Method for producing 7-substituted 4,4-dimethyl-9-oxo-4,4a-dihydro-9h-xanten-2-carbonic acids and their cytotoxic activity
SUBSTANCE: invention relates to the method for producing 7-substituted 4,4-dimethyl-9-oxo-4,4 and-dihydro-9H-xanten-2-carboxylic acids of the general formula (I) , where: R=CH3O (Ia); R=CH3 (Ib); R=H (Ic); R=Br (Id); R=CL (Ie), by reacting 6-substituted 3-(4-oxo-4H-chrome-3-yl) acrylic acids, where the substituents have the above values, with enamine N-(2-methylprop-1-enil) pyrrolidine at a temperature of 20 to 80°C for 0.5 to 4 hours in the presence of a catalyst of lanthanum nitrate (III) in an amount of 0 to 20 moll. % in a medium of the solvent selected from dichloromethane, ethyl acetate, or acetonitrile and N-(2-methylprop-1-enil) pyrrolidine is used in 10-100% excess, relative to acrylic acids, followed by crystallization of the target product upon acidification of the reaction mass.
EFFECT: reduction of process time, simplification of the technology of isolation of target compounds exhibiting a cytotoxic activity.
2 cl, 1 tbl, 6 ex
SUBSTANCE: invention refers to new compounds of the formula (I) that are characterized by the properties of M3 muscarine receptor antagonist that is applicable in treatment or prevention of the disease or state (the abnormity of) which includes activity of the M3 muscarine receptor such as respiratory diseases. In the formula (I) A is represented by the oxygen atom or the group -N(R12)-; (i) R1 is represented by C1-C6-alkyl or the hydrogen atom; and R2 is represented by the hydrogen atom or the group -R5, -Z-Y-R5, -Z-NR9R10, -Z-NR9CO-R5 or -Z-CO2H; and R3 is absent or is represented by C1-C6-alkyl, and in this case the nitrogen atom to which it is bound is represented by tetradic nitrogen and bears a positive charge; or (ii) R1 and R2 together with nitrogen to which they are bound form heterocycloalkyl ring; the mentioned ring is displaced by the group -Y-R5 or -Z-Y-R5, and R3 is absent or is represented by C1-C6-alkyl, and in this case the nitrogen atom to which it is bound is represented by tetradic nitrogen and bears a positive charge; R4 is represented by the formula group (a), (b), (c) or (d); Z is represented by C1-C16-alkylene group; Y is represented by the link or the oxygen atom; R5 is represented by C1-C6-alkyl, aryl, phenyl condensed with C3-C6cycloalkyl, phenyl condensed with heterocycloalkyl, heteroaryl, aryl(C1-C8-alkyl)-, heteroaryl(C1-C8-alkyl)-, C3-C6cycloalkyl or heteroC3-C6cycloalkyl group; R6 is represented by C1-C6-alkyl or the hydrogen atom; n and m equal 0; R8a and R8b are independently chosen from the group consisting of aryl, phenyl condensed with heterocycloalkyl, heteroaryl, C1-C6-alkyl, C3-C6cycloalkyl; R8c is represented by -OH or C1-C6-alkyl; R9 and R10 are represented independently by the hydrogen atom, C1-C6-alkyl, aryl, phenyl condensed with heterocycloalkyl and other components mentioned in the invention formula.
EFFECT: new compounds applicable in treatment or prevention of the disease or state (the abnormity of) which includes activity of the M3 muscarine receptor such as respiratory diseases.
10 cl, 49 ex
FIELD: pharmaceutical industry, in particular new bioactive chalcones.
SUBSTANCE: invention relates to new chalcones of formula I
, pharmaceutically acceptable salts or solvates thereof, wherein Ar is optionally substituted C5-C10-carbocycle group or 5- or 6-membered heterocycle group having sulfur atom in cycle, and Ar substituents are selected independently from Cl, Br, F, CN, SCH3 and OR10, wherein R10 is linear or branched C1-C6-hydrocarbon; R is OH or R10; R2 and R3 are independently phenyl, saturated linear or branched C1-C6-hydrocarbon, or R2 and R3 together with carbon atom attached thereto form 5- or 6-membered carbocycle group with the proviso, that in compounds where R is OH and both R2 and R3 are methyl, Ar is not phenyl, 4-chlorophenyl, 4-chlorophenyl, 4-methylphenyl, 2-chlorophenyl, 3,4-dimethoxyphenyl, or 4-methoxyphenyl. Also disclosed are drug component for treatment or prophylaxis of neoplasm and pharmaceutical compositions with antiproliferation effect based on compounds of formula I.
EFFECT: new chalcone derivatives with value bioactive action.
26 cl, 2 tbl, 22 ex
FIELD: organic chemistry, pharmacology.
