Heteroarylbenzamide derivatives applied as glk activators in diabetes treatment

FIELD: medicine.

SUBSTANCE: invention refers to the compound 3-{[5-(azetidine-1-ylcarbonyl)pyrazine-2-yl] oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazine-5-yl)benzamide or to its pharmaceutically acceptable salt. Also, it refers to a pharmaceutical composition for treating insulin-independent diabetes or obesity containing said compound.

EFFECT: there is produced and described a new compound which can be effective in treating insulin-independent diabetes and obesity.

5 cl, 64 ex

 

The text descriptions are given in facsimile form.

1. The compound 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-{[(1S)-1-methyl-2-(metiloksi)ethyl]oxy}-N-(5-methylpyrazine-2-yl)benzamide or its pharmaceutically acceptable salt.

2. The compound according to claim 1, which represents 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-{[(1S)-1-methyl-2-(metiloksi)ethyl]oxy}-N-(5-methylpyrazine-2-yl)benzamide.

3. Pharmaceutical composition for the treatment of type 2 diabetes or obesity, containing a compound according to claim 1 or 2 together with a pharmaceutically acceptable diluent or carrier.

4. The compound according to claim 1 or 2 for use in the treatment of type 2 diabetes.

5. The compound according to claim 1 or 2 for the application of the Oia in the treatment of obesity.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to oxazolidinone derivatives of formula (I) or pharmaceutically acceptable salts thereof, synthesis method thereof and pharmaceutical compositions containing said derivatives which are used as an antibiotic. Oxazolidinone derivatives, where R1 and R1' independently denote hydrogen or fluorine; R2 denotes -OR7, fluorine, monophosphate or metal phosphate; and R7 denotes hydrogen, C1-3alkyl or an acylated amino acid group, where the amino acid is alanine, glycine, proline, proline, isoleucine, leucine, phenylalanine, β-alanine or valine; R3 denotes hydrogen, a C1-4alkyl group which is unsubstituted or substituted cyano, , -(CH2)m-OR7 (m equals 0, 1, 2, 3, 4) or a ketone group. Oxazolidinone derivatives of formula (I) have antibacterial activity against different human and animal pathogens.

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

27 cl, 4 tbl, 73 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrrolidine derivatives of general formula (1) or its pharmaceutically acceptable salts where R101 and R102 values are described by the patent claim. The compounds inhibit serotonin and/or norepinephrine and/or dopamine reabsorption thereby allowing to be used for treating depression and anxiety disorder. A method for preparing thereof is described.

EFFECT: preparation of new pyrrolidine derivatives.

10 cl, 162 tbl, 7 ex

FIELD: medicine, pharmaceutics.

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

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

8 cl, 1 tbl, 301 ex

FIELD: chemistry.

SUBSTANCE: invention describes compounds of formula I

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

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

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

19 cl, 1 tbl, 24 ex

FIELD: medicine, pharmaceutics.

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

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

19 cl, 18 tbl

FIELD: chemistry.

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

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

54 cl, 412 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to compounds of formula (I), where R1 denotes a 5- or 6-member ring of formulae

(II) or (III), respectively: R2 denotes H, C1-C7-alkyl, C3-C6-cycloalkyl or -(CH2)m,-Ra; R3 denotes aryl or heteroaryl, which can be substituted with CN, Cl, F, Br, CF3, CHF2, C3-C6-cycloalkyl or denotes heteroaryl which can be possibly substituted with C1-C7-alkyl; R4 denotes H, -OH, Cl, F, Br, CN, -CHF2, CF3, C1-C7-alkyl, C3-C6-cycloalkyl or -(CH2)m-Re; R5 denotes C1-C7-alkyl, -(CH2)n-O-Rf, or -(CH2)n-Re; Ra denotes -OH; Re denotes -OH; Rf denotes C1-C7-alkyl; m equals 1-4; n equals 2-6; and pharmaceutically acceptable salts thereof. The invention also relates to a medicinal agent containing said derivatives, use thereof in preparing medicinal agents suitable for treating diseases of the central nervous system.

