Substituted arylimidazolones and triazolones as vasopressin receptor inhibitors

FIELD: chemistry.

SUBSTANCE: described are novel 1,2,4-triazolones of general formula (I):

, where A denotes N and values of other radicals are given in the claim, which are vasopressin receptor inhibitors, synthesis method thereof and use thereof to prepare medicinal agents for treating and/or preventing diseases, particularly for treating and/or preventing cardiovascular diseases.

EFFECT: high efficiency of using said derivatives.

6 cl, 512 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

in which a represents a N,
R1is a (C1-C6)-alkyl, which may be from one to two times substituted, identically or differently, the remnants of a number of fluorine, oxo, trifluoromethyl, (C3-C6-cycloalkyl, phenyl, -OR10, -C(=O)-OR13and-C(=O)-NR14R15where
(i) (C3-C6-cycloalkyl may be substituted up to two times, identically or differently, (C1-C4)-alkyl, hydroxy and/or (C1-C4)-alkoxy,
(ii) phenyl may be substituted up to two times, identically or differently, remnants of izrada fluorine, chlorine, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxymethyl, (C1-C4)-alkoxy, hydroxycarbonyl, triptoreline, (C1-C4-alkoxycarbonyl, aminocarbonyl, mono-(C1-C4-alkylaminocarbonyl and di-(C1-C4-alkylaminocarbonyl, and
(iii) R10, R13, R14and R15at each occurrence independently of one another denote hydrogen, (C1-C4)-alkyl or (C3-C6-cycloalkyl, and (C1-C4)-alkyl in its turn can be substituted up to two times, identically or differently, with hydroxy, (C1-C4)-alkoxy, hydroxycarbonyl and/or (C1-C4-alkoxycarbonyl and
(C3-C6-cycloalkyl, in turn, can be substituted up to two times, identically or differently, (C1-C4)-alkyl, hydroxy and/or (C1-C4)-alkoxy,
or
R1is a (C2-C6)-alkenyl, which can be substituted by hydroxycarbonyl or (C1-C4-alkoxycarbonyl, or
(C3-C6-cycloalkyl, which can be substituted up to two times, identically or differently, (C1-C4)-alkyl, (C1-C4)-alkoxy and/or hydroxy;
R2represents phenyl or thienyl, which can be substituted one to two times, identically or differently, remnants from the range fluorine, chlorine is, bromine, (C1-C4)-alkyl, trifluoromethyl, (C1-C4)-alkoxy, triptoreline;
L1represents a group of formula CR5AR5B-where
R5Aand R5Bindependently of one another denote hydrogen or methyl;
L2represents a group of formula *-CR6AR6B-(CR7AR7B)q-where
* means the place of connection with the N-atom of amide group;
q means the number 0 or 1,
R6Ameans hydrogen or methyl,
R6Bmeans hydrogen, methyl, trifluoromethyl or a residue of formula-C(=O)-OR16or-C(=O)-NR17R18where
R16, R17and R18independently of one another represent hydrogen, (C1-C4)-alkyl or (C3-C6-cycloalkyl, or
R17and R18together with the nitrogen atom to which they are attached, form a 4-6-membered heterocycle, which can contain an O atom as one heteroatom,
or
R6Aand R6Bconnected to each other and together form -(CH2)r-the bridge, where
r means the number 2, 3, 4 or 5,
and CH2group of the bridge can be replaced by-O-;
R7Ameans hydrogen, fluorine or methyl;
R7Bmeans hydrogen, fluorine, methyl or a residue of formula-C(=O)-OR23or-C(=O)-NR24R25where
R23, R24and R25independently from each other represent odor is d, (C1-C4)-alkyl or (C3-C6-cycloalkyl,
or
R24and R25together with the nitrogen atom to which they are attached, form a 4-6-membered heterocycle, which can contain an O atom as one heteroatom,
or
R7Aand R7Btogether form oxoprop,
or
R7Aand R7Bconnected to each other and together form -(CH2)s-bridge,
where s means the number 2, 3, 4 or 5,
and CH2group of the bridge can be replaced by-O-,
or
L2represents a group of the formula

where * means the place of connection with the N-atom of the amide group,
x means the number 1, 2, 3,or 4
and CH2group rings may be replaced by-O-,
and
R6Band R7Bin each case have the above values;
and
R3represents phenyl, naphthyl, pyridyl, chinoline or ethenolysis, which may be one or two times substituted, identically or differently, the remainder of the series fluorine, chlorine, cyano, (C1-C4)-alkyl, trifluoromethyl, (C1-C4)-alkoxy, triptoreline, (C1-C4)-alkylthio and phenyl,
and last named phenyl residue may be substituted up to two times, identically or differently, by fluorine, chlorine, cyano, (C1-C4)-alkyl, (C1-C4)-alkoxy, trifluoromethyl and/or triptorelin and,
as well as its pharmaceutically acceptable salt.

