3,4-substituted 1h-pirazole compounds and their application as cyclin-dependant kinases (cdk) and modulators of glycogen synthase kinase-3 (gsk-3)

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compounds of formula (Ia) or their pharmaceutically acceptable salts, tautomers, or N-oxides, for use in prevention or treatment of unhealthy conditions or diseases, mediated with cyclin-dependent kinase and glycogen synthase-kinase-3, such as cancerous diseases. In formula (Ia) X stands for group R1-A-NR4; A stands for link, C=O, or NRg(C=O, where R8 stands for hydrogen or C1-3 alkyl; Y stands for link or alkylene chain, made of 1, 2 or 3 atoms of carbon; R1 stands for carbocyclic or heterocyclic group, containing from 3 to 12 circular units; or saturated C1-8hydrocarbyl group, optionally substituted with one or more substituents selected from halogen (for instance, fluorine), hydroxygroups, C1.4alkoxygroups, and carbocyclic or heterocyclic groups, and where 1 or 2 atoms of hydrocarbyl group carbon may be optionally substituted with atom or group selected from O, S, NH, SO, SO2; R2 stands for hydrogen or methyl; R3 is selected from hydrogen and carbocyclic or heterocyclic groups, containing from 3 to 6 circular units; and R4 stands for hydrogen or methyl. Specified carbocyclic and heterocyclic groups are determined in formula of invention and may be optionally substituted with groups specified in invention formula. Objects of invention are also a pharmaceutical composition based on proposed compounds, their application to produce medicinal agents and methods of their application.

EFFECT: production of pharmaceutical composition based on proposed compounds for use in prevention or treatment of unhealthy conditions or diseases, mediated with cyclin-dependent kinase and glycogen synthase-kinase-3, such as cancerous diseases.

48 cl, 6 tbl, 254 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (Ia)

or its pharmaceutically acceptable salts, tautomers or N-oxides, where
X denotes a group R1-A-NR4;
And denotes a bond, C=O or NRg(C=O), where Rgdenotes hydrogen or C1-3alkyl;
Y represents a bond or alkilinity chain consisting of 1, 2 or 3 carbon atoms;
R2denotes hydrogen or methyl;
R4denotes hydrogen or methyl;
R1denotes a carbocyclic or heterocyclic group; or saturated With1-8hydrocarbonous group, optionally substituted by one or more mandated what teli, selected from fluorine, hydroxy-group, With1-4alkoxygroup and carbocyclic or heterocyclic groups, with 1 or 2 carbon atoms saturated With1-8hidrocarburos groups can be optionally substituted by an atom or group selected from O, S, NH, SO, SO2; carbocyclic or heterocyclic group selected from:
(i) substituted or unsubstituted phenyl;
(ii) a heteroaryl group selected from furanyl, indolyl, 2,3-dihydrobenzo[1.4]dioxine, pyrazolyl, pyrazolo[1.5-a]pyridinyl, oxazolyl, isoxazolyl, pyridyl, chinoline, pyrrolyl, imidazolyl and tanila;
(iii) unsubstituted or substituted monocyclic cycloalkyl groups selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; and
(iv) a 5-, 6 - and 7-membered monocyclic, heterocyclic groups selected from the research, piperidine, pyrrolidine, pyrrolidone, Piran, dihydrothiophene, dihydropyran, dihydrofuran, dihydrothiazolo, tetrahydrofuran, tetrahydrothiophene, dioxane, tetrahydropyran, imidazoline, imidazolidinone, oxazoline, thiazoline, 2-pyrazoline, pyrazolidine, piperazine,
where the carbocyclic and heterocyclic groups optionally can be substituted by 1, or 2, or 3, or 4 substituents R10selected from halogen, ceanography, nitro and monocyclic carbocycle the ical or heterocyclic groups, containing in a loop from 3 to 7 atoms; and groups of Ra-Rbwhere Radenotes a bond, O, CO, X1With(X2), With(X2X1X1With(X2X1, S, SO, SO2, NRc, SO2NRcor NRcSO2; a Rbselected from hydrogen, monocyclic carbocyclic or heterocyclic groups containing in the cycle from 3 to 7 atoms, and saturated With1-8hidrocarburos group, optionally substituted by one or more substituents selected from hydroxyl, carbonyl group, halogen, ceanography, nitro, carboxyl group, amino group, mono - or di-saturated With1-4hidrochromotherapy, monocyclic carbocyclic or heterocyclic groups containing in the cycle from 3 to 7 atoms, where one or more carbon atoms saturated With1-8hidrocarburos group may be optionally replaced by groups O, S, SO, SO2, NRCX1C(X2), With(X2X1or X1C(X2X1;
where Rcchosen from hydrogen and saturated With1-4hidrocarburos group; and
X1denotes O, S or NRcand X2means =O, =S or =NRcprovided that if the group is a substituent R10consists of, or includes carbocyclic or heterocyclic group named carbocyclic or heterocyclic group can be unsubstituted or may itself be substituted by one or more substituting groups R 10and such additional substituents R10not contain a monocyclic carbocyclic or heterocyclic groups selected but otherwise listed above in the definition of R10groups;
R3choose from a monocyclic carbocyclic and heterocyclic groups containing from 3 to 6 ring members, and carbocyclic or heterocyclic group is unsubstituted or has one or more substituents selected from
halogen;
With1-4alkoxygroup, optionally substituted by one or more substituents selected from halogen, hydroxy-group, With1-2alkoxygroup or 5 - or 6-membered saturated heterocyclic rings containing 1 or 2 heteroatoms selected from O, N and S, the heterocycle optionally substituted optionally one or more saturated With1-4hydratability groups, and in which S if it is present, is in the form of S, SO or SO2;
With1-4the alkyl, optionally substituted by one or more substituents selected from halogen, hydroxy-group, With1-4alkoxygroup, amino, C1-4alkylsulfonamides, from 3 - to 6-membered cycloalkyl groups, such as cyclopropyl, phenyl, optionally substituted by one or more substituents selected from halogen, methyl, metoxygroup and amino groups is, and 5 - and 6-membered saturated heterocycle containing 1 or 2 heteroatoms selected from O, N and S, the heterocycle optionally substituted optionally one or more saturated With1-4hydratability groups, and in which S if it is present, is in the form of S, SO or SO2;
hydroxy-group;
amino, mono-C1-4alkylamino, di-C1-4alkylamino, benzyloxycarbonylamino and C1-4alkoxycarbonylmethyl;
carboxypropyl and C1-4alkoxycarbonyl group;
With1-4alkylaminocarbonyl and C1-4alkylsulfonamides;
With1-4alkylsulfonyl group;
group 0-Hetsor NH-Hetswhere Hetsdenotes a 5 - or 6-membered saturated, a heterocycle containing 1 or 2 heteroatoms selected from O, N and S, the heterocycle optionally substituted optionally one or more saturated With1-4hydratability groups such as methyl, and in which S if it is present, is in the form of S, SO or SO2;
5 - or 6-membered saturated heterocycle containing 1 or 2 heteroatoms selected from O, N and S, the heterocycle optionally additionally substituted by one or more saturated With1-4hydratability groups such as methyl, and in which S if it is present, is in the form of S, SO or SO2;
oxoprop is, and
6-membered aryl and heteroaryl rings containing up to two ring nitrogen atoms, which are optionally substituted by one or more substituents selected from halogen, methyl and metoxygroup.

