Piperidine/piperazine derivatives

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to DGAT inhibitor of formula (I), its N-oxide, pharmaceutically acceptable salt and solvate, based on it pharmaceutical composition and its application for treatment of diseases, mediated by DGAT activity, such as obesity and diabetes. In general formula (I) A represents CH or N; X represents -C (=O)-C(=O); -O-C(=O)-; -NRX-C(=O)-; -Z1-C(O)-; -Z1-NRx-C(O)-; -C(O)-Z1-; -NRx-C(O)-Z1-; -S(=O)p-; -NRX-C(=S) -; Y represents NRx-C(=O)-Z2-; -NRx-C(=O)-Z2-NRy-; -NR*-C(=O)-Z2-NRy-C(=O)-; -NRx-C(=O)-Z2-NRy-C(=O)-O-; -NRx-C(O)-Z2-O-; -NRx-C(=O)-Z2-O-C(=O)-; -NRx-C(=O)-Z2-C(=O)-O-; -NRx-C(=O)-Z2-C(=O)-NRy-; -NRx-C(=O)-Z2-NRy-C(=O)-NRy-, -C(<))-Z2-; -C(=O)-NRx-Z2-; -C(=O)-NRx-Z2-O-; R1 represents C1-12alkyl, optionally substituted with cyano, C1-4alkyloxy, C1-4alkyloxy C1-4alkyloxy, C3-6cycloalkyl or aryl; C2-6alkenyl, C2-6alkinyl; C3-6cycloalkyl; adamantanyl; aryl1; aryl1C1-6alkyl; Het1; or HetC1-6alkyl, on condition that when Y represents -NRxC(=O)-Z2-; -NRx-C(=O)-Z2-NRy; -NRx-C(=O)-Z2-C(=O)-NRy-, -C(=O)Z2-; -NRx-C(=O)-Z2-NRy-C(=O)-NRy-; -C(=O)-NRx-Z2-; -C(=O)-NRx-O-Z2- or -C(=O)-NRx-Z2-NRy-; then R1 can also represent hydrogen; R2 represents R3; R3 represents phenyl, naphthalenyl, 2,3-dihydrobenzofuranyl or 6-membered aromatic heterocycle, containing 1 or 2 N atoms, where each of said cycles can optionally be substituted with, at least, one substituent, in particular, one-five substituents, said substituents represent halogen, C1-6alkyl, optionally substituted with hydroxy, polyhalogen C1-6alkyl, C1-6alkylthio, polyhalogen-C1-6alkyloxy, carboxyl, hydroxyl, C1-6alkylcarbonyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, nitro, R5R4N-C(=O)-; R5R4N-C1-6alkyl; HetC1-4alkyl, Het-C(=O)-C1-4alkyl, Het-C(=O)-; R8 represents hydrogen, halogen, C1-4alkyl, substituted with hydroxyl Values of other radicals are given in invention formula.

EFFECT: obtaining pharmaceutical composition for treatment of diseases, mediated by DGAT activity, such as obesity and diabetes.

31 cl, 5 tbl, 352 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula

including any stereochemical isomeric form,
where a represents CH or N;
the dashed line represents an optional bond in case a represents a carbon atom;
X represents-C(=O)-C(=O)- O-C(=O)-; -NRx-C(=O)-; -Z1-C(=O)-; -Z1-NRx-C(O)-; -C(=O)-Z1-; -NRx-C(=O)-Z1-; -S(=O)p-; -NRx-C(=S) -;
Z1is a divalent radical selected from C1-6Alcantara,2-6Alcantara, where each of the specified1-6Alcantara,2-6alkerdeel the optional is tion may be substituted by hydroxyl or amino; and where two hydrogen atoms linked to the same carbon atom in the C1-6alcantera, optional can be replaced With1-6Alcantara;
Y represents NRx-C(=O)-Z2-; -NRx-C(=O)-Z2-NRy-; -NRx-C(=O)-Z2-NRy-C(=O)-; -NRx-C(=O)-Z2-NRy-C(=O)-O-; -NRx-C(=O)-Z2-O-; -NRx-C(=O)-Z2-O-C(=O)-; -NRx-C(=O)-Z2-C(=O)-O-; -NRx-C(=O)-Z2-C(=O)-NRy-; -NRx-C(=O)-Z2-NRy-C(=O)-NRy-, -C(=O)-Z2-; -C(=O)-NRx-Z2-; -C(=O)-NRx-Z2-O-;
Z2is a divalent radical selected from C1-6Alcantara,2-6Alcantara or2-6alcindoro, where each of the specified C1-6Alcantara,2-6Alcantara or2-6alcindoro optionally may be substituted With1-4alkyloxy,1-4alkylthio, hydroxyl, cyano or aryl; and where two hydrogen atoms linked to the same carbon atom in the definition of Z, may not necessarily be replaced With1-6Alcantara;
Rxrepresents hydrogen or C1-4alkyl;
Ryrepresents hydrogen; C1-4alkyl; C2-4alkenyl; or-S(=O)p-aryl;
R1represents a C1-12alkyl, optionally substituted by cyano, C1-4alkyloxy,1-4alkalosis1-4alkyloxy,3-6the CEC is valkila or aryl; With2-6alkenyl,1-6quinil; C3-6cycloalkyl; adamantyl; aryl1; aryl1With1-6alkyl; Het1; or Het1C1-6alkyl; provided that when Y is-NRxC(=O)-Z2-; -NRx-C(=O)-Z2-NRy; -NRx-C(=O)-Z2-C(=O)-NRy-, -C(=O)-Z2-; -NRx-C(=O)-Z2-NRy-C(=O)-NRy-; -C(=O)-NRx-Z2-; -C(=O)-NRx-O-Z2- or-C(=O)-NRx-Z2-NRy-; then
R1may also represent hydrogen;
R2is an R3;
R3represents phenyl, naphthalenyl, 2,3-dihydrobenzofuranyl or 6-membered aromatic heterocycle containing 1 or 2 N atom, where each of these cycles optionally may be substituted by at least one Deputy, in particular one to five substituents, these substituents are halogen, C1-6alkyl, optionally substituted hydroxy, polyhalogen1-6alkyl, C1-6alkylthio, polyhalogen-C1-6alkyloxy, carboxyl, hydroxyl, C1-6alkylsulphonyl,1-6alkyloxy,1-6allyloxycarbonyl, nitro, R5R4N-C(=O)-; R5R4N-C1-6alkyl; HetC1-4alkyl, Het-C(=O)-C1-4alkyl, Het-C(=O)-;
R4represents hydrogen; C1-4alkyl, optionally substituted by hydroxyl or1-4Ala is lexi; R7R6N-C1-6alkyl; HetC1-4alkyl; R7R6N-C(=O)-C1-4alkyl;
R5represents hydrogen or C1-4alkyl;
R6represents hydrogen; C1-4alkyl; C1-4alkylsulphonyl;
R7represents hydrogen or C1-4alkyl; or
R6and R7may, taken together with the nitrogen to which they are linked, form a saturated monocyclic 5-, 6 - or 7-membered heterocycle, which may optionally contain one or more heteroatoms, each of which is independently selected from O or N;
R8represents hydrogen, halogen, C1-4alkyl substituted by hydroxyl;
aryl represents phenyl or phenyl substituted by at least one Deputy, in particular one or two substituents, each Deputy independently selected from halogen; C1-6of alkyl, polyhalogen1-6of alkyl; C1-6alkyloxy,1-6allyloxycarbonyl, nitro, amino;
aryl1represents phenyl or naphthalenyl; where phenyl optionally is substituted by at least one Deputy, in particular one or two substituents, each Deputy independently selected from hydroxyl; halogen; C1-6of alkyl; C1-6alkyloxy; C1-6allyloxycarbonyl; Het;
Het is a 5-6-membered monocyclic auromatically or aromatic heterocycle, containing at least one heteroatom, each of which is independently selected from O or N; optionally substituted by one Deputy, selected from C1-6the alkyl, optionally substituted C1-6alkyloxy; C1-6allyloxycarbonyl; -S(=O)p-C1-4of alkyl;
Het1represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom, each of which is independently selected from O, S or N; or a bicyclic non-aromatic a heterocycle containing at least one heteroatom About; specified monocyclic heterocycle or specified the bicyclic heterocycle optionally is substituted by at least one Deputy, in particular one or two substituents, each Deputy independently selected from halogen; C1-6of alkyl; C1-6allyloxycarbonyl; -S(=O)p-C1-4of alkyl; aryl; arils1-4of alkyl;
p represents 2;
its N-oxide, pharmaceutically acceptable salt or MES,

