Substituted 2-quinolyloxazoles suitable as pde4 inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-quinolyloxazoles of formula (I) or pharmaceutically acceptable salts thereof, having PDE4 inhibiting properties, a pharmaceutical composition based on said compounds and use thereof to prepare a medicinal agent which inhibits inflammatory cell recruitment in respiratory tracts. , where is , X is O, R1 is alkyl, R3 and R4 are independently selected from H, R5 and R6 are independently selected from a group comprising H, alkyl, hydroxyalkyl, t equals 1 or 2. Values of substitutes R7-R11, R13 are given in the formula of invention.

EFFECT: high efficiency of using the composition.

24 cl, 1 dwg, 64 ex

 

The text descriptions are given in facsimile form.

1. The compound represented by structural formula

or its pharmaceutically acceptable salt,
where
is
X is O;
R1is alkyl;
R3and R4independently of the choice is up from N;
R5and R6independently selected from the group comprising H, alkyl, hydroxyalkyl;
t is 1 or 2;
R7is H, alkyl, alkenyl, hydroxyalkyl, cycloalkyl or-CH2-C(O)-O-alkyl;
R8is H, alkyl, alkoxyalkyl, hydroxyalkyl,
R23-heteroallyl where heteroaryl represents a monocyclic, bicyclic or benzododecinium heteroaromatic group of 5 to 10 atoms, containing 2 to 9 carbon atoms and 1 to 4 heteroatoms, independently selected from the group comprising N, O and S, and N-oxides of the nitrogen atoms of the ring, provided that the rings do not include adjacent oxygen atoms and/or sulfur, R36-heterocyclization where heteroseksualci represents a non-aromatic saturated monocyclic ring containing 5 atoms, in which 1 atom independently selected from nitrogen and sulfur, R17-phenyl, (R17-phenyl)alkyl, (R17-naphthyl)alkyl, R17-benzyloxy, -alkyl-C(O)-NR18R19, -alkyl-C(O)-(R17-phenyl), -alkyl-C(O)-(R36-heterocyclization), where heteroseksualci represents a non-aromatic saturated monocyclic ring containing 4-6 atoms, where from 1 to 2 atoms independently selected from nitrogen and oxygen,
-alkyl-N(R30)-C(O)Valkila, -alkyl-N(R30)-C(O)NR18R19, -alkyl-N(R30)-C(O)Valkila, -lkyl-N(R 30)-C(O)-(perakyla), -alkyl-N(R30)-C(O)-(R39-cycloalkyl), -alkyl-N(R30)-C(O)-(R17-phenyl), -alkyl-N(R30)-C(O)-(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms comprising from 4 to 5 carbon atoms and from 1 to 2 heteroatoms independently selected from nitrogen and oxygen, -alkyl-N(R30)-C(O)-alkylene-(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 5 or 6 atoms comprising from 3 to 5 carbon atoms and from 1 to 2 heteroatoms independently selected from nitrogen and sulfur, -alkyl-N(R30)-(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 5 or 6 atoms comprising from 3 to 5 carbon atoms and from 1 to 2 heteroatoms independently selected from nitrogen and sulfur, -alkyl-O-(R17-phenyl), -alkyl-N(R30)-SO2-alkyl, alkyldimethyl-, alkyl-SO2-alkyl-, (R35-phenylalkyl)-S-alkyl-, (hydroxyalkyl)-S-alkyl-, -alkyl-CO2-alkyl, R45-hydroxyalkyl, dihydroxyaluminum, substituted R17-benzyloxy, dihydroxyaluminum, substituted R17-phenyl, (R17-phenyl)alkyl, substituted
-CO2the alkyl, R17-phenyl)alkyl, substituted-C(O)N(R30)2, alkyl, substituted (R23-heteroaryl), where GE is Eroare represents a monocyclic heteroaromatic group of 5 or 6 atoms, comprising from 4 to 5 carbon atoms and 1 heteroatom independently selected from nitrogen and oxygen, -C(O)NR37R38, halogenation, substituted CO2the alkyl, R12-cycloalkyl, (R12-cycloalkyl)alkyl,
,,,,
,,,,
,,,or
;
or R7and R8and the nitrogen atom to which they are attached, together form a ring system selected from the group consisting of
,,,,,
,,,,
,,,
,,,,
,,, ,,
,or;
p is 0 or 1;
q is 0 or 1;
the dotted line indicates an optional double bond;
R9is H, halogen, alkyl or CF3;
R10, R11and R13independently selected from H;
R12is 1-3 substituents, independently selected from the group comprising H, -C(O)Alkyl, -(CH2)n-N(R30)-C(O)-cycloalkyl, -(CH2)n-N(R30)-C(O)alkyl, -(CH2)n-N(R30)-(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms, including 4 carbon atoms, and 2 heteroatoms, represents nitrogen, -(CH2)n-N(R30)-C(O)-NR18R19, -(CH2)n-C(O)-NR18R19, R17-phenyl, R35-heteroaromatic where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms comprising from 4 to 5 carbon atoms and 1 or 2 heteroatoms, represents a nitrogen, R35-heteroaromatic where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms, including 4 carbon atoms, and 2 heteroatoms, represents nitrogen, -C(O)-heteroseksualci where heteroseksualci represents a nonaromatic feast upon the TES monocyclic ring, contains 4 atoms, one of which is a nitrogen, -O-C(O)-heteroseksualci where heteroseksualci represents a non-aromatic saturated monocyclic ring containing 6 atoms, where from 1 to 2 atoms independently selected from nitrogen and oxygen, -O-C(O)-NR18R19, -NH-SO2-alkyl and-NH-C(=NH)NH2; or two R12substituent on the same carbon atom form =O,
=NOR30or =CH2;
R14is 1 or 2 substituents, independently selected from the group including H, HE, halogen, alkoxy, CN, R17-phenyl, (R17-phenyl)alkyl, -(CH2)n-C(O)HE, -(CH2)n-C(O)Alkyl, -(CH2)n-C(O)(R35-phenyl), -(CH2)n-C(O)(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms comprising from 4 to 5 carbon atoms and 1 or 2 heteroatoms, represents nitrogen, -(CH2)n-C(O)NR18R19, -(CH2)n-C(O)N(R30)-(CH2)n-(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms, containing 5 carbon atoms and 1 heteroatom, representing nitrogen, -(CH2)n-N(R30)-C(O)alkyl, -(CH2)n-N(R30)-C(O)-(cycloalkyl), -(CH2)n-N(R30)-C(O)(R35-phenyl), -(CH2)n-N(R )-C(O)(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 5 atoms, including 4 carbon atoms and 1 heteroatom represents oxygen,
-(CH2)n-N(R30)-C(O)Alkyl, -(CH2)n-N(R30)(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms, including 4 carbon atoms, and 2 heteroatoms, represents nitrogen, -(CH2)n-N(R18)SO2alkyl, -(CH2)n-N(R20)SO2-(R17-phenyl),
-CH2S(O)0-2(R35-phenyl), -(CH2)n-OC(O)N(R30)alkyl, R23-heteroaryl where heteroaryl represents a monocyclic or benzododecinium heteroaromatic group of 5, 6 or 9 atoms, comprising from 3 to 6 carbon atoms and from 1 to 3 heteroatoms selected from nitrogen and sulfur, (R23-heteroaryl)alkyl, where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms comprising from 4 to 5 carbon atoms and 1 or 2 heteroatoms, represents nitrogen, (R23-heteroaryl)hydroxy, where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms, including 4 carbon atoms, and 2 heteroatoms, represents nitrogen, (R23-heteroaryl)amino, where heteroaryl represents the FDS is th monocyclic heteroaromatic group of 6 atoms, including 4 carbon atoms, and 2 heteroatoms, represents nitrogen, -CH(OH)-(R17-phenyl), -CH(OH)-(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms, containing 5 carbon atoms and 1 heteroatom, representing nitrogen,
-C(=NOR30)-(R17-phenyl), -C(=NOR30)-(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms, containing 5 carbon atoms and 1 heteroatom, representing nitrogen,
,,,,,
,or,
w is 0 or 1;
