Pyrroleylthiazoles and their application as reverse agonists of receptor cb1

FIELD: chemistry.

SUBSTANCE: invention relates to the bonds of the formula (I) and their pharmaceutically acceptable salts in the capacity of modulators of receptors CB1 and to the pharmacological composition on their basis. Bonds can be used for treatment and prophylaxis of diseases, which are associated with the modulation of receptor CB1, for example, obesity and diabetes of type II. In the general formula (I) R1 means hydrogen or the lowest alkyl; R2 means hydrogen, the lowest alkyl, the lowest alkenyl, the lowest alkoxy-lowest alkyl, the lowest alkoxycarbonilamino-group or - (CH2)m-R2a; or R1 and R2 form together with atom of nitrogen to which they are attached, a 5-or 6-member saturated heterocyclic ring; R2a means cycloalkyl, which is not necessarily mono- or tetra-substituted independently by hydroxy-group, the lowest alkyl; C3-6cycloalkenyl, 5- or 6-member monovalent saturated heterocyclic ring, which contains from one to two heteroatoms, independently selected from nitrogen and oxygen; 5- or 6-member monovalent heteroaromatic ring, which contains from one to two heteroatoms, independently selected from nitrogen and oxygen, here note that the said heteroaromatic ring is not necessarily mono-substituted independently with the lowest alkyl; or phenyl which is not necessarily mono- or di-substituted independently with the lowest of the alkoxy group, halogen, halogenated lowest alkyl, halogenated lowest alkoxy group or nitro-group; R3 means the lowest alkyl, the lowest alkoxy-lowest alkyl, diphenyl-lowest alkyl or - (CH2)n-R3a; R3a means C3-6cycloalkyl which can be not necessarily condensed with the phenol ring; or C3-6cycloalkyl, which can be not necessarily mono-, di- or trisubstituted independently hydroxy-group, the lowest alkyl, C3-6cycloalkenyl, 5- or 6-member monovalent saturated heterocyclic ring, which contains from one to two heteroatoms, independently selected from nitrogen and oxygen, here note that the said heterocyclic rings are not necessarily mono-substituted independently by the lowest alkyl, 5- or 6-member monovalent heteroaromatic ring containing one heteroatom, independently selected from oxygen and sulfur, the aforesaid heteroaromatic ring being not necessarily mono-substituted independently with the lowest alkyl, or the phenyl, which can be not necessarily mono-, di- or trisubstituted independently by the hydroxy-group, lowest alkyl, lowest alkoxy-group, halogen, halogenated lowest alkyl, halogenated lowest alkoxy-group or nitro-group; R4 means the lowest alkyl the lowest alkoxycarbonyl; C3-6 cycloalkyl, 5- or 6-member monovalent heteroaromatic ring, which contains one or two heteroatoms, independently selected from nitrogen, the said heteroaromatic ring being not necessarily mono-substituted independently with the lowest alkyl, lowest alkoxy-group; phenoxy-lowest alkyl, in which the phenyl part is not necessarily mono-, di- or trisubstituted independently by the lowest alkoxy-group; or the phenyl, which not necessarily can be mono-, di- or trisubstituted independently, by the lowest alkyl, by the lowest alkoxy-group, by halogen, halogenated lowest alkyl, halogenated lowest alkoxy-group or nitro-group; or two adjusted substitutes of the said phenyl remainder indicate together -O-(CH2)p-O- or -(CH2)2-O-; R5 and R6 each indicates a substitute independently selected from hydrogen of lowest alkyl; R7 indicates hydrogen; m indicates 0,1 or 2; n indicates 1.

EFFECT: new bonds possess useful biological properties.

28 cl, 4 dwg, 380 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

where R1means hydrogen or lower alkyl;

R2means hydrogen, lower alkyl, lower alkenyl, lower alkoxy-lower alkyl, lower alkoxycarbonylmethyl or -(CH2)m-R2a; or

R1and R2form together with the nitrogen atom to which they are attached, a 5 - or 6-membered saturated heterocyclic ring;

R2ameans cycloalkyl, optionally mono - or Tetra-substituted independently by hydroxy-group, the lower alkyl; With3-6cycloalkenyl, 5 - or 6-membered monovalent saturated heterocyclic ring containing one to two heteroatoms independently selected from nitrogen and oxygen; a 5 - or 6-membered monovalent heteroaromatic ring containing one to two heteroatoms independently selected from nitrogen and oxygen, and mentioned heteroaromatic ring is optionally MES is independently substituted lower alkyl; or phenyl which may be optionally mono - or disubstituted independently lower alkoxygroup, halogen, halogenated lower alkyl, halogenated lower alkoxygroup or nitrogroup;

R3means lower alkyl, lower alkoxy-lower alkyl, diphenyl-lower alkyl or -(CH2)n-R3a;

R3Ameans3-6cycloalkyl, which may be optionally condensed with a phenyl ring; or (C3-6cycloalkyl, which may be optionally mono-, di - or tizamidine independently a hydroxy-group, a lower alkyl, C3-6cycloalkenyl, 5 - or 6-membered monovalent saturated heterocyclic ring containing one to two heteroatoms independently selected from nitrogen and oxygen, and mentioned heterocyclic ring is optionally monosubstituted independently lower alkyl, 5 - or 6-membered monovalent heteroaromatic ring containing one heteroatom independently selected from oxygen and sulfur, and mentioned heteroaromatic ring is optionally monosubstituted independently lower alkyl; or phenyl which may be optionally mono-, di - or tizamidine independently a hydroxy-group, lower alkyl, lower alkoxygroup, halogen, halogenated lower alkyl, halogen the trated lower alkoxygroup or nitro-group;

R4means lower alkyl, lower alkoxycarbonyl; C3-6cycloalkyl, 5 - or 6-membered monovalent heteroaromatic ring containing one to two heteroatoms independently selected from nitrogen, and mentioned heteroaromatic ring optionally is monosubstituted independently lower alkyl, lower alkoxygroup; phenoxy-lower alkyl in which the phenyl portion may not necessarily be mono-, di - or tizamidine independently lower alkoxygroup; or phenyl, which optionally can be mono-, di - or tizamidine independently lower alkyl, lower alkoxygroup, halogen, halogenated lower alkyl, halogenated lower alkoxygroup or nitro-group; or two adjacent substituent mentioned phenyl balance means together-O-(CH2)p-O - or -(CH2)2-O-;

R5and R6each mean Deputy, is independently selected from hydrogen or lower alkyl;

R7means hydrogen;

m means 0, 1 or 2;

n means 0, 1 or 2;

R means 1

and their pharmaceutically acceptable salts.

