8-substituted isoquinoline derivatives and use thereof

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (1) or a salt thereof, where D1 is a single bond, -N(R11)- or -O-, where R11 is a hydrogen atom or C1-C3 alkyl; A1 is C2-C4 alkylene, or any of divalent groups selected from the following formulae , and ,

where n1 equals 0 or 1; n2 equals 2 or 3; n3 equals 1 or 2; R12 and R13 are each independently a hydrogen atom or C1 -C3 alkyl; v is a bond with D1; and w is a bond with D2; D2 is a single bond, C1-C3 alkylene, -C(O)-, S(O)2-, -C(O)-N(R15)-, or -E-C(O)-, where E is C1-C3 alkylene, and R15 is a hydrogen atom; R1 is a hydrogen atom, C1-C6 alkyl, a saturated heterocyclic group which can be substituted with C1-C6 alkyl groups, an aromatic hydrocarbon ring which can be substituted with C1-C3 alkyl groups, C1-C4 alkoxy groups, halogen atoms, cyano groups, a monocyclic aromatic heterocyclic ring containing one or two heteroatoms selected from a group consisting of a nitrogen atom, a sulphur atom and an oxygen atom, or the following formula ,

where n1 equals 0, 1 or 2; m2 equals 1 or 2; D12 is a single bond, -C(O)- or -S(O)2-; R18 and R19 denote a hydrogen atom; R17 is a hydrogen atom or C1-C3 alkyl; and x is a bond with D2; under the condition that when R17 denotes a hydrogen atom, D12 denotes a single bond; under the condition that when D1 denotes a single bond, A1 denotes a divalent group of said formula (1a-5) or (1a-6); when D1 denotes -N(R11)-, -O-, or -S(O)2-, A1 denotes a single bond, C2-C4 alkylene, or any of divalent groups selected from formulae (1a-1)-(1a-3), where, when A1 denotes a single bond, D2 denotes -E-C(O)-; and D3 is a single bond, -N(R21)-, -N(R21)-C(O) - or -S-, where R21 is a hydrogen atom; and R2 denotes a group of formula ,

where Q denotes an aromatic hydrocarbon ring, a monocyclic aromatic heterocyclic ring containing one or two heteroatoms selected from a group consisting of a nitrogen atom, a sulphur atom and an oxygen atom, a condensed polycyclic aromatic ring containing one or two heteroatoms selected from a group consisting of a nitrogen atom, a sulphur atom and an oxygen atom, or a partially unsaturated monocyclic or a condensed bicyclic carbon ring and a heterocyclic ring; and y denotes a bond with D3; and R23, R24 and R25 each independently denotes a hydrogen atom, a halogen atom, a cyano group, C1-C3 alkyl, which can be substituted with hydroxyl groups, halogen atoms or cyano groups, C1-C4 alkoxy group, which can be substituted with halogen atoms, alkylamino group, dialkylamino group, acylamino group, or the formula ,

where D21 denotes a single bond or C1-C3 alkylene; D22 denotes a single bond or -C(O)-; R26 and R27 each independently denotes a hydrogen atom or C1-C3 alkyl; and z denotes a bond with Q; under the condition that when D22 denotes a single bond, R27 is a hydrogen atom. The invention also relates to specific compounds, a pharmaceutical composition based on the compound of formula , a IKKβ inhibitor, a method of inhibiting IKKβ, a method of preventing and/or treating an NF-kB-associated or IKKβ-associated disease, and intermediate compounds of formulae and .

EFFECT: obtaining novel isoquinoline derivatives, having useful biological properties.

46 cl, 3 dwg, 38 tbl, 89 ex

 

The text descriptions are given in facsimile form.

1. The compound represented by the following formula (1)or its salt:

where
D1denotes a single bond, -N(R11)- or-O-, where R11denotes a hydrogen atom or C1-C3 alkyl group;
A1denotes a C2-C4 alkylene, or any of divalent groups selected from the following formulas (1a-1)to(1a-3), (1a-5) and (1a-6):

where
n1one is by an integer 0 or 1;
n2is an integer 2 or 3;
n3is an integer 1 or 2;
R12and R13may be the same or different, each independently represents a hydrogen atom or C1-C3 alkyl group;
v denotes a connection with the D1;
w denotes a connection with the D2;
D2denotes a single bond, C1-C3 alkylene, -C(O)-, S(O)2-, -C(O)-N(R15)-, or-E-C(O)-, where E denotes C1-C3 alkylene, a R15denotes a hydrogen atom;
R1denotes a hydrogen atom,
C1-C6 alkyl group,
saturated heterocyclic group which may be substituted by C1-C6 alkyl groups,
aromatic hydrocarbon ring which may be substituted by C1-C3 alkyl groups, C1-C4-alkoxycarbonyl, halogen atoms, cyano groups,
monocyclic aromatic heterocyclic ring containing one or two heteroatoms of one or more types selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, or the following formula (1b-3):

