Additional heterocyclic compounds and their applicaition as antagonists of metabotropic glutamate receptor

FIELD: pharmacology.

SUBSTANCE: invention concerns compounds of the formula and other compounds listed in cl. 1 of invention claim, and pharmaceutical composition based on them, as well as method of mGluR5 receptor activity inhibition involving claimed compounds.

EFFECT: application in treatment and prevention of diseases mediated by mGluR5 receptor activity.

4 cl, 18 dwg, 1009 ex

 

The text descriptions are given in facsimile form.

1. The compound or its pharmaceutically acceptable salt selected from the group consisting of the compounds listed in the following table:

2. Pharmaceutical composition having the property of mGluR5 receptor antagonist containing as an active ingredient a therapeutically effective amount of a compound according to claim 1 in Association with one or more pharmaceutically acceptable diluent, excipients and/or inert carrier.

3. The compound according to claim 1, having the property of mGluR5 receptor antagonist.

4. Method of inhibiting activation of receptors, mGluRS, in which the cell containing the specified receptor, is treated with an effective amount of a compound according to claim 1.



 

Same patents:

FIELD: medicine.

SUBSTANCE: according to the invention there is provided substituted indolequinoxalines of the formula (I), where R1 represents hydrogen or represents one or more similar or different substituent in positions from 7 to 10, selected of the group of halogen, low alkyl/alkoxy, hydroxy, triflouromethyl, trichloromethyl, triflouromethoxy, R2 represents similar or different C1-C4 alkyl substituents, X represents CO or CH2, Y represents OH, NH2, NH-(CH2)n-R3, where R3 represents low alkyl, OH, NH2, NHR4 or NR5R6, where R4, R5 and R6 represent low alkyl or cycloalkyl independently and n represents integer from 2 to 4 provided that X represents CH2, Y represents OH or NH-(CH2)n-OH and its pharmaceutically acceptable salt. There is also provided pharmaceutical composition, containing these compounds, methods of compound producing, formula (I).

EFFECT: compounds are applied as medicine for treatment and prevention of autoimmune diseases.

15 cl, 1 ex, 5 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to antagonists of serotonin 5-HT6 receptors - substituted 4-sulphonylpyrazoles and 3-sulphonyl-pyrazolo[1,5-a]pyrimidines of general formula 1 or general formula 1.2. These compounds can be used for treating and preventing development of different cognitive and neurodegenerative diseases of the central nervous system. In general formulae 1 and 1.2, 1 1.2 respectively, Ar is optionally substituted phenyl or optionally substituted 5-6-member heteroaryl, containing a nitrogen, oxygen or sulphur atom as a heteroatom; R1 is a hydrogen atom, optionally substituted C1-C5 alkyl, lower acyl or optionally substituted phenyl; R2 is an optionally substituted amino group or substituted hydroxy group or R1, together with the nitrogen atom to which it is bonded, and R2, together with the carbon atom to which it is bonded, form a substituted pyrimidine ring; R3 is a hydrogen atom, optionally substituted C1-C5alkyl, substituted hydroxyl group or substituted sulphanyl group, R5 is a hydrogen atom, optionally substituted C1-C5alkyl, substituted hydroxyl group or substituted sulphanyl group, R7 and R9 independently represent a hydrogen atom, C1-C3alkyl or phenyl, R8 is a hydrogen atom.

EFFECT: new compounds have useful biological properties.

