1n-quinazoline-2,4-diones

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 1H-quinazoline-2,4-diones of formula and to their pharmaceutically acceptable salts where R1 and R2 have the values specified in cl. 1 of the patent claim. The specified compounds exhibit antagonistic activity with respect to the AMPA receptor.

EFFECT: reception of a pharmaceutical composition for preparing a preparation used for treating a condition mediated by the AMPA receptor and first of all for treating epilepsy or schizophrenia.

8 cl, 81 ex

 

The text descriptions are given in facsimile form.

1. The compounds of formula (I)

where R1means CF3or isopropyl, and
R2means heterocyclyl, optionally substituted with one to three substituents selected from the group comprising halogen, hydroxy, amino, nitro, cyano, (C1-C4)alkyl, hydroxy-(C1-C4)alkyl, (C1-C4)alkoxyalkyl, amino-(C1-C4)alkyl, (C1-C4)alkylamino-(C1-C4)alkyl, di(C1-C4)alkylamino-(C1-C4)alkyl, NSO, (C1-C4)alkylsulphonyl, (C1-C4)alkoxy, acyloxy, (C1-C4 )alkoxycarbonyl, (C1-C4)alkylamino, di-(C1-C4)alkylamino, acylamino, (C1-C4)alkoxycarbonyl; heterocyclyl consists of 3 to 11 ring atoms of which 1-3 ring atoms are heteroatoms selected from nitrogen, oxygen and sulfur, and which heterocycle is attached to the phenyl ring via a carbon atom,
and their pharmaceutically acceptable salts.

2. N-[7-isopropyl-6-(2-methyl-2H-pyrazole-3-yl)-2,4-dioxo-1,4-dihydro-2H-hinzelin-3-yl]methanesulfonamide and its pharmaceutically acceptable salts.

3. N-[-[7-isopropyl-6-(2-methyl-2H-pyrazole-3-yl)-2,4-dioxo-1,4-dihydro-2H-hinzelin-3-yl]methanesulfonamide according to claim 2 in the form of its pharmaceutically acceptable salts.

4. N-[7-isopropyl-6-(2-methyl-2H-pyrazole-3-yl)-2,4-dioxo-1,4-dihydro-2H-hinzelin-3-yl]methanesulfonamide according to claim 2 in free form.

5. Compounds according to any one of claims 1 to 4 for use as a pharmaceutical, which has antagonistic activity against AMPA receptor.

6. Pharmaceutical composition having antagonistic activity against AMPA receptor, comprising a compound according to any one of claims 1 to 4.

7. The use of compounds according to any one of claims 1 to 4 for obtaining a medicinal product intended for the treatment of condition mediated by the AMPA receptor.

8. The use of compounds according to any which one of claims 1 to 4 to obtain medicines designed for treatment of epilepsy or schizophrenia.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (1), where A1, A2, A3, A4, A5 ad A6 are independently selected from a group comprising CR3 and N; provided that the biggest one of A1, A2, A , A4, A5 and A6 denotes N; B1, B2 and B3 are independently selected from a group comprising CR2 and N; each R3 independently denotes H or C1-C6 alkyl; and R1, R2, R4, R5, W and n are as given in the description, or salts thereof which are suitable for use in agriculture. The invention also relates to compositions containing compounds of formula (1), and insect-pest control methods which involve contact between the pest or habitat thereof with a biologically effective amount of the compound or composition according to the present invention, as well as to methods of protecting seeds and animals from insects-pests.

EFFECT: high effectiveness of the obtained compounds in insect-pest control.