where
n1is an integer 0, 1 or 2;
m is the integer 1 or 2;
D12denotes a single bond, -C(O)- or-S(O)2-;
R18and R19represent a hydrogen atom;
R17denotes a hydrogen atom or C1-C3 alkyl group; and
x designates the connection with the D2;
when the condition is and, what
when R17denotes a hydrogen atom, D12indicates a single bond;
provided that when D1denotes a single bond, A1denotes a divalent group represented by the above formula (1a-5) or (1a-6);
when D1represents-N(R11)-, -O-, or-S(O)2-, A1denotes a single bond, C2-C4 alkylene, or any of divalent groups selected from the formulas (1A-1)to(1A-3), where, when And1denotes a single bond, D2means-E-C(O)-;
and
D3denotes a single bond, -N(R21)-, -N(R21)-C(O) - or-S-, where R21
denotes a hydrogen atom; and
R2denotes the following formula (2a-1):

where
Q represents an aromatic hydrocarbon ring,
monocyclic aromatic heterocyclic ring containing one or two heteroatoms of one or more types selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom,
the condensed polycyclic aromatic ring containing one or two heteroatoms of one or more types selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom, or partially unsaturated monocyclic or
condensed-bicyclic carbon ring and a heterocyclic ring; and
y denotes a bond with D3/sup> ;
R23, R24and R25may be the same or different and each independently denotes a hydrogen atom, halogen atom, cyano,
C1-C3 alkyl group which may be substituted by hydroxyl groups, halogen atoms, or cyano groups,
C1-C4 alkoxygroup, which may be substituted by halogen atoms,
alkylamino,
dialkylamino,
allmenalp, or
the following formula (2b-1):

where
D21denotes a single bond or C1-C3 alkylene;
D22denotes a single bond or-C(O)-;
R26and R27may be the same or different and each independently denotes a hydrogen atom or C1-C3 alkyl group;
and
z represents a bond with Q;
provided that when D denotes a single bond, R27denotes a hydrogen atom.

2. The compound according to claim 1 or its salt, where A1denotes a C2-C4 alkylene or any of divalent groups selected from the formulas (1a-1)to(1a-3) and (1a-5), in which n1n2, R12, R13, v and w have the same meanings as defined above.

3. The compound according to claim 1 or 2, or a salt, where a1denotes any one of divalent groups selected from the formulas (1a-1)to(1a-3) and (1a-5), in which n1n2, R12, R13, v and w have the same meanings as defined above.

4. The compound according to claim 1 or 2, the sludge is its salt, where D2denotes a C1-C3 alkylene, -C(O)- or-S(O)2-.

5. The compound according to claim 1 or 2, or its salt, where D2denotes-C(O)- or-S(O)2-.

6. The compound according to claim 1 or 2, or its salt, where R1denotes a hydrogen atom, C1-C6 alkyl group,
aromatic hydrocarbon ring which may be substituted by C1-C3 alkyl groups, C1-C4-alkoxygroup, by halogen atoms or cyano groups, or
monocyclic aromatic heterocyclic ring containing one or two heteroatoms of one or more types selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom.

7. The compound according to claim 1 or 2, or its salt, where R1denotes a divalent group of the formula (1b-3), in which n1n2D12, R17, R18, R19and x have the same meanings as defined above.

8. The compound according to claim 1 or 2, or its salt, where D denotes a single bond or-N(R21)-C(O) -, where R21has the same meaning as defined above.

9. The compound according to claim 1 or 2, or its salt, where D3denotes a single bond.

10. The compound according to claim 1 or 2, or its salt, where Q in the formula (2A-1) denotes
aromatic hydrocarbon ring,
monocyclic aromatic heterocyclic ring containing one or two heteroatoms of one or more types selected from the group, when standing from a nitrogen atom, the sulfur atom and oxygen atom.

11. The compound according to claim 2, or its salt, where D denotes a C1-C3 alkylene, -C(O)- or-S(O)2-.

12. The compound according to claim 3 or its salt, where D denotes a C1-C3 alkylene, -C(O)- or-S(O)2-.

13. The compound according to claim 2, or its salt, where D2denotes-C(O)-or-S(O)2-.

14. The compound according to claim 3 or its salt, where D2denotes-C(O)-or-S(O)2-.

15. The connection 13 or its salt, where R1denotes a hydrogen atom, C1-C6 alkyl group,
aromatic hydrocarbon ring which may be substituted by C1-C3 alkyl groups, C1-C4-alkoxygroup, by halogen atoms or cyano groups, or
monocyclic aromatic heterocyclic ring containing one or two heteroatoms of one or more types selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom.