2. The compound according to claim 1, where a denotes C=O.

3. The compound according to claim 1, where R4denotes hydrogen.

4. The compound according to claim 3, where Y denotes the connection.

5. The compound according to claim 1, where R2denotes hydrogen.

6. The compound according to claim 1, where R1denotes unsubstituted or substituted, or carbocyclic, or heterocyclic group.

7. The connection according to claim 6, where unsubstituted or substituted carbocyclic or heterocyclic group is a monocycle.

8. The compound according to claim 1, in which the optional substituents R10for carbocyclic or heterocyclic groups selected from halogen, ceanography, nitro group and Ra-Rbwhere Radenotes a bond, O, CO, X1With(X2), C(X2X1X1C(X2X1, S, SO or SO2, a Rbchosen from hydrogen and saturated With1-8hidrocarburos group, optionally substituted by one or more substituents selected from a hydroxy-group, carbonyl group, halogen, ceanography, nitro, carboxypropyl and monocyclic non-aromatic carbocyclic or heterocyclic group containing from 3 to kalcevic members, and where one or more carbon atoms saturated With1-8hidrocarburos group can be optionally replaced by O, S, SO, SO2X1C(X), (X2X1or X1C(X2X1; where X1denotes O or S, and X2represents =O or =s

9. The connection of claim 8, where the above optional substituents selected from a halogen group and Ra-Rbwhere Rameans a connection or, a Rbselected from hydrogen and saturated With1-4hidrocarburos group, optionally substituted by one or more substituents selected from a hydroxy-group, halogen and a 5 - or 6-membered saturated carbocyclic or heterocyclic group.

10. The connection of claim 8, in which R1means phenyl ring having 1, 2 or 3 substituent as defined in claims 1, 8 or 9, located at positions 2, 3, 4, 5 or 6 rings.

11. The connection of claim 10, where the phenyl group
(i) monogamist in position 2 or tizamidine in positions 2 and 3, or tizamidine in positions 2 and 6 substituents selected from fluorine, chlorine and Ra-Rbwhere Radenotes O and Rbstands With1-4alkyl, or
(ii) monogamist in position 2 Deputy selected from fluorine, chlorine and C1-4alkoxygroup, optionally substituted by one or more fluorine atoms, or tizamidine in positions 2 and 5 mandated what teli, selected from fluorine, chlorine and metoxygroup.

12. The compound according to claim 1, having the formula (II):

where R1, R2, R3and Y defined in any one of claims 1 to 11.

13. The connection indicated in paragraph 12
where (a) R1denotes phenyl, optionally substituted by one or more substituents selected from fluorine; chlorine; hydroxy-group; saturated With1-3hydrocarbonsoluble and saturated C1-3hidrocarburos group; where rich With1-3gidrolabilna group optionally substituted by one or more substituents selected from a hydroxy-group, fluorine,1-2alkoxygroup, amino, mono - and di-C1-4alkylamino, saturated carbocyclic groups having 3 to 7 ring members, or a saturated heterocyclic group with 5 or 6 atoms in the ring containing up to two heteroatoms selected from O, S and N; or
(b) R1denotes unsubstituted phenyl group or 2-monosubstituted, 3-monosubstituted, 2,3-disubstituted, 2,5-disubstituted or 2,6-disubstituted phenyl group, or 2,3-dihydrobenzo[1,4]dioxin, where the substituents are selected from halogen; hydroxyl; C1-3alkoxygroup and C1-3alkyl groups, where C1-3alkyl group optionally substituted by a hydroxy-group, fluorine,1-2alkoxygroup, amino group, mono - and di-C1-4alkylaminocarbonyl, or on imennyh carbocyclic groups, having 3 to 6 ring members and/or saturated heterocyclic groups of 5 or 6 ring members containing 1 or 2 heteroatoms selected from N and O; or
(C) R1selected from unsubstituted phenyl, 2-ftoheia, 2-hydroxyphenyl, 2-methoxyphenyl, 2-methylphenyl, 2-(2-(pyrrolidin-1-yl)ethoxy)phenyl, 3-ftoheia, 3-methoxyphenyl, 2,6-dipthera, 2-fluoro-6-hydroxyphenyl, 2-fluoro-3-methoxyphenyl, 2-fluoro-5-methoxyphenyl, 2-chloro-6-methoxyphenyl, 2-fluoro-6-methoxyphenyl, 2,6-dichlorophenyl and 2-chloro-6-ftoheia; and optional extras choose from 5-fluoro-2-methoxyphenyl; or
(g) R1choose from 2,6-dipthera, 2-fluoro-6-methoxyphenyl, 2,6-dichlorophenyl and 2-chloro-6-ftoheia.

14. The connection according to one of claims 1 to 13, where R3denotes optionally substituted non-aromatic group selected from such groups as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydropyran, tetrahydrofuran, piperidine and pyrrolidine.

15. The connection according to one of claims 1 to 14, in which the carbocyclic and heterocyclic groups, R3substituted by 1, 2 or 3 substituents defined in claim 1.

