Bicyclic amides as kinase inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to specific derivatives of bicyclic amides disclosed in the claim, as well as a pharmaceutical composition.

EFFECT: compounds having protein kinase inhibiting activity, meant for use in treating protein kinase-dependant diseases, preferably proliferative diseases such as tumorous diseases.

13 cl, 115 ex

 

The text descriptions are given in facsimile form.

1. (3-Triptoreline)amide 7-(2-aminopyrimidine-4-yloxy)-2,3-dihydrobenzo[1,4]oxazin-4-carboxylic acid (4-morpholine-4-ylmethyl-3-triptoreline)amide 7-(2-aminopyrimidine-4-yloxy)-2,3-dihydrobenzo[1,4]oxazin-4-carboxylic acid,
or tautomer, or its salt.

2. The compound of the formula

where

denotes a group selected from
,,, ,or,
or tautomer, or its salt.

3. (4-Methyl-3-triptoreline)amide 6-(2-aminopyrimidine-4-yloxy)-naphthalene-1-carboxylic acid, or
(2-triptorelin-4-yl)amide 6-(2-aminopyrimidine-4-yloxy)-naphthalene-1-carboxylic acid, or its tautomer, or its salt.

4. The compound of the formula

where

denotes a group selected from
,,,or,
or tautomer, or its salt.

5. (3-Triptoreline)amide 6-(2-acetylpiperidine-4-yloxy)-naphthalene-1-carboxylic acid,
(3-triptoreline)amide 6-(2-methoxycarbonylaminophenyl-4-yloxy)naphthalene-1-carboxylic acid,
(4-methyl-3-triptoreline)amide 7-(2-acetylpiperidine-4-yloxy)-2,3-dihydrobenzo[1,4]oxazin-4-carboxylic acid,
(4-methyl-3-triptoreline)amide 7-(2-methoxycarbonylamino-pyrimidine-4-yloxy)-2,3-dihydrobenzo[1,4]oxazin-4-carboxylic acid,
[4-(4-methylpiperazin-1-ylmethyl)-3-triptoreline]amide 7-(2-aminopyrimidine-4-yloxy)-2,3-dihydrobenzo[1,4]oxazin-4-carboxylic acid,
(4-morpholine-4-yl-3-triptoreline)amide 6-(2-aminopyrimidine-4-yloxy)naphthalene-1-carboxylic acid,
CIS/TRANS-(-isopropylcyclohexane)amide 6-(2-aminopyrimidine-4-yloxy)-naphthalene-1-carboxylic acid,
(3-triptoreline)amide 6-(2-amino-6-chloropyrimidine-4-yloxy)-benzooxazol-3-carboxylic acid,
(3-triptoreline)amide 6-(2-aminopyrimidine-4-yloxy)benzooxazol-3-carboxylic acid, or
(3-trifluoromethyl-4-chlorophenyl)amide 6-(2-amino-6-chloropyrimidine-4-yloxy)naphthalene-1-carboxylic acid, or its tautomer, or its salt.

6. (4-Fluoro-3-triptoreline)amide 6-(2-amino-6-chloropyrimidine-4-yloxy)benzooxazol-3-carboxylic acid,
(4-fluoro-3-triptoreline)amide 6-(2-aminopyrimidine-4-yloxy)-benzooxazol-3-carboxylic acid,
(3-trifluoromethyl-4-chlorophenyl)amide 6-(2-aminopyrimidine-4-yloxy)-naphthalene-1-carboxylic acid,
[4-(4-methylpiperazin-1-ylmethyl)-3-triptoreline] amide of 6-(2-aminopyrimidine-4-yloxy)naphthalene-1-carboxylic acid, or
[3,4-bis(trifluoromethyl)phenyl]amide of 6-(2-aminopyrimidine-4-yloxy)-naphthalene-1-carboxylic acid,
the compound of the formula