EFFECT: novel compounds suitable for treating diseases of the central nervous system are obtained and described.

29 cl, 111 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel antibacterial compounds of formula (I). Compounds of formula (I) Q-NH-CO-R3, where Q stands for group of the following structure , R1 represents hydrogen, halogen, hydroxy, amino, mercapto, alkyl, heteroalkyl, alkeloxy, heteroalkyloxy, cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, cycloalkyloxy, alkylcycloalkyloxy, heterocycloalkyloxy or heteroalkylcycloalkyloxy, X1, X2, X3, X4, X5 and X6 each independently on each other represent nitrogen atom or group of formula CR2, R2 represents hydrogen, halogen or hydroxy, amino, alkyl, alkenyl, alkinyl or heteroalkyl group, R3 is selected from the following groups R5 represents group of formula -B-Y, where B represents alkylene, alkenylene, alkinylene, -NH- or heteroalkylene, and Y represents aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl or heteroalkylcycloalkyl, or their pharmaceutically acceptable salt, solvate, hydrate or pharmaceutically acceptable composition, as well as to pharmaceutical composition, which possesses antibacterial activity, based on said compounds and to their application for preparation of medication, intended for treatment of bacterial infections.

EFFECT: obtained and described are compounds, which can be useful in medicine.

9 cl, 147 ex

FIELD: chemistry.

SUBSTANCE: described are novel derivatives of genera formula (1) (where A denotes an oxygen or sulphur atom, -CH2- or -NH- group; R1 denotes C1-6alkyl group, possibly substituted ; R1A denotes a hydrogen atom or a C1-6 alkyl group; or these two radicals together with a carbon atom to which they are bonded form a cyclic C3-6 alkyl group; R2 denotes a C1-6 alkyl group or a C3-6 cycloalkyl group; R3 denotes an aryl group or a heteroaryl group, which can be substituted; R4 denotes a hydrogen atom; R5 denotes C1-6 alkyl group, aryl or heteroaryl group, which can be substituted), a pharmaceutical composition containing said derivatives and intermediate compounds. Said compounds (1) can inhibit bonding between SIP and its receptor Edg-1 (SIP1).

EFFECT: possibility of use in medicine.

