Positive allosteric modulators of m1 receptors based on pyranyl aryl methylbenzoquinazolinone

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyranyl aryl methylbenzoquinazolinone compounds of formula (I), which are positive allosteric modulators of the M1 receptor and which can be used to treat diseases associated with the M1 receptor, such as Alzheimer's disease, schizophrenia, pain disorders or sleep disturbance. In formula (I) X-Y are selected from a group comprising (1) -O-CRARB-, (2) -CRARB-O-, (3) -CRARB-SRC-, (4) -CRARB-NRC- and (5) -NRC-CRARB-, where each RA and RB is a hydrogen atom, and RC is selected from a group comprising (a) hydrogen, (b) -C(=O)-C1-6alkyl, (c) -C1-6alkyl, (d) -C(=O)-CH2-C6H5, (e) -S(=O)2-C1-6 alkyl, R1 is a hydroxy group, R2 is selected from a group comprising (1) -phenyl, (2) - heteroaryl, where the phenyl or heteroaryl group R2 is optionally substituted; the rest of the values of the radicals are given in the claim.

EFFECT: obtaining novel pyranyl aryl methylbenzoquinazolinone compounds.

28 cl, 12 tbl, 37 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

or its pharmaceutically acceptable salt, in which X-Y is chosen from the group including
(1) -O-CRARB-,
(2) -CRARB-O-,
(3) -CRARB-SRC-,
(4) -CRARB-NRCand
(5) -NRC-CRARB-,
where each RAand RBrepresent a hydrogen atom, and RCchoose from a group that includes
(a) hydrogen,
(b) -C(=O)-C1-6alkyl,
(c) -C1-6alkyl,
(d) -C(=O)-CH2-C6H5,
(e) -S(=O)2-C1-6alkyl,
R1predstavljaet a hydroxy-group,
provided that when X-Y is-O-CRARB-, CRARB-O -, or CRARB-SRC-, R1represents hydroxy in the isomeric state:

R2choose from a group that includes
(1) - phenyl,
(2) -heteroaryl, which represents a monocyclic aromatic group containing from 5 to 6 atoms in the cycle, is selected from C and one or two atoms selected from N, N→O or S, or a bicyclic aromatic group containing from 9 to 10 atoms in a bicyclic system, selected from C and from one to three atoms selected from N or S,
where the phenyl or heteroaryl group, R2optionally substituted by one or more (a) halogen,
(b)hydroxy,
(c) -NR3R4,
(d) -C1-6the alkyl,
(e) -O-C1-6the alkyl,
(f) -C2-8alkenyl,
(g) -C(=O)-(O)m-R5,
(h) -C(=O)-NR5,
(i) -S(=O)2-R5,
(J) -CN,
(k) -phenyl,
(1) -heteroaryl represents an aromatic monocyclic group containing from five to six atoms of the cycle, while the atoms of the cycle are selected from C, and one or two N, N→O or S,
(m)=S,
where alkyl, phenyl or heteroaryl group optionally substituted by one or more
(a) halogen,
(b) hydroxyl,
(c) -C1-6the alkyl,
(d) -S-R6,
(e) -NR8R9,
(f) -O-C1-6the alkyl,
where and what Celina group optionally substituted by one or more halogen atom; R3and R4or R8and R9independently selected from the group including
(1) hydrogen or
(2) -C1-6alkyl,
where alkyl optionally substituted by one or more
(a) halogen,
(b) hydroxyl,
(c) -O-C1-6the alkyl,
(d) -NR10R11,
or R3and R4joined together with the nitrogen atom to which they relate, with the formation of a 4-6-membered carbocyclic ring in which one or two carbon atoms of the cycle is optionally substituted by a nitrogen atom, oxygen or sulfur, and the cycle is optionally substituted by one or more
(a) halogen,
(b)- (C1-6the alkyl,
(c) -O-C1-6the alkyl,
(d) -C(=O)-(O)n-C1-6the alkyl, R5choose from a group that includes
(1) hydrogen,
(2) -C1-6alkyl,
(3) -C2-8alkenyl,
R6represents a C1-6alkyl,
R10and R11independently selected from the group including
(1) hydrogen or
(2) -C1-6alkyl, m is 0 or 1;
n is 0, 1 or 2.

