-1H-imidazole. The invention also relates to a pharmaceutical composition based on the formula I compound and to formula II compounds, radicals of which are defined in the formula of invention.

EFFECT: obtaining novel compounds with inhibitory effect on the bond between S1P and its Edg-1 (SIP1) receptor.

32 cl, 43 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel benzene derivatives of general formula (I) or salts thereof: [Chem. 12]

(Symbols in the given formula have the following values X1:-NR12-C(=O)- or -C(=O)-NR12-, X2 : -NR13 -C(=O)-, Ring A is a 6-member ring, if necessary having 1 or 2 double bonds and if necessary having 1-3 heteroatoms selected from N, O, Ring B is a benzene ring or a 6-member heteroaryl ring having 1-3 heteroatoms selected from N, R is a hydrogen atom or a residue of β-D- glucopyranoside uronic acid; R1-R8 are identical or different and each denotes a hydrogen atom, a halogen atom, -O-(lower alkyl), R9-R11 are identical or different and each denotes a hydrogen atom, lower alkyl, -O-(lower alkyl), -(CH2)n-N(lower alkyl)2, -(CH2)n-NH(lower alkyl), -(CH2)n-N(lower alkyl) (if necessary substituted with -C=O; a 6-member heterocycle having 1-3 heteroatoms selected from N, S, O) -(CH2)n-(C=O)-N(lower alkyl)2, -(CH2)n-(C-O)-N(lower alkyl) (if necessary substituted with -C=O, alkyl, a 6-member heterocycle having 1-3 heteroatoms selected from N) -(CH2)n- if necessary substituted with alkyl, -COCH3, -SO2CH3, -COOCH3, -C=O, CF3, -OCH3, OH, halogen; 5-7-member heterocycle having 1-3 heteroatoms selected from N, S, O), -(CH2)n-O- (if necessary substituted with alkyl; 6-member heterocycle having 1-3 heteroatoms selected from N), n is an integer from 0 to 3, R12 and R13 denote a hydrogen atom, provided that in R1-R11, when two lower alkyls are bonded to a nitrogen atom, they can together form a 3-8-member nitrogen-containing heterocycle.) The invention also relates to benzene derivatives of general formula (II), to a pharmaceutical composition, as well as to use of the said compounds.

EFFECT: obtaining novel biologically active compounds which are active as inhibitors of activated blood-coagulation factor X.

16 cl, 365 ex, 42 tbl

FIELD: chemistry.

SUBSTANCE: formula (I) compounds, radicals of which are defined in the formula of invention, are described. A pharmaceutical composition containing formula (I) compounds is also described.

EFFECT: obtaining compounds which have inhibitory activity on protein kinase MEK1/2 and are meant for use as a therapeutically active substance which is useful for treating MEK1/2 mediated diseases.

13 cl, 18 ex

FIELD: chemistry.

SUBSTANCE: benzamide derivatives are presented by the formula [1] or its salt, where Z is -O-, -NR5-, -S-, -SO-; 1 is 0 or 1; m is 0 or 1; R1 is hydrogen atom, C1-6-alkyl group, R2 is hydrogen atom, hydroxylic group, C1-6- alkyl group, carboxyl group, C1-6-alkoxycarbonyl group or -CONR10R11, or R2 and R1 together form =O; R3 is hydrogen atom or C1-6-alkyl group; R4 is hydrogen atom or halogen atom; V is direct bond or -(CR21R22)n-; P1 and P2 rings are the same or different, and each is aromatic or saturated carbocyclic group, or 5-10-member saturated or unsaturated heterocyclic group containing 1-3 heteroatoms selected out of N, O, S.

EFFECT: obtainment of compound with excellent inhibition effect on vanilloid receptor type 1 activity, efficiency in treatment of diseases involving vanilloid receptor type 1 activity.