each n is independently 0, 1, 2 or 3;
R15is H, alkyl, halogenation, -C(O)Valkila, -C(O)O(R30-cycloalkyl), R17-phenyl, (R17-phenyl)alkyl, -CH-(R17-phenyl)2, R23-heteroaryl where heteroaryl represents a monocyclic or benzododecinium heteroaromatic group of 5, 6 or 9 atoms, including from 3-5, 7 carbon atoms and from 1 to 3 heteroatoms selected from nitrogen and sulfur, -(CH2)n-C(O)NR18R19, -SO2-alkyl, -SO2-cycloalkyl, -SO2(R35-phenyl), -SO 2-NR18R19-C(O)alkyl, -C(O)-(foralkyl), -C(O)-(CH3)(CF3)2, -C(O)-(R17-phenyl), -C(O)-(R23-heteroaryl), where heteroaryl represents a monocyclic or benzododecinium heteroaromatic group of 5, 6 or 10 atoms, containing from 3-5, 8 carbon atoms and from 1 to 2 heteroatoms selected from nitrogen, oxygen and sulfur, -C(O)-hydroxyalkyl, -C(O)-alkoxyalkyl, -C(O)-(R39-cycloalkyl), -C(O)-alkylene-(R17-phenyl), -C(O)-alkylene-S-C(O)alkyl, -C(=S)-(R17-phenyl), hydroxyalkyl, substituted R17-phenyl,
or,
where z is 0, 1 or 2;
R16is 1-4 substituents, independently selected from the group comprising H, alkyl, R17-phenyl, (R23-heteroaryl)alkyl, where heteroaryl represents a monocyclic heteroaromatic group of 5 atoms, including 4 carbon atoms and 1 heteroatom, which is a sulfur, hydroxyalkyl, alkoxyalkyl and-C(O)Alkyl, or two R16group and the carbon atom to which they are both attached, form-C(O)-;
R17is 1-3 substituents, independently selected from the group including H, halogen, alkyl, -HE, alkoxy, -CN, -CF3, -OCF3, -OCHF2,
-C(O)HE, -C(O)Alkyl, -SO, -SO2alkyl, alkylthio, -NR43R44, R35-phenyl, R35-heteroaryl, where heteroaryl represents a monocyclic heteroaromatic group of 5 or 6 atoms comprising from 3 to 4 carbon atoms and 1 or 2 heteroatoms selected from nitrogen and sulfur, R35-heteroaromatic where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms comprising from 4 to 5 carbon atoms and 1 or 2 heteroatoms, represents a nitrogen, R36-heteroseksualci where heteroseksualci represents a non-aromatic saturated monocyclic ring containing 6 atoms, where from 1 to 2 atoms independently selected from nitrogen and oxygen,
-C(O)-(R36-heteroseksualci), where heteroseksualci represents a non-aromatic saturated monocyclic ring containing 4-6 atoms, one of which is a nitrogen, hydroxyalkyl-NH-,
-N(R43)-(R35-cycloalkyl) and-C(=NOR30);
R18and R19independently selected from the group comprising H, alkyl, hydroxyalkyl, halogenated, R17is phenyl, naphthyl and cycloalkyl;
R20is H, alkyl or cycloalkyl;
R22is 1-4 substituents, independently selected from the group including H, halogen, and-CF3;
R23is 1 to 4 substituents, independently selected from the group comprising H, alkyl, alkoxy, halogen, -CF3, -NR18R19, -CN, -SO2-alkyl, -NHSO2-al the sludge, R35-phenyl, R35-heteroaryl where heteroaryl represents a monocyclic heteroaromatic group of 5 or 6 atoms comprising from 3 to 5 carbon atoms and 1 or 2 heteroatoms selected from nitrogen, oxygen and sulfur, morpholinyl and -(CH2)n-C(O)-N(R30)2;
R24is H or HE;
R25is R35-phenyl;
R27is 1-3 substituents, independently selected from the group including H, HE, alkyl, alkoxy, alkoxyalkyl, halogenated,
-C(O)Alkyl, -C(O)N(R30)(R18), R17-phenyl, (R17-phenyl)-alkyl, R23-heteroaryl where heteroaryl represents a monocyclic heteroaromatic group of 5 or 6 atoms comprising from 3 to 5 carbon atoms and 1 or 2 heteroatoms selected from nitrogen and sulfur and N-oxides of the nitrogen atoms of the ring, provided that the rings do not include adjacent oxygen atoms and/or sulfur, R23-heteroaryl)hydroxy, where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms, including 4 carbon atoms, and 2 heteroatoms, represents nitrogen, (R23-heteroaryl)amino, where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms, including 4 carbon atoms, and 2 heteroatoms, represents nitrogen, -(CH2)n-N(R30)-C(O)alkyl, -(CH2)n-N(R30 )-C(O)-(foralkyl),
-(CH2)n-N(R30)-C(O)(cycloalkyl), -(CH2)n-N(R30)-(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 5 or 6 atoms comprising from 3 to 5 carbon atoms and 1 or 2 heteroatoms selected from nitrogen and sulfur, -(CH2)n-N(R30)-C(O)-(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms, containing 5 carbon atoms and 1 heteroatom, representing nitrogen, -(CH2)n-N(R30)-C(O)O-alkyl,
-(CH2)n-N(R30)-C(O)O-(CF3-alkyl), -(CH2)n-N(R30)-C(O)O-(R39-cycloalkyl), -(CH2)n-N(R30)-C(O)-N(R30)(R20), -(CH2)n-N(R30)-SO2-alkyl, -(CH2)n-N(R30)-SO2-CF3, -(CH2)n-N(R30)-SO2-N(R30)2and
;
or two R27group and the carbon atom to which they are both attached, form-C(O)-;
R28is H, alkyl or-alkyl-C(O)O-alkyl;
R29is halogenation, -C(O)Valkila, -C(O)alkyl, -C(O)CF3,
-C(O)-(R12-cycloalkyl), -C(O)-(R17-phenyl), -C(O)-(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms, including 5 atomo the carbon and 1 heteroatom, represents nitrogen, -SO2-alkyl, -SO2-(R35-phenyl), -C(O)NR18R19or R23-heteroaryl where heteroaryl represents a monocyclic heteroaromatic group of 5 or 6 atoms comprising from 3 to 4 carbon atoms and 2 heteroatoms selected from nitrogen and sulfur;
R30independently selected from the group comprising H and alkyl;
R31is tenoxicam;
R33is H or HE;
R34is H, hydroxyalkyl, alkoxyalkyl or-C(O)Valkila;
R35is 1-3 substituents, independently selected from the group including H, halogen, alkyl, HE, CF3, alkoxy and-CO2alkyl;
R36is 1-2 substituents independently selected from the group comprising H and-NR18R19;
R37and R38independently selected from alkyl, or R37and R38together are -(CH2)3- or -(CH2)4-and, together with the nitrogen atom to which they are attached, form a ring;
R39is H, HE, alkyl or CF3;
R40is-NHC(O)alkyl;
R41is H or-SO2by alkyl;
R42is -(CH2)n-(R35-phenyl), -(CH2)n-(R23-heteroaryl), where heteroaryl represents a monocyclic heteroaromatic group of 6 atoms, including 4 carbon atoms, and heteroatom, selected from nitrogen and sulfur, or-C(O)alkyl;
R43and R44selected from H and alkyl; and
R45is 1 or 2 substituents selected from the group comprising R17is phenyl and R23-heteroaryl where heteroaryl is benzododecinium heteroaromatic group of 9 atoms, including 8 carbon atoms and 1 heteroatom, which is a sulfur, and
"alkyl" means an aliphatic hydrocarbon group which may be straight or branched and contains from 1 to 6 carbon atoms in the chain;
"alkenyl" means an aliphatic hydrocarbon group containing at least one double bond in the carbon-carbon and which may be straight or branched and contains from 2 to 6 carbon atoms in the chain;
"alkylene" means difunctional group obtained by removing hydrogen atom from the alkyl group, such as defined above;
"cycloalkyl" means a non-aromatic mono - or cyclical system of rings containing from 3 to 10 carbon atoms;
"halogen" means fluorine, chlorine, bromine or iodine;
"alkoxy" means alkyl-O-group in which an alkyl group such as defined above, and coupling with a primary group via the oxygen atom of simple ether;
"alkylthio" means alkyl-S-group in which an alkyl group such as defined above, and St. the relationship with the main group via a sulfur atom.