2. The compound according to claim 1, in which R1represents a hydroxy-group in the isomeric state:

3. The compound according to claim 1, in which X-Y is-O-CRARBor CRARB-O-,
where each RAand RBrepresents hydrogen.

4. The compound according to claim 1, in which R2represents phenyl.

5. The compound according to claim 1, to which m R 2is heteroaryl, which represents a monocyclic aromatic group containing 5 atoms in the cycle, is selected from C and one or two atoms selected from N, N→O and S.

6. The compound according to claim 1, in which R2is heteroaryl represents an aromatic monocyclic group containing 6 atoms in the cycle, is selected from C and one or two atoms selected from N or N→o

7. The compound according to claim 1, in which R represents heteroaryl, which represents a bicyclic aromatic group containing from 9 to 10 atoms in a bicyclic system, selected from s and from one to three atoms selected from N or S.

8. The compound according to claim 1 in which the compound of formula (I) is a compound of formula (II):

or its pharmaceutically acceptable salt in which X, Y and R2such as defined in claim 1.

9. The connection of claim 8, in which X-Y is-O-CRARBor CRARB-O-, where each RAand RBrepresents hydrogen.

10. The connection of claim 8, in which R2represents phenyl.

11. The connection of claim 8, in which R represents heteroaryl, which represents a monocyclic aromatic group containing 5 atoms in the cycle, is selected from C and one or two atoms selected from N, N→O S.

12. The connection of claim 8, in which R2is heteroaryl represents an aromatic monocyclic group containing 6 atoms in the cycle, is selected from C and one or two atoms selected from N or N→o

13. The connection of claim 8, in which R2is heteroaryl, which represents a bicyclic aromatic group containing from 9 to 10 atoms in a bicyclic system, selected from s and from one to three atoms selected from N or S.

14. The compound according to claim 1 in which the compound of formula (I) is a compound of formula (III):

and its pharmaceutically acceptable salt in which X, Y and R2such as defined above, a R7choose from a group that includes
(1) halogen,
(2) -NR3R4,
(3) -C1-6alkyl,
(4) -O-C1-6alkyl,
(5) -C1-8alkenyl,
(6) -C(=O)-(O)m-R5,
(7) -C(=O)-NR5,
(8) -S(=O)2-R5,
(9) -SR5,
(10) -CN,
(11) -C6-10aryl,
(12) -heteroaryl, which is a monocyclic aromatic group containing from five to six atoms of the cycle, while the atoms of the cycle are selected from C, and one or two N, N→O or S,
(13) =S or
(14) hydrogen,
where alkyl, phenyl or heteroaryl group optionally substituted by one or more
(a) halogen,
(b) hydroxyl,
(c) -C1-6 (d) -S-R6,
(e) -NR8R9,
(f) -O-C1-6the alkyl,
where the alkyl group is optionally substituted by one or more halogen atoms.

15. The connection 14, in which R7choose from a group that includes
(1) halogen,
(2) hydroxyl,
(3) -NR3R4,
(4) -C1-6alkyl,
(5) -O-C1-6alkyl,
(6) -S(=O)2-R5or
(7) -SR5.

16. The connection 14, in which X-Y is chosen from the group including
(1) -O-CRARBor
(2) -CRARB-O-.

17. The compound according to claim 1 in which the compound of formula (I) is a compound of formula (IV):

in which R2such as defined in claim 1.

18. The connection of claim 8, in which R2represents phenyl.

19. The connection 17 in which R2is heteroaryl, which represents a monocyclic aromatic group containing 5 atoms in the cycle, selected from s and one or two atoms selected from N, N→O and S.

