1-cyanocyclopropyl derivatives as cathepsin k inhibitors

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (I) where values of substituents are given in description, possessing inhibiting activity with respect to cathepsin K as well as to pharmaceutical compositions for treating diseases, associated with cysteine protease activity and to methods of inhibiting cathepsin K in mammals, requiring such treatment by introduction of efficient amount of compound to mammal.

EFFECT: claimed is application of formula (I) compound or its pharmaceutically acceptable salt in manufacturing medication for application in cathepsin K inhibition in a warm-blooded animal.

10 cl, 45 ex, 5 dwg

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

where a represents the qi is logicalname ring;
R represents hydrogen;
R1and R2together with the nitrogen atom to which they are attached, form a 5-7-membered monocyclic saturated heterocyclic ring which has at least one common atom with a second monocyclic saturated or unsaturated ring so as to form a bicyclic ring system;
where the bicyclic ring system has at least one common atom with the third saturated or unsaturated ring so as to form a tricyclic ring system containing up to 19 ring atoms, and
where tricyclic ring system may contain up to three heteroatoms, each of which is independently selected from the atoms O or N, and possibly replaced by alternates in the amount of up to three, each of which is independently selected from C1-6of alkyl, halogen, COOR3or or3and
tricyclic ring system may be substituted on adjacent carbon atoms by a group-O-C(R8)2-O-, where each R8represents a hydrogen atom or halogen so as to form a group of 1,3-dioxolo, and where
(1) phenyl, represents part of a tricyclic ring system may additionally substituted by substituents in the amount of up to three, each of which is independently selected from halogen, SO2R3, cyano,OR 3and C1-6of alkyl, which may substituted by substituents in the amount of up to three independently selected from NR4R5and
(2) a bicyclic heteroaryl represents part of a tricyclic ring system may additionally substituted by substituents in the amount of up to three, each of which is independently selected from halogen, SO2R3or1-6of alkyl, which may substituted by substituents in the amount of up to three independently selected from OR3and C3-7carbocycle;
R3selected from hydrogen, C1-6of alkyl, phenyl, a 4-7-membered monocyclic saturated heterocyclic ring containing up to three heteroatoms, each of which is independently selected from the atoms O or N, and where each1-6the alkyl can be substituted by groups of up to three, independently selected from halogen and NR4R5;
R4and R5independently represent a1-6alkyl;
and its pharmaceutically acceptable salts.

2. The compound according to claim 1, where R1and R2together with the nitrogen atom to which they are attached, form a 5-6-membered monocyclic saturated heterocyclic ring which has two common atom with the second saturated or unsaturated ring so as to form a bicyclic ring C is a topic which has one or two common atoms with the third saturated or unsaturated ring so as to form a tricyclic ring system containing in total up to 15 ring atoms, where the tricyclic ring system can contain up to three heteroatoms, each of which is independently selected from the atoms O or N, and may possibly be replaced by alternates in the amount of up to three, as defined in claim 1.

3. The compound according to claim 2, where the second ring is a 5 to 6 membered unsaturated ring containing one heteroatom selected from N and O, and the third ring is a 6-membered ring possibly containing one heteroatom selected from n