18 cl, 2 tbl, 28 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to new compounds of formula (1) or its pharmaceutically acceptable salts, with properties of antagonist CXCR2 of human neutrophils receptor. In formula (1) R1 represents a group selected from C1-8alkyl; where this group is possibly substituted with 1 substituent, independently selected from phenyl or 5-6-unit heteroaryl, containing 1-2 heteroatoms selected from N, S; where phenyl and heteroaryl are possibly substituted by 1, 2 or 3 substitutors, independently selected from halogeno, cyano, -OR4, -COOR7, -SO2R10, C1-6alkyl; X represents -CH2-, oxygen, sulfur; R2 represents C3-7carbocyclil, possibly substituted with 1, 2 or 3 substituents, independently selected from -OR4; or R2 represents 5-unit ring, containing 2 heteroatoms, selected from O, -NR8, and where this ring is possibly substituted with 1 substituent, independently selected from C1-3alkyl; or R2 represents group, selected from C1-8alkyla, where this group is substituted with 1, 2 or 3 substituents, independently selected from hydroxy, amino, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino, N-C1-6alkylcarbamoyl, N,N-di(C1-6alkyl)carbamoyl, carboxy, -NR8COR9 and -CONR5R6; R3 represents group -NR5R6, or R3 represents phenyl, possibly condensed with 6-unit heterocyclil, containing nitrogen, naphthyl, 4-8-unit monocyclic heterocyclil, containing 1-3 heteroatoms, selected from N, O, S, possibly condensed with benzole ring or 3-unit nitrogen-containing ring, where heteroring may be non-saturated, partially or fully saturated, and one or more than one circular atom of carbon may form carbonyl group, and where each phenyl or heterocyclil group is possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, cyano, phenyl, 5-6-unit heteroaryl, containing 1-2 atoms of nitrogen, -OR4, -NR5R6, -CONR5R6, -COR7, -COR20, -COOR7, -NR8COR9, -SO2R10, -SO2NR5R6 or C1-6alkyl [possibly additionally substituted with 1, 2 or 3 substituents, independently selected from halogeno, cyano, -OR20, -COOR20, -NR18R19, -CONR18R19, phenyl or 5-6-unit of monocyclic heteroaryl, containing 1-2 heteroatoms O, N, S, or 10-unit bicyclic heteroaryl, containing 1 heteroatom O, where heteroring may be partially or fully saturated, and where each phenyl or heteroaryl is group possibly substituted with 1 or 2 substituents, independently selected from halogeno, cyano, nitro, -OR20, -NR5R6, -COOR7, -NR8COR9, 6-unit heterocyclil, containing two heteroatoms, selected from O and N, 5-unit heteroaryl, containing 3 heteroatoms N, C1-6alkyl (possibly additionally substituted with 1 substituent, independently selected from halogeno, cyano, nitro, -OR20, -COOR20; or R3 represents group, selected from C3-7carbocyclil, C1-8alkyl, where this group is possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4, -NR5R6; R4 represents hydrogen; R5 and R6 independently represent hydrogen or group, selected from C1-6alkyl and monocyclic 6-unit saturated heterocyclil containing 1 heteroatom N; where C1-6alkyl is possibly substituted with 1 substituent, independently selected from -NR15R16; or R5 and R6 together with atom of nitrogen, to which they are linked, form 4-7-unit saturated heterocyclic circukar system, possibly containing additional heteroatom, selected from oxygen, -SO(n)- (where n equals 0, 1 or 2) and atoms of nitrogen; R10 represents hydrogen or group, selected from C1-6alkyl; and each of R7, R8, R9, R15, R16, R17 independently represents hydrogen, C1-6alkyl; R18, R19 and R20 represent hydrogen or group, selected from C1-6alkyl, where this group is possibly substituted with 1 substituent, independently selected from -NR8R9, -CONR8R9.

EFFECT: production of new compounds, which may find application in production of medicinal agent for use in treatment of diseases and disorders mediated with chemokines, such as asthma, allergic rhinitis, chronic obstructive pulmonary disease, inflammatory intestine disease, irritable colon syndrome, osteoarthritis, osteoporosis, rheumatoid arthritis or psoriasis, and also for treatment of cancer.

12 cl, 155 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I) , where the dotted line is either absent or denotes a double bond; R1 denotes H or C1-6-alkyl, possibly substituted with a CN group, or denotes a phenyl or sulphonyl phenyl, substituted with one or more B groups, or denotes -(CH2)m-Ra, where Ra denotes: NRiRii, C3-6-cycloalkyl, 6-member heterocycloalkyl, which denotes a univalent saturated group which contains one nitrogen heteroatom, the rest are carbon atoms, aryl, which can be substituted with one or more B groups, or denotes -(CH2)n-(CO)-Rb or -(CH2)n-(SO2)-Rb, where Rb denotes: NRiRii, 5-6-member heterocycloalkyl, which denotes a univalent saturated group containing one or more heteroatoms selected from nitrogen, oxygen, the rest are carbon atoms, aryl or 5- or 6-member heteroaryl, which denotes an aromatic ring containing two heteroatoms as ring members, the said heteroatoms selected from N or O, the rest are carbon atoms; which can possibly be substituted with one or more B groups, R2 denotes one or more H, halo, C1-6-alkyl, C1-6-alkoxy, R3 denotes H or-(CO)-Rc, where Rc denotes: C1-6-alkyl, 5-member heterocycloalkyl, which denotes a univalent saturated group containing one nitrogen heteroatom, the rest are carbon atoms possibly substituted with C1-6-alkyl, or denotes C1-6-alkyl; R4 denotes H; R5 denotes H, C1-6-alkyl, -(CH2)m-NRiRii, -(CH2)n-(CO)-Rb, where Rb denotes NRiRii or a 6-member heterocycloalkyl which denotes a univalent saturated group which contains one nitrogen heteroatom, the rest are carbon atoms, when the dotted line is absent or is absent when the dotted line denotes a double bond; R6 is absent, when the dotted line denotes a double bond; R7 denotes Cl or NReRf, where Re and Rf denotes H or C1-6-alkyl, or Re and Rf together with the nitrogen atom to which they are bonded form a 6-member heterocycloalkyl which denotes a univalent saturated group containing one or two heteroatoms selected from nitrogen, oxygen, the rest are carbon atoms; which can be substituted with C1-6-alkyl, or R6 and R7 together form a C=O group, when the dotted line is absent; B denotes halogen, C1-6-alkoxy, (CRiiiRiv)n-phenyl; Ri and Rii denote H, C1-6-alkyl -C(O)-C1-6-alkyl; Riii and Riv denote C1-6-alkyl; m equals to 1 or 2, n equals 0 or 1; as well as to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition, as well as to use of compounds of formula (I), (I-a) or (1-b).