17 cl, 56 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I , where R1 is selected from a group comprising hydrogen, lower alkyl, cycloalkyl or lower cycloalkylalkyl, where the cycloalkyl ring can be substituted with lower alkoxyalkyl, lower alkoxyalkyl, and tetrahydropyranyl and lower heterocyclylalkyl, where the heterocyclic ring is oxetanyl or tetrahydropyranyl, which can be substituted with a halogen; R2 is selected from a group comprising hydrogen, lower alkyl, cycloalkyl or lower cycloalkylalkyl, where the cycloalkyl ring can be substituted with lower alkoxyalkyl, lower alkoxyalkyl, and tetrahydropyranyl or lower heterocyclylalkyl, where the heterocyclic ring is oxetanyl or tetrahydropyranyl which can be substituted with a halogen; or R1 and R2 together with the nitrogen atom to which they are bonded form a 4-, 5- or 6-member saturated or partially unsaturated heterocyclic ring which optionally contains the same heteroatom selected from oxygen or sulphur, where the said saturated or partially heterocyclic ring is unsubstituted or substituted with one or two groups independently selected from a group consisting of lower alkyl, halogen, halogenalkyl, cyano group, hydroxy group, lower hydroxyalkyl, lower alkoxy group, oxo group; A is selected from , and , where m equals 0 or 1; R3 is a lower alkyl; n equals 0; R4 is a lower alkyl; p equals 1; q equals 0, 1 or 2; R5 is hydrogen; and their pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition based on formula I compounds.

EFFECT: new quinoline derivatives are obtained, which have antagonistic effect on histamine 3 receptors (H3 receptors).

18 cl, 4 tbl, 86 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of the formula (I) where: A is an aryl or a 5-member heteroaryl containing a S heteroatom, possibly substituted with one or two substitutes selected from a group consisting of halogen, C1-6-alkyl or C1-6-alkoxy; n equals 1 or 2; p equals 1, 2, 3 or 4; q equals 1; r equals 0 or 1; R1 is C2-6-alkynyl substituted with aryl, or C1-6-alkyl possibly substituted with one-five substitutes selected from a group consisting of halogen, hydroxy, C1-6-alkyl, C1-6-halogenoalkyl, -OC(O)-C1-6-alkyl, C3-10-cycloalkyl, C1-6-alkoxy, possibly substituted with one, two or three halogens or aryl, aryl which is possibly substituted with a halogen or C1-6-alkoxy, 5-9-member heteroaryl, one, two or three ring atoms of which are heteroatoms selected from N or O, and the rest of the ring atoms are C atoms, possibly substituted with C1-6-alkyl, and phenoxyl, or is C1-6-alkoxy, or is C3-10-cycloalkyl which is possibly substituted with one or more Ra, or is a 5- or 6-member heterocycloalkyl containing one, two or three heteroatoms selected from nitrogen, oxygen or sulphur, possibly substituted with one or more Ra, or is an aryl possibly substituted with one or more Ra, or is a 5-10-member heteraryl, one, two or three ring atoms of which are heteroatoms selected from N, O and S, and the rest of the ring atoms are C atoms, possibly substituted with one or more Ra, or is -NRbRc, where Rb is H or C1-6-alkyl and where Rc is H, C1-6-alkyl or aryl, possibly substituted with one or more Ra, where Ra is selected from: halogen, cyano, oxo, hydroxy, halogenobenzenesulfonyl, C1-6-alkyl, possibly substituted with one, two or three substitutes selected from a group consisting of 5-10-member heterocycloalkyl and aryl, which is possibly substituted with halogen or C1-6-alkoxy, C1-6-halogenoalkyl, C1-6-halogenoalkoxy, C1-6-alkoxy, possibly substituted with aryl or 5-10-member heteroaryl, one, two or three ring atoms of which are heteroatoms selected from N, O and S, and the rest of the ring atoms are C atoms, which is possibly substituted with C1-6-alkyl, aryloxy, -NH(CO)-C1-6-alkyl, -O(CO)-C1-6-alkyl, C1-6-alkylsulfonyl, aryl, 4-6-member heterocycloalkyl containing one, two or three heteroatoms selected from nitrogen, oxygen or sulphur, possibly substituted with hydroxy, C1-6-alkyl or oxo, 5-10-member heteroaryl,one, two or three ring atoms of which are heteroatoms selected from N and O, and the rest of the ring atoms are C atoms, possibly substituted with C1-6-alkyl or oxo, and di(C1-6)alkylamino; R2 is H, OH, C1-6-alkyl or halogen; as well as their pharmaceutically acceptable salts. The invention also relates to medicine and to use of the compounds in any of paragraphs 1-24.