4. The compound according to claim 1 or its pharmaceutically acceptable salt, selected from any of:
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(8-fluoro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-2-[(8-chloro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]-N-(1-cyanocyclohexyl)cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(6-fluoro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-(1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-ylcarbonyl)cyclohexanecarboxylate;
(1R,2R)-2-[(8-bromo-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]-N-(1-cyanocyclohexyl)cyclohexanecarboxylate;
(1R2R)-N-(1-cyanocyclohexyl)-2-[(6-methyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-{[8-(trifluoromethyl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl]carbonyl}cyclohexanecarboxylic;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(8-methoxy-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(8-isopropyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(9-fluoro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(7-fluoro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(8-fluoro-5-methyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-2-[(6-bromo-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]-N-(1-cyanocyclohexyl)cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(1,3,4,5-tetrahydro-1H-pyrido [4,3-b]-7-azaindole-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-({8-[(dimethylamino)methyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}carbonyl)cyclohexanecarboxylic;
(1R,2R)-N-(1-cyanocyclohexyl)-2-{[8-(methylsulphonyl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl]carbonyl}cyclohexanecarboxylic;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(6-methoxy-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-(1H-Spiro[and chinolin-4,4'-piperidine]-2(3H)-ylcarbonyl)cyclohexanecarboxylate;
(1R,2R)-2-[(6-chloro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]-N-(1-cyanocyclohexyl)cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(6-cyano-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(9-methyl-5,7,8,9-tetrahydro-6N-pyrrolo[2,3-b:4,5-C']dipyridine-6-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(benzofuro[3,2-C]-1,2,3,4-tetrahydropyrido)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-{[6-(triptoreline)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl]carbonyl}cyclohexanecarboxylic;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(6-ethoxy-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(5-cyclopropylmethyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(5-methoxyethyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-{[6-(trifluoromethyl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl]carbonyl}cyclohexanecarboxylic;
(1R,2R)-N-(1-cyanocyclohexyl)-2-{[6-(methylsulphonyl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl]carbonyl}cyclohexanecarboxylic;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(6-hydroxy-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-(6-propoxy-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-(6-(2-(dimethylamino)ethoxy)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxylate;
(1R,2R)-N-(1-cyanocyclohexyl)-2-[(5-methanesulfonyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylate;
(1R,2R)-2-(7,8-dihydro-5H-furo[2,3-b:4,5-C']dipyridine-6-carbonyl)-cyclohexanecarboxylic acid (1-cyanocyclohexyl)amide;
(1R,2R)-2-(7-methanesulfonyl-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxylic acid(1-cyanocyclohexyl)amide;
(1R,2R)-2-(9-methanesulfonyl-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxylic acid(1-cyanocyclohexyl)amide;
(1R,2R)-N-(1-cyanocyclohexyl)-2-(2,2-debtor-7,8,9,10-tetrahydro-6N-[1,3]dioxolo[4,5-g]pyrido[4,3-b]indole-7-carbonyl) cyclohexanecarboxylic and
(1R,2R)-N-(1-cyanocyclohexyl)-2-(8-fluoro-6-methoxy-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxylic.

5. The compound according to claim 4 or pharmaceutically acceptable salt, representing the (1R,2R)-N-(1-cyanocyclohexyl)-2-[(8-fluoro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylic.

6. The compound according to claim 4 or pharmaceutically acceptable salt, representing the (1R,2R)-N-(1-cyanocyclohexyl)-2-[(6-methoxy-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxylic.

7. The compound of formula (I) according to any one of claims 1 to 6, with ingibiruet is her activity against cathepsin K.

8. Pharmaceutical composition having inhibitory activity against cathepsin K, containing an effective amount of the compounds of formula (I) according to any one of claims 1 to 6, or its pharmaceutically acceptable salt and a pharmaceutically acceptable diluent or carrier.

9. Method of inhibiting cathepsin K in a mammal in need of such treatment, comprising the introduction of a given mammal an effective amount of a compound according to any one of claims 1 to 6, or its pharmaceutically acceptable salt.

10. The use of the compounds of formula (I) according to any one of claims 1 to 6, or its pharmaceutically acceptable salts in the manufacture of a medicinal product for use in the inhibition of cathepsin K in a warm-blooded animal.



 

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11 cl; 1 tbl; 34 ex

FIELD: chemistry.

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14 cl, 2 tbl, 8 ex

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14 cl, 3 dwg, 1 tbl, 4 ex

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23 cl, 1 tbl, 57 ex

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5 cl, 17 tbl, 33 ex

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7 cl, 1 dwg, 24 ex

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9 cl, 1 tbl, 9 ex

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17 cl, 7 tbl, 16 ex

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FIELD: chemistry.

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27 cl, 1 tbl, 354 ex

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13 cl, 1 tbl

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16 cl, 479 ex

FIELD: medicine, pharmaceutics.

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12 cl, 79 ex, 2 tbl

FIELD: medicine, pharmaceutics.

