Imidazopyridine kinase inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to novel imidazopyridine compounds of formula (I) and pharmaceutically acceptable salts thereof, which inhibit kinase activity, selected from IGF-1R, IR, EGFR and Erb2 and have cell proliferation inhibitor properties. In formula (I) halogeno denotes a halogen; X1 is H or halogen, R1 is H, halogen or halogen-C1-C4alkyl; R2 is H or O-C1-C4alkyl; each R3 is identical or different and is independently selected from H, halogen, C1-C4alkyl, halogen-C1-C4alkyl and O-C1-C4alkyl; one of R4 and R5 is selected from H, halogen, C1-C4alkyl and O-C1-C4alkyl; and the other is a group selected from: (i), (ii) and (iii) where:(1) each R7 is H; a equals 0, 1, 2 or 3; R8 is selected from NH2, N(H)C1-C4alkyl, N(C1-C4alkyl)2 and a group of formula (iv): (iv), where: ring D is a 5-6-member saturated N-heterocycle, possibly containing 1 or 2 additional heteroatoms selected from N and O. Other values of radicals are given in the claim.

EFFECT: compounds can be used in treating different types of cancer.

4 tbl, 250 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I):

where
Halo is a halogen;
X1represents H or halogeno;
R1represents H, halogen or halogen-C1-C4alkyl;
R2represents H or O-C1-C4alkyl;
each R3is the same or different and independently selected from H, halogeno,1-C4of alkyl, halogen-C1-C4the alkyl group and O-C1-C4alkyl;
one of R4and R5selected from N, halogeno,1-C4the alkyl group and O-C1-C4alkyl and the other represents a group chosen from:

and

where
(1) each R7represents H;
and is equal to 0, 1, 2 or 3;
R8selected from the group of NH2N(H)1-C4alkyl, N(C 1-C4alkyl)2and groups of the formula (iv):

where
ring D is a 5-6-membered saturated N-heterocycle may contain 1 or 2 additional heteroatoms selected from N and O, and
R14selected from H, C1-C4of alkyl, HE, groups O-C1-C4alkyl, SO2-C1-C4alkyl, C1-C4alkylen-O-C1-C4alkyl and C1-C4alkylen-SO2-C1-C4alkyl;
(2) b is 0, 1, 2 or 3;
each R9represents H;
ring a is selected from 5-to 10-membered saturated heterocycles containing 1, 2 or 3 heteroatoms selected from N and O, and 5-6-membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N and O;
n is 0, 1 or 2;
each R10is the same or different and independently selected from C1-C4of alkyl, halogen-C1-C4of alkyl, HE, groups O-C1-C4alkyl, NH2N(H)1-C4alkyl, N(C1-C4alkyl)2N(C1-C4alkylen-O-C1-C4alkyl)2, SO2-C1-C4alkyl, C1-C4alkylen-O-C1-C4alkyl, C1-C4alkylene-NH2With1-C4alkylene-N(H)1-C4alkyl, C1-C4alkylene-N(C1-C4alkyl)2and C1-C4alkylen-SO2-C1-C4 alkyl;
(3) with 0, 1 or 2;
each R12represents H;
ring selected from cyclohexene, 5-6-membered heterocycle containing 1, 2 or 3 heteroatoms selected from N and O, and 5-6-membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N and O;
q 0;
the ring represents a 5-10 membered saturated, a heterocycle containing 1, 2 or 3 heteroatoms selected from N, O and S;
p is 0, 1 or 2;
each R13is the same or different and independently selected from halogeno,1-C4of alkyl, halogen-C1-C4of alkyl, groups, HE, O-C1-C4alkyl, oxo, C(O)1-C4alkyl, SO2-C1-C4alkyl, C1-C4alkylen-O-C1-C4alkyl, C1-C4alkylen-S(O)1-C4alkyl and C1-C4alkylen-SO2-C1-C4alkyl; and
each R6is the same or different and independently selected from H, halogeno,1-C4of alkyl, halogen-C1-C4the alkyl groups, O-C1-C4alkyl and O-halogen-C1-C4alkyl;
or its pharmaceutically acceptable salt.

2. The compound according to claim 1, where X1represents halogen, and R1represents N.

3. The compound according to claim 1, where R2represents H or O-C1-3alkyl.

4. The compound according to claim 1, where at least one R3p is ecstasy a H, and the other is selected from H, halogeno, C1-3of alkyl, halogen-C1-3the alkyl group and O-C1-3alkyl.