29 cl, 12 tbl, 5 ex

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 substituted oxadiazole derivatives of general formula , where X denotes CH, CH2, CH=CH, CH2CH2, CH2CH=CH or CH2CH2CH2, R1 denotes an unsubstituted or mono- or disubstituted phenyl or pyrrolyl residue or an unsubstituted or mono- or disubstituted phenyl connected through a C1-C3alkyl or a thienyl or indolyl residue, where the said substitutes are selected from a group comprising F, Cl, Br, OCF3, O-C1-C6alkyl or C1-C6alkyl, R2 denotes an unsubstituted or mono- or disubstituted phenyl or thienyl residue or an unsubstituted or mono- or disubstituted phenyl residue connected through a C1-C3alkyl, where the said substitutes are selected from a group comprising F, Cl, and R3 and R4 denote a saturated straight C1-C6alkyl in form of a racemate, diastereomers, mixture of enantiomers and/or diastereomers, or a specific diastereomer, bases and/or salts with physiologically compatible acids. The invention also relates to a method of producing said compounds and a medicinal agent based on said compounds and having affinity to the µ-opioid receptor.

EFFECT: obtaining novel compounds and a medicinal agent based on said compounds, which can be used in medicine to pain killing and for treating depression, enuresis, diarrhoea, skin itching, alcohol and drug abuse, drug induced addiction, aspontaneity or for anxiolyis.

11 cl, 2 tbl, 331 ex

FIELD: chemistry.

SUBSTANCE: described are novel benzofuroxanes of general formula

, where R is phenylamino-, N-[4-methoxyphenyl]amino-, N-piperidyl-, which have fungicidal and bactericidal activity and which can be used in veterinary, medicine and agriculture.

EFFECT: high efficiency of the compositions.

2 cl, 2 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel 3,4-dihydrobenzoxazine compounds of general formula [1] (where X denotes a nitrogen atom or CR3; R1 denotes a hydrogen atom or a halogen atom; R2 denotes a C1-6alkoxy group which can be substituted with 1-5 identical or different substitutes selected from a halogen atom and a hydroxyl group; and R3 denotes a halogen atom. However, R1 denotes a halogen atom when X denotes CR3). Said compounds are effective when treating diseases where activity of vanilloid receptors subtype 1 (VR1) is involved, e.g. pain.

EFFECT: more efficient use of pharmaceutical compositions based on said compounds, more effective treatment or pain killing.

19 cl, 4 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: disclosed compounds have activity and selectivity towards the GABA A receptor subunit α5. In formula I , R1 denotes hydrogen, halogen, phenyl, a 6-member heterocycyl with 2 heteroatoms selected from N, O, a 5-member heteroaryl with 1-2 heteroatoms selected from S, N, cyano, lower alkyl, -(CH2)n-C3-C7-cycloalkyl, -(CH2)n-N(R)2, -(CH2)n-O-lower alkyl or -(CH2)n-OH; equals 0, 1 or 2; R denotes hydrogen or lower alkyl; R2 denotes C3-C7-cycloalkyl, phenyl, 5-6-member heteroaryl with 1 heteroatom selected from N, S or a 9-10-member bicyclic heteroaryl with 1-3 heteroatoms selected from N, which are possibly substituted with one or more substitutes selected from a group comprising halogen, cyano, nitro, oxo group, lower alkyl, lower alkyl substituted with a halogen, lower alkoxy, lower alkoxy substituted with a halogen, -C(O)O-lower alkyl, lower alkylsulphonyl, -NRaRb, -C(O)-NRaRb, -C(O)-(6-member heterocyclyl with 2 heteroatoms selected from N, O), benzyloxy, 6-member heterocyclyl with 1-2 heteroatoms selected from N, S, O, possibly substituted with hydroxy, 1-2 oxo-groups, halogen or lower alkyl, or selected from a 5-6-member heteroaryl with 1-3 heteroatoms selected from N, possibly substituted with lower alkyl; Ra and Rb independently denote hydrogen, lower alkylsulphonyl, -C(O)H, -(CH2)n-N(R)2, -(CH2)n-O-lower alkyl, -(CH2)n-S-lower alkyl, -(CH2)n-S(O)2-lower alkyl, (5-member heteroaryl with 1 heteroatom selected from S)-sulphonyl, lower alkyl, -(CH2)n-(5-6-member heterocyclyl with 1 heteroatom selected from O, N), possibly substituted with lower alkyl, oxo group, or denotes -(CH2)n-C3-C7-cycloalkyl, -(CH2)n-(5-6-member heteroaryl with 1-2 heteroatoms selected from N), possibly substituted with an oxo group, -(CH2)n-OH, -(CO)-R', where R' denotes C3-C7-cycloalkyl, a 5-member heteroaryl with 1 heteroatom selected from S, or lower alkyl; R' denotes a phenyl or a 6-member heteroaryl with 1 heteroatom selected from N which are possibly substituted with a halogen or lower alkyl, optionally substituted with a halogen. The invention also relates to a medicinal agent containing one or more compounds of formula I and use of the disclosed compounds to prepare a medicinal agent.