20. The connection 17 in which R2is heteroaryl represents an aromatic monocyclic group containing 6 atoms in the cycle, is selected from C and one or two atoms selected from N or N→o

21. The connection 17 in which R2is heteroaryl, which represents a bicyclic aromatic group, with the holding from 9 to 10 atoms in a bicyclic system, selected from C and from one to three atoms selected from N or S.

22. The compound according to claim 1, which is selected from the group including
6-[(6-chloropyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-6-{[(6-methylthio)pyridine-3-yl)methyl]benzo[h]hinzelin-4(3H)-he;
3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-6-[(6-methylpyridin-3-yl)methyl]benzo[h]hinzelin-4(3H)-he;
3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-6-{[6-(1-methyl-1H-pyrazole-4-yl)pyridine-3-yl]methyl}benzo[h]hinzelin-4(3H)-he;
3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-6-{[6-(1H-pyrazole-1-yl)pyridine-3-yl]methyl}benzo[h]hinzelin-4(3H)-he;
3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-6-(pyridine-3-ylmethyl)benzo[h]hinzelin-4(3H)-he;
3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-6-[(6-methoxypyridine-3-yl)methyl]benzo[h]hinzelin-4(3H)-he;
5-({3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-4-oxo-3,4-dihydrobenzo [h]hinzelin-6-yl}methyl)pyridine-2-carbonitrile;
6-[(6-ethylpyridine-3-yl)methyl]-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
6-[(6-acetylpyridine-3-yl)methyl]-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
6-{[6-(1-hydroxy-1-methylethyl)pyridine-3-yl]methyl}-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-6-(4-(morpholine-4-ylbenzyl)benzo[h]hinzelin-4(3H)-he;
3-[(3R,4S)-3-hidroxi is trihydro-2H-Piran-4-yl]-6-{[6-(l,3-thiazol-4-yl)pyridine-3-yl]methyl}benzo[h]hinzelin-4(3H)-he;
6-[(6-chloro-1-oxidability-3-yl)methyl]-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
6-[(2-chloropyridin-4-yl)methyl]-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-6-{[6-(methylsulphonyl)pyridine-3-yl]methyl}benzo[h]hinzelin-4(3H)-he;
3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-6-{[6-(methylsulfinyl)pyridine-3-yl]methyl}benzo[h]hinzelin-4(3H)-he;
5-({3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-4-oxo-3,4-dihydrobenzo[h]hinzelin-6-yl}methyl)pyridine-2-carboxylic acid;
5-({3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-4-oxo-3,4-dihydrobenzo[h]hinzelin-6-yl}methyl)-N,N-dimethylpyridin-2-carboxamide;
3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-6-{[6-(1-methoxy-1-methylethyl)pyridine-3-yl]methyl}benzo[h]hinzelin-4(3H)-he;
6-{[6-(hydroxymethyl)pyridine-3-yl]methyl}-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
6-{[6-(permitil)pyridine-3-yl]methyl}-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
6-{[6-(deformity)pyridine-3-yl]methyl}-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
6-[(2-chloro-1-oxidability-4-yl)methyl]-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
6-[(2-herperidin-4-yl)methyl]-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]-6-[(2-methoxypyridine-4-yl)methyl]b is the site, located between[h]hinzelin-4(3H)-he;
6-[(6-ethoxypyridine-3-yl)methyl]-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
6-[(6-hydroxypyridine-3-yl)methyl]-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
6-{[6-(deformedarse)pyridine-3-yl]methyl}-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
6-{[2-(deformedarse)pyridine-4-yl]methyl}-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
6-[(3-bromo-1-methyl-1H-pyrrol[2,3-b]pyridine-4-yl)methyl]-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
6-[(1-ethyl-1H-pyrrol[2,3-b]pyridine-4-yl)methyl]-3-[(3R,4S)-3-hydroxytyramine-2H-Piran-4-yl]benzo[h]hinzelin-4(3H)-he;
6-[(6-chloropyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytyramine-2H-thiopyran-4-yl]benzo[h]hinzelin-4(3H)-he;
3-[(5S,4S)-4-hydroxycitrate-2H-Piran-3-yl]-6-[(6'-methyl-2,3-bipyridine-5-yl)methyl)benzo[h]hinzelin-4(3H)-he;
rat-6-[(6-chloropyridin-3-yl)methyl]-3-[{3R,4R)-3-hydroxypiperidine-4-yl]benzo[h]hinzelin-4(3H)-he;
rat-3-[(3R,4R)-1-acetyl-3-hydroxypiperidine-4-yl]-6-[(6-chloropyridin-3-yl)methyl]benzo[h]hinzelin-4(3H)-he;
6-[(6-chloropyridin-3-yl)methyl]-3-piperidine-4-albenza[h]hinzelin-4(3H)-he;
or their pharmaceutically acceptable salts.

