Dihydroptheridinone derivatives, method of obtaining thereof and pharmaceutical application

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel dihydropteridinone derivatives of formula (I), method of obtaining thereof (versions) and their pharmaceutical application as Plk kinase derivatives. In formula

R1 and R2 each is independently selected from the group, consisting of a hydrogen atom and C1-6alkyl; R3 is selected from the group, consisting of C1-6alkyl and C5-6cycloalkyl; R4 and R5 each is independently selected from the group, consisting of a hydrogen atom, C1-6alkyl, where the alkyl is optionally substituted with one or more groups, selected from the group, consisting of C1-6alkoxyl and -NR9R10; R6 is selected from the group, consisting of C1-3alkyl, C5-6cycloalkyl, heterocyclic alkyl, selected from a 6-membered heterocyclic alkyl with 1 nitrogen atom, hexahydrocyclopenta(c)pyrrol or cyclopenta(c)piperidine, where C1-3alkyl, C5-6cycloalkyl or heterocyclic alkyl each is optionally substituted with one or more groups, selected from the group, consisting of C1-6alkyl, C1-6alkoxyl, hydroxyl, C3-6cycloalkyl, C3-6cycloalkylC1-6alkyl, heterocyclic alkyl, N-methylmorpholine, hexahydropyrrolo[2,1-c][1,4]oxazine, -C(O)R9, -NR9R10 and C1-6alkylcarbonyloxygroup; where R9 and R10 together with a nitrogen atom which they are bound to form a 4-8-membered heterocycle, where the 4-8-membered heterocycle contains one or more N or O heteroatoms and the 4-8-membered heterocycle is optionally substituted with C1-6alkyl, optionally substituted with C3-6cycloalkyl; R7 and R8 each is independently selected from a hydrogen atom or C1-6alkyl; R9 and R10 each is independently selected from a hydrogen atom or C1-6alkyl. The invention also relates to a novel intermediate compound of formula (IA), where R1, R2 R3 R4, R5, R7, R8 R9 and R10 have the said values; R11 is selected from the group, consisting of hydroxyl or C1-6alkoxyl. The method of obtaining the formula I compound consists in the interaction of the formula

compound with R6NH2 compound, or in the interaction of the formula (IB) compound with the formula (IC) compound. Formulae (IB) and (IC) are given in the invention formula.

EFFECT: compounds can be used for obtaining the medication for treating a cell proliferation disorder, in particular, in case of a disorder, which is cancer, which is selected from the group, consisting of non-small lung cancer, squamous cell carcinoma, breast cancer, ovarian cancer, cervical cancer, papillary carcinoma or colorectal carcinoma, preferably cervical cancer or colorectal carcinoma.

11 cl, 2 tbl, 47 ex

 



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel crystalline forms of (6R)-L-erythro-tetrahydrobiopterin dihydrochloride, hydrates and/or solvates (versions) thereof, for which characteristic powder diffraction patterns with radiation CuKα1 are given, with characteristic peaks expressed in values of d (Å). Said modifications can be used to treat neurological disorder. The invention also relates to pharmaceutical compositions (versions) which may additionally contain folate, separately or together with arginine in an effective amount. The folate is folic acid or tetrahydrofolate selected from tetrahydrofolic acid, 5,10-methylene-tetrahydrofolic acid, 10-formyl-tetrahydrofolic acid, 5-formyl-tetrahydrofolic acid or 5-methyl-tetrahydrofolic acid, or polyglutamate thereof or pharmaceutically acceptable salt thereof. The invention also relates to methods of producing (versions) said crystalline modifications. For example, the method of producing crystalline form A of (6R)-L-erythro-tetrahydrobiopterin dihydrochloride involves dissolving (6R)-L-erythro-tetrahydrobiopterin dihydrochloride in water at ambient temperature, and (1) cooling the solution to a low temperature with solidification of the solution, and removing water at pressure ranging from 0.01 to 1 mbar, or (2) removing water from said aqueous solution by filtering and drying with evaporation of water, and extracting said crystalline form.

EFFECT: improved properties of compounds.

42 cl, 18 tbl, 15 dwg, 6 ex

FIELD: chemistry.

SUBSTANCE: source of radioactive iodine or radioactive bromine is added to an aqueous solution of an alkaline salt of folic acid so that pH of this solution is approximately 7 in order to obtain a solution which contains folic acid or an iodide or bromide ion. PH of this solution is then lowered to 3.5-4.9 by adding an oxidising agent selected from N-chlorosulfamides of acids in a buffer solution to the said solution. The oxidising agent is mainly chloramines T or chloramines B.

EFFECT: possibility of adding isotopic tags to folic acid through radicals.