provided that
4-[4-[(2-ethyl-1-oxohexyl)amino]phenyl]-N-phenyl-1-piperazinecarboxamide;
4-[4-[(1-oxoethyl)amino]phenyl]-N-phenyl-1-piperazinecarboxamide; and
4-[4-[(1-oxohexyl)amino]phenyl]-N-phenyl-1-piperazinecarboxamide excluded.

2. The compound according to claim 1, having the following formula

including any stereochemical isomeric form,
where a represents CH or N;
the dashed line represents an optional bond in case a represents a carbon atom;
X represents-NRxC(=O)-; -Z1-C(=O)-; -Z1-NRx-C(=O)-; -C(=O)-Z1-; -NRx-C(=O)-Z1-; -S(=O)p-; -NRx-C(=S)-;
Z1is a divalent radical selected from C1-6Alcantara,2-6Alcantara, where each of the specified1-6Alcantara,2-6Alcantara optionally may be substituted by hydroxyl;
Y represents NRxC(=O)-Z2-; -NRxC(=O)-Z2-NRy-; -NRx-C(=O)-Z2-NRy-C(=O)-; -NRx-C(=O)-Z2-NRy-C(=O)-O-; -NRx-C(=O)-Z2-O-; -NRx-C(=O)-Z2-O-C(=O)-; -NRx-C(=O)-Z2-C(=O)-O; -NRx-C(=O)-Z2-C(=O)-NRy-; -NRx-C(=O)-Z2-NRy-C(=O)-NRy-; -C(=O)-Z2-; -C(=O)-NRx-Z2-; -C(=O)-NRx-Z2-O-;
Z2is a divalent radical selected from C1-6Alcantara,2-6Alcantara or2-6alcindoro, where each of the specified1-6Alcantara,2-6Alcantara or2-6alcindoro optionally may be substituted With1-4alkyloxy,1-4alkylthio, hydroxyl, cyano or aryl; and where two hydrogen atoms, wired the e with the same carbon atom in the definition of the Z 2not necessarily may be replaced by C1-6Alcantara;
Rxrepresents hydrogen or C1-4alkyl;
Ryrepresents hydrogen; C1-4alkyl; C2-4alkenyl; or-S(=O)p-aryl;
R1represents a C1-4alkyl, optionally substituted by cyano, C1-4alkyloxy,1-4alkalosis1-4alkyloxy,3-6cycloalkyl or aryl; C2-6alkenyl,2-6quinil; C3-6cycloalkyl; aryl1; aryl1With1-6alkyl; Het1; or Het1C1-6alkyl; provided that when Y is-NRx-C(=O)-Z2-; -NRx-C(=O)-Z2-NRy; -NRxC(=O)-Z2-C(=O)-NRy-; -C(=O)-Z2-; -NRx-C(=O)-Z2-NRy-C(=O)-NRy-; -C(=O)-NRx-Z2-; -C(=O)-NRx-O-Z2- or-C(=O)-NRx-Z2-NRy-; then R1may also represent hydrogen;
R2is an R3;
R3represents phenyl, naphthalenyl, where phenyl optionally may be substituted by one to five substituents, each Deputy independently selected from hydroxyl; carboxyl; halogen, C1-6the alkyl, optionally substituted by hydroxy; polyhalogen1-6of alkyl, C1-6alkyloxy; C1-6alkylthio; polyhalogen-C1-6alkyloxy; C1-6allyloxycarbonyl; C1-6alkylboron the La, nitro, R5R4N-C(=O)-; R5R4N-C1-6of alkyl; HetC1-4of alkyl, Het-C(=O)-;
R4represents hydrogen; C1-4alkyl, optionally substituted by hydroxyl or1-4alkyloxy; R7R6N-C1-4alkyl; R7R6N-C(=O)-C1-4alkyl;
R5represents hydrogen or C1-4alkyl;
R6represents hydrogen; C1-4alkyl; C1-4alkylsulphonyl;
R7represents hydrogen or C1-4alkyl; or
R6and R7may, taken together with the nitrogen to which they are linked, form a saturated monocyclic 5-, 6 - or 7-membered heterocycle, which may optionally contain one or more heteroatoms, each of which is independently selected from O or N;
aryl represents phenyl or phenyl substituted by at least one Deputy, in particular one or two substituents, each Deputy independently selected from halogen; C1-6of alkyl; polyhalogen1-6of alkyl; C1-6alkyloxy; C1-6allyloxycarbonyl; nitro; amino;
aryl1represents phenyl or naphthalenyl, where phenyl optionally is substituted by at least one Deputy, in particular one or two substituents, each Deputy independently selected from hydroxyl; halogen; C1-6of alkyl; C1-6 alkyloxy; C1-6allyloxycarbonyl;
Het is a 5-6-membered monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom, each of which is independently selected from O or N; optionally substituted by one Deputy, selected from C1-6the alkyl, optionally substituted C1-4alkyloxy; C1-6allyloxycarbonyl; -S(=O)p-C1-4of alkyl;
Het1represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom, each of which is independently selected from O, S or N; or a bicyclic non-aromatic a heterocycle containing at least one heteroatom About; specified monocyclic heterocycle or specified the bicyclic heterocycle optionally is substituted by at least one Deputy, in particular one or two substituents, each Deputy independently selected from halogen; C1-6of alkyl; C1-6allyloxycarbonyl; -S(=O)p-C1-4of alkyl; aryl; arils1-4of alkyl;
p represents 2;
its N-oxide, pharmaceutically acceptable salt or MES.