23. The compound according to claim 1, which is selected from the group including









or their pharmaceutically acceptable salts.

24. Pharmaceutical composition having the properties of a modulator of the activity of allosteric muscarinic receptor M1 containing a therapeutically effective amount of a compound according to claim 1, or its pharmaceutically acceptable salts, and pharmaceutically acceptable carrier.

25. Pharmaceutical composition for treatment of a disease or disorder mediated by the muscarinic M1 receptor, where the disease or disorder is Alzheimer's disease containing a therapeutically effective amount of a compound according to claim 1, or its pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier.

26. The use of the pharmaceutical composition according A.25 for the treatment of a disease or disorder mediated by the muscarinic M1 receptor, wherein the disease is Alzheimer's disease.

27. The use of compounds according to claim 1, or its pharmaceutically acceptable salts, and pharmaceutically acceptable carrier, to obtain drugs for the treatment of diseases or RA is disorder, mediated by the muscarinic M1 receptor, wherein the disease or disorder is Alzheimer's disease.

28. The method of treatment of a disease or disorder mediated by the muscarinic M1 receptor, wherein the disease or disorder is Alzheimer's disease, in need thereof of a patient, comprising the introduction of this patient a therapeutically effective amount of a compound according to claim 1 or its pharmaceutically acceptable salts, and pharmaceutically acceptable carrier.



 

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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 .

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46 cl, 3 dwg, 38 tbl, 89 ex

FIELD: chemistry.

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11 cl, 4 tbl, 126 ex

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13 cl, 1 ex

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17 cl, 1 tbl, 14 dwg, 4 ex

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8 cl, 1047 ex, 78 tbl

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67 cl, 1 tbl, 4393 ex

FIELD: chemistry.

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16 cl, 2 tbl, 26 ex

Organic compounds // 2491285

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I), wherein V is specified in -O- or a single bond; W is specified in -N(R5)C(O)-, -S(O)t- and -C(O)O-; X is specified in C(H) or N; Y is specified in S, N(H) or N(CH3); p means 0 or 2; t means 1 or 2; R1 is specified in a group consisting of hydrogen, C1-6alkyl optionally substituted by 1 or 2 halogroups, C3-7cycloalkylC1-6alkyl, 2,3-dihydro-1H-indenyl, C6arC1-6alkyl optionally substituted by one or two halogroups and heteroarylC1-6alkyl, wherein a heteroaryl fragment of the heteroarylalkyl group means 5-6-member monocyclic heteroaryl containing 1 or 2 heteroatoms independently specified in a group consisting of nitrogen optionally oxidated, oxygen and sulphur, or a heteroaryl fragment of the heteroarylalkyl group means 9-member bicyclic heteroaryl containing 1 or 2 heteroatoms independently specified in a group consisting of nitrogen, oxygen and sulphur, wherein monocyclic heteroaryl of the heteroarylalkyl group may be optionally substituted by one or two substitutes independently specified in a group consisting a halogroup, a cyanogroup, C1-6alkyl, haloC1-6alkyl and C1-6alkyl-O-C(O)-; R2 is specified in a group consisting of hydrogen, C1-6alkyl optionally substituted by phenoxy, hydroxy C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-6alkyl, phenyl optionally substituted by a halogroup, haloC1-6alkyl, C6arC1-6alkyl (optionally substituted by a halogroup, haloC1-6alkyl or haloC1-6alkoxygroup), 2-oxo-imidazolidinyl, heterocyclylC1-6alkyl and heteroarylC1-6alkyl, wherein heterocyclyl of heterocyclylalkyl means 5- or 6-member monocycle containing oxygen, and wherein a heteroaryl fragment of the heteroarylalkyl group means 5-6-member monocycle containing 1-3 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, or a heteroaryl fragment of the heteroarylalkyl group means 9- or 10-member bicycle containing 1 to 2 heteroatoms specified in a group consisting of nitrogen and sulphur, wherein monocyclic heteroaryl of the heteroaryl alkyl group may be optionally substituted by 1 or 2 substitutes independently specified in a group consisting of a halogroup, C1-6alkyl, haloC1-6alkyl and phenyl optionally substituted by a halogroup; R3 is specified in a group consisting of hydrogen and alkyl; two adjacent R4 groups together with carbon atoms whereto attached can form phenyl; R5 means hydrogen; or a pharmaceutically acceptable salt thereof.

