Pyrrolotriazine compounds as kinase inhibitors

FIELD: chemistry.

SUBSTANCE: new pyrrolotriazine derivatives of general formula (I) are described, where R1 is possibly substituted piperidinyl or piperazinyl; R2 is possibly substituted phenyl; R3 is hydrogen; X is -NH-; Y is -CH2-; as well as their pharmaceutically acceptable salts or steroisomers, and pharmaceutical compositions containing said compounds.

EFFECT: given compounds are kinase inhibitors and can be used in medicine, for example as anticancer agents.

9 cl, 267 ex, 2 dwg

 

The text descriptions are given in facsimile form.

1. The compound of the formula I
,
where R1means heterocyclyl or substituted heterocyclyl, where
gatecycle selected from piperidinyl or piperazinil, and possible zamesitelj independently selected from one to three-NH2-, -HE-DOUBT(C1-4the alkyl), -OCONH2With1-4of alkyl, NHCONH2and NHSO2(C1-4the alkyl);
R2denotes a substituted or unsubstituted phenyl, in which 1 or 2 are possible substituent selected from hydrogen, halogen,
With1-4of alkyl, C1-4the quinil,1-4alkoxy, OCF3, CF3, CONH2, NHCOCH3, morpholinyl and-CN;
R3denotes hydrogen;
X represents-NH-;
Y represents-CH2-;
or its pharmaceutically acceptable salts or stereoisomers.

2. The compound of formula II

where X is-NH;
Z represents-R6-CH -, or-NR7-;
R2about who appoints a substituted or unsubstituted phenyl, which 1 or 2 are possible substituent selected from hydrogen, halogen, C1-4of alkyl, C1-4the quinil,1-4alkoxy, OCF3, CF3, CONH2, NHCOCH3, morpholinyl and-CN;
R3denotes hydrogen;
R6, R6aand6bindependently selected from the group consisting of hydrogen, -NH2, -OH, -CONH(C1-4the alkyl), -OCONH2With1-4of alkyl, NHCONH2and NHSO2(C1-4the alkyl), while two of these substituents may be attached to the same carbon atom in the ring;
R7denotes hydrogen, C1-4alkyl or-NH2;
n is equal to 1;
or its pharmaceutically acceptable salt or stereoisomer.

3. The compound of formula III

where X represents NH;
R2denotes a substituted or unsubstituted phenyl, in which 1 or 2 are possible substituent selected from hydrogen, halogen, C1-4of alkyl, C1-4the quinil,1-4alkoxy, OCF3, CF3, CONH2, NHCOCH3, morpholinyl and-CN;
R3denotes hydrogen;
R6, R6aand R6bindependently selected from the group consisting of hydrogen, -NH2, -OH, -CONH(C1-4the alkyl), -OCONH2With1-4of alkyl, NHCONH2and NHSO2(C1-4of alkyl, where two of these substituents may be attached to the same carbon atom in the ring;
n is equal to 1;
or is th pharmaceutically acceptable salt or stereoisomer.

4. The compound according to claim 3, wherein R6, R6aand R6bindependently selected from-NH2, -OH, -CONH(C1-4the alkyl), NHSO2(C1-4the alkyl), -OCONH2.

