Imidazole versions as modulators of gamma-aminobutyric acid (gaba) receptor for treating gastrointestinal (gi)

FIELD: chemistry.

SUBSTANCE: present invention relates to new imidazole derivatives of general formula I , where R1 is C1-C10alkyl or C3-C10cycloalkyl, each possibly and independently substituted with 1 substitute selected from C3-C10cycloalkyl or aryl or a heteroaryl group, possibly substituted with one or two halogens; aryl or heteroaryl; R2 is C1-C10alkoxy or C1-C10thioalkyl; R3 is C1-C10alkoxy, possibly substituted with one C1-C10alkoxy or nitrile, where the said alkoxy group can be cyclic or can contain one O heteroatom; R4 is C1-C10alkyl; C2-C10alkenyl; C1-C10alkoxy or C3-C10cycloalkyl, each possibly and independently substituted with 1 or 2 substitutes selected from C1-C10alkoxy, C3-C10cycloalkyl, carboxylic ester, or with one or two aryl or heteroaryl groups, possibly substituted with one substitute selected from C1-C10alkyl, C3-C10cycloalkyl, nitro or halogen; aryl or heteroaryl, each possibly and independently substituted with 1-3 substitutes selected from C1-C10alkyl, C3-C10cycloalkyl, C1-C10alkoxy, phenoxy, thiophenyl, halogen, nitro, nitrile or aryl group, possibly substituted with one halogen; where up to three hydrogen atoms of the alkyl group can be substituted with fluorine atoms; where the said cycloalkyl can independently have one or two carbon atoms substituted with O or N; where the said aryl denotes an aromatic ring having 6 to 10 carbon atoms, including mono- and bicyclic compounds; and where the said heteroaryl denotes an aromatic ring having 3 to 10 carbon atoms, including mono- and bicyclic compounds in which one to three ring atoms are oxygen, nitrogen or sulphur atoms; except compounds given in paragraph 1. The invention also pertains to use of the said compounds for making a medicinal agent, a treatment and prevention method, a compound of formula II (values of radicals are given in the formula of invention).

EFFECT: new imidazole derivatives having positive allosteric modulator effect on GABAB receptor are obtained.

30 cl, 6 ex

 

The text descriptions are given in facsimile form.

1. The compound of General formula I

where R1represents a C1-C10alkyl or C3-C10cycloalkyl, each of which may independently substituted by 1 Deputy, selected from C3-C10cycloalkyl or aryl or heteroaryl groups, possibly substituted by one or two halogen;
aryl or heteroaryl;
R2represents a C1-C10alkoxy or C1-C10thioalkyl;
R3represents a C1-C10alkoxy may someseni is one of C 1-C10alkoxy or nitrile, where specified, the alkoxy group may be cyclic and may contain one heteroatom About;
R4represents a C1-C10alkyl; C2-C10alkenyl; C1-C10alkoxy or3-C10cycloalkyl, each of which may independently substituted by 1 or 2 substituents selected from C1-C10alkoxy, C3-C10cycloalkyl, complex ether carboxylic acids, or one or two aryl or heteroaryl groups, possibly substituted by one Deputy, selected from C1-C10of alkyl, C3-C10cycloalkyl, nitro or halogen;
aryl or heteroaryl, each of which may independently substituted by 1-3 substituents selected from C1-C10of alkyl, C3-C10cycloalkyl, C1-C10alkoxy, phenoxy, thiophenyl, halogen, nitro, nitrile or aryl groups may be substituted with one halogen;
where up to three of the hydrogen atoms of the alkyl group may be substituted by fluorine atoms;
where specified cycloalkyl independently may have one or two carbon atoms replaced by O or N;
where specified aryl means an aromatic ring having from 6 to 10 carbon atoms, including mono - and bicyclic compounds; and
where specified heteroaryl means aromatic Kohl is about, having 3 to 10 carbon atoms, including mono - and bicyclic compounds in which one to three ring atoms are oxygen, nitrogen or sulfur;
except:
ethyl ester of 4-(acetylamino)-1-methyl-2-(methylthio)-1H-imidazole-5-carboxylic acid;
ethyl ester of 4-(acetylamino)-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylic acid;
ethyl ester of 4-[(4-chlorobenzoyl)amino]-1-(2-furylmethyl)-2-(methylthio)-1H-imidazole-5-carboxylic acid;
ethyl ester of 4-(acetylamino)-1-(2-furylmethyl)-2-(methylthio)-1H-imidazole-5-carboxylic acid;
ethyl ester of 4-(acetylamino)-2-(methylthio)-1-(2-thienylmethyl)-1H-imidazole-5-carboxylic acid;
ethyl ester of 2-(methylthio)-4-[[(5-nitro-2-furanyl)carbonyl]amino]-1-(2-thienylmethyl)-1H-imidazole-5-carboxylic acid.