2 cl, 2 ex

FIELD: vitamins, chemical technology, food industry, pharmacy.

SUBSTANCE: invention relates to crystalline alkaline-earth salts of 5-methyl-(6R,S)-, -(6S)- and -(6R)-tetrahydrofolic acid with the content of at least one equivalent of crystallizing water per equivalent of 5-methyltetrahydrofolic acid, in particular, 5-methyl-(6R)-tetrahydrofolic acid crystalline calcium salt or to different types of 5-methyl(6S)-tetrahydrofolic acid crystalline calcium salts. These salts can be used in preparing medicinal agents or as a nutrition supplement for treatment or prophylaxis of folic acid-mediated diseases. Also, invention relates to a method for preparing crystalline salts of 5-methyl-(6R,S)-, -(6S)- and -(6R)-tetrahydrofolic acid by crystallization of the corresponding salt of 5-methyl-(6R,S)-, -(6S)- or -(6R)-tetrahydrofolic acid from a polar medium by using heat treatment at temperature above 60°C followed, if necessary, by drying the prepared product. Also, invention relates to a composition for pharmaceutical agents or nutrition supplements.

EFFECT: improved preparing method, valuable properties of salts and composition.

13 cl, 5 dwg, 4 tbl, 11 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new azaheterocycles comprising fragment of piperidin-2-yl- of the general formula (1):

as separate enantiomers or mixture of enantiomers, or their pharmaceutically acceptable salts, oxides or hydrates. In compounds of the formula (1) R1 represents hydrogen atom, inert substitute or NH-protecting substitute; W represents optionally substituted azaheterocycle, such as: pyridin-3-yl, pyrazolo[1,5-a]pyridin-6-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-7-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-9-yl, imidazo[1,2-a]pyrimidin-6-yl, imidazo[1,2-a]pyrimidin-8-yl or [1,8]naphthyridin-3-yl. Compounds elicit activity with respect to nicotine receptors and can be used in pharmaceutical industry. Also, invention relates to the focused library for search of physiologically active compound-leaders, and to pharmaceutical compositions based on new compounds of the formula (1).

EFFECT: valuable medicinal and pharmacological properties of compounds.

9 cl, 1 tbl, 15 sch, 22 ex

The invention relates to a method for producing calcium folinata

The invention relates to new stable crystalline calcium or magnesium salts of (6R,S),(6S) - or (6R)-tetrahydrofolate acid, method for their production and pharmaceutical compositions based on them

The invention relates to crystalline forms of 6(R) or 6(S)-tetrahydrofolate acid, method for their production and pharmaceutical compositions

FIELD: chemistry.

SUBSTANCE: present invention relates to biotechnology and provides a α1,6-glucan-containing compound of Helicobacter pylori. The present invention also discloses a conjugate for inducing immune response against H.pylori, which contains said compound conjugated with a carrier protein. The present invention also discloses an immunogenic composition, use of said composition and a method of inducing immune response against H.pylori using said composition. The present invention also discloses immune serum for neutralising H.pylori in mammals, which is obtained by immunising said mammal with an immunogenic composition containing said immunogenic composition. The present invention discloses an antibody which recognises said α1,6-glucan-containing compound of H.pylori, use of said antibody and a method of inducing complement-mediated bacteriolysis of H.pylori strains which express α1,6-glucan using said antibody.

EFFECT: invention improves the effectiveness of immunogenic compositions against Hpylori.

27 cl, 8 dwg, 21 tbl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to pharmaceutical compositions for the combined therapy of arthropathies, except for rheumatoid arthritis, degenerative disk diseases, joint pains and/or autoimmune disease (particularly alopecia, neurodermitis). There are presented: a pharmaceutical composition for the above application containing a glucocorticoid, exosomes prepared of autologous blood and a cytokine antagonist ortokin or anakinra; a method for producing it involving the pharmaceutical composition containing the exosomes prepared of autologous blood and the cytokine antagonist ortokin or anakinra, and the pharmaceutical composition containing the glucocorticoid and the cytokine antagonist ortokin or anakinra, and versions of using the above substances for producing the pharmaceutical composition for the combined therapy.

EFFECT: technical effect consists in achieving the synergetic effect both on the exposure rate and remote outcomes of the specified diseases with reducing side effects of the glucocorticoid (cortisone).

33 cl, 1 dwg

FIELD: medicine.

SUBSTANCE: group of inventions relates to the strain of Bifidobacterium longum NCIMB 41675, a composition, containing thereof, and a food product, containing the said strain or composition. The claimed strain possesses an ability to induce the production of cytokins and control IL-10:IL-12 ratio is suitable for application in immunomodulation, treatment of an autoimmune disease.