16. The connection according to one of claims 1 to 15, where R3denotes a carbocyclic or heterocyclic group selected from phenyl; C3-6cycloalkyl; 5 - or 6-membered saturated non-aromatic heterocycles containing up to 2 hetero the volume, selected from O, N, S and SO2; 6-membered heteroaryl rings containing 1 or 2 ring nitrogen atoms; and 5-membered heteroaryl rings containing up to 2 heteroatoms selected from O, N and S, and each carbocyclic or heterocyclic group is unsubstituted.

17. The compound of formula (IV):
.
or its pharmaceutically acceptable salts or tautomers or N-oxides,
where R1and R2specified in one of the preceding paragraphs;
between the carbon atoms marked with numbers 1 and 2, may not necessarily be a double bond;
one of the groups U and T are selected from CH2, CHR13, CR11R13, NR14N(O)R15, O and S(O)t; and the other of U and T is selected from NR14, O, CH2, CHR11C(R11)2and C=O; r=1, 2, 3 or 4; t=0, 1, or 2;
R11selected from hydrogen, halogen, C1-3the alkyl and C1-3alkoxygroup;
R13selected from hydrogen, other14, NOH, NOR14and Ra-Rb;
R14selected from hydrogen and Rd-Rb;
Rdchoose from the communication, CO, C(X2X1, SO2and SO2NRc;
Ra, Rband Rcspecified in one of the preceding paragraphs and
R15choose from C1-4rich hidrocarburos group, optionally substituted hydroxy-group, With1-2alkoxy is POI, halogen or a monocyclic 5 - or 6-membered carbocyclic or heterocyclic group, provided that U and T cannot mean O.

18. The connection 17, having the formula (IVa):

or its pharmaceutically acceptable salts or tautomers or N-oxides,
where one of the groups U and T are selected from CH2, CHR13, CR11R13, NR14N(O)R15, O and S(O)t; and the other of the groups U and T are selected from CH2, CHR11C(R11)2and C=O; r=1 or 2; t=0, 1, or 2;
R11selected from hydrogen and C1-3of alkyl;
R13selected from hydrogen and Ra-Rb;
R14selected from hydrogen and Rd-Rb;
Rdchoose from the communication, CO, C(X2X1, SO2and SO2NRc;
R15choose from a saturated1-4hidrocarburos group, optionally substituted hydroxy-group, With1-2alkoxygroup, halogen or a monocyclic 5 - or 6-membered carbocyclic or heterocyclic group; and
R1, R2, Ra, Rband Rcspecified in one of the preceding paragraphs.

19. Connection p, where T is chosen from CH2, CHR13, CR11R13, NR14N(O)R15, O and S(O)ta U is chosen from CH2, CHR11With(R11)2and C=O; and R11selected from hydrogen and methyl, preferably hydrogen is.

20. The connection according to claim 19, where R14selected from hydrogen and Rd-Rbwhere Rbchoose from hydrogen; monocyclic carbocyclic and heterocyclic groups having from 3 to 7 members in the ring; and saturated With1-4hidrocarburos group, optionally substituted by one or more substituents selected from a hydroxy-group, carbonyl group, halogen, amino, mono - or di-saturated With1-4hidrochromotherapy, and monocyclic carbocyclic and heterocyclic groups having from 3 to 7 ring members, and where one or more carbon atoms saturated With1-4hidrocarburos group can be optionally replaced by O, S, SO, SO2, NRcX1C(X2), C(X2X1; Rcchosen from hydrogen and saturated With1-4hidrocarburos group; and X1denotes O, S or NRcand X2means =O, =S or =NR.

21. Connection at one PP-19 having the formula (Va):

or its pharmaceutically acceptable salts or tautomers or N-oxides,
where R14aselected from hydrogen, C1-4the alkyl, optionally substituted by fluorine, cyclopropylmethyl, phenyl-C1-2of alkyl, C1-4alkoxycarbonyl, phenyl-C1-2alkoxycarbonyl,1-2alkoxy-C1-2the alkyl and C1-2alkylsulfonyl, where phenyl fragments, the EU and they are present, optionally substituted from 1 to 3 substituents selected from fluorine, chlorine, C1-4alkoxygroup, optionally substituted by fluorine or1-2alkoxygroup, and C1-4the alkyl, optionally substituted by fluorine or1-2alkoxygroup;
w=0, 1, 2 or 3;
R2denotes hydrogen or methyl;
R11and r is defined in one of PP-19;
R19selected from fluorine; chlorine; C1-4alkoxygroup, optionally substituted by fluorine or1-2alkoxygroup; and (C1-4the alkyl, optionally substituted by fluorine or1-2alkoxygroup.

22. Connection item 21, where R2denotes hydrogen.

23. The connection to item 21 or 22, where w=0 or w=1, 2, or 3 and the phenyl ring is 2-monosubstituted, 3-monosubstituted, 2,6-disubstituted, 2,3-disubstituted, 2,4-disubstituted, 2,5-disubstituted, 2,3,6-triple-substituted or 2,4,6-triple-substituted, and the substituents for the phenyl ring selected from R19as defined in item 21, and R11denotes hydrogen.

24. Connection item 23, where the phenyl ring is replaced twice in the 2nd and 6th positions by substituents selected from fluorine, chlorine and metoxygroup.

25. Connection at one PP-24, where R14adenotes hydrogen or methyl.

26. Connection item 21, having the formula (VIb):

or its pharmaceutically acceptable salts or tautomers or N-OK the IDA; where
R20selected from hydrogen and methyl;
R21aselected from fluorine and chlorine; and
R22aselected from fluorine, chlorine and metoxygroup.

27. Connection p that choose from:
piperidine-4-ylamide 4-(2,6-differentiating)-1H-pyrazole-3-carboxylic acid;
(1 methylpiperidin-4-yl)amide of 4-(2,6-differentiating)-1H-pyrazole-3-carboxylic acid;
piperidine-4-ylamide 4-(2,6-dichloraniline)-1H-pyrazole-3-carboxylic acid; and
piperidine-4-ylamide 4-(2-fluoro-6-methoxybenzylamine)-1H-pyrazole-3-carboxylic acid.