2. The compound according to claim 1, where R2represents a C1-C10alkoxy.

3. The compound according to claim 2, where R2represents a C1-C5alkoxy.

4. The compound according to claim 1, where R2represents a C1-C10thioalkyl.

5. The compound according to claim 4, where R2represents a C1-C5thioalkyl.

6. The compound according to claim 1, where
R1represents a C1-C7alkyl or C3-C7cycloalkyl, each of which may independently substituted by 1 Deputy, selected from C3-C10cyclo is Lila or aryl or heteroaryl groups;
aryl or heteroaryl.

7. The connection according to claim 6, where R1represents a C1-C4alkyl may and independently substituted by one aryl or heteroaryl group.

8. The compound according to claim 1, where R3represents a C1-C7alkoxy may and independently substituted with one nitrile.

9. The compound according to claim 1, where R4represents a C1-C7alkyl, C2-C7alkenyl or3-C7cycloalkyl, each of which may independently substituted by 1 or 2 substituents selected from C1-C7alkoxy, complex ether carboxylic acids, or one or two aryl or heteroaryl groups.

10. The compound according to claim 1, where R4represents aryl or heteroaryl, each of which may independently substituted by 1-3 substituents selected from C1-C10of alkyl, C3-C10cycloalkyl, C1-C10alkoxy, thiophenyl, halogen, nitro, nitrile or aryl group.

11. The compound of formula I according to claim 1, selected from
ethyl ester of 4-[(4-chlorobenzoyl)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylic acid,
ethyl ester of 4-[(3,4-dichlorobenzoyl)amino]-2-(methylthio)-1-(2-thienylmethyl)-1H-imidazole-5-carboxylic acid,
ethyl ester of 4-[(4-bromobenzoyl)amino]-2-(methylthio)-1-(phenylmethyl)-1H-imidazole-5-carboxylic acid,
Atila the CSOs ester 4-[(4-chlorobenzoyl)amino]-2-(methylthio)-1-(2-thienylmethyl)-1H-imidazole-5-carboxylic acid,
ethyl ester of 2-(methylthio)-4-[(1-oxo-2-phenylbutyl)amino]-1-(phenylmethyl)-1H-imidazole-5-carboxylic acid,
ethyl ester of 4-[(4-chlorobenzoyl)amino]-2-(methylthio)-1-(phenylmethyl)-1H-imidazole-5-carboxylic acid,
ethyl ester of 4-[(4-methoxybenzoyl)amino]-2-(methylthio)-1-(2-thienylmethyl)-1H-imidazole-5-carboxylic acid,
ethyl ester of 4-[(4-methoxybenzoyl)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylic acid,
ethyl ester of 4-[[4-(1,1-dimethylethyl)benzoyl]amino]-2-(methylthio)-1-(phenylmethyl)-1H-imidazole-5-carboxylic acid,
ethyl ester of 4-[(3,4-dichlorobenzoyl)amino]-2-(methylthio)-1-(phenylmethyl)-1H-imidazole-5-carboxylic acid,
ethyl ester of 4-[(4-chlorobenzoyl)amino]-1-(3-methylbutyl)-2-(methylthio)-1H-imidazole-5-carboxylic acid,
ethyl ester of 4-[(3,4-dichlorobenzoyl)amino]-1-(3-methylbutyl)-2-(methylthio)-1H-imidazole-5-carboxylic acid,
ethyl ester of 2-(methylthio)-4-[(1-oxo-2-phenoxypropan)amino]-1-(phenylmethyl)-1H-imidazole-5-carboxylic acid,
ethyl ester of 2-(methylthio)-4-[(1-oxo-2-phenylbutyl)amino]-1-phenyl-1H-imidazole-5-carboxylic acid,
ethyl ester of 4-[(4-Ioganson)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylic acid,
tert-butyl 4-[(4-perbenzoic)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylate,
2-methoxy-1-methylethyl-4-[(4-chlorobenzoyl)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylate,
cyclopentyl-4-[(4-chlorine is benzoyl)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylate,
tert-butyl 4-[(methoxyacetyl)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylate,
isopropyl-4-[(4-chlorobenzoyl)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylate,
2.2-dimethylpropyl-4-[(4-chlorobenzoyl)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylate,
1-cyano-1-methylethyl-4-[(4-chlorobenzoyl)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylate,
1,1-dimethylpentyl-4-[(4-chlorobenzoyl)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylate,
tetrahydrofuran-3-yl-4-[(4-chlorobenzoyl)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylate,
2-methoxy-1,1-dimethylethyl-4-[(4-chlorobenzoyl)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylate,
1,1-dimethyl-2-oxopropyl-4-[(4-chlorobenzoyl)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylate,
1-(methoxymethyl)propyl-4-[(4-chlorobenzoyl)amino]-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylate,
2-methoxy-1,1-dimethylethyl-4-[(2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl)amino]-2-methoxy-1-phenyl-1H-imidazole-5-carboxylate,
2-methoxy-1,1-dimethylethyl-4-{[(3-chlorophenoxy)acetyl]amino}-2-methoxy-1-phenyl-1H-imidazole-5-carboxylate,
2-methoxy-1,1-dimethylethyl-4-[(4-chlorobenzoyl)amino]-2-methoxy-1-phenyl-1H-imidazole-5-carboxylate,
2-methoxy-1,1-dimethylethyl-4-[(2,4-dichlorobenzoyl)amino]-2-methoxy-1-phenyl-1H-imidazole-5-carboxylate.