2. The compound according to claim 1, where R10, R11and R13each is H; R1is alkyl; and R9is H, alkyl or-CF3.

3. The compound according to claim 2, in which R10, R11and R13each is H, R1is alkyl and R9is-CF3.

4. The compound according to claim 3, where t is 1, R5is H, R6is H, alkyl or hydroxyalkyl, and R3and R4each is N.

5. The compound according to claim 4, where R7is H, alkyl, cycloalkyl or hydroxyalkyl, and R8is R12-cycloalkyl, (R12-cycloalkyl)alkyl, R45-hydroxyalkyl, R17-phenyl, (R17-phenyl)alkyl, (R23-heteroaryl)alkyl, -alkyl-N(R30)-C(O)-NR18R19,
-alkyl-N(R30)-C(O)-alkyl, -alkyl-N(R30)-C(O)-(R17-phenyl), -alkyl-N(R30)-C(O)-(R23-heteroaryl),-alkyl-N(R30)-(R23-heteroaryl),
,or

6. The compound according to claim 5, in which R8is R12-cycloalkyl, R45-hydroxyalkyl, (R17-phenyl)alkyl, (R23-heteroaryl)alkyl, -alkyl-N(R30)-C(O)-(R23-heteroaryl),-alkyl-N(R30)-C(O)-alkyl,
,,
where p is 0, or
where R is equal to 1.

7. The connection according to claim 6, in which R12is -(CH2)n-N(R30)-C(O)-cycloalkyl or -(CH2)n-N(R30)-(R23-heteroaryl), R45is R17-phenyl, or R29is heteroaryl, -C(O)alkyl or-C(O)cycloalkyl.