where

selected from
,,,,,,
,,,or,
(3-triptoreline)amide 6-(6-cyanopyrimidine-4-yloxy)-naphthalene-1-Carbo the OIC acid,
(3-triptoreline)amide 6-(6-aminomethylpyrimidine-4-yloxy)-naphthalene-1-carboxylic acid,
methyl ester {6-[5-(3-cryptomaterial)naphthalene-2-yloxy]pyrimidine-4-ylmethyl}carbamino acid, ethyl ester of 6-[5-(3-cryptomaterial)naphthalene-2-yloxy]-pyrimidine-4-carboxylic acid,
6-[5-(3-cryptomaterial)naphthalene-2-yloxy]pyrimidine-4-carboxylic acid,
dimethylamide 6-[5-(3-cryptomaterial)naphthalene-2-yloxy]-pyrimidine-4-carboxylic acid,
amide 6-[5-(3-trifluoromethyl an phenylcarbamoyl)naphthalene-2-yloxy]-pyrimidine-4-carboxylic acid,
methylamide 6-[5-(3-cryptomaterial)naphthalene-2-yloxy]-pyrimidine-4-carboxylic acid,
isopropylated 6-[5-(3-cryptomaterial)naphthalene-2-yloxy]-pyrimidine-4-carboxylic acid,
(3-triptoreline)amide 6-(6-chloromethylpyridine-4-yloxy)-naphthalene-1-carboxylic acid,
(3-triptoreline)amide 6-(6-methylaminomethyluridine-4-yloxy)-naphthalene-1-carboxylic acid,
(3-triptoreline)amide 6-(6-dimethylaminomethylene-4-yloxy)naphthalene-1-carboxylic acid,
tert-butyl ether ({6-[5-(4-fluoro-3-cryptomaterial)-naphthalene-2-ylsulphonyl]pyrimidine-4-yl}carbamino acid, (4-fluoro-3-triptoreline)amide 6-(6-aminopyridin-4-yl-sulfanyl)naphthalene-1-carboxylic acid,
(3-triptoreline)amide 6-(6-amino shall eremein-4-ylsulphonyl)-naphthalene-1-carboxylic acid,
(3-triptoreline)amide 6-(6-aminopyrimidine-4-sulfinil)-naphthalene-1-carboxylic acid,
(3-triptoreline)amide 6-(6-aminopyrimidine-4-sulfonyl)-naphthalene-1-carboxylic acid,
(3-trifloromethyl)amide 6-(6-aminopyrimidine-4-ylsulphonyl)-naphthalene-1-carboxylic acid,
(3-triptoreline)amide 6-[2-(2-aminopyrimidine-4-yl)ethyl]-naphthalene-1-carboxylic acid,
(3-triptoreline)amide 6-(6-aminopyrimidine-4-ylethynyl)naphthalene-1-carboxylic acid,
(4-piperazine-1-ylmethyl-3-triptoreline)amide 6-(6-acetylamino-pyrimidine-4-yloxy)naphthalene-1-carboxylic acid, methyl ester {6-[5-(4-piperazine-1-ylmethyl-3-cryptomaterial)naphthalene-2-yloxy]pyrimidine-4-yl}carbamino acid, [4-(4-methylpiperazin-1-ylmethyl)-3-triptoreline] amide of 6-(6-acetylpiperidine-4-yloxy)naphthalene-1-carboxylic acid, methyl ester (6-{5-[4-(4-methylpiperazin-1-ylmethyl)-3-trifluoromethyl-phenylcarbamoyl]naphthalene-2-yloxy}pyrimidine-4-yl)carbamino acid,
[4-(4-isopropylpiperazine-1-ylmethyl)-3-triptoreline]amide of 6-(6-acetylpiperidine-4-yloxy)naphthalene-1-carboxylic acid, methyl ester (6-{5-[4-(4-isopropylpiperazine-1-ylmethyl)-3-cryptomaterial]naphthalene-2-yloxy}pyrimidine-4-yl)-carbamino acid,
[4-(4-methylpiperazin-1-ylmethyl)-3-triptoreline]amide 7-(6-acetylpiperidine-4-yloxy)isoquinoline-4-carbon is acid, or methyl ether (6-{4-[4-(4-methylpiperazin-1-ylmethyl)-3-trifluoromethyl-phenylcarbamoyl]isoquinoline-7-yloxy}pyrimidine-4-yl)-carbamino acid,
or tautomer, or its salt.