12. The compound of General formula I

where R1represents a C1- 10alkyl or C3-C10cycloalkyl, each of which may independently substituted by 1 Deputy, selected from C3-C10cycloalkyl or aryl or heteroaryl groups, possibly substituted by one or two halogen;
aryl or heteroaryl;
R2represents a C1-C10alkoxy or C1-C10thioalkyl;
R3represents a C1-C10alkoxy, possibly substituted by one C1-C10alkoxy or nitrile, where specified, the alkoxy group may be cyclic and may contain one heteroatom About;
R4represents a C1-C10alkyl; C2-C10alkenyl; C1-C10alkoxy or3-C10cycloalkyl, each of which may independently substituted by 1 or 2 substituents selected from C1-C10alkoxy, C3-C10cycloalkyl, complex ether carboxylic acids, or one or two aryl or heteroaryl groups, possibly substituted by one Deputy, selected from C1-C10of alkyl, C3-C10cycloalkyl, nitro or halogen;
aryl or heteroaryl, each of which may independently substituted by 1-3 substituents selected from C1-C10of alkyl, C3-C10cycloalkyl,1-C10alkoxy, phenoxy, thiophenyl, halogen, nitro, n is trila or aryl group, possibly substituted with one halogen;
where up to three of the hydrogen atoms of the alkyl group may be substituted by fluorine atoms;
where specified cycloalkyl independently may have one or two carbon atoms replaced by O or N;
where specified aryl means an aromatic ring having from 6 to 10 carbon atoms, including mono - and bicyclic compounds; and
where specified heteroaryl means an aromatic ring having from 3 to 10 carbon atoms, including mono - and bicyclic compounds in which one to three ring atoms are oxygen, nitrogen or sulfur;
except:
ethyl ester of 4-(acetylamino)-1-methyl-2-(methylthio)-1H-imidazole-5-carboxylic acid;
ethyl ester of 4-(acetylamino)-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylic acid;
ethyl ester of 4-[(4-chlorobenzoyl)amino]-1-(2-furylmethyl)-2-(methylthio)-1H-imidazole-5-carboxylic acid;
ethyl ester of 4-(acetylamino)-1-(2-furylmethyl)-2-(methylthio)-1H-imidazole-5-carboxylic acid;
ethyl ester of 4-(acetylamino)-2-(methylthio)-1-(2-thienylmethyl)-1H-imidazole-5-carboxylic acid;
ethyl ester of 2-(methylthio)-4-[[(5-nitro-2-furanyl)carbonyl]amino]-1-(2-thienylmethyl)-1H-imidazole-5-carboxylic acid;
for use in the treatment of gastrointestinal diseases.