8. The compound according to claim 4, in which R7and R8and the nitrogen atom to which they are attached, form
,,or

9. The connection of claim 8, in which R7and R8and the nitrogen atom to which they are attached, formoptional double bond is present, and R14selected from the group including H, HE, alkoxy, -(CH2)n-N(R30)-(R23-heteroaryl), R23-heteroaryl and (R23-heteroaryl)-alkyl; or R7and R8and the nitrogen atom to which they are attached, form, R15selected from the group including alkyl, R17-phenyl, R23-heteroaryl, -C(O)alkyl, -C(O)(foralkyl), -C(O)-(R23-heteroaryl), -C(O)-alkoxyalkyl, -C(O)-(R38-cycloalkyl), -SO2-alkyl,
-SO2-NR18R19andand R16selected from the group comprising h, alkyl, or two R16group and the carbon atom to which they shall uedineny, form-C(O)-.

10. The connection of claim 8, where R7and R8and the nitrogen atom to which they are attached, form, q is 1, and R27is 1, 2 or 3 substituents, independently selected from the group including H, HE, alkyl, alkoxy, alkoxyalkyl, R17-phenyl, -C(O)Alkyl, R23-heteroaryl, (R23-heteroaryl)amino, and -(CH2)n-N(R30)-C(O)(cycloalkyl), where n is equal to 0.

11. The connection of claim 8, where R7and R8and the nitrogen atom to which they are attached, formwhere p is 0, R34is N, and R35is 1 or 2 substituents, independently selected from the group including H, HE, halogen and alkyl.

12. The compound according to claim 5, in which R7is H or alkyl, and R8is (R17-phenyl)alkyl, R45-hydroxyalkyl or-alkyl-N(R30)-(R23-heteroaryl), where R45is R17-phenyl; heteroaryl is pyridinyl, pyrimidinyl, or pyrazinium; R17is 1-3 substituents, independently selected from the group comprising halogen, HE, alkoxy and alkyl; and R23is 1 or 2 substituents, independently selected from the group comprising H, alkyl, alkoxy and halogen.

13. The compound according to claim 1, selected from the group including

















and

14. The compound according to claim 1, having the formula

15. The compound according to claim 1, having the formula

16. The compound according to claim 1, having the formula

17. The compound according to claim 1, having the formula

18. The compound according to claim 1, having the formula

19. The compound according to claim 1, having the formula

20. The compound according to claim 1, having the formula

21. The compound according to claim 1, having the formula

22. The compound according to claim 1, having the formula

23. Pharmaceutical composition having the properties of the inhibitor PDE, where the composition contains an effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.

24. The use of compounds according to claim 1 for the floor is to be placed medicines inhibiting the recruitment of inflammatory cells in the Airways.



 

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SUBSTANCE: present invention refers to oxazolidinone derivatives covered by general graphic formula (I) and to their pharmaceutically acceptable salts. In formula (I) R1, R2, R3 and R4 are independently chosen from a group including -H and halogen; A is chosen from a group including R5 and R6 are independently chosen from a group including -H, -F, -CI, -Br, -OH, alkyl(C1-C6), haloalkyl(C1-C6), alkoxygroup(C1-C6); R7 is chosen from a group including -H, alkyl(C1-C6); either R7 and R5 or R6 taken together form a cycle of 2 carbon atoms and include 1 group chosen from O which in turn can be substituted by one substitute chosen from alkyl(C1-C6); R12 is chosen from a group including -H, -COR14, -CSR14, -COOR14; R14 is chosen from a group including alkyl (C1-C6), cycloalkyl(C3-C6), alkenyl(C2-C6), R16, R17 and R18 represent -H; R21 is chosen from a group including -H, alkyl(C1-C6); X is chosen from a group including O, S, and Y is chosen from a group including O, S, SO, SO2, and NR12; and optional substitutes of alkyl(C1-C6) groups can represent one or two groups chosen from the following: -OR21, -CN.

EFFECT: invention refers to methods for preparing the compounds of the invention, to application of oxazolidinone derivatives for preparing a drug for treating bacterial infections and to a pharmaceutical composition for treating bacterial infections, including a therapeutically effective amount of the compound of the invention.

36 cl, 10 tbl, 44 ex

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SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates or tautomers thereof, where substitute M is selected from groups D1 and D2, having structural formulae given below, and R1, E, A and X are as described in the formula of invention. Disclosed also are pharmaceutical compositions which contain these compounds, methods for synthesis of these compounds, intermediate compounds and synthesis methods thereof, as well as use of compounds of formula (I) in preventing or treating diseases mediated by CDK kinases, GSK-3 kinases or Aurora kinases.

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40 cl, 8 dwg, 18 tbl, 84 ex

Aromatic compound // 2416608

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound of general formula (1), where radicals R1, R2, X1, Y and A are as described in claim 1 of the invention. The invention also describes a method of obtaining compounds of formula (1), as well as a pharmaceutical composition based on said compounds, for treating fibrosis.

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62 cl, 2717 ex, 432 tbl

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30 cl, 9 tbl, 944 ex

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5 cl, 64 ex

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EFFECT: oxazolidinone derivatives, having inhibiting activity towards a wide range of bacteria and having low toxicity.

27 cl, 4 tbl, 73 ex

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10 cl, 162 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula I and to their pharmaceutically acceptable salts. In formula I p is integer, equal to 0-1; L2 is selected from group including -XOX-, -XSX- and -XSXO-; where X is independently selected from group, including bond and C1-C4alkylene; R13 is selected from group, including halogen, C1-C6alkyl, C1-C6alkoxygroup, -C(O) C1-C6alkyl; R14 is selected from group, including -XOXC(O)OR17 and -C1-C4alkylene-C(O)OR17; where X represents bond or C1-C4alkylene; and R17 is selected from group, including hydrogen and C1-C6alkyl; R15 and R16 are independently selected from group, including -R18 and -YR18; where Y represents C2-C6alkenylene, and R18 is selected from group, including C6-C10aryl, benzo[1,3]dioxolyl, pyridinyl, pyrimidinyl, quinolyl, phenoxatiinyl, benzofuranyl, dibenzofuranyl, benzoxasolyl, 2,3-dihydrobenzofuranyl, 2-oxo-2,3-dihydrobenzooxasolyl, indolyl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazinyl, 2,3-dihydrobenzo[1,4]dioxinyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, where any C6-C10aryl, pyridinyl, benzoxasolyl, indolyl in R18 is optionally substituted by 1-2 radicals, independently selected from group, including halogen, nitrogroup, cyanogroup, C1-C6alkyl, C1-C6alkoxygroup, C1-C6alkylthiogroup, hydroxy-C1-C6alkyl, halogen-substituted C1-C6alkyl, halogen-substituted C1-C6alkoxygroup, piperidinyl, morpholinyl, pyrrolidinyl, phenyl, XS(O)0-2R17, -XNR17R17, -XNR17S(O)2R17, -XNR17C(O)R17, -XC(O)NR17R17, -XC(O)NR17R19, -XC(O)R17, -XC(O)R19 and -XOXR19, where X represents bond; R17 is selected from group, including hydrogen, C1-C6alkyl, halogen-substituted C1-C6alkyl, and R19 is selected from group, including C3-C12cycloalkyl, phenyl, piperidinyl, morpholinyl.