5. The compound according to claim 1, where one of R4and R5represents a group:

6. The compound according to claim 1, where R4represents N, and R5represents a group:

7. The compound according to claim 1, where a is equal to 2 or 3.

8. The compound according to claim 1, where R8selected from the group N(C1-C4alkyl)2and groups of the formula (iv):

9. The compound according to claim 1, where one of R4and R5represents a group:

10. The compound according to claim 1, where R5represents N, and R4represents a group:

11. The compound according to claim 1, where b is 0, 1 or 2.

12. The compound according to claim 1 in which the ring a is selected from 5-6-membered heterocycle or heteroaryl containing 1 or 2 heteroatoms selected from N and O.

13. The compound according to claim 1, where n is 0 or 1, and R10selected from C1-C4of alkyl, halogen-C1-C4the alkyl groups, O-C1-C4alkyl, NH2N(H)1-C4alkyl, N(C1-C4alkyl)2, SO2-C1-C4alkyl, C1-C4alkylene-N(C1-C4alkyl)2and C1-C4alkylen-SO2-C1-C4alkyl

14. The compound according to claim 1, where one of R4and R5represents a group:

15. The compound according to claim 1, where R5represents H, F, Cl or methyl, and R4is a group (iii-a):

16. The compound according to claim 1, where R5represents N, and R4is a group (iii-b):

17. A compound selected from:
3-[3-(2-{[4-(1,4'-bipiperidine-1'-yl)-2-(metiloksi)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridine-2-yl]-N-(2,6-differenl)benzamide;
N-(2,6-differenl)-3-[3-(2-{[4-{4-[4-(2-foradil)-1-piperazinil]-1-piperidinyl}-2-(metiloksi)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridine-2-yl]benzamide;
N-(2,6-differenl)-3-(3-{2-[(2-(metiloksi)-4-{4-[4-(methylsulphonyl)-1-piperazinil]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridine-2-yl)benzamide;
N-(2,6-differenl)-3-(3-{2-[(5-methyl-2-(metiloksi)-4-{4-[2-(methylsulphonyl)ethyl]-1-piperazinil}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridine-2-yl)benzamide;
N-(2,6-differenl)-2-(ethyloxy)-5-(3-{2-[(5-methyl-2-(metiloksi)-4-{4-[2-(methylsulphonyl)ethyl]-1-piperazinil}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridine-2-yl)benzamide;
N-(2,6-differenl)-2-(ethyloxy)-5-(3-{2-[(5-methyl-2-(metiloksi)-4-{1-[2-(methylsulphonyl)ethyl]-4-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridine-2-yl)benzamide and
N-(2,6-differenl)--(7-fluoro-3-{2-[(2-(metiloksi)-4-{4-[4-(methylsulphonyl)-1-piperazinil]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridine-2-yl)-2-(metiloksi)benzamide;
N-(2,6-differenl)-5-(3-{2-[(2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulphonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridine-2-yl)-2-(metiloksi)benzamide;
N-(2,6-differenl)-5-(3-{2-[(5-ethyl-2-(metiloksi)-4-{4-[4-(methylsulphonyl)-1-piperazinil]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridine-2-yl)-2-(metiloksi)benzamide;
and its pharmaceutically acceptable salts.

18. N-(2,6-differenl)-5-(3-{2-[(5-ethyl-2-(metiloksi)-4-{4-[4-(methylsulphonyl)-1-piperazinil]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridine-2-yl)-2-(metiloksi)benzamide

or its pharmaceutically acceptable salt.

19. Pharmaceutical composition having the properties of an inhibitor of cell proliferation and containing a compound according to any one of claims 1 to 18 in a therapeutically effective amount and a pharmaceutically acceptable carrier, diluent or excipient.

20. The pharmaceutical composition according to claim 19, additionally containing an effective amount of a chemotherapeutic agent, having the properties of an inhibitor of protein tyrosine kinase EGFR/ErbB2, such as lapatinib.

21. Method of inhibiting cell proliferation in a mammal, comprising an introduction to the specified mammal a therapeutically effective amount of a compound according to any one of claims 1 to 18.

