Antineoplastic agents (A61P35)

A   Human necessities(308424)
A61P35                 Antineoplastic agents(3496)
A61P35/02 - Specific for leukemia(103)
A61P35/04 - Specific for metastasis(103)

Salts and crystalline forms of apottosis-inducing agent // 2628560
FIELD: pharmacology.SUBSTANCE: invention relates to a compound having the systematic name 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy) benzamide (compound 1) in the form of a free base crystalline anhydrate, a free base hydrate of crystalline form, a solvate of crystalline form, a hydrochloride salt of crystalline form, or a sulfate salt of crystalline form. The invention also relates to a pharmaceutical composition having an inhibitory activity against anti-apoptotic proteins of the Bcl-2 family comprising a therapeutically effective amount of the compound of the invention and one or more pharmaceutically acceptable excipients.EFFECT: crystalline forms of compound 1 suitable for use as an active pharmaceutical ingredient.21 cl, 14 dwg, 14 tbl, 17 ex
Tricyclic nitrogen-containing derivatives of imidazo[4,5-c]pyridine, having inhibiting activity in response to hystamine 4 receptor (hh4r) // 2628074
FIELD: pharmacology.SUBSTANCE: invention relates to a heterocyclic compound of formula 1 , or to a racemate, isomer, or pharmaceutically acceptable salt thereof, wherein X1 and X2 are C; each of X3 and X4 is independently C or N, provided that one of X3 and X4 is N; R1 is a saturated 4-9 member mono- or bi-heterocyclyl containing 1-2 heteroatoms (where the heteroatoms are N), where R1 is unsubstituted or substituted by 1 to 3 substituents selected from -NR6R7 and R8; or R1 is selected from -NR6R7 and R8; R2, R3, R4 and R5 may be the same or different; and each is independently selected from -H; -C1-C6alkyl; -C1-C6haloalkyl; -C1 -C6perhaloalkyl; -halogen (-F, -Cl, -Br, -I); -CN; -C1-C6talkoxy; -C1-C6haloalkoxy; -C1-C6perhaloalkoxy; C2alkenyl; -C2-C3alkynyl; -amino; -OH; -nitro (-NO2); -C6-C1aryl; and furan; provided that, when X3 is N, R4 is absent; and when X4 is N, R5 is absent, each of Y1, Y2, Y3, Y4 and Y5 is independently C or a heteroatom (preferably a heteroatom independently selected from N, O and S), provided that at least two of Y1, Y2, Y3, Y4 and Y5 are heteroatoms independently selected from N and O; each of Y2 and Y3 can be independently substituted by R9; Y4 may be substituted with -H or -C1-C6alkyl; each of R6 and R7 is independently selected from -H; -C1-C6alkyl; and -carboxyl (-COOH); R8 is -C1-C6alkyl or -C3cycloalkyl; and R9 is selected from -H; -C1-C6alkyl; and -C3cycloalkyl; wherein the alkyl and heterocyclyl may be independently unsubstituted or substituted by one or more substituents (for example, 1 to 3 substituents) selected from the group consisting of -C1-C4alkyl, -C1-C4alkoxy and -OH. The invention also relates to particular compounds and a pharmaceutical composition based on the said compounds.EFFECT: new heterocyclic compounds useful for human histamine receptor 4 inhibition are obtained.13 cl, 13 tbl, 144 ex