EFFECT: preparing the heterocyclic derivatives which modulate activity of stearoyl CoA desaturase, methods of using the above derivatives for modulating activity of stearoyl CoA desaturase and pharmaceutical compositions containing the above derivatives.

26 cl, 1 tbl, 153 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a dye which contains a binding group in its molecular structure, wherein said binding group provides covalent bonding of said dye to a surface, and said binding group is represented by formula 1 , in which the binding site of said binding group inside said molecular structure of said dye is located at the terminal carbon atom marked with an asterisk in said formula. G is selected from -COOH, -SO3H, -PO3H2, -BO2H2 -SH, -OH, -NH2, A is selected from a group consisting of H, -CN, -NO2, -COOR, -COSR, -COR, -CSR, -NCS, -CF3, -CONR2, -OCF3, C6H5.mFm, in which m=1-5, R is H or any linear or branched alkyl chain of general formula -CnH2n+1 n=0-12, preferably 0-4, or any substituted or unsubstituted phenyl or biphenyl, where said dye is represented by formula (2) or formula (4), where said chromophore is a squarylium dye derivative or a croconium dye derivative, which is capable of absorbing light with a wavelength in the visible and/or infrared range, preferably in the range from 300 to 1200 nm or part thereof, wherein each derivative of said squarylium dye and said croconium dye has aromatic ring systems Ar1 and Ar2, that are bonded to the squarylium dye or croconium dye derivatives. The invention also relates to methods of producing chromophore which is part of a dye and is a dye itself, as well as devices using said dye and applications thereof as a sensitising agent and a sensor.

EFFECT: disclosed dyes are also capable of absorbing light in the long-wave spectral range.

32 cl, 23 ex, 20 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a 2H-chromen compound or a derivative thereof having action of a S1P1 agonist. The above may be used for preventing and/or treating a disease caused by undesired lymphocyte filtration, or a disease caused by abnormal cell proliferation or accumulation.

EFFECT: preparing the compounds for preventing and/or treating the disease caused by undesired lymphocyte filtration, or the disease caused by abnormal cell proliferation or accumulation.

8 cl, 131 tbl, 156 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted pyrrolidine-2-carboxamides of formula I or their pharmaceutically acceptable salts, where values X, Y, R1, R2, R3, R3, R4, R5, R6 and R7 are given in item 1 of the formula. Compounds can be used in pharmaceutical composition, inhibiting interaction of MDM2-p53.

EFFECT: compounds can be used as anti-cancer medications.

46 cl, 4 dwg, 347 ex

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

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrrole derivatives of the formula (1): or pharmaceutically acceptable salts thereof, where: R1 denotes H, halogen; R2 denotes an 8-10-member bicyclic hydrocarbon group, optionally substituted, or a bicyclic heterocyclic group consisting of one or two atoms selected from nitrogen, oxygen and sulphur and 5-9 carbon atoms, optionally substituted, where the optional substitute is halogen, lower alkyl, OH, lower alkoxy, oxo, NO2, CN; R3 denotes H.

