Piperizinylpyridine derivatives as anti-obesity agents

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.

EFFECT: obtaining novel compounds and pharmaceutical compositions based on the said compounds, which are suitable for treating and/or preventing diseases which are associated with modulation of H3 receptors.

25 cl, 2 tbl, 93 ex

 

The text descriptions are given in facsimile form.

1. Compounds of General formula

R means hydrogen or (ness.)alkyl;
R1means (ness.)alkyl or (C3-C7)cycloalkyl;
X means nitrogen, a Y means the carbon or
Y represents nitrogen, and X is carbon;
m denotes 0 or 1;
Z means With(O) or SO2;
R2selected from the group consisting of (ness.)of alkyl, (C3-C7)cycloalkyl or (C3-C7)cycloalkyl, substituted (ness.)the alkyl, (ness.)phenylalkyl, where the phenyl ring is unsubstituted or mono - or disubstituted by (ness.)alkoxy or halogen, pyridyl, mono-or disubstituted by halogen, NR3R4or in the case where Z denotes C(O)R2can also be (ness.)alkoxy;
R3means hydrogen or (ness.)alkyl;
R4selected from the group consisting of (ness.)of alkyl, (ness.)alkoxyalkyl, (C3-C7)cycloalkyl, unsubstituted phenyl or phenyl, monosubstituted (ness.)alkoxy or (ness.)phenylalkyl, where phenyl assetmanagement or mono - or disubstituted by halogen; or
R3and R4form together with the nitrogen atom to which they are attached, a 5-, 6-or 7-membered heterocyclic ring, optionally containing an additional heteroatom selected from oxygen, mentioned heterocyclic ring is unsubstituted or substituted by one or two groups independently selected from (ness.)of alkyl, halogen and haloalkyl, or is condensed with a phenyl or tsiklogeksilnogo ring;
and their pharmaceutically acceptable salts.

2. The compounds of formula I according to claim 1, where R1means (C3-C7)cycloalkyl.

3. The compounds of formula I according to claim 1 or claim 2, where R1means ethyl or isopropyl.

4. The compounds of formula I according to claim 1 or 2, where m is 0.

5. The compounds of formula I according to claim 1 or 2, where m means 1.

6. The compounds of formula I according to claim 1 or 2, where R is hydrogen, and R2selected from the group consisting of (ness.)of alkyl, (C3-C7)cycloalkyl (ness.)phenylalkyl, where the phenyl ring is unsubstituted or mono - or disubstituted by (ness.)alkoxy or halogen, pyridyl, mono - or disubstituted by halogen, NR3R4or in the case where Z denotes C(O)R2can also be (ness.)alkoxy.

7. The compounds of formula I according to claim 1 or 2, where R2selected from the group consisting of (ness.)of alkyl, (C3-C7)cycloalkyl or (C3-C7/sub> )cycloalkyl, substituted (ness.)the alkyl, (ness.)phenylalkyl, where the phenyl ring is unsubstituted or mono - or disubstituted by (ness.)alkoxy or halogen, pyridyl, mono - or disubstituted by halogen, NR3R4or in the case where Z denotes C(O)R2can also be (ness.)alkoxy.

8. The compounds of formula I according to claim 1 or 2, where R2selected from the group consisting of (ness.)of alkyl or (C3-C7)cycloalkyl.

9. The compounds of formula I according to claim 1 or 2, where R2means (ness.)phenylalkyl, where phenyl is unsubstituted or mono - or disubstituted by (ness.)alkoxy or halogen.

10. The compounds of formula I according to claim 1 or 2, where R2means-NR3R4, a R3and R4have the meanings given in claim 1.

11. The compounds of formula I of claim 10, where R3and R4mean (ness.)alkyl.

12. The compounds of formula I of claim 10, where R3means hydrogen or (ness.)alkyl, and R4selected from the group consisting of (ness.)of alkyl, (ness.)alkoxyalkyl, (C3-C7)cycloalkyl, unsubstituted phenyl or phenyl, monosubstituted (ness.)alkoxy, and (ness.)phenylalkyl, in which phenyl is unsubstituted or mono - or disubstituted by halogen.

13. The compounds of formula I of claim 10, where R3and R4form together with the nitrogen atom to which they are attached, a 5-, 6 - or 7-membered heterocyclic Ko is ICO, optionally containing an additional heteroatom selected from oxygen, mentioned heterocyclic ring is unsubstituted or substituted by one or two groups independently selected from (ness.)of alkyl, halogen and (ness.)haloalkyl, or is condensed with a phenyl or tsiklogeksilnogo ring.