13. The compound according to any one of claims 1 to 11 for use as a position is positive allosteric modulator of the receptor γ-aminobutyric acid (GABA B).

14. The use of the compounds of formula I according to item 12 or 13, possibly in combination with an agonist of the receptor for GABABfor the preparation of drugs for the treatment of gastroesophageal reflux disease (GAFR).

15. The use of the compounds of formula I according to item 12 or 13, possibly in combination with an agonist of the receptor for GABABfor preparing a medicinal product for the prevention of reflux.

16. The use of the compounds of formula I according to item 12 or 13, possibly in combination with an agonist of the receptor for GABABfor the preparation of drugs for the treatment of functional gastrointestinal disorders.

17. The application of article 16, where the specified functional gastrointestinal disorder is a functional dyspepsia.

18. The use of the compounds of formula I according to item 12 or 13, possibly in combination with an agonist of the receptor for GABABfor the preparation of medicines for treatment of irritable bowel syndrome (IBS).

19. Use p where specified IBS IBS is a with the prevalence of constipation.

20. Use p where specified IBS IBS is a with the prevalence of diarrhea.

21. Use p where specified IBS IBS is a dominated alternating bowel movements.

22. A method of treating gastroesophageal reflux (GAFR), in which the subject, nujdayas is in such treatment, enter pharmaceutically and pharmacologically effective amount of the compounds of formula I according to item 12, possibly in combination with an agonist of the receptor for GABAB.

23. The way to prevent reflux, wherein the subject in need of such prevention, enter a pharmaceutically and pharmacologically effective amount of the compounds of formula I according to item 12, possibly in combination with an agonist of the receptor for GABAB.

24. A method of treating a functional gastrointestinal disorder, wherein the subject in need of such treatment, administered pharmaceutically and pharmacologically effective amount of the compounds of formula I according to item 12, possibly in combination with an agonist of the receptor for GABAB.

25. The method according to paragraph 24, where the specified gastrointestinal disorder is a functional dyspepsia.

26. A method of treating irritable bowel syndrome (IBS), wherein the subject in need of such treatment, administered pharmaceutically and pharmacologically effective amount of the compounds of formula I according to item 12, possibly in combination with an agonist of the receptor for GABAB.

27. The method according to p where specified IBS IBS is a with the prevalence of constipation.

28. The method according to p where specified IBS IBS is a with the prevalence of diarrhea.

29. The method according to p where specified IBS represents IBS with alternating predominance de is ekali.

30. The compound of formula II

where R1represents a C1-C10alkyl or C3-C10cycloalkyl, each of which may independently substituted by 1 Deputy, selected from C3-C10cycloalkyl or aryl group;
aryl;
R2represents a C1-C10thioalkyl;
R3represents a C1-C10alkoxy, possibly substituted With one1-C10alkoxy or one nitrile where the specified alkoxy group may be cyclic and may contain one heteroatom About;
where specified aryl means an aromatic ring having from 6 to 10 carbon atoms, including mono - and bicyclic compounds;
with the exception of
ethyl ester of 4-amino-1-methyl-2-(methylthio)-1H-imidazole-5-carboxylic acid;
[4-amino-1-methyl-2-(methylthio)-1H-imidazol-5-yl]phenyl-methanone;
[4-amino-2-(methylthio)-1-phenyl-1H-imidazol-5-yl]phenyl-methanone; and
ethyl ester of 4-amino-2-(methylthio)-1-phenyl-1H-imidazole-5-carboxylic acid.



 

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6 cl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) , where R is hydrogen or (lower)alkyl; R1 is a (lower)alkyl or (C3-C7)cycloalkyl; X is nitrogen while Y is carbon or Y is nitrogen while X is carbon; m equals 0 or 1; Z is C(O) or SO2; R2 is selected from a group consisting of (lower)alkyl, (C3-C7)cycloalkyl or (C3-C7)cycloalkyl substituted with (lower)alkyl, (lower)phenylalkyl, where the phenyl ring is not substituted or is mono- or disubstituted with (lower)alkoxy or halide, pyridyl which is mono- or disubstituted with a halide, and NR3R4 or when Z is C(O), R2 can also be a (lower)alkoxy; R3 is hydrogen or (lower)alkyl; R4 is selected from a group consisting of (lower)alkyl, (lower)alkoxyalkyl, (C3-C7)cycloalkyl, unsubstituted phenyl or phenyl which is mono-substituted with (lower)alkoxy, or (lower)phenylalkyl, where phenyl is not substituted or is mono- or disubstituted with a halide; or R3 and R4 together with the nitrogen atom to which they are bonded form a 5-, 6- or 7-member heterocyclic ring which optionally contains an additional heteroatom selected from oxygen, the said heterocyclic ring is unsubstituted or substituted with one or two groups independently selected from (lower)alkyl, halide and alkyl halide, or is condensed with a phenyl or cyclohexyl ring, and to their pharmaceutically acceptable salts, as well as to pharmaceutical compositions containing these compounds.