2. Compounds according to claim 1, where R1means hydrogen.

3. Compounds according to claim 1, where R2means a lower alkyl or a residue -(CH2)m-R2a.

4. Compounds according to claim 3, where R2aoz ACHAT cycloalkyl remains with 3-6 carbon atoms, which optionally can be mono - or Tetra-substituted independently lower alkyl and/or hydroxy-group.

5. Compounds according to claim 3, where R2ameans cyclohexenyl.

6. Compounds according to claim 3, where R2ameans unsubstituted five-membered monovalent saturated heterocyclic ring containing one or two heteroatoms independently selected from nitrogen and oxygen.

7. Compounds according to claim 3, where R2ameans piperidinyl, morpholino or tetrahydrofuranyl.

8. Compounds according to claim 3, where R2ameans 5 - or 6-membered monovalent heterocyclic ring containing one or two heteroatoms independently selected from nitrogen.

9. Compounds according to claim 3, where R2ameans pyridinyl, pyrimidinyl, thiazolyl or isoxazolyl.

10. Compounds according to claim 3, where R2ameans phenyl residue, which optionally is mono - or disubstituted independently lower alkoxy, halogen, halogenated lower alkyl, halogenated lower alkoxygroup or nitrogroup.

11. Compounds according to claim 1, where m denotes 0 or 1.

12. Compounds according to claim 1, where R1and R2form together with the nitrogen atom to which they are attached, a 5 - or 6-membered saturated heterocyclic ring.

13. The connection section 12, where R1and R2means together with the nitrogen atom to which they are attached, asamese the nye pyrrolidinyl or piperidinyl.

14. Compounds according to claim 1, where R3means the residue -(CH2)n-R3a.

15. Connection 14, where R3ameans3-6cycloalkyl condensed with a phenyl ring.

16. Connection 14, where R3ameans unsubstituted cycloalkenyl balance with five or six carbon atoms.

17. Connection 14, where R3ameans 5 - or 6-membered monovalent saturated heterocyclic ring containing one or two heteroatoms independently selected from nitrogen and oxygen, and mentioned heterocyclic ring optionally is monosubstituted independently lower alkyl.

18. Connection 14, where R3ameans 5 - or 6-membered heteroaromatic ring containing one heteroatom selected from oxygen and sulfur, and mentioned heteroaromatic ring optionally monogamist lower alkyl.

19. Connection 14, where R3ameans phenyl, optionally mono - or disubstituted independently a hydroxy-group, lower alkyl, lower alkoxygroup, halogen, halogenated lower alkyl, halogenated lower alkoxygroup or nitrogroup.

20. Connection 14, where n is 1 or 2.

21. Compounds according to claim 1, where R4means unsubstituted cyclohexyl.

22. Compounds according to claim 1, where R4means 5 - or 6-membered, heteroarm eticheskoe ring, containing one or two heteroatoms independently selected from nitrogen, and mentioned heteroaromatic ring optionally monogamist lower alkyl.

23. Compounds according to claim 1, where R4means phenyl, mono - or disubstituted independently lower alkoxygroup.

24. Compounds according to claim 1, where two adjacent substituent of the phenyl residue R4mean along-O-(CH2)-O - or -(CH2)2-O-.

25. Compounds according to claim 1, selected from the group including:

butylamide 1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-(4-methoxybenzyl)-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

second-butylamide rat-1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

second-butylamide rat-1-cyclohexylmethyl-5-[2-(4-methoxyphenoxy)-thiazol-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

isobutylene 1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1 H-pyrrole-3-carboxylic acid,

isobutylene 1-furan-2-yl-methyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1 H-pyrrole-3-carboxylic acid,

isobutylene 1-(4-methoxybenzyl)-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

Alleluia 1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-METI what-1H-pyrrole-3-carboxylic acid,

cyclohexylethylamine 1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

cyclohexylethylamine 1-cyclohexylmethyl-2-methyl-5-(2-pyrazin-2-yl-thiazol-4-yl)-1H-pyrrole-3-carboxylic acid,

cyclohexylethylamine 1-(4-methoxybenzyl)-5-[2-(4-methoxyphenyl 1)thiazol-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

cyclohexylethylamine 5-[2-(4-methoxyphenoxy)thiazol-4-yl]-1-(3-methoxypropyl)-2-methyl-1H-pyrrole-3-carboxylic acid,

ethyl ester of 4-[1-[2-(3,4-acid)ethyl]-4-(3-methoxypropylamine)-5-methyl-1H-pyrrol-2-yl]thiazole-2-carboxylic acid,

piperidine-1-yl-amide 1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

ethyl ester of N′-{1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carbonyl}hydrazinecarboxamide acid,

second-butylamide rat-1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

{1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrol-3-yl}-piperidine-1-yl-methanon,

phenylamide 1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

pyrimidine-2-yl-amide 1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

(5-hydroxy-2,2,6-t is emailcollector)amide rat-1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1-(3-cryptomaterial)-1H-pyrrole-3-carboxylic acid,

butylamide 1-benzyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

{1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrol-3-yl}-pyrrolidin-1-yl-methanon,