14. The compounds of formula I according to claim 1 or 2, where R2means unsubstituted phenyl or phenyl mono - or disubstituted by (ness.)alkoxy or halogen.

15. The compounds of formula I according to claim 1 or 2, where Z means SO2.

16. The compounds of formula I according to claim 1 or 2, where Z means With(O).

17. The compounds of formula I according to claim 1 or 2, where Z denotes C(O), and R2means-NR3R4.

18. The compounds of formula I according to claim 1 or 2, where X is N, a Y means C.

19. The compounds of formula I according to claim 1 or 2, where X is s and Y represents N.

20. The compounds of formula I according to claim 1 or 2, where R is hydrogen.

21. The compounds of formula I according to claim 1 or 2, where R is methyl.

22. The compounds of formula I according to claim 1, selected from the group consisting of
1-[2-(4-ethylpiperazin-1-yl)pyridine-4-yl]-3-propylbetaine,
3-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-1,1-dieselmachine,
N-[2-(4-ethylpiperazin-1-yl)pyridine-4-yl]propionamide,
N-[2-(4-ethylpiperazin-1-yl)pyridine-4-yl]butyramide,
N-[2-(4-ethylpiperazin-1-yl)pyridine-4-yl]-C-phenylmethanesulfonyl,
S-(4-chlorophenyl)-N-[2-(4-this is piperazin-1-yl)pyridine-4-yl]methanesulfonamide,
N-[2-(4-ethylpiperazin-1-yl)pyridine-4-yl]-3-forbindelsesfaneblad,
4-chloro-N-[2-(4-ethylpiperazin-1-yl)pyridine-4-yl]benzosulfimide,
1-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-3-(4-terbisil)urea,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]propionamide,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]butyramide,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide cyclohexanecarbonyl acid,
N-[2-(4-cyclopentylpropionyl-l-yl)pyridin-4-yl]-3-methoxybenzamide,
S-(4-chlorophenyl)-N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-methanesulfonamide,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide cyclopropanecarboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide cyclobutanecarbonyl acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide cyclopentanecarbonyl acid,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-2-ethylbutylamine,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-2-fermentated,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-4-fermentated,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-2-methoxybenzamide,
2-chloro-N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]nicotinamide,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-2-phenylacetamide,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-2-(4-forfinal)ndimethylacetamide,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-2-(3-methoxyphenyl)ndimethylacetamide is,
isobutyl ether[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]carbamino acid,
1-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-3-propylbetaine,
1-cyclohexyl-3-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]urea,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide piperidine-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide morpholine-4-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of pyrrolidin-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide 4,4-deformability-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 2-methylpiperidin-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 3-methylpiperidin-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 4-methylpiperidin-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 2,6-dimethylpiperidin-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 4-foreperiod-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl] amide 3,3-deformability-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl] amide of 4-triftormetilfosfinov-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of octahedrally-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)PIR is DIN-4-yl]amide of octahydronaphthalene-2-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 3,4-dihydro-2-N-quinoline-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 3,4-dihydro-1H-isoquinoline-2-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 2-methylpyrrolidine-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 2-triftormetilfullerenov-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 2-isopropylpyrimidine-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide 1,3-dihydroindol-2-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide 2,3-dihydroindol-1-carboxylic acid,
3-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-1-isopropyl-1-(2-methoxyethyl)-urea,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide azepin-1-carboxylic acid,
3-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-1-ethyl-1-phenylacetone,
3-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-1-(4-methoxyphenyl)-1-methyl-urea,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-ylmethyl]butyramide, [2-(4-cyclopentylpropionyl-1-yl)pyridine-4-ylmethyl]amide cyclohexanecarbonyl acid,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-ylmethyl]-2-phenylacetamide,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-ylmethyl]-4-fermentated,
2-(4-chlorophenyl)-N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-ylmethyl]-3-methyl-who tyramide,
1-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-ylmethyl]-3-propylbetaine,
1-cyclohexyl-3-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-ylmethyl]urea,
1-benzyl-3-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-ylmethyl]urea,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-ylmethyl]amide propane-1-sulfonic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-ylmethyl]aminodimethylaniline-1-sulfonic acid,
S-(4-chlorophenyl)-N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-ylmethyl]-methanesulfonamide,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-ylmethyl]benzosulfimide,
N-[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]propionamide,
[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]amide cyclopropanecarboxylic acid,
N-[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]butyramide,
N-[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]-2-methoxyacetate,
[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]amide cyclopentanecarbonyl acid,
N-[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]-2-ethylbutylamine,
[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]amide cyclohexanecarbonyl acid,
N-[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]-2-fermentated,
N-[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]-3-fermentated,
N-[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]-4-fermentated,
N-[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]-2-methoxybenzamide,
N-[4-(4-cyclopentolate Azin-1-yl)pyridin-2-yl]-3-methoxybenzamide,
N-[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]-4-methoxybenzamide,
2-chloro-N-[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]nicotinamide,
2-methoxyethanol ester of 4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]carbamino acid,
1-[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]-3-(2-methoxyphenyl)urea,
1-[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]-3-(1-phenylethyl)urea,
[2-(4-isopropylpiperazine-1-yl)pyridine-4-yl]amide cyclohexanecarbonyl acid,
[2-(4-isopropylpiperazine-1-yl)pyridine-4-yl]amide of 3-methylcyclohexanecarboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]methylamide cyclopentanecarbonyl acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]methylamide 3-methylcyclohexanecarboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl] methylamide cyclohexanecarbonyl acid,
[2-(4-isopropylpiperazine-1-yl)pyridine-4-yl]methylamide 3-methyl-cyclohexanecarbonyl acid,
[2-(4-isopropylpiperazine-1-yl)pyridine-4-yl]methylamide cyclohexanecarbonyl acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]methylamide piperidine-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]methylamide pyrrolidin-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]methylamide 4,4-deformability-1-carboxylic acid,
3-cyclohexyl-1-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-1-is amylocaine,
3-cyclopentyl-1-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-1-metalmachine,
and their pharmaceutically acceptable salts.