13 cl, 2 dwg, 4 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: new derivative of diaminopyrroloquinazolines of formula (I) and their pharmaceutically acceptable salts possess properties of proteintyrosine posphatase PTP1 inhibitors which can be used for treating the diseases mediated by action of the latter, particularly for decreasing glucose content in blood. In formula (I) , A stands for 6-membered aromatic ring, or 5- or 6-membered aromatic ring which contains 1 or 2 heteroatoms chosen from S, N and O; R1 is specified from the group including the following radicals: C1-6alkyl, hydroxyC1-6alkyl, mono- or dihydroxy-substituted C1-6alkyl, phenyl-(C1-6alkyl), benzyloxyC1-6alkyl and phenyl-(C1-6alkoxy)C1-6alkyl; R2 is specified from the group including the following radicals: hydrogen, C1-6alkyl, hydroxyC1-6alkyl, mono- or dihydroxy-substituted C1-6alkyl, phenyl-(C1-6alkyl) and phenyl-(C1-6alkoxy)C1-6alkyl; R3 represents hydrogen or methyl; Ra is specified from the group including the following radicals: hydrogen, C1-6alkyl, C1-6alkoxy, hydroxyC1-6alkyl, mono- or dihydroxy-substituted C1-6alkyl, phenyl(C1-6alkyl), benzyloxyC1-6alkyl or ; R10 represents hydrogen or ; x and y separately stand for integers 0 to 4; Rb and Rc are separately specified from the group including the following radicals: hydrogen, C1-6alkyl, perfluorochemical C1-6alkyl, substituted C1-6alkyl, C1-6alkoxy, phenoxy, halogen, (unsubstituted C1-6alkyl)-(substituted phenyl)-(C1-6alkyl), phenyl-(C1-6alkoxy) or ; R11 represents hydrogen, phenyl or unsubstituted C1-6alkyl; p stands for integer 0 to 1; Rd represents hydrogen, substituted C1-6alkyl or perfluorochemical C1-6alkyl; Re represents hydrogen, halogen, substituted C1-6alkyl and perfluorochemical C1-6alkyl; Rf represents hydrogen or C1-6alkyl; the substitutes found in alkyl groups are independently specified from the following groups: hydroxy, C1-6alkoxy, C1-6alkanoyl; and the substitutes found in substituted phenyl as Rb and Rc, are independently specified from the following groups: C1-6alkyl, C1-6alkoxy, hydroxyC1-6alkyl, hydroxyl, hydroxylC1-6alkoxy, halogen, perfluorC1-6alkyl and C1-6alkanoyl.

EFFECT: improved properties of the derivatives.

29 cl, 2 dwg, 48 ex

FIELD: medicine.

SUBSTANCE: invention covers new pyrrolopyrimidine and pyrrolotriazine derivatives substituted with carbamoyl group of formula [I], characterised as a CRF (corticotrophin release factor) receptor antagonist. The compounds can be effective as a therapeutic or preventive agent for such diseases, as depression, anxiety, Alzheimer's disease, Parkinson's disease, etc. in formula [I]: E means N or CR10; R1 means -OR4, -S(O)1R4 or-NR4R5; R2 means hydrogen, C1-6alkyl; R3 means hydrogen; R4 and R5 are identical or different, and independently mean hydrogen, C1-9alkyl, di(C3-7cycloalkyl)-C1-6alkyl, C1-6alkoxy-C1-6alkyl, di(C1-6alkoxy)-C1-6alkyl, hydroxy-C1-6alkyl, cyano-C1-6alkyl, carbamoyl-C1-6alkyl or di(C1-6alkyl)amino-C2-6alkyl, or R4 and R5 together form (CH2)m-A-(CH2)n where A means CHR9; R9 means hydrogen, hydroxy-C1-6alkyl, or cyano-C1-6alkyl; R10 means hydrogen; I means an integer 0, 1 and 2; m means an integer 1, 2, 3 and 4; n means an integer 0, 1, 2 and 3; Ar means phenyl, and specified phenyl is substituted by one or more substitutes being identical or different, and chosen from the group consisting of halogen, C1-6alkyl, trifluoromethyl; their individual isomers or pharmaceutically acceptable salts.

EFFECT: extended application.

9 cl, 2 dwg, 2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula I where R1 stands for phenyl; G stands for C1-C7-alkylene; Q stands for -NH-; and X stands for C1-C7- alkylene, or to its salts. In addition, the invention concerns a pharmaceutical composition, to application of compound of formula I as defined in claims 1-5 item, as well as the method for making the compound of formula I.

EFFECT: production of the new biologically active compounds inhibiting protein tyrosine kinase.