2. The compound of formula (I) according to claim 1, in which
And is represented by N,
R1is a (C1-C6)-alkyl, which may be one or two times substituted, identically or differently, a remnant of the number of fluorine, oxo, hydroxy, (C1-C4)-alkoxy, trifluoromethyl, (C3-C6-cycloalkyl and phenyl,
and phenyl, in turn, can be substituted up to two times,
identically or differently, the remainder of the series fluorine, chlorine, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxymethyl, (C1-C4)-alkoxy, triptoreline, hydroxycarbonyl, aminocarbonyl and di-(C1-C4-alkylaminocarbonyl,
or
R1is a (C2-C4)-alkenyl or (C3-C6-cycloalkyl;
R2represents phenyl or thienyl, which may be one or two times substituted, identically or differently, the remainder of the series fluorine, chlorine, bromine, (C1-C4)-alkyl and (C1-C4)-alkoxy;
L1represents-CH2- or-CH(CH3)-;
L2represents a group of formula *-CR6AR6B-(CR7AR7B)q-where
* means the place of connection with the N-atom of the amide group,
q means the number 0 or 1,
R6Ameans hydrogen or methyl,
R6Bmeans hydrogen, methyl, trifluoromethyl or OST is OK formula-C(=O)-NR 17R18where R17and R18independently of one another represent hydrogen, (C1-C4)-alkyl or (C3-C6-cycloalkyl,
or
R17and R18together with the nitrogen atom to which they are attached, form a 4-6-membered heterocycle, which can contain an O atom as one heteroatom,
or
R6Aand R6Bconnected to each other and together form -(CH2)r-bridge,
where r means the number 2, 3, 4 or 5
and CH2group of the bridge can be replaced by-O-,
R7Ameans hydrogen, fluorine or methyl,
R7Bmeans hydrogen, fluorine, methyl or a residue of formula-C(=O)-OR23or-C(=O)-NR24R25where
R23, R24and R25independently of one another represent hydrogen or (C1-C4)-alkyl,
or
R24and R25together with the nitrogen atom to which they are attached, form a 4-6-membered heterocycle, which can contain an O atom as one heteroatom,
or
R7Aand R7Btogether form oxoprop,
or
R7Aand R7Bconnected to each other and together form -(CH2)s-bridge,
where s means the number 2, 3, 4 or 5,
and CH2group of the bridge can be replaced by-O-,
or
L2represents a group of the formula

where * means the place of connection with the N-atom of the amide is Oh group,
x means the number 1, 2, 3,or 4
and
R6Band R7Bin each case have the above values,
and
R3represents phenyl or pyridyl, which may be one or two times substituted, identically or differently, the remainder of the series fluorine, chlorine, (C1-C4)-alkyl, trifluoromethyl, (C1-C4)-alkoxy, triptoreline, or represents naphthyl,
as well as its pharmaceutically acceptable salt.

3. The compound of formula (I) according to claim 1, in which
And is represented by N,
R1is a (C1-C6)-alkyl, which may be one or two times substituted, identically or differently, a remnant of the number of fluorine, oxo, hydroxy, methoxy, ethoxy, trifluoromethyl, cyclopropyl and phenyl,
and phenyl, in turn, can be substituted up to two times, identically or differently, the remainder of the series fluorine, chlorine, cyano, methyl, hydroxymethyl, methoxy, hydroxycarbonyl, aminocarbonyl and dimethylaminoethyl,
or
R1represents vinyl, allyl or cyclopropyl,
R2represents phenyl or thienyl that one or two times can be substituted, identically or differently, the remainder of the series fluorine, chlorine, methyl and methoxy,
L1represents-CH2-,
L2represents a group of formula *-CR6AR6B-(CR7AR7B)q-where
* means the place of connection with the N-and the Ohm amide group,
q means the number 0 or 1,
R6Ameans hydrogen or methyl,
R6Bmeans hydrogen, methyl, trifluoromethyl or a residue of formula-C(=O)-NR17R18where R17and R18independently of one another represent hydrogen, methyl, ethyl or cyclopropyl,
or
R17and R18together with the nitrogen atom to which they are bound, form azetidinone, pyrolidine, piperidine and morpholine ring,
or
R6Aand R6Bconnected to each other and together with the carbon atom to which they are attached, form a group of the formula
or
R7Ameans hydrogen, fluorine or methyl,
R7Bmeans hydrogen, fluorine, methyl or a residue of formula-C(=O)-OR23or-C(=O)-NR24R25where
R23, R24and R25independently of one another represent hydrogen, methyl or ethyl,
or
R24and R25together with the nitrogen atom to which they are bound, form azetidinone, pyrolidine, piperidine or morpholine ring,
or
R7Aand R7Btogether form oxoprop,
or
R7Aand R7Bconnected to each other and together form -(CH2)s-bridge,
where s means the number 2, 3, 4 or 5,
and CH2group of the bridge can be replaced by-O-,
or
L2represents a group of the formula

and,
R3represents phenyl, which may be one or two times substituted, identically or differently, by fluorine, chlorine, trifluoromethyl and/or triptoreline, or represents 1-naphthyl,
as well as its pharmaceutically acceptable salt.

4. The compound of formula (I) according to one of claims 1 to 3, in which
And is represented by N,
R1is a (C1-C4)-alkyl, 2-methoxyethyl, cyclopropyl, cyclohexylmethyl, benzyl or 1-phenethyl,
moreover, the phenyl ring in the said benzyl and 1-fenetylline residues may be substituted by fluorine, chlorine, stands, trifluoromethyl, methoxy or triptoreline,
R2represents phenyl or thienyl, which may be one or two times substituted, identically or differently, by fluorine, chlorine, bromine, stands and/or methoxy,
L1represents-CH2-,
L2represents-CH2-, -CH(CH3)- or-C(CH3)2-,
and
R3represents phenyl, which may be one or two times substituted, identically or differently, by fluorine, chlorine, trifluoromethyl and/or triptoreline, or is 1-naphthyl,
as well as its pharmaceutically acceptable salt.

5. The method of preparation of compounds of formula (I), as defined in claims 1 to 4, characterized in that the compound of formula (II)

in which A, L1, R1R 2in each case, are specified in claims 1 and 2 values,
subject of combination reaction in an inert solvent with activated carboxylic acid with the compound of the formula (III)

in which L2and R3are specified in claims 1 and 2 values,
and the resulting compound of formula (I), if necessary, with the appropriate (i) solvents and/or (ii) bases or acids is converted into its pharmaceutically acceptable salt.

6. The use of the compounds of formula (I), as defined in claims 1 and 2, for preparing a medicinal product for the treatment and/or prevention of acute and chronic heart failure, giperwolemicescoy and euvolemic hyponatremia, liver cirrhosis, ascites, edema, and syndrome of inappropriate secretion of antidiuretic hormone (SIADH).