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7 cl, 1 tbl, 160 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of indole with formula (I) or indole pharmaceutically acceptable salts: where: ring A stands for a benzene or a tiofen ring; R1 stands for a C1-.6 alkyl that may be substituted by one or several groups selected from among -OH, - O-C1-6 alkyl, an amino group that may be substituted by one or two C1-6 alkyls; -O-C1-6 alkyl; a halogen; CN; 5-6-membered cyclic amine; n is equal to 0 - 4 and to 0- 2 if ring A is a benzene or a tiofen ring accordingly; R2 stands for -H, -C1-6 alkyl; R3 stands for H, -C1-6 alkyl that may be substituted by phenyl, C3-6 cycloalkyl; R4 stands for C1-6 alkyl that may be substituted by one or several groups selected from among -OH, -O- C1-6 alkyl, an amino group that may be substituted by one or two C1-6 alkyls and 5-6-membered cyclic amine; C3-6 cycloalkyl, phenyl or-OH; X1 stands for -CH2-, -O-, -S-, -CH(R)-; X2 stands for -C(RA)(RB)-, -O-; X3 stands for -C(RC)(RD)-; m is equal to 1 - 3; R stands for -H, or R, together with R4, form C3-6 alkylene; RA, RB, RC and RD are identical or different and stand for -H, C1-6 alkyl where, in case m is equal to 2 or 3, each RC and R may be identical or different provided 1- methyl-4a-phenyl-2,3,4,4a,5,9b-hexahydro-1H-indeno [1,2-b] pyridine, 4a-phenyl-2,3,4,4a,5,9b-hexahydro-4aH-indeno [1,2-b] pyridine and 2-(1,2,3,4,5,9b-hexahydro-4aH-indeno [1,2-b] pyridine -4a-yl)-N,N-dimethylethanamine are excluded).

EFFECT: compounds possess antagonistic activity regarding NMDA receptor which enables their usage in pharmaceutical compositions for treatment of Alzheimer disease, vascular dementia, Parkinson disease, chronic depression, attention deficit hyperactivity disorder, migraines etc.

18 cl, 40 tbl, 84 ex

FIELD: chemistry.

SUBSTANCE: invention relates to azabenzofuranyl compounds of formula I and salts thereof, where: Z1 denotes CR1, Z2 denotes N, Z3 denotes CR3, Z4 denotes CR4, R1, R3 and R4 are independently selected from H, halogen, CN, -(CR14R15)nC(=Y)OR11, - (CR14R15)nOR11, C1-C12 alkyl; W denotes or R5 and R6 are independently selected from H or C1-C12 alkyl; X1 is selected from R11, -OR11 and -S(O)2R11; if X1 denotes R11 or -OR11 from X1 and -R5 optionally taken together with a nitrogen atom with which they are bonded form a 4-6-member saturated or unsaturated ring containing 0-2 additional heteroatoms selected from O, S, where said ring is optionally substituted with one or more groups selected from oxo, -(CR19R20)nNR16R17, -(CR19R20)nOR16, (CR19R20)nS(O)2R16 and R21; X is selected from aryl, where said aryl is optionally substituted with one or more groups selected from halogen, CN, -Si(C1-C6alkyl), -(CR19R20)nOR16, -(CR19R20)nSR16, C1-C12alkyl; R11, R12 and R13 independently denote H, C1-C12alkyl, aryl, azetidine, pyrrolidinyl, piperidinyl, tetrahydropyranyl; R14 and R15 are independently selected from H or C1-C12 alkyl; n is independently selected from 0, 1; Y independently denotes O; where each of said alkyl, alkenyl, aryl and heteroaryl from R1, R2, R3, R4, R5, R6, X1, X2, R11, R12, R13, R14 and R15 is independently and optionally substituted with one or more groups independently selected from -(CR19R20)nC(=Y')OR16, -(CR19R20)nNR16R17, -(CR19R20)nOR16, -(CR19R20)nNR16C(=Y')R17, -(CR19R20)nNR16C(=Y')OR17, - (CR19R20)nNR17SO2R16 and R21; each R16, R17 independently denotes H, C1-C12 alkyl, C2-C8alkenyl, aryl, or pyridinyl, where said alkyl, alkenyl or aryl is optionally substituted with one or more groups selected from -OH; R19 and R20 are independently selected from H, C1-C12 alkyl; R21 denotes C1-C12 alkyl, aryl, imidazolyl, pyridinyl, pyrazolyl, pyrrolidinyl, 2-oxo-pyrrolidinyl, piperidinyl, or 2,2-dimethyl-1,3-dioxolanyl; each Y' independently denotes O. The invention also relates to specific compounds, a pharmaceutical composition based on the disclosed compounds, a method of inhibiting anomalous cell growth or a method of treating hyperproliferative disorders, inflammatory diseases and other diseases.

EFFECT: novel azabenzofuranyl derivatives which can be used in treating cancer and inflammatory diseases are obtained.