SUBSTANCE: invention relates to new flavone, xanthone and coumarone derivatives of formula I
[R and R1 each are independently lower C1-C6-alkyl or together with nitrogen atom attached thereto form 4-8-membered heterocycle, optionally containing one or more heteroatoms, selected from group comprising N or O, wherein said heterocycle is optionally substituted with benzyl; Z has formula (A) , wherein R3 and R4 each are independently hydrogen, optionally substituted aromatic group containing in cyclic structure from 5 to 10 carbon atoms, wherein substituents are the same or different and represent lower C1-C4-alkyl, OR10 (OR10 is hydrogen, saturated or unsaturated lower C1-C6-alkyl or formula ) or linear or branched C1-C6-hydrocarbon; or R2 and R3 together with carbon atom attached thereto form 5-6-membered carbocycle; and R4 represents hydrogen or attaching site of group –OCH2-C≡CCH2NRR1; or formula (B) , wherein R5 is hydrogen, linear or branched lower C1-C6-hydrocarbon, with the proviso, that when Z represents R and R1 both are not methyl or R and R1 together with nitrogen atom attached thereto cannot form groups , or ]. Also disclosed are drug component with proliferative activity for prophylaxis or treatment of neoplasm and pharmaceutical composition with proliferative activity based on the same. Derivatives of present invention have antyproliferative properties and are useful as modulators of drug resistance in cancer chemotherapy; as well as in pharmaceuticals for prophylaxis or treatment of neoplasm, climacteric disorders or osteoporosis.
EFFECT: new compounds with value bioactive effect.
31 cl, 2 tbl, 32 ex
Y is a bond or-O-;
p = 1-16; and
Z is-H or-G-Q, where G is a simple bond or-CH= CH-;
and Q is phenyl, substituted C1-C3the alkoxy group
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
SUBSTANCE: claimed invention relates to the field of biotechnology. Claimed are versions of a humanised anti-CD79b antibody, each of which is characterised by the presence of a light and heavy chain and a set of 6 CDR with a determined amino acid sequence. An epitope of the antibody from 11 amino acids is determined by the Biacore method. Disclosed are: an immunoconjugate of the antibody with a medication or means for inhibiting cell growth, where the antibody is bound with means covalently, and versions of the composition, based on an effective quantity of the immunoconjugate or the antibody, used for inhibiting B-cell proliferation; as well as a method of determining CD79b in a sample with the application of the antibody. Described are: an antibody-coding polynucleotide, as well as an expression vector and an isolated cell, containing the vector for obtaining the antibody. Disclosed are versions of applying the antibody or immunoconjugate for obtaining the medication for inhibiting the growth of CD79b-expressing cells for the treatment of an individual, affected with cancer, for the treatment of proliferative disease or for inhibiting B-cell proliferation.
EFFECT: invention provides novel antibodies, which can find further application in the therapy of proliferative CD79b-associated diseases.
91 cl, 8 tbl, 9 ex, 20 dwg
SUBSTANCE: invention refers to biotechnology, virology and medicine. The method provides administering a pox virus containing the defect F2L gene into a host body or a cell. What is also described is using this pox virus for producing a drug preparation for treating proliferative diseases or diseases accompanied by osteoclast hyperactivity. The invention can be used in medicine.
EFFECT: what is presented is the method of treating proliferative diseases or diseases accompanied by osteoclast hyperactivity.
28 cl, 10 dwg, 3 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to methods of obtaining heteroaryl compounds, represented by structural formulae (I) or (II): where R1-R4 have values, given in subcl. 1,14 of the formula.
EFFECT: compounds can be used for treatment or prevention of cancer, inflammatory states, immunological states, etc.
29 cl, 20 ex
SUBSTANCE: invention relates to novel choline salt of 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid, corresponding to formula and to its crystalline form. Crystalline form of salt (A) has characteristic peaks at diffraction angles (2θ(E)) 7.1, 11.5, 19.4, 20.3, 21.5, 22.0, 22.6, 23.5 and 26.2 in diagram of powder diffraction of X-rays, characteristic peaks of values of chemical shifts (δ(ppm)) 155.8, 149.8, 145.3, 118.0, 113.7, 111.6, 110.3, 98.1, 69.8, 58.7, 57.1 and 55.5 in solid-state 13C NMR spectrum and characteristic peaks of values of chemical shifts (δ(ppm)) -131.6, -145, and -151.8 in solid-state 19F NMR spectrum, as well as endothermic peak about 213°C in diagram of differential-thermal analysis.
EFFECT: compound has excellent solubility and stability in storage.
5 cl, 5 dwg, 3 tbl, 8 ex
SUBSTANCE: invention relates to biotechnology, specifically to novel hetero-multimeric proteins obtained from modified ubiquitin, and can be used in medicine to treat or diagnose diseases associated with hyperprodution of the extradomain B of fibronectin (ED-B). The protein includes two monomeric ubiquitin links which are differently modified through substitutions of at least 6 amino acids in positions 4, 6, 8, 62, 63, 64, 65 and 66 of SEQ ID NO: 1. In the first monomer link the substitutions include: F4W, K6(H, W or F), Q62N, E64(K, R or H), S65(L, F or W), T66(S or P), and in the second monomer link: K6(T, N, S or Q), L8(Q, T, N or S), Q62(W or F), K63(S, T, N or Q), E64(N, S, T or Q), S65(F or W), T66(E or D).