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel phenyl-pyrimidinyl-amino derivatives of formula (I), as well as agriculturally acceptable salts thereof, having fungicidal activity, a composition and a method of controlling phytopathogenic fungi of agricultural crops. In formula (I) Q1 independently represents a halogen atom, C1-C8alkyl, C1-C8halogenalkyl, having 1-5 halogen atoms, C2-C8alkenyl, C2-C8alkenyloxy, C1-C8alkoxy, C1-C8halogenalkoxy, having 1-5 halogen atoms, C1-C8alkylcarbonyl, C1-C8alkylcarbonylamino, C1-C8halogenalkylcarbonylamino, having 1-5 halogen atoms, C1-C8alkylsulphanyl, C1-C8halogenalkylsulphanyl, having 1-5 halogen atoms, C1-C8alkylsulphonyl, C1-C8halogenalkylsulphonyl, having 1-5 halogen atoms, C1-C8alkoxyalkyl, C1-C8halogenalkoxyalkyl, having 1-5 halogen atoms; p= 0, 1, 2, 3, 4 or 5; Ra represents a hydrogen atom, C1-C8alkylcarbonyl; Rb and Rc independently represent a hydrogen atom, L1 represents an unsubstituted pyridin-3-yl or pyridin-4-yl; where the group Q2-L2-CY lies in the alpha-position relative the nitrogen ring atom; Y represents O, S, NRd; L2 represents a direct bond, O, NRg; Q2 represents a hydrogen atom, substituted or unsubstitured C1-C8alkyl, substituted or unsubstituted C3-C8cycloalkyl; C2-C8alkenyl, (2-oxopyrrolidin-1-yl)-C1-C8alkyl, (2-oxoazepan-1-yl)-C1-C8alkyl, (2-oxopyrrolidin-1-yl)-C1-C8halogenalkyl, having 1 -5 halogen atoms; (2-oxoazepan-1-yl)-C1-C8halogenalkyl, having 1-5 halogen atoms; where the substitutes are selected from a group consisting of a halogen atom, a hydroxy group, di C1-C8alkylamino, C1-C8alkoxy; or L2 and Q2 together can form a substituted or unsubstituted 4-, 5-, 6- or 7-member heterocycle, containing up to 4 heteroatoms, selected from a list consisting of N, O, S, where the substitutes are independently selected from a group consisting of a halogen atom, a hydroxy group, di C1-C8alkylamino, C1-C8alkoxy; Rd represents a hydroxy group, C1-C8alkoxy, C2-C8alkenyloxy; Rg represents a hydrogen atom, C1-C8alkyl, C3-C6cycloalkyl, C2-C8alkenyl or C1-C8alkoxy.

EFFECT: obtaining novel phenyl-pyrimidinyl-amino derivatives of formula (I), as well as agriculturally acceptable salts thereof, having fungicidal activity.

11 cl, 11 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new piperazine amide derivatives of formula wherein X represents N or CH; Y represents N or CH; R1 represents lower alkyl, phenyl, phenyl-lower alkyl wherein phenyl can be optionally substituted by 1-2 substitutes independently specified in a group consisting of halogen, lower alkyl; R2 represents lower alkyl, phenyl, naphthyl or heteroaryl specified in dimethylisoxazolyl, quinolinyl, thiophenyl or pyridinyl wherein phenyl or heteroaryl are optionally substituted by 1 substitute optionally specified in a group consisting of halogen, lower alkoxy group, fluor-lower alkyl, lower alkoxy-carbonyl and phenyl; R3 represents phenyl, pyridinyl or pyrazinyl wherein phenyl, pyridinyl or pyrazinyl are substituted by 1-2 substituted optionally specified in a group consisting of halogen, lower alkyl and fluor-lower alkyl; R4, R5, R6, R7, R8, R9, R10 and R11 independently represent hydrogen, as well as to their physiologically acceptable salts. These compounds are bound with LXR alpha and LXR beta, and are applicable as therapeutic agents for treatment and/or prevention of high lipid levels, high cholesterol levels, low HDL cholesterol, high LDL cholesterol, atherosclerotic diseases, diabetes, non insulin dependent diabetes mellitus, metabolic syndrome, dislipidemia, sepsis, inflammatory diseases, infectious diseases, skin diseases, colitis, pancreatitis, cholestasis, liver fibrosis, psoriasis, Alzheimer's disease, etc.

EFFECT: preparing new piperazine amide derivatives.

15 cl, 88 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I),

, where groups and radicals R1, R2 independently denote H, C1-8-alkyl or C3-7-cycloalkyl, where the alkyl or cycloalkyl group can be mono- or poly-substituted with identical or different groups R11; or R2 denotes a -CH2- or -CH2-CH2- bridge which is bonded with a group Y, and R1 is as defined above, or denotes a group selected from C1-4-alkyl-CO-, C1-4-alkyl-O-CO-, (C1-4-alkyl)NH-CO- or (C1-4-alkyl)2N-CO-, where the alkyl groups can be mono- or polyfluorinated; or R1 and R2 form an alkylene bridge such that R1R2N- denotes a group selected from: azetidine, pyrrolidine, piperdine, azepan, 2,5-dihydro-1H-pyrrole, 1,2,3,6-tetrahydropyridine, 2,3,4,7-tetrahydro-1H-azepine, 2,3,6,7-tetrahydro-1H-azepine, piperazine, in which the free amino group is substituted with R13, piperidin-4-one, morpholine, thiomorpholine, 4-C1-4-alkoxy iminopiperidin-1-yl and 4-hydroxy iminopiperidin-1-yl. Wherein, when R1 and R2 form an alkylene bridge, one or more H atoms in the alkylene bridge can be substituted with identical or different groups R14, and X denotes a C1-3-alkylene bridge which can contain one, two or three identical or different C1-3-alkyl substitutes; and Y denotes a group of subformula selected from: and , where the group can be mono-substituted with a substitute R20; Z denotes -CH2-CH2- or -C(=O)-CH2-; U, V both denote CH, one of groups U, V denotes N, and the other of U, V denotes CH, where CH can be substituted with L; and L independently denotes halogen, cyano or C1-3-alkyl; and k equals 0, 1 or 2; W is selected from a group consisting of -CH2-O- and -O-CH2-; B is selected from a group consisting of phenyl, pyridyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furyl, thiophenyl and thiazolyl; each of which can be mono- or poly-substituted with identical or different substitutes R20; radicals R11, R13, R14, R20 assume values given in claim 1. The invention also relates to a pharmaceutical composition containing at least one compound of formula I and having action on MCH receptor.