23 cl, 3 tbl, 34 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae

and ,

which can be used to inhibit lipid kinase, including PI3K, and treat lipid kinase-mediated disorders. Values of radicals are given in claim 1.

EFFECT: improved properties of the compound.

11 cl, 2 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I:

or pharmaceutically acceptable salts thereof, in which Q is a divalent or trivalent radical selected from C6-10aryl and heteroaryl; where said aryl or heteroaryl in Q is optionally substituted up to 3 times with radicals independently selected from halogen, C1-6 alkyl, C1-6 alkyl substituted with halogen, C1-6 alkoxy group, C1-6 alkoxy group substituted with halogen, -C(O)R20 and -C(O)OR20; where R20 is selected from hydrogen and C1-6 alkyl; and where optionally, the carbon atom neighbouring W2 can be bonded through CR31 or O with a carbon atom of Q to form a 5-member ring condensed with A and Q rings; where R31 is selected from hydrogen and C1-6 alkyl; W1 and W2 are independently selected from CR21 and N; where R21 is selected from hydrogen and -C(O)OR25; where R25 denotes hydrogen; ring A can contain up to 2 carbon ring atoms substituted with a group selected from -C(O)-, -C(S)- and -C(=NOR30)- and can be partially unsaturated and contain up to 2 double bonds; where R30 denotes hydrogen ; L is selected from C1-6alkylene, C2-6alkenylene, -OC(O)(CH2)n-, -NR26(CH2)n- and -O(CH2)n-; where R26 is selected from hydrogen and C1-6 alkyl; where n is selected from 0, 1, 2, 3 and 4; q is selected from 0 and 1; t1, t2, t3 and t4 are each independently selected from 0, 1 and 2; R1 is selected from -X1S(O)0-2X2R6a, -X1S(O)0-2X2OR6a, -X1S(O)0-2X2C(O)R6a, -X1S(O)0-2X2C(O)OR6a, -X1S(O)0-2X2OC(O)R6a and -X1S(O)0-2NR6aR6b; where X1 is selected from a bond, O, NR7a and C1-4alkylene; where R7a is selected from hydrogen and C1-6alkyl; X2 is selected from a bond and C1-6alkylene; R6a is selected from hydrogen, cyanogroup, halogen, C1-6alkyl, C2-6alkenyl, C6-10aryl, heteroaryl, heterocycloalkyl and C3-8cycloalkyl; where said aryl, heteroaryl, cycloalkyl and heterocycloalkyl in R6a is optionally substituted with 1-3 radicals independently selected from hydroxy group, halogen, C1-6alkyl, C1-6alkyl substituted with a cyano group, C1-6alkoxy group and C6-10aryl-C1-4alkoxy group; and R6b is selected from hydrogen and C1-6alkyl; R3 is selected from hydrogen, halogen, hydroxy group, C1-6alkyl, C1-6alkyl substituted with halogen, C1-6alkyl substituted with a hydroxy group, C1-6alkoxy group, C1-6alkoxy group substituted with halogen, -C(O)R23 and -C(O)OR23; where R23 is selected from hydrogen and C1-6alkyl; R4 is selected from R8 and -C(O)OR8; where R8 is selected from C1-6alkyl, heteroaryl, C3-8cycloalkyl and heterocycloalkyl; where said heteroaryl, cycloalkyl or heterocycloalkyl in R8 is optionally substituted with 1-3 radicals independently selected from halogen, C1-6alkyl, C3-8cycloalkyl and C1-6alkyl substituted with halogen; R5 is selected from hydrogen, C1-6alkyl substituted with a hydroxy group, and a C1-6alkoxy group; heteroaryl denotes a monocyclic or condensed bicyclic aromatic ring complex containing 5-9 carbon atoms in the ring, where one or more ring members are heteroatoms selected from nitrogen, oxygen and sulphur, and heterocycloalkyl denotes a saturated monocyclic 4-6-member ring in which one or more said carbon atoms in the ring are substituted with a group selected from -O-, -S- and -NR-, where R denotes a bond, hydrogen or C1-6alkyl. The invention also relates to pharmaceutical compositions containing said compounds, and methods of using said compounds to treat or prevent diseases or disorders associated with GPR119 activity, such as obesity, type 1 diabetes, type 2 sugar diabetes, hyperlipidemia, type 1 autopathic diabetes, latent autoimmune diabetes in adults, type 2 early diabetes, child atypical diabetes, adult diabetes in children, malnutrition-associated diabetes and diabetes in pregnant women.

