N-pyperonyl derivatives of daunorubicine, with antiprofliferative properties
SUBSTANCE: invention relates to the N-piperonyl derivatives of daunorubicine, which can be used in medicine, of general formula I
where R=H, OCH3.
EFFECT: new daunorubicine derivatives with antiproliferative properties and relatively low acute toxicity are proposed for cancer treatment, including non-small cell lung cancer, rhabdomyosarcoma, bowel carcinoma, breast adenocarcinoma.
2 cl, 1 tbl, 2 ex
SUBSTANCE: claimed invention relates to method of synthesising salt of 4-demethoxydaunorubicine, which has chemical structure of formula (I): where An- represents anion, which can be used in treatment of acute myeloid leukosis. At the first stage of claimed method hydrochloride salt of daunorubicine is converted into 3'-protected daunorubicine (3'-prot.-daunorubicine) of formula (III) by bringing in contact with azide-forming reagent or in 3'-prot.-daunorubicine of formula (IV) by bringing in contact with trifluoroacetylating reagent. At the second stage demethylation of 3'-prot.-daunorubicine of formula (III) or (IV) by contact with "mild" Lewis acid in water-free solvent results in obtaining 4-demethyl-3'-prot.-daunorubicine of formula (V) or (VI) respectively, whose further trifluoromethanesulphonylation by bringing in contact with trifluoromethanesulphonylating reagent results in 4-O-trifluoromethanesulphonyl-3'-(prot.daunorubicine) of formula (VII) or (VIII) respectively, 4-T1-3'-protective daunorubicine. Reduction of compound of formula (VII) or (VIII) by bringing in contact with reducing agent results in obtaining 4-demethoxy-3'-prot.-daunorubicine of formula (IX) or (X) respectively, 3'-protective-4-demethoxydaunorubicine, and the following removal of protective group 3'-prot. from 4-demethoxy-3'-prot.- daunorubicine of formula (IX) or formula (X), at which compound of formula (IX) is brought in contact with azide-reducing reagent, with compound (X) being brought in contact with alkali solution, results in obtaining 4-demethoxydaunorubicine. In contact of the latter with acid of formula H+An- salt of 4-demethoxydaunorubicine is obtained.
EFFECT: claimed method makes it possible to obtain target product with high output.
12 cl, 1 tbl, 7 ex
SUBSTANCE: invention relates to tetracyclic antibiotic anthraquinone derivatives having anticancer activity.
EFFECT: tetracyclic antibiotic anthraquinone derivatives described in the present invention have the same or higher activity than current medicinal agents such as doxorubicin, daunorubicin or similar, in a cellular level, and at the same time have better tolerance than doxorubicin and daunorubicin for animal organism.
15 cl, 54 ex, 3 tbl
SUBSTANCE: invention relates to anthracycline derivatives of general structural formula given below
where R1, R2 and R3 are H or OH; R4 denotes H, OH, C1-C5alkyl, or O-(C1-C5)alkyl; R5 is O or NH; and R6 is selected from a group comprising H, OH and a sugar residue which is The invention also relates to a method of producing said derivatives by reacting 13-ketoanthracycline or acid salt thereof with benzenidesulphonylhydrazide in an alcohol solvent at temperature of approximately 35-50°C for approximately 10-24 hours. The invention also pertains to a method of producing 13-deoxyanthracyclines, involving preparation of an alcoholic solution of the said 13-benzenidesulphonylhydrazine anthracycline; addition of a reducing agent and acid to the said solution; heating said solution without stirring, agitation or dephlegmation in order to reduce said 13-benzenidesulphonylhydrazine anthracycline; neutralisation of said solution with an aqueous solution of a base to obtain said 13-deoxyanthracycline derivative and precipitation; and, additionally, filtration of said precipitate, extraction of said 13-deoxyanthracycline from said precipitate, as well as extraction of said 13-deoxyanthracycline from the filtrate. The invention also relates to a method of producing 5-imino-13-deoxyanthracyclines involving synthesis of 13-deoxyanthracyclines as described above; dissolution of said 13-deoxyanthracyclines in an alcohol and conversion of said 13-deoxyanthracyclines to the corresponding 5-imino-13-deoxyanthracyclines under the effect of ammonia at temperature lower than approximately 20°C. The invention also relates to a method of producing 13-deoxyanthracyclines involving preparation of an alcoholic solution of 13-benzenidesulphonylhydrazine anthracycline having structural formula given below; addition of a reducing agent and a pyridinium acid salt to the said solution and heating said solution to reduce said 13-benzenidesulphonylhydrazine anthracycline. The invention also relates to a method of producing 5-imino-13-deoxyanthracyclines involving preparation of said 13-deoxyanthracycline and its conversion to the corresponding 5-imino-13-deoxyanthracycline under the effect of ammonia at temperature lower than approximately 20°C.