EFFECT: disclosed pharmaceutical compositions are useful in treating metabolic disorders or eating disorders, especially obesity, bulimia, anorexia, hyperphagia and diabetes.

FIELD: chemistry.

SUBSTANCE: invention relates to novel azoles of general formula 1A and 1B and pharmaceutically acceptable salts thereof, having activity on hepatitis C and hepatitis GBV-C virus. Said compounds have NS5A viral protein ligand properties and can be used as active components for a pharmaceutical composition and a medicinal agent for treating diseases caused by said viruses. In general formula 1A and 1B, the solid lines accompanied by dotted lines denote a single or double bond, wherein if one of them is a single bond, the other is a double bond; X and Y optionally assume different values and denote a nitrogen, oxygen or sulphur atom or a NH group; R1 and R2 optionally denote identical radicals 2.1-2.20, in which the asterisk (*) indicates site of the bond to azole fragments. Said fragments and values of A and B are given in the claim.

EFFECT: more value of the compounds.

10 cl, 1 tbl, 16 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: this invention relates to new compounds with formula (I) possessing the properties of mGLuR2 antagonists, to their obtainment methods, their application for production of medicines for prevention and treatment of disorders wherein mGLuR2 plays the activation role (in particular - central nervous system disorders). In formula (I) either any of X and Y represents N while the other represents CH or each of X and Y represents N; A represents aryl representing phenyl or 5- or 6-membered heteroaryl containing in the cycle 1-3 atoms selected from among nitrogen, oxygen or sulphur, the heteroaryl selected from among amidazolyl, [1,2,4] oxadiazolyl, pyrrolyl, 1H-pyrazolyl, pyridinyl, [1,2,4] triazolyl, tiazolyl and pyrimidinyl, each of them substitutable by C1-6-alkyl; B represents H, cyano or represents a possibly substituted aryl selected from among phenyl or possibly substituted by 5- or 6-membered heteroaryl containing in the cycle 1-3 atoms selected from among nitrogen, oxygen or sulphur where the substitutes are selected from the group consisting of nitro, C1-6-alkyl, possibly substituted hydroxy, NRaRb where Ra and Rb independently represent H, C1-6-alkyl etc. R1 represents H, a halogen atom, C1-6-alkyl, possibly substituted hydroxy, C1-6-alcoxy, C1-6-halogenoalkyl, C3-6-cycloalkyl represents H cyano, a halogen atom, C1-6-halogenoalkyl, C1-6-alcoxy, C1-6-halogenoalcoxi-, C1-6-alkyl or C3-6-cycloalkyl R3 represents a halogen atom, H, C1-6-alcoxy, C1-6-halogenoalkyl, C1-6-alkyl, C3-6-cycloalkyl, C1-6-halogenoalcoxy R4 reprsents H or halogeno.

EFFECT: creation of new compounds of formula (I) possessing mGLuR2 antagonist properties.

104 cl, 465 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I)

, where: n equals 0, 1, 2; G denotes CH2, CHR3; R1 denotes H, C1-C6-alkyl, C3-C6-alkenyl, -CH2Ph; R2, R3, R4 independently denote H, CH3, -CH2F, -CHF2, CF3; A denotes 1,4-Ph, 1,3-Ph, which can be optionally substituted with 1-4 substitutes selected from halogen, C1-C4-alkyl, C1-C4alkoxy, fluorinated C1-C4-alkyl and fluorinated C1-C4alkoxy; E denotes NR5, where R5 denotes H, C1-C3-alkyl; Ar denotes a radical of formula

and

where: Ra denotes halogen, C1-C6-alkyl, fluorinated C1-C6-alkyl, C1-C6-alkoxy, fluorinated C1-C6-alkoxy, phenyl sulphonyl, CN, -NR6R7, where R6 and R7, together with an N atom, form a 5- or 6-member saturated ring or denotes a 5-member saturated or unsaturated aromatic or non-aromatic heterocyclic ring containing, as ring members, 1, 2 or 3 heteroatoms selected from N, O and S, and where the heterocyclic ring can carry 1, 2 or 3 substitutes selected from halogen and C1-C6-alkyl, or denotes a 6-member saturated heterocyclic ring containing, as ring members, one N and one O atom; Rb and Rc independently denote H, halogen, CH3, OCH3, CH2F, OCH2F, CHF2, OCHF2, CF3, OCF3, CH2CH2F, OCH2CH2F, CH2CHF2, OCH2CHF2, CH2CF3 or OCH2CF3; Rd denotes Ra or a 5- or 6-member heteroaromatic ring containing, as ring members, 1, 2 or 3 heteroatoms selected from N, O and S, and where the heteroaromatic ring can carry 1 substitute selected from C1-C6-alkyl and C1-C6-alkylthio; Re denotes H or is defined as Ra; Rf is defined as Ra; k equals 0, 1, 2, 3; j equals 0, 1, 2, 3, 4; provided that Ra does not denote F, CH2F, CHF2, CF3, OCF3, if A denotes 1,4-Ph, Ar denotes a radical of formula (A) and Rb and Rc denote H, halogen; except compounds, where R1 denotes propyl, G denotes CH2, n equals 1, A denotes 1,4- Ph, E denotes NH, Ar denotes a radical of formula (F) and Rd denotes halogen, C1-C6-alkyl, C2-C6-alkenyl or a 5-member heteroaromatic ring; and physiologically acceptable acid addition salts thereof.