22. The method according to item 21, where the specified cell ProLife the situation is a proliferative disease in a mammal, selected from breast cancer, sarcomas, lung cancer (including non-small cell carcinoma of the lung), prostate cancer, colorectal cancer, kidney cancer, pancreatic cancer, blood cancers (including multiple myeloma, neuroblastoma, primary CNS tumors and secondary CNS tumors, head and neck cancer, thyroid cancer, hepatocarcinoma, ovarian cancer, vulvar cancer, cervical cancer, endometrial cancer, testicular cancer, bladder cancer, esophageal cancer, stomach cancer, cancer of the cheeks, cancer of the mouth, GIST (gastrointestinal stromal tumor) and skin cancer (including melanoma).

23. A method of treating cancer selected from breast cancer, sarcomas, lung cancer, non-small cell lung carcinoma, prostate cancer, colorectal cancer, pancreatic cancer, blood cancer, multiple myeloma, head and neck cancer and ovarian cancer, in a mammal, comprising an introduction to the specified mammal a therapeutically effective amount of a compound according to any one of claims 1 to 18.

24. A method of obtaining a compound according to any one of claims 1 to 18, including the interaction of the compounds of formula (V):

with an aniline of formula (VI):

where all radicals such as defined in claim 1, to obtain the compounds of formula (I).

25. The method of obtaining compounds of any and the claims 1 to 18, including the interaction of the compounds of formula (XV):

where Rarepresents an alkyl or cycloalkyl,
with an aniline of formula (IX):

where all radicals such as defined in claim 1, to obtain the compounds of formula (I).

26. The compound according to any one of claims 1 to 18, having the properties of an inhibitor of IGF-1R, IR, EGFR and rb2-kinases for use in therapy.

27. The compound according to any one of claims 1 to 18 for inhibiting cell proliferation in a mammal.

28. Connection item 27 where the specified cell proliferation is a proliferative disease is selected from breast cancer, sarcomas, lung cancer (including non-small cell carcinoma of the lung), prostate cancer, colorectal cancer, kidney cancer, pancreatic cancer, blood cancers (including multiple myeloma, neuroblastoma, primary CNS tumors and secondary CNS tumors, head and neck cancer, thyroid cancer, hepatocarcinoma, ovarian cancer, vulvar cancer, cervical cancer, endometrial cancer, testicular cancer, bladder cancer, esophageal cancer, stomach cancer, cancer of the cheeks cancer of the mouth, GIST (gastrointestinal stromal tumor) or skin cancer (including melanoma), in a mammal.

29. The compound according to any one of claims 1 to 18 for use in the treatment of breast cancer, sarcomas, lung cancer, NEMAK is cell lung carcinoma, prostate cancer, colorectal cancer, pancreatic cancer, blood cancer, multiple myeloma, head and neck cancer or ovarian cancer in a mammal.

30. The use of compounds according to any one of claims 1 to 18 for the manufacture of a medicinal product for the treatment of a proliferative disease in a mammal.

31. The application of article 30, where the specified proliferative disease is selected from breast cancer, sarcomas, lung cancer (including non-small cell carcinoma of the lung), prostate cancer, colorectal cancer, kidney cancer, pancreatic cancer, blood cancers (including multiple myeloma, neuroblastoma, primary CNS tumors and secondary CNS tumors, head and neck cancer, thyroid cancer, hepatocarcinoma, ovarian cancer, vulvar cancer, cervical cancer, endometrial cancer, testicular cancer, bladder cancer, esophageal cancer, stomach cancer, cancer of the cheeks, oral cancer, GIST (gastrointestinal stromal tumor) or skin cancer (including melanoma) in a mammal.

32. The use of compounds according to any one of claims 1 to 18 for the manufacture of a medicinal product for the treatment of breast cancer, sarcomas, lung cancer, non-small cell lung carcinoma, prostate cancer, colorectal cancer, pancreatic cancer, blood cancer, multiple myeloma, head and neck cancer or cancer AIC the ICA in a mammal.