8 cl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to new pyridine derivatives or to their pharmaceutically acceptable salts of general formula 1: wherein R1, R2, R3, R4, R5, R6 and R7 are independently chosen from the group including hydrogen atom, halogen, amino, C1-C6lower alkyl, C2-C6lower alkenyl, C1-C6lower alkoxy, C1-C10alkylamino, C4-C9cycloalkylamino, C4-C9heterocycloalkylamino, C1-C10aralkylamino, arylamino, acylamino, saturated heterocyclyl, acyloxy, aryl, heteroaryl, C1-C10aralkyl, aryloxy; X represents oxygen or sulphur atom; Y represents oxygen atom or N-R8, wherein R8 is chosen from the group including hydrogen atom; aforesaid aryl group is chosen from phenyl, naphthyl and condensed phenyl group; aforesaid heteroaryl and saturated heterocyclic groups represent pentagonal or hexagonal heterocyclic ring containing 1 to 2 heteroatoms chosen from oxygen, nitrogen and sulphur atom; or condensed heterocyclic ring; and aforesaid aryl and heteroaryl groups are those that 1 to 4 assistants chosen from group including halogen, C1-C6lower alkyl, C1-C6lower alkoxy are substituted. And specified compounds or their pharmaceutically acceptable salt of formula 1 are not compounds as follows 6-methyl-3,4-dihydro-pyrano[3,4-c]pyridin-1-one, 5-vinyl-3,4-dihydro-pyrano[3,4-c]pyridin-1-one, 6-methyl-8-furan-2-yl-3,4- dihydropyrano[3,4-c]pyridin-1-one, 3-tert-butyl-5,6,7,8-tetrahydro-[2,7]naphthyridine-8-one and dimethyl ether (3S)-6,8-dimethyl-1-oxo-1,2,3,4-tetrahydro-[2,7]naphthyridine-3,5-dicarboxylic acids.

EFFECT: compounds possess inhibitory action with respect to formation of cytokines involved in inflammatory reactions, can be used as a therapeutic agent for treatment of inflammatory diseases, immune diseases, chronic inflammations; it provides antiinflammatory and analgesic action.

21 cl, 7 tbl, 144 ex

FIELD: chemistry.

SUBSTANCE: described is novel application of 2-methylthio-5-methyl-6-nitro-1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-on. Substance possesses anti-viral activity with respect to flue A (H5N1) virus, West Nile virus and other viral infections. Wide-spectrum anti-viral activity is discovered for the first time.

EFFECT: obtaining anti-viral substance with wide spectrum of action.

1 cl, 8 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to novel derivatives of 2,6-dihydro-7H- pyrazolo[3,4-d]pyradazin-7-one, 1,4-dihydropyrazolo[3,4-b]thiazin-5(6H)-one; N-acylated 4-imidazo[1,2-a]pyridin-2-yl- and 4-imidazo[1,2-a]pyrimidin-2-yl- anilines; amides of [(4H-thieno[3,2-b]pyrrol-5-yl)carbonyl]pyperidin-4-carboxylic acid; amides of 2-(4-carbamoylpyperidin-1-yl)isonicotinic acid; amides of N-sulfonyl-1,2,3,4-tetrahydrochinolin-6-carboxylic acid; as well as to N-acylated 3-azolyl derivatives of 2-amino-4,5,6,7-tetrahydtithieno[2,3-c]pyridine possessing properties of Hh-signal cascade inhibitors.

EFFECT: compounds can be applied for use in pharmaceutical compositions and medications for treating diseases induced by abberant activity of Hedgehog (Hh) signal system, in particular, oncological diseases, for instance, for pancreatic carcinoma treatment.

23 cl, 13 dwg, 11 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel diazaindoledicarbonylpiperazinyl compounds of formula I, including its pharmaceutically acceptable salts, which possess antiviral activity and can be used for HIV-infection treatment. In compounds of formula I Q represents , T represents -C(O)- or -CH(CN)-; R1 represents hydrogen; R3 represents hydrogen; R5 is independently selected from group including halogen, cyano, XR9 and B; R2 and R4 are absent; R6 represents hydrogen; -- represents carbon-carbon bond; -Y- is selected from group including , each of R10, R11, R12, R13, R14, R15, R16 and R17 represents H; R18 is selected from group including C(O)-phenyl, isoquinolyl, quinazolyl; D is selected from group including cyano, 5-member heteroaryl containing 3 heteroatoms selected from nitrogen and oxygen; A is selected from group including phenyl, pyridinyl; B is selected from group including -C(O)CH3; piperazinyl; 5-, 6-member heteroaryl containing 1-3 N atoms and possibly O atom; where said heteroaryl optionally is substituted with from one to three similar or different substituents selected from F; F is selected from group including (C1-6)alkyl, phenyl, pyridinyl, COOR26, -COR21, and -CONR24R25; where phenyl is optionally substituted with (C1-6)alkoxy, CF3, or halogen atom; R9, R24, R25 and R26 each is independently selected from group including hydrogen and (C1-6)alkyl; X represents O; R27 represents piperazinyl, N-methylpiperazinyl, or 3-pirazolyl. Invention also relates to pharmaceutical composition.

EFFECT: obtaining compounds and pharmaceutically acceptable salts, which possess antiviral activity and can be used for treatment of HIV infection.

19 cl, 50 dwg, 4 tbl, 43 ex

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

FIELD: medicine.