butylamide 1-cyclohexylmethyl-5-[2-(3,4-acid)thiazol-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-5-[2-(3-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 5-(2-benzo[1,3]dioxol-5-yl-thiazol-4-yl)-1-cyclohexylmethyl-2-methyl - 1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-5-[2-(4-forfinal)thiazol-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-5-[2-(2-forfinal)thiazol-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-2-methyl-5-[2-(4-trifloromethyl)thiazol-4-yl]-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-5-[2-(3,5-acid)thiazol-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-2-methyl-5-(2-m-tolyltriazole-4-yl)-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-2-methyl-5-(2′-methyl-[2,4′]betazole-4-yl)-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexene is l-5-[2-(4-ethylphenyl)thiazol-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 5-[2-(4-chlorophenyl)thiazol-4-yl]-1-cyclohexylmethyl-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 5-[2-(4-tert-butylphenyl)thiazol-4-yl]-1-cyclohexylmethyl-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-5-[2-(2,3-dihydrobenzofuran-5-yl)thiazol-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-2-methyl-5-(2-n-tolyltriazole-4-yl)-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-5-[2-(6-methoxypyridine-3-yl)thiazol-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-5-[2-(2,4-dichlorophenyl)thiazol-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-2-methyl-5-[2-(4-nitrophenyl)thiazol-4-yl]-1H-pyrrole-3-carboxylic acid,

pencilled 1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

propelled 1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

cyclohexylamin 1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

cyclopentolate 1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

cyclopropylamino 1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

cyclobe ilamed 1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

(2-hydroxycyclopent)amide(TRANS)rat-1-cyclohexylmethyl-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-(4-Chlorobenzyl)-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-(3,4-dichlorobenzyl)-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-(3,4-dimethylbenzyl)-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-(3,4-dimethoxybenzyl)-5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-5-[2-(4-hydroxyphenyl)thiazol-4-yl]-2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-(4-isopropylbenzyl)-5-[2-(4-methoxyphenyl)thiazole-4-yl] -2-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 5-[2-(4-methoxyphenyl)thiazole-4-yl]-2-methyl-1-pyridin-2-yl-methyl-1H-pyrrole-3-carboxylic acid,

butylamide 1-cyclohexylmethyl-5-(2-cyclohexylthio-4-yl)-2-methyl-1H-pyrrole-3-carboxylic acid,

and their pharmaceutically acceptable salts.

26. The compounds of formula (I)as defined in claim 1, having the property of receptor modulator SW.

27. The compounds of formula (I)as defined in claim 1, for use as therapeutically active substances for the treatment and/or prevention of diseases associated with the modulation is of eceptor SW.

28. Pharmaceutical composition having the property of a modulator of the receptor SW containing compound according to any one of claims 1 to 25 and a pharmaceutically acceptable carrier and/or excipient.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to new bonds in the formula (I-0): or its pharmaceutically acceptable salts, where X represents a carbon atom or nitrogen atom; X1, X2, X3 and X4, each independently, represents a carbon atom or a nitrogen atom; ring A of the formula (II): represents tiazolil, imidazolil, izotiazolil, tiadiazolil, triazolil, oxazolil, oxadiazolil, izoxazolil, pirazinil, piridil, piridazinil, pirazolil or pirimidinil; R¹ represents aryl or represents a 4-10- membered monocyclic or bicyclic heteroring, which has in the ring from 1 to 4 heteroatoms, selected from the group, consisting of a nitrogen atom, sulphur atom and an oxygen atom, and R¹ can be independently substituted with 1-3 R4, and, when the specified heteroring is an aliphatic heteroring, then it can have 1 or 2 double bonds; R² independently represents hydroxy, formyl, -CH3-aFa, -OCH3-aFa, amino, CN, halogen, C1-6 alkyl or -(CH2)1-4OH; R3 represents -C1-6 alkyl, -(CH2)1-6-OH, -C(O)-OC1-6 alkyl, -C(O)-OC1-6 alkyl, -(CH2)1-6-NH2, cyano, -C(O)-C1-6 alkyl, halogen, -C2-6 alkenyl, -OC1-6 alkyl, -COOH, -OH or oxo; R4 independently represents -C1-6 alkyl, and the alkyl can be substituted with identical or different 1-3 hydroxyls, halogens, -OC(O)-C1-6 alkyls, and the alkyl can be substituted with 1-3 halogens or -OC1-6 alkyls, -C3-7 cycloalkyl, -C2-6 alkenyl, -C(O)-N(R51)R52, -S(O)2-N(R51)R52,-O-C1-6 alkyl, and C1-6 alkylcan be substituted with a halogen or N(R51)R52, -S(O)0-2-C1-6 alkyl, -C(O)-C1-6 alkyl, and C1-6 alkyl can be substituted with a halogen, amino, CN, hydroxy, -O-C1-6 alkyl, -CH3-aFa, -OC(O)-C1-6 alkyl, -N(C1-6 alkyl)C(O)O-C1-6 alkyl, -NH-C(O)O-C1-6 alkyl, phenyl, -N(R51)R52, -NH-C(O)-C1-6 alkyl, -N(C1-6 alkyl)-C(O)-C1-6 alkyl or -NH-S(O)0-2-C1-6 alkyl, -C(S)-C3-7 cycloalkyl, -C(S)- C1-6 alkyl, -C(O)-O- C1-6 alkyl, -(CH2)0-4-N(R53)-C(O)-R54, -N(R53)-C(O)-O-R54,-C(O)-aryl, it is optional to substitute the halogen, -C(O)-aromatic heteroring, -C(O)-aliphatic heteroring, heteroring, and the heteroring can be substituted with C1-6 alkyl, optionally substituting the halogen or -O-C1-6 alkyl, phenyl, optionally substituting the halogen, -C1-6 alkyl, -O-C1-6 alkyl, halogen, CN, formyl, COOH, amino, oxo, hydroxy, hydroxyamidine or nitro; R51 and R52, each independently, represents a hydrogen atom, C1-6 alkyl or a nitrogen atom, R51 and R52 together form 4-7-member heteroring; R53 represents a hydrogen atom or C1-6 alkyl, R54 represents -C1-6 alkyl or alkyls for R53 and R54 and -N-C(O)- together form 4-7-member hydrogen containing heteroring, or alkyls for R53 and R54 and -N-C(O)-O- together form 4-7-member hydrogen containing aliphatic heteroring and an aliphatic heteroring can be substituted with oxo, or an aliphatic heteroring can have 1 or 2 double bonds in the ring; X5 represents -O-, -S-, -S(O)-, -S(O)2-, a single bond or -O-C1-6 alkyl; a independently denotes a whole number 1, 2 or 3; q denotes a whole number from 0 till 2; m denotes a whole number from 0 till 2, except in the case when one of the X5 represents -O-, -S-, -S(O)- or -S(O)2-, and the other from X5 represents a single bond, and R1 represents aryl, optionally substituted with 1-3 R4, or a hydrogen containing aromatic heteroring, consisting of from 1 to 4 heteroatoms, selected from the group, comprising of a hydrogen atom, sulphur atom and an oxygen atom, in the case, when X5, both represent single bonds or in cases, when R1, both represent aliphatic heteroring. The invention also relates to the bonding in the formula (I-12), and also to the bonding in the formula (I-0), to the pharmaceutical composition, to the glucokinase activator and to the medication.