New cc-1065 analogs and their conjugates // 2628069
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula or a pharmaceutically acceptable salt thereof, wherein DB is a DNA-binding group and is DB6 group ; R1 is chlorine; R2, R2', R3, R3', R4, R4', R12 and R19are H; X2 is selected from C(R14)(R14'), where R14' has the same value as defined for R7' and is independently selected, and R14' and R7' are absent, which gives a double bond between the atoms carrying R7' and R14'; R5, R6 and R7 are independently selected from H, R, where Re are selected from C1Alkyl, and R5'+R6', are absent, which gives a double bond between the atoms carrying R5 and R6, and/or R6 and R7, and/or R7 and R14 respectively; X1 is selected from O; X3 is selected from S, N, and NR15; X4 is selected from N and CR16; X5 is selected from O; X6* is selected from CR11; X7 is selected from CR8, N; X8 is selected from CR9, N; X9* is selected from CR10; X10* is selected from CR20; X11* is selected from C; X7* and X8* have the same values as those defined for X7 and X8 respectively, and are chosen independently; X34 is selected from C; annular atom B in X11* in DB6 is connected to the ring atom of ring A, so that ring A and ring B in DB6 are directly connected through a direct link; fig. implies that the said bond can be a or a non-cumulated direct bond, optionally delocalized, double bond; R8, R9, R10, R11, R15, R16, R20 are each independently selected from H, N(Rh)C(O)Ri, where Rh, Ri are independently selected from H and optionally substituted C6 aryl, one optional substituent in Ri is -OH or -NH2; a is 0 and b is 1. The invention relates to a pharmaceutical composition for tumour treatment or prevention for a mammal, comprising a therapeutically effective amount of formula (I) compound and a pharmaceutically acceptable carrier.EFFECT: DNA-alkylating agent SS-1065 analogues.6 cl, 13 dwg, 1 tbl, 23 ex
Compound as wnt signal inhibitor, its compositions and application // 2627712
FIELD: pharmacology.SUBSTANCE: invention relates to a heterocyclic compound of the general formula (I) or an N-oxide thereof, wherein X1, X2, X3 and X4 independently represent CR4 or N, where 0 or 1 of X1-X4 can be N; Y1, Y2 and Y3 are hydrogen; R1 is selected from hydrogen, , C6 aryl, 6-member heterocycloalkyl containing 2 heteroatoms selected from N and O, and 5- or 6-member heteroaryl containing 1-4 heteroatoms selected from N, O and S, wherein each of C6 aryl, 6-member heterocycloalkyl and 5- or 6-member heteroaryl may be optionally substituted with one R4; R2 is selected from hydrogen, halogen, C1-6 alkyl, , C6 aryl and 6-member heteroaryl containing 1 to 2 N atoms, where each of C6 aryl and 6-member heteroaryl may be optionally substituted with one R4. If X5 is N, R2 is selected from halogen, C1-6 alkyl, , C6 aryl and 6-member heteroaryl containing 1 to 2 N atoms, where each of C6 aryl, and 6-member heteroaryl may be optionally substituted with one R4; each R4 Is independently selected from hydrogen, halogen, cyano, oxo, C1-6 alkoxy, -C(O)OR5, -C(O)R5, C1-6 alkyl. Moreover , C1-6 alkyl may be optionally substituted with 1 to 3 substituents selected from halogen and cyano; R5 is C1-6 alkyl; and where the central structure of Formula I, limited by X5, X6, X7 and X8, is: or The invention also relates to particular compounds, a method for inhibiting the secretion of WNT signalling in a cell, use of a compound of formula (I), a method for treatment of a disorder mediated by WNT. .EFFECT: new heterocyclic compounds have been obtained that are useful for treatment of cancer, fibrosis and osteoarthritis.22 cl

Sterines derivatives and their application for treatment of diseases related to transformed astrocytal cells, or for treatment of malignant blood diseases // 2627710
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula having a basic structure of 7 beta-hydroxycholesterol, where A is a group of -(R1)n, where R1 is an amino acid residue of glycine or alanine attached to its C-terminus, and n is 1 or 2. Moreover, R1 are the same or differentt and the N-terminus of the said amino acid is substituted with -C(O)-R2, where R2 is a benzyloxy group or a -(R1)n group, where R1 is an amino acid residue of glycine or alanine, n is 1 or 2, and the N-terminus of the said amino acid is substituted with benzyloxycarbonyl; or -C(O)-R6 group, where R6 is a five-member heterocycle comprising 2 oxygen heteroatoms unsubstituted or substituted with at least one unbranched or branched C1-C6alkyl; B is a -C(O)-R7 group, where R7 is C1-C6alkyl, unbranched or branched; or R7 is OR8, where R8 is C1-C6alkyl unbranched or branched. The invention also relates to individual compounds, a process for the preparation of a formula (I) compound, and a pharmaceutical composition having activity against transformed astrocyte cells.EFFECT: new compounds of the formula are obtained that can be used to treat diseases associated with transformed astrocytes.15 cl, 4 tbl, 16 ex
Derivatives of indolin-2-she as inhibitors of proteinkinas // 2627706
FIELD: pharmacology.SUBSTANCE: invention relates to indoline-2-one derivatives, the formula A, which are protein kinase inhibitors for the treatment of hyperproliferative diseases such as lung cancer, colorectal cancer, liver cancer and acute myelomonocytic leukemia.EFFECT: increased efficiency of treatment.15 cl, 3 dwg, 6 tbl, 1 ex