EFFECT: high effectiveness of derivatives.

16 cl, 145 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof , where D denotes phenyl; n equals 0; A, B and Q denote hydrogen; Z is selected from a group comprising a bond, straight C1-3alkylene; R1 is selected from a group comprising hydrogen, C1-10alkyl, C3-8cycloalkyl, benzyl, a 6-member monocyclic, 9-10-member bicyclic aromatic carbon-containing ring system and a spiro-ring system of formula (V): where X1 and X3 denote O; and where the said alkyl, cycloalkyl or benzyl from the R1 group is optionally substituted with 1-3 substitutes selected from a group comprising C1-3alkyl, cyano, phenyl, wherein the said phenyl is optionally substituted with 1-3 substitutes selected from halogen. The invention also relates to compounds of formulae .

Values of radicals of the said compounds are given in the claim. The invention also relates to a pharmaceutical composition having ORL1 receptor or µ opioid receptor inhibiting properties, containing an effective amount of the disclosed compound, a method of curing pain and a method of modulating pharmacological response from the opioid receptor, including the ORL1 or µ opioid receptor.

EFFECT: improved method.

41 cl, 5 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula as well as separate enantiomers, diastereomers, racemic mixures and pharmaceutically acceptable salts thereof, having mitotic kinesin KSP inhibiting activity, as well as inhibitory action on tumour cells, use thereof in preparing a medicinal agent and a pharmaceutical composition based on said compounds. In said formula, R denotes Z-NR2R3, Z-OH, Ar1 and Ar2 independently denote a phenyl which, if needed, is substituted with one or more groups independently selected from: F, CI, Br, I, OH, Z denotes an alkylene having 1-6 carbon atoms which, if needed, is substituted with C1-6alkyl, and R1 assumes values given in the claim.

EFFECT: improved method.

16 cl, 3 dwg, 124 ex

Iap inhibitors // 2425838

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

, which can inhibit binding of protein Smac with apoptosis protein inhibitor (IAP).

EFFECT: improved properties of the inhibitor.

4 cl, 198 ex

Heterocompound // 2425832

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

or pharmaceutically acceptable salt thereof, where symbols assume the following values; ring denotes

or , X denotes a single bond, -CH2-, -NR3-, -O-, -S-, R1 denotes a halogen; phenyl; pyridyl; (C3-C8)cycloalkyl; or (C1-C6) alkyl or (C2-C6) alkenyl, each of which can contain a halogen, -CONH2, phenyl or (C3-C8)cycloalkyl as a substitute, R2 denotes CN, -O-(C1-C6)alkyl, -C(=O)H, halogen; or (C1-C6)alkyl, which can be substituted with a halogen or -OH, R3 can form morpholino or 1-pyrrolidinyl together with R1 and nitrogen, and when X denotes a single bond, R1 and R2 can jointly form a 5-member ring and additionally contain -(C1-C6)alkyl as a substitute, R4 denotes the following ring: , , , , , , , , , , or , where any one of the bonds in the ring is linked to an oxazole ring, R5 denotes -H, (C1-C6)alkyl, which can be substituted by not less than one group selected from: -C(=O)NRXRY, -NHRX and -ORX- (C2-C6)alkenyl-; -C(=O)H; -C(=O)NRXRY, RX and RY can be identical or different and denote -H; or (C1-C6)alkyl. The invention also relates to a pharmaceutical composition based on said compounds, having SlP1 agonist activity.

EFFECT: compounds and compositions can be used in medicine for preventing and treating rejection during organ transplant, bone marrow or tissue transplant and autoimmune diseases.