28. Connection p, which is a
piperidine-4-alamid 4-(2,6-dichloraniline)-1H-pyrazole-3-carboxylic acid.

29. The connection according to one of claims 1 to 28, where the connection is in the form of pharmaceutically acceptable salts.

30. The method of prevention or treatment of cancer, comprising an introduction to the needy in the subject of the connection defined in one of claim 2 to 29.

31. The compound as defined in one of claims 1 to 29, intended for the prevention or treatment of a disease or condition mediated by a cyclin-dependent kinase.

32. Pharmaceutical composition for prevention or treatment of a disease or condition mediated by a cyclin dependent kinase, comprising the compound defined in any one of claims 1 to 29, and a pharmaceutically acceptable carrier.

33. Farmatsevticeski the composition according p, which is in a form suitable for intravenous administration.

34. The pharmaceutical composition according p that is suitable for administration by injection or infusion.

35. The use of compounds as defined in one of claims 1 to 29, for obtaining a medicinal product intended for the prevention or treatment of a disease or condition mediated by a cyclin-dependent kinase.

36. The connection according to one of claims 1 to 29, intended for the prevention or treatment of a disease or condition which is a proliferative disorder.

37. Connection p, where proliferative violation is cancer.

38. The connection clause 37, where the cancer is chosen from the group including carcinoma of the bladder, breast, colon, kidney, epidermis, liver, lung, esophagus, gall bladder, ovary, pancreas, stomach, cervix, thyroid, prostate, or skin, hematopoietic tumors of lymphoid origin, hematopoietic tumors of myeloid origin, follicular thyroid cancer; a tumour of mesenchymal origin; a tumour of the Central or peripheral nervous system, melanoma, seminoma, teratocarcinoma, osteosarcoma, pigmentary xeroderma, keratocanthoma, thyroid follicular cancer and Kaposi's sarcoma.

39. The connection p is § 38, where hematopoietic tumors of lymphoid origin are leukemia, acute limfocitna leukemia, b-cell lymphoma, T-cell lymphoma, Hodgkin's lymphoma, nahodkinskuju lymphoma, hairy cell lakomy or lymphoma Burkett.

40. The connection clause 37, where the cancer is selected from breast cancer, ovarian cancer, colon cancer, prostate cancer, esophageal cancer, squamous cancer and non-small cell carcinoma of the lung.

41. The use of the connection defined in one of claims 1 to 29, for obtaining a medicinal product intended for the prevention or treatment of a disease or condition which is a proliferative disorder.

42. The application of paragraph 41, where the proliferative violation is cancer.

43. The application of § 42 where the cancer is chosen from the group including carcinoma of the bladder, breast, colon, kidney, epidermis, liver, lung, esophagus, gall bladder, ovary, pancreas, stomach, cervix, thyroid, prostate, or skin, hematopoietic tumors of lymphoid origin, hematopoietic tumors of myeloid origin, follicular thyroid cancer; a tumour of mesenchymal origin, tumors of the Central or peripheral nervous system, melanoma, seminoma, teratocarcinoma, osteosarcoma, pigmentary xeroderma, is ratattadaa, thyroid follicular cancer and Kaposi's sarcoma.

44. Use p.43, where hematopoietic tumors of lymphoid origin are leukemia, acute limfocitna leukemia, b-cell lymphoma, T-cell lymphoma, Hodgkin's lymphoma, nahodkinskuju lymphoma, hairy cell lakomy or lymphoma Burkett.

45. The application of § 42, where the cancer is selected from breast cancer, ovarian cancer, colon cancer, prostate cancer, esophageal cancer, squamous cancer and non-small cell carcinoma of the lung.

46. The use of the connection defined in one of claims 1 to 29, to obtain drugs for treatment or prevention of the disease condition or disease in a patient, the last survey, which established disease or risk of disease, and found that the disease or diseased state is susceptible to treatment with a compound having activity against cyclin-dependent kinases.

47. A method of obtaining a compound defined in one of claims 1 to 29, in which X denotes R1C(=O)NH, comprising the reaction of carboxylic acids of formula R1-CO2H or its activated derivative with 4-aminopyrazole formula (XII):

where Y, r1, r2and r3defined in one of claims 1 to 24.

48. The method of obtaining from the organisations, defined in one of claims 1 to 29, comprising the reaction of compounds of formula (XIII):

with the compound of the formula R3-Y-NH2where X, Y, R2and R3defined in one of claims 1 to 24.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compounds with common formulae I, II, IV and V: (I), (III), (IV), (V), values of radicals, such as provided in invention formula. Besides, proposed invention relates to pharmaceutical composition on the basis of above-described compounds, to their application, and also to method for treatment of repeated urination, incontinence and higher activity of urinary bladder, besides, to method to treat pain.

EFFECT: new compounds have been produced and described, which may be useful for treatment of diseases related to fatty-acid amide-hydrolase (FAAH), in particular to treat repeated urination and incontinence, higher activity of bladder and/or pain.

16 cl, 442 ex, 73 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compounds with common formulae I, II, IV and V: (I), (III), (IV), (V), values of radicals, such as provided in invention formula. Besides, proposed invention relates to pharmaceutical composition on the basis of above-described compounds, to their application, and also to method for treatment of repeated urination, incontinence and higher activity of urinary bladder, besides, to method to treat pain.

EFFECT: new compounds have been produced and described, which may be useful for treatment of diseases related to fatty-acid amide-hydrolase (FAAH), in particular to treat repeated urination and incontinence, higher activity of bladder and/or pain.

16 cl, 442 ex, 73 tbl

FIELD: chemistry.

SUBSTANCE: described are heterobicyclic derivatives of formula (I)

, in which V denotes -C(R7)-; W denotes a single bond or -C(R8R9)-; X denotes O, S, SO, SO2 or N(R10); Y denotes -C(R11R12)-, -C(R11R12)C(R13R14)C(R11R12)C(R13R14)C(R15R16)-, -C(R11R12)C(R13R14)C(R15R16)C(R17R18)- or- C(R11)=C(R12)-; R1, R2, R3, R4 and R5 independently denote hydrogen, halogen, (lower)alkyl, fluoro(lower)alkyl, (lower)alkoxy group, fluoro(lower)alkoxy group, NH2-C(O); R6 denotes a phenyl, pyridyl, pyrazolyl or thiazolyl group, where the group is optionally substituted with 1-4 substitutes selected from a group consisting of halogen, cyano group, (lower)alkyl, (lower)alkoxy group, COOH, 1H-tetrazol-5-yl, 5-oxo-4H-[1,2,4]oxadiazol-3-yl, where (lower)alkyl is optionally substituted with COOH. A pharmaceutical composition is also described.