EFFECT: ensuring application of invention compounds for production of medication, modulating activity of activated receptors of peroxisome proliferators δ (ARPPδ), to pharmaceutical composition, possessing properties of ARPPδ activity modulator, including therapeutically efficient quantity of invention compound and to application of pharmaceutical composition for medication manufacturing.

8 cl, 1 tbl, 301 ex

FIELD: chemistry.

SUBSTANCE: invention describes compounds of formula I

, where R1 is selected from a group comprising hydrogen, lower alkyl, lower hydroxyl, lower alkoxyalkyl, lower halogenalkyl, lower cyanoalkyl; unsubstituted or substituted phenyl; lower phenylalkyl, where the phenyl ring can be unsubstituted or substituted; and heteroaryl, selected from pyridyl and pyrimidinyl; R2 denotes hydrogen or halogen; G denotes a group selected from

, where m equals, 0, 1; R3 is selected from lower alkyl, cycloalkyl and lower cycloalkylalkyl; n equals 0, 1; R4 denotes lower alkyl, as well as pharmaceutical compositions.

EFFECT: said compounds are used to treat or prevent diseases associated with histaminase receptor modulation.

19 cl, 1 tbl, 24 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula 1, its pharmaceutically acceptable salts and stereoisomers: $ (1), where: R1 means H, amidino, C1-C4-alkyl amidino, C1-C4alkanoylamidino, C1-C10-alkyl, C3-C7-cycloalkyl, C6-C10-aryl, 6-members heterocycle with O atom, 5-members heterocycle with two N atoms, 6-members heteroaryl with one or two N atoms, 5-members heteroaryl with two heteroatoms, one of which is N, and the other is S, C1-C6-alkylcarbonyl, C3-C7-cycloalkylcarbonyl, C1-C4-alkoxycarbonyl, C6-C10-aryl-C1-C4-alkoxycarbonyl, -SO2-C1-C4-alkyl, -C(O)-N(R6)(R7) or -C(S)-N(R6)(R7); and, R6, R7 means H, C1-C6-alkyl, C3-C7-cycloalkyl; alkyl, cycloalkyl, heterocycle, aryl or heteroaryl are unsubstituted or substituted; R2 means C6-C10-aryl which is unsubstituted or mono- or disubstituted; R3 means H, CN, C1-C6-alkyl, C3-C7-cycloalkyl, C2-C6-alkenyl, monocyclic 5-members heterocycle with N and O, monocyclic 5-members heteroaryl with two heteroatoms, one of which is N, and the other is O or S, C(O)-R8 or -C(S)-R8; and R8 means OH, C1-C4-alkyl, C1-C4-alkyloxy or N(R9)(R10); R9, R10 mean N, C1-C6-alkyl, C3-C7-cycloalkyl, C1-C4-alkyloxy, phenyl or 5-members heteroaryl with two heteroatoms, one of which is N, and the other is S, 6-members heteroaryl with N; R9, R10 together with N whereto attached can form a single 4-6-members ring which can include in addition O or S; and alkyl, cycloalkyl, heterocycle, phenyl or heteroaryl are unsubstituted or substituted. R4 means C3-C8-cycloalkyl, C6-C10-aryl, 5-members heteroaryl with two heteroatoms, one of which is N, and the other is S, 6-members heteroaryl with N, 6-members heterocycle with O, and C6-C10-aryl or heteroaryl are unsubstituted or mono- or polysubstituted. R5 means N, C1-C6-alkyl, -C(O)-R11, C1-C6-alkylsulphonyl, C6-C10-arylsulphonyl, -(CH2)p-C6-C10-aryl, -(CH2)p-heteroaryl or -(CH2)p-C3-C8-cycloalkyl where heteroaryl means 5-members heteroaryl with O or with N or with S which can contain in addition N. p is equal to 1 or 2; R11 means C1-C10-alkyl, C1-C6-alkenyl, C3-C8-cycloalkyl, C3-C8-cycloalkenyl, NH2, C1-C4alkylamino, (C1-C4-alkyl)(C1-C4-alkyl)amino, C6-C10-aryl, 5-members heteroaryl with N or with O or with 8 which can contain in addition N, 6-members heterocycle with N and O, 5- or 6-members heterocycle with O, and alkyl is unsubstituted or substituted with one substitute. Aryl, heteroaryl, cycloalkyl, cycloalkenyl or heterocycle are unsubstituted or mono- or disubstituted.

EFFECT: compounds are melanocortin receptor agonists so presented to be used in a pharmaceutical composition for treatment and prevention of obesity, diabetes, inflammation, erectile dysfunction.