EFFECT: getting new bioactive compounds which can be used for treatment and/or prophylaxis of diabetes or obesity.

23 cl, 603 ex

FIELD: chemistry; obtaining of medicinal preparations.

SUBSTANCE: description is given of a compound with general formula where R1 represents a halogen, C1-C6alkyl, CF3, CF2H or cyano, R2 represents C1-C6alkyl, R3 represents 5- or 6 - member hetero-aryl, optionally substituted with one, two or three substitutes, chosen from a group, consisting of a halogen, C1-C6alkyl, C3-C6cycloalkyl, C1-C6alkylhalogen, C1-C6alkoxy, NR'R", or substituted with a 1-morpholinyl group or substituted with thiomorpholinyl groups, 1-oxothiomorpholinyl or 1,1-dioxothiomorpholinyl; R', R" independently represent hydrogen, C1-C6alkyl, (CH2)0,1-(C3-C6)cycloalkyl, R represents hydrogen as well as its pharmaceutical salts and the method of obtaining them. The invention also relates to use of the given amidazole derivatives for obtaining medicinal preparations and to medicinal preparations containing them, meant for prevention or treatment of damages, through the mGluR5 receptor, such as acute and/or chronic neurologic damages, primarily shock pain, or for treatment of chronic and sharp pain.

EFFECT: obtaining of new compounds, with useful biological properties.

40 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new derivatives of benzimidazol of the general formula I R1 designates phenyl group which unessentially contains up to three substitutors independently chosen of the group including F, Cl, Br, J, R4; R2 designates monocyclic or bicyclic 5-10-terms heteroaryl group which contains 1-2 heteroatoms, chosen of N, S and O; R3 designates H; R4 designatesC1-6alkyl; A designates C2-6 alkylene group; B designates group COOH, CONH2, CONHR5 or CONR5R5, in each case attached to atom of carbon of group A; R5 and R5 ' independently designate the residue chosen from group includingC1-6 alkyl where one C-atom can be replaced by O, and(C0-3 alkandiil-C3-7 cycloalkyl); and to their pharmaceutically acceptable salts, except for following compounds: 6 [[1-phenyl-2 (pyridine-4-il)-1H-benzimidazol-6-il] oxi] hexanic acid and 6 [[1-phenyl-2 (benzothien-2-il)-1H-benzimidazol-6-il] oxi] hexanic acid. The invention relates also to pharmaceuticals and to application of compounds of general formula I.

EFFECT: new biologically active compounds possess inhibiting effect on activation of microglia.

10 cl, 34 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): and their pharmaceutically acceptable salts and esters wherein R1 means phenyl, naphthyl, 5-6-membered heterocyclyl comprising oxygen (O), nitrogen (N) or sulfur atom (S) as heteroatoms and wherein phenyl, naphthyl and heterocyclyl are optionally substituted with 1-3 substitutes chosen from halogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy, halogen-(C1-C6)-alkyl, halogen-(C1-C6)-alkoxy, nitro; di-(C1-C6)-alkylamino or (C1-C6)-alkoxy groups; R2 means hydrogen atom; R3 means (C1-C6)-alkyl or trifluoromethyl; A1 means C-R3 or nitrogen atom; A2 means piperidine or pyrrolidine wherein nitrogen atom in piperidine or pyrrolidine ring is added to A3 wherein A3 means -S(O)2- or -C(O)-; n = 0, 1 or 2. Also, invention relates to a pharmaceutical composition based on compounds proposed by the invention. Proposed compounds possess properties of NPY receptors antagonists and can be used in treatment arthritis, diabetes mellitus, nutrition disorders, obesity and others.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