EFFECT: invention enables to obtain a modified heterodimeric ubiquitin protein, capable of binding with ED-B with high affinity.
28 cl, 18 dwg, 3 tbl, 7 ex
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
SUBSTANCE: invention relates to field of organic chemistry, namely to polymorphs of form 1 and form 2 of (-)trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolon-I-yl)-4-(1H-indol-3-yl)pyrrolidin-2,5-dione. Invention also relates to methods of obtaining said polymorphs and pharmaceutical composition on their basis.
EFFECT: novel polymorphs of (-)trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolon-I-yl)-4-(1H-indol-3-yl)pyrrolidin-2,5-dione are obtained, useful in cancer treatment.
23 cl, 26 dwg, 2 tbl, 27 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to biotechnology and represents an immunogenic composition for preventing and treating cancer diseases, which contains the non-functional BORIS protein, a sequence of which is free from the zinc finger protein. The present invention also discloses an immunotherapeutic cancer composition containing the above non-functional BORIS protein or a bacterial, mammalian or yeast cell, or a viral particle able to express the above non-functional BORIS protein. The present invention also discloses a method for immunising a patient by administering an effective amount of the above immunotherapeutic composition, as well as using the above immunotherapeutic composition for preparing the cancer vaccine.
EFFECT: invention enables increasing the efficacy of the immunoprophylactic and therapeutic cancer vaccine.
22 cl, 7 dwg, 2 tbl, 8 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, namely to a method for producing a complex compound of dihydroquercetin with metal ions specified in zinc, copper (II) or calcium possessing antioxidant activity. A method consists in the fact that dihydroquercetin and metal salt is mixed in the dry state in a reactor in certain molar ratio; that is followed by adding water at a certain temperature or ethanol or aqueous-alcoholic solution at a room temperature at the controlled medium acidity; using metal salts containing weak acid anions provides medium pH equal to 5.0-5.6; using the metal salts containing strong acid anions requires reducing pH to 7 by adding an alkaline solution; the reaction is completed almost immediately for the first 5 minutes; the precipitation is filtered in water and/or ethanol; dried in air, then in a drying box to constant weight, and a complex compound is produced. The declared method enables reducing the production costs substantially and cheapening the technological process in achieving the target yield with the preset properties.
EFFECT: method enables producing the stable metal structures and individual powdered substances.
3 cl, 3 dwg, 3 tbl, 12 ex
SUBSTANCE: method for producing an agent inhibitory the tumour cell growth, involving preparing a mixture of aqueous solution of selenious acid and PEG 400; that is followed by preparing a mixture of aqueous solution of hydrazine hydrochloride and PEG 400; the produced mixtures are combined; the solution is put to dialyse against distilled water; surplus of water is driven off in a rotary evaporator; the produced solution is added with silymarin dissolved in Solufor with dialysis against distilled water; pH is reduced to 7.2-7.4; the method is implemented in certain circumstances.
EFFECT: agent produced by the given method possesses high inhibitory action on the tumour cell growth.
4 dwg, 2 tbl, 2 ex
SUBSTANCE: water soluble composition consists of L-arginine and dihydromeletin in specified molar ratio. Method of obtaining water-soluble pharmaceutical composition consists in the following: mechanical activation of mixture L-arginine and dihydromeletin hydrate in argon atmosphere is carried out.
EFFECT: composition possesses high water solubility and higher biological activity.
3 cl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to medicine, namely to oncology, and can be used for treatment of cerebral glioma. For this purpose combination of cannabinoids-tetrahydrocannabinol (THC) and cannabidiol (CBD) and non-cannabinoid chemotherapeutic agent is claimed. THC and CBD ratio constitutes from 5:1 to 1:5.
EFFECT: combination of anti-tumour medications provides efficient reduction of brain tumour volume due to selective death of transformed cells.
14 cl, 2 tbl, 8 dwg
SUBSTANCE: therapeutic composition of dihydroquercetine in the form of nanoparticles, containing herbal phosphatidylcholine, maltose and dihydroquercetin in certain propotions.
EFFECT: composition possesses the high pharmacological activity, low toxicity; it is long-storable.
3 dwg, 1 tbl, 4 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to compositions of an antioxidant composition aimed at the suppression of oxidative stress in type 2 diabetes. The said compositions contain, counted per 1 dose: 50-120 mg of coenzyme Q10, 30-160 mg of dihydroquercetin, and 30-60 mg of A-lipoic acid or 50-100 mg of coenzyme Q10, 50-100 mg of dihydroquercetin, 30-60 mg of A-lipoic acid and 50-100 mg of nicotineamide.
EFFECT: compositions possess an antioxidant activity and prevent the development of the fatty tissue dysfunction.
2 cl, 1 dwg, 2 tbl, 2 ex