16. The connection 14 or its salt, where R1denotes a hydrogen atom, C1-C6 alkyl group,
aromatic hydrocarbon ring which may be substituted by C1-C3 alkyl groups, C1-C4-alkoxygroup, by halogen atoms or cyano groups, or
monocyclic aromatic heterocyclic ring containing one or two heteroatoms of one or more types selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom.

17. The connection 13 or its salt, R 1denotes a divalent group of the formula (1b-3), in which m1m2D12, R17, R18, R19and x have the same meanings as defined above.

18. The connection 14 or its salt, where R1denotes a divalent group of the formula (1b-3), in which m1m2D12, R17, R18, R19and x have the same meanings as defined above.

19. The compound of claim 8 or its salt, where Q in the formula (2A-1) represents an aromatic hydrocarbon ring or
monocyclic aromatic heterocyclic ring containing one or two heteroatoms of one or more types selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom.

20. The connection according to claim 9 or its salt, where Q in the formula (2A-1) represents an aromatic hydrocarbon ring or
monocyclic aromatic heterocyclic ring containing one or two heteroatoms of one or more types selected from the group consisting of nitrogen atom, sulfur atom and oxygen atom.

21. A compound selected from the following group, or its salt:



















22. A compound selected from the following group, or its salt:

23. The compound or its salt according to item 22, which represents:

24. The compound or its salt according to item 22, which represents:

25. The compound or its salt according to item 22, which represents:

26. The compound or its salt according to item 22, which represents:

27. The compound or its salt according to item 22, which represents:

28. The compound or its salt according to item 22, which represents:

29. The compound or its salt according to item 22, which represents:

30. Pharmaceutical composition having IKKβ-inhibitory activity containing a compound according to any one of claims 1 to 29 or its pharmaceutically acceptable salt as an active component.

31. Pharma is eticeskaja the composition according to item 30 for the prevention and/or treatment of NF-KB-associated disease or symptom.

32. The pharmaceutical composition according to item 30 for the prevention and/or treatment of IKKβ-associated disease or symptom.

33. The pharmaceutical composition according to item 30 for the prevention and/or treatment of TNF-α-associated disease or symptom.

34. The pharmaceutical composition according to item 30 for the prevention and/or treatment of rheumatoid arthritis in a mammal.

35. The pharmaceutical composition according to item 30 for the prevention and/or treatment of autoimmune diseases in a mammal.

36. The pharmaceutical composition according to item 30 for the prevention and/or treatment of inflammatory diseases in a mammal.

37. The pharmaceutical composition according to item 30 for the prevention and/or treatment of cardiovascular disease in a mammal.

38. The pharmaceutical composition according to item 30 for the prevention and/or treatment of cancer in a mammal.

39. The pharmaceutical composition according to item 30 for the prevention and/or treatment of a disease or symptom associated with acute or chronic inflammatory response in mammals.

40. The IKKβ inhibitor containing the compound according to any one of claims 1 to 29 or its salt as an active component.

41. Method of inhibiting IKKβ, including the introduction of an effective amount of a compound according to any one of claims 1 to 29 or its pharmaceutically acceptable salt.

42. The method of prevention and/or treatment of NF-KB-associated what about the disease or symptom, including the introduction of an effective amount of a compound according to any one of claims 1 to 29 or its pharmaceutically acceptable salt.

43. The method of prevention and/or treatment of IKKβ-associated disease or symptom involving the introduction of an effective amount of a compound according to any one of claims 1 to 29 or its pharmaceutically acceptable salt.

44. The method of prevention and/or treatment of a disease or symptom associated with acute or chronic inflammatory reaction in a mammal, comprising introducing an effective amount of a compound according to any one of claims 1 to 29 or its pharmaceutically acceptable salt.

45. The compound represented by the following formula (2A)or its salt:

where
R3denotes a hydrogen atom;
R4denotes a C1-C3 alkyl group; and
R5denotes a halogen atom.

46. The compound represented by the following formula (2b)or its salt:

where
R4denotes a hydrogen atom, C1-C3 alkyl group or benzyl group; and
R5denotes a halogen atom;
provided that excluded 8-forsakenly-6-ol.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to use of novel pyrrolopyrazine derivatives of formula , where variables Q and R are as defined in the claim, which inhibit JAK and SYK.

EFFECT: high effectiveness when treating autoimmune and inflammatory diseases.

11 cl, 59 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to 7-benzoyl-8-hydroxy-6-phenyl-9-(3-phenyl-2-quinoxalinyl)-10H-pyrido[1,2-a]quinoxalin-10-one of formula (1)

EFFECT: obtaining a novel compound which can be used in medicine as a drug having analgesic activity.