EFFECT: new compounds have useful biological properties.
21 cl, 4 tbl, 4 ex
SUBSTANCE: invention relates to cytotoxic compounds with directional effect, which are peptide derivatives of camtothecin, doxyrubicin and palitaxel, their pharmaceutical compositions and use in making medicinal agents for treating pathological conditions, related to aberrant or undesirable proliferation, migration and/or physiological activity of cells.
EFFECT: agents are highly effective.
43 cl, 79 ex, 1 tbl
SUBSTANCE: invention relates to improved method of obtaining 4-R-substituted anthracyclines of formula (I) , and their corresponding salts from 4-demethyldaunorubicin. Steps of treating 4-demethyldaunorubicin with a sulfonylating agent to form 4-demethyl-4-sulfonyl-R3-daunorubicin. 4-Demethyl-4-R3-sulfonyl-daunorubicin are performed, then it is processed with reducing agent in the presence of a transition metal catalyst in a temperature range from 30°C to 100°C in polar aprotic solvent in an inert atmosphere. Protected 4-demethoxy-4-R-daunomycin then undergoes hydrolysis in a basic solution to form the 4-R-substituted anthracyclines. Application of novel method makes it possible to avoid stage of forming stereospecific glycoside bond between aglycone and aminoglycoside. The method also increases the yield of final product up to 30-40%.
EFFECT: elaboration of efficient method of obtaining 4-R-substituted demethyldaunorubicin.
13 cl, 10 ex
FIELD: radiolabeled compounds, medicine, oncology, pharmacy.
SUBSTANCE: invention relates to a novel physiologically active uniformly tritium-labeled compound, namely, [3H]-14-hydroxydaunomycin of adriamycinone of the formula (I): .
EFFECT: valuable medicinal property of compound.
1 dwg, 1 ex
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to a method for synthesis of optically active tetraline of the formula (I): . Synthesis is carried out from 5,8-dimethoxy-3,4-dihydronaphthalene by the following steps: (1) acylation in the presence of AlCl3 excess at temperature -35-25°C; (2) enantioselective dihydroxylation by Sharpless in the presence of the catalytic amount of osmium salt; (3) preparing 1-chloro-2-acetyl derivative; (3) dihydrochlorination and the following hydrolysis. Method provides the significant increasing the yield of the end substance.
EFFECT: improved method of synthesis.