EFFECT: improved properties of compounds.

27 cl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae and including their stereoisomers, as well as pharmaceutically acceptable salt, where X denotes O or S; R1 is selected from H, F, CI, Br, I, CN, -CR14R15-NR16R17, -CR14R15-NHR10, -(CR14R15)NR10R11, -(CR14R15)nNR12C(=Y)R10, -(CR14R15)nNR12S(O)2R10, -(CR14R15)mOR10, -(CR14R15)nS(O)2R10, -C(OR10)R11R14, -C(R14)=CR18R19, -C(=Y)OR10, -C(=Y)NR10R11, -C(=Y)NR12OR10, -C(=O)NR12S(O)2R10, -C(=O)NR12(CR14R15)mNR10R11, -NHR12, -NR12C(=Y)R10, -S(O)2R10, -S(O)2NR10R11, C2-C12 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C4 carbocyclyl, piperidinyl, thiopyranyl, phenyl or C5-C6 heteroaryl; R2 is selected from H, C2-C12 alkyl and thiazolyl; R3 denotes a condensed bicyclic heteroaryl selected from indazole, indole, benzoimidazole, pyrrolopyridine, imidazopyridine and quinoline; R10, R11 and R12 independently denote H, C2-C12 alkyl, C3 carbocyclyl, heterocyclyl selected from pyrrolidine, morpholine and piperazine, phenyl or heteroaryl selected from pyrazole, pyridine, benzothiophene; or R10 and R11 together with a nitrogen atom with which they are bonded possibly form a saturated C3-C6 heterocyclic ring, possibly containing one additional ring atom selected from N or O, where said heterocyclic ring is possibly substituted with one or more groups independently selected from oxo, (CH2)mOR10, NR10R11, SO2R10, C(=O)R10, NR12S(O)R11, C(=Y)NR10R11, C1-C12 alkyl and heterocyclyl selected from pyrrolidine; R14 and R15 are independently selected from H or C1-C12 alkyl; R16 and R17 independently denote H or phenyl; R18 and R19 together with a carbon atom with which they are bonded form a C3-C20 heterocyclic ring, where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, phenyl, heteroaryl, piperidinyl and condensed bicyclic heteroaryl possibly substituted with one or more groups independently selected from F, CI, Br, I, CF3, -C(=Y)R10, -C(=Y)OR10, oxo, R10, -C(=Y)NR10R11, -(CR14R15)nNR10R11, -NR10R11, -NR12C(=Y)R10, -NR12C(=Y)NR10R11, -NR12SO2R10, OR10, SR10, -S(O)2R10, -S(O)2NR10R11, possibly substituted with carbocyclyl, selected from cyclopropyl, possibly substituted heterocyclyl selected from piperazine, possibly substituted with alkyl and alkylsulphonyl, pyrrolidine, morpholine, piperdine, possibly substituted CH3, phenyl and possibly substituted heteroaryl selected from imidazole and triazole; Y denotes O; m equals 0, 1 or 2; n equals 1 and t equals 2. The invention also relates to a pharmaceutical composition which modulates lipid kinase activity, based on said compounds.

EFFECT: obtaining novel compounds and a composition based on said compounds, which can be used to treat lipid kinase-mediated diseases, for example, cancer.

48 cl, 2 tbl, 372 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I:

or a pharmaceutically acceptable salt thereof, in which: one of A, B, C and D denotes N, and the rest independently denote CH and C(R1); m equals a whole number from 1 to 4; n equals a whole number from 0 to 4; R1 denotes halogen; R2 and R3 denote hydrogen; R4 is selected from H, C1-6alkyl; Ar denotes aryl, optionally substituted with one or more halogen atoms; X denotes -C(Ra)(Rb)-, where Ra and Rb denote H; Y denotes -S(O)2-. The invention also relates to a pharmaceutical composition having CRTH2 receptor antagonist properties and containing a compound of formula I, to use of a compound of formula I when producing a drug for treating or preventing CRTH2 mediated diseases and a method for antagonistic action on CRTH2 receptor in mammals.

EFFECT: novel compound, which can be useful as a CRTH2 receptor antagonist, is obtained and described.

16 cl, 6 ex, 2 tbl

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