3 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel imidazopyridine or imidazopyrimidine derivatives of formula (I) and to pharmaceutically acceptable salts and esters thereof, where A is N or C(R6); R1 is hydrogen, lower alkyl; R2 is halogen, C(O)NR7R8 or C(O)OR9; R3 is hydrogen, NR10R11; R4 is hydrogen, lower alkyl; R5 is phenyl or thiazolyl or pyridine, which can be substituted with one substitute independently selected from a group consisting of halogen; R6 is hydrogen, halogen, CN, C3-C6cycloalkyl; R7 and R8 are independently selected from a group consisting of hydrogen, lower alkyl, lower alkoxy-lower alkyl, fluoro-lower alkyl, C3-C6cycloalkyl, N(H,lower alkyl)-lower alkyl, hydroxy- lower alkyl, hydroxy-lower alkoxy- lower alkyl, N(lower alkyl2)C(O)- lower alkyl, lower alkoxy, hydroxy-lower alkyl-oxetanyl- lower alkyl, oxo-tetrahydrofuranyl, tetrahydrofuranyl-lower alkyl, hydroxy-fluoro-lower alkyl, tetrahydrofuranyl, phenyl and thiazolyl or pyridine, or R7 and R8 together with a nitrogen atom with which they are bonded form a heterocyclyl selected from a group consisting of pyrrolidinyl, azetidinyl, morpholinyl, 5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazinyl, 3,4-dihydro- 1H-pyrrolo[1,2-a]pyrazinyl, 2-oxa-6-aza-spiro[3.3]heptyl, 5,6-dihydro- 8H-imidazo[1,2-a]pyrazinyl, [1,4]oxazepanyl, piperazinyl, thiomorpholinyl and 2-oxa-5-aza-bicyclo[2.2.1]heptyl, where the heterocyclyl is optionally substituted with 1 or 2 substitutes independently selected from a group consisting of halogen, lower alkyl, lower alkyl-C(O), lower alkoxy-lower alkyl, oxo, hydroxy, hydroxy-lower alkyl, N(lower alkyl2); R9 is lower alkyl; R10 and R11 together with a nitrogen atom with which they are bonded form a heterocyclyl selected from a group consisting of piperidinyl, morpholinyl. The invention also relates to a pharmaceutical composition based on the compound of formula (I), a method of treating said pathological conditions and use of the compound of formula (I).

EFFECT: obtaining novel imidazopyridine or imidazopyrimidine derivatives which are PDE10A inhibitors.

24 cl, 94 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to pyrazolo[3,4-b]pyridine compounds and a method for production thereof. Described are 2-(6-aryl-4-aroyl-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)-2-oxo-N-arylacetamides of formula ,

where Ar1=Ph, C6H4Me-4; Ar2=Ph, C6H4Me-4, C6H4Br-4, and a method for production thereof by boiling 1-aryl-4,5-diaroyl-1H-pyrrole-2,3-diones with 5-amino-3-methyl-1-phenyl-1H-pyrazole in a medium of inert aprotic solvent.

EFFECT: obtaining novel compounds which can be used as primary products for synthesis of novel heterocyclic systems and in pharmacology as potential medicinal agents with analgesic activity.

4 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) where "----" denotes a bond or is absent; R1 is a C1-4alkoxy group or halogen; R1b is H or C1-3alkyl; U and V each independently denote CH or N; W is CH or N, or, if "----" is absent, W is CH2 or NH; under the condition that at least one of U, V and W is CH or CH2; A is -CH2-CH(R2)-B-NH-* or -CH(R3)-CH2-N(R4)-[CH2]m-*; where asterisks indicate a bond which binds said fragments through a CH2-group with an oxazolidinone fragment; B is CH2 or CO; and R2 is hydrogen, OH or NH2; R3 and R4 both denote hydrogen, or R3 and R4 together form a methylene bridge; m equals 0, 1 or 2; and G is a phenyl which is monosubstituted in position 3 or 4, or disubstituted in positions 3 and 4, where each substitute is independently selected from a group comprising C1-4alkyl, C1-3alkoxy group and halogen; or G is a group selected from groups G1 and G5 where M is CH or N; Q' is S or O; Z1 is N, Z2 is CH and Z3 is CH; or Z1 is CH, Z2 is N and Z3 is CH or N; or Z1 is CH, Z2 is CR5 and Z3 is CH; or Z1 is CH, Z2 is CH and Z3 is N; and R5 is hydrogen or fluorine; or a pharmaceutically acceptable salt thereof. The compound of formula (I) or a pharmaceutically acceptable salt thereof are used as a medicinal agent for preventing or treating bacterial infections.

EFFECT: oxazolidinone derivatives used as antimicrobial agents.