5. A compound selected from the group including:
5-[(4-amino-1-piperidinyl)methyl]-N-(3-chloro-4-forfinal)pyrrole[2,1-f] [1,2,4]triazine-4-amine,
5-[(4-amino-1-piperidinyl)methyl]-N-phenylpyrrole[2,1-f][1,2,4]triazine-4-amine,
5-[(4-amino-1-piperidinyl)methyl]-N-(3-methoxyphenyl)pyrrole[2,1-f] [1,2,4]triazine-4-amine,
5-[(4-aminopiperidin-1-yl)methyl]-N-(4-fluoro-3-methoxyphenyl)pyrrole[2,1-f][1,2,4]triazine-4-amine,
(3R,4R)-4-amino-1-[[4-[(3-chloro-4-forfinal)amino]pyrrole[2,1-f][1,2,4]-triazine-5-yl]methyl]piperidine-3-ol,
(3S,4S)-4-amino-1-[[4-[(3-chloro-4-forfinal)amino]pyrrole[2,1-f][1,2,4]-triazine-5-yl]methyl]piperidine-3-ol,
(3R,4R)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrole[2,1-f][1,2,4]-triazine-5-yl]methyl]piperidine-3-ol,
(3S,4S)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrole[2,1-f][1,2,4]triazine-5-yl]methyl]piperidine-3-ol,
(3R,4R)-4-amino-1-[[4-[(3-mrtaxi-4-forfinal)amino]pyrrole[2,1-f] [1,2,4]triazine-5-yl]methyl]piperidine-3-ol,
(3R,4R)-4-amino-1-({4-[(3-ethylphenyl)amino]pyrrole[2,1-f] [1,2,4]triazine-5-yl}methyl)piperidine-3-ol,
(3R,4R)-4-amino-1-({4-[(3-ethoxyphenyl)amino]pyrrole[2,1-f] [1,2,4]triazine-5-yl}methyl)piperidine-3-ol,
(3R,4R)-4-amino-1-({4-[(3-mrtaxi-4-were)amino]pyrrole[2,1-f][1,2,4]triazine-5-yl)methyl)piperidine-3-ol,
(3R,4R)-4-amino-1-({4-[(3-bromophenyl)amino]pyrrole[2,1-f] [1,2,4]triazine-5-yl}methyl)p is piridin-3-ol,
(3R,4R)-4-amino-1-({4-[(3-fluoro-5-Metoxyphenyl)amino]pyrrole[2,1-f] [1,2,4]triazine-5-yl}methyl)piperidine-3-ol,
(3S,4R)-4-amino-1-({4-[(3-methoxyphenyl)amino]pyrrole[2,1-f] [1,2,4]-triazine-5-yl}methyl)piperidine-3-ol,
(3R,4S)-4-amino-1-({4-[(3-methoxyphenyl)amino]pyrrole[2,1-f] [1,2,4]-triazine-5-yl}methyl)piperidine-3-ol,
(3S,4R)-4-amino-1-({4-[(3-chlorophenyl)amino]pyrrole[2,1-f] [1,2,4]triazine-5-yl}methyl)piperidine-3-ol,
(3S,4R)-4-amino-1-({4-[(3-chloro-4-forfinal)amino]pyrrole[2,1-f] [1,2,4]-triazine-5-yl}methyl)piperidine-3-ol,
(3S,4R)-4-amino-1-({4-[(3-ethynylphenyl)amino]pyrrole[2,1-f][1,2,4]triazine-5-yl}methyl)piperidine-3-ol,
(3R,4S)-4-amino-1-({4-[(3-ethylphenyl)amino]pyrrole[2,1-f][1,2,4]triazine-5-yl)methyl)piperidine-3-ol,
(3R,4S)-4-amino-1-({4-[(3-chlorophenyl)amino]pyrrole[2,1-f][1,2,4]triazine-5-yl}methyl)piperidine-3-ol,