Crystalline forms of 1-(3-tret-butyl-1-p-tolyl-1h-pyrazol-5-yl)-3-(5-fluoro-2-(1-(2-hydroxyetil)-1h-indasol-5-yloxy)benzyl) hydrochloride urea // 2627702
FIELD: pharmacology.SUBSTANCE: invention relates to a crystalline polymorphic Form B of the hydrochloride salt of 1-(3-t-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)benzyl) urea, which is characterized by the presence of peaked diffraction peaks (degrees 2θ at ± 0.3) at about 12.3, 13.0, 15.9, 16.9 and 17.6 and to a pharmaceutical composition for proliferative disorders treatment comprising the said polymorphic Form B. The invention also relates to a method for proliferative diseases treatment with the claimed pharmaceutical composition, pharmaceutical composition and method application for preparation of the said polymorphic Form B.EFFECT: increased efficiency of treatment.89 cl, 7 dwg, 23 tbl, 10 ex
Compounds of pyridazinamide and their use as synthetic syneckinasis inhibitors (syk) // 2627661
FIELD: chemistry.SUBSTANCE: invention relates to novel pyridazinamides of the formula I , where all variable substituents are defined in the claims, and their pharmaceutically acceptable salts, as well as a pharmaceutical composition based on them.EFFECT: compounds of the formula are SYK inhibitors and are useful for the treatment of autoimmune and inflammatory diseases.10 cl, 1 tbl, 43 ex
ethods for cancer treatment using autophagy inhibitor based on thioxanthone // 2627588
FIELD: medicine.SUBSTANCE: autophagy inhibitor based on thioxanthone is used to manufacture a medicament for cancer treatment in combination with an autophagy-causing compound. A pharmaceutical composition and a pharmaceutical kit for cancer treatment containing an autophagy inhibitor based on thioxanthone and an autophagic compound are also provided.EFFECT: increased anticancer activity of therapy due to decreased cell viability and increased apoptosis.8 cl, 26 dwg, 7 ex

Preparations of {2-[(1s)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-3-oxo-2,3-dihydro-1h-isoindol-4-yl} amide of cyclopropanecarboxylic acid // 2627471
FIELD: pharmacology.SUBSTANCE: invention relates to an oral dosage form comprising an amorphous dispersion of {2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl} amide of cyclopropanecarboxylic acid or a pharmaceutically acceptable salt thereof in a hydrophilic polymer, wherein the hydrophilic polymer is hydroxypropylmethylcellulose. Also, methods for treatment, control or prevention of various diseases such as cancer or inflammatory disease are proposed.EFFECT: creation of a dosage form with rapid disintegration, reduced friability, content uniformity, rheological properties required for production, solubility, bioavailability, stability and desired hardness.9 cl, 4 dwg, 2 tbl, 1 ex
Bicyclic heterocyclic derivatives, their production and application // 2627269
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of general formula (I) , as well as to a method for their preparation, pharmaceutical compositions based thereon, and their application.EFFECT: new compounds have been obtained that can be used to treat or prevent pathology for which it is necessary to inhibit the mTOR kinase.20 cl, 4 tbl, 30 ex
Aza-aryl-1-h-pyrazol-1-yl-sulphonamides // 2627268
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula (I) ,in which radicals and characters have values specified in the claims and their versions. The proposed compounds act as potent antagonists of CCR (9) receptor. Animal testing has shown that these compounds are useful for treatment of inflammation, disease with a hallmark for CCR (9). The compounds as a whole are arylsulfamide derivatives and are used in pharmaceutical compositions, methods for treatment of CCR (9) mediated diseases and as a control in assays for identification of CCR (9) antagonists.EFFECT: increased efficiency of compounds application.26 cl, 2 tbl, 33 ex

Exotoxin a pseudomonas with less immunogenic t-and/or b-cell epithopes // 2627216
FIELD: biotechnology.SUBSTANCE: A Pseudomonas (PE) ectotoxin is proposed with substitution of one or more amino acid residues at L423, F443 and L477 positions. Also a chimeric molecule containing a targeting agent fused to PE and a molecule containing a targeting agent conjugated to PE. In addition, nucleic acids encoding PE and chimeric molecule; a recombinant expression vector; a host cell for PE production; a pharmaceutical composition for cell growth inhibition; a method for cancer treatment or prevention in a mammal; a method for target cell growth inhibition; methods for production of PE, chimeric molecule containing a targeting agent fused to PE, and molecules where PE is covalently bound to the targeting agent are described.EFFECT: A Pseudomonas exotoxin of this invention exhibits reduced immunogenicity while maintaining cytotoxicity.23 cl, 12 dwg, 20 tbl, 16 ex