EFFECT: claimed strain, composition and food product possess probiotic properties.

25 cl, 16 dwg, 4 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to field of biotechnology, namely to internalisation of therapeutic molecules into cell, and can be applied in medicine. Obtained is composition for delivering molecules of nucleic acids into cells, containing at least one peptide with at least 92% identity to GAAEAAARVYDLGLRRLRQRRRLRRERVRA (SEQ ID NO: 2); IREIMEKFGKQPVSLPARRLKLRGRKRRQR (SEQ ID NO: 3); or YLKVVRKHHRVIAGQFFGHHHTDSFRMLYD (SEQ ID NO: 4), bound to one or several molecules of nucleic acids.

EFFECT: invention makes it possible to increase efficiency of delivery of molecules of nucleic acids into mammalian cell due to peptide, capable of internalisation into mammalian cell with efficiency, constituting at least 200% of efficiency of internalisation of peptide TAT, which has amino acid sequence GRKKRRQRRRPPQ (SEQ ID NO: 1).

8 cl, 16 dwg, 1 tbl, 8 ex

Crystals // 2556206

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention describes crystals of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulphonyl)acetamide ("compound A"), as a form I of the compound A crystal, which shows diffraction peaks at 9.4 degrees, 9.8 degrees, 17.2 degrees and 19.4 degrees in its power X-ray diffraction spectrum, as a form II of the compound A crystal, which shows diffraction peaks at 9.0 degrees, 12.9 degrees, 20.7 degrees and 22.6 degrees in its power X-ray diffraction spectrum, as a form III of the compound A crystal, which shows diffraction peaks at 9.3 degrees, 9.7 degrees, 16.8 degrees, 20.6 degrees and 23.5 degrees in its power X-ray diffraction spectrum. There are also described methods for producing the forms I, II and III of the compound A crystal, based pharmaceutical composition and PGI2 receptor agonist agent, an accelerating agent for angiogenic therapy, gene engineering or autoimmune bone marrow transplantation, and an accelerating agent for angiogenesis for peripheral artery recovery or angiogenic therapy on the basis thereof; there are also described a preventive or therapeutic agent for a wide range of diseases and conditions.

EFFECT: preparing the new therapeutic agent for the wide range of diseases and conditions.

11 cl, 6 dwg, 6 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: presented invention refers to immunology. What is presented is a monoclonal anti-IFNAR1 antibodies with L234F, L235E and P331S Fc mutations of human IgG1 possessing a lower affinity to Fcgamma RI, Fcgamma RIIIA and c1q receptors as compared to a non-modified antibody. There are described the recovered nucleic acid providing expression of the above antibody containing a nucleotide sequence coding the antibody, and a pharmaceutical composition based on the above antibody.

EFFECT: using the invention provides the antibody possessing the lower affinity to Fcgamma RI, Fcgamma RIIIA and c1q receptors that provides reducing the undesired effector functions in treating chronic inflammation and autoimmune conditions.

9 cl, 34 dwg, 7 tbl, 36 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates for composition for treatment or prevention of disorders, associated with reduced level of defensins. Composition contains from 0.005 to 1000 mg of Lactobacillus johnsonii Lal (NCC533, No CNCM 1-1225) per a daily dose, with at least 90% of L. johnsonii Lal (NCC533, No CNCM 1-1225) being transferred into state in which they become non-replicating at temperature110-140°C for 5-30 s.

EFFECT: invention provides enhancement of expression of defensin hBD1 mRNA.