(3R,4R)-4-amino-1-({4-[(3-methoxyphenyl)amino]pyrrole[2,1-f]][1,2,4]-triazine-5-yl)methyl)piperidine-3-yl-carbamate,
(3R,4R)-4-amino-1-({4-[(3-ethynylphenyl)amino]pyrrole[2,1-f][1,2,4]triazine-5-yl)methyl)piperidine-3-yl-carbamate,
(3R,4R)-4-amino-1-({4-[(3-chloro-4-forfinal)amino]pyrrole[2,1-f] [1,2,4]-triazine-5-yl)methyl)piperidine-3-yl-carbamate,
(3S,4R)-4-amino-1-({4-[(3-chloro-4-forfinal)amino]pyrrole[2,1-f] [1,2,4]-triazine-5-yl)methyl)piperidine-3-yl-carbamate,
(3S,4R)-4-amino-1-({4-[(3-ethynylphenyl)amino]pyrrole[2,1-f][1,2,4]triazine-5-yl)methyl)piperidine-3-yl-carbamate,
(3S,4R)-4-amino-1-({4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]-triazine-5-yl)methyl)-3-methylpiperidin-3-ol,
(3R/S,5R/S)-4-amino-1-({4-[(3-methoxyphenyl)aminopyrrolo[2,1-f][1,2,4]-triazine-5-yl}methyl)piperidine-3,5-diol,
(3S,5S)-4-amino-1-({4-[(4-fluoro-3-methoxyphenyl)amino]pyrrole[2,1-f] [1,2,4]triazine-5-yl)methyl)piperidine-3,5-diol,
(3R,5R)-4-amino-1-({4-[(3-ethynylphenyl)amino]pyrrole[2,1-f][1,2,4]triazine-5-yl}methyl)piperidine-3,5-diol,
5-{[(3R,4R)-4-amino-3-methoxypiperidine-1-yl]methyl}-N-(3-methoxyphenyl)pyrrole [2,1-f][1,2,4]triazine-4-amine,
5-(((4aR,8aR)-rel-hexahydro-1H-pyrido[3,4-b][1,4]oxazin-6(7H)-yl)-methyl)-N-(3-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazine-4-amine,
(3R,4R)-4-amino-1-({4-[(3-methoxyphenyl)amino]pyrrole[2,1-f][1,2,4]-triazine-5-yl}methyl)-N-(methylsulphonyl)piperidine-3-carboxamide,
(3R,4R)-4-amino-1-({4-[(3-ethynylphenyl)amino]pyrrole[2,1-f][1,2,4]triazine-5-yl}methyl)-N-methylpiperidin-3-carboxamide,
(3R,4R)-4-amino-1-({4-[(3-methoxyphenyl)amino]pyrrole[2,1-f][1,2,4]-triazine-5-yl}methyl)-N-methylpiperidin-3-carboxamide,
(3R,4R)-4-amino-1-({4-[(3-methoxyphenyl)amino]pyrrole[2,1-f][1,2,4]-triazine-5-yl)methyl)piperidine-3-carboxamide,
[(3R,4R)-1-((4-(3-methoxybenzylamine)pyrrole[2,1-f][1,2,4]triazine-5-yl}-methyl)-4-((R)-1-amino)piperidine-3-yl)methanol,
N-[(3R,4R)-4-amino-1-({4-[(3-methoxyphenyl)amino]pyrrole[2,1-f][1,2,4]-triazine-5-yl}methyl)piperidine-3-yl]urea,
N-[(3R,4R)-4-amino-1-({4-[(3-methoxyphenyl)amino]pyrrole[2,1-f][1,2,4]-triazine-5-yl}methyl)piperidine-3-yl]methanesulfonamide and
N-[(3S,4R)-4-amino-1-({4-[(3-methoxyphenyl)amino]pyrrole[2,1-f][1,2,4]-triazine-5-yl}methyl)piperidine-3-yl]methanesulfonamide or their pharmaceutically acceptable salts.