EFFECT: said compounds inhibit L-CPT1 and can be used as medicinal agents.

27 cl, 120 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (III): , in which D is a benzene ring, 2-pyridone ring, pyridine ring, benzoxalone ring, benzoxadinone ring or benzimidazole ring; R1 denotes carboxy or hydroxy; R2 independently denotes a halogen atom; alkyl optionally substituted with a halogen atom, aryl or alkylamine; alkynyl, optionally substituted alkoxy; hydroxy; carboxy; alkoxy optionally substituted with phenyl, aromatic heterocyclic ring which denotes a 5-6-member aromatic monocyclic carbocyclic ring containing one or two heteroatoms, independently selected from oxygen and nitrogen atoms; alkylsulphonyl; aryloxy; amino optionally substituted with alkyl; acyl optionally substituted with alkyl or alkyloxy; alkyloxycarbonyl; alkanesulphonyl; arylsulphonyl or alkylcarbamoyl; carbamoyl optionally substituted with alkyl, phenyl, cycloalkyl, acetyl, alkanesulphonyl, heteroarylalkyl, cycloalkylalkyl, heteroaryl which denotes a 5-6-member aromatic monocyclic ring containing one or three heteroatoms independently selected from oxygen and nitrogen atoms, and which is optionally substituted with alkyl or cycloalkyl; acylcyano; nitro, aryl; heteroaryl which denotes a 5-6-member aromatic ring containing one or more heteroatoms independently selected from oxygen, sulphur and nitrogen atoms, and which is optionally substituted with alkyl; alkylsulphonyl; morpholinylsulphonyl; non-aromatic heterocyclic group which denotes a 5-6-member non-aromatic heterocyclic ring containing one or more nitrogen atoms and optionally an oxygen and/or sulphur atom; R3 denotes C1-C6alkyloxy, C1-C6alkylthio; R4 denotes a halogen atom or alkyloxy; R5 denotes alkyl; M denotes sulphonyl; L3 independently denotes alkylene optionally containing one oxygen or nitrogen atom, alkenylene, or -N(R7)-; R7 independently denotes a hydrogen atom, alkyl; Y denotes a single bond or CO; Z denotes CH or N; n equals 0 or 1; p equals 0, 1, or 2; q equals 0 or 1; provided that R1 does not denote carboxy when ring D is a benzene ring, -L3- denotes -(O-alkylene)- and the substitution position of L3 and Y is an ortho-position in ring D; to pharmaceutically acceptable salts thereof. The invention also relates to compounds of formula (IV), a pharmaceutical composition, a method of treating diseases associated with the DP receptor, use of compounds in any of the claims 1-17, as well as compounds of general formula (V).

EFFECT: obtaining novel biologically active compounds having DP receptor antagonist activity.

30 cl, 8 ex, 62 tbl

FIELD: medicine.

SUBSTANCE: invention refers to derivatives of 2-pyridylmethylenecarboxamide of formula (I), where: -A represents a substituted or unsubstituted 5-member heterocyclyl group bound with carbonyl through carbon atom; -Z1 and Z2 which can be equal or different, represent hydrogen atom; C1-C5-alkyl; C5-alkoxycarbonyl; -Z3 represents substituted or unsubstituted C3-C7cycloalkyl; -Y represents C1-C5-halogenalkyl, containing to 5 halogen atoms which can be equal or different; X which can be equal or different, represents halogen atom, - n=0, 1, 2 or 3; and to their salts. Besides the invention describes a method of plant pathogenic fungi control with the use of such compounds.

EFFECT: there are prepared and described new derivatives of 2-pyridylmethylenecarboxamide which can be effective as fungicidal active agents.

8 cl, 96 ex, 4 tbl

FIELD: medicine.

SUBSTANCE: invention refers to new compounds exhibiting antiproliferative activity of formula (1) where W means N or C-R2; X means -NH-; Y means CH; Z means halogen, -NO2, C2-C3alkynyl-, halogen-C1-C3alkyl- and -C(=O)-C1-C3alkyl, A means a group of formula (i), (ii) or (iii) Q1 means phenyl; B1, B2, B3 and B4 independently mean C-RgRh, N-Ri or O; R1 means hydrogen; R2 means a residue specified from the group including hydrogen, halogen and -OR4; Ra, Rb, Rc, Rd, Re and Rf independently mean hydrogen; Rg and Rh independently mean a residue specified from the group including hydrogen, =O, -OR4 and -NR4C(=O)R5; or mean optionally a residue monosubstituted or twice-substituted with equal or different substitutes and specified from the group including C1-C6alkyl and phenyl, the substitute/substitutes is/are specified from the group including R8/, -OR4, -C(=O)R4, -C(=O)OR4 and -C(=O)NR4R5 where R8/ and other values of radicals are specified in the patent claim, optionally in the form of their pharmacologically noncontaminating acid addition salts. The invention also concerns a pharmaceutical composition.

EFFECT: new compounds have effective biological properties.

8 cl, 6 dwg, 1086 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel compounds of formula (I), where R1 represents hydroxymethyl; R2 is selected from -C(O)NR4R5; HET-1 represents 5- or 6-member heteroaryl ring, bound by atom C; R3 represents halogeno; R4 and R5 together with nitrogen atom, to which they are bound, can form heterocyclyl ring system, as it is defined for HET-3; HET-3 represents possibly substituted azetidinyl; m equals 1; n equals 0, 1 or 2; or their pharmaceutically acceptable salt, which can be applied as glucokinase (GLK) activators or active ingredient of pharmaceutical compositions, also described are methods of obtaining them.

EFFECT: creation of novel compounds applied as glucokinase (GLK) activators in treatment of diabetes.