3. The compound according to claim 1, where X represents-O-C(=O) -, C(=O)-C(=O)- NRx-C(=O)-; -Z1-C(=O)-; -C(=O)-Z1-; -Z1-NRxC(=O)-; -NRx-C(=S) -, or-S(=O)p-.

4. The connection is about to claim 3, where X represents-NRx-C(=O)- or-Z1-NRx-C(=O)-.

5. The compound according to claim 4, where X represents a-NRx-C(=O)-.

6. The compound according to any one of claims 1 to 5, where a represents N.

7. The compound according to any one of claims 1 and 3-5, where R1represents a C3-6cycloalkyl; adamantyl; aryl1; aryl1With1-6alkyl; Het1or Het1C1-6alkyl.

8. The compound according to claim 1, where R1represents aryl1or Het1.

9. The connection of claim 8, where Het1is morpholinyl, pyrrolidinyl, piperazinil, homopiperazine, piperidine, furanyl, imidazolyl, thienyl, pyridyl, 1,3-benzodioxolyl, tetrahydropyranyl, each of these heterocycles, optionally is substituted by one or two substituents, each Deputy is independently selected from C1-6of alkyl, C1-6allyloxycarbonyl, -S(=O)p-C1-4of alkyl, aryl, arils1-4the alkyl.

10. The connection of claim 8, where the aryl1represents phenyl, naphthalenyl or phenyl substituted by one or two substituents, each Deputy independently selected from hydroxyl, halogen, C1-6of alkyl, C1-6alkyloxy,1-6allyloxycarbonyl or Het.

11. The compound according to claim 1, where R1represents phenyl, substituted C1-6alkyloxy.

12. The compound according to claim 1, g is e R 3represents phenyl, naphthalenyl or 2,3-dihydrobenzofuranyl, each of these cycles is optional substituted with one to five substituents, each of these substituents independently selected from halogen, C1-6the alkyl, optionally substituted hydroxy, polyhalogen1-6of alkyl, C1-6alkylthio, polyhalogen-C1-6alkyloxy, carboxyl, hydroxyl, C1-6alkylsulphonyl, C1-6alkyloxy, C1-6allyloxycarbonyl, nitro, R5R4N-C(=O)-; R5R4N-C1-6of alkyl, HetC1-4of alkyl, Het-C(=O)-C1-4of alkyl, Het-C(=O)-.

13. The connection section 12, where R3represents phenyl, substituted with three substituents, each of which is independently selected from halogen or HetC1-4the alkyl.

14. The compound according to claim 1, where the compound of formula (I) is a compound of formula (I)

where each of R3aand R3bindependently represents hydrogen; halogen; C1-6alkyl; polyhalogen1-6alkyl; C1-6alkyloxy; C1-6alkylthio; polyhalogen1-6alkyloxy; C1-6allyloxycarbonyl; C1-6alkylsulphonyl; nitro; and R3crepresents hydrogen; halogen; C1-6alkyl; polyhalogen1-6alkyl, C1-6alkyloxy; C1-6alkylthio; polyhalogen-C1-6alkyloxy; C1-6and biloxicasino; C1-6alkylsulphonyl; nitro; R5R4N-C(=O)-; R5R4N-C1-6alkyl; HetC1-4alkyl; Het-C(=O)-C1-4alkyl; Het-C(=O)-.

15. The compound according to claim 1, where the compound of formula (I) is a compound of formula (I")

where each of R3aand R3bindependently represents hydrogen; halogen; C1-6alkyl; polyhalogen1-6alkyl; C1-6alkyloxy; C1-6alkylthio; polyhalogen1-6alkyloxy; C1-6allyloxycarbonyl; C1-6alkylsulphonyl; nitro; and R3crepresents hydrogen; halogen; C1-6alkyl; polyhalogen1-6alkyl, C1-6alkyloxy; C1-6alkylthio; polyhalogen-C1-6alkyloxy; C1-6allyloxycarbonyl; C1-6alkylsulphonyl; nitro; R5R4N-C(=O)-; R5R4N-C1-6alkyl; HetC1-4alkyl; Het-C(=O)-C1-4alkyl; Het-C(=O)-.