16 cl, 84 tbl, 198 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel benzimidazole derivatives of formula any isomers thereof or any mixture of isomers thereof or a pharmaceutically acceptable salt, where R is -(CR'R")n-Rc, where Rc is C1-6-alkyl, R' is hydrogen or C1-6-alkyl, and R" is hydroxy; n equals 1; X is N; and Y, Z and W is CRd, where each Rd is hydrogen; Ro is halogen. The invention also relates to a pharmaceutical composition containing a compound of formula I, use of the compound of formula I and a GABAA-receptor complex modulating method.

EFFECT: obtaining novel benzimidazole derivatives which are sensitive to GABAA-receptor complex modulation.

8 cl, 1 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: pharmaceutical compositions containing at least one compound of formula (IIIa) or (IIIb) or (IVa) or (IVb), where -X- and Y are described in the claims, or pharmaceutically acceptable salts, esters or amides thereof and a pharmaceutically acceptable carrier, which can be used in processes with modulation or E- and P-selectin expression.

EFFECT: obtaining low-molecular non-glycoside and non-peptide compounds, capable of creating antagonism to selectin-mediated processes.

11 cl, 38 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula or salts thereof, and compounds of formula or salts thereof, where R3 denotes C1-C7alkyl or C3-C8cycloalkyl, and R4 denotes C1-C7alkyl or C3-C8cycloalkyl, and Act denotes an activating group selected from an amino protective group, mainly carbamate, as well as methods of producing said compounds. The invention also discloses a method, novel steps of the method and novel intermediate compounds for use in synthesis of pharmaceutically active compounds, mainly renin inhibitors, such as aliskiren. Also, when compounds (VI) react with organometallic compounds (VII) , where Y denotes a metal-containing group such as Li, -MgX, magnesate, aryl-magnesium compound, alkylmagnesium compound, -MnX, (alkyl)3MnLi- or -CeX2, where X is a halogen such as Cl, I or Br, more preferably Br, novel compounds are obtained, R3 and R4 assume values given for compounds of formula (II), and Act denotes an activating group selected from an amino protective group, mainly carbamate, R1 denotes a halogen, hydroxyl, halogen(C1-C6)alkyl, C1-C6alkoxy(C1-C6)alkyloxy or C1-C6alkoxy(C1-C6)alkyl, R2 denotes a halogen, hydroxyl, C1-C4alkyl or C1-C4alkoxy, which are direct precursors for producing aliskiren.

EFFECT: novel compounds and synthesis methods thereof are obtained and described.

61 cl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (I) where R1 represents or and values of R2, R3 and R4 radicals are given in the invention formula, as well as to pharmaceutical compositions based on said compounds.

EFFECT: compounds of formula (I) and based on them compositions can be applied for treatment of cancer diseases: both solid tumours and hematologic cancers, such as leukemia, lymphoma and multiple myelomas.

11 cl, 10 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to enantiomerically pure compound, represented by the following formula (I) or to its pharmaceutically acceptable salt where R1 represents phenyl, which is substituted with 2 different substituents selected from: halogen, fluoromethyl, difluoromethyl and trifluoromethyl, on condition that if one of substituents on phenyl group represents halogen, the other substituent is not halogen; R2 and R3 each is independently selected from: hydroxyl and OR8; where R8 represents substituted or unsubstituted C1-C10-alkyl, C1-C4-alkanoyl, substituted or unsubstituted aroyl; R4 represents C1-C4-alkylene hydroxyl; and R9 represents hydrogen or C1-C4-alkyl, to its enantiomerically pure intermediates, to methods of obtaining enantiomerically pure compound (I) and its intermediates, and to pharmaceutical composition, which includes enantiomerically pure compound of formula (I), as well as to application of formula (I) compound for manufacturing medication for cancer treatment.

EFFECT: obtained and described is novel enantiomerically pure compound, which can be usefull in treatment of diseases or disorders, mediated by inhibiting of cyclin-dependent kinase, for instance, cancer.