 

Same patents:

Chemical compounds // 2469034

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention describes compounds of formula (I) wherein: R1 means C1-6alkyl or C3-6cycloalkyl; wherein R1 may be optionally carbon-substituted by one or more R6; R2 means hydrogen; R3 and R4 are carbon substitutes, and each is independently specified in carboxy, carbamoyl, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, C1-6alkanoylamino, N-(C1-6alkyl)carbamoyl, N,N-(C1-6alkyl)2carbamoyl, N-(C1-6alkoxy)carbamoyl, phenyl-R9 - or heterocyclyl-R10-; wherein R3 and R4 may be independently carbon-substituted by one or more R11; and wherein provided said heterocyclyl contains -NH - residue, then nitrogen may be optionally substituted by a group specified in R12; m has the value of 0, 1 or 2; wherein the values R3 may be equal or different; p has the value of 0, 1 or 2; wherein the values R4 may be equal or different; the ring A means nitrogen-containing 5- or 6-member heterocyclic group; wherein drawn nitrogen represents = N- and is found in an ortho-position to R1R2NC(O)NH group in formula (I); the ring B means phenyl or heterocyclyl; wherein provided said heterocyclyl contains -NH- residue, then nitrogen may be optionally substituted by a group specified in R14; R5 is specified in hydroxy, C1-6alkoxy or -N(R15)(R16); R6 and R11 are carbon substitutes and each is independently specified in halo, C1-6alkyl or C1-6alkoxy; R15 and R16 are independently specified in hydrogen, C1-6alkyl, C1-6alkoxy, cyclopropyl or cyclopentyl; R12 and R14 mean C1-6alkyl; wherein R14 may be optionally carbon specified by one or more R23; R9 and R10 mean a direct link; and R23 means halo or methoxy; wherein said heterocyclyl means pyridine, imidazole, triazole, thiazole, benzothiazole, imodazolepyridine, dihydroquinoline or thiadiazole, or its pharmaceutically acceptable salt; provided said compound represents other than ethyl ester of 5-[2-[[(ethylamino)carbonyl]amino]pyridin-4-yl]-4-methyl-4H-1,2,4-triazole-3-carboxylic acid or their pharmaceutically acceptable salts. There are also described pharmaceutical compositions on the basis of said compounds, a method for bacterial DNA-hydrase and/or bacterial topoisomerase IV inhibition in a homoiothermal animal, as well as a method of treating an infection in a homoiothermal animal.

EFFECT: there are prepared and described new compounds showing antibacterial activity.

24 cl, 165 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to fluorinated compounds of formula , where: D, G and L are independently selected from a group consisting of: CH, C and N, and J and M are independently selected from a group consisting of C and N, under the condition that one of J and M denotes C and the other denotes N, wherein at least two of D, G, M, J and L denote N; X denotes CH2; Y is absent; Z denotes NR1R2; R1 and R2 are independently selected from a group consisting of: hydrogen, C1-C10 alkyl, aryl and heteroaryl, which is associated with aromatic radicals having 6 ring atoms, where 1-2 of these ring atoms are N; each of which can be substituted with one or more halogen atoms; or R1 and R2, together with nitrogen to which they are bonded, form a heterocyclic ring having 5 ring members; R3 is selected from a group consisting of: halogen, C1-C10 alkyl; E denotes aryl which can be substituted with one or more fluoro-substitutes or one or more of the following substitutes: C1-C6 alkyl, QC1-C10 alkyl, QC2-C10 alkenyl, each of which can be substituted with one or more fluoro-substitutes, and where Q denotes O; m denotes a number from 1 to 2; under the condition that: R3 is a fluoro-substitute, or group E includes a fluoro-substitute, or group Z includes a fluoro-substitute, with the condition that E does not denote 4-fluorophenyl or a compound of formula , where D, G and L are independently selected from a group consisting of: CH, C and N, and J and M are independently selected from a group consisting of C and N, under the condition that one of J and M denotes C and the other denotes N, wherein at least two of D, G, M, J and L denote N; X denotes CH2; Y is absent; Z denotes NR1R2; R1 and R2 are independently selected from a group consisting of: hydrogen, C1-C10 alkyl, aryl and heteroaryl, which is associated with aromatic radicals having 6 ring atoms, where 1-2 of these ring atoms are N; each of which can be substituted with one or more of the following substitutes: chlorine, bromine, iodine; or R1 and R2, together with nitrogen to which they are bonded, form a heterocyclic ring having 5 ring members; R3 is selected from a group consisting of: chlorine, bromine, iodine, C1-C10 alkyl; E denotes aryl which can be substituted with one or more chlorine, bromine or iodine atoms, and/or one or more of the following substitutes: C1-C6 alkyl, QC1-C10 alkyl, QC2-C10 alkenyl, each of which can be substituted with one or more substitutes selected from chlorine, bromine, iodine or hydroxy, where Q denotes O, wherein when E denotes phenyl, E does not contain, as a substitute, iodine which is directly bonded to it at position 4; m denotes a number from 1 to 2; wherein at least one of Z, E and R3 includes iodine; under the condition that E does not denote 4-iodophenyl and under the condition that said compound is not a compound of formula (Ia), defined in the following table:

The invention also relates to a pharmaceutical composition based on the compound of formula (I) or (Ia), a diagnosis method, a method of treating said disorders, based on use of the compound of formula (I) or (Ia), and use of the compound of formula (I) or (Ia).