EFFECT: compounds exhibit 5HT6 receptor simulating activity, which allows for their use in a pharmaceutical composition.

25 cl, 6 tbl, 107 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula in which: X denotes S, N-R5 or O; R denotes H; alkyl; heteroaryl, which is a thienyl optionally substituted with alkyl; R1 denotes alkyl; aryl, optionally substituted with a halogen; heteroaryl which is a thienyl optionally substituted with an alkyl, a a halogen, a methoxy group; R2 denotes heteroaryl which is 2-, 3- or 4-pyridyl; R3 denotes H; aryl, optionally substituted with a halogen, a methoxy group; heteroaryl, which is a thienyl optionally substituted with a halogen; alkyl, optionally substituted with oxytetrahydropyranyl; R4 denotes H; R5 denotes H; alkyl; or salt thereof.

EFFECT: invention also relates to a method of producing said compounds, which can be used as antifungal agents for crops, as well as agents against other pests, such as insects or mites and weeds which can harm crops.

10 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention describes a compound of formula (I): or pharmaceutically acceptable salt thereof, or stereoisomer, in which: n equals 0 or 1; X denotes CH2, C=O; R1 denotes a) -(CH2)mR3 or -CO(CH2)mR3, where m equals 0, 1; and R3 denotes a 5-10-member aryl or heteroaryl, where the heteroaryl denotes a mono- or bicyclic aromatic ring containing 5-10 ring atoms, from which at least one or two atoms are heteroatoms selected oxygen, nitrogen or sulphur, optionally substituted with one or more halogens; b) -C=YR4, where Y denotes O; and R4 denotes: (C1-C10)alkyl; (C1-C10)alkoxy; (C0-C10)alkyl-(5-10-member heteroaryl), where "heteroaryl" denotes a mono- or bicyclic aromatic ring containing 5-10 ring atoms, from which at least one or two atoms are heteroatoms selected from oxygen, nitrogen or sulphur, said heteroaryl is optionally substituted with one or more substitutes selected from halogen, oxo or 2-(C1-C6)alkyl, where Z denotes S; (C0-C10)alkyl-(5-10-member aryl), said aryl is optionally substituted with one or more substitutes selected from halogen; (C1-C6)alkoxy, which itself is optionally substituted with one or more halogens; (C1-C6)alkyl, which itself is optionally substituted with one or more halogens; or -Z-(C1-C6)alkyl, where Z denotes S or SO2, and where said (C1-C6)alkyl can be optionally substituted with one or more halogens; or (C1-C6)alkyl-CO-O-R12, where R12 denotes H or (C1-C6)alkyl; or c) -C=ZNHR6, where Z denotes O or S; and R6 denotes: (C1-C10)alkyl; (C1-C10)alkoxy; 5-10-member aryl or heteroaryl, where "heteroaryl" denotes a bicyclic aromatic ring containing 9 ring atoms, from which at least one or two atoms are oxygen atoms; optionally substituted with one or more substitutes selected from halogen; cyano; (C1-C6)alkoxy, which itself is optionally substituted with one or more halogens; (C1-C6)alkyl, which itself is optionally substituted with one or more halogens; and R2 denotes H or (C1-C6)alkyl. Also described is a pharmaceutical composition for inhibiting TNFα, based on the compound of formula I.

EFFECT: novel compounds which can regulate production of certain cytokines, including TNF-α, are obtained and described.

27 cl, 81 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to 6-piperidinyl-substituted isoquinoline derivatives of formula (I)

, where values of radicals are given in the claim, and compositions containing said compounds.

EFFECT: said compounds and compositions can be useful in treating and preventing diseases associated with Rho-kinase and mediated by Rho-kinase through myosin light chain phosphatase phosphorylation.

31 cl, 378 ex, 12 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of the formula (I) that are characterized by the properties of M3 muscarine receptor antagonist that is applicable in treatment or prevention of the disease or state (the abnormity of) which includes activity of the M3 muscarine receptor such as respiratory diseases. In the formula (I) A is represented by the oxygen atom or the group -N(R12)-; (i) R1 is represented by C1-C6-alkyl or the hydrogen atom; and R2 is represented by the hydrogen atom or the group -R5, -Z-Y-R5, -Z-NR9R10, -Z-NR9CO-R5 or -Z-CO2H; and R3 is absent or is represented by C1-C6-alkyl, and in this case the nitrogen atom to which it is bound is represented by tetradic nitrogen and bears a positive charge; or (ii) R1 and R2 together with nitrogen to which they are bound form heterocycloalkyl ring; the mentioned ring is displaced by the group -Y-R5 or -Z-Y-R5, and R3 is absent or is represented by C1-C6-alkyl, and in this case the nitrogen atom to which it is bound is represented by tetradic nitrogen and bears a positive charge; R4 is represented by the formula group (a), (b), (c) or (d); Z is represented by C1-C16-alkylene group; Y is represented by the link or the oxygen atom; R5 is represented by C1-C6-alkyl, aryl, phenyl condensed with C3-C6cycloalkyl, phenyl condensed with heterocycloalkyl, heteroaryl, aryl(C1-C8-alkyl)-, heteroaryl(C1-C8-alkyl)-, C3-C6cycloalkyl or heteroC3-C6cycloalkyl group; R6 is represented by C1-C6-alkyl or the hydrogen atom; n and m equal 0; R8a and R8b are independently chosen from the group consisting of aryl, phenyl condensed with heterocycloalkyl, heteroaryl, C1-C6-alkyl, C3-C6cycloalkyl; R8c is represented by -OH or C1-C6-alkyl; R9 and R10 are represented independently by the hydrogen atom, C1-C6-alkyl, aryl, phenyl condensed with heterocycloalkyl and other components mentioned in the invention formula.