16. The connection 14 or 15, where each of R3aand R3bindependently represents halogen, C1-6alkyl or C1-6alkyloxy.

17. The connection clause 16, where each of R3aand R3bindependently represents a halogen.

18. The connection 14, where R3cis an R5R4N-C(=O)-; R5R4N-C1-4alkyl; Het-C(=O)-; HetC1-4alkyl or Het-C(=O)-C1-4alkyl.

19. Connection p, where R3cis own the th HetC 1-4alkyl.

20. The compound according to claim 1, where Z2represents a C1-6alcander or2-6alcander.

21. The compound according to claim 1, where Y is-NRx-C(=O)-Z2-, and Z2represents methylene.

22. The compound according to claim 1, where Rxrepresents hydrogen.

23. The compound according to claim 1, where Ryrepresents hydrogen or C1-4alkyl, or-S(=O)p-aryl.

24. The compound according to claim 1, having the following formula

where a represents CH or N;
X represents-O-C(=O)-; -C(=O)-C(=O)-; -NRx-C(=O)-; -Z1-C(=O)-; -Z1-NRx-C(=O)-, -C(=O)-Z1-; -S(=O)p-; -NRx-C(=S)-;
Z1represents a C1-6alcander; where specified With1-6alcander optionally may be substituted by hydroxyl or amino; and where two hydrogen atoms linked to the same carbon atom in the C1-6alcantera, optional can be replaced With1-6Alcantara;
Y represents NRx-C(=O)-Z2-; -NRx-C(=O)-Z2-NRy-; -NRx-C(=O)-Z2-NRy-C(=O)-; -NRx-C(=O)-Z2-NRy-C(=O)-O-; -NRx-C(=O)-Z2-O-; -NRx-C(=O)-Z2-O-C(=O)-; -NRx-C(=O)-Z2-C(=O)-O-; -NRx-C(=O)-Z2-C(=O)-NRy-; -NRx-C(=O)-Z2-NRy-C(=O)-NRy-, -C(=O)-Z2-; -C(=O)-NRx-Z2-; -C(=O)-NRx-Z2-O;
Z is a divalent radical selected from C1-6Alcantara, C2-6Alcantara or2-6alcinder, where each of the specified C1-6Alcantara,2-6Alcantara or2-6alcindoro optionally may be substituted With1-4alkyloxy,1-4alkylthio, hydroxyl, cyano or aryl; and where two hydrogen atoms linked to the same carbon atom in the definition of the Z2not necessarily can be replaced With1-6Alcantara;
Rxrepresents hydrogen or C1-4alkyl;
Ryrepresents hydrogen; C1-4alkyl; C2-4alkenyl; or-S(=O)p-aryl;
R1represents a C1-12alkyl, optionally substituted by cyano, C1-4alkyloxy,1-4alkalosis1-4alkyloxy,3-6cycloalkyl or aryl; C2-6alkenyl,2-6quinil; C3-6cycloalkyl; adamantyl; aryl1; Het1; or Het1C1-6alkyl; provided that when Y represents NRx-C(=O)-Z2-; -NRx-C(=O)-Z2-NRy-; -NRx-C(=O)-Z2-C(=O)-NRy-; -C(=O)-Z2-; NRx-C(=O)-Z2-NRy-C(=O)-NRy; -C(=O)-NRx-Z2-; -C(=O)-NRx-Z2-O; or-C(=O)-NRx-Z2-NRy-; then R1may also represent hydrogen;
R2is an R3;
R3 represents a phenyl, naphthalenyl, 2,3-dihydrobenzofuranyl or 6-membered aromatic heterocycle containing 1 or 2 N atom, where each of the specified phenyl, naphthalenyl, 2,3-dihydrobenzofuranyl or 6-membered aromatic heterocycle containing 1 or 2 N atom may be substituted by one, two, three, four, or five substituents, each Deputy independently selected from halogen; C1-6the alkyl, optionally substituted by hydroxy; polyhalogen1-6of alkyl; C1-6alkyloxy; C1-6alkylthio; polyhalogen-C1-6alkyloxy; C1-6allyloxycarbonyl; C1-6alkylcarboxylic; nitro; R5R4N-C(=O)-; R5R4N-C1-6of alkyl; HetC1-4of alkyl, Het-C(=O)-C1-4of alkyl, Het-C(=O)-;
R4represents hydrogen; C1-4alkyl, optionally substituted by hydroxyl or1-4alkyloxy; R7R6N-C1-4alkyl; Het-C1-4alkyl; R7R6N-C1-4alkyl;
R5represents hydrogen or C1-4alkyl;
R6represents a C1-4alkyl or C1-4alkylsulphonyl;
R7represents hydrogen or C1-4alkyl; or
R6and R7may, taken together with the nitrogen to which they are linked, form a saturated monocyclic 5-, 6 - or 7-membered heterocycle, which may optionally contain one or more heteroatoms, it is gdy of which is independently selected from O or N;
R8represents hydrogen, halogen, C1-4alkyl substituted by hydroxyl;
aryl represents phenyl or phenyl substituted by one or two substituents, each Deputy independently selected from halogen; C1-6of alkyl, polyhalogen1-6of alkyl; C1-6alkyloxy; nitro;
aryl1represents phenyl or naphthalenyl; where phenyl optionally is substituted by one or two substituents, each Deputy independently selected from hydroxyl; halogen; C1-6of alkyl; C1-6alkyloxy; C1-6alkyloxy-carbonyl or Het;
Het is a 5-6-membered monocyclic non-aromatic or aromatic heterocycle containing at least one N atom; specified monocyclic heterocycle optionally is substituted by one Deputy, selected from C1-6the alkyl, optionally substituted C1-6alkyloxy; C1-6alkylcarboxylic or-S(=O)p-C1-4of alkyl;
Het1represents a monocyclic non-aromatic or aromatic heterocycle containing at least one heteroatom, each of which is independently selected from N, O or S, or a bicyclic non-aromatic a heterocycle containing at least one atom About; specified monocyclic heterocycle or specified the bicyclic heterocycle, the long the flax is substituted by one or two substituents, each Deputy independently selected from halogen; C1-6of alkyl; C1-6allyloxycarbonyl; -S(=O)p-C1-4of alkyl; aryl or arils1-4of alkyl;
p represents 2.