EFFECT: obtaining novel biologically active compounds with affinity to dopamine D3 receptor and to serotonin 5- HT2a receptor.

27 cl, 86 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I and their pharmaceutically acceptable salts. The disclosed compounds have inhibitory effect on CDK1 kinase. In formula I , R1 is hydrogen or R2-(X)n-; X is a lower alkylene or cyclic lower alkylene; R2 denotes ; where denotes phenyl; cycloalkyl containing 3-6 carbon atoms; 4-6-member heterocycloalkyl ring having 3-5 carbon atoms and 1-2 oxygen atoms; R5, R6 and R7 are independently selected from a group containing hydrogen or halide; R4 is hydrogen or -(O)k(CH2CH2O)y-R10; R19 is hydrogen; R20 is hydrogen or -C(O)-R11; R10 and R11 is a lower alkyl; n and k are equal to 0 or 1; y is an integer from 0 to 3.

EFFECT: obtaining a pharmaceutical composition with inhibitory effect on CDK1 kinase, containing one or more of the disclosed compounds.

15 cl, 10 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to cyclic derivatives of aminobenzoic acid and to their pharmaceutically acceptable salts of general formula , in which ring Ar is a phenyl group, a 5-member aromatic heterocyclic group containing 1-2 heteroatoms selected from nitrogen, sulphur and oxygen, or a benzothiazolyl group; where the said groups can have 1-2 substitutes selected from a group comprising lower alkyl; a phenyl group; a phenyl group substituted with 1-2 halogens; a phenyl group substituted with a lower alkoxy group; a phenyl group substituted with a halogen-substituted lower alkyl group; a phenoxy group substituted with a halogen; a halogen; Z is an oxygen atom or -(CH2)-n (where n equals 0, 1 or 2); Y is C1-C4 alkylene, C2-C4 alkenylene or general formula (2) -T-A-U- (2) in which T is a single bond, C1-C4 alkylene or C2-C4 alkenylene; U is single bond, C1-C4 alkylene; values of the rest of radicals are given in the formula of invention.

EFFECT: obtaining a PPARα, agonist which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid, and an agent which reduces the level of lipids which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid.

12 cl, 16 tbl, 184 ex

FIELD: chemistry.

SUBSTANCE: agent is a 6-bromo-5-methoxy-indole-3-carboxylic acid derivative of general formula (I) , where B is a N(R)2 group, where both R groups together with the nitrogen atom to which they are bonded form a 5-6-member heterocyclic ring containing 1-2 heteroatoms selected from nitrogen, such as pyrrolidine, piperidine, piperazine or morpholine, where each of the said heterocyclic rings can be substituted with C1-4alkyl, phenyl, benzyl, phenethyl, carbonylamino, -COOC1-4alkyl group or -COOC1-4alkyl group and phenyl, which can also be substituted or have substitutes selected from halogen, C1-4alkyl, C1-4alkoxy, and alkyl in the said groups can be linear or branched; R1 is C1-4alkyl, phenyl, possibly substituted with C1-4alkyl or C1-4alkoxy, halogen atoms; R2 is -S-phenyl, -S-benzyl, -O-phenyl, where in each of the said groups, the phenyl ring is possibly substituted with C1-4alkyl, C1-4alkoxy, halogen atoms, or R2 denotes a -N(R)2 group, or pharmaceutically acceptable salts thereof.

EFFECT: agent has antiviral activity towards influenza A virus.