15 cl, 2 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted 4-aminocyclohexane derivatives of general formula I: where: R1 and R2 independently denote C1-3-alkyl, H or R1 and R2 together with an N tom form a (CH2)3, (CH2)4 ring; R3 optionally denotes a phenyl or thienyl linked through a C1-3-alkyl chain, each unsubstituted; or an unsubstituted C1-6-alkyl; R4 denotes indole, pyrrolo[2,3-b]pyridine, pyrrolo[2,3-c]pyridine, pyrrolo[3,2-c]pyridine, pyrrolo[3,2-b]pyridine, optionally mono- or multi-substituted with a substitute selected from a group comprising F, CI, Br, CN, CH3, C2H5,' NH2, tert-butyl, Si(ethyl)3, Si(methyl)2(tert-butyl), SO2CH3, SO2-phenyl, C(O)CH3, NO2, SH, CF3, OCF3, OH, OCH3, OC2H5, N(CH3)2; in form of a racemate; enantiomers, diastereomers, mixtures of enantiomers or diastereomers or separately an enantiomer or diastereomers; bases and/or salts of physiologically compatible acids or cations; as well as a drug based on compounds I for treating neuropathic pain.

EFFECT: improved properties.

14 cl, 73 ex

FIELD: chemistry.

SUBSTANCE: invention relates to imidazopyridines of formula I and to a pharmaceutically acceptable salt thereof, where Z1 is CR1; R1 is H; R1' is H; Z2 is CR2; Z3 is CR3; R2 and R3 are H; R4 is H; Y is W-C(O)-; W is or ; R5 is H; X1 is selected from R11' and -OR11'; R11 is independently H or C1-C6 alkyl, optionally substituted -(CR19R20)nCOR16; X4 is ; R6 is halogen, carbocyclyl or -(CR19R20)n-SR16, wherein said carbocyclyl is cyclopropyl or cyclobutyl; R6' is halogen; p equals 1, 2; n equals 0, 1; each R16 is independently H or C1-C6 alkyl; R19 and R20 are independently selected from H or C1-C6 alkyl. The invention also relates to a pharmaceutical composition based on the compound of formula I and a method of inhibiting anomalous cell growth or treating a hyperproliferative disorder, based on use of the compound of formula I.

EFFECT: obtaining novel imidazopyridine derivatives of formula I, which are useful in treating hyperproliferative disorders.

7 cl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel imidazo[4,5-b]pyridine derivatives of formula I as well as salts, hydrates and stereoisomers thereof, where B-R2 and R4-A-R3 are selected from groups indicated in claim 1, R1 denotes a C1-C6 alkyl group, optionally branched, R5 denotes a hydrogen atom. The invention also relates to a compound of formula II 3-substituted 7-chloro-5-iodo-imidazo[4,5b]pyridine, a method of producing imidazo[4,5-b]pyridine derivatives of formula I, a pharmaceutical composition based on the compound of formula I and use thereof.

EFFECT: obtaining novel derivatives having CDK inhibiting properties.

10 cl, 17 dwg, 6 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: present invention describes compounds of formula I: wherein: X1 and X2 independently represent CH or N; R1 represents fluorine or hydrogen; R2 represents hydrogen, halogen; Ar represents phenyl substituted by 1-3 groups optionally substituted in each specific case in a group consisting of hydrogen, halogen, cyano group; R3 is independently specified in each specific case in a group consisting of: (i) CH2OH; (ii) CH2O-C(=O)(CH2)nCO2R4, wherein n has a value of 2 to 5; (iii) CH2O-C(=O)CH2OCH2CO2R4; (iv) CH2OCOR5; (v) CH2OC(=O)CHR6NH2; (vi) C(=O)R5, and (vii) CH2OP(=O)(OH)2; R4 represents hydrogen or C1-10 alkyl; R5 represents hydrogen or C1-10 alkyl, C1-3 dialkylamino-C1-10 alkyl, C1-6 alkoxy or pyridinyl, R6 represents C1-6 alkyl or a side chain of a natural amino acid; or a pharmaceutically acceptable salt thereof. Besides, the invention describes a pharmaceutical composition having HTVRT inhibitory activity and containing a compound according to cl.1.

EFFECT: there are prepared and described new compounds inhibiting HIV-1 reverse transcriptase and effective for preventing and treating HIV-1 infections and treating AIDS or ARC.

13 ex, 3 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new individual compounds of pyrazolo[3,4-b]pyridine and to a method for preparing them to be used as a primary product for synthesis of new heterocyclic systems and in pharmacology. There are described methyl 3-methyl-5- [2-(4-arylamino)-2-oxoacetyl]-1,6-diphenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylates and methyl 3-methyl-5-[2-(4-arylamino)-2-oxoacetyl]-6-styryl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylates of general formula such as below, wherein R=Ph, Ar=C6H4Me-4 (a), C6H4Cl-4 (b), C6H4Br-4 (c); R=Ph-CH=CH, Ar=Ph (d), C6H4Me-4 (e), C6H4OMe-4 (f).