7. (3-Triptoreline)amide 6-(2-aminopyrimidine-4-yloxy)naphthalene-1-carboxylic acid, or its tautomer, or its salt.

8. (3-Triptoreline)amide 6-(2-amino-6-chloropyrimidine-4-yloxy)-naphthalene-1-carboxylic acid, or its tautomer, or its salt.

9. Pharmaceutical composition having inhibitory activity against protein kinase, comprising the compound according to any one of claims 1 to 8 and a pharmaceutically acceptable carrier.

10. The compound according to any one of claims 1 to 8 or its salt intended for treatment-dependent protein kinase disease.

11. The connection of claim 10, where the treated disease-dependent protein kinase, preferably a proliferative disease, depends on one or more of the following protein kinases: EphB4, C-Abl, Bcr-Abl, c-Kit, Raf, RET, PDGF-R and/or VEGF-R, preferably VEGF-R.

12. The use of compounds according to any one of claims 1 to 8 or its salts for the preparation of pharmaceutical compositions intended for the treatment of dependent protein kinase disease.

13. The application indicated in paragraph 12, where the disease-dependent protein kinase, preferably a proliferative disease, depends on one or more of the following about Encinas: EphB4, c-Abl, Bcr-Abl, c-Kit, Raf, RET, PDGF-R and/or VEGF-R, preferably VEGF-R.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: described are novel 7-member heterocyclic compounds of general formula (values of radicals are given in the claim) or salts thereof or solvates thereof having chymase inhibiting activity and suitable for preventing or treating different diseases in which chymase is involved, a method of producing said compounds, intermediate compounds and a pharmaceutical composition for preventing or treating diseases in which chymase is involved, including compounds of formula (I) or pharmaceutically acceptable salts or solvates thereof.

EFFECT: improved properties of the compound.

23 cl, 12 tbl, 308 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula I wherein the substitutes A, B, B', Q and R1-R5 in formula I are specified as follows: A and B' are one of the following groups: (i) (R6)N(CH2)n, wherein n is 0 or 1; (ii) (CH2)n, wherein n is 0, 1 or 2; (iii) C(O)(CH2)n, wherein n is 0 or 1; or provided each of A and B' represents nitrogen, together they can form a bivalent radical of formula: -(CH2)s-X1-(CH2)t- (a), wherein each s and t is independently 1 or 2, and X1 represents (CH2)n, wherein n is 0 or 1; B is one of the following groups: (i) (R6)N; (ii) oxygen; (iii) C=δ, wherein δ represents oxygen or sulphur; (iv) C(R6)=C(R7); each R6 and R7 independently represent hydrogen, C1-4-alkyl; R1 is specified in the following groups: (i) phenyl group substituted by one or more substitute such as: - halogen specified in F, CI, Br or I, or alkyl1 group; aryl1 or heteroaryl group1; cyano, NH-alkyl1, N(alkyl1)(alkyl1) and amino; - NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl group, or (ii) pyridinyl group which can be substituted by one substitute, such as halogen specified in I, F, Cl or Br; alkyl1 group; aryl1 group; cyano, NH-alkyl1, N(alkyl1)(alkyl1), and amino; -NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl1 group; each R2, R3, R4 and R5 are independently specified in hydrogen or linear or branched alkyl group containing 1 to 10 carbon atoms; Q is specified in the following groups: (i) alkyl1; (ii) aryl1; (iii) heteroaryl1. The compounds of formula (I) are used for preparing a drug showing the c-kit inhibitor properties and aiming at treating a disease specified in neoplastic, allergic, inflammatory and autoimmune diseases.

EFFECT: use of oxazole derivatives as tyrosine kinase inhibitors.