9 cl, 98 ex, 2 tbl, 3 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-quinolyloxazoles of formula (I) or pharmaceutically acceptable salts thereof, having PDE4 inhibiting properties, a pharmaceutical composition based on said compounds and use thereof to prepare a medicinal agent which inhibits inflammatory cell recruitment in respiratory tracts. , where is , X is O, R1 is alkyl, R3 and R4 are independently selected from H, R5 and R6 are independently selected from a group comprising H, alkyl, hydroxyalkyl, t equals 1 or 2. Values of substitutes R7-R11, R13 are given in the formula of invention.

EFFECT: high efficiency of using the composition.

24 cl, 1 dwg, 64 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrrole derivatives of the formula I: , where R1 and R2 independently denote Ph; mono- or disubstituted in different positions of the ring Ph, where substitute denotes -OCH3; C5-heteroaryl with one heteroatom selected from O or S; R2 denotes H, NO2, NH2, C(O)NH2; R4 denotes H, a straight or branched C1-C6-alkyl; n equals the number of methylene groups and is between 1 and 8 inclusively; X denotes O, S, NH; Y NH, -CH2-; Z denotes O, S; W denotes -OH, hydroxylamine, hydrazine, alkylhydrazine.

EFFECT: compounds can inhibit histone deacetylase, which enables their use in cancer treatment.

10 cl, 9 dwg, 18 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new cyclopenta[b]benzofuranyl derivatives of formula wherein substitutes R1, R2, R3, R4, R5, R6 and R7 and n are specified in the patent clam. These compounds exhibit properties of NF-kB-activity and/or AP-1 inhibitor/modulator. Also, the inventive subject matter are methods for preparing intermediate compounds thereof, a pharmaceutical composition containing them, administration thereof for prevention and/or treatment of inflammatory and autoimmune diseases, neurodegenerative diseases and hyperproliferative diseases caused by NF-kB- and/or AP-1-activity, and a method for prevention and/or treatment of said diseases.

EFFECT: preparation of new cyclopenta[b]benzofuranyl derivatives.

21 cl, 3 tbl, 151 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel AMPA receptor antagonists - 1H-quinazoline-2,4-dione derivatives, selected from the group: N-(6-imidazol-1-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-morpholin-4-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrrol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(7-nitro-2,4-dioxo-6-[1,2,4]triazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrrolidin-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-azetidin-1-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-[1,2,3]triazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-morpholin-4-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(2,4-dioxo-6-[1,2,4]triazol-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; (2,4-dioxo-6-[1,2,4]triazol-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)amide ethanesulphonic acid; N-(6-imidazol-1-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(2,4-dioxo-6-thiomorpholin-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(6-[1,4]oxazepan-4-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide and N-(6-azetidin-1-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide and physiologically acceptable salts thereof.

EFFECT: compounds can be used in treating such diseases as epilepsy and schizophrenia.

9 cl, 106 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing a compound of formula (IIa)

and its salt, involving use of protective groups which can be easily incorporated into the compound, have large mass, are stable in the presence of organometallic reagents and be easily, and with high output, removed from in an acidic medium, as well as to novel intermediate compounds used during steps of this method, having general formula (IVe)

, where R5 and R'5 independently denote C1-C7-alkyl, R6 and R8 denote hydrogen, R7 and R9 together form C2-C5-alkylene.

EFFECT: easy production of angiotensin receptor blocker.

8 cl, 11 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel benzimidazole derivatives of formula any isomers thereof or any mixture of isomers thereof or a pharmaceutically acceptable salt, where R is -(CR'R")n-Rc, where Rc is C1-6-alkyl, R' is hydrogen or C1-6-alkyl, and R" is hydroxy; n equals 1; X is N; and Y, Z and W is CRd, where each Rd is hydrogen; Ro is halogen. The invention also relates to a pharmaceutical composition containing a compound of formula I, use of the compound of formula I and a GABAA-receptor complex modulating method.

EFFECT: obtaining novel benzimidazole derivatives which are sensitive to GABAA-receptor complex modulation.

8 cl, 1 tbl, 9 ex

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