EFFECT: obtaining novel biologically active compounds having activity on V1a receptor.

12 cl, 48 ex

FIELD: chemistry.

SUBSTANCE: invention relates to oxazolidinone derivatives of formula (I) or pharmaceutically acceptable salts thereof, synthesis method thereof and pharmaceutical compositions containing said derivatives which are used as an antibiotic. Oxazolidinone derivatives, where R1 and R1' independently denote hydrogen or fluorine; R2 denotes -OR7, fluorine, monophosphate or metal phosphate; and R7 denotes hydrogen, C1-3alkyl or an acylated amino acid group, where the amino acid is alanine, glycine, proline, proline, isoleucine, leucine, phenylalanine, β-alanine or valine; R3 denotes hydrogen, a C1-4alkyl group which is unsubstituted or substituted cyano, , -(CH2)m-OR7 (m equals 0, 1, 2, 3, 4) or a ketone group. Oxazolidinone derivatives of formula (I) have antibacterial activity against different human and animal pathogens.

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

27 cl, 4 tbl, 73 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrrolidine derivatives of general formula (1) or its pharmaceutically acceptable salts where R101 and R102 values are described by the patent claim. The compounds inhibit serotonin and/or norepinephrine and/or dopamine reabsorption thereby allowing to be used for treating depression and anxiety disorder. A method for preparing thereof is described.

EFFECT: preparation of new pyrrolidine derivatives.