13 cl, 1 tbl, 31 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula

and ,

where the ring X represents benzole or pyridine; R1 represents substituted alkyl; R2 represents optionally substituted aryl or optionally substituted 4-7-member monocyclic heterocyclic group or optionally substituted condensed group of heterocyclic group with the benzole ring where the substitutes of optionally substituted aryl, optionally substituted 4-7-member monocyclic heterocyclic group and optionally substituted condensed group of heterocyclic group with the benzole ring are selected from a group consisting of; (1) alkyl optionally substituted by a group selected from halogen and alkoxycarbonyl, (2) alkoxy optionally substituted by halogen, (3) halogen, (4) 4-7-member monocyclic heterocyclic group or (5) amino, optionally mono- or disubstituted alkyl, and (6) hydroxyl, R3 represents hydrogen or alkyl: R4 represents hydrogen, halogen or alkyl; R5 represents hydrogen or alkyl; R6 and R7 are identical or different, and each represents hydrogen or halogen; or pharmaceutically acceptable salt. Also, the invention refers to a IKur blocker containing the compounds described above as an active ingredient, and also to a preventive and therapeutic agent for cardiac arrhythmia and atrial fibrillation.

EFFECT: there are produced and described new compounds applicable as a IKur blocker effective for preventing or treating cardiac arrhythmia, such as atrial fibrillation.

12 cl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

,

and pharmaceutically acceptable salts and solvates thereof, in which R1 is an optionally substituted alkyl or similar, R2 is a group of formula: -Y-R5, where Y is -O- or S; R5 is a substituted alkyl (the substitute is an optionally substituted cycloalkyl or similar), a branched alkyl or similar; R4 is hydrogen or C1-10 alkyl; R3 is a group of formula: -C(=O)-Z-R6, where Z is -NR7- or -NR7-W-; R6 is an optionally substituted cycloalkyl or similar; R7 is hydrogen or C1-10 alkyl, W is C1-10 alkylene; X is =N- provided that a compound in which R2 is 2-(4-morpholino)ethoxy, 2-, 3- or 4-pyridylmethoxy, 1-methylpiperidinyl-2-methoxy, benzyloxy or 4-substituted benzyloxy is excluded; and R3 is N-(1-adamantyl)carbamoyl, N-(2-adamantyl)carbamoyl and N-(3-noradamantyl)carbamoyl. Said compound is an 11β-hydroxysteroid dehydrogenase type 1 inhibitor. The invention also relates to a pharmaceutical composition containing said compound as an active ingredient.

EFFECT: improved properties of the compound.

23 cl, 72 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound of general formula I

,

and a pharmaceutically acceptable salt thereof, where X denotes CH2, CHF or S, Y denotes CN, R1, R2, R3 and R4 denotes hydrogen, n equals 1, m equals 0 or 1, R denotes R11, R12 or R13, where R11 includes at least one group selected from the following b) or c), where optionally substituted heterocyclic and heteroaryl groups are bonded with a noradamantyl part either directly or through a methylene adjacent group or a C-C bond or C-N bond; b) the substituted 5-member heteroaryl group, in which the heteroaryl ring is a monocyclic aromatic ring system, includes two or more heteroatoms selected from nitrogen and oxygen; c) the heterocyclic group is optionally substituted with a C1-C3 alkyl or oxo group, where the heterocyclic ring system is a 5-9-member mono- or bicyclic ring system with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where heteroatoms can also be present as functional groups, where the heterocyclic ring system can contain one or two double bonds, and where the monocyclic heterocyclic ring can be condensed with a phenyl ring, R12 is selected from hydrogen, halogen, hydroxy, amino and C1-C4 alkoxy; R13 is a substituted phenyl, where the substitutes, which can be identical or different, include at least one group selected from a) hydrogen; b) nitro, amino; c) the saturated or unsaturated monocyclic heterocyclic ring system is optionally substituted with one or more groups selected from C1-C3 alkyl and oxo, where the heterocyclic ring system is a 5-member ring with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where the heteroatoms can also be present as functional groups. The present invention also relates to a pharmaceutical composition having dipeptidyl peptidase IV inhibiting activity, methods of obtaining the novel compound of formula I and use in treating type II diabetes and diabetic complications as well as for treating dyslipidaemia, hypercholesteremia, obesity and hyperglycaemia.

EFFECT: novel dipeptidyl peptidase IV inhibitors.

10 cl, 1 tbl, 43 ex

FIELD: chemistry.