3 dwg, 2 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) and to their pharmaceutically acceptable salts, optical isomers or their mixture as glucokinase activators. In general formula (I) where R1 is C3-8-cycloalkyl, C3-8-cycloalkenyl, a 6-member heterocyclyl with 1 nitrogen atom, condensed phenyl-C3-8-cycloalkyl, each of which is possibly substituted with one or two substitutes R3, R4, R5 and R6; R2 is C3-8-cycloalkyl, a 5-6-member heterocyclyl with 1-2 heteroatoms selected from N, O, or S, each of which can be substituted with one or two substitutes R30, R31, R32 and R33, and R3, R4, R5, R6, R30, R31, R32 and R33 are independently selected from a group consisting of halogen, hydroxy, oxo, -CF3; or -NR10R12; or C1-6-alkyl, phenyl, C1-6-alkoxy, C1-6-alkyl-C(O)-O-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; or -C(O)-R27, -S(O)2-R27; or two substitutes selected from R3, R4, R5 and R6 or R30, R31, R32 and R33, bonded to the same atom or to neighbouring atoms, together form a -O-(CH2)2-O- radical; R10 and R11 independently represent hydrogen, C1-6-alkyl, -C(O)-C1-6-alkyl, -C(O)-O- C1-6-alkyl, -S(O)2- C1-6-alkyl; R27 is C1-6-alkyl, C1-6-alkoxy, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, phenyl, phenyl-C1-6-alkyl, a 5-6-member heteroaryl with 1-2 heteroatoms selected from N or S, a 6-member heteroaryl-C1-6-alkyl with 1 nitrogen atom, a 6-member heterocyclyl-C1-6-alkyl with 1-2 heteroatoms selected from N or O, R10R11-N- C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; R12 is a halogen, CF3, C1-6-alkoxy, -NR10R11; A is a 5-9-member heteroaryl with 1-3 heteroatoms selected from N, O or S, which is possibly substituted with one or two substitutes independently selected from R7, R8 and R9; R7, R8 and R9 are independently selected from halogen, cyano, -CF3; or C1-6-alkyl, C2-6-alkenyl, C1-6-alkoxy, C1-6-alkylthio, -C(O)-O-C1-6-alkyl, formyl, - C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-O-C(O)-C1-6-alkyl or hydroxy-C1-6-alkyl, each of which is possibly substituted with a substitute independently selected from R16; or phenyl, 5-member heteroaryl-C1-6-alkylthio with 2-4 nitrogen atoms, phenylthio, 5-6-member heteroarylthio with 1-2 nitrogen atoms, each of which is possibly substituted on the aryl or heteroaryl part with one or two substitutes independently selected from R17; or C3-8-cycloalkyl; or a 6-member heterocyclyl with 2 nitrogen atoms, 5-7-member heterocyclyl-C1-6-alkylthio with 1-2 heteroatoms selected from N or O, each of which is possibly substituted with one substitute independently selected from R16; or C1-6-alkyl-NR19R20, -S(O)2-R21 or -S(O)2-NR19R20; or -C(O)NR22R23; R16, R17 and R18 independently represent C1-6-alkyl, carboxy, -C(O)-O-C1-6-alkyl, -NR19R20, -C(O)NR19R20; R19 and R20 independently represent hydrogen, C1-6-alkyl, phenyl, 5-member heteroaryl with 2 heteroatoms selected from N or S, 6-member heterocyclyl with 1 nitrogen atom, -C(O)-O-C1-6-alkyl or -S(O)2-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R24; or R19 and R20 together with a nitrogen atom to which they are bonded form a 5-7-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring possibly contains one additional heteroatom selected from nitrogen, oxygen and sulphur, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R21 is selected from C2-6-alkenyl; or R22 and R23 are independently selected from hydrogen, -C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-S(O)2-C1-6-alkyl, C3-8-cycloalkyl; or R22 and R23 together with a nitrogen atom to which they are bonded form a 6-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R24 is oxo, C1-6-alkyl, carboxy- C1-6-alkyl, a 6-member heterocyclyl with 1 nitrogen atom, -NH-S(O)2R28 or -S(O)2R28, where each cyclic group is possibly substituted with one substitute independently selected from R29; R28 is C1-6-alkyl, -C1-6-alkyl-C(O)-O- C1-6-alkyl or -N(CH3)2; R29 is C1-6-alkyl.

EFFECT: obtaining compounds which can be used for treating and preventing diseases mediated by low glucokinase activity.

21 cl, 1 dwg, 608 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound N-(1-{(3R)-3-(3,5-difluorophenyl)-3-[1-(methylsulfonyl) piperidin-4-yl]propyl}piperidin-4-yl)-N-ethyl-2-[4- (methylsufonyl)phenyl]acetamide or its pharmaceutically acceptable salts. The invention also relates to a method for synthesis of the compound in paragraph 1, as well as to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with activity towards CCR5 (chemokine receptor 5).