EFFECT: synthesis of non-reported methyl 3-methyl-5- [2-(4-arylamino)-2-oxoacetyl]-1,6-diphenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylates and methyl 3-methyl-5-[2-(4-arylamino)-2-oxoacetyl]-6-styryl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylates which possess analgesic activity.

4 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) where "----" denotes a bond or is absent; R1 is a C1-4alkoxy group or halogen; R1b is H or C1-3alkyl; U and V each independently denote CH or N; W is CH or N, or, if "----" is absent, W is CH2 or NH; under the condition that at least one of U, V and W is CH or CH2; A is -CH2-CH(R2)-B-NH-* or -CH(R3)-CH2-N(R4)-[CH2]m-*; where asterisks indicate a bond which binds said fragments through a CH2-group with an oxazolidinone fragment; B is CH2 or CO; and R2 is hydrogen, OH or NH2; R3 and R4 both denote hydrogen, or R3 and R4 together form a methylene bridge; m equals 0, 1 or 2; and G is a phenyl which is monosubstituted in position 3 or 4, or disubstituted in positions 3 and 4, where each substitute is independently selected from a group comprising C1-4alkyl, C1-3alkoxy group and halogen; or G is a group selected from groups G1 and G5 where M is CH or N; Q' is S or O; Z1 is N, Z2 is CH and Z3 is CH; or Z1 is CH, Z2 is N and Z3 is CH or N; or Z1 is CH, Z2 is CR5 and Z3 is CH; or Z1 is CH, Z2 is CH and Z3 is N; and R5 is hydrogen or fluorine; or a pharmaceutically acceptable salt thereof. The compound of formula (I) or a pharmaceutically acceptable salt thereof are used as a medicinal agent for preventing or treating bacterial infections.

EFFECT: oxazolidinone derivatives used as antimicrobial agents.

15 cl, 2 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) , where is a substituted 5-member heteroaryl ring selected from thienyl, thiazolyl, oxazolyl, pyrrolyl, imidazolyl or pyrazolyl, W is selected from a group comprising N and -C=; M is selected from a group comprising -C(O)N(R1)OR2, -CXCONR1R2 and -C(O)OR1, or M is -C1-C2alkyl-C(O)N(R1)OR2, wherein is , R1 and R2 are independently selected from a group comprising -H, C1-C3-alkyl, C6-aryl, and C1-C3-alkyl-C6-aryl; R is selected from a group comprising H, C1-C3alkyl, halogen, NR1R2, -OR1 and C6aryl; n is an integer from 0 to 1; L and Y are as indicated in the claim; and to compounds of formula (II) , where L2 is selected from a group comprising H, - C0-C3alkyl- C6aryl, -C0-C3alkyl-heteroaryl, where the heteroaryl is pyridyl; -C1-C6alkyl, Y and M are the same as for compounds of formula (I). The invention also relates to a pharmaceutical composition based on compounds (I) and (II), having inhibiting action on histone deacetylase (HDAC), a method of inhibiting and a method of treating a disease which is sensitive to the HDAC inhibitor.

EFFECT: compounds of formula I and II as histone deacetylase inhibitors.

18 cl, 18 dwg, 10 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyridin-2-one and pyridazin-3-one derivatives, having Btk inhibiting activity. In formulae I-IV:

,

R denotes -R1-R2-R3 or -R2-R3; R1 denotes a heteroaryl containing 6 ring atoms, including one N heteroatom; R2 denotes -C(=O), -C(=O)N(R2'), where R2' denotes H; R3 denotes R4; where R4 is a lower alkyl, heterocycloalkyl, (lower alkyl) heterocycloalkyl or heterocycloalkyl (lower alkyl), where the heterocycloalkyl contains 6 ring atoms, including two heteroatoms selected from N and O; and where R4 can be substituted with one or more substitutes selected from lower alkyl, oxo group and lower alkoxy group; X denotes CH or N; Y1 denotes lower alkyl; n and m are equal to 0; values of radicals Y2, Y4 are given in the claim.

EFFECT: improved properties of compounds.