Recombinant target toxin specific to her2 receptor expressing cells // 2627215
FIELD: biotechnology.SUBSTANCE: recombinant targeted toxin, specific for HER2 receptor expressing cells is proposed. The recombinant target toxin comprises a HER2-specific targeting module represented by the HER2-specific darpin DARPin class coding sequence and a toxic module in the form of a fragment of pseudomonade exotoxin A ETA interconnected by a flexible hydrophilic 16-amino acid linker represented by the sequence of SEQ ID NO: 1, oligogistidine sequence His6 and KDEL sequence at the C-terminus of the molecule. The recombinant target toxin is represented by the sequence of SEQ ID NO: 2.EFFECT: increased toxic effect on the HER2 receptor expressing cells and increased effectiveness of targeted therapy.2 cl, 6 dwg

New binding molecules with anti-tumour activity // 2627185
FIELD: biotechnology.SUBSTANCE: binding molecule specifically binding to two different epitopes on HER2 and a method for its preparation, as well as a nucleic acid encoding it, expressing a vector comprising this nucleic acid molecule, a host cell for expression of a binding molecule transformed with the expression vector, and a pharmaceutical composition for cancer treatment comprising a binding molecule or a nucleic acid molecule encoding it, or an expression vector, are proposed. The proposed binding molecule comprises the first polypeptide comprising an amino acid sequence that is at least 90% identical to SEQ ID NO:1, and the second heavy and light chain antibody polypeptide comprising amino acid sequences at least 95% identical to SEQ ID NO:NO:154 and SEQ ID NO:155, respectively. The presented group of inventions is applicable in medicine for anti-tumour therapy.EFFECT: binding molecule effectively suppresses the tumour cells growth and shows high antiproliferative activity.17 cl, 13 dwg, 1 tbl, 14 ex

Novel peptide with 5 linked ctl epitopes // 2627175
FIELD: biotechnology.SUBSTANCE: peptide made from 5 CTL epitopes of cancer antigens linked through amino acid linkers is obtained. The resulting peptide is used to stimulate peripheral blood lymphocytes in order to obtain a combination of CTL specific for the cancer antigen.EFFECT: invention provides a peptide vaccine for cancer treatment for wide range of cancer patients without the need for HLA typing and regardless of patients' HLA types.6 cl, 2 dwg, 2 tbl, 4 ex