19 cl, 18 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: compound of formula pharmaceutically acceptable salt or solvate of a compound or salt (I), ring Q represents optionally substituted monocyclic or condensed (C6-C12)aryl or optionally substituted monocyclic or condensed heteroaryl where said substitutes are chosen from: halogen; (C1-C6)alkyl optionally substituted by 1-3 halogen atoms; (C1-C6)alkylsulphonyl; phenyl optionally substituted by 1 or 2 substitutes chosen from halogen, (C1-C6)alkyl which can be substituted by 1-3 halogen atoms, groups (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl optionally substituted by halogen; or oxo; Y1 represents a bond or -NR6-CO-, where R6 represents hydrogen, ring A represents optionally substituted a nonaromatic heterocyclyldiyl where said substitutes are chosen from (C1-C6)alkyl optionally substituted by groups hydroxy, (C1-C6)alkylamino, di(C1-C6)alkylamino, morpholino, (C1-C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl; cyano; (C3-C6)cycloalkyl; (C1-C6)alkoxy; (C1-C6)alkoxy(C1-C6)alkyl; phenyl; benzyl; benzyloxymethyl; thienyl; 4-8-members monocyclic nonaromatic heterocycle having 1 or 2 heteroatoms chosen from N or O, and optionally substituted by 1 or 2 substitutes chosen from (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and oxo; (C1-C6)alkylamino; di(C1-C6)alkylamino; a group of formula: -Y2Z'- represents a group of formula: [Formula 2] each R7 independently represents hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl, each of R8 and R9 independently represents hydrogen or (C1-C6)alkyl, n is equal to an integer 0 to 3, Z1 represents a bond, -O-, -S- or-NR9 - where R9 represents hydrogen, (C1-C6)alkyl, acyl or (C1-C6)alkylsulphonyl, ring B represents optionally substituted aromatic carbocyclediyl or optionally substituted aromatic heterocyclediyl where said substitutes are chosen from (C1-C6)alkyl, halogen, (C1-C6)alkoxy and oxo; Y3 represents a bond optionally substituted (C1-C6)alkylene or (C3-C6)cycloalylene, optionally interrupted -O- or optionally substituted (C2-C6)alkenylene where said substitutes are chosen from (C1-C6)alkyl, (C3-C6)cycloalkyl, halogen and (C1-C6)alkoxycarbonyl; Z2 represents COOR3; R3 represents hydrogen or (C1-C6)alkyl.

EFFECT: preparation of new compounds.

30 cl, 9 tbl, 944 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel AMPA receptor antagonists - 1H-quinazoline-2,4-dione derivatives, selected from the group: N-(6-imidazol-1-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-morpholin-4-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrrol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(7-nitro-2,4-dioxo-6-[1,2,4]triazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrrolidin-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-azetidin-1-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-[1,2,3]triazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-morpholin-4-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(2,4-dioxo-6-[1,2,4]triazol-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; (2,4-dioxo-6-[1,2,4]triazol-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)amide ethanesulphonic acid; N-(6-imidazol-1-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(2,4-dioxo-6-thiomorpholin-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(6-[1,4]oxazepan-4-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide and N-(6-azetidin-1-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide and physiologically acceptable salts thereof.

EFFECT: compounds can be used in treating such diseases as epilepsy and schizophrenia.

9 cl, 106 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel pyrazole derivatives of formula (I) or pharmaceutically acceptable salts thereof, having tyrosine kinase Trk inhibiting properties and used for treating or preventing malignant growths accompanied by high level of Trk, to a method of producing said derivatives, use thereof to prepare a medicinal agent, pharmaceutical compositions based on said derivatives, a method of inhibiting Trk activity and a method of obtaining antiproliferative action. where A denotes a single bond or C1-2alkylene; where the said C1-2alkylene can be optionally substituted with one R22; ring C is a phenyl or a 5-6-member heterocyclic ring with 1-2 heteroatoms selected from N or S. Values of R1-R7, R22 and n are given in the formula of invention.

EFFECT: obtaining pharmaceutically acceptable salts having tyrosine kinase Trk inhibiting properties and used for treating or preventing malignant growths.

20 cl, 5 dwg, 193 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula I and to their pharmaceutically acceptable salts. In formula I p is integer, equal to 0-1; L2 is selected from group including -XOX-, -XSX- and -XSXO-; where X is independently selected from group, including bond and C1-C4alkylene; R13 is selected from group, including halogen, C1-C6alkyl, C1-C6alkoxygroup, -C(O) C1-C6alkyl; R14 is selected from group, including -XOXC(O)OR17 and -C1-C4alkylene-C(O)OR17; where X represents bond or C1-C4alkylene; and R17 is selected from group, including hydrogen and C1-C6alkyl; R15 and R16 are independently selected from group, including -R18 and -YR18; where Y represents C2-C6alkenylene, and R18 is selected from group, including C6-C10aryl, benzo[1,3]dioxolyl, pyridinyl, pyrimidinyl, quinolyl, phenoxatiinyl, benzofuranyl, dibenzofuranyl, benzoxasolyl, 2,3-dihydrobenzofuranyl, 2-oxo-2,3-dihydrobenzooxasolyl, indolyl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazinyl, 2,3-dihydrobenzo[1,4]dioxinyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, where any C6-C10aryl, pyridinyl, benzoxasolyl, indolyl in R18 is optionally substituted by 1-2 radicals, independently selected from group, including halogen, nitrogroup, cyanogroup, C1-C6alkyl, C1-C6alkoxygroup, C1-C6alkylthiogroup, hydroxy-C1-C6alkyl, halogen-substituted C1-C6alkyl, halogen-substituted C1-C6alkoxygroup, piperidinyl, morpholinyl, pyrrolidinyl, phenyl, XS(O)0-2R17, -XNR17R17, -XNR17S(O)2R17, -XNR17C(O)R17, -XC(O)NR17R17, -XC(O)NR17R19, -XC(O)R17, -XC(O)R19 and -XOXR19, where X represents bond; R17 is selected from group, including hydrogen, C1-C6alkyl, halogen-substituted C1-C6alkyl, and R19 is selected from group, including C3-C12cycloalkyl, phenyl, piperidinyl, morpholinyl.

EFFECT: ensuring application of invention compounds for production of medication, modulating activity of activated receptors of peroxisome proliferators δ (ARPPδ), to pharmaceutical composition, possessing properties of ARPPδ activity modulator, including therapeutically efficient quantity of invention compound and to application of pharmaceutical composition for medication manufacturing.

8 cl, 1 tbl, 301 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula [I-D1] or pharmaceutically acceptable salt thereof,

,

where each symbol is defined in the claim. The invention also relates to pharmaceutical compositions containing said compound and having HCV polymerase inhibiting activity.