23. The compounds of formula I according to claim 1, selected from the group consisting of
1-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-3-(4-terbisil)urea,
N-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]butyramide,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide cyclohexanecarbonyl acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide cyclopentanecarbonyl acid,
1-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]-3-propylbetaine,
1-cyclohexyl-3-[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]urea,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide piperidine-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide 4,4-deformability-1 carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 3-methylpiperidin-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 4-methylpiperidin-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 2,6-dimethylpiperidin-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of 4-foreperiod-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of octahedrally-1-carboxylic acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide of octahydronaphthalene-2-carboxylic key is lots
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]amide azepin-1-carboxylic acid,
[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]amide cyclopropanecarboxylic acid,
[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]amide cyclopentanecarbonyl acid,
[4-(4-cyclopentylpropionyl-1-yl)pyridin-2-yl]amide cyclohexanecarbonyl acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]methylamide-methyl-
cyclohexanecarbonyl acid,
[2-(4-cyclopentylpropionyl-1-yl)pyridine-4-yl]methylamide 4,4-deformability-1-carboxylic acid, and their pharmaceutically acceptable salts.

24. Compounds according to any one of claims 1 to 23, intended for use as therapeutically active substances for the treatment and/or prevention of diseases associated with the modulation of H3 receptors.

25. Pharmaceutical composition for treatment and/or prevention of diseases associated with the modulation of H3 receptors, comprising the compound according to any one of claims 1 to 23 and a pharmaceutically acceptable carrier and/or excipient.



 

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21 cl, 3 tbl, 191 ex

FIELD: chemistry.

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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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17 cl, 3 tbl, 1 ex

FIELD: chemistry.

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8 cl, 44 ex

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16 cl, 5 tbl, 40 ex

FIELD: medicine.

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16 cl, 406 ex, 73 tbl

V:

FIELD: chemistry.

SUBSTANCE: described is a compound selected from a group consisting of formula II formula III and formula IV , or its salt or ester, where G1 is selected from a group which includes - (CR1R2)n-, n equals 0 or 1; R1 and R2 are independently selected from a group which includes hydrogen; X1, X2 and X3 are independently selected from a group consisting of hydrogen, optionally substituted lower alkyl, halogen, optionally substituted lower alkoxy, G2 is a heterocycloalkyl linker optionally substituted with X4 and X5, where the heterocycloalkyl linker is selected from a group consisting of piperazinyl, 3,6-dihydro-2N-pyridinyl, [1,4]diazepanyl, 3,9-diazabicyclo[3,3,1]nonyl; X4 and X5 are independently selected from a group consisting of hydrogen and optionally substituted lower alkyl; CO2R; R is selected from a group consisting of optionally substituted lower alkyl and hydrogen; G3 is a bond; G4 is selected from a group consisting of hydrogen, aryl, selected from phenyl which is optionally substituted with a lower alkyl, halogen, lower haloalkyl or lower haloalkoxy; heteroaryl selected from pyridinyl which is optionally substituted with a halogen or lower haloalkyl; and optionally substituted cycloheteroalkyl selected from 1,3-benzodioxolyl. Described also are specific compounds and a pharmaceutical composition.