EFFECT: obtaining novel compounds useful in treating disorders in mammals, characterised by anomalous density of peripheral benzodiazepine receptors.

24 cl, 13 dwg, 9 tbl, 23 ex

FIELD: chemistry.

SUBSTANCE: compounds, which have formula I , in which A, B, R1, R1a, R2, R3, R4, R5 R6, R7 and R8 have values given in description and are inhibitors of receptor tyrosinkinases, useful in treatment of diseases, mediated by class 3 and class 5 receptor tyrosinkinases. It has been also discovered that specific compounds of the claimed invention are Pim-1 inhibitors. Also claimed is method of obtaining formula I compound.

EFFECT: increase of compound efficiency.

27 cl, 51 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of [1,8]naphthyridine, described by formula I(a), where Z represents -NR41-; A represents phenyl; each R10, R17, R31, R33, R35 and R41 in each case is independently selected from group, consisting of hydrogen, C1-C6alkyl, C1-C6haligenalkyl, phenyl, C3-C6cycloalkyl, -Ls-O-Rs, -Ls-C(O)Rs, -Ls-C(O)ORs and LE-Q-LE-(morpholine); X is selected from group, consisting of bond, -Ls-O-, -Ls-S- and -Ls-C(O)N(Rs)-; R22 is selected from group, consisting of halogen, C1-C6alkyl, phenyl, and phenyl C1-C2alkyl, and, optionally, is substituted with one R26, where R26 in each case is independently selected from group, consisting of halogen, hydroxy, nitro, C1-C6alkyl, -Ls-OSO2Rs; Y is selected from group, consisting of bond, -Ls-O-, -Ls-S(O)-, -Ls-C(O)N(R15) - and -Ls-S-, where R15 represents hydrogen; R50 represents -L1-A1, where A1 is selected from group, consisting of C1-C6alkyl and phenyl and L1 is selected from group, consisting of bond and C1-4alkylene, where A1 is optionally substituted with from one to three R30, and R30 in each case is independently selected from group, consisting of halogen, hydroxy, amino, azido, C1-C6alkyl, -Ls-O-Rs, -Ls-C(O)ORs, -LS-N(RSRS), -Ls-C(=NRs)RS', -Ls-C(O)N(RsRsO, -Ls-N(Rs)C(O)Rs', -LE-Q-LE'- (phenyl or naphthyl) and -LE-Q-LE'-(M5-M6heterocyclyl, which represents pyridine, pyrazine, pyrrolodine, furan, thiophene, piperidine); Ls in each case is independently selected from group, consisting of bond and C1-4alkylene; each RS and Rs' in each case is independently selected from group, consisting of hydrogen, C1-C6alkyl, C3-6alkenyl, C1-6alkoxy, C1-6alkoxyC1-C6alkyl and C1-6alkoxycarbonylC1-C6alkyl; each LE and LE' in each case is independently selected from group, consisting of bond, C1-4alkylene, -C1-4alkylene-NC(O)-C1-4alkylene-; Q in each case is independently selected from group, consisting of bond, -O-, -N(Rs)C(O)-, -C(O)N(Rs)- and -O-SO2-; each R17 and R30 in each case is optionally independently substituted with from one to three substituent(s), selected from group, consisting of halogen and hydroxy; and each heterocyclyl group in -LE-Q-LE'-(M5-M6heterocyclyl) in each case is optionally independently substituted with at least one or two substituents, selected from group, consisting of hydrogen, hydroxy, C1-C6alkyl, C1-6alkoxy, C1-6alkoxycarbonyl, phenyloxy and phenylC1-6alkoxycarbonyl, or to their pharmaceutically acceptable salts. Invention also relates to compounds of formula II(a), pharmaceutical composition based on claimed compounds, application of claimed compounds, method of inhibition of HCV virus replication, method of treating HCV infection.