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25 cl, 2 tbl, 93 ex

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21 cl, 3 tbl, 191 ex

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4 cl, 1 tbl, 6 ex

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2 cl, 485 ex, 3 tbl

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9 cl, 151 ex

FIELD: chemistry.

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31 cl, 6 tbl, 175 ex

FIELD: chemistry.

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11 cl, 3 tbl, 6 ex

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FIELD: chemistry.

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17 cl, 3 tbl, 1 ex

FIELD: chemistry.

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8 cl, 44 ex

FIELD: chemistry.

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6 cl, 23 ex

FIELD: chemistry.

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3 dwg, 2 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel 4-phenylpyrimidine-2-carbonitrile of formula

(values of R, R1, R2 are given in the formula of invention) or their pharmaceutically acceptable salts which have inhibition properties towards catepsin K and catepsin S. The invention also relates to use of derivatives of formula I for treating catepsin K and catepsin S related disorders, as well as to a pharmaceutical composition containing the said derivative.

EFFECT: improved properties of derivatives.

9 cl, 151 ex

FIELD: chemistry.

SUBSTANCE: described are compounds of formula ; or their pharmaceutically acceptable salts, where A is phenyl, X is CH2- or C=O; Y is O; k equals 1; m equals 0; R2 and R3 each independently represents hydrogen or alkyl, R4 is a group of formula or . Disclosed compounds have selective affinity to 5-HT6 and 5-HT2A receptors. Also described is a pharmaceutical composition containing said compounds and use of the said compounds in making a medicinal agent for treating diseased conditions of the central nervous system.

EFFECT: more effective treatment.

49 cl, 1 tbl, 16 ex

FIELD: medicine.

SUBSTANCE: invention refers to compound of formula I wherein X represents -S- or -NH-; R1 represents C1-12alkyl, C2-12alkenyl, phenyl C1-12alkel, phenyl C2-12alkenyl or phenyl-O-C1-12alkyl and wherein said phenyl groups are optionally substituted with one or two assistants chosen from the group consisting of lower C1-7alkyl, C C1-7alkoxy and halogen C1-7alkyl; R2 represents hydrogen, lower C1-7alkyl or C3-6cycloalkyl; R3/R4 together with N-atom whereto attached, form nonaromatic 5,6-members heterocyclic ring system which optionally contains in addition to N-atom one additional heteroatom chosen from the group, consisting of O or N and where the ring system is optionally substituted group lower C1-7alkyl, lower C1-7alkoxy, -NR2, -CONR2; or R3/R4 together with N-atom whereto attached, can form heterocyclic ring system which contains at least two rings and which optionally contains one or two additional heteroatoms chosen from group, consisting of N and O; R represents hydrogen or lower C1-7alkyl; R5 represents hydrogen or lower C1-7alkyl; or to pharmaceutically acceptable additive salts with acid of this compound. The invention also concerns a medical product.

EFFECT: improved clinical effectiveness.

16 cl, 4 dwg, 3 tbl, 43 ex

FIELD: chemistry.

SUBSTANCE: proposed invention relates to a method of producing symmetrical gem-diamines with general formula where , involving reacting secondary acyclic or cyclic amines R2NH with excess N,N,N1,N1-tetramethyl methanediamine in the presence of a copper chloride (CuCl) catalyst at temperature 80°C and atmospheric pressure for 2-4 hours. Output of symmetrical gem-diamines is 85-98%.

EFFECT: improved method.

2 dwg, 7 ex

FIELD: chemistry.

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

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

6 cl, 6 ex, 2 tbl

FIELD: medicine.

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

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

11 cl, 156 ex, 8 tbl

FIELD: medicine.