6. The pharmaceutical composition inhibiting activity is insincerity receptor growth factor, containing one or more compounds according to claim 1 and a pharmaceutically acceptable carrier.

7. The pharmaceutical composition inhibiting the activity of tyrosine kinase receptors growth factor containing one or more compounds according to claim 2 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition inhibiting the activity of tyrosine kinase receptors growth factor containing one or more compounds according to claim 3 and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition inhibiting the activity of tyrosine kinase receptors growth factor containing one or more compounds according to claim 5 and a pharmaceutically acceptable carrier.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to new derivatives of imidazo[1,2-c]pyrimidinyl acetic acid of formula (I) or to its salts: , where R1 is ,, in which n is an integer ranging from 0 to 6; Y is aryl, where the said aryl is optionally substituted at a substitutable position with one or more substitutes selected from a group which consists of halogen or C1-6alkyl, optionally substituted with mono-, di- or trihalogen; R2 is hydrogen; R3 is hydrogen or halogen; and R4 is hydrogen. The invention also relates to derivatives of imidazo[1,2-c]pyrimidinyl acetic acid of formula (I-i) or to its salts, to a drug, to use of compounds in paragraph 1, as well as to a drug in form of a standard single dosage.

EFFECT: obtaining new biologically active compounds, which are active towards CRTH2.

23 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: in compounds of formula (I) , Q is: (IIa) or (IIb) , R1 is chosen from a group which consists of carboxylic aryl and carboxylic aryl which is substituted with substitute(s) independently chosen from a group which consists of halogen, cyano, nitro, C1-10alkyl, C1-10alkyl which is substituted with substitute(s) independently chosen from a group which consists of halogen, C1-9alkoxy, C1-9alkoxy which is substituted with substitute(s) independently chosen from a group which consists of halogen, mono-C1-5alkylamino, and heterocyclyl or heterocyclyl which is substituted with substitute(s) independently chosen from a group which consists of halogen, C1-5alkyl; R2 is C1-5alkyl, C1-5alkyl which is substituted with halogen, C1-5alkyl which is substituted with carboxylic aryl, C1-5alkoxy, -N(R2a)(R2b); where R2a and R2b are each independently hydrogen, C1-5alkyl or C1-5alkyl, substituted with substitute(s) independently chosen from a group which consists of hydroxyl, carboxylic aryl; L represents formula (IIIa); , where R3 and R4 are each hydrogen; A is a single bond, and B is a single bond or -CH2-; Z1, Z3, and Z4 are each independently hydrogen, halogen, C1-5alkyl, C1-5alkyl, substituted with carboxylic aryl, C1-5alkoxy, mono-C1-5alkylamino, di-C1-5alkylamino, carboxylic aryl, heterocyclyl or substituted heterocyclyl; Z2 is hydrogen, C1-5alkyl, C1-5alkyl which is substituted with carboxylic aryl, C1-5alkoxy, mono-C1-5alkylamino, di-C1-5alkylamino, carboxylic aryl, heterocyclyl or substituted heterocyclyl; Y is -C(O)NH-, -C(O)-, -C(S)NH-, -C(O)O- or -CH2-; where carboxylic aryl is phenyl; heterocyclyl is 1H-indolyl, 9H- xanthenyl, benzo[1,3]dioxolyl, furyl, imidazolyl, isoxazolyl, morpholinyl, piperazinyl, pyridyl, pyrrolidyl; halogen is fluorine, chlorine, bromine or iodine. The invention also relates to a pharmaceutical composition.

EFFECT: compounds can be used for treating central nervous system diseases, and for improving memory functioning, sleep, awakening, diabetes.

16 cl, 8 dwg, 4 tbl, 525 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a tetrazole compound with general formula I , where X3 and X4 are independently N and C, where one of X3 and X4 is certainly C; P is phenyl; m equals 1 or 2, where if m equals 1, R1 is bonded to P through a carbon atom on ring P in the meta-position of ring P relative the point at which P is bonded to X3, and if m equals 2, R1 is bonded to P through a carbon atom on ring P in positions 2 and 5 of ring P; R1 is halogen, C1-6alkyl, OC1-6alkyl or cyano group; X1 is C2-3alkyl, C2-3alkenyl, NR3, O, S, CR3R4, SO, SO2; X2 is a bond, CR3R4, O, S, NR3, SO, SO2; R3 and R4 are independently chosen from a group which consists of hydrogen, hydroxy, C1-6alkyl; Q is triazolyl, piperazinyl, or triazole or imidazole ring, condensed with a 6- or 7-member heterocyclic ring with one or two N atoms as heteroatoms; R is C1-6alkyl, C3-6cycloalkyl, pyridinyl, which can be substituted with a nitro, cyano, halogen or OC1-4alkyl group; phenyl, which can be substituted with a halogen, C1-4alkyl, OC1-4alkyl group; (CO)OC1-4alkyl; pyrimidinyl, which can be substituted with a OC1-4alkyl group; p equals 0, 1 or 2, or pharmaceutically acceptable salt or hydrate thereof.

EFFECT: invention also relates to method of inhibiting activity of mGluR5 receptors.

11 cl, 44 ex

FIELD: pharmacology.