EFFECT: obtained are novel derivatives, useful in treatment of HCV infection.

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of dihydroquinone and dihydronaphthyridinone of formula (I) or to its pharmaceutically acceptable salts, in which X represents group CR11 or N; Y represents group -C(O)R3, oxazolyl or isoxazolyl; Z represents phenyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydropyranyl, pyridinyl, pyrimidinyl or pyrazolyl, and is substituted with groups R1 and R2; R1 and R2 each independently represents H, halogen, CN group, C1-6alkyl or group -Y1-Y2-Y3-R8, or R1 and R2 together form group -O(CH2)nO-, where n represents 1 or 2; Y1 represents group -O-, -C(O)-, -C(O)O-, -C(O)NR9-, -NR9C(O), -S-, -SO2- or bond; Y2 represents heterocycloalkylene, C1-6alkylene or bond, where heterocycloalkylene stands for cycloalkylene group, in which one, two carbon atoms are substituted with heteroatoms O or N, where heterocycloalkylene group also contains, at least, two carbon atoms and cycloalkylene represents ; Y3 represents group -O-, -C(O)-, -C(O)O-, -C(O)NR9-, -NR9C(O)-, -SO2- or bond; R8 represents H, C1-6alkyl, C1-6alkoxy, cyclohexyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, tetrahydropyranyl, or group -NR9R10, where R8, different from H, is optionally substituted with C1-6alkyl, halogen, group -CF3 or group -OH; R9 and R10 each independently represents H or C1-6alkyl; R3 represents OH, C1-6alkyl, C1-6alkoxy, (C1-6alkoxy)-C1-6alkoxy; R4 represents C1-6alkyl, phenyl, cyclopropyl, cyclobutyl, cyclobutyl, cyclohexyl, tetrahydropyranyl or tetrahydrothiophene 1,1 -dioxide, and is optionally substituted with C1-6alkyl, hydroxyl group, C1-6alkoxy, halogen, nitro group, amino group, cyano group or halo-lower alkyl; R5 and R6 each independently represents H, halogen, C1-6alkyl, group -CF3, C1-6alkoxy; R7 represents H; R11 represents H. Invention also re4lates to pharmaceutical composition based on formula (I) compound.

EFFECT: obtained are novel dihydroquinone and dihydronaphthyridinone derivatives, useful for treatment of disease mediated by JNK kinase.

9 cl, 4 tbl, 38 ex

FIELD: medicine.

SUBSTANCE: invention refers to an agent for activation of lipoprotein lipase containing a benzene derivative of general formula (1) which is used for preventing and treating hyperlipidemia and obesity. The invention also refers to the benzene derivatives of general formula (1a).

EFFECT: composition improvement.

8 cl, 6 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of general formula 1:

wherein Q, X1, X2, Y, Z, R1, R2, R3, R3', R4, R4', R5, R6, R6' have the values specified in the description.

EFFECT: compounds are the IAP inhibitors which can be used as therapeutic agents for malignant diseases.

13 cl, 20 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new bicyclic heterocyclic derivatives of general formula wherein radicals and symbols are specified in the patent claim. Said compounds are FGFR receptor (fibroblast growth factor receptor) inhibitors. The invention also refers to a method for preparing a preferential group of compounds of formula (I), to a pharmaceutical composition containing said compounds, and to the use of said compounds for treating diseases, e.g. cancer.

EFFECT: preparing the new bicyclic heterocyclic derivatives.

22 cl, 16 tbl, 422 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel bicyclic heterocyclic derivatives, which are compounds of formula where values of X1-X5, A, B, R1, R2, q are given in claim 1, as well as pharmaceutical compositions containing said compounds, and use of said compounds to treat cancer.

EFFECT: high efficiency of treatment.

22 cl, 43 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 9-(quinonyl-2)-2-n-ethoxyphenylethyl-4,5,6,7,8,9,10,11-octahydropyrido[1,2-a] pyrazine-1,4-dione of formula I or pharmaceutically acceptable complex derivatives thereof. The invention also relates to use of the compound of formula I.

EFFECT: novel derivative which can be used as an antiulcer agent is obtained.