16 cl, 1 tbl, 1 dwg, 26 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compound of the formula (I) possessing inhibitory effect on production of interleukin-12 (IL-12) wherein R1 represents group of the formula , aryl or heteroaryl; each among R2 and R4 represents independently hydrogen atom, (C1-C6)-alkyl or (C1-C6)-alkoxy group; R3 represents Rc, alkenyl, -ORc, -OC(O)Rc, -SRc, -NRcCORd, -NRcC(O)ORd, -NRcC(O)NRcRd, -NRcSO2Rd, -CORc, -C(O)ORc or -C(O)NRcRd; R5 represents hydrogen atom (H); n = 0, 1, 2, 3, 4, 5 or 6; X represents oxygen atom (O) or -NRc; Y represents a covalent bond. -CH2, O or -NRc; Z represents nitrogen atom (N); one of values U and V represents N and another represents -CRc; W represents O, sulfur atom (S) or -S(O)2 wherein each radical among Ra and Rb represents independently H, (C1-C6)-alkyl, aryl or heteroaryl; each radical among Rc and Rd represents independently H, (C1-C6)-alkyl, phenyl, heteroaryl, cyclyl, heterocyclyl or (C1-C6)-alkylcarbonyl wherein term "aryl" relates to hydrocarbon cyclic system (monocyclic or bicyclic) comprising at least one aromatic ring; term "heteroaryl" relates to hydrocarbon cyclic system (monocyclic or bicyclic) comprising at least one aromatic ring that comprises at least one heteroatom, such as O, N or S as a part of cyclic system and wherein other atoms mean carbon; term "cyclyl" and "heterocyclyl" relate to partially or completely saturated monocyclic or bicyclic system comprising from 4 to 14 carbons in rings wherein heterocyclic ring comprises one or some heteroatoms (for example, O, N or S) as part of cyclic system and wherein other atoms mean carbon, and under condition that when X represents -NH, Y represents a covalent bond, n = 0, and R3 represents H or CH3 then R1 doesn't mean thiazolyl or pyrimidinyl. Also, invention relates to a pharmaceutical composition and a method for treatment of disorder associated with hyperproduction of interleukin-12.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

49 cl, 43 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of pyrrolidinium of the general formula (I): possessing antagonistic effect with respect to muscarinic receptors M3 wherein B means phenyl or thienyl group; each radical among R1, R2 and R means independently hydrogen, fluorine, chlorine atom or hydroxyl; n means a whole number from 0 to 1; A means group chosen from groups -CH2 and -O-; m means a whole number from 0 to 6; R means (C1-C8)-alkyl; X- represents a pharmaceutically acceptable anion of mono- or multibasic acid, and involving all separate stereoisomers and their mixtures. Also, invention relates to methods for synthesis of such compounds, pharmaceutical compositions containing such compounds and to their using in therapy as antagonists of muscarinic receptors M3.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

17 cl, 51 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes compounds of the formula (I) or their pharmaceutically acceptable salts wherein R1 and R2 are similar or different and chosen independently from group comprising aryl and heteroaryl. Each of them as a substitute comprises optionally from one to sic groups chosen from group comprising the following groups: (a) halogen atom; (b) -OCF3 or -OCHF2; (c) -CF3; (d) -CN; (e) alkyl; (f) R18-heteroaljyl; (k) hydroxyl; (l) alkoxyl comprising cyclopropylmethoxyl, and (s) trifluoroalkoxyl; R3 means hydrogen atom (H); R4, R5, R7 and R8 are similar or different and chosen independently from group comprising H, -OH, alkyl, heteroalkyl and

under condition that if Z and/or X means nitrogen atom (N) then all radicals R4, R5, R7 and R8 don't mean -OH; R6 means -C(O)R15; R9 and R10 mean H; R11 is chosen from group comprising H and alkyl; R12 is chosen from group comprising H and alkyl; R13 is chosen from group comprising alkyl and alkoxyl; R14 means H; R15 is chosen from group comprising -NR16R17, -OR16 and alkyl wherein R16 and R17 are similar or different and chosen independently from group comprising H and alkyl; R18 means a substitute chosen from group comprising lower alkyl, halogen alkyl, halogenalkyl, alkoxycarbonyl, dialkylamino-group and piperidinyl; X and Z are similar or different and chosen independently from carbon atom (C) and N. Proposed compounds possess properties of inhibitor of 17β-hydroxysteroid dehydrogenase of type 3. Also, invention describes a pharmaceutical composition based on compound of the formula (I).

EFFECT: valuable medicinal and biochemical properties of compound and pharmaceutical composition.

16 cl, 23 tbl, 651 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to substituted 2-thio-3,5-dicyano-4-phenyl-6-aminopyridines represented by the formula (I): wherein n means 2, 3 or 4; R1 means hydrogen atom or alkyl with 1-4 carbon atoms; R2 means pyridyl or thiazolyl that can be substituted with alkyl with 1-4 carbon atoms, halogen atom, amino-, dimethylamino-, acetylamino-, guanidino-, pyridylamino-group, thienyl, pyridyl, morpholinyl and thiazolyl substituted if necessary with alkyl with 1-4 carbon atoms or phenyl comprising if necessary up to three substitutes as halogen atom, alkyl with 1-4 carbon atoms or alkoxy-group with 1-4 carbon atoms, and to their salts, hydrates, salt hydrates and solvates, and also to substituted 2-thio-3,5-dicyano-4-phenyl-6-aminopyridine of the formula (I) possessing properties of agonist of A1-adenosine receptors. Also, invention describes a medicinal agent possessing properties of agonist of A1-adenosine receptors. Invention provides synthesis of novel compounds possessing valuable biological properties.

EFFECT: valuable medicinal and pharmacological properties of compounds and drug.

7 cl, 3 tbl, 27 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes novel nitrogen-containing aromatic derivatives of the general formula (I): wherein X1 means nitrogen atom (N) or group -CR10= wherein R10 means hydrogen atom (H), halogen atom or -CN; X2 means N or group -CR11= but X1 and X2 can't mean N simultaneously; Y means oxygen atom (O) or group -NRY- wherein RY means hydrogen atom or (C1-C6)-alkyl group; R1 means phenoxy-group, group -NR12aR12b, group , group and other values; each radical among R3, R4, R5, R6 and R11 means hydrogen atom; R7 means hydrogen atom or (C1-C6)-alkyl group; R8 means hydrogen atom or (C1-C6)-alkyl group; R10 means hydrogen atom, halogen atom or cyano-group; R9 means group -NR16aR16b or group of the formula: wherein T2 means pyrrolidine, piperazine ring possibly substituted with (C1-C6)-alkyl group, or morpholine ring; R12a and R12b mean independently hydrogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group; R2 means hydrogen atom or (C1-C6)-alkyl; R16a means hydrogen atom or (C1-C6)-alkyl, and R16b means (C1-C6)-alkyl possibly substituted with phenyl, (C1-C6)-alkoxy-group, (C1-C6)-alkylthio-group or di-(C1-C6)-alkylamino-group, (C3-C6)-alkynyl, (C3-C8)-cycloalkyl, phenyl possibly substituted with halogen atom, thiazolyl or piperidinyl possibly substituted with (C1-C6)-alkyl, and their salts or hydrates. Also, invention describes a pharmaceutical composition, method for treatment or prophylaxis of tumor diseases and using the novel compounds for preparing an agent useful in treatment abovementioned diseases.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method for treatment.