13 cl, 40 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel acylsulfonamide peri-substituted condensed bicyclic compounds of general formula (I), values of radicals are given in invention formula. Also described is pharmaceutical composition based on formula (I) compound.

EFFECT: compounds can be used for inhibition of prostaglandin E2 binding with receptor EP3.

30 cl, 371 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: in embodiments of the invention, specific compounds are used to prepare a medicinal agent for treating, relieving and preventing conditions associated with dysfunction of monoamine transmission. The compounds have general formula (1) , where: R1 and R2 are identical or different and denote hydrogen, alkyl, alkenyl, alkynyl, aryl, thio or alkylthio, or R1 and R2 may have extra substitutes which are selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkyloxy, morpholin-4-ylalkoxy, piperidin-1-ylalkyloxy, alkylamino, dialkylamino, arylamino.

EFFECT: more efficient use of compounds in preparing medicinal agents.

8 cl, 3 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline or quinazoline derivatives of general formula

Ib, where R1 is C1-6-alkyl or C1-6-alkoxy; X is N or CH; R3 and R4 independently denote hydrogen, C1-6-alkyl, C1-6-alkylsulphonyl or a group of formula (IIa), where A is oxygen or sulphur; D is -(CH2)t, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur, (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or a group of formula (IIb), where A is oxygen or sulphur; D is -(CH2)t-, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or R3 and R4 together with the nitrogen atom with which they are bonded form a 3-7-member ring or a 6-10-member bicyclic ring which can be saturated, partially saturated or unsaturated and contain 1, 2 or 3 heteroatoms selected from nitrogen, sulphur and oxygen, where each group is optionally substituted with 1 or 2 substitutes selected from oxo, C1-6-alkyl, C1-6-alkoxy, aryl and aryl-C1-6-alkyl (where aryl and aryl-C1-6-alkyl are also optionally substituted with 1 or 2 with C1-6-alkyls or C1-6-alkoxy). The invention also relates to use of formula Ib compounds in preparing a medicinal agent, to a pharmaceutical composition based on formula Ib compound and preparation method thereof.

EFFECT: obtaining novel quinoline and quinazoline derivatives having high affinity to 5-HT1-receptors.

12 cl, 171 ex

FIELD: chemistry.

SUBSTANCE: in compounds of formula:

, A and B denote a pair of condensed saturated or unsaturated 5- or 6-member rings, where the said system of condensed rings A/B contains 0-2 nitrogen atoms, and said rings are further substituted with 0-4 substitutes independently selected from halogen, lower alkyl or oxo; and a and b are bonding positions for residues Y and D, respectively, and these positions a and b are in the peri-position relative each other on the said condensed ring system A/B; d and e are condensed positions between ring A and ring B in the said condensed ring system A/B; D is an aryl or heteroaryl cyclic system which denotes a 5- or 6-member aromatic ring containing 0-3 heteroatoms selected from O, N or S; which can be further substituted with 0-4 substitutes independently selected from lower alkyl and amine; Y is selected from -CH2 and -O-; M is selected from aryl, aryl substituted with a halogen or alkoxy; R1 is selected from aryl, aryl substituted with a halogen, heteroaryl, heteroaryl substituted with a halogen, where heteraryl denotes a 5- or 6-member aromatic ring containing 0-3 heteroatoms selected from O, N or S, and CF3; and if Y denotes -CH2- or -O-, then R1 further denotes a lower alkyl. The invention also pertains to use of compounds in claim 1, a pharmaceutical composition, a screening method on selective ligands of prostanoid receptors, as well as compounds of the formula.

EFFECT: obtaining novel biologically active compounds for inhibiting binding of prostanoid E2 with EP3 receptor.

25 cl, 46 ex

FIELD: medicine.

SUBSTANCE: invention refers to derivatives of 2-pyridylmethylenecarboxamide of formula (I), where: -A represents a substituted or unsubstituted 5-member heterocyclyl group bound with carbonyl through carbon atom; -Z1 and Z2 which can be equal or different, represent hydrogen atom; C1-C5-alkyl; C5-alkoxycarbonyl; -Z3 represents substituted or unsubstituted C3-C7cycloalkyl; -Y represents C1-C5-halogenalkyl, containing to 5 halogen atoms which can be equal or different; X which can be equal or different, represents halogen atom, - n=0, 1, 2 or 3; and to their salts. Besides the invention describes a method of plant pathogenic fungi control with the use of such compounds.

EFFECT: there are prepared and described new derivatives of 2-pyridylmethylenecarboxamide which can be effective as fungicidal active agents.

8 cl, 96 ex, 4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compound of general formula (I) and its pharmaceutically acceptable salts. In general formula (I) , Y represents group -CONH(Q)- or -NHCONH(Q)-; Q represents 6-member aromatic ring or 5-10-member heteroaromatic ring, containing one or two N heteroatoms or two O heteroatoms; R represents hydrogen, halogen, linear or branched (C1-C6)alkyl; (C1-C6)alkoxy; di-(C1-C6)alkylamino, 5-member heteroaromatic ring, containing one O or S heteroatom; 6- or 9-member heteroaromatic ring, containing one or two N heteroatoms; phenyl, mono- or disubstituted with halogen, (C1-C6)alkyl, halogeno(C1-C6)alkyl, (C1-C6)alkoxy, acyl; hydroxy; piano; di-(C1-C6)alkylamino, acylamino' carbamoyl; X represents group : where Z represents CH2, N or O; m represents integer number from 1 to 3; p is equal 0, 1; R" is selected from group, consisting of di-( C1-C6)alkylaminocarbonyl, (C1-C6)alkyl, acyl. Invention also relates to pharmaceutical composition, containing as active ingredient, invention compound, to application of invention compound for manufacturing pharmaceutical composition, to method of inhibition of nicotinic acetylcholine receptor α7.

EFFECT: obtaining compound, which possesses agonistic activity with respect to nicotinic acetylcholine receptor (nAChR) α7.