10 cl, 162 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula: or to its pharmaceutically acceptable salt, where: Ar2 represents phenyl or pyridyl, each of which is substituted by 0-4 substituents, independently selected from R2; X and Z represent N; Y represents CRX; D represents N; F represents N, CH or carbon, substituted by substituent, representing R1 or R10; Rx in each case is independently selected from hydrogen, halogen, C1-C4alkyl, amino, cyano and mono- or di-(C1-C4alkyl)amino; R1 represents 0-3 substituents, independently selected from: (a) halogen, cyano and nitro; (b) groups of formula -Q-M-Ry; R10 represents one substituent, selected from: (a) groups of formula -Q-M-Ry; so that R10 is not hydroxy, amino or unsubstituted group, selected from C1-C6alkyl, C2-C6alkenyl, C2-C6alkinyl, C1-C6aloxy, C2-C6alkyl, ether, C2-C6alkanoyl, C3-C6alcanone, C1-C6halogenalkyl, C1-C6halogenoalkoxy, mono- or di-(C1-C6alkyl)amino, C1-C6alkylsulfonyl, mono- or di-(C1-C6alkyl)aminosulfonyl or mono- or di-(C1-C6alkyl)aminocarbonyl; each Q is independently selected from C0-C4alkylene; each M is independently absent or is selected from O, C(=O), OC(=O), C(=O)O, S(O)m, N(RZ), C(=O)N(Rz), C(=NH)N(Rz), N(Rz)C(=O), N(Rz)C(=NH), N(Rz)S(O)m, S(O)mN(Rz) and N[S(O)mRz]S(O)m, where m equals 2; and Rz in each case is independently selected from hydrogen, C1-C8alkyl and groups, which taken together with Ry, form possibly substituted (4-7)-member heterocycle; and each Ry independently represents hydrogen, C1-C8halogenalkyl, C1-C8alkyl, C2-C8alkenyl, (C3-C8carbocycle)C0-C4alkyl, ((4-7)-member heterocycle)C0-C4alkyl or taken together with Rz forms (4-7) member heterocycle, where each alkyl, carbocycle and heterocycle is substituted by 0-4 substituents, independently selected from hydroxy, halogen, amino, cyano, nitro, -COOH, aminocarbonyl, aminosulfonyl, C1-C6alkyl, C3-C7cecloalkyl, C2-C6alkyl ether, C1-C6alkanoyl, C1-C6alkylsulfonyl, C1-C8alkoxy, C1-C8hydroxyalkyl, mono- and di-(C1-C6alkyl)aminocarbonyl, mono- and di-(C1-C6alkyl)aminosulfonyl, mono- and di-(C1-C6alkyl)amino, C1-C6alkanoylamino and phenyl; so that Ry is not hydrogen, if Q represents C0alkyl and M is absent; each R2: (a) is independently selected from (1) hydroxyl, amino, cyano, halogen, -COOH, nitro and (2) C1-C6alkyl, (C3-C8cycloalkyl)C0-C4alkyl, C1-C6halogenalkyl; R3 is selected from: (1) hydrogen; (2) C1-C6alkyl and (C3-C8cycloalkyl)C0-C2alkyl; and (3) groups of formula: where L represents C0-C6alkylene; R5 and R6: (a) are independently selected from C1-C12alkyl, (C3-C8cycloalkyl)C0-C4alkyl; or (b) are combined with formation of (4-6)-member heterocycle, containing one or two heteroatoms independently selected from O and N; and where each of (2) and (3) is substituted by 0-4 substituents, independently selected from: C1-C6alkyl and (C3-C8cycloalkyl)C0-C2alkyl, each of which is substituted by 0-4 secondary substituents, independently selected from hydroxy, C1-C4alkyl and C1-C4alkoxy; and R4 represents 0-2 substituents, independently selected from C1-C3alkyl.

EFFECT: claimed are pharmaceutical compositions for modulation of capsaicin receptor activity and methods of applying said compounds for treatment of such disorders as pain, itch, cough, hiccup, urinary incontinence or obesity.

65 cl, 1 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a sodium salt N-(4-chloro-3-methyl-5-isoxazolyl)-2-[2-methyl-4,5-(methylenedioxy)phenylacetyl]thiophene-3-sulfonamide in form of a polymorph, characterised by peaks on an x-ray powder diffraction (XRD) pattern at approximately 22.38 and 23.38 degrees 2-theta. The invention also relates to methods of producing said polymorph and to a pharmaceutical composition based on said polymorph, having endothelin antagonist activity.

EFFECT: polymorphous form is more stable and can be used in medicine to treat pulmonary hypertension.

17 cl, 9 tbl, 31 dwg, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to thiophene derivatives of formula (I):

where A denotes -CONH-CH2-, -CO-CH=CH-, -CO-CH2CH2-, -CO-CH2-O-, -CO-CH2-NH-, or ; R1 denotes hydrogen, C1-5-alkyl or C1-5-alkoxy; R2 denotes hydrogen, C1-2-alkyl, C1-5-alkoxy, trifluoromethyl or halogen, R3, R31, R32, R33, R34, R4, R5, R6, R7, k, m, n are described in claim 1. The invention also relates to a pharmaceutical composition for preventing or treating diseases and disorders associated with an activated immune system, based on said compounds and to use thereof as therapeutically active compounds for preventing or treating diseases or disorders such as graft rejection, graft versus host reaction and autoimmune syndromes.

EFFECT: improved properties of the compound.

27 cl, 2 tbl, 525 ex

FIELD: chemistry.