EFFECT: disclosed compound exhibits anti-HCV activity, based on HCV polymerase inhibiting activity and is useful as an agent for preventing and treating hepatitis C.

32 cl, 497 tbl, 1129 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel derivatives of cis-2,4,5-triarylimidazoline of general formula I and pharmaceutically acceptable salts thereof, where X1 is selected from a group comprising lower alkoxy; X2 and X3 are independently selected from a group comprising hydrogen, halogen, cyano, lower alkyl, lower alkoxy, piperidinyl, -NX4X5, -SO2NX4X5, -C(O)NX4X5, -C(O)X6, -SOX6, -SO2X6, -NC(O)-lower alkoxy, -C≡C-X7, provided that both X2 and X3 do not denote hydrogen, lower alkyl or lower alkoxy, provided that when X2 or X3 denote hydrogen, the other does not denote lower alkyl, lower alkoxy or halogen, provided that when X2 denotes -HX4X5, X3 does not denote hydrogen, X2 and X3 together can form a ring selected from 5-7-member unsaturated rings which can contain three heteroatoms selected from S, N and O, X4 and X5 are independently selected from a group comprising hydrogen, lower alkyl, lower alkoxy, lower alkyl, substituted by a lower alkoxy, -SO2-lower alkyl, -C(O)piperazinyl-3-one; X6 is selected from a group comprising lower alkyl, morpholine, piperidine, pyrrolidine; X7 is selected from a group comprising hydrogen, lower alkyl, trifluoromethyl; Y1 and Y2 are independently selected from a group comprising halogen; R is selected from a group comprising lower alkoxy, piperidinyl substituted with a five-member heterocyclic ring which contains one nitrogen heteroatom, piperidinyl substituted with a hydroxy, -CH2OH or -C(O)NH2, piperazinyl substituted with one or two R1 [1,4]diazepanyl, substituted R1, R1 can denote one or two substitutes selected from a group comprising oxo, lower alkyl substituted with one R2, -C(O)R3, -SO2-lower alkyl, -SO2-five-memer heterocyclyl, which is selected from isoxazolyl, dimethylisoxazolyl, pyrrolidinyl, pyrrolyl, thiophenyl, imidazolyl, thiazolyl, thiazolidinyl, imidazolidinyl; R2 is selected from a group comprising -SO2-lower alkyl, hydroxy, lower alkoxy, -NH-SO2-lower alkyl, -cyano, -C(O)R4; R3 is selected from a group comprising a five-member heterocyclyl which is selected from isoxazolyl, dimethylisoxazolyl, pyrrolidinyl, pyrrolyl, thiophenyl, imidazolyl, thiazolyl, thiazolidinyl, imidazolidinyl, lower alkyl, lower alkenyl, lower alkyl substituted with a six-member heterocyclyl selected from piperidinyl, piperazinyl, 3-oxopiperazinyl, morpholinyl, C3-cycloalkyl; R4 is selected from a group comprising hydroxy, morpholine, piperidine, 4-acetylpiperazinyl, -NR5R6; R5 and R6 are independently selected from a group comprising hydrogen, lower alkyl, lower alkyl substituted with lower alkoxy or cyano, lower alkoxy and C3-cycloalkyl. The invention also relates to a pharmaceutical composition based on the formula I compound, use of the formula I compound in preparing a medicinal agent and a method for synthesis of the formula I compound.

EFFECT: novel derivatives of cis-2,4,5-triarylimidazoline of general formula I are obtained, which can be used to treat diseases, based on reaction of the MDM2 protein with p53-like protein, particularly as anticancer agent.

54 cl, 412 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel derivatives of 1H-imidazole of formula I, in which R1 represents hydrogen, halogen atom, C1-3-alkyl group, and said C1-3-alkyl groupcan include 1-3 fluorine atoms or R1 represents cyclopropyl, piano, or methylsulfanyl group, R2 represents phenyl group, which can be substituted with 1 substituent Y, selected from methoxy, chlorine, fluorine, trifluoromethyl and cyano, or R2 represents pyridyl group, on condition that R2 is not 6-methyl-2-pyridyl group, or R2 represents fully saturated 6-7-member monocyclic, condensed bicyclic ring system or benzothiazolyl, benzodioxane or thiazole group, and said groups can be substituted by 1 fluorine atom, or R2 represents group of general formula CH2-R5, in which R5 represents phenyl group or fully saturated 7-member condensed bicyclic carbocyclic ring system, or R5 represents piperidine or tetrahydrofuran ring system, which can be substituted by methyl, or R2 represents methylsulfonylamino(C3)alkyl group, R3 represents hydrogen, halogen atom, C1-6-alkylsulfonyl, cyanogroup, or R3 represents C1-8-alkyl group, and said C1-8-alkyl group can be substituted by 1-3 fluorine atoms, or R3 represents phenyl group, which is substituted by substituent Y, where Y has value, specified above, or R3 represents furanyl group, R4 represents one of subgroups (i) or (ii), where R6 represents C4-8-branched or linear alkyl group or naphtyl group, R7 represents hydrogen atom, linear C1-6-alkyl group, R8 represents C2-6-alkyl group, substituted by 1-3 fluorine atoms, or R8 represents C3-8-cycloalkyl group, piperidine group, C3-8-cycloalkyl- C1-2-alkyl group, tetrahydrofuranyl- C1-2-alkyl group, C5-10-bicycloalkyl group, C5-10-bicycloalkyl-C1-2-alkyl group, C6-10-tricycloalkyl group, C6-10-tricycloalkyl-C1-2-alkyl group, and said groups can be substituted by 1-3 substituents, selected from methyl or hydroxyl, or R8 represents phenyl group, substituted by 1-2 substituents Y, specified above, or R8 represents naphtyl, 1,2,3,4-tetrahydronaphtyl or indanyl group, and said groups can be substituted by 1 substituent Y, or R8 represents phenyl- C1-3-alkyl group, diphenyl- C1-3-alkyl group, and said groups can be substituted ob their phenyl ring by 1 substituent Y, where Y has value specified above, or R8 represents benzyl group, substituted by 2 substituents Y, or R8 represents quinilinyl, pyridinyl, benzimidazole or naphtylmethyl group which can be substituted by substituent Y, where Y has value, specified above, or R8 represents asabicyclo[3,3,0]octanyl group, on condition that R8 is neither 6-methoxybenzothiazole-2-yl group, nor [3-chlor-5-(trifluoromethyl)pyrid-2-yl]methyl group, or R7 and R8 together with nitrogen atom, to which they are bound, form saturated, non-aromatic, monocyclic or bicyclic heterocyclic group, including only one nitrogen atom, having 7-10 ring atoms, which can be subslituted by 3 C1-3-alkyl groups, or R7 and R8 together with nitrogen atom, to which they are bound, form saturated, monocyclic heterocyclic group, optionally including another N atom, having 6 ring atoms, and said heterocyclic group is substituted by C1-3-alkyl groups, on condition that R7 and R8 together with nitrogen atom, to which they are bound, do not form trimethylsubstituted asabicyclo[3,3,0]octanyl group, as well as their stereoisomers and pharmacologically acceptable salts of said formula (I) compounds and their stereoisomers Invention also relates to intermediate compounds of formula XIV, pharmaceutical composition based on formula I compound, method of obtaining such pharmaceutical composition and application of formula T compound.