SUBSTANCE: invention refers to the compound of the formula (I) , where R1 is a group of the formula and, in which R2, R3, R4, R5, R6, R7 and R8, each one independently represents a hydrogen atom or C1-6alkyl or its salt, to the method of its producing, to the method of antagonist effect on angiotensin II in the mammal, to the application of compounds of formula (I) as well as to methods of diseases prevention or treatment.

EFFECT: there are produced and provided new compounds that can be applied for prevention or treatment of disturbed circulation.

16 cl, 2 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: invention refers to salt N,2-dimetyl-6-[7-(2-morpholinoethoxy)chinoline-4-iloxy]benzofuran-3-carboxamide, particularly bismaleate N,2-dimetyl-6-[7-(2-morpholinoethoxy)chinoline-4-iloxy]benzofuran-3-carboxamide with antitumor activity.

EFFECT: cancer treatment availability.

11 cl, 35 dwg, 9 tbl, 12 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to compounds of general formula (I) in the state of base salt or acid-addition salt, to method of their preparation and to the pharmaceutical composition thereof In the said formula R1 is (C1-C6)alkyl; (C3-C7)cycloalkyl unsubstituted or substituted once or more than once; (C3-C7)cycloalkylmethyl unsubstituted or substituted once or more than once; phenyl unsubstituted or substituted ; benzyl unsubstituted or substituted once or twice ; thienyl unsubstituted or substituted ; R2 is atom hydrogen or (C1-C3)alkyl; R3 is (C1-C5)alkyl; R4, R5, R6, R7, each R8 and R9 independently represents the atom of hydrogen, atom of halogen, (C1-C7)alkyl, (C1-C5)alkoxy or trifluoromethyl radical; n is 0, 1 or 2; Alk is (C1-C4)alkyl.

EFFECT: new compounds possess useful biological activity.

5 cl, 5 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the aminopyridin compound of general formula (I) or its salt wherein X1, X2, X3, Z, Y1, Y2 are carbon or nitrogen atom, R, R1, R5, R6 are hydrogen atom, alkyl group, further see formula of the invention, and R7 is hydrogen or halogen atom, nitro or cyano group, -CpH2(p-1)(Ra1)(Ra2)-O-Ra3, -C(=O)-Rd1, 5-or 6-membered saturated heterocycle group, aromatic heterocycle group, -N(Rh1)(Rh2), further see formula of the invention. The invention refers also to the pharmaceutic composition thereof intended for treatment or prevention of allergic diseases, autoimmune diseases caused by malignant tumour, to the Syk inhibitor containing the compound of formula I and to the therapeutic and/or preventive agent.

EFFECT: compounds which not only possess high Syk inhibition activity but are selective Syk inhibitors are obtained and described.

24 cl, 24 ex, 2 tbl

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

FIELD: chemistry, medicine.

SUBSTANCE: invention refers to the triheterocylic compounds of formula (Ia) and their pharmaceutically acceptable salts used as growth inhibitors of the cancer or tumor cells, to the preparation method and pharmaceutical compositions thereof, to the treatment method used aforesaid compounds as well as to the intermediates of formula (II) the to the method of its preparation. In general formulas (Ia) and

, Q1 is -N(R1)-; Q2 is -C(R3)-; Q3 is -C(R5)-; Q4 is -C(R9)-; R1 is -Ym(Ra), where -Ra is -H, -OH, -C(O)R14, -O-C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OS(O)2ONa-; R2 is -H; R3, R4 and R5 independently are -Ym(Rb), where Rb is -H, halogen, -C1-C8 alkyl, -O-(C1-C8 alkyl) or -OR14, -at condition that if value m of radical Ym(Rb) is equal 0, then R5 is not H; R6 is -H; R7 is -Ym-(RC), where -RC is -O-(C1-C8 alkyl) or -NH(phenyl), R8 is -Ym(Rd), where - Rd is -H, -OH, R9, R10, R11, R12 and R13 independently are -Ym(Re), where Re is -H, halogen, 5-6-membered heterocycle containing 2 heteroatoms selected from N or O, -OR14, or -O-C(O)OR14; every R14 independently is -H, -C1-C8 alkyl, -phenyl, 5-6-membered heterocycle containing one heteroatom being S; every Y independently is -C1-C8 alkylene-; every m independently is equal 0 or 1.

EFFECT: claimed compounds can find application for treatment of different cancer species.

41 cl, 4 tbl, 4 dwg, 8 ex

FIELD: chemistry; medicine.