SUBSTANCE: disclosed compounds can be used as a medicinal agent which modulates PPARδ (peroxisome proliferator-activated receptor δ). In formula I

, p is equal to 1; L2 is selected from a group which includes -XOX- and -XSX-, where X is independently selected from a group which includes a bond and C1-C4alkylene; R13 is selected from a group which includes halogen, C1-C6alkyl; R14 is selected from a group which includes -XOXC(O)OR17 and -XC(O)OR17, where X denotes a bond or C1-C4alkylene and R17 denotes hydrogen; R15 and R16 are independently selected from a group which includes -R18 and -YR18, where Y is selected from a group which includes C2-C6alkenylene, and R18 is selected from a group which includes C6-C10aryl, pyridinyl, pyrimidinyl, quinolinyl, benzo[b]furanyl, benzoxazolyl, 1,5-benzodioxanyl, 1,4-benzodioxanyl and 3,4-dihydro-2H-benzo[b][1,4]dioxepin; where any of phenyl, pyridinyl, pyrimidinyl, benzoxazolyl in R18 is independently substituted with 1-2 radicals, independently selected from a group which includes halogen, C1-C6alkyl, C2-C7alkenyl, C1-C6alkoxy group, halogen-substituted C1-C6alkyl, halogen-substituted C1-C6alkoxy group, C3-C12cycloalkyl, phenyl, morpholinyl, pyrrolidinyl, piperidinyl, -XNR17R17, -XC(O)NR17R17, -XC(O)R19 and -XOXR19, where X denotes a bond or C1-C4alkylene; R17 is selected from a group which includes C1-C6alkyl, and R19 is selected from a group which includes C3-C12cycloalkyl, piperidinyl and phenyl. The invention also relates to use of the disclosed compounds to prepare a medicinal agent which modulates PPARδ activity, a pharmaceutical composition having PPARδ activity modulating properties, which contains a therapeutically effective amount of the disclosed compound and to use of the pharmaceutical composition in preparing a medicinal agent which modulates PPARδ activity.

EFFECT: improved properties of compounds.

10 cl, 1 tbl, 69 ex

FIELD: medicine, pharmaceutics.