EFFECT: obtained are novel derivatives of IH-imidazole, which are modulators of cannabinoid CB2-receptors.

8 cl, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel amide derivatives of general formula [1] in any of versions (A) or (B), or its pharmaceutically acceptable salt, which possess properties of tyrosinkinase BCR-ABL inhibitor. Amide derivative of general formula [1] represents compound: , where according to Version (A) R1 represents any of the following groups (1)-(3): (1) -) -CH2-R11 [R11 represents saturated 4-6 member nitrogen-containing heterocyclic group, optionally containing additional nitrogen atom; saturated 5-6-member nitrogen-containing heterocyclic group, optionally containing additional nitrogen atom, which is substituted by group selected from group, consisting of oxo, -CH2-R111 (R111 represents saturated 5-member nitrogen-containing heterocyclic group), saturated 5-member nitrogen-containing heterocyclic group, aminomethyl, monoalkylaminomethyl, dialkylaminomethyl and (5-methyl-2-oxo-1,3-Dioxol-4-yl)methyl, and in addition, can be substituted by 1 or 2 similar or different substituents, selected from group, consisting of (C1-C4)alkyl, (C1-C4 alkoxycarbonyl, halogen, halogen(C1-C4)alkyl, hydroxy(C1-C4)alkyl, amino, carbamoyl], (2) -O-R12 [R12 represents saturated 4-6-member nitrogen-containing heterocyclic group]; and (3) - CH=R13 [R13 represents saturated 4-6-member nitrogen-containing heterocyclic group, which can contain additional nitrogen atom, and which can be substituted by 1-3 similar or different substituents, selected from group, consisting of oxo, (C1-C4)alkyl]; R2 represents (C1-C4)alkyl, halogen, halogen(C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy and carbamoyl; R3 represents hydrogen, halogen; Het1 represents any of groups with the following chemical formulae [4] and [6]: [4] [6] [19] [10] Het2 represents pyridyl or pyrimidinyl. According to Version (B) R1 represents -CH2-R14 [R14 represents saturated 4-6-member nitrogen-containing heterocyclic group, optionally containing additional nitrogen atom; saturated 5-6-member nitrogen-containing heterocyclic group, which can be substituted by 1-3 similar groups, selected from (C1-C4)alkyl] R2 represents (C1-C4)alkyl, halogen, halogen(C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkoxy (C1-C4)alkyl, (C1-C4)alkoxycarbonyl, (C1-C4)acyl, amino, mono(C1-C4)alkylamino, di(C1-C4)alkylamino, nitro, carbamoyl, mono(C1-C4)alkylcarbamoyl, di(C1-C4)alkylcarbamoyl or cyano; R3 represents hydrogen or halogen; Het1 represents any of groups with the following chemical formulas [9] and [10], Het2 represents pyridyl.

EFFECT: invention can be applied for treatment of chronic myeloleukosis, acute lymphoblastic leukosis and acute myeloblastic leukosis.

6 cl, 89 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel anhydrous tetomilast type A crystalline form, having powder X-ray diffraction spectrum essentially the same as the powder X-ray diffraction spectrum having characteristic peaks at 2θ = 10.5°, 13.1°, 18.4°, 21.9° and 25.8°, pharmaceutical compositions based thereon and synthesis methods thereof.

EFFECT: considerable advantages in terms of industrial production owing to significantly better filterability.

8 cl, 14 dwg, 8 ex

FIELD: chemistry.

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

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

8 cl, 32 ex, 4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to oxazolidinone derivatives covered by general graphic formula (I) and to their pharmaceutically acceptable salts. In formula (I) R1, R2, R3 and R4 are independently chosen from a group including -H and halogen; A is chosen from a group including R5 and R6 are independently chosen from a group including -H, -F, -CI, -Br, -OH, alkyl(C1-C6), haloalkyl(C1-C6), alkoxygroup(C1-C6); R7 is chosen from a group including -H, alkyl(C1-C6); either R7 and R5 or R6 taken together form a cycle of 2 carbon atoms and include 1 group chosen from O which in turn can be substituted by one substitute chosen from alkyl(C1-C6); R12 is chosen from a group including -H, -COR14, -CSR14, -COOR14; R14 is chosen from a group including alkyl (C1-C6), cycloalkyl(C3-C6), alkenyl(C2-C6), R16, R17 and R18 represent -H; R21 is chosen from a group including -H, alkyl(C1-C6); X is chosen from a group including O, S, and Y is chosen from a group including O, S, SO, SO2, and NR12; and optional substitutes of alkyl(C1-C6) groups can represent one or two groups chosen from the following: -OR21, -CN.

EFFECT: invention refers to methods for preparing the compounds of the invention, to application of oxazolidinone derivatives for preparing a drug for treating bacterial infections and to a pharmaceutical composition for treating bacterial infections, including a therapeutically effective amount of the compound of the invention.

36 cl, 10 tbl, 44 ex

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