SUBSTANCE: invention concerns novel compounds of formula (1a), formula (1b), formula (1c) and formula (1d), as well as pharmaceutical composition based on them and their application in medicine obtainment. R1-R4, G, W, X, X1, U, V, a, b are defined in the invention claim.

EFFECT: compound with antagonistic effect on vasopressin V1A receptor.

73 cl, 133 ex

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

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: chemistry.

SUBSTANCE: invention relates to new derivatives of imidazo[1,2-c]pyrimidinyl acetic acid of formula (I) or to its salts: , where R1 is ,, in which n is an integer ranging from 0 to 6; Y is aryl, where the said aryl is optionally substituted at a substitutable position with one or more substitutes selected from a group which consists of halogen or C1-6alkyl, optionally substituted with mono-, di- or trihalogen; R2 is hydrogen; R3 is hydrogen or halogen; and R4 is hydrogen. The invention also relates to derivatives of imidazo[1,2-c]pyrimidinyl acetic acid of formula (I-i) or to its salts, to a drug, to use of compounds in paragraph 1, as well as to a drug in form of a standard single dosage.

EFFECT: obtaining new biologically active compounds, which are active towards CRTH2.

23 cl, 2 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, oncology, and can be used for thermochemoradiation therapy of oesophagus cancer. That is ensured by local transoesophageal hyperthermia, gamma-ray teletherapy and chemotherapy as preoperative actions. Herewith gamma-ray therapy is carried out within 2 weeks in average fractionation mode at 3 Gy 5 times a week to total focal dose 30 Gy. Chemotherapy accompanies the whole course of gamma therapy by daily introduction of fluorouracil dosed 300 mg/m2 to the central vein in continuous infusion mode and daily intravenous introduction of cisplatin dosed 6 mg/m2 daily within 1 hour. Hyperthermia is applied on 4th, 8th and 12th days of gamma therapy immediately before irradiation session at temperature 42-44°C within 60 minutes.

EFFECT: method allows optimising treatment of the patients suffering from oesophagus cancer and improving clinical effectiveness owing to advanced local control.

3 ex

FIELD: medicine.

SUBSTANCE: invention concerns medical products and covers applications of O- and S-glycosides 5-hydroxy-1,4-naphthoquinone (judlone) derivatives of formula 1 as an agent that stimulates human leukaemia cell apoptosis. Disclosed compounds selectively stimulate human leukemia cell apoptosis as comparrf with a prototype juglone without affecting normal cells of human immune system (neutrophils).

EFFECT: invention allows extending range of products selectively stimulating leukaemia cell apoptosis.

4 cl, 13 dwg, 5 tbl, 14 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to oncology, and can be used in chemotherapeutic treatment of locally advanced and general breast cancer. It is ensured by autoplasmochemotherapy. Every time before introduction of cytostatic agents incubated with autoplasma, Trental is introduced intravenously drop-by-drop in a dose 100 mg dissolved in physiologic saline 200 ml.

EFFECT: method improves clinical effectiveness and reduces toxicity of autoplasmochemotherapy due to potentiation of anticancer action of chemoprepatations and protection of blood and bone marrow cells.

2 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, namely oncology and can be used for neoadjuvant treatments of stomach cancer that is ensured by intraarterial introduction of taxotere 75 mg/m2 and cisplatin 75 mg/m2 with selective catheterisation of celiac trunk. Regional chemotherapy in number of 2 to 4 courses is performed.

EFFECT: application of the invention enables higher operability and clinical effectiveness ensured by downsising of tumour and loc-regional metastases.

2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine area, namely to oncology, and can be used for treatment of locally advanced non-small cell lung cancer. The therapy involves neoadjuvant chemotherapy, introduction of a radio sensitiser, surgical treatment and intraoperative radiation therapy. The preoperative period involves 2 courses of neoadjuvant chemotherapy with Taxol and carboplatin. Two hours before irradiation, gemcitabine is introduced in a dose 300 mg/m2, then radical operation with intraoperative radiation therapy in a single dose 15 Gy on regional lymphatic cancer spread area is performed.