Anti-clusterin antibodies and antigen-binding fragments and their use for tumours volume reduction // 2627163
FIELD: biotechnology.SUBSTANCE: clusterin-binding antibody and an antigen-binding fragment thereof are proposed. Nucleic acids encoding variable regions of antibodies, an expression vector; a cell; a kit and a method for production of an antibody or an antigen-binding fragment thereof are described. Also a pharmaceutical composition for cancer cell growth reduction or tumour cells volume reduction; combination for cancer treatment, and a pharmaceutical composition comprising a chemotherapeutic agent; a method for cancer cell growth reduction or tumour cells volume reduction; a method for carcinomas treatment; kit for application in cancer treatment or detection; use of an antibody or an antigen-binding fragment thereof for tumour volume reduction. The invention may find further application for treatment of diseases associated with clusterin.EFFECT: antibody of the present invention is a humanized form of murine antibody 16B5 and has an approximately equal binding affinity for clusterin.28 cl, 16 dwg, 1 tbl, 6 ex
ethod for treatment of locally advanced breast cancer with tumour skin ulceration // 2626914
FIELD: medicine.SUBSTANCE: to treat locally advanced breast cancer with tumour skin ulceration, radiation therapy is performed in the mode of medium dose fractionation on the area of the mammary gland base and regional lymph drainage zone. In addition, prior to irradiation, a "Coletex-5-ftor" hydrogel tissue is applied to the tumour region for 5-7 days, 2-3 times daily. Prior to irradiation, a "Coletex-5-ftor" hydrogel tissue is applied to the area of skin tumour ulcers, where nitric acid silver is added as 0.2-2.0 wt %. At that, the marginal zones of skin tumour ulceration are treated with a hydrogel material on the basis of "Coletex-gel-DNA" sodium alginate, where betulin-containing birch bark extract is added as 0.1-1.5 wt %. After application of these hydrogels, a thermo-net is placed on top of them on the breast area, the net is cut out to overlap the ulcer area by 1.0-1.5 cm. Prior to radiotherapy, field markings in the ulcer area is carried out on the thermo-net.EFFECT: method ensures accelerated tumour ulcers healing, reduced drug load, reduced toxicity and a possibility of carrying out radiation therapy without interruption, reduced traumatization of tissues in the irradiation zone, and cessation of inflammatory processes.2 ex
Adamantyl derivatives useful for treatment of jnk-mediated disorder // 2626890
FIELD: chemistry.SUBSTANCE: invention relates to the field of organic chemistry, namely to the heterocyclic compound of I formula or a pharmaceutically acceptable salt thereof, wherein R represents phenyl optionally substituted with one or more R'; R' is halo or methoxy; X represents CH; X1 represents C(=O)OCH3; Y represents N; Y1 It is OH, N(Y1')2, NHS(=O)2Y1', NHC(=O)Y1', NHC(=O)C(CH3)2OH or NHC(=O)C(CH3)2OC(=O)Y1'; each Y1' independently represents H, C1-6-alkyl or lower cycloalkyl; Y2 It is H. The invention also relates to formula I based on the compound of the pharmaceutical composition and the use thereof.EFFECT: new heterocyclic compounds useful for treating JNK-mediated disorder are obtained.12 cl, 5 tbl, 31 ex
eans for polyps treatment in sinuses and prevention of their repeated growth, and method of its application // 2626829
FIELD: medicine.SUBSTANCE: method for polyps treatment in the sinuses is proposed. The method is characterized by application of aqueous solutions of acetic acid in concentrations of 3-6% as means or drug component for the treatment of polyps in the nose sinuses, and 1-2 drops of solution are injected into each sinus within 1-2 weeks, 3-5 times a day.EFFECT: improved safety and effectiveness of polyps treatment in the sinuses, prevention of repeated growth, reduced duration and costs of treatment.3 ex
Composition for application in photodynamic therapy of cancer // 2626600
FIELD: pharmacology.SUBSTANCE: composition includes a mixture of perfluorodecalin (PFD) and perfluoro-N-(4-methylcyclohexyl)piperidine (PMCP) as a fluorocarbon phase at PFD and PMC weight ratio of 2:1, in an amount of 5-30 wt %, meso-tetrakis(2,3,5,6-tetrafluoro-4-(1,1-H, H-perfluoroheptyloxy)phenyl)porphyrin or meso-tetrakis(6-H-perfluorohexyl-1)porphyrin in an amount of 0.01-0.04 wt % as a photosensitizer, proxanol-268 in an amount of 2-8 wt % as a stabiliser, NaCl in an amount of 0.7-0.9 wt % and water in an amount of up to 100 wt %.EFFECT: increased phototoxicity of the photosensitizer with respect to the human colon adenocarcinoma cell line when administered as part of the claimed composition.2 cl, 2 tbl, 2 ex
Concentrated protein pharmaceutical compositions and their application // 2626512
FIELD: pharmacology.SUBSTANCE: group of inventions concerns low-viscosity hypotonic pharmaceutical compositions containing a concentrated PRO 140 monoclonal antibody in an amount of 100 to 200 mg/ml, a tonicity regulator in the form of a salt selected from sodium chloride, sodium gluconate or sodium lactate in an amount of 90 to 95 mM, and a buffer solution. They are used in pharmaceutical compositions and finished products.EFFECT: possibility of subcutaneous administration or delivery of a high concentration of a protein drug, such as PRO 140 monoclonal antibody, to a subject suffering from a disease or condition that can be cured with the said protein drug.81 cl, 7 ex, 1 tbl