EFFECT: new compounds applicable in treatment or prevention of the disease or state (the abnormity of) which includes activity of the M3 muscarine receptor such as respiratory diseases.

10 cl, 49 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine derivatives of formula (1) in free form or in form of a salt. In formula (1): X1 and X2 all independently denote halogen; A denotes a radical of formula where (R1)1-2 denotes 1-2 identical or different substitutes selected from a group comprising C1-C4-alkyl, halogen-C1-C4-alkyl, hydroxy-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl, R2R3N-C1-C4-alkyl, halogen, hydroxy group, C1-C4-alkoxy group, halogen-C1-C4-alkoxy group, C1-C4-alkylthio group, C1-C4-alkanoyl, C1-C4-alkanoylamino group, C1-C4-alkylsulphonylamino group, C1-C4-alkylsulphonyl, C1-C4-alkylthionyl, NR2R3 and morpholinyl; or A denotes a radical of formula where ring (a) denotes a 5-member heterocyclic ring containing 1 or 2 heteroatoms selected from a group comprising O and N, which can further be substituted with C1-C4-alkyl, and which is annelated in positions 3 and 4; and R2 and R3 all independently denote hydrogen or C1-C4-alkyl. The invention also relates to a parasite control composition containing said compounds, a parasite control method on warm-blooded animals and use of compounds of formula (1) to prepare a parasite control composition.

EFFECT: high efficiency of using said compounds.

11 cl, 7 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new compound of formula A

the radicals R1, R2, R3, R4, R5, R25, R26, U, T, W, V, Y are those as specified in clause 1 of the patent claim. Also, the invention refers to a method for preparing the compound of formula A, the drug based on this compound applied for treating disorders or diseases which are at least partially mediated by vanilloid receptor VR1 /NRPV1, as well as use of this compound for preparing the drug.

EFFECT: there are prepared and described new compounds which can be effective in treating diseases which are at least partially mediated by vanilloid receptor VR1 /NRPV1.

43 cl, 367 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted methyl-amines of general formula 1, having serotonin 5-HT6 receptor antagonist properties. In formula 1 , W is naphthalene, indolysin or quinoline; R1 is hydrogen, fluorine, chlorine, methyl; R2 is hydrogen, fluorine, methyl, phenyl, thiophen-2-yl, furan-2-yl, pyridyl, piperazin-1-yl or 4-methylpiperazin-1-yl; R3 is methyl; or W is benzene, R3 assumes the value given above; R1 is 3-Cl, R2 is 3-piperazin-1-yl or 3-(4-methylpiperazin-1-yl); or R1 is hydrogen, R2 is phenyl or pyridyl; or R1 is hydrogen, fluorine, chlorine, methyl; R2 is 4-piperazin-1-yl or 4-(4-methylpiperazin-1-yl); or W is oxazole, R3 is optionally substituted methyl; R1 is chlorine or fluorine, R2 is methyl, or R1 is hydrogen, fluorine, chlorine, methyl; R2 is piperazin-1-yl, 4-methylpiperazin-1-yl, or R1 is chlorine, fluorine or methyl; R2 is furan-2-yl, or R1 is hydrogen, fluorine, chlorine, methyl; R2 is furan-2-yl, R3 is (tetrahydrofuran-2-yl)methyl, or R1 is hydrogen, fluorine, chlorine, methyl; R2 is thiophen-2-yl, R3 is 2-methoxyethyl, or R1 is chlorine or fluorine, R2 is thiophen-2-yl, R3 is methyl.

EFFECT: compounds can be used to treat central nervous system (CNS) diseases, such as psychiatric disorders, schizophrenia, anxiety disorders, as well as for improving mental capacity, for treating obesity or for studying the molecular mechanism of inhibiting serotonin 5-HT6 receptors.

15 cl, 27 dwg, 2 tbl, 25 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel antibacterial chinolin derivatives of formula (1a), their stereochemically isomeric forms, N-oxides and pharmaceutically acceptable salts and solvates , where p equals 1; q equals 0, 1, 2, 3 or 4; R1 represents hydrogen, halogen, aryl or Het; R2 represents hydrogen or alkyloxy; R3 represents arylalkyl; each R4 and R5 independently represent hydrogen or alkyl; R7 represents hydrogen, alkyl or aryl; where aryl is selected from phenyl or naphtyl and is optionally substituted with 1, 2 or 3 substituents selected from hydroxy, halogen, cyano, nitro, amino, mono- or dialkylamino, alkyl, C2-6alkenyl, optionally substituted with phenyl, halogenalkyl, alkyloxy, halogenalkyloxy, carboxyl, alkyloxycarbonyl, aminocarbonyl, morpholinyl or mono- or dialkylaminocarbonyl; where Het is selected from furanyl, thienyl, pyridinyl, benzofuranyl, optionally substituted with 1, 2 or 3 substituents selected from halogen, hydroxyl, alkyl or alkyloxy.

EFFECT: compounds can be used for creation of preparations on their base for treatment of bacterial infection

21 cl, 4 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (IC-2), to their pharmaceutically acceptable salts, N- oxides or solvates. In formula (IC-2) Z represents carbomoyl group, which can be replaced with C1-4 alkyl or hydroxy; R1 represents C1-8 alkyl or C1-8 alkoxy; R4 and R4-1 each independently represent hydrogen atom or C1-8 alkyl; m represents integer number from 1 to 5, when m equals 2 or larger number, all R1 can have same or different values. Invention also relates to compounds, representing 1-({6-[(2-methoxy-4-propylbenzyl)oxy]-1-methyl-3,4-dihydro-2-napthlenyl}methyl)-3-azetidinecarbonic acid, 1-({6-[(4-isobutyl-2-methoxybenzyl)oxy]-1-methyl-3,4-dihydro-2-naphthalinyl}methyl)-3- azetidinecarbonic acid and other, given in formula of claimed invention.