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

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

19 cl, 18 tbl

Organic compounds // 2411239

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I, in which R1 denotes alkyl or cycloalkyl; R2 denotes phenyl-C1-C7-alkyl, di-(phenyl)- C1-C7-alkyl, naphthyl- C1-C7-alkyl, phenyl, naphthyl, pyridyl-C1-C7-alkyl, indolyl- C1-C7-alkyl, 1H-indazolyl- C1-C7-alkyl, quinolyl C1-C7-alkyl, isoquinolyl- C1-C7-alkyl, 1,2,3,4-tetrahydro-1,4-benzoxazinyl- C1-C7-alkyl, 2H-1,4-benzoxazin-3(4H)-onyl-C1-C7-alkyl, 9-xanthenyl-C1-C7-alkyl, 1-benzothiophenyl-C1-C7-alkyl, pyridyl, indolyl, 1H-indazolyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydro-1,4-benzoxazonyl, 2H-1,4-benzoxazin-3(4H)-onyl, 9-xanthenyl, 1-benzothiophenyl, 4H-benzo[1,4]thiazin-3-only, 3,4-dihydro-1H-quinolin-2-onyl or 3H-benzoxazol-2-onyl, where each phenyl, naphthyl, pyridyl, indolyl, 1H-indazolyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydro-1,4-benzoxazonyl, 2H-1,4-benzoxazin-3(4H)-onyl, 1-benzothiophenyl, 4H-benzo[1,4]thiazin-3-only, 3,4-dihydro-1H-quinolin-2-onyl or 3H-benzoxazol-2-onyl are unsubstituted or contain one or up to 3 substitutes independently selected from a group comprising C1-C7-alkyl, hydroxy-C1-C7-alkyl, C1-C7-alkoxy- C1-C7-alkyl, C1-C7-alkoxy- C1-C7-alkoxy-C1-C7-alkoxy- C1-C7-alkyl, C1-C7-alkanoyloxy- C1-C7-alkyl, amino- C1-C7-alkyl, C1-C7-alkoxy- C1-C7-alkylamino- C1-C7-alkyl, C1-C7-alkanoylamino- C1-C7-alkyl, C1-C7-alkylsulphonylamino- C1-C7-alkyl, carboxy- C1-C7-alkyl, C1-C7-alkoxycarbonyl- C1-C7-alkyl, halogen, hydroxy group, C1-C7-alkoxy group, C1-C7-alkoxy- C1-C7-alkoxy group, amino- C1-C7-alkoxy group, N-C1-C7-alkanoylamino-C1-C7-alkoxy group, carbamoyl- C1-C7-alkoxy group, N-C1-C7-alkylcarbamoyl-C1-C7-alkoxy group, C1-C7-alkanoyl, C1-C7-alkoxy-C1-C7-alkanoyl, C1-C7-alkoxy- C1-C7-alkanoyl, carboxyl, carbamoyl and N-C1-C7-alkoxy-C1-C7-alkylcarbamoyl; W denotes a fragment selected from residues of formulae IA, IB and IC, where () indicates the position in which the fragment W is bonded to the carbon atom in position 4 of the piperidine ring in formula I, and where X1, X2, X3, X4 and X5 are independently selected from a group containing carbon and oxygen, where X4 in formula IB and X1 in formula IC can assume one of these values or can be additionally selected from a group comprising S and O, where carbon and nitrogen ring atoms can include a number of hydrogen atoms or substitutes R3 or R4 if contained, taking into account limitations given below, required to bring the number of bonds of the carbon ring atom to 4 and 3 for the nitrogen ring atom; provided that in formula IA at least 2, preferably at least 3 of the atoms X1-X5 denote carbon and in formulae IB and IC at least one of X1-X4 denotes carbon, preferably 2 of the atoms X1-X4 denote carbon; y equals 0 or 1; z equals 0 or 1; R3, which can be bonded with any of the atoms X1, X2, X3 and X4, denotes hydrogen or a C1-C7-alkyloxy-C1-C7-alkyloxy group, phenyloxy-C1-C7-alkyl, phenyl, pyridinyl, phenyl- C1-C7-alkoxy group, phenyloxy group, phenyloxy-C1-C7-alkoxy group, pyridyl-C1-C7-alkoxy group, tetrahydropyranyloxy group, 2H,3H-1,4-benzodioxynyl-C1-C7-alkoxy group, phenylaminocarbonyl or phenylcarbonylamino group, where each phenyl or pyridyl is unsubstituted or contains one or up to 3 substitutes, preferably 1 or 2 substitutes independently selected from a group comprising C1-C7-alkyl, hydroxy group, C1-C7-alkoxy group, phenyl-C1-C7-alkoxy group, where phenyl is unsubstituted or substituted with a C1-C7-alkoxy group and/or halogen; carboxy- C1-C7-alkyloxy group, N-mono- or N,N-di-(C1-C7-alkyl)aminocarbonyl-C1-C7-alkyloxy group, halogen, amino group, N-mono- or N,N-di-(C1-C7-alkyl)amino group, C1-C7-alkanoylamino group, morpholino-C1-C7-alkoxy group, thiomorpholino-C1-C7-alkoxy group, pyridyl-C1-C7-alkoxy group, pyrazolyl, 4- C1-C7-alkylpiperidin-1-yl, tetrazolyl, carboxyl, N-mono- or N,N-di-(C1-C7-alkylamino)carbonyl or cyano group; or denotes 2-oxo-3-phenyltetrahydropyrazolidin-1-yl, oxetidin-3-yl-C1-C7-alkyloxy group, 3-C1-C7-alkyloxetidin-3-yl- C1-C7-alkyloxy group or 2-oxotetrahydrofuran-4-yl- C1-C7-alkyloxy group; provided that if R3 denotes hydrogen, then y and z are equal to 0; R4, if contained, denotes a hydroxy group, halogen or C1-C7-alkoxy group; T denotes carbonyl; and R11 denotes hydrogen, or pharmaceutically acceptable salts thereof. The invention also relates to use of formula I compounds, a pharmaceutical composition, as well as a method of treating diseases.