Application of 3-(r)-[3-(2-methoxyphenylthio)-2-(s)-methylpropyl]amino-3,4-dihydro-2h-1,5-benzoxathiepin for treatment of cancer and, particularly, for prevention and/or treatment of cancer metastasis // 2626511
FIELD: pharmacology.SUBSTANCE: an application method of 3-(R)-[3-(2-methoxyphenylthio)-2-(S)-methylpropyl]amino-3,4-dihydro-2H-1,5-benzoxathiepin or its pharmaceutically acceptable salts for the prevention of cancer metastasis is proposed. Herewith the cancer cells express a voltage-sensitive sodium channel Nav1.5. Also, a pharmaceutical composition for the same purpose and application method of 3-(R)-[3-(2-methoxyphenylthio)-2-(S)-methylpropyl]amino-3,4-dihydro-2H-1,5-benzoxathiepin or its pharmaceutically acceptable salts for the prevention of cancer metastasis in patients having one or more cancer cells which express a voltage-sensitive sodium channel Nav1.5, are proposed.EFFECT: said compound reduces the metastatic current in mammary adenocarcinoma cells and does not interfere with the normal function of the heart even at high doses.11 cl, 1 dwg
ethod for treating proliferative disorders and other pathological conditions mediated by activity of kinase bcr-abl, c-kit, ddr1, ddr2 or pdgf-r // 2625835
FIELD: pharmacology.SUBSTANCE: invention relates to medicine and can be used for the application of the hydrochloride salt of 4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-N-[5-(4-methyl-1H-imidazole-1-yl)-3-(trifluoromethyl)phenyl]benzamide in the form of monohydrate (nilotinib) for the manufacture of a drug for the treatment of chronic myeloid leukemia. Thus, the hydrochloride salt of 4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-N-[5-(4-methyl-1H-imidazole-1-yl)-3-(trifluoromethyl)phenyl]benzamide in the form of monohydrate and pharmaceutically acceptable carriers are dispersed in apple sauce.EFFECT: flexibility of dosing, reduction of difficulty in swallowing, bioequivalence of therapeutic results in the treatment of patients with chronic myeloid leukemia.1 tbl, 2 ex
Tienopyrimydine [3,2-d] production, which has inhibitory activity against protein kinases // 2625799
FIELD: chemistry.SUBSTANCE: invention relates to thieno [3,2-d] pyrimidine of formula in which A represents C6-10aryl or 5-10 membered heteroaryl; W represents O, NH or -NHNH-; X and Y are each independently CH or N; Z is hydrogen or NR3R4, wherein said R3 and R4 are each independently hydrogen, C1-6alkyl or - (CH2)q-B, B represents NR5R6 or C3-6cycloalkyl; R1 It represents hydrogen or C1-3alkyl, wherein said alkyl is unsubstituted or substituted by one or more halogen atoms; each R2 independently represents hydrogen, halogen, -CF3-OH, -CN, C1-6alkoxy, C1-6alkyl, C2-4alkynyl, -NR7R8, -NHSO2R9, -SO2R10, -C(O)R11, -NHC(O)R12, -S(O)R14, 5-10 membered heterocycloalkyl, C6-10aryloxy or 5-10 membered heteroaryl, wherein said R2 is attached to A with Using - (CH2)p- or substituted by C1-4alkyl, C2-4alkynyl or one or more halogen atoms; R5, R6, R7, R8, R9, R10, R11, R12 and R14 are each independently hydrogen, -NH2, C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl, mentioned alkyl, alkoxy or cycloalkyl being unsubstituted or substituted by one or more halogen atoms; or a pharmaceutically acceptable salt thereof.EFFECT: compounds have inhibitory activity against protein kinases.57 cl, 5 tbl, 128 ex

ethods for inhibiting fucosylation of proteins in vivo using fucose analogues // 2625768
FIELD: pharmacology.SUBSTANCE: inhibiting protein fucosylation a mammal is administered an effective amount of a fucose analogue selected from the group consisting of one of the following scab formulas (V) or (VI). Also, a pharmaceutical composition for inhibiting protein fucosylation in mammals is proposed.EFFECT: inhibition of protein fucosylation, particularly, E-selectin fucosylation, which facilitates the suppression of autoimmunity.11 cl, 9 dwg, 5 tbl, 8 ex