EFFECT: disclosed compounds are used as modulators of receptors activated by a peroxisomal proliferator.

5 cl, 2 tbl, 117 ex

Triazole derivative // 2383536

FIELD: chemistry.

SUBSTANCE: described are novel triazole derivatives with general formula where values of radicals are given in the formula of invention, a pharmaceutical composition containing said derivatives, and a method of treating autoimmune diseases. Compounds with general formula (1) and their pharmaceutically acceptable salts have inhibition effect on S1P and its Edg-1 receptor (S1P1).

EFFECT: possibility of use as a pharmaceutical product.

43 cl, 10 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

where R1 is hydrogen, alkyl, cycloalkyl, hydroxy group, hydroxyalkyl, alkoxy group, alkoxyalkyl, aminoalkyl, aryl, heterocyclyl, alkylsulfonyl, alkylsulfanyl, alkylcarbonylalkyl, alkylcarbonyloxyalkyl, aminocarbonylalkyl, heterocyclylcarbonylalkyl, alkoxycarbonylalkyl, alkoxyalkylaminocarbonylalkyl, cycloalkylalkoxyalkyl, arylalkyloxyalkyl, aryloxyalkyl, haloidalkyl, haloidalkoxy group or haloidalkoxyalkyl, R2 is hydrogen, alkyl, cycloalkylalkoxyalkyl, alkoxyalkyl, arylalkoxyalkyl, haloidalkoxyalkyl, pyrrolidyl, morpholinyl, thiomorpholinyl, arylalkyl, arylalkoxy group, aryloxy group or heterocyclylalkyl, R3 is hydrogen or alkyl, R4 is hydrogen, alkyl or haloid, R5 is phenyl, naphthyl, piperidyl or 1,2,3,4-tetrahydroisoquinolinyl optionally substituted with one or more substitutes independently selected from alkyl, cycloalkyl, haloid, alkoxy group, nitro group, trifluoromethyl, trifluoromethoxy group, trifluoromethylcarbonyl group, aryl, aryloxy group, alkoxycarbonylalkoxy group and alkylsulfonyl, R6 is hydrogen or alkyl, and their pharmaceutically acceptable salts and esters, under the condition that N-(6-(1,1-dimethylethyl)-2-pyridinyl)-4-methylbenzenesulfamide is excluded, and in cases when R1 is hydrogen or methyl, R2 is not hydrogen or methyl, as well as a pharceutical composition based on these compounds.

EFFECT: novel chemical compounds which can be used in treating and preventing diabetes, obesity and eating disorders are obtained and described.

15 cl, 192 ex

FIELD: chemistry.

SUBSTANCE: novel compound is N-(5-hydroxy-2,4-di-tert-butylphenyl)-4-oxo-1H-quinoline-3-carboxamide or its pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with CFTR activity modulation properties.

2 cl, 485 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: described are compounds of formula , where X, R1, R2, R3, R4 and R5 assume values given in the description and paragraphs of the formula of invention, and their pharmaceutically acceptable salts.

EFFECT: compounds have antagonistic activity on histamine receptor 3 (H3).

25 cl, 3 tbl, 215 ex

FIELD: chemistry.

SUBSTANCE: according to the invention, optically pure esomeprazole and its salt can be easily produced by dissolving (S)-(-)-binol, a weak base and a racemic form of omeprazole in a mixture of a water miscible solvent and water at high temperature, cooling the mixed solution to crystallisation of the inclusion esomeprazole complex and (S)-(-)-binol and removal of the (S)-(-)-binol fragment from the crystallised inclusion complex obtained at step A.

EFFECT: design of an improved method of separating optical isomers of omeprazole, which allows for obtaining optically pure end product.

13 cl, 2 dwg, 3 tbl, 20 ex

FIELD: medicine.