26 cl, 17 tbl, 221 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to novel derivatives of nicotinamide of the general formula (I): wherein R1 is chosen from hydrogen atom, unsubstituted or substituted (C1-C6)-alkyl, (C2-C6)-alkenyl, (C3-C7)-cycloalkyl, phenyl or heteroaryl; R2 is chosen from hydrogen atom, (C1-C6)-alkyl and group -(CH2)q-(C3-C7)-cycloalkyl, or -(CH2)mR1 and R2 in common with nitrogen atom to which they are bound form (four-six)-membered heterocyclic ring; R3 represents chlorine atom or methyl group; R4 represents group -NH-CO-R7 or -CO-NH-(CH2)q-R8; R7 is chosen from hydrogen atom, (C1-C6)-alkyl, group -(CH2)q-(C3-C7)-cycloalkyl and others; R8 is chosen from hydrogen atom, (C1-C6)-alkyl, (C3-C7)-cycloalkyl and others; each X and Y is chosen independently from hydrogen atom, methyl group and halogen atom; Z represents halogen atom; m is chosen from 0,1, 2, 3 and 4; n and q are chosen from 0, 1 and 2, and to pharmaceutically acceptable salts or their solvates. Indicated compounds possess inhibitory activity with respect to p38 kinase and can be used in medicine.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

15 cl, 127 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new bonds in the formula (I-0): or its pharmaceutically acceptable salts, where X represents a carbon atom or nitrogen atom; X1, X2, X3 and X4, each independently, represents a carbon atom or a nitrogen atom; ring A of the formula (II): represents tiazolil, imidazolil, izotiazolil, tiadiazolil, triazolil, oxazolil, oxadiazolil, izoxazolil, pirazinil, piridil, piridazinil, pirazolil or pirimidinil; R¹ represents aryl or represents a 4-10- membered monocyclic or bicyclic heteroring, which has in the ring from 1 to 4 heteroatoms, selected from the group, consisting of a nitrogen atom, sulphur atom and an oxygen atom, and R¹ can be independently substituted with 1-3 R4, and, when the specified heteroring is an aliphatic heteroring, then it can have 1 or 2 double bonds; R² independently represents hydroxy, formyl, -CH3-aFa, -OCH3-aFa, amino, CN, halogen, C1-6 alkyl or -(CH2)1-4OH; R3 represents -C1-6 alkyl, -(CH2)1-6-OH, -C(O)-OC1-6 alkyl, -C(O)-OC1-6 alkyl, -(CH2)1-6-NH2, cyano, -C(O)-C1-6 alkyl, halogen, -C2-6 alkenyl, -OC1-6 alkyl, -COOH, -OH or oxo; R4 independently represents -C1-6 alkyl, and the alkyl can be substituted with identical or different 1-3 hydroxyls, halogens, -OC(O)-C1-6 alkyls, and the alkyl can be substituted with 1-3 halogens or -OC1-6 alkyls, -C3-7 cycloalkyl, -C2-6 alkenyl, -C(O)-N(R51)R52, -S(O)2-N(R51)R52,-O-C1-6 alkyl, and C1-6 alkylcan be substituted with a halogen or N(R51)R52, -S(O)0-2-C1-6 alkyl, -C(O)-C1-6 alkyl, and C1-6 alkyl can be substituted with a halogen, amino, CN, hydroxy, -O-C1-6 alkyl, -CH3-aFa, -OC(O)-C1-6 alkyl, -N(C1-6 alkyl)C(O)O-C1-6 alkyl, -NH-C(O)O-C1-6 alkyl, phenyl, -N(R51)R52, -NH-C(O)-C1-6 alkyl, -N(C1-6 alkyl)-C(O)-C1-6 alkyl or -NH-S(O)0-2-C1-6 alkyl, -C(S)-C3-7 cycloalkyl, -C(S)- C1-6 alkyl, -C(O)-O- C1-6 alkyl, -(CH2)0-4-N(R53)-C(O)-R54, -N(R53)-C(O)-O-R54,-C(O)-aryl, it is optional to substitute the halogen, -C(O)-aromatic heteroring, -C(O)-aliphatic heteroring, heteroring, and the heteroring can be substituted with C1-6 alkyl, optionally substituting the halogen or -O-C1-6 alkyl, phenyl, optionally substituting the halogen, -C1-6 alkyl, -O-C1-6 alkyl, halogen, CN, formyl, COOH, amino, oxo, hydroxy, hydroxyamidine or nitro; R51 and R52, each independently, represents a hydrogen atom, C1-6 alkyl or a nitrogen atom, R51 and R52 together form 4-7-member heteroring; R53 represents a hydrogen atom or C1-6 alkyl, R54 represents -C1-6 alkyl or alkyls for R53 and R54 and -N-C(O)- together form 4-7-member hydrogen containing heteroring, or alkyls for R53 and R54 and -N-C(O)-O- together form 4-7-member hydrogen containing aliphatic heteroring and an aliphatic heteroring can be substituted with oxo, or an aliphatic heteroring can have 1 or 2 double bonds in the ring; X5 represents -O-, -S-, -S(O)-, -S(O)2-, a single bond or -O-C1-6 alkyl; a independently denotes a whole number 1, 2 or 3; q denotes a whole number from 0 till 2; m denotes a whole number from 0 till 2, except in the case when one of the X5 represents -O-, -S-, -S(O)- or -S(O)2-, and the other from X5 represents a single bond, and R1 represents aryl, optionally substituted with 1-3 R4, or a hydrogen containing aromatic heteroring, consisting of from 1 to 4 heteroatoms, selected from the group, comprising of a hydrogen atom, sulphur atom and an oxygen atom, in the case, when X5, both represent single bonds or in cases, when R1, both represent aliphatic heteroring. The invention also relates to the bonding in the formula (I-12), and also to the bonding in the formula (I-0), to the pharmaceutical composition, to the glucokinase activator and to the medication.