25. The compound according to claim 1, where the compound selected from

their N-oxides, pharmaceutically acceptable salt or solvate.

26. The compound according to claim 1, where the connection is a

including its N-oxide, pharmaceutically acceptable salt or MES.

27. The compound according to claim 1 for use as a medicinal product that has the property of DGAT1 inhibitor.

28. The compound according to claim 1 for use in the treatment of obesity or diabetes.

29. Connection p for use in the treatment of type II diabetes.

30. Pharmaceutical composition having the property of DGAT1 inhibitor containing a pharmaceutically acceptable carrier and as active ingredient a therapeutically effective amount of a compound according to any one of claims 1 to 26.

31. The use of compounds according to claim 1 to obtain drugs for prevention or treatment of obesity or diabetes.



 

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6 cl, 5 tbl, 19 ex

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25 cl, 1 dwg, 2 tbl, 19 ex

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9 cl, 2 tbl, 40 ex

FIELD: chemistry; medicine.

SUBSTANCE: compounds of claimed invention possess properties of positive allosteric modulator mGluR5. In general formula I , W represents 6-member heterocycloalkyl ring with 1-2 heteroatoms, selected from N, O; R1 and R2 independently represent hydrogen, C1-C6-alkyl; P and Q each independently is selected from: , R3, R4, R5, R6 and R7 independently represent hydrogen; halogen; -CN; nitro; C1-C6-alkyl; C3-C6-cycloalkyl; halogen-C1-C6-alkyl; 5-6-member heteroaryl with 1-2 atoms N as heteroatoms; 6-member heterocycle with 2 heteroatoms representing N, O; phenyl, optionally substituted with halogen; naphtyl; -OR8; where optionally two substituents together with located between them atoms form 9-10-member bicyclic aryl or heteroaryl ring with 1-2 heteroatoms, selected from N, S; R8 represents hydrogen, C1-C6-alkyl; D, E, F, G and H independently represent -C(R3)=, -O-, -N=, -N(R3)- or -S-; A represents ethinyl, -C(=O)NR8- or group of formula . B represents -C(=O)-C0-C2-alkyl-, -C(=O)-C2-C6-alkenyl-. Invention also relates to pharmaceutical composition based on invention compounds.

EFFECT: novel compounds possess useful biological proprties.

20 cl, 3 dwg, 75 ex

FIELD: chemistry.

SUBSTANCE: compounds of the invention have chemokine antagonistic properties and can be applied in treatment of immunoinflammatory diseases, such as atherosclerosis, allergy diseases. In general formula (I) R1 is hydrogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxyl, cyclopropylmethoxy group, (C1-C4)-alkylthio group; R2 is halogen atom, (C1-C8)-alkyl, perfluoro-(C1-C4)-alkyl, (C3-C10)-cycloalkyl, phenyl, (C1-C8)-alkoxyl, values of the other radicals are indicated in the claim of the invention.

EFFECT: improved properties.

14 cl, 7 tbl, 20 dwg, 17 ex

FIELD: chemistry.

SUBSTANCE: invention concerns chemistry of adamantane derivatives, particularly new method of obtaining N,N-dialkyl-substituted amides of adamantylalkylcarboxylic acids of the general formula

which can be of interest as semiproducts in synthesis of some bioactive substances with antivirus effect. Method involves interaction of adamantane derivative with carboxylic acid dialkylamide, where 1,3-dehydroadamantane is used as adamantane derivative, and N,N-dimethylacetamide, N,N-diethylacetamide, N-acethylpiperidine, N-propionylpiperidine, N-(2-methyl)propionylpiperidine are used as carboxylic acid dialkylamides, and process runs at reagent mol ratio of 1:2-3 respectively, in original carboxylic acid dialkylamide medium at 120-130°C for 5-6 hours.

EFFECT: alternative method of obtaining compounds of the claimed structural formula, with omitted stage of obtaining adamantylalkylcarboxylic acids.

5 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to a new piperidine derivative, with the following general formula (I) where R1 - R4 each stands for any of the univalent groups, indicated below: R1 stands for a hydrogen atom, halogen atom, inferior alkyl, which can be substituted with a halogen atom or OH; -O-inferior alkyl, which can be substituted with a halogen atom; -O-aryl, aryl, -C(=O)-inferior alkyl, COOH, -C(=O)-O-inferior alkyl, -C(=O)-NH2, -C(=O)NH-inferior alkyl, -C(=O)N-(inferior alkyl)2, OH, -O-C(=O)-inferior alkyl, NH2, -NH-inferior alkyl, -N-(inferior alkyl)2, NH-C(=O)- inferior alkyl, CN or NO2; R2 and R3 each stands for a hydrogen atom; and R4 stands for any of the univalent groups (a), (b) and (c), shown below in formula 2 where in the above indicated groups (a), (b) and (c), A stands for a pyrrolidine, piperidine, morpholine, piperizine or oxazepane ring; B stands for a pyrrolidine or piperidine ring; R5 and R8-R11 can be identical or different from each other and each stands for a hydrogen atom, -C(=O)-O-inferior alkyl, cycloalkyl or tetrahydropyrane; R6 stands for a hydrogen atom, -C(=O)-O-inferior alkyl, OH, -inferior alkylene-OH or -C(=O)-pyridine; and R7 stands for a hydrogen atom. The invention also pertains to pharmaceutical salts of the piperidine derivative, as well as medicinal compositions.

EFFECT: obtaining new biologically active compounds and a medicinal composition, based on these compounds, which is a sodium channel inhibitor.