EFFECT: invention allows improving clinical effectiveness of locally advanced non-small cell lung cancer owing to reduced post-radiation complications and higher survival rate of patients.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and pharmacy, namely to agents for inhibition of development or progression of liver cancer in hepatitis C positive patients suffering from cirrhosis, wherein the agent contains three types of amino acids, namely isoleucine, leucine and valine, wherein mass ratio of isoleucine, leucine and valine makes 1:1.5-2.5:0.8-1.7.

EFFECT: invention provides effective inhibition of development or progression of liver cancer in hepatitis C positive patients suffering from cirrhosis.

18 cl, 1 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of formula (I) and pharmaceutically acceptable salts of the said compound, which has c-met kinase inhibitory properties. In general formula (I) W is -N=, and X is hydrogen, Y is hydrogen or A2-R group; A2 is C1-C5alkylene; R is hydroxy; n equals 1, and Z is benzyloxy; or alternatively W is -CH=, and X is hydrogen, OR1; R1 is chosen from A1-Q1group; A1 is 1,2-ethylene or 1,3-propylene group; Q1 is hydroxyl; Y is a A2-R group; A2 is C1-C5alkylene; R is hydroxy; n equals 1, and Z is C1-C3alkoxy, substituted with pyridinyl, and pharmaceutically acceptable salts of the said compound.

EFFECT: can be used for treating cancer and cancer-related diseases.

8 cl, 36 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new phosphates of nitrophenylpyrite and nitrophenylaziridine alcohols of general formula , where: X represents -CONH- in any accessible position of the ring; R is a lower C1-6alkyl; Y represents -N-aziridinyl in any accessible position of the ring, -N(CH2CH2W)2 or -N(CH2CHMeW)2, where W is independently chosen from halogen or -OSO2Me; Z represents NO2 or -SO2Me in any accessible position of the ring; and its pharmaceutically acceptable salts. The invention also pertains to a method of producing phosphates of formula (I) and formulae , and (particular cases of formula (I)), a method of anticancer treatment and a method of destroying hypoxic cells using formula (I) compounds, as well as to a pharmaceutical composition based on formula (I) compounds.

EFFECT: obtaining new compounds which can be used as targeted cytotoxic agents.

14 cl, 5 tbl, 4 dwg, 39 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, oncology, and can be used for integrated treatment of locally advanced malignant bronchial and/or tracheal tumours. It is ensured by argon-plasma recanalisation of bronchial and/or tracheal lumen at power 60-90 W. It is followed with photodynamic therapy with using a preparation Photoditasine 1.5 mg/kg and semiconductor laser light of wavelength 662 nm at power density of 300 mW/cm2 of total power dose 400 J/cm2. Combined radiation therapy includes brachytherapy and remote radiation therapy. Herewith brachytherapy is performed at source motion path length 5-20 cm of step 5 mm and reference isodose depth 10 mm from the source with an applicator enabled to travel above and below the tumour 1 to 3 cm and ensured dose 14-28 Gy in the mode 7 Gy once a week. Remote radiation therapy is carried out 5 times a week 1-2 Gy up to "СОД" 45-55 Gy. In addition, the radiation is accompanied with 4 courses of chemotherapeutical intravenous infusions of cisplatin in a dose 100 mg/m2 in the 1st day with gemcitabine in a dose 1000 mg/m in the 1st, 8th, 15th days every 4 weeks. Besides, cisplatin is allowed in a dose 80 mg/m2 in the 1st day with etoposide in a dose 120 mg/m2 in 1st, 3rd, 5th days every 3 weeks.

EFFECT: invention ensures reduction of tumour burden, recovered patency of airways, managed inflammation, intoxication and pain syndrome, local and system antineoplastic action of chemotherapy, longer and improved life quality of the patients.

3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted 2-[2-(3-oxomorpholin-4-yl)ethylthio]benzimidazoles of general formula: , where R1, R2, R3, R4, R5 are identical or different: H, lower alkyls or alkoxy groups.

EFFECT: obtaining new compounds with anxiolytic properties, which allows for their potential use in medicine for treating neuropsychic disorders.

2 cl, 4 tbl, 9 ex

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