EFFECT: getting new bioactive compounds which can be used for treatment and/or prophylaxis of diabetes or obesity.

23 cl, 603 ex

FIELD: chemistry; oxa-and thiazole derivatives.

SUBSTANCE: oxa- and thiazole derivatives have general formula . Their stereoisomers and pharmaceutical salts have PPARα and PPARγ activity. The compounds can be used for treating diseases, eg. diabetes and anomaly of lipoproteins through PPARα and PPARγ activity. In the general formula, x has value of 1, 2, 3 or 4; m has value of 1 or 2; n has value of 1 or 2; Q represents C or N; A represents O or S; Z represents O or a bond; R1 represents H or C1-8alkyl; X represents CH; R2 represents H; R2a, R2b and R2c can be the same or different and they are chosen from H, alkoxy, halogen; R3 represents aryloxycarbonyl, alkyloxycarbonyl, alkyl(halogen)aryloxycarbonyl, cycloalkylaryloxycarbonyl, cycloalkyloxyaryloxycarbonyl, arylcarbonylamino, alkylsulphonyl, cycloheteroalkyloxycarbonyl, heteroarylalkenyl, alkoxyaryloxycarbonyl, arylalkyloxycarbonyl, alkylaryloxycarbonyl, halogenalkoxyaryloxycarbonyl, alkoxycarbonylaryloxycarbonyl, arylalkenyloxycarbonyl, aryloxyarylalkyloxycarbonyl, arylalkenylsulphonyl, heteroarylsulphonyl, arylsulphonyl, arylalkenylarylalkyl, arylalkoxycarbonyl-heteroarylalkyl, heteroaryloxyarylalkyl, where alkyl is in form of C1-8alkyl; Y represents CO2R4, where R4 represents H or C1-8alkyl; including all their stereoisomers and pharmaceutical salts, under the condition that, if A is O, then R3 is not aryloxycarbonyl or alkoxyaryloxycarbonyl.

EFFECT: the compounds can be used in curing such diseases as diabetes and lipoprotein anomalies.

10 cl, 30 dwg, 12 tbl, 584 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention describes novel derivatives of 1,2,4-triazole of the general formula (I): wherein A and b can be taken separately or in common being when they are taken separately then A means (C1-C6)-alkyl or phenyl, and B means (C1-C6)-alkyl; A and B taken in common mean (C2-C5)-alkanediyl, and they form with C-atoms 3-6-membered cycle optionally substituted with (C1-C4)-alkylene, oxo, ethylenedioxy group, (C1-C4)-alkyl, 1-2 halogen atoms, (C1-C3)-alkoxy-(C1-C3)-alkoxy or hydroxy group; each R1 means independently hydrogen atom, -OH, halogen atom, (C3-C6)-cycloalkyl, (C1-C6)-alkyl optionally substituted with 1-3 halogen atoms; or two R1 groups near adjacent carbon atoms form 6-membered aryl cycle; R2 and R3 can be taken in common or separately, and when they are taken in common then they represent (C3-C8)-alkanediyl that forms condensed 5-10-membered nonaromatic cycle; when R2 and R3 are taken separately then R2 means (C1-C6)-alkyl possibly substituted with 1-3 halogen atoms or cyclopropyl, and R3 means cyclopropyl possibly substituted with (C1-C4)-alkyl, naphthyl, phenyl possibly substituted with halogen atom, -OH, (C1-C6)-alkyl wherein indicated (C1-C6)-alkyl is optionally substituted with 1-3 halogen atoms, -O-(C1-C6)-alkyl wherein indicated -O-(C1-C6)-alkyl is optionally substituted with 1-3 halogen atoms, phenyl or benzyloxy group, dihydrobenzofuranyl, benzothiadiazolyl or benzoimidazolyl possibly substituted with (C1-C6)-alkyl, their pharmaceutically acceptable salts or solvates, and pharmaceutical composition based on thereof. Proposed compounds are inhibitor of 11β-hydroxysteroid dehydrogenase I, and can be used in medicine in treatment of diabetes mellitus, obesity and dyslipidemia.

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical composition.

19 cl, 17 tbl, 4 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): and/or stereomer form of compound of the formula (I), and/or physiologically compatible salt of compound of the formula (I) wherein X and M are similar or different and mean independently of one another nitrogen atom (N) or -CH; R1 and R11 are similar or different and mean independently of one another: (1.) hydrogen atom; (2.) fluorine (F), chlorine (Cl), iodine (J) or bromine (Br) atom; R2 means: (1.) heteroaryl residue of group comprising 1,3,4-oxadiazole, oxadiazolylidinedione, oxadiazolone, thiazole, and heteroaryl residue is unsubstituted or 1-3-times substituted independently of one another: (1.1.) keto-group; (2) -C(O)-R5 wherein R5 means hydrogen atom or -(C1-C4)-alkyl, or (3.) -C(O)-N(R7)-R8 wherein R7 and R8 mean independently of one another hydrogen atom, -(C1-C4)-alkyl-OH, -O-(C1-C4)-alkyl or -(C1-C4)-alkyl; R3 means hydrogen atom or -(C1-C4)-alkyl; R4 means: (1.) heteroaryl residue of group comprising thiazole, isothiazole, pyridine, pyrazine, pyrimidine wherein heteroaryl residue is unsubstituted or 1-3-times substituted independently of one another with -(C1-C5)-alkyl, halogen atom, trifluoromethyl, or (2.) aryl residue of group comprising phenyl. Also, invention relates to a method for preparing a medicinal agent and to using compounds based on the formula (I) possessing activity with respect to IkB kinase. Invention provides synthesis of novel compounds possessing useful biological properties.