SUBSTANCE: invention refers to the chemistry of N,N-disubstituted nicotinamide-(Z)-O-methyloximes with the general formula I where if X denotes a methylene group, then R denotes phenyl, benzyl or 2-furyl, R' denotes methyl or n-chlorophenyl, if X denotes a carbonyl group, then R denotes styryl, n-chlorostyryl or benzyl, R' denotes methyl that is characterized by the fungicidal activity.

EFFECT: new compounds that can be efficient against maleficent fungi.

1 cl, 10 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to new indazole derivants with the formula (1.0) or to their pharmaceutically acceptable salts and isomerides that act as inactivators in relation to ERK2. In formula (1.0): meanings of the chemical groups Q, R1, R2 are given in the invention formula. The invention also refers to the pharmaceutical composition containing the mentioned compounds and to application of the compounds with the formula (1.0) for production of crude drugs used in malignant growth treatment.

EFFECT: application of the compounds for production of crude drugs used in malignant growth treatment.

65 cl, 611 ex, 27 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to oxadiazolidinone compounds presented by following formula (I), or to their pharmaceutically acceptable salts, (symbols in the presented formula represent the following values, R1: -H, R0: lower alkyl, Rz: the same or different from each other, and each represents -H or lower alkyl, L: *-CH2-O- or *-CH2-NH-, where the symbol * in L represents binding with the ring A and a substitution position in the group L in the ring B represents the 4-position, the ring A: benzole, the ring B: benzole or pyridine, R2; the same or different respectively, and each represents -halogen or -R0, n: 0 or 1, R3: phenyl which can be substituted by a group selected from the group G3, The group G3: halogen, -R0, halogen-lower alkyl, -ORz, -CON(Rz)2, -CON(Rz)-heteroring group, -O-S(O)2-R0, -O-lower alkylene-ORz, -O-lower alkylene-O-COR2, -O-lower alkylene-N(RZ)2, -O-lower alkylene-N(Rz)CO-Rz, -O-lower alkylene-CO2Rz, -O-lower alkylene-CON(Rz)2, -O-lower alkylene-CON(Rz)-(lower alkyl substituted by the group-ORz), -O-lower alkylene-SR0, -O-lower alkylene-cycloalkyl, -O-lower alkylene-CON(Rz)-cycloalkyl, -O-lower alkylene-heteroring group and -O-lower alkylene-CON(Rz)-heteroring group, where lower alkylene in the group G3 can be substituted by halogen or -ORz, and cycloalkyl and the heteroring group in the group G3 can be substituted by the group selected by the group G1, The group G1: halogen, cyano, -R0, -ORz, -N(RZ)2, -S-R0, -SO2-R0, -SO2N(Rz)2, -CO-R2, -CON(Rz)2, -CON(Rz)-lower alkylene-OR2, -N(Rz)CO-Rz, oxo, -(lower alkylene which can be substituted by the group -ORz)-aryl, heteroring group and lower alkylene-heteroring group where aryl and the heteroring group in the group G1 can be substituted by the group selected from the following group G2, the group G2: halogen, cyano where the heteroring group means a group containing a ring selected from i) a monocyclic 5-7-members, saturated or unsaturated heteroring containing 1 to 3 heteroatoms selected from O, S and N, ii) a bicyclic heteroring in which the heterorings selected in i) mentioned above are ring-condensed where the condensed rings can be the same or different, and iii) the bicyclic heteroring in which the heteroring selected in i) mentioned above is condensed with a benzoic ring or 5-7-members cycloalkane, R4: -H. The invention refers to a pharmaceutical composition, to application of the compounds under cl.1, as well as to a method for preventing and/or treating diabetes.

EFFECT: making new biologically active compounds representing GPR40 agonist, an agent stimulating insulin secretion and/or an agent for preventing and/or treating diabetes.

9 cl, 27 ex, 138 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula or pharmaceutically acceptable salt thereof, synthesis methods thereof, pharmaceutical compositions containing said compounds, and use thereof to prepare a medicinal agent having mTOR kinase and/or PI3K kinase inhibiting action.

EFFECT: improved properties of the derivatives.