EFFECT: obtaining pharmaceutical composition, which has agonistic activity with respect to EDG-1, EDG-6 and/or EDG-8, containing as active component invention compound, to method of prevention and/or treatment of disease, conditioned by EDG-1, EDG-6 and/or EDG-8 invention compounds, to method of prevention and/or treatment of disseminated sclerosis and method of immune reaction suppression and/or induction of lymphopenia, to application of invention compounds for obtaining medication for prevention and/or treatment of disease, conditioned by EDG-1, EDG-6 and/or EDG-8, to application of compounds for obtaining medication for prevention and/or treatment of disseminated sclerosis, to application of compounds for obtaining immunodepresant and/or medication inducing lymphopenia and to crystal forms of some individual compounds.

17 cl, 10 dwg, 5 tbl, 251 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of 2,6-substituted-4-monosubstituted aminopyrimidines of formula (I) or pharmaceutically acceptable salts thereof, which have prostaglandin D2 receptor antagonist properties. In formula R1 is 2,4-dichlorophenyl or 4-trifluoromethoxyphenyl, and when R1 is 2,4-dichlorophenyl, R2 is 3-carboxypyrrolidinyl, 3,5-di-(1-hydroxy-1-methylethyl)phenyl, 3-aminopiperdin-1-yl, 4-aminopiperidin-1-yl, 4-acetamidepiperidin-1-yl, 1-methyl-2-carboxy-2,3-dihydro-1H-indol-5-yl, 3-(1-tert-butylsulphonylaminocarbonyl-1-methylethyl)phenyl, 3-(1-dimethylaminosulphonylaminocarbonyl-1-methylethyl)phenyl, 3-(1-thiomorpholin-4-ylcarbonyl-1-methylethyl)phenyl, 3-(1-aminocarbonyl-1-methylethyl)phenyl, 3-(1-dimethylaminocarbonyl-1-methylethyl)phenyl, 3-carboxymethylpiperidin-1-yl, 3-methylsulphonylaminocarbonylpiperidin-1-yl, 3-ethylsulphonylaminocarbonylpiperidin-1-yl, 3-tert-butylsulphonylaminocarbonylpiperidin-1-yl, 3-trifluoromethylsulphonylaminocarbonylpiperidin-1-yl, 3-[(1H-tetrazol-5-yl)aminocarbonyl]piperidin-1-yl, 3-aminocarbonylpiperidin-1-yl, 3-dimethylaminocarbonylpiperidin-1-yl, 3-dimethylaminosulphonylaminocarbonylpiperidin-1-yl or 2-carboxy-2,3-dihydrobenzofuran-5-yl, and when R1 is 4-trifluoromethoxyphenyl, R2 is 3-(1-methyl-1-carboxyethyl)piperidinyl, 3-carboxypiperidinyl, 3-methylsulphonylaminocarbonylpiperidin-1-yl, 5-carboxythiophen-2-yl. The invention also relates to a pharmaceutical composition containing the said compounds.

EFFECT: high efficiency of using said compounds.

3 cl, 1 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel benzimidazole derivatives of formula

and pharmaceutically acceptable salts and esters thereof, where R1 denotes C1-10alkyl, lower alkoxy group-lower alkyl, lower alkoxy group-carbonyl-lower alkyl, C3-6cycloalkyl, C3-6cycloalkyl-lower alkyl, phenyl, phenyl-lower alkyl, di(phenyl)-lower alkyl, heterocyclyl, such as piperidinyl, tetrahydropyranyl, 2-oxo-pyrrolidinyl-lower alkyl, where the cycloalkyl, phenyl or heterocyclyl group is optionally substituted with 1-2 substitutes independently selected from a group comprising lower alkyl, lower alkoxy group, lower alkoxy group-carbonyl, morpholinyl, formylamino group and halogen; R2 denotes hydrogen or lower alkyl; R3 denotes lower alkyl, C3-6cycloalkyl, partially unsaturated cyclohexyl, phenyl, phenyl-lower alkyl, pyridinyl, benzodioxolyl, tetrahydropyranyl, where the phenyl group is optionally substituted with 1-2 substitutes independently selected from a group comprising a halogen, lower alkyl, lower alkoxy group, fluoro-lower alkyl, fluoro-lower alkoxy group, N(lower alkyl)2; R4 denotes: a) heteroaryl which is an aromatic 5-6-member monocyclic ring or a 9-10-member bicyclic ring containing 1 or 2 heteroatoms selected from nitrogen, oxygen and/or sulphur, which is optionally substituted with 1-2 substitutes independently selected from a group comprising lower alkyl, phenyl, lower alkoxy group, -N(lower alkyl)2, oxo group, NH2, halogen, cyano group and morpholinyl; b) unsubstituted naphthyl, naphthyl or phenyl, which are substituted with 1-3 substitutes independently selected from a group comprising halogen, hydroxy group, NH2, CN, hydroxy-lower alkyl, lower alkoxy group, lower alkyl-carbonyl, lower alkoxy group-carbonyl, sulphamoyl, di-lower alkyl-sulphamoyl, lower alkyl-sulphonyl, thiophenyl, pyrazolyl, thiadiazolyl, imidazolyl, triazolyl, tetrazolyl, 2-oxopyrrolidinyl, lower alkyl, fluoro-lower alkyl, fluoro-lower alkoxy group, N(lower alkyl)2, carbamoyl, lower alkenyl, benzoyl, phenoxy group and phenyl which is optionally substituted with 1-2 substitutes independently selected from halogen and fluoro-lower alkyl; or c) if R3 denotes cycloalkyl and R1 denotes cycloalkyl, then R4 can also denote phenyl; R5, R6, R7 and R8 independently denote H, halogen, lower alkoxy group or lower alkyl, or R6 and R7, which are bonded to each other, form a 6-member aromatic carbocyclic ring together with carbon atoms to which they are bonded; provided that the compound of formula (I) is not selected from a group comprising butylamide 2-[2-(2-chlorophenyl)benzoimidazol-1-yl]-4-methylpentanoic acid and 2-(2-benzo[1,3]dioxol-5-ylbenzoimidazol-1-yl)-N-benzyl-butyric acid amide. The invention also relates to a pharmaceutical composition based on the formula I compound.