4 cl, 1 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula (I) and its pharmaceutically acceptable salts possessing dihydroorotate dehydrogenase inhibitory ability, to a based pharmaceutical composition, to application thereof in preparing a drug compound and to a combined preparation containing the presented compounds and the other active compound (I) in effective amounts wherein both groups G1 mean CRC, G2 mean a nitrogen atom or group CRd, of the groups G3 and G4 mean a nitrogen atom and the other one means group CH, M means a hydrogen atom or a pharmaceutically acceptable cation, while R1, R2, Ra, Rb, Rc and Rd have the values specified in the patent claim.

EFFECT: preparing pharmaceutically acceptable salts possessing dihydroorotate dehydrogenase inhibitory ability.

25 cl, 115 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to oncology, and may be used in integrated treatment of stomach cancer. That is ensured by a surgical intervention to place a microirrigator into an abdominal cavity. Then 4 weeks after the surgery, blood 300 ml is taken on the first day to be centrifuged and to recover autoplasma. Autoplasma and chemopreparations are placed into a first flask, autoplasma - into second and third flasks, blood corpuscles and chemopreparations - into a forth force. The 2nd and 3rd flasks are frozen, the 1st and 4th flasks are separately incubated for 40 minutes at 37°C. The incubated blood corpuscles and chemopreparations from the 4th flask are introduced intravenously drop-by-drop. Autoplasma and chemopreparations from the 1st flask are introduced intraperitoneally through the microirrigator. It is followed by 1 session of radiation therapy on the abdominal cavity at single dose 2 Gy. On the 2nd and 4th therapeutic days, only sessions of radiation therapy are applied. On the 3rd and 5th days, the sessions of radiation therapy are preceded by freezing one flask with autoplasma added with chemopreparations, and the flasks are incubated for 40 minutes at 37°C. Then autoplasma and chemopreparations are introduced intraperitoneally through the microirrgator, and the session of radiation therapy is conducted. On the 6th and 7th days, a pause is made. Starting from 8th and 15th days, a five-day therapeutic course is repeated.

EFFECT: method enables reducing rate of metastases in the peritoneum caused by stomach cancer and increasing survival rate of the patients due to combined surgical and chemoradiation therapy in a certain mode.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, oncology, and may be used for treating locally advanced unresectable oesophageal cancer. Preliminary argon-plasma coagulation of a tumour is followed by high-power intraluminal brachytherapy on 1st, 8th and 15th day of the therapeutic course at single basic dose 7 Gy combined with the intravenous introduction of taxane preparations and carboplatine. Further, the tumour is exposed to tele-radiation at single basic dose 1.8 Gy, 5 fractions/week, SOD 40-45 Gy, supported by the use of fluoropyrimidine derivatives in the following doses: oral administration of capecitabine 600 mg/m2 in degree 0-1 dysphagia in days of radiation therapy, intravenous infusions of 5-fluorouracil 1000 mg/m2 in degree 2-3 dysphagia every week.

EFFECT: method provides optimising cytoreductive reaction of chemoradiation therapy components and more complete response of the tumour with relieved severe systemic and local reactions.

2 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine, more specifically to oncology and concerns methods of treating or personalising therapy of cancer in a subject by specific removal of malignant cells from a cell population of peripheral blood, as well as a such method for specific removal of malignant cells from a cell population of peripheral blood intended for autologous transplantation. A cell population of peripheral blood containing malignant and non-malignant cells is taken from a subject and analysed for activity of at least one cancer marker in said cell population. It is followed by introducing into the cells a polynucleotide coding the selected marker and a polypeptide lethal for said malignant cells wherein expression of the lethal polypeptide is under direct or indirect control of a cancer marker promoter. The cells are exposed in selection conditions to produce cells containing said polynucleotide. The produced cells are treated in the conditions of expression induction of the lethal polypeptide which kills the cells expressing the cancer marker. Then the killed cells are separated from the living cells to be returned to the subject body.

EFFECT: presented new method for specific removal of malignant cells enables both cancer cell reinfusion into the patient's body in autologous transplantation, and makes it possible to personalise therapy of a malignant disease in the subject by structuring an individual therapeutic polynucleotide depending on subject's genotype.