15 cl, 72 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of diazepane of formula , where A, X, R3, R4, R5, R6, R8, R9, R10, R11, R12, R13, n and m have values, given in description and formula of invention, as well as their physiologically acceptable salts. Said compounds are antagonists of chemokine receptors CCR-2, CCR-5 and/or CCR-3 receptor and can be used in medicine as medications.

EFFECT: obtaining novel diazepane derivatives.

20 cl, 505 ex, 4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (IB) or to their pharmaceutically acceptable salts:

, wherein R means formula: R1 means -C(O)NR3R4, -C(O)R3 and -C(O)OR3; each R3 and R4 independently means H, C1-10 alkyl, wherein alkyl is optionally substituted by one -OH; R3 and R4 are bound together with N atoms to form a 5-6-member heterocyclic ring which additionally contains one O heteroatom; R5 means H; R6 means CN; R7 means H; W means C. What is described is a method for producing both them and intermediate compounds of formula (1-1c): , wherein: R1 means -C(O)NR3R4; R3 and R4 are specified above.

EFFECT: compounds (IB) shows DPP-IV inhibitory activity that allows them being used in a pharmaceutical composition.

9 cl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula I

and/or to all isomer forms of a compound of formula I and/or to mixtures of these forms in any proportions, and/or to physiologically acceptable salts of the compound of formula I, wherein R1 represents 1) -(C6-C14)-aryl-Z, wherein Z represents aminomethylene, 2) Het-Z, wherein Z represents amino group, and wherein Het is unsubstituted or additionally monosubstituted by group T, R2 represents 1) -(C0)-alkylene-(C6-C14)aryl, wherein aryl is unsubstituted or mono- or disubstituted by group T or 2) -(C0)-alkylene-Het, wherein Het is unsubstituted or monosubstituted by group T, R3 represents 1) -(C0)-alkylene-(C6-C14)-aryl, wherein aryl is unsubstituted or mono- or disubstituted by group T, 2) -O-(C6-C14)-alkylene(C6-C14)-aryl, wherein aryl is unsubstituted or monosubstituted by group T, 3) -(C0)-alkylene-Het, wherein Het is unsubstituted or mono-, di- or trisubstituted by group T, 4) -(C0)-alkylene-(C6-C14)-aryl-Q-(C6-C14)-aryl, wherein both aryl radicals are unsubstituted, 5) -(C0)-alkylene-(C6-C14)-aryl-Q)-Het, wherein aryl and Het in each case are independently unsubstituted or disubstituted by group T, 6) -(C0)-alkylene-Het-Q-Het, wherein both radicals Het are unsubstituted, Q represents a covalent bond, -(C1-C4)-alkylene, -N((C1-C4)-alkyl)- or -O-, T represents 1) halogen, 2) -(C1-C6)-alkyl, wherein alkyl is unsubstituted disubstituted by group -(C1-C3)-fluoralkyl or -N-C(O)-(C1-C4)-alkyl, 3) -(C1-C3)-fluoralkyl, 4) -(C3-C8)-cycloalkyl, 5) -O-(C1-C4)-alkyl, 6) -O-(C1-C3)-fluoralkyl, 7) -N(R10)(R11), wherein R(10) and R(11) independently represent hydrogen atom or -(C1-C6)-alkyl, 8) -C(O)-NH-R10, 9) -SO2-(C1-C4)-alkyl, 10) -SO2-(C1-C3)-fluoralkyl, R4 and R5 are identical and represent hydrogen atom, and R6 represent hydrogen atom with said Het being 5-10-member ring system consisting of 1 or 2 coupled ring systems, and wherein one or two identical or different heteroatoms are selected from oxygen, nitrogen and sulphur. Also, the invention refers to the use of the compound of formula I for preparing a drug.

EFFECT: there are prepared new compounds exhibiting antithrombotic activity, which particularly inhibit blood coagulation factor lXa.