6 cl, 2 tbl, 42 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula or a pharmaceutically acceptable salt thereof, wherein G1 is phenyl or pyridyl, each of which is optionally additionally substituted by one substitute presented by T; G2 is phenyl, 1,3-thiazolyl or 1,3-oxazolyl, wherein G2 is bound to G1 in the para position in relation to a place of attachment of G1 to group NH in formula (I), wherein G2 means phenyl, G3 is bound to G2 in the para position of G2 in relation to G1, and wherein provided G2 represents 1,3-thiazolyl or 1,3-oxazolyl, G2 is bound to G1 in the position of 5 G2 and G3 is bound to G2 in the position of 2 G2; T in each case is independently specified in a group containing C1-6alkyl and halogen; G3 is presented by formula or by formula ; W1 is -C(R3)(R4)-C(R3)(R4)-, and W2 represents N; or W3 represents O; W4 is -C(R3)(R4) -; each R3 and R4 is hydrogen; each R5 and R6 kis hydrogen; Rc and Rd together with a carbon atom whereto attached, are a 4-5-member cycloalkyl or monocyclic heterocycle of formula ; wherein one hydrogen atoms attached to the carbon atom of the cycloalkyl ring and monocyclic heterocycle is optionally substituted by a radical specified in a group -C(O)O(R8); W5 is -CH2- or -CH2-CH2-; W6 is O or N(RX), wherein Rx is hydrogen, C1-6alkyl or -C(O)O(Rz); RZ in each case is independently C1-6alkyl; R8 is hydrogen; L1 is O; and X is hydrogen, C1-6alkyl, or - (CRgRh)u-C(O)O(R10); or L1 is -CH2- and X is -C(O)OH; R10 is hydrogen; or Q is G4 or Y1-Y3; or Q is described for formula wherein Z is phenyl; G4 is benzothiazole or benzoxazole optionally additionally substituted by 1 or 2 substitutes specified in a group consisting of C1-6alkyl, halogen and -OR1; Y1 in each case is independently -C(O)-, -C(O)O- or -C(O)N(Rw)-, wherein the right side -C(O)O- and -C(O)N(Rw)- of the groups is attached to Y3 or (CRJRk)v, Y3 in each case is independently phenyl, benzyl, piperidinyl or bicyclo[4.2.0]octa-1,3,5-triene, wherein the phenyl and benzyl residues are optionally additionally substituted by 1 or 2 substitutes specified in a group consisting of halogen and haloC1-6alkyl; Rg and Rh in each case is independently hydrogen, or C1-6alkyl; R1 in each case is independently halogenC1-6alkyl; Rw is hydrogen; and u means 1.

EFFECT: compounds being the type 1 diacylglycerol O-acyltransferase (DGAT-1) enzyme inhibitors.

7 cl, 1 tbl, 61 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new benzodiazepine compounds of general formula , wherein each R1, R2, R3 and R4 independently represent hydrogen or alkyl, or R2 and R3 together represent lower alkylene; A1 is lower alkylene optionally substituted by hydroxy; and R5 is a fragment of formula , wherein each R6 and R7 independently represents hydrogen, lower alkyl, cycloalkyl, phenyl, furyl, thienyl, pyrazolyl, etc.; each XA and XB independently represents a bond, lower alkylene, -CO-, -SO2- etc., a pharmaceutical composition containing them, and using the above compound as the pharmaceutical composition or for preparing the same.

EFFECT: new compounds may be used for preventing and treating cardiac arrhythmia.

8 cl, 1047 ex, 78 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds being aspartyl protease inhibitors applicable for treating cardiovascular, neurodegenerative disorders and fungal infection of formula , wherein W represents -C(=O)-; X represents -NH-; U represents -C(R6)(R7)-; R1 represents methyl, R2, R3 and R6 represent H, R4 and R7 represent optionally substituted phenyl, as well as tautomers and pharmaceutically acceptable salts thereof.

EFFECT: there are presented new effective aspartyl protease inhibitors specified in rennin, cathepsin D, BACE-1, for treating cardiovascular diseases, cognitive and neurodegenerative diseases, as well as fungal infections.

67 cl, 1 tbl, 4393 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to indolyl-substituted derivatives of thiadiazinones prepared from oxamic acid thiohydrazide of general formula: , wherein R represents H; R1 represents pyridinyl; phenyl substituted by alkyl C1-C5, Hal, CF3; R2 represents H; alkyl C1-C5; -CH2COOR4; benzyl substituted by Hal, OR4; benzoyl substituted by Hal, OR4, while R4 represents unsubstituted alkyl C1-C4.

EFFECT: there are prepared new compound which can find application in medicine for developing the therapeutic agent possessing pathogenic bacteria inhibitory activity.