SUBSTANCE: invention relates to compounds of general formula (I) and their pharmaceutically acceptable salts and pharmaceutically acceptable asters, possessing activity with respect to LXRα and/or LXRβ receptors. Compounds can be applied for treatment and prevention of diseases mediated by LXRα and/or LXRβ receptors, namely: increased level of lipids and cholesterol level, atherosclerotic diseases, diabetes, metabolic syndrome, dyslipidermia, sepsis, inflammatory diseases, pancreatitis, liver cholestasis/fibrosis, and diseases which include inflammatory component, such as Alzheimer's disease and reduced/improvable cognitive function. In general formula n represents integer number from 0 to 3; R1 is independently selected from group consisting of halogen, -CN, -NO2, -SO2Me, lower alkyl, -OR11, pyperidinyl and -N(R11)(R11), where R11 is independently selected from lower alkyl and H, X1, X2, X3 and X4 are independently selected from nitrogen and carbon, on condition that, not more than two of X1, X2, X3 and X4 can simultaneously represent nitrogen, and in case when two of X1, X2, X3 and X4 represent nitrogen, n represents 0,1 or 2; k represents integer number 0 or 1; R2 represents H; R3 represents H, lower alkyl or halogen; R4 represents aryl, heteroaryl, lower alkylaryl or lower alkylheteroaryl, each of which is optionally substituted with substituents in amount from one to five, which are independently selected from group consisting of halogen, lower alkyl, -OR41, lower alkinyl and NR42R43, where R41 represents lower alkyl, R42 and R43 independently on each other represent hydrogen or lower alkyl, or NR42R43 represents pyrrolidinyl, or R4 represents lower alkyl; R5 is selected from group, heteroaryl, consisting of and , said aryl and heteroaryl being optionally substituted in one or more positions with one or more substituents, independently selected from group consisting of H, halogen, lower alkyl and (CH2)VR53, where R51 is selected from group consisting of H, lower alkyl, lower alkenyl and lower alkylaryl, said lower alkylaryl is optionally substituted in one or more positions with one or more lower alkyl, -CN, halogen, group -COOR54 and group -CH2OR54, where R54 represents lower alkyl or H; R52 represents lower alkyl or -H; R53 represents H, lower alkyl, C3-C6-cycloalkyl, -COOR55, -N(R55)(R56), -CH2OH, -CN, CF3, -CONH2 or -CH2OR55, where R55 is independently selected from group consisting of lower alkyl, -H, -C(O)aryl or -C(O)-lower alkyl, and R56 is selected from group consisting of H, lower alkyl, -C(O)CF3, -C(O)aryl, -C(O)-lower alkyl and lower alkylaryl, and where said aryl and lower alkylaryl are optionally substituted in one or more positions with one or more lower alkyl, halogen, group COOR57 and group -CH2OR57, where R57 represents lower alkyl or -H, or R55 and R56 together with atom to which they are bound, form ring system; or R53 represents aryl, which can be optionally substituted with benzyloxy, carboxy, lower alkoxycarbonyl, hydroxy-(lower alkyl), halogen, carbamoyl, (lower alkyl)carbamoyl, di-(lower alkyl)carbamoyl, m represents integer number from 0 to 2; v represents integer number from 0 to 4; where term "lower alkyl" separately or in combination with other groups refers to branched or linear monovalent alkyl radical, containing from one to six carbon atoms, where term "aryl" separately or in combination with other groups refers to phenyl or naphthyl, and where term "hetyeroaryl" refers to aromatic 5- or 6-member ring, which can include 1-3 heteroatoms selected from nitrogen, oxygen and/or sulphur, and which can be condensed with phenyl group.

EFFECT: increase of compound application efficiency.

38 cl, 5 dwg, 137 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) which are protein tyrosine kinase 1B(PTP-1B) inhibitors and can be used in medicinal preparations for treating and preventing diseases related to high concentration of glucose in blood, for example diabetes and obesity. In formula (I) X is a X-1 group or X-2: , where R1 and R2 are each independently selected from a group consisting of hydrogen, lower alkyl, alkoxy-lower alkyl and hydroxyl-lower alkyl, under the condition that, R1 and R2 both represent hydrogen; R3, R4, R6 and R7 are each independently selected from a group consisting of hydrogen, lower alkyl; lower alkyl substituted with halogen or hydroxy; lower alkoxy; lower alkoxy substituted with halogen, hydroxy or lower alkoxy; hydroxyl, halogen, lower alkylthio, lower alkylsufanyl, lower alkylsufanyl, aminosufonyl, cyano, nitro, carbamoyl, lower mono- or dialkylcarbamoyl, lower alkanoyl, benzoyl, phenyl, phenyl substituted with halogen, phenyloxy, lower mono- or dialkylamino, hydroxy-substituted lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, heterocycloalkyl, hydroxy-substituted heterocycloalkyl, heterocyclyloxy, heterocyclylcarbonyl; where each heterocycloalkyl in the said values represents a 5-6-membr ring containing 1-2 heteroatoms selected from nitrogen and oxygen, and which can be substituted with lower alkyl or phenyl-lower alkyl; carboxyl, lower alkoxycarbonyl and a substitute of formula: ; R8 is selected from a group consisting of hydrogen, lower alkylthio, halogen, alkoxy-lower alkoxy, lower alkoxy, halogen-lower alkyl, hydroxy-lower alkyl; represents a 5-member heteroaromatic ring containing 1 or 2 heteroatoms selected from a group consisting of hydrogen, sulphur and nitrogen; R8 and R9 each independently represents hydrogen or lower alkyl.