EFFECT: compounds have inhibiting action of production of IL-6, which enables use thereof in a pharmaceutical composition and when treating a range of diseases.

12 cl, 1 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrrole compounds of formula I or pharmaceutically acceptable salts thereof: I, where: Ar denotes phenyl, thiophenyl; R1 denotes imidazolyl, imidazolyl substituted with C1-C6alkyl, chlorine, bromine, fluorine, hydroxy group, methoxy group; R2 denotes H, CH3, Cl, F, OH, OCH3, OC2H5, propoxy group, carbamoyl, dimethylamino group, NH2, formamide group, CF3; X denotes CO and SO2. The compounds inhibit S-nitrosoglutathione reductase (GSNOR).

EFFECT: using the compound to produce a pharmaceutical composition and for treating asthma.

17 cl, 1 tbl, 14 dwg, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to organic chemistry, namely to new phenylimidazole derivatives of general formula , wherein R1 represents a hydrogen atom, a phenyl lower-alkyl group or a pyridyl lower-alkyl group with a benzene ring and a pyridine ring are optionally substituted by 1 or 2 substitutes specified in a group consisting of halogen atoms, cyano group and halogen-substituted lower-alkyl groups; one or R2 and R3 represents a hydrogen atom, and another one represents a lower alkoxy group; R4 represents a lower-alkyl group, a difurylglyoxal group, a thienyl group or a phenyl group optionally substituted by 1 or 2 substitutes specified in a group consisting of lower-alkyl groups, lower-alkoxy groups, halogen atoms, a carboxyl group, lower alkoxycarbonyl groups, and halogen-substituted lower-alkyl groups; R5 and R6 are identical or different, and represent a hydrogen atom or a lower alkyl group; R7 and R8 are identical or different, and represent a hydrogen atom or a lower alkoxy group; provided R1 represents an unsubstituted phenyl lower-alkyl group, R2 represents a lower alkoxy group, R3 represents a hydrogen atom, R4 represents an unsubstituted phenyl group or a phenyl group containing 1 or 2 halogen-substituted lower-alkyl groups, and R5 represents a hydrogen atom, then R6 is other than a hydrogen atom. Also, the invention refers to an LPL activator, an agent for preventing or treating hyperlipidaemia, an agent for treating arteriosclerosis, and an agent for treating obesity on the basis of the compound of formula (1).

EFFECT: there are prepared new phenylimidazole derivatives effective for LPL activation.

23 cl, 10 tbl, 7 ex

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 relates to compound of formula (I): or to its pharmaceutically acceptable ester, amide, carbamate, solvate or salt, including salt of such ester, amide or carbamate and solvate of such ester, amide, carbamate or salt, where values R1, R2, R3, R4, R5 and R6 are given in item of the formula, with the exception: 4-[3-(4,5-dihydro-1H-imidazol-2-yl)-2-(3,5-dimethylisoxazol-4-yl)indole-1-yl]phenol; 1-(4-hydroxyphenyl)-2-(4-methylimidazol-1-yl)-1H-indole-3-carbonitryl; 1-(4-hydroxyphenyl)-2-(1H-pyrazol-3-yl)-1H-indole-3-carbonitryl; 1-(3-chloro-4-hydroxyphenyl)-2-(1-methyl-1H-pyrazol-4-yl)-1H-indole-3-carbonitryl; 1-(4-hydroxyphenyl)-2-prop-1-inyl-1H-indole-3-carboxylic acid amide.

EFFECT: compounds I possess affinity of binding with estrogen receptor of p-subtype, which makes it possible to use them in pharmaceutical composition and in treatment or prevention of state, associated with disease or disorder, associated with activity of estrogen receptors of β-subtype.