2 cl, 2 dwg, 2 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel heterocyclic nitrogen- and oxygen-containing compounds having insecticidal activity. In formulae (A) (B) (C) (D) R1 is a 5- or 6-member heterocyclic ring containing a nitrogen, oxygen and/ or sulphur atom, a halogen-substituted 5- or 6-member heterocyclic ring containing a nitrogen, oxygen and/or sulphur atom, a substituted or unsubstituted phenyl, where the substitutes are one or more groups selected from a group consisting of halogen atoms, C1-4 halogen alkyl or C1-4 chloroalkoxyl; R5, R6, R7, R8 and R9 are H, saturated or unsaturated C1-4 alkyl, halogen atom, saturated or unsaturated C1-4 alkoxyl, saturated C1-4 halogenalkoxyl, C1-4 alkylcarbonyl, C1-8 alkyl ester, C1-4 alkylsulphonyl, phenyl, benzyl or trifluoromethane sulphonyl ether group; Y is nitro, cyano, trifluoromethyl, trifluoroacetyl or trifluoromethylsuphonyl. Values of radicals R, R2-R4 are given in the claim.

EFFECT: invention also relates to an agrochemical composition containing said compounds, use of the agrochemical composition in pest control and a method of producing said compounds.

12 cl, 7 tbl, 36 ex

Azole compounds // 2493154

FIELD: chemistry.

SUBSTANCE: invention relates to compounds which are pyridin-3-yl 4-(3-phenyl-1H-1,2,4-triazol-5-yl)piperidine-1-carboxylate, 6-methylpyridin-3-yl 4-[3-(4-fluoromethyl)-1H-1,2,4-triazol-5-yl]piperidine-1-carboxylate, 6-methylpyridin-3-yl 4-[5-(4-fluorophenyl)-1,3-oxazol-2-yl]piperidine-1-carboxylate, 2,6-dimethylpyridin-3-yl 4-[5-(3,4-difluorophenyl)-1,2,4-oxadiazol-3-yl]piperidine-1-carboxylate, 2-methylpyridin-3-yl 4-[3-(2-fluorophenyl)-1H-1,2,4-triazol-5-yl]piperidine-1-carboxylate, 6-methylpyridin-3-yl 4-(3-phenyl-1H-pyrazol-1-yl)piperidine-1-carboxylate, 2-methylpyridin-3-yl 4-[5-(3-fluorophenyl)-1,3-oxazol-2-yl]piperidine-1-carboxylate and 6-methylpyridin-3-yl 4-[4-(4-fluorophenyl)-1,3-oxazol-2-yl]piperidine-1-carboxylate or to a pharmaceutically acceptable salt thereof. The invention also relates to a pharmaceutical composition based on said compounds, having inhibiting effect on fatty acid amide hydrolase (FAAH).

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine for treating neuropathic pain.

13 cl, 38 tbl, 159 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound, which is N3-1H-indol-5-yl-5-pyridin-4-ylpyrazine-2,3-diamine, or a pharmaceutically acceptable salt thereof, which can act as inhibitors of protein kinase, especially FLT3 tyrosine kinase. The invention also relates to a pharmaceutical composition which contains said compound in combination with another molecularly directed (target) agent, which is a traditional cytotoxic agent or a compound used after chemotherapy, supporting therapy targeted on stem cells and in case of MLL rearrangement acute lymphoblastic leukaemia in children.

EFFECT: obtaining a novel compound which can be used in medicine for preventing or treating haematological malignant growths such as AML, MLL, T-ALL, B-ALL and CMML, myeloproliferative diseases, autoimmune diseases and skin diseases, such as psoriasis and atopic dermatitis.

16 cl, 2 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) where "----" denotes a bond or is absent; R1 is a C1-4alkoxy group or halogen; R1b is H or C1-3alkyl; U and V each independently denote CH or N; W is CH or N, or, if "----" is absent, W is CH2 or NH; under the condition that at least one of U, V and W is CH or CH2; A is -CH2-CH(R2)-B-NH-* or -CH(R3)-CH2-N(R4)-[CH2]m-*; where asterisks indicate a bond which binds said fragments through a CH2-group with an oxazolidinone fragment; B is CH2 or CO; and R2 is hydrogen, OH or NH2; R3 and R4 both denote hydrogen, or R3 and R4 together form a methylene bridge; m equals 0, 1 or 2; and G is a phenyl which is monosubstituted in position 3 or 4, or disubstituted in positions 3 and 4, where each substitute is independently selected from a group comprising C1-4alkyl, C1-3alkoxy group and halogen; or G is a group selected from groups G1 and G5 where M is CH or N; Q' is S or O; Z1 is N, Z2 is CH and Z3 is CH; or Z1 is CH, Z2 is N and Z3 is CH or N; or Z1 is CH, Z2 is CR5 and Z3 is CH; or Z1 is CH, Z2 is CH and Z3 is N; and R5 is hydrogen or fluorine; or a pharmaceutically acceptable salt thereof. The compound of formula (I) or a pharmaceutically acceptable salt thereof are used as a medicinal agent for preventing or treating bacterial infections.

EFFECT: oxazolidinone derivatives used as antimicrobial agents.

15 cl, 2 tbl, 44 ex

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