EFFECT: novel compounds have useful biological properties.

31 cl, 7 dwg, 152 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula , where Qa is phenyl or heteroaryl, and Qa can possibly carry 1 or 2 substitutes selected from hydroxy, halogen, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; R1 and R2 are each independently selected from hydrogen and (1-6C)alkyl; Qb is phenyl or heteroaryl, and Qb can possibly carry 1 or 2 substitutes selected from hydroxy, halogen, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulfinyl and (1-6C)alkylsulfonyl; where any of the substitutes Qa and Qb defined above, containing a CH2 group which is bonded to 2 carbon atoms, or a CH3 group bonded to a carbon atom, can possibly carry on each of the said CH2 or CH3 group one or more substitutes selected from hydroxy, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; where heteroaryl is an aromatic 5- or 6-member monocyclic ring which can contain up to three heteroatoms selected from oxygen, nitrogen and sulphur, and can be condensed with a benzene ring or a five-member nitrogen-containing ring containing 2 nitrogen atoms; as well as pharmaceutically acceptable salts thereof. The invention also relates to a method of producing formula I compounds, a pharmaceutical composition and use of these compounds for treating conditions mediated by effect of TNF cytokines.

EFFECT: more effective treatment.

13 cl, 3 tbl, 46 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a crystalline salt of 1,2-ethanedisulfonic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinoline-5-yl)ethylamino]methyl} -5- methoxyphenylcarbamoyl)ethyl]piperadin-4-yl ether biphenyl-2-ylcarbamic acid or its solvate. The invention also relates to a pharmaceutical composition containing such a salt, a combination containing the salt in paragraph 1 and a steroid anti-inflammatory agent, a method of treating pulmonary disorder, a method of producing the salt in paragraph 1 and use of the salt in paragraph 1 in making a medicinal agent.

EFFECT: novel crystalline salt of the compound given above, having useful biological properties, is obtained.

34 cl, 6 dwg, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

where R1 is hydrogen, alkyl, cycloalkyl, hydroxy group, hydroxyalkyl, alkoxy group, alkoxyalkyl, aminoalkyl, aryl, heterocyclyl, alkylsulfonyl, alkylsulfanyl, alkylcarbonylalkyl, alkylcarbonyloxyalkyl, aminocarbonylalkyl, heterocyclylcarbonylalkyl, alkoxycarbonylalkyl, alkoxyalkylaminocarbonylalkyl, cycloalkylalkoxyalkyl, arylalkyloxyalkyl, aryloxyalkyl, haloidalkyl, haloidalkoxy group or haloidalkoxyalkyl, R2 is hydrogen, alkyl, cycloalkylalkoxyalkyl, alkoxyalkyl, arylalkoxyalkyl, haloidalkoxyalkyl, pyrrolidyl, morpholinyl, thiomorpholinyl, arylalkyl, arylalkoxy group, aryloxy group or heterocyclylalkyl, R3 is hydrogen or alkyl, R4 is hydrogen, alkyl or haloid, R5 is phenyl, naphthyl, piperidyl or 1,2,3,4-tetrahydroisoquinolinyl optionally substituted with one or more substitutes independently selected from alkyl, cycloalkyl, haloid, alkoxy group, nitro group, trifluoromethyl, trifluoromethoxy group, trifluoromethylcarbonyl group, aryl, aryloxy group, alkoxycarbonylalkoxy group and alkylsulfonyl, R6 is hydrogen or alkyl, and their pharmaceutically acceptable salts and esters, under the condition that N-(6-(1,1-dimethylethyl)-2-pyridinyl)-4-methylbenzenesulfamide is excluded, and in cases when R1 is hydrogen or methyl, R2 is not hydrogen or methyl, as well as a pharceutical composition based on these compounds.

EFFECT: novel chemical compounds which can be used in treating and preventing diabetes, obesity and eating disorders are obtained and described.

15 cl, 192 ex

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