6 cl, 2 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula

and ,

where the ring X represents benzole or pyridine; R1 represents substituted alkyl; R2 represents optionally substituted aryl or optionally substituted 4-7-member monocyclic heterocyclic group or optionally substituted condensed group of heterocyclic group with the benzole ring where the substitutes of optionally substituted aryl, optionally substituted 4-7-member monocyclic heterocyclic group and optionally substituted condensed group of heterocyclic group with the benzole ring are selected from a group consisting of; (1) alkyl optionally substituted by a group selected from halogen and alkoxycarbonyl, (2) alkoxy optionally substituted by halogen, (3) halogen, (4) 4-7-member monocyclic heterocyclic group or (5) amino, optionally mono- or disubstituted alkyl, and (6) hydroxyl, R3 represents hydrogen or alkyl: R4 represents hydrogen, halogen or alkyl; R5 represents hydrogen or alkyl; R6 and R7 are identical or different, and each represents hydrogen or halogen; or pharmaceutically acceptable salt. Also, the invention refers to a IKur blocker containing the compounds described above as an active ingredient, and also to a preventive and therapeutic agent for cardiac arrhythmia and atrial fibrillation.

EFFECT: there are produced and described new compounds applicable as a IKur blocker effective for preventing or treating cardiac arrhythmia, such as atrial fibrillation.

12 cl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

,

and pharmaceutically acceptable salts and solvates thereof, in which R1 is an optionally substituted alkyl or similar, R2 is a group of formula: -Y-R5, where Y is -O- or S; R5 is a substituted alkyl (the substitute is an optionally substituted cycloalkyl or similar), a branched alkyl or similar; R4 is hydrogen or C1-10 alkyl; R3 is a group of formula: -C(=O)-Z-R6, where Z is -NR7- or -NR7-W-; R6 is an optionally substituted cycloalkyl or similar; R7 is hydrogen or C1-10 alkyl, W is C1-10 alkylene; X is =N- provided that a compound in which R2 is 2-(4-morpholino)ethoxy, 2-, 3- or 4-pyridylmethoxy, 1-methylpiperidinyl-2-methoxy, benzyloxy or 4-substituted benzyloxy is excluded; and R3 is N-(1-adamantyl)carbamoyl, N-(2-adamantyl)carbamoyl and N-(3-noradamantyl)carbamoyl. Said compound is an 11β-hydroxysteroid dehydrogenase type 1 inhibitor. The invention also relates to a pharmaceutical composition containing said compound as an active ingredient.

EFFECT: improved properties of the compound.

23 cl, 72 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound of general formula I

,

and a pharmaceutically acceptable salt thereof, where X denotes CH2, CHF or S, Y denotes CN, R1, R2, R3 and R4 denotes hydrogen, n equals 1, m equals 0 or 1, R denotes R11, R12 or R13, where R11 includes at least one group selected from the following b) or c), where optionally substituted heterocyclic and heteroaryl groups are bonded with a noradamantyl part either directly or through a methylene adjacent group or a C-C bond or C-N bond; b) the substituted 5-member heteroaryl group, in which the heteroaryl ring is a monocyclic aromatic ring system, includes two or more heteroatoms selected from nitrogen and oxygen; c) the heterocyclic group is optionally substituted with a C1-C3 alkyl or oxo group, where the heterocyclic ring system is a 5-9-member mono- or bicyclic ring system with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where heteroatoms can also be present as functional groups, where the heterocyclic ring system can contain one or two double bonds, and where the monocyclic heterocyclic ring can be condensed with a phenyl ring, R12 is selected from hydrogen, halogen, hydroxy, amino and C1-C4 alkoxy; R13 is a substituted phenyl, where the substitutes, which can be identical or different, include at least one group selected from a) hydrogen; b) nitro, amino; c) the saturated or unsaturated monocyclic heterocyclic ring system is optionally substituted with one or more groups selected from C1-C3 alkyl and oxo, where the heterocyclic ring system is a 5-member ring with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where the heteroatoms can also be present as functional groups. The present invention also relates to a pharmaceutical composition having dipeptidyl peptidase IV inhibiting activity, methods of obtaining the novel compound of formula I and use in treating type II diabetes and diabetic complications as well as for treating dyslipidaemia, hypercholesteremia, obesity and hyperglycaemia.

EFFECT: novel dipeptidyl peptidase IV inhibitors.