6 cl, 6 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention concerns derivatives of thiazolidine-4-one of general formula (I) and general formula (II), to their isomers and pharmaceutically acceptable salts which can be used as a medical product with immunosuppressive activity. In formulae (I) and (II), R1 and R14 independently represent lower alkyl, lower alkenyl; cycloalkyl; 5,6,7,8-tetrahydronaphth-1-yl; phenyl group or phenyl group independently mono- or disubstituted with lower alkyl, halogen, lower alkoxy or group -CF3; R2 and R15 independently represent lower alkyl; allyl; cyclopropyl; or di- lower alkylamino; R3 represents -NR5R6 or -O-CR7R8-CR9R10-(CR11R12)n-O-R13; R23 represents hydrogen; hydroxycarbonyl-lower alkyl or 1-glyceryl. Values of the other radicals are specified in the patent claim. The invention also concerns application of one or more compounds of general formula (I) or (II) for preparation of a medical product with immunosuppressive activity.

EFFECT: agent exhibits improved efficiency.

24 cl, 1 tbl, 157 ex

FIELD: medicine.

SUBSTANCE: in formula (1), R1 is di-C1-6alkoxyphenyl group; A is one of the following groups (i)-(vi); (i) -CO-B-, where B is C1-6alkylene group; (ii) -CO-Ba-, where Ba is C2-6alkenylene group; (iii) -CH(OH)-B-; (iv) -COCH((C)OOR3)-Bb-, where R3 is C1-6alkyl group and Bb is C1-6alkylene group. Values of the other radicals are specified in the patent claim. Invention also concerns the pharmaceutical composition exhibiting properties of a phosphodiesterase PDE4 inhibitor containing the compound under the invention; the phosphodiesterase 4 inhibitor containing as an active component the compound of the invention; preventive or therapeutic preparation for atopic dermatitis containing as an active component the compound of the invention.

EFFECT: higher effectiveness of application of the compound.

8 cl, 24 tbl, 262 ex

FIELD: medicine.