EFFECT: novel benzimidazole derivatives which are useful as farnesoid X receptor antagonists are obtained.

30 cl, 379 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula , where R1 is a 3-7-member carbocyclic ring and n is a number ranging from 1 to 8, and the rest of the radicals are described in the claim.

EFFECT: possibility of using such compounds and compositions in therapy as metabotropic glutamate receptor modulators.

33 cl, 367 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to chemical-pharmaceutical industry. Pharmaceutical compositions including, at least, one compound of formula where -X- represents, for instance, group of formula and Y represents, for instance, group of formula or its pharmaceutically acceptable salts, esters or amides, or pro-drugs and pharmaceutically acceptable carrier, which is acceptable in therapy, can be applied for modulation in vitro and in vivo processes of binding, mediated by binding of E-, P- or L- selectin.

EFFECT: obtaining novel floroglucin derivatives.

9 cl, 10 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: in formula (I) Cy1 is a 6-member heterocyclyl containing N as a heteroatom, a 5,6-member monocyclic or 9,10-member bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S and O, phenyl or phenyl condensed with a 5-member heterocycle containing O as a heteroatom, each optionally having 1-3 identical or different substituting Cy1 groups which are: (C1-C6)-acyl, cyano, carboxy, hydroxy, (C1-C6)alkylsulphonyl, (C3-C6)-cycloalkyl, a 6-member heterocyclyl containing 1-2 heteroatoms selected from O and N, phenyl, a 5-member heteroaryl containing 1-3 heteroatoms selected from N, S and O, Y1Y2N-, Y1Y2NC(=O)-, Y1Y2NSO2-, (C1-C6)-alkyl-SO2-N(R5)-C(=O)-, R6-C(=O)-N(R5)-, R7-NH-C(=O)-NH-; (C1-C6)-alkoxycarbonyl; (C1-C6)-alkyl, which optionally contains 1-3 identical or different substitutes which are halogen, carboxy, cyano, hydroxy, Y1Y2N-, Y1Y2N-C(=O)-, R6-C(=O)-N(R5)-, R8-SO2-N(R5)-C(=O)-, 5-member heterocyclyl, containing N as a heteroatom, 5-member heteroaryl containing 1-3 heteroatoms selected from N and O; or (C1-C6)-alkoxycarbonyl; as well as (C1-C6)-alkoxy which optionally have 1-3 identical or different substitutes which are carboxy, (C1-C6)-alkoxycarbonyl, cyano, 3-member heterocyclyl containing O as a heteroatom, or 5-member heteroaryl containing 1-3 heteroatoms selected from N and O; where phenyl or heteroaryl fragments in the substituting Cy1 groups optionally and independently have substitutes represented by hydroxy, (C1-C6)-alkyl, (C1-C6)-alkoxy, carboxy, (C1-C6)-alkoxycarbonyl or R8-SO2-N(R5)-C(=O)-; and where cycloalkyl fragments in the substituting Cy1 groups which optionally and independently have substitutes represented by (C1-C6)-alkoxy, carboxy; Cy2 is a 9-member cycloalkenyl, phenyl, 5,6-member monocyclic or 9,10-member bicyclic heteroaryl containing 1-3 heteratoms selected from N, S and O, or phenyl condensed with a 5,6-member heterocycle containing 1-2 heteroatoms selected from N and O, each independently and optionally having 1-3 identical or different substitutes represented by (C1-C6)-alkoxy, (C1-C3)-alkyl, hydroxy, halogen, halogen-(C1-C6)-alkoxy, nitro, Y1Y2N-; L1 is an alkylene with a straight or branched chain containing 1-6 carbon atoms, optionally substituted carboxy; or L1 is -CH2-(C1-C5)halogenalkylene; L2 is a bond, -O- or -CH2-O-. Other values of radicals are given in the formula of invention.

EFFECT: novel compounds have prostaglandin D2 receptor antagonist properties, can be used in treating primarily allergic disorders such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergy and other diseases.

39 cl, 1 tbl, 99 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to heterocyclic compounds of formula (I), where R1 represents C1-6 alkyl, optionally substituted with hydroxy, monocyclic C3-8 cycloaliphatic radical, optionally substituted with hydroxy, or phenyl; R2 represents H, C1-6 alkyl, optionally substituted with hydroxy or morpholine, monocyclic C3-8 cycloaliphatic radical, optionally substituted with a hydroxy group or a heterocycloaliphatic radical, where the heterocycloaliphatic radical is piperidine, pyrrolidine or morpholine; each of a, a', b and c independently represents N or C(R3); each of R3, R5 and R6 independently represents H, halogen, phenyl, substituted with one substitute selected from methoxy methyl, amino, methoxy or trifluoromethoxy, or heteroaryl substituted with alkyl, hydroxy or alkoxy; R4 represents H; K represents -N(RX')-; J represents a bond, -O, alkylene, -C(O)-, -C(O)-O-, or -C(O)-N(Rx')-; RX' represents H; n equals 0; and under the condition that if R1 represents an unsubstituted alkyl, J represents -O-, then R2 represents H. The invention also relates to a pharmaceutical composition based on a compound of formula (I).

EFFECT: obtaining novel heterocyclic compounds, useful as modulators of interleukin receptor-associated kinase IRAK.

20 cl, 18 ex

Up!