10 cl, 1 tbl, 43 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new indazole derivants with the formula (1.0) or to their pharmaceutically acceptable salts and isomerides that act as inactivators in relation to ERK2. In formula (1.0): meanings of the chemical groups Q, R1, R2 are given in the invention formula. The invention also refers to the pharmaceutical composition containing the mentioned compounds and to application of the compounds with the formula (1.0) for production of crude drugs used in malignant growth treatment.

EFFECT: application of the compounds for production of crude drugs used in malignant growth treatment.

65 cl, 611 ex, 27 tbl

FIELD: chemistry.

SUBSTANCE: present invention refers to the compound 5-[3-[(2S)-1-(difluoromethoxy)-propane-2-yl]-oxy-5-[(5-methylpyrazin-2-yl)-carbamoyl]]phenoxy]-N,N-dimethyl-pyrazine-2-carboxamide. The invention also refers to a pharmaceutical composition, and also to application of the compound under cl.1.

EFFECT: making the new biologically active compounds showing GLK (glucokinase) activator activity.

5 cl, 6 ex, 2 tbl, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula I or their pharmaceutically acceptable salts exhibiting the properties of voltage-dependent sodium channel inhibitors, such as NaV1.8. The latter play a central role in generating the action potentials in all excitable cells such as neurons and myocytes, and can be used for treating such diseases as epilepsy, irritable bowel syndrome, chronic pain, etc. In the compounds of formula I: R1 and R2 together with nitrogen atom a substituted ring selected from: (A),(B),(C),(D) or (E), which are specified in the patent claim, where in the ring (A): each of m1 and n1 is independently equal to 0-3, provided m1+n1 is equal to 3-4; z1 is equal to 0-4; Sp1 represents -O-, -S-, -NR'- or C1-C4alkylidene linker in which one methylene ring is optionally or independently substituted by -O-, provided Sp1 is bound with carbonyl group through an atom different from carbon; the ring B1 represents a 5-6-members saturated or aromatic, monocyclic or heterocyclic ring containing 1-4 heteroatoms selected from O or N with the ring B1 is optionally substituted by w1 independent variants -R11 with w1 being equal to 0-1; where in the ring (B): G2 represents CH; each of m2 and n2 is independently equal to 0-3, provided m2+n2 is equal to 2-4; p2 is equal to 0-2; q2 is equal to 0 or 1; z2 is equal to 0-4; Sp2 represents a bond or C1-C6alkylidene linker in which up to two methylene links are optionally or independently substituted by -O-. The other radical values are specified in the patent claim.

EFFECT: making new compounds of formula I or to their pharmaceutically acceptable salts showing the properties of voltage-dependent sodium channel inhibitors.

67 cl, 4 tbl, 503 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula

, where X denotes a 5-member heterocylic group bonded through a carbon atom, selected from thiophenyl, furanyl, pyrazolyl and pyrrolyl, which can be substituted with 1-3 Ra groups; T denotes O, S; B is as indicated in the claim; Z1 denotes an unsubstituted cyclopropyl; Z2 denotes a hydrogen atom, C1-C8alkyl; or C1-C8alkoxycarbonyl; Z3 independently denotes a hydrogen atom. The invention also relates to a fungicidal composition containing a compound of formula (I) as an active ingredient, and a plant pathogenic fungus control method in agricultural plants.

EFFECT: obtaining compounds of formula (I), having fungicidal activity.

9 cl, 3 dwg, 255 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula or pharmaceutically acceptable salt thereof, synthesis methods thereof, pharmaceutical compositions containing said compounds, and use thereof to prepare a medicinal agent having mTOR kinase and/or PI3K kinase inhibiting action.

EFFECT: improved properties of the derivatives.

15 cl, 72 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 4-(4-bromo-2-fluoroanilino)-6-methoxy-7(1-methylpiperidin-4ylmethoxy)quinazoline having the formula given below, and salts thereof, from compounds of formula X The invention also relates to a method of producing an intermediate compound of formula X and salts thereof, as well as to methods of producing other defined intermediate compounds which are suitable for producing (ZD6474).

EFFECT: high efficiency of the compounds.

25 cl, 1 dwg, 2 tbl, 19 ex

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