Pharmaceutical composition for histone deacetylase inhibitors // 2625758
FIELD: pharmacology.SUBSTANCE: pharmaceutical composition for topical application is shown. It comprises of a therapeutically effective amount of active pharmaceutical ingredient (API) - a compound of the structural formula of at least one acidifying agent and a base carrier comprising of at least one pharmaceutically acceptable nonaqueous solvent. The acidifying agent is separated from citric acid, acetic acid and phosphoric acid. The measured pH value of the pharmaceutical composition is from 3 to 5. Preferably, the pharmaceutically acceptable nonaqueous solvent is a mixture of ethanol and propylene glycol. Also, a kit for preparing a pharmaceutical composition and a method for treating a proliferative, immune and skin diseases in a subject are desribed. The values of n, R1 and R2 in the structural formula (I) are defined in the claims.EFFECT: stabilized pharmaceutical composition is obtained.26 cl, 1 dwg, 18 tbl, 3 ex
Substance with anti-angiogenic activity // 2625752
FIELD: pharmacology.SUBSTANCE: invention can be used for application of N-succinyl-L-glutamyl-L-lysine amide as an agent having anti-angiogenic activity.EFFECT: invention suppresses pathological neoangiogenesis.2 tbl, 2 ex
2-amino-substituted 6-methoxy-4-trifluoromethyl-9h-pyrimido[4,5b]indoles, method for their production, application and prediminaries // 2625316
FIELD: pharmacology.SUBSTANCE: invention relates to new 2-amino-substituted 6-methoxy-4-trifluoromethyl-9H-pyrimido[4,5-b]indoles of general formula I and their pharmaceutically acceptable salts, as well as to the new compounds of formula (II), preceding the compounds of formula (I). The compounds of formula I possess anti-tumor activity and are useful in the therapy of myelogenous leukemia and colon cancer. In the formula (I), R=C1-C6-alkyl; C1-C3-alkyl-O-CH2CH2-; R1C6H4CH2-, where R1=H, Me, MeO; , where R2=H or Me. In the formula (II), X means S (IIa), SO2 (IIb). The method for preparation of formula (I) compounds comprises intramolecular cyclization of N-(5-iodo-2-methylthio-6-trifluoromethylpyrimidin-4-yl)-N-methyl-N-(4-methoxyphenyl) amine to form 9-methyl-2-methylthio-6-methoxy-4-trifluoromethyl-9H-pyrimido[4,5-b]indole, at heating in the presence of a base and a catalyst, subsequent oxidation and nucleophilic substitution of the 2-methylsulfonyl group in the resulting product with the corresponding primary amine.EFFECT: increased activity of the composition.11 cl, 1 tbl, 8 ex
8-carbamoyl-2-(2,3-di-substituted pyrid-6-yl)-1,2,3,4-tetrahydroisoquinoline derivatives as apoptosis-inducing agents for cancer treatment // 2625315
FIELD: pharmacology.SUBSTANCE: invention relates to organic chemistry, namely a heterocyclic compound of formula (I) or to a therapeutically acceptable salt thereof, where X is benzo[d]thiazolyl, thiazolo[5,4-b]pyridinyl, thiazolo[4,5-c]pyridinyl, imidazo[1,2-a]pyridinyl, thiazolo[5,4-c]pyridinyl, thiazolo[4,5-b]pyridinyl, imidazo[1,2-a]pyrazinyl or imidazo[ 1,2-b]pyridazinyl; Y1 means pyrrolyl, pyrazolyl, triazolyl or pyridinyl; where Y1 is optionally substituted with 1 or 2 substituents independently selected from R5, CN and Cl; L1 is selected from (CR6R7)q, (CR6R7)s-O-(CR6R7)r, (CR6R7)s-S-(CR6R7)r, (CR6R7)s-S(O)2-(CR6R7)r and (CR6R7)s-NR6A-(CR6R7)r; Y2 means mono- or tricyclic C8-C10-cycloalkyl, spiro[2.5]octyl, spiro[3.5]nonyl, oxatricyclo[3.3.1.13,7]decyl or azabicyclo[3.2.1]octyl; where Y2 is optionally substituted with 1, 2 or 3 substituents independently selected from R8, OR8, SO2R8, CO(O)R8, OH and Br; Z1 is selected from , R1 and R3 are absent; R2 is deuterium or C1-C6-alkyl; R5 is C1-C6-alkyl; R6A is selected from hydrogen and C1-C6-alkyl; each R6 and R7 are hydrogen; R8 is selected from the group consisting of C1-C3-alkyl, morpholinyl and dioxydothiomorpholinyl; where R8, meaning C1-C6-alkyl, is optionally substituted with a substituent selected from R16, OR16, SO2R16 and NHR16; Rk is selected from C1-C6-alkyl, morpholinyl, cyclopropyl and C1-haloalkyl; R16 Is selected from C1-C4-alkyl, phenyl, morpholinyl and tetrahydropyranyl; where R16, meaning C1-C4-alkyl, is optionally substituted with 1 substituent selected from OCH3, OCH2CH2OCH3 and OCH2CH2NHCH3; q is 1 or 2; s, m and p is 0; r is 0 or 1; N is 0, 1, or 2. The invention also relates to specific compounds, pharmaceutical compositions based on these compounds and a method for treatment of these diseases.EFFECT: new heterocyclic compounds are obtained, that are useful for treatment of some cancers.16 cl, 3 tbl, 86 ex