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical agent.

6 cl, 67 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of carboxylic acid represented by the general formula (I): , their pharmaceutically acceptable salts or esters wherein values Y, L, X, T, Z, M, R1, W and are given in the invention claim. Proposed compounds possess insulin-sensitizing effect and they are double agonists with respect to PPARα and γ, and triple agonists with respect to PPARα, β(δ) and γ. Except for, the invention relates to a medicinal agent and pharmaceutical compositions based on the claimed derivatives of carboxylic acid, to methods for prophylaxis or treatment of diseases, and to using derivatives carboxylic acid for preparing a medicinal agent.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

56 cl, 2 tbl, 609 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I) and their pharmaceutically acceptable salts and esters. In the general formula (I) X means oxygen (O) or sulfur (S) atom; R means hydrogen atom (H) or (C1-C6)-alkyl; R1 means H, -COOR, (C3-C8)-cycloalkyl or (C1-C6)-alkyl, (C2-C6)-alkenyl or (C1-C6)-alkoxyl and each of them can be unsubstituted or comprises substitutes; values of radicals R2, R3, R4, R5 and R6 are given in the invention claim. Also, invention relates to a pharmaceutical composition based on compounds of the general formula (I) and to intermediate compounds of the general formula (II) and the general formula (III) that are used for synthesis of derivatives of indane acetic acid. Proposed compounds effect on the blood glucose level and serum triglycerides level and can be used in treatment of such diseases as diabetes mellitus, obesity, hyperlipidemia and atherosclerosis.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

28 cl, 6 tbl, 6 sch, 251 ex

FIELD: organic chemistry, biochemistry, enzymes.

SUBSTANCE: invention relates to compounds represented by the formula: wherein values of substitutes are given in the invention description. Also, invention relates to pharmaceutically acceptable salts of the compound that can be used in treatment and/or prophylaxis of cathepsin-dependent states or diseases of mammals. Proposed compound are useful in treatment of diseases wherein bone resorption inhibition is desired, such as osteoporosis, increased mineral density of bone and reducing risk of fractures. Proposed claimed compounds are designated for preparing a drug possessing the inhibitory activity with respect to cathepsin.

EFFECT: valuable medicinal and biochemical properties of compounds.

24 cl, 13 sch, 4 tbl, 15 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to using compounds of the general formula (I): and their pharmaceutically acceptable acid-additive salts. Compounds are used for preparing medicinal agents used in treatment diseases and state associated with system of adenosine receptors A2A, such as Alzheimer's disease, Parkinson's diseases, Huntington's syndrome, schizophrenia, anxiety state, pain, depression, narcomania to such substances as amphetamine, cocaine, opioides, ethyl alcohol, nicotine, cannabinoids, or in treatment of hypoxia, ischemia, epileptic attack. Also, proposed compounds exert neuroprotective effect and can be used as sedative, antipsychotic or anti-epileptic agents.

EFFECT: valuable medicinal properties of compounds.

18 cl, 1 tbl, 49 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new compounds of general formula I , wherein one from V or X is N and another is CRa or both V and X are CRa (each CRa is independently hydrogen atom); Y is O, S; Z is N(R2)(R3); R1 is hydrogen, C1-C10-alkyl, C3-C7-cycloalkyl, etc.; R4 is hydrogen, C1-C6-alkyl, C3-C7-cycloalkyl, etc.; A is hydrogen, C1-C10-alkyl, halo-C1-C6-alkyl, etc.; B is optionally substituted 5-membered aromatic ring containing at least one nitrogen atom and 0-3 additional heteroatoms; U is -NR5; meanings of the rest substituents are as defined in specification, and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical composition and intermediates of formula I.

EFFECT: new biologically active compounds and pharmaceutical compositions based on the same having inhibition activity in relates to IKK-β enzyme.

26 cl, 13 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to compounds of the general formula (I): wherein R1 means hydrogen atom or lower alkyl; R2 means lower alkyl, -(CH2)n-O-lower alkyl, -(C3-C6)-cycloalkyl or -(CH2)n-NR'2 wherein R' means hydrogen atom, lower alkyl or -(CH2)n-O-lower alkyl independently of one another for R'2; or R'2 in common with nitrogen atom can form pyrrolidine ring, and wherein n = 1, 2 or 3. Also, invention relates to a pharmaceutical composition possessing antagonistic activity with respect to A2 receptors and containing one or some compounds of the general formula (I) and its pharmaceutically acceptable excipients. Invention provides synthesis of compound of the general formula (I) possessing antagonistic activity with respect to A2 receptors.

EFFECT: valuable medicinal property of compounds and pharmaceutical composition.

11 cl, 19 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to the obtaining of the new derivatives of benzamide of the formulas (I), which possess the activating influence on glucokinase, which can be used for treating of diabetes and obesity: where X1 and X2 represent oxygen, R1 represents alkylsufonyl, alkaneyl, halogen or hydroxyl; R2 represents alkyl or alkenyl, R3 represents alkyl or hydroxyalkyl, ring A represents phenyl or pyridyl, the ring B represents thiazolyl, thiadiazolil, isoxazoleyl, pyridothiazolyl or pyrazolyl, in which the atom of carbon of ring B, which is connected with the atom of nitrogen of the amide group of the formula(I), forms C=N bond with ring B.

EFFECT: obtaining new bioactive benzamides.

12 cl, 166 ex, 4 tbl

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