5 cl, 6 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel biologically active compounds. Invention describes compounds or their salts of the general formula (I): A-B-N(O)s (I) wherein s = 2; A means R-T1- wherein R represents radical of a medicinal substance under condition that a medicinal substance by the formula R-T1-Z or R-T1-OZ wherein Z represents hydrogen atom (H) or (C1-C5)-alkyl is taken among paracetamol, salbutamol, ambroxol, alendronic acid,, cetirizine, ampicillin, aciclovir, doxorubicin, simvastatin, diphylline, tacrine, clopidogrel, dimethylomeprazol, diclofenac, ferulic acid, enalapril, propranolol, benfurodil hemisuccinate, tolrestate or sulindac; T1 means (CO), oxygen atom (O) or NH; B means TB-X2-O- wherein TB means bivalent radical R1B-X-R2B wherein R1B and R2B are similar or different and represent linear or branched (C1-C6)-alkylenes and X represents a bond, oxygen (O), sulfur (S) atom or NR1C wherein NR1C represents hydrogen atom (H) or linear or branched (C1-C6)-alkyl; corresponding precursor B is represented by the formula -TB-X2-OH wherein TB means (CO) and free valence in TB represents -OZ wherein Z is determined above, or TB means oxygen atom (O), and free valence in TB represents hydrogen atom (H) under condition that in the formula (I) when X2 in precursor B represents linear or branched (C2-C20)-alkylene then a medicinal substance by the formula R-T1-Z or R-T1-OZ used in the formula (I) doesn't belong to the following substances: enalapril (ACE inhibitors) and diclofenac (NSAID). Also, invention describes pharmaceutical compositions for using in cases of oxidative stress and 4-nitroxybutanoic acid 4'-acetylaminophenyl ester. Invention provides preparing novel compounds possessing useful biological properties.
EFFECT: valuable medicinal properties of medicinal substances and compositions.
7 cl, 8 tbl, 32 ex
FIELD: organic chemistry, chemical technology, antibiotics.
SUBSTANCE: invention relates to a method for preparing antibiotic carminomycine or its hydrochloride. Method involves glycosylation of carminomycinone with 1,4-di-O-substituted N-acyldaunosamine (2,3,6-trideoxy-3-amino-L-lyxo-hexapyranose) of the formula (3):
wherein R1 means trifluoroacetyl, N-(9H-fluorene-2-ylmethoxy)carbonyl, allyloxycarbonyl; R2 means acetyl, trifluoroacetyl, 4-nitrobenzoyl, allyloxycarbonyl; R3 means trichloroacetamidyl, trialkylsilyl, acetyl, trifluoroacetyl, 4-nitrobenzoyl, allyloxycarbonyl in the presence of trimethylsilyltrifluoromethane sulfonate in mixture of anhydrous aprotonic organic solvents followed by removing blocking groups and isolation of carminomycine as a base or hydrochloride. Glycosyl-donor is used as a mixture of α- and β-isomers or as individual α- or β-isomers. As anhydrous aprotonic organic solvent method involves using mixtures of dioxane with chloroform, methylene chloride, diethyl ether, acetone and tetrahydrofuran. The reaction is carried out in presence of molecular sieves at temperature 10°C, nor above, in atmosphere of dried air or dried inert gas. Removal of protecting groups is carried out in the presence of alkaline metal hydroxides in an aqueous-organic medium: water - methanol, water - dioxane, water - tetrahydrofuran, water - acetone. Method provides increasing yield of carminomycine by 3 times as compared with the prototype.
EFFECT: improved preparing method, enhanced yield.
5 cl, 7 ex
where R1, R2and R3are H, HE or och3group and R4represents the following groups:
The proposed pharmaceutical composition having antitumor activity, containing at least one derivative of 5-imino-13-deoxy of anthracycline
FIELD: medicine, pharmaceutics.
SUBSTANCE: what is disclosed is a new aminoglycoside antibiotic which possesses excellent antibacterial activity against a bacterium inducing an infection, particularly MRSA, and also possesses low renal toxicity. A method for making said antibiotic is described. More specifically, there are disclosed a compound presented by formula (Ia) wherein the radical values are specified in the description, or its pharmaceutically acceptable salt or solvate, or mixed diastereomers of the compound; an antibacterial agent containing the compound, pharmacologically acceptable salt, solvate or mixed diastereomers; and a method for producing said compound.
EFFECT: what is disclosed is a new aminoglycoside antibiotic which possesses excellent antibacterial activity against a bacterium inducing an infection, particularly MRSA, and also possesses low renal toxicity.
23 cl, 21 ex, 1 tbl, 13 dwg
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