7 cl, 2 tbl, 4 dwg, 270 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds, which possess properties inhibiting HIV replication, of general formula (I) , in form of E-isomer, in which -a1=a2-a3=a4- represents bivalent radical of formula -CH=CH-CH=CH- (a-1); -b1=b2-b3=b4. Represents bivalent radical of formula -CH=CH-CH=CH- (b-1); n equals 0; m equals 2; each of R1 radicals independently on each other stands for hydrogen atom; C1-6alkyl; R2a stands for cyanogroup; X1 stands for -NR1-; R3 represents C2-6alkenyl, substituted with cyanogroup; R4 stands for C1-6alkyl; R5 represents radical of formula -Y-Alk-L, -Alk'-Y-L or -Alk'-Y-Alk-L; each of radicals Alk or Alk' independently represents bivalent C1-6alkyl or C2-6 alkenyl group; L stands for aryl or Het; Y stands for NR1; -CH=N-O-; Het stands for 5- or 6-member fully saturated ring system, in which one, two or three ring elements represent heteroatoms, each of which is independently selected from group, including nitrogen, oxygen and sulphur, and in which other ring elements represent carbon atoms; and, if possible, any nitrogen ring element can be optionally substituted with C1-6alkyl; and ring system can be optionally bound with benzene ring; and in which any carbon atom of ring, including any carbon atom of optionally bound benzene ring, each independently can be substituted with substituent selected from such groups as halogen atom, C1-6alkyl, hydroxyC1-4alkyl, carboxyC1-4alkyl, C1-4 alkylcarbonyloxyC1-4alkyl, di(C1-4alkyl)aminoC1-4alkyl, aryloxy, morpholinyl, aryl, Het1; Het1 stands for thienyl, isoxazolyl, thiadiazolyl, each of which can be optionally substituted with one or two C1-4alkyl radicals; Q stands for hydrogen atom; each aryl represents phenyl or phenyl, substituted with one, two substituents, each of which is independently selected from such groups as halogen atom, C1-6alkyl, C2-6alkinyl, cyano, polyhalogen C1-6alkyl or Het1, as well as to its pharmaceutically acceptable additive salts Invention also relates to pharmaceutical composition.

EFFECT: creation of novel compounds, which possess properties inhibiting HIV replication

5 cl, 7 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel acylsulfonamide peri-substituted condensed bicyclic compounds of general formula (I), values of radicals are given in invention formula. Also described is pharmaceutical composition based on formula (I) compound.

EFFECT: compounds can be used for inhibition of prostaglandin E2 binding with receptor EP3.

30 cl, 371 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel heterocyclic compounds of formula (1) , where ring Q represented by is , (where is NH-CH2-, -N-CH-, -CH2-NH- or -CH=N-; and the carbon-carbon bond between the 3rd position and the 4th position of the heterocyclic skeleton which contains Z and Y, is a single or double bond); ring Q can have at least one substitute selected from a group consisting of a lower alkyl group, lower alkenyl group, lower alkynyl group, hydroxy group, lower alkoxy group, halogenated lower alkyl group, aryl group, aryl lower alkyl group, aryl lower alkoxy group, arylcarbonyl group, lower alkenyloxy group, lower alkanoyl group, lower alkanoyloxy group, cycloalkyl group, cycloalkyl lower alkyl group, halogen atom, carbamoyl group which can have a lower alkyl group, carboxy group, lower alkoxycarbonyl group, amino group which can have a lower alkanoyl group, nitro group, hydroxy lower alkyl group, amino lower alkyl group which can have a lower alkyl group, thienyl group, lower alkyl group substituted with a saturated 3-8-member monoheterocyclic group containing 1-2 nitrogen atoms, and an oxo group; R2 is a hydrogen atom or a lower alkyl group; and A is -O-A1- (where A1 is an alkylene group which can be substituted with a hydroxy group (where the alkylene group may contain one oxygen atom) or a lower alkenylene group or a lower alkylene group; provided that if A is a lower alkylene group, Q is a bicyclic group selected from a group consisting of: (where the carbon-carbon bond is a single or double bond)] or salts thereof. The invention also relates to a pharmaceutical composition, to a method of preparing the pharmaceutical composition, to use of the formula (1) heterocyclic compound, as well as a method for synthesis of the heterocyclic compound.

EFFECT: obtaining novel biologically active compounds which have activity as a dopamine D2 receptor partial agonist and a serotonin receptor 5-HT2A antagonist, and an adrenaline receptor α1 antagonist, and serotonin uptake inhibitor or serotonin reuptake inhibitor.

15 cl, 197 ex, 24 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline or quinazoline derivatives of general formula

Ib, where R1 is C1-6-alkyl or C1-6-alkoxy; X is N or CH; R3 and R4 independently denote hydrogen, C1-6-alkyl, C1-6-alkylsulphonyl or a group of formula (IIa), where A is oxygen or sulphur; D is -(CH2)t, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur, (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or a group of formula (IIb), where A is oxygen or sulphur; D is -(CH2)t-, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or R3 and R4 together with the nitrogen atom with which they are bonded form a 3-7-member ring or a 6-10-member bicyclic ring which can be saturated, partially saturated or unsaturated and contain 1, 2 or 3 heteroatoms selected from nitrogen, sulphur and oxygen, where each group is optionally substituted with 1 or 2 substitutes selected from oxo, C1-6-alkyl, C1-6-alkoxy, aryl and aryl-C1-6-alkyl (where aryl and aryl-C1-6-alkyl are also optionally substituted with 1 or 2 with C1-6-alkyls or C1-6-alkoxy). The invention also relates to use of formula Ib compounds in preparing a medicinal agent, to a pharmaceutical composition based on formula Ib compound and preparation method thereof.

EFFECT: obtaining novel quinoline and quinazoline derivatives having high affinity to 5-HT1-receptors.