5 cl, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel N-containing heteroaryl derivatives of formula I or II or their pharmaceutically acceptable salts, which possess properties of JAK kinase, in particular JAK3, and can be applied for treating such diseases as asthma and chronic obstructive pulmonary disease (COPD). In formulae A represents carbon and B represents nitrogen or A represents nitrogen and B represents carbon; W represents CH or N; R1 and R2, independently represent hydrogen, C1-4alkyl, halogenC1-4alkyl, -CN; R3 represents C1-4alkyl, R9-C1-4alkyl, Cy1, where Cy1 is optionally substituted with one or several substituents R10; R4 represents hydrogen, C1-4alkyl, R12R7N-C0alkyl, where one of R7 and R12 represents hydrogen, and the other represents C1-4alkyl or group R13, which is selected from C1-5alkyl, Cy2-C0alkyl; R5 represents hydrogen; R6 represents hydrogen, C1-4alkyl, C1-4alkoxyC1-4alkyl, hydroxyC1-4alkyl, R12R7N-C1-4alkyl, R16CO-C0alkyl, Cy1; R7 represents hydrogen or C1-4alkyl; R9 represents halogen, -CN, -CONR7R12, -COR13, CO2R12, -OR12, -SO2R13, -SO2NR7R12, -NR7R12, -NR7COR12; R10 represents C1-4alkyl or R9-C0-4alkyl; R11 represents C1-4alkyl, halogen, -CN, -NR7R14; R12 represents hydrogen or R13; R13 represents C1-5alkyl, hydroxyC1-4alkyl, cyanoC1-4alkyl, Cy2-C0alkyl or R14R7N-C1-4alkyl; where Cy2 is optionally substituted with one or several constituents R11; R14 represents hydrogen or C1-4alkyl; R16 represents C1-4alkyl, halogenC1-4alkyl, C1-4alkoxyC1-4alkyl, hydroxyC1-4alkyl or cyanoC1-4alkyl; Cy1 represents monocyclic carbocyclic unsaturated or saturated ring, selected from C3-C6cycloalkyl, phenyl, or saturated monocyclic 4-6-membered heterocyclic ring, containing from 1 to 2 heteroatoms, selected from N and S, or partially unsaturated 10-membered bicyclic heterocyclic ring, containing oxygen atom as heteroatom, which can be substituted with group R11, where said ring is bound with the remaining part of molecule via any available C atom, and where one or several ring C or S atoms are optionally oxidised with formation of CO or SO2; and Cy2 represents monocyclic carbocyclic unsaturated ring, selected from C3-C6cycloalkyl, or aromatic monocyclic 4-6-membered heterocyclic ring, containing from 1 to 2 heteroatoms, selected from N and S, or unsaturated 10-membered bicyclic heterocyclic ring, containing oxygen atom as heteroatom, which can be substituted with group R11, where said ring is bound with the remaining part of molecule via any available atom C or N.

EFFECT: obtaining novel heteroaryl derivatives.

27 cl, 41 ex

FIELD: medicine.

SUBSTANCE: invention refers to biochemistry, particularly to affinity-matured CRIg versions. Declared is the CRIg versions, which is an alternative complement pathway inhibitor at least twice stronger than human CRIg with a native sequence, and optionally possesses C3b-bindingaffinity at least twice as much. There are also declared a chimeric molecule and a pharmaceutical composition, both containing the above CRIg version. The CRIg version can be used for preparing a therapeutic agent for treating a complement-associated disease or condition.

EFFECT: invention enables improving the therapeutic effectiveness of CRIg polypeptides.

17 cl, 17 dwg, 4 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to quinolines substituted by phosphorus-containing group of formula and applicable in medicine, wherein Z represents V1 and V2 are independently specified in hydrogen or halogen; one of R and R` represent phosphorus-containing substitute Q; the other one is specified in hydrogen or methoxyl; wherein the phosphorus-containing substitute Q represents A represents O; L represents C1-6alkyl; J represents NH or C3-6heterocycloalkyl and J is optionally substituted by G3; X is absent or represents -C(=O)-; X is absent or represents C1-6alkyl; each of R1 and R2 are independently specified in C1-6alkyl or C1-6alkoxy; G3 represents C1-6alkyl, R3S(=O)m-, R5C(=O)- or R3R4NC(=O)-; R3, R4 and R5 are independently specified in 3 or C1-6alkyl; m is equal to 0-2.

EFFECT: there are presented new protein kinase inhibitors effective for treating the diseases associated with abnormal protein kinase activity.

20 cl, 42 ex, 8 tbl, 3 dwg

FIELD: chemistry.

SUBSTANCE: present invention relates to biotechnology and provides a α1,6-glucan-containing compound of Helicobacter pylori. The present invention also discloses a conjugate for inducing immune response against H.pylori, which contains said compound conjugated with a carrier protein. The present invention also discloses an immunogenic composition, use of said composition and a method of inducing immune response against H.pylori using said composition. The present invention also discloses immune serum for neutralising H.pylori in mammals, which is obtained by immunising said mammal with an immunogenic composition containing said immunogenic composition. The present invention discloses an antibody which recognises said α1,6-glucan-containing compound of H.pylori, use of said antibody and a method of inducing complement-mediated bacteriolysis of H.pylori strains which express α1,6-glucan using said antibody.

EFFECT: invention improves the effectiveness of immunogenic compositions against Hpylori.

27 cl, 8 dwg, 21 tbl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 2-(3-amino-1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide. As well as to a pharmaceutical composition containing the above compound, to the use thereof and a set for treating.

EFFECT: 2-(3-amino-1-(2,4-difluorophenyl)-1H-1,2,4-triazol-5-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide inhibiting PI3 kinase (PI3K).

6 cl, 15 dwg, 1 tbl, 610 ex

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