27 cl, 271 ex

Organic compounds // 2491285

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I), wherein V is specified in -O- or a single bond; W is specified in -N(R5)C(O)-, -S(O)t- and -C(O)O-; X is specified in C(H) or N; Y is specified in S, N(H) or N(CH3); p means 0 or 2; t means 1 or 2; R1 is specified in a group consisting of hydrogen, C1-6alkyl optionally substituted by 1 or 2 halogroups, C3-7cycloalkylC1-6alkyl, 2,3-dihydro-1H-indenyl, C6arC1-6alkyl optionally substituted by one or two halogroups and heteroarylC1-6alkyl, wherein a heteroaryl fragment of the heteroarylalkyl group means 5-6-member monocyclic heteroaryl containing 1 or 2 heteroatoms independently specified in a group consisting of nitrogen optionally oxidated, oxygen and sulphur, or a heteroaryl fragment of the heteroarylalkyl group means 9-member bicyclic heteroaryl containing 1 or 2 heteroatoms independently specified in a group consisting of nitrogen, oxygen and sulphur, wherein monocyclic heteroaryl of the heteroarylalkyl group may be optionally substituted by one or two substitutes independently specified in a group consisting a halogroup, a cyanogroup, C1-6alkyl, haloC1-6alkyl and C1-6alkyl-O-C(O)-; R2 is specified in a group consisting of hydrogen, C1-6alkyl optionally substituted by phenoxy, hydroxy C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-6alkyl, phenyl optionally substituted by a halogroup, haloC1-6alkyl, C6arC1-6alkyl (optionally substituted by a halogroup, haloC1-6alkyl or haloC1-6alkoxygroup), 2-oxo-imidazolidinyl, heterocyclylC1-6alkyl and heteroarylC1-6alkyl, wherein heterocyclyl of heterocyclylalkyl means 5- or 6-member monocycle containing oxygen, and wherein a heteroaryl fragment of the heteroarylalkyl group means 5-6-member monocycle containing 1-3 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, or a heteroaryl fragment of the heteroarylalkyl group means 9- or 10-member bicycle containing 1 to 2 heteroatoms specified in a group consisting of nitrogen and sulphur, wherein monocyclic heteroaryl of the heteroaryl alkyl group may be optionally substituted by 1 or 2 substitutes independently specified in a group consisting of a halogroup, C1-6alkyl, haloC1-6alkyl and phenyl optionally substituted by a halogroup; R3 is specified in a group consisting of hydrogen and alkyl; two adjacent R4 groups together with carbon atoms whereto attached can form phenyl; R5 means hydrogen; or a pharmaceutically acceptable salt thereof.

EFFECT: preparing the heterocyclic derivatives which modulate activity of stearoyl CoA desaturase, methods of using the above derivatives for modulating activity of stearoyl CoA desaturase and pharmaceutical compositions containing the above derivatives.