12 cl, 171 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medication, reducing desire for alcohol, which represents substituted 1H-benzimidazoles of general formula 1 or their pharmaceutically acceptable salts and/or hydrates, pharmaceutical composition, and medication on their basis. Compounds can be applied in treatment of alcohol abuse with application of ethanol-containing products, if necessary, together with antidepressants. In compounds of general formula 1 , where: W represents sulfur atom or group S=O; R1 represents one or more substituents, selected from hydrogen, halogen, C1-C4alkyl, C1-C4alkyloxy, optionally substituted 5-6-member azaheterocyclyl with 1-2 atoms of nitrogen and/or oxygen in cycle; R2 represents atom of hydrogen or optionally substituted C1-C4alkyl; R3 and R4 independently on each other represent optionally similar substituents, selected from hydrogen, optionally substituted C1-C4alkyl, C3-C6cycloalkyl; R5 represents alkyl substituent, selected from hydrogen or optionally substituted C1-C7alkyl, C1-C7alkenyl, C1-C4alkynyl, optionally substituted phenyl, optionally substituted 5-6-member heterocyclyl with 1-3 heteroatoms, selected from nitrogen, oxygen and sulfur, possibly condensed with benzene ring; C1-C4-alkoxycarbonyl, optionally substituted amino carbonyl, or group CR3R4R together stands for group , where Alk stands for C1-C4alkyl.

EFFECT: medication allows to reduce symptoms of alcohol abuse considerably as compared with earlier known compounds and does not produce unfavorable effect on liver function.

12 cl, 3 tbl, 2 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: in formula (1) A is a nitrogen atom or CH; when A is a nitrogen atom, B is NR9 (where R9 is a C1-10alkyl group), when A is CH, B is a sulphur atom, R1 is a phenyl group (where the phenyl group is substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-10alkyl group and C1-10alkoxy groups (where C1-10alkyl groups and C1-10alkoxy groups are not substituted of substituted with one or more halogen atoms)); L1 is a bond; X is OH; R2 is a C1-6alkyl group; L2 is a bond; L3 is NH; L4 is a bond or NH; Y is an oxygen atom or sulphur atom; R3 is a thienyl group (where the thienyl group is substituted with CONR29R30 (where R29 is hydrogen or a C1-10alkyl group, and R30 is an amino group (where the amino group is not substituted or substituted with a pyridyl group), mono- or di-C1-10alkylamino group, N-methylpiperzinyl group, piperidine group, morpholine group or C1-10alkyl group (C1-10alkyl group is substituted with one or more substitutes selected from a group consisting of a carboxyl group, carbamoyl groups, pyrroldinyl groups, tetrahydrofuryl groups or morpholine groups) or R29 and R30 together denote -(CH2)m3-G-(CH2)m4- (where G is CR31R32 (where R31 is a hydrogen atom and R32 is a C1-10alkylcarbonylamino group or pyrrolidinyl group) and each of m3 and m4 is independently equal to an integer from 0 to 5 provided that m3+m4 equals 3, 4 or 5), or NR29R30 as a whole denotes a piperidine group or pyrrolidinyl group (where the piperidine group or pyrrolidinyl group is substituted with two substitutes independently selected from a group consisting of: hydroxyl groups and C1-10alkoxy groups) or 2-(4-oxopyrridin-1(4H)-yl)acetyl group), phenyl group (where the phenyl group is substituted with one substitute selected from a group consisting of C1-10alkyl groups, C1-10alkylcarbonyl groups and C1-10alkylaminocarbonyl groups, (where C1-10alkyl group, C1-10alkylcarbonyl group and C1-10alkylaminocarbonyl group are substituted with one or two substitutes selected from a group consisting of hydroxyl groups, carboxyl groups and carbamoyl groups)), phenyl group (where the phenyl group is substituted with one C1-10alkylaminocarbonyl group or one halogen atom), dihydrobenzo[1,4]dioxine group or benzo[1,4]oxazine group. The invention also relates to a medicinal agent containing the disclosed compound as an active ingredient and to a thromopoeitin receptor activator which is a formula (1) compound.

EFFECT: disclosed compounds have thrombopoietin receptor agonist properties.

8 cl, 11 tbl, 128 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a method for preparing 1-(3-(2-(1-benzothiophene-5-yl)ethoxy)propyl)azetidine-3-ol or its salts which involves the use as a parent compound, (phenylthio)acetic acid derivative or its salts presented by general formula: where X1 represents halogen atom, and is applicable as a safe method of volume production of 1-(3-(2-(1-benzothiophene-5-yl)ethoxy)propyl)azetidine-3-ol or its salts effective as an agent in disorders of the central nervous system and peripheral nervous system.

EFFECT: there is provided high yield, safety for human body, low environment loads.

36 cl, 1 tbl, 33 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I: or its pharmaceutically acceptable salt or stereoisomer, where a is independently equal to 0 or 1; b is independently equal to 0 or 1; R1 is selected from aryl, heterocyclyl and NR10R11; said aryl or heterocyclyl group is optionally substituted with between one and five substitutes, each independently selected from R8; R5 is selected from C1-6alkyl, C2-6alkenyl, -C(=O)NR10R11, NHS(O)2NR10R11 and NR10R11, each alkyl, alkenyl or aryl is optionally substituted with between one and five substitutes, each independently selected from R8; R8 independently denotes (C=O)aObC1-C10alkyl, (C=O)aObaryl, (C=O)aObheterocyclyl, OH, Oa(C=O)bNR10R11 or (C=O)aCbC3-C8cycloalkyl, said alkyl, aryl, heterocyclyl are optionally substituted with one, two or three substitutes selected from R9; R9 is independently selected from (C=O)aCb(C1-C10)alkyl and N(Rb)2; R10 and R11 is independently selected from H, (C=O)Cb(C1-C10)alkyl, C1-C10alkyl, SO2Ra, said alkyl is optionally substituted with one, two or three substitutes selected from R8 or R10 and R11 can be taken together with nitrogen to which they are bonded with formation of a monocyclic heterocycle with 5 members in each ring and optionally contains one or two heteroatoms, in addition to the nitrogen, selected from N and S, said monocyclic heterocycle is optionally substituted with one, two or three substitutes selected from R9; Ra is independently selected from (C1-C6)alkyl, (C2-C6)alkenyl; and Rb is independently selected from H, (C1-C6)alkyd, as well as to a pharmaceutical composition for inhibiting receptor tyrosine kinase MET based on this compound, as well as a method of using said compound to produce a drug.

EFFECT: novel compounds which can be used to treat cell proliferative diseases, disorders associated with MET activity and for inhibiting receptor tyrosine kinase MET are obtained and described.

8 cl, 32 ex, 4 tbl

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