45 cl, 8 dwg, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and represents gel-forming mixed dextran esters containing phosphate and carbamate groups of general formula: {C6H7O2(OH)3-x-y{[(OP(O)ONa)mONa)]xl[(O2P(O)ONa)k]x2}x(OCONH2)y}n, wherein x=x1+x2 is a degree of substitution in phosphate groups (mono- and diesters), x=0.47-1.09; X1 is a degree of substitution in monoesters, X1=0.01-0.48; m is a number of phosphates in monoesters, m=1-2; x2 is a degree of substitution in diesters, x2=0.01-1.09; k is a number of phosphates in diesters, k=1-2; y is a degree of substitution in carbamate groups, y=0.39-1.23; n is a degree of polymerisation, 20≥n≤1000.

EFFECT: invention provides producing low-toxic low- and high-substituted dextran phosphates in the form of hydrogels containing additionally carbamate groups and possessing antiproliferative activity with respect to cancer cells.

2 cl, 3 dwg, 14 ex

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine, namely to oncology, and can be used for treatment of subject's bone tumour. For this purpose bone tumour in subject is, at least, partially ablated. Area, adjacent to the bone section, where tumour was, at least, partially ablated, is brought into contact with gel, containing taurolidine, taurultam, their mixture or their solution, which is in equilibrium. Also claimed is prevention of development of bone tumour recurrence in subject.

EFFECT: group of inventions ensures treatment and prevention of osteosarcoma in subject due to application of gel of suggested medications.

40 cl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical field and deals with drug form for peroral introduction, containing solid dispersion of tyrosine kinase inhibitor, which represents N-[4-(3-amino-1H-indasol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea (ABT869), at least, one pharmaceutically acceptable polymer and pharmaceutically acceptable solubiliser or combination of two or more pharmaceutically acceptable solubilisers, selected from pharmaceutically acceptable non-ionic surgace-active substances, where pharmaceutically acceptable solubiliser has value HLB in the range from 3.5 to 13 and where combination of pharmaceutically acceptable solubilisers has the average HLB value in the range from 4.5 to 12. Invention also relates method of obtaining said drug form.

EFFECT: invention ensures creation of safe drug form, characterised by low level of products of active substance destruction.

11 cl, 3 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: to induce cytological action on tumour cells, culture of human tumour cells linear - K562 or freshly isolated - cells of primary epidermoid carcinoma of oral cavity are subjected to combined impact of colloidal solution of silver nanoparticles in concentration 34 mcg/ml and SHF-irradiation with frequency 915 MHz. Impact is performed during 30 minutes.

EFFECT: essential increase of cytotoxic effect.

1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to immunology and biotechnology. Claimed is isolated monoclonal antibody, inducing cytotoxicity with respect to cancer cells, produced by hybridome, deposited in collection ID AC under number 051206-01, or its antigen-binding fragment. Described are: chimeric and hymanised versions, obtained from said antibody. Described is hybridome, producing monoclonal antibody and deposited in collection ID AC under number 051206-01, as well as composition based on said antibody for treatment of human cancer tumour.

EFFECT: application of invention ensures versions of monoclonal antibodies capable of inducing cytotoxicity in vitro in the absence of effector cells with respect to lung adenocarcenoma cells, which can be applied in tumour therapy.

5 cl, 5 dwg, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

where X is S or O, mor is a morpholine group, and R3 is a monocyclic heteroaryl group, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, which are used to modulate lipid kinase activity, including PI3K, and for treating lipid kinase mediated disorders such as cancer.

EFFECT: obtaining compounds which are used to modulate lipid kinase activity, including PI3K, and for treating lipid kinase mediated disorders such as cancer.

27 cl, 1 tbl, 354 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to compounds of formula I or their pharmaceutically acceptable salts showing activity with respect to HIV reverse transcriptase, as well as to a based pharmaceutical composition (I). In formula I R1 means phenyl(C1-C3)alkyl, heteroaryl(C1-C3)alkyl, phenyl or heteroaryl optionally substituted by one-three substitutes independently specified in groups (a)-(r), R2 means -CN, -CH=CHCN or halogen; R3 means hydrogen, halogen, amino group, halogen(C1-C6)alkyl, -CN or methyl; R4 means hydrogen, Br or amino group; R5a and R5b independently mean hydrogen, C1-C6alkyl, C1-C6alkoxy group or halogen; R6a and R6b either independently mean hydrogen, or together mean ethylene; X means NH or O. The groups (a)-(r) are such as presented in the patent claim.

EFFECT: preparing pharmaceutically acceptable salts possessing activity with respect to HIV reverse transcriptase.

17 cl, 42 ex, 6 dwg, 5 tbl

Up!