26 cl, 1 tbl, 153 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new quinolone derivatives of general formula (1) or a pharmaceutically acceptable salts thereof, wherein R1 represents a hydrogen atom, a lower alkyl group, cyclo C3-8 alkyl, a lower alkyl group or a lower alkoxy, a lower alkyl group; R2 represents a hydrogen, a lower alkyl group or a halogen-substituted lower alkyl group; R3 represents a phenyl group, a difurylglyoxal group, a thienyl group or pyridyl group with each group of the above is optionally substituted by one or two groups specified in a group consisting of the following (1) to (16) in an aromatic or heterocyclic ring, presented by the above R3: (1) lower alkyl groups, (2) lower alkoxy groups, (3) halogen-substituted lower alkoxy groups; (4) a phenoxy group, (5) lower alkylthio groups, (6) a hydroxy group, (7) hydroxy lower alkyl groups, (8) halogen atoms, (9) lower alkanoyl groups, (10) lower alkoxycarbonyl groups, (11) amino groups optionally substituted by one or two lower alkyl groups, (12) carbamoyl groups optionally substituted by one or two lower alkyl groups, (13) cyclo C3-8 alkyl lower alkoxy groups, (14) pyrrolidinyl carbonyl groups, (15) morpholinyl carbonyl groups and (16) a carboxyl group; R1 represents a halogen atom; R5 represents a hydrogen atom or a halogen atom; R6 represents a hydrogen atom; and R7 represents any of the above groups (1) to (15): (1) a hydroxyl group, (2) a halogen atom, (3) a lower alkoxy group, (4) a halogen-substituted lower alkoxy group, (5) a hydroxy lower alkoxy group, (6) a lower alkoxy lower alkoxy group, (7) an amino group optionally substituted by one or two members specified in a group consisting of lower alkyl groups, lower alkoxy lower alkyl groups and cyclo C3-8 alkyl groups, (8) an amino lower alkoxy group optionally substituted in an amino group by one or two members specified in a group consisting of lower alkyl groups, lower alkanoyl group, lower alkyl sulphonyl groups and carbamoyl groups optionally substituted by one or two lower alkyl groups, (9) a cyclo C3-8 alkoxy group, (10) a cyclo C3-8 alkyl lower alkoxy group, (11) a tetrahydrofuryl lower alkoxy group, (12) a lower alkylthio group, (13) a heterocyclic group specified in a group consisting of morpholinyl groups, pyrrolidinyl groups, difurylglyoxal groups, thienyl groups and benzothienyl groups, (14) a phenyl lower alkoxy lower alkoxy group and (15) a pyrrolidinyl carbonyl group. Also, the invention refers to a pharmaceutical composition, and a preventive and/or therapeutic agent based on the compound of formula (1), using the compound of formula (1), a method of treating or preventing the above diseases, to a method of preparing the compound of formula (1).

EFFECT: there are prepared new quinolone derivatives effective for treating and/or preventing the neurodegenerative diseases, diseases caused by neurological dysfunction, or diseases induced by deterioration of mitochondrial function.

11 cl, 1 tbl, 104 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula (I) or pharmaceutically acceptable salts thereof wherein A, R1, R2, R3 and m are specified in the patent claim. The present invention also refers to the number of specific compounds, and to a pharmaceutical composition containing the above compounds effective for inhibition of kinases, such as glycogen synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus kinase (JAK), AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.

EFFECT: preparing the specific compounds and pharmaceutical composition containing the above compounds effective for kinase inhibition.

18 cl, 393 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to 5-phenyl-1H-pyrazin-2-one derivatives of general formula II or pharmaceutically acceptable salts thereof, where R denotes -R1 or - R1-R2-R3; R1 denotes aryl or heteroaryl, and is optionally substituted with one or two R1'; where each R1' independently denotes C1-6alkyl, halogen or C1-6halogenalkyl; R2 denotes -C(=O), -CH2-; R3 denotes R4; where R4 denotes an amino group or heterocycloalkyl, and is optionally substituted with one or two substitutes selected from C1-6alkyl, hydroxy group, oxo group, C1-6hydroxyalkyl, C1-6alkoxy group; Q denotes CH2; Y1 denotes C1-6alkyl; Y2 denotes Y2b; where Y2b denotes C1-6alkyl, optionally substituted with one Y2b'; where Y2b' denotes a hydroxy group, n and m are equal to 0; Y4 denotes Y4c or Y4d; where Y4c denotes lower cycloalkyl, optionally substituted with halogen; and Y4d denotes an amino group, optionally substituted with one or more C1-6alkyl; where "aryl" denotes phenyl or naphthyl, "heteroaryl" denotes a monocyclic or bicyclic radical containing 5 to 9 atoms in the ring, which contains at least one aromatic ring containing 5 to 6 atoms in the ring, with one or two N or O heteroatoms, wherein the remaining atoms in the ring are carbon atoms, under the condition that the binding point of the heteroaryl radical is in the aromatic ring, "heterocycloalkyl" denotes a monovalent saturated cyclic radical consisting of one ring containing 5 to 6 atoms in the ring, with one or two ring heteroatoms selected from N, O or SO2. The invention also relates to use of the compound of formula II or a pharmaceutical composition based on the compound of formula II.

EFFECT: obtaining novel compounds that are useful for modulating Btk activity and treating diseases associated with excessive activity of Btk.

7 cl, 2 tbl, 53 ex

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