EFFECT: obtaining novel biologically active compounds having activity towards rennin.

11 cl, 338 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: described are novel derivatives of genera formula (1) (where A denotes an oxygen or sulphur atom, -CH2- or -NH- group; R1 denotes C1-6alkyl group, possibly substituted ; R1A denotes a hydrogen atom or a C1-6 alkyl group; or these two radicals together with a carbon atom to which they are bonded form a cyclic C3-6 alkyl group; R2 denotes a C1-6 alkyl group or a C3-6 cycloalkyl group; R3 denotes an aryl group or a heteroaryl group, which can be substituted; R4 denotes a hydrogen atom; R5 denotes C1-6 alkyl group, aryl or heteroaryl group, which can be substituted), a pharmaceutical composition containing said derivatives and intermediate compounds. Said compounds (1) can inhibit bonding between SIP and its receptor Edg-1 (SIP1).

EFFECT: possibility of use in medicine.

18 cl, 2 tbl, 28 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to administration of formula (I) described new triazole derivatives as greline-like ligands of growth hormone secretion stimulating receptors (GHSS receptors) that can be effective in treatment or prevention of GHSS receptors mediated physiological and/or pathophysiological conditions in mammals, preferentially in humans. Formula (I): where R1 is chosen from a group including hydrogen atom, (C1-C12)alkyl phenyl, naphthyl, (C5-C14)phenyl(C1-C12)alkyl, indolylalkyl which can contain up to 3 substitutes independently chosen from a group including halogen, -F, -CI, -Br, -I, -NO2, (C1-C12)alkyl, phenyl, naphthyl, -O-(C1-C12)alkyl; R2 is chosen from a group including (C1-C12)alkyl, phenyl, naphthyl, (C5-C14)phenyl (C1-C12)alkyl, indolylalkyl which can contain up to 3 substitutes independently chosen from a group including halogen, -F, -Cl, -Br, -I, -NO2, (C1-C12)alkyl, phenyl, naphthyl, -O-(C1-C12)alkyl; one of radicals R3 and R4 represents hydrogen atom, and other radical are chosen from a group including hydrogen atom, phenyl, naphthyl, indolylalkyl; R5 is chosen from a group including hydrogen atom, phenyl, naphthyl, -CO-(C3-C8)cycloalkyl, -CO-phenyl, -CO-(C5-C7)heteroaryl containing 1, 2 nitrogen atoms, -CO-(C3-C7)heteroaryl(C1-C4)alkyl containing 1, 2 nitrogen atoms, -CO-(C5-C6)heterocyclyl containing 1, 2 nitrogen or oxygen atoms, -CO-C*(R9R10)-NH2, -CO-CH2-C*(R9R10)-NH2, -CO-C*(R9R10)-CH2-NH2, phenylsulfonyl which can contain up to 3 substitutes independently chosen from a group including halogen, -F, -CI, -Br, -I, -N3, -CN, -NR7R8, -OH, -NO2, (C1-C4)alkyl; R6 represents hydrogen atom; R7 and R8 represent hydrogen atom; R9 and R10 are independently chosen from a group including hydrogen atom and (C1-C4)alkyl; m relates to 0, 1 or 2, and preferentially 0; and * means carbon atom in a R or S configurations, if it is chiralene.

EFFECT: invention refers to GHSS receptors antagonists and agonists which can be used for modulation of these receptors and are effective in treatment of said conditions, particularly growth impairment, cachexia, short-term, intermediate and/or long-term energy balance control; short-term, intermediate and/or long-term food intake control (stimulation and/or suppression); adipogenesis, adiposity and/or obesity; body weight growth and/or reduction in mammals.

22 cl, 6 tbl, 15 ex, 46 dwg

Up!