SUBSTANCE: compounds can be used for treatment and prevention of diseases associated with activity of specified enzyme, such as diabetes, obesity, diseases associated with food intake, dyslipidemia and hypertension. In general formula (I) , R1 represents methyl, ethyl, cyclopropyl, cyclobutyl, isopropyl, tert-butyl, methoxymethyl, cyclopropyl methoxymethyl, 2-methyl thiazolyl, morpholinyl methyl or phenyl; R2 represents hydrogen, C1-4alkyl or phenyl; R3 represents hydrogen, C1-4alkyl or phenyl; R4 represents phenyl, naphthyl, thiophenyl, quinolyl or piperidyl where phenyl, naphthyl, thiophenyl, quinolyl and piperidyl are optionally substituted with one to three substitutes independently chosen of C1-4alkyl, halogen, C1-4alkoxy, cyano, trifluoromethyl, phenyl, phenyls C1-4alkyl, phenyloxy, oxasolyl and pyridinyl; R5 represents hydrogen, C1-4alkyl, phenyl-C1-4alkyl, C3-6dicloalkyl-C1-4alkyl or aminocarbonylC1-4alkyl.

EFFECT: higher clinical effectiveness.

17 cl, 2 dwg, 72 ex

FIELD: chemistry.

SUBSTANCE: invention relates to formula (I) compounds and to their use in treating diseases related to lipid storage disorders, such as atherosclerosis and diabetes. In R1 represents hydrogen, alkyl, halogen, formyl, hydroxyalkyl or trifluoromethyl, R2 represents hydrogen, alkyl or halogen, R3 represents hydrogen or alkyl, R4 represents hydrogen, alkyl, hydroxy or alkoxy, R5 and R6 are chosen from hydrogen, alkyl, phenylalkyl, hydroxyalkyl, alkoxycarbonyl and phenyl, A represents aryl or heterocyclyl, m equals 0-3, n equals 0-1, p equals 0-3, sum of m, n and p equals 1-4, the bond between carbon atoms Ca and Cb is a single or double carbon-carbon bond.

EFFECT: obtaining new biologically active compounds.

27 cl, 147 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel 1-thio-D-glucitol compounds of formula I or to pharmaceutically acceptable salts thereof or hydrates of the compound or salts: , [where R1, R2, R3 and R4 are identical or different, and each is a hydrogen atom, C1-C6-alkyl group), A is -(CH2)n-, -CONH(CH2)n-, -O- or -(CH2)nCH=CH- (where n is an integer from 0 to 3, Ar1 is an arylene group, heteroarylene group, which is an unsaturated 5-9-member mono- or bicyclic group, containing 1-2 heteroatoms, selected from S and N, Ar2 is an aryl group or heteroaryl group which is an unsaturated 5-9-member mono- or bicyclic group containing 1-2 heteroatoms selected from O, S and N, and R5, R6, R7, R8, R9 and R10 are identical or different, and each is (i) a hydrogen atom, (ii) a halogen atom, (iii) a hydroxyl group, (iv) C1-8-alkyl group, optionally substituted with hydroxyl group(s), (v) -(CH2)m-Q {where m is an integer from 0 to 4, and Q is -CO2H, -ORc1, -CO2Ra3, -SRe1, -NHRa6 or -NRa7Ra7 (where each of Ra3, Ra6 and Ra7 is a C1-6-alkyl group, Rc1 is a C1-6-alkyl group, and Rc1 is a C1-6-alkyl group)}, (vi) -O-(CH2)m'-Q' {where m' is an integer from 1 to 4, and Q' is a hydroxyl group,-CO2H, -CO2Ra8, -CONRa10Ra10, -NRa12Ra12 (where each of Ra8, Ra10 and Ra12 is a C1-6-alkyl group)}, (vii) -ORf {where Rf is C3-7-cycloalkyl group or tetrahydropyranyl group)}, (viii) morpholine group, (ix) phenyl group, (x) pyridyl group]. The invention also relates to 1-thio-D-glucitol compounds of formulae IA, II, III, IV, to a pharmaceutical agent, to methods of obtaining 1-thio-D-glucitol compounds, as well as to compounds of formulae XIII, XIV.

EFFECT: obtaining novel biologically active compounds which are inhibitors of sodium-dependent co-transporter-2-glucose.

25 cl, 140 ex, 3 tbl

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