SUBSTANCE: compounds of claimed invention possess properties of positive allosteric modulator mGluR5. In general formula I , W represents 6-member heterocycloalkyl ring with 1-2 heteroatoms, selected from N, O; R1 and R2 independently represent hydrogen, C1-C6-alkyl; P and Q each independently is selected from: , R3, R4, R5, R6 and R7 independently represent hydrogen; halogen; -CN; nitro; C1-C6-alkyl; C3-C6-cycloalkyl; halogen-C1-C6-alkyl; 5-6-member heteroaryl with 1-2 atoms N as heteroatoms; 6-member heterocycle with 2 heteroatoms representing N, O; phenyl, optionally substituted with halogen; naphtyl; -OR8; where optionally two substituents together with located between them atoms form 9-10-member bicyclic aryl or heteroaryl ring with 1-2 heteroatoms, selected from N, S; R8 represents hydrogen, C1-C6-alkyl; D, E, F, G and H independently represent -C(R3)=, -O-, -N=, -N(R3)- or -S-; A represents ethinyl, -C(=O)NR8- or group of formula . B represents -C(=O)-C0-C2-alkyl-, -C(=O)-C2-C6-alkenyl-. Invention also relates to pharmaceutical composition based on invention compounds.

EFFECT: novel compounds possess useful biological proprties.

20 cl, 3 dwg, 75 ex

FIELD: chemistry.

SUBSTANCE: invention can be applied in medicine and concerns inhibitors of MaR-kinase p38 of formula where W represents N or O, when Y represents C, and W represents C, when Y represents N; U represents CH or N; V represents C-E or N; X represents O, S, SO, SO2, NH, C=O,-C=NOR1 or CHOR1; B represents H or NH2; R1, E and A stands for H or various alkyl, heteroalkyl, aromatic and heteroaromatic substitutes.

EFFECT: production of new biologically active compounds.

48 cl, 138 ex, 54 dwg

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to novel 2,4-pyridindiamine compounds of formula (1). In structural formula (I) L1 is direct bond; L2 is direct bond; R2 is phenyl group, three times substituted with three groups R8; R4 is X represents N; Y is selected from group consisting of O, NH, S, SO and SO2; Z is selected from group consisting of O, NH; on condition that if Y is selected from group consisting of NH, S, SO and SO2, Z is not the same as Y; R5 is selected from group consisting from R6, halogen; each R6 is independently selected from group consisting of hydrogen, halogen; R8 is selected from group consisting from Ra, Rb, Ra substituted with one or several similar or different groups Ra or Rb, -ORa, -O-CHRaRb; each R35 independently on others is selected from group consisting of hydrogen and R35, or in alternative case, two groups R35, bound to one and the same carbon atom are taken together with formation of oxogroup (=O), and the remaining two groups R35 each independently on each other are selected from group consisting from hydrogen and R8; each Ra is independently selected from group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl; each Rb is suitable group which is independently selected from group consisting of -ORd, halogen, -CF3, -C(O)NRcRc, and -OC(O)ORd; each Rc is independently protective group or Ra; each Rd is independently protective group or Ra; each index m is independently integer number from 1 to 3.

EFFECT: novel compounds can be used for treatment or prevention of autoimmune diseases, for instance such as rheumatoid arthritis and/or related to it symptoms, systemic lupus erythematosus and/or related to it symptoms, as well as and/or related to it symptoms.

41 cl, 14 dwg, 1 ex

FIELD: chemistry.

SUBSTANCE: described is novel compound of formula (I)

or its pharmaceutically acceptable salt, values of radicals are given in invention formula Compound has ability to inhibit receptor mGluR5, which intends it for prevention and/or treatment of receptor mGluR5- associated disturbances. Also described is pharmaceutical composition, method of inhibiting activation of receptors mGluR5, using compound of formula (I). Described is method of obtaining compound of formula 1a or 1b structure.

EFFECT: increasing output of suitable product.

18 cl, 825 ex

FIELD: pharmacology.

SUBSTANCE: invention concerns indazol derivatives of general formulae (I) or (II) , where radicals and groups are defined as shown in cl. 1 of invention claim, and their pharmaceutically acceptable salts. Also invention claims medicine, method of medicine obtainment and application of claimed compounds in treatment and/or prevention of fatty acid metabolism derangement and glucose assimilation disorders.

EFFECT: inhibition of hormone-sensitive lipases.

13 cl, 1 tbl, 103 ex

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