SUBSTANCE: invention is related to new compounds of common formula IC1: , where A represents cyano; B represents hydrogen; R1, R2, R3 and R4 independently represent hydrogen; alkyl; halogen or nitro; R5 and R6 independently represent hydrogen; alkyl; cycloalkyl; cycloalkylalkyl; heteroaryl; heteroarylalkyl; alkenyl; carboxyalkyl; cyanoalkyl; diphenylalkyl; aryl, arylalkoxyaryl, arylalkyl, arylalkylaryl, arylcarbonylaryl or aryloxyaryl, or R5 and R6, together with atom of nitrogen, to which they are connected, create heterocyclic ring system; or to salts of such compound; at the same time "heteroaryl" used separately or in combination, is related to mono-, bi- or tricyclic aromatic ring system, which contains up to 14 atoms included in ring, in which at least one ring contains at least one heteroatom, independently chosen from nitrogen, oxygen or sulfur, besides specified heteroaryl group may be unsubstituted or substituted with one to three substituents, independently selected from alkyl and alkoxy; "diphenylalkyl" is related to alkyl group, where each of two atoms of hydrogen is substituted with unsubstituted phenyl group; "aryl" is related to carbocyclic group, selected from group, which consists of phenyl, biphenyl, 1,2,3,4-tetrahydronaphthyl, naphthyl, antryl, phenantryl, fluorenyl, indanyl, 2,3-dihydrobenzo[1,4]dioxynyl and benzo[1,3]dioxolyl group, besides specified aryl group may be unnecessarily substituted with functional groups in number from one to three, which are separately and independently selected from alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, cyano, halogen, halogenlkoxy, halogenalkyl and nitro groups, where in certain specific cases, if aryl group represents condensed system from several rings, in which not all the rings are aromatic, one of carbon atoms of which is not included into aromatic ring may be in oxidised condition, and according fragment of ring -CH2- will be substituted by fragment-C(O); "arylalkoxy", used separately or in combination, is related to aryl group, which is connected to initial molecular fragment via alkoxygroup, where aryl group is unsubstituted; "arylalkyl", used separately or in combination, is related to aryl group, which is connected to initial molecular fragment via alkyl group, where aryl group may be unsubstituted or substituted with 1-3 substituents, independently selected from group, which consists of halogen; "aryloxy", used separately or in combination, is related to aryl group, which is connected to initial molecular fragment via oxygen bridge, where aryl group may be unsubstituted or substituted with 1-3 substituents, independently selected from group, which consists of halogen; "arylcarbonyl", used separately or in combination, is related to aryl group, which is connected to initial molecular fragment via carbonyl group, where aryl group is unsubstituted; "heterocyclic ring system", used separately or in combination, is related to monocyclic, bicyclic or polycyclic ring system, which contains up to 15 atoms included into ring, at least one of which represents heteroatom, independently selected from nitrogen, oxygen or sulfur, besides specified ring system may be saturated, partially unsaturated, unsaturated or aromatic, where specified heterocyclic fragment may be unnecessarily substituted with one or more substituents, every of which separately and independently is selected from group made of halogen and halogenalkyl, excluding the following compounds: {3-[(E)-2-cyano-2-(4-fluorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; [3-((E)-2-cyano-2-m-tolylcarbamoylvinyl)indole-1-yl]acetic acid; (3-[(E)-2-(3-bromophenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; [3-((E)-2-cyano-2-phenylcarbamoylvinyl)indole-1-yl]acetic acid; [3-((E)-2-benzylcarbamoyl-2-cyanovinyl)indole-1-yl]acetic acid; [3-((E)-2-cyano-2-o-tolylcarbamoylvinyl)indole-1-yl]acetic acid; [3-((E)-2-cyano-2-t-tolylcarbamoylvinyl)indole-1-yl]acetic acid; (3-[(E)-2-(4-bromophenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(4-ethylphenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(4-methoxyphenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2~cyano-2-(4- ethoxyphenylcarbamoyl)vinyl]indole-1-yl}acetic acid; [3-((E)-2-cyano-2-isopropylcarbamoylvinyl)indole-1-yl]acetic acid; {3-[(E)-2-cyano-2-(3-etoxyphenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-3-[[2-(1H-indole-3-yl)ethyl]amino]-3-oxo-1-propenyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(4-chlorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-3-(4-methyl-piperidine-1-yl)-3-oxopropenyl]indole-1-yl}acetic acid; {3-[(E)-2-(3-chloro-4-methylphenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(3-phenylpropylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(2,3-dichlorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-(5-chloro-2-methylphenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(4-methoxybenzylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(2-fluorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; and {3-[(E)-2-cyano-3-oxo-3-(4-phenyl-piperazine-1-yl)propenyl]indole-1-yl}acetic acid. Invention is also related to pharmaceutical composition, and also to application of compounds of clause 1.

EFFECT: production of biologically active compounds, which have activity of antagonist coupled with G-protein of chemoattractant receptor of molecules homologue released by Th2-cells.

11 cl, 156 ex, 8 tbl

FIELD: pharmacology.

SUBSTANCE: invention concerns indazol derivatives of general formulae (I) or (II) , where radicals and groups are defined as shown in cl. 1 of invention claim, and their pharmaceutically acceptable salts. Also invention claims medicine, method of medicine obtainment and application of claimed compounds in treatment and/or prevention of fatty acid metabolism derangement and glucose assimilation disorders.

EFFECT: inhibition of hormone-sensitive lipases.

13 cl, 1 tbl, 103 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, oncology, and can be used for treatment of malignant lung neoplasms in experiment. For this purpose performed is extracorporal irradiation of autoblood with red incoherent light λ=0.67 mcm dose W=3.06 J/cm2 in continuous mode with exposition duration to three minutes. After that 15-20 minutes later into said blood added is cyclophosphane in dose 40 mg/kg and the mixture is incubated for 40 minutes at T=37°C. After that it is re-infused into subclavian vein of the animal.

EFFECT: claimed method allows to reduce terms of anti-tumour treatment, increase efficiency of cyclophosphane action, reduce its toxic manifestations, increase animals' life term, increase non-specific anti-tumour resistance, activate anti stressor mechanisms.

2 tbl

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