10 cl, 91 ex, 22 tbl

FIELD: chemistry, pharmaceutics.

SUBSTANCE: invention relates to compounds of formula 1 and their pharmaceutically acceptable salts as inhibitors of post-proline aminopepdidases, as well as to pharmaceutical composition based on them and application for manufacturing such composition, and to method of inhibition with their application. Compounds can be applied for treatment of diseases mediated by activity of post-proline aminopeptidases, such as type II diabetes and disturbed tolerance to glucose. In general formula 1 ,

either G1 represents -CH2-X2-(CH2)a-G3, and G2 represents H, or G2 represents -CH2-(CH2)a-G3, and G1 represents H; G3 is selected from group according to general formula 2 ,

group according to general formula 3

and group according to general formula 4 ;

a is 0, 1 or 2; b is 1 or 2; X1 is selected from CH2, S, CF2, CHF and O; X2 is selected from CH2; X3, X4 and X5 are selected from N; X6 is selected from NH; X7 is selected from NH; R1 is selected from H and CN; R2 represents H; R3 is selected from H, Cl, OH, NH2, NH-C1-C10alkyl and N(C1-C10alkyl)2; R4, R5, R6, R7 and R8 are independently selected from H, Br, Cl, F, OH, NO2; R9 represents H; R10, R11, R12, R13 and R14 are independently selected from H, Cl and CF3; R15 and R16 are independently selected from H, C1-C10alkyl, C1-C10alkenyl, C3-C10cycloalkyl, C3-C10cycloalkenyl, quinoline, naphtyl and -CH2-L-R17; R17 is selected from C1-C10alkyl, phenyl, naphtyl, quinolinyl and indolyl; L is selected from covalent bond, CH=CH and -C6H4-; on condition that when R15 and R16 both represent H, and b is 1, then X1 does not represent S or CH2.

EFFECT: obtaining compounds that can be applied for treatment of diseases mediated by activity of post-proline aminopeptidases, such as type II diabetes and disturbed tolerance to glucose.

58 cl, 10 tbl, 1705 ex

FIELD: organic chemistry, chemical technology, pharmacy.

SUBSTANCE: invention relates to novel derivatives of urea of the general formula (I): and their pharmaceutically acceptable salts wherein A represents -CH- or nitrogen atom; R1 represents (C3-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkyl-(C1-C10)-alkyl, 6-membered nitrogen-containing heterocycle, 6-membered nitrogen-containing heterocyclyl-(C1-C10)-alkyl, phenyl, phenyl-(C1-C10)-alkyl, 5-10-membered heteroaryl or 5-10-membered heteroaryl-(C1-C10)-alkyl, and others; R2 represents hydrogen atom, (C1-C6)-alkyl, (C0-C2)-alkyl-(C3-C10)-cycloalkyl, (C0-C2)-alkylphenyl, (C3-C10)-cycloalkyl-(C0-C2)-alkyl or phenyl-(C0-C2)-alkyl; R5 represents (C1-C6)-alkyl, (C3-C10)-cycloalkyl, 6-membered nitrogen-containing heterocyclyl, and others; L1 represents -S-, -S(O)-, -S(O2)-, -C(O)-, -N(Rc)-, -CH2-, and others; L2 represents a covalent bond, -O-, -C(O)-, -OC(O)-, -N(Rc)-, and others; W represents oxygen (O) or sulfur (S) atom; Z represents -C(O)ORd wherein Rc, Rd and Re represents hydrogen atom or alkyl; Rb represents -ORe, -NO2, halogen atom, -CN, -CF, (C1-C6)-alkyl; p represents a whole number from 0 to 4. Compounds of the formula (I) and their salts possess antagonistic activity with respect to α4-integrin and can be used in medicine for inhibition or prophylaxis of cellular adhesion in patient body mediated by α4β1- and/or α4β7-integrins.

EFFECT: improved methods of synthesis, valuable medicinal properties of compounds and pharmaceutical composition.

17 cl, 2 tbl, 180 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of piperidine of the general formula (I): or their pharmaceutically acceptable salts wherein rings A and B represent optionally substituted benzene rings; R1 represents alkyl, hydroxyl, thiol, carbonyl, sulfinyl, unsubstituted or substituted sulfonyl group and others; R2 represents hydrogen atom, hydroxyl, amino-group, alkyl, unsubstituted or substituted carbonyl group or halogen atom; Z represents oxygen atom or group -N(R3)- wherein R3 and R4 represent hydrogen atom or alkyl group under condition that N-acetyl-1-benzyloxycarbonyl-2-phenyl-4-piperidineamine is excluded. Compounds of the formula (I) or their salts possess antagonistic activity with respect to tachykinin NK1-receptors and can be used in medicine in treatment and prophylaxis of inflammatory, allergic diseases, pain, migraine, diseases of central nervous system, digestive organs and others.

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

18 cl, 138 tbl, 527 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to novel substituted derivatives of cyclohexane of the formula (I): wherein U means a free electron pair; V means a simple bond, -CH2-, -CH=CH-, -CH=CH-CH2-O-, -C≡C-; W means -COO, -CSO or -SO2; m and n mean independently of one another numbers from 0 to 4; m + n = 0-7; A1 means hydrogen atom (H), lower alkyl, hydroxy-(lower)-alkyl or lower alkenyl; A2 means pyrrolyl, pyrimidinyl, optionally substituted (lower)-alkyl or lower alkyl optionally substituted with R2; or A1 and A2 are bound to form ring; -A1-A2- means lower alkylene optionally substituted with R2 wherein one group -CH2- in -A1-A2- can be optionally replaced for -NR3 or oxygen atom (O); A3, A4, A5, A6, A7 and A8 mean H; R9 means H, lower alkyl; R10 means (lower)-alkyl, phenyl wherein phenyl can be substituted with 1-3 substitutes chosen independently from the group comprising halogen atom, -CF3, (lower)-alkyl; p means 0, 1; R2 means H; R3 means H, lower alkyl, and their pharmaceutically acceptable salts. Compounds of the formula (I) possess the inhibitory effect on activity of enzyme oxidosqualene lanosterol cyclase and can be used in pharmaceutical composition. Also, method relates to a method for treatment and/or prophylaxis of hyperlipemia, artheriosclerosis, hypercholesterolemia and others.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

27 cl, 9 sch, 10 tbl, 43 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, particularly to a product containing an insulin response. A method for producing the product containing the insulin response involving mixing at least one polyphenol-containing herbal material specified in a group consisting of fruit, vegetables, tea, green tea, coffee, cocoa, chocolate and bark, and at least aqueous edible solvent for making the mixture; heating said mixture; adding at least one lactic acid bacilli strain specified in Lactobacillus plantarum, and optionally at least one protein source specified in a group including peptones, tryptones, yeast extracts and their combinations to said heated mixture for making the fermented mixture; and exposing said fermented mixture to the conditions suitable for fermentation for making the product reducing the insulin response, and optionally eliminating the Lactobacillus plantarum strain. The use of the product reducing the insulin response for preparing a composition for preventing or treating diabetes, metabolic syndrome, obesity and cardiovascular diseases.

EFFECT: product prepared by the method described above effectively reduces the insulin response.

15 cl, 7 dwg, 11 tbl

FIELD: chemistry.

SUBSTANCE: compounds activate glucokinase and can be used to prepare medicine for treating of metabolic disorders, for lowering blood glucose level, for treating hyperglycemia, for treating IGT, for treating Syndrome X, for treating impaired fasting glucose (IFG), for treating type 2 diabetes, for treating type 1 diabetes, for delaying the progression of impaired glucose tolerance (IGT) to type 2 diabetes, for delaying the progression of non-insulin requiring type 2 diabetes to insulin requiring type 2 diabetes, for treating dyslipidemia, for treating hyperlipidemia, for treating hypertension, for lowering food intake, for appetite regulation, for for treating obesity, for regulating feeding behaviour, or for enhancing the secretion of enteroincretins. In compounds of formula , A denotes , R3 is selected from a group consisting of phenoxy and benzyloxy, each possibly substituted with one or more substitutes independently selected from R12; R12 is F, CI, Br, -CF3, -CN methyl, ethyl, isopropyl, tert-butyl, methoxy, methylthio, ethoxy, cyclopropyl-methoxy, -NHC(O)CH3 or -S(O)2-CH3; R30 is methyl, ethyl, propyl, isopropyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, methoxy, ethoxy, propoxy, butoxy, tert-butoxy, benzyloxy or cyclopropyl-methoxy, each possibly substituted with one or more substitutes independently selected from R12; R8 is methylthio, isopropylthio, ethylthio or 2-methylpropylthio, each substituted with one or more substitutes independently selected from R34; R34 is carboxy.

EFFECT: improved properties of the compound.

13 cl, 1 tbl, 242 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to oxadiazolidinone compounds presented by following formula (I), or to their pharmaceutically acceptable salts, (symbols in the presented formula represent the following values, R1: -H, R0: lower alkyl, Rz: the same or different from each other, and each represents -H or lower alkyl, L: *-CH2-O- or *-CH2-NH-, where the symbol * in L represents binding with the ring A and a substitution position in the group L in the ring B represents the 4-position, the ring A: benzole, the ring B: benzole or pyridine, R2; the same or different respectively, and each represents -halogen or -R0, n: 0 or 1, R3: phenyl which can be substituted by a group selected from the group G3, The group G3: halogen, -R0, halogen-lower alkyl, -ORz, -CON(Rz)2, -CON(Rz)-heteroring group, -O-S(O)2-R0, -O-lower alkylene-ORz, -O-lower alkylene-O-COR2, -O-lower alkylene-N(RZ)2, -O-lower alkylene-N(Rz)CO-Rz, -O-lower alkylene-CO2Rz, -O-lower alkylene-CON(Rz)2, -O-lower alkylene-CON(Rz)-(lower alkyl substituted by the group-ORz), -O-lower alkylene-SR0, -O-lower alkylene-cycloalkyl, -O-lower alkylene-CON(Rz)-cycloalkyl, -O-lower alkylene-heteroring group and -O-lower alkylene-CON(Rz)-heteroring group, where lower alkylene in the group G3 can be substituted by halogen or -ORz, and cycloalkyl and the heteroring group in the group G3 can be substituted by the group selected by the group G1, The group G1: halogen, cyano, -R0, -ORz, -N(RZ)2, -S-R0, -SO2-R0, -SO2N(Rz)2, -CO-R2, -CON(Rz)2, -CON(Rz)-lower alkylene-OR2, -N(Rz)CO-Rz, oxo, -(lower alkylene which can be substituted by the group -ORz)-aryl, heteroring group and lower alkylene-heteroring group where aryl and the heteroring group in the group G1 can be substituted by the group selected from the following group G2, the group G2: halogen, cyano where the heteroring group means a group containing a ring selected from i) a monocyclic 5-7-members, saturated or unsaturated heteroring containing 1 to 3 heteroatoms selected from O, S and N, ii) a bicyclic heteroring in which the heterorings selected in i) mentioned above are ring-condensed where the condensed rings can be the same or different, and iii) the bicyclic heteroring in which the heteroring selected in i) mentioned above is condensed with a benzoic ring or 5-7-members cycloalkane, R4: -H. The invention refers to a pharmaceutical composition, to application of the compounds under cl.1, as well as to a method for preventing and/or treating diabetes.

EFFECT: making new biologically active compounds representing GPR40 agonist, an agent stimulating insulin secretion and/or an agent for preventing and/or treating diabetes.

9 cl, 27 ex, 138 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to endocrinology and can be used for reduction of hypoglycemia acute exacerbation or severe hypoglycemia exacerbation in patients with type II diabetes after treatment with insulin. For this purpose vildagliptin or its salt is introduces to patient in combination with insulin.

EFFECT: invention ensures reduction of risk of hypoglycemia development, as well as necessity to apply several antihyperglycemic medications.

12 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) , where X is C(R8R9), NR10, O, S; R1 is phenyl which is substituted with 1-3 substitutes selected from a group which includes halogen, hydroxy group, lower alkyl, hydroxy-lower alkyl and CN; R2 is hydrogenor lower alkyl; R3 and R4 are hydrogen; R5 and R6 are hydrogen; R7 is oxadiazolyl or triazolyl, where oxadiazolyl or triazolyl is substituted with R11; R8 and R9 denote hydrogen; R10 denotes hydrogen, lower alkyl, lower alkyl-carbonyl or lower alkyl-sulfonyl, R11 denotes aryl or hetearyl, selected from a group comprising pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-one, oxadiazolyl, indazolyl, 1,3-dihydrobenzimidazol-2-one, 1,3-dihydroindol-2-one, benzotriazolyl, imidazopyridinyl, triazolepyridinyl, tetrazolepyridinyl, benzimidazolyl, 2-oxo-2,3-dihydro-1H-indol-5-yl, pyrimidin-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidin-2,4-one, benzoxazin-3-one, 1,4-dihydrobenzoxazin-2-one, indolyl, thiophenyl, oxazolyl, benzooxazin-2-one; 3,4-dihydroquinazolin-2-one, pyridazinyl, quinoxalinyl, benzothiazolyl, benzothiadiazolyl, naphthyridinyl, cinnolinyl, 1,4-dihydroquinoxalin-2,3-dione and 1,2-dihydroindazol-3-one, where the aryl or heteroaryl is optionally substituted with 1-3 substitutes selected from a group which includes lower alkyl, hydroxy group, B(OH)2, carboxy-lower alkoxy group, carbamoyl-lower alkoxy group, cyano group, hydroxy-lower alkyl, fluoro-lower alkyl, lower alkoxy group, halogen, S(O2)R13, C(O)R14, NO2, NR15R16, phenyl-lower alkoxy group, [1,3,4]oxadiazol-2-one, oxadiazolyl, triazolyl and isoxazolyl, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl, where imidazolyl is optionally substituted with lower alkyl, and where isoxazolyl is substituted with lower alkyl; R12 denotes hydrogen or lower alkyl; R13 denotes lower alkyl, NR17R18 or fluoro-lower alkyl; R14 denotes NR19 R20, lower alkoxy group, lower alkenyl-oxy group or lower alkyl; R15 and R16 independently denote hydrogen, lower alkyl, lower alkyl-carbonyl, lower alkyl-SO2, lower alkenyl-oxycarbonyl and lower alkyl-NH-carbonyl; or NR15R16 denotes heterocyclyl selected from a group which includes morpholinyl, thiomorpholinyl, 1,1-dioxothiomorpholinyl, piperidinyl, piperidin-2-one, piperazin-2-one, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperazinyl, pyrrolidinyl, 1,1-dioxoisothiazolidinyl, pyrrolidin-2-one, imidazolidine-1,4-dione, 2,4-dihydro[1.2.4]triazol-3-one, pyrrolidine-2,5-dione, azetidin-2-one and 1,3-dihydroimidazol-2-one, where the heterocycle is optionally substituted with hydroxy-lower alkyl or lower alkyl-carbonyl; R17 and R18 independently denote hydrogen, lower alkyl, hydroxy-lower alkyl, lower alkoxy group-lower alkyl; or NR17 R18 denotes morpholinyl; R19 and R20 independently denote hydrogen, lower alkyl, cycloalkyl, hydroxy-lower alkyl, lower alkoxy group-lower alkyl or cyano-lower alkyl; or NR19 R20 denotes heterocyclyl selected from a group which includes morpholinyl, pyrrolidinyl, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperidinyl, piperazinyl, piperazin-2-one, thiazolidinyl, thiomorpholinyl, 1,3,8-triaza-spiro[4.5]decane-2,4-dione and spiro(1- phthalan)piperidin-4-yl, where the heterocyclyl is optionally substituted with a hydroxy group, lower alkyl-(SO2), lower alkyl, lower alkyl-carbonyl or lower alkoxy group, carboxyl group, carbamoyl, cyano group and phenyl; and to their pharmaceutically acceptable salts. Invention also pertains to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds which inhibit hepatic carnitine palmitoyltransferase 1 (L-CPT1).

35 cl, 565 ex, 10 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to pharmaceutical industry and concerns a composition for glucose delivery through an oral mucosa for increasing of glucose (sugar) blood level of an individual. The composition contains: a. effective amount of glucose, b. effective amount of sodium glycocholate, c. effective amount of a pharmaceutically acceptable carrier; the composition it is free from additional active pharmaceutical agents.

EFFECT: development of the effective method for increasing glucose (sugar) blood level.

13 cl, 9 ex, 4 tbl, 7 dwg

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: medicine.

SUBSTANCE: present invention concerns new, selectable hybrid polypeptides expressing at least two hormonal activities containing a first biologically active module of a peptide hormone covalently bonded with at least one additional biologically active module of the peptide hormone.

EFFECT: polypeptides can be used as agents for treatment and prevention of metabolic diseases and disorders associated with overweight.

19 cl, 6 dwg, 6 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new 2-alkylsufanyl-3-arylsufonyl-cycloalkano[e]pyrazolol[1,5-a]pyrimidines of general formula 1 or 2-alkylsufanyl-3-arylsufonyl-cycloalkano[d]pyrazolo[1,5-a]pyrimidines of general formula 2, which are antagonist of 5-HT6 receptors. In compounds of formula 1

and 2 ,

R1 is a hydrogen atom or C1-C3 alkyl; R2 is C1-C3 alkyl; R3 is a hydrogen atom, one or two optionally identical halogen atoms, C1-C3 alkyl or hydroxyl, optionally substituted with C1-C3 alkyl; n is an integer equal to 1, 2 or 3.

EFFECT: compounds can be used in preventing and treating diseases of the central nervous system, anxiolytics and as compounds with nootropic effect and suitable for enhancing memory.

12 cl, 1 dwg, 4 tbl, 9 ex

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