Substituted diamino-carboxamide and diamino-carbonitrile pyrimidine derivatives, their compositions and methods of treatment using them // 2625309
FIELD: pharmacology.SUBSTANCE: in formula (I) , R1 and R2 independently represent unsubstituted C1-8alkyl; C1-8alkyl substituted with one or more halogen atoms, hydroxy, C1-3alkoxy, C1-3alkoxy, C1-3alkyl, halogenC1-3alkoxy or hydroxyC1-3alkyl; unsubstituted saturated 3-7-membered monocycloalkyl or 5-8-membered bicycloalkyl; substituted saturated 3-7-membered monocycloalkyl or 5-8-membered bicycloalkyl, wherein the substituents are selected from halogen, C1-6alkyl, hydroxy, oxo, C1-3alkoxy, C1-3alkoxyC1-3alkyl, halogenC1-3alkyl, halogenC1-3alkoxy, hydroxyC1-3alkyl, aminoC1-3alkyl, O-cyclopropyl, NH2, NH(C1-3)alkyl, N(C1-3alkyl)2, C(O)-C1-3alkyl, NHC(O)-C1-3alkyl, C(O) NH2, C(O) NHC1-3alkyl, C(O)N(C1-3alkyl)2 and NHSO2(C1-3alkyl) and pyrrolidine; unsubstituted C1-3alkyl-C3-6cycloalkyl; 4-6-membered nonaromatic monocyclic heterocyclyl, optionally N-substituted with group of C1-3alkyl-C(O) or optionally substituted with C1-3alkyl, oxo or hydroxy, wherein heteroatoms are selected from 1-2 oxygen atoms or 1 nitrogen atom, or dioxaspirodecanyl.EFFECT: compounds can be used for the treatment or prevention of fibrotic liver diseases or metabolic syndrome, which lead to the development of fibrotic liver diseases such as: nonalcoholic steatohepatitis, steatosis, cirrhosis, primary sclerosing cholangitis, primary biliary cirrhosis, hepatitis, hepatocellular carcinoma or liver fibrosis, connected with chronic or recurrent alcohol consumption, infection, liver transplantation or liver injury caused by taking drugs, and as well as for treatment or prevention of interstitial pulmonary fibrosis.67 cl, 3 tbl, 62 ex
Quinolines as fgfr kinase modulators // 2625303
FIELD: pharmacology.SUBSTANCE: invention related to a new quinoline derivative of formula (I), where W us -N(R3)- or -C(R3aR3b)-; each R2 is independently selected from halogen, C1-4alkoxy, Y is -E-D; D is phenyl or 5-6-membered monocyclic heterocyclyl, containing one or two heteroatoms selected from N or O, wherein the mentioned heterocyclyl can be optionally substituted with one group of R1; E is a link; R1 is hydrogen, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkyl which is substituted with -S(=O)2-C1-6alkyl, R6; R3a is hydroxyl, hydroxyC1-6alkyl, cyanoC1-6alkyl, C1-6alkyl which is substituted with -NR10R11, C1-6alkyl which is substituted with -C(=O)-NR10R11; R3b is hydrogen; or R3a and R3b are combined to obtain =O or to obtain =CH-C0-4alkyl which is substituted with R3c; R3c is cyano; R3 is C2-6alkynyl, hydroxyC1-6alkyl, hydroxyhaloC1-6alkyl, C1-6alkyl which is substituted with R9, C2-6alkynyl which is substituted with R9, C1-6alkyl which is substituted with -NR10R11; R6 is 6-membered monocyclic heterocyclyl, containing one O atom; R9 is 5- or 6-membered monocyclic heterocyclyl, containing one or two heteroatoms, seleceted from N or O, each is optionally and each is independently substituted with substitute selected from =O, C1-4alkyl, C1-4alkoxy, S(=O)2-NR14R15, C1-4alkyl which is substituted with -NH-S(=O)2-haloC1-4alkyl, 6-membered aromatic monocyclic heterocyclyl, containing two N atoms, wherein the mentioned heterocyclyl is optionally substituted with R16; each R10 and R11 independently represent hydrogen, C1-6alkyl, haloC1-6alkyl; each R14 and R15 independently represent C1-4alkyl; R16 is C1-4alkoxy; n independently represent a whole number equal to 2, 3 or 4; as well as to its pharmaceutically acceptable salt and to any tautomeric or stereochemically isomeric form thereof. The invention also relates to pharmaceutical compositions based on compound of formula (I), application of the compound of formula (I), method for the prevention or treatment of a disease and product based on the compound of formula (I).EFFECT: new quinoline derivatives are obtained, useful in the treatment of diseases mediated by FGFR kinase.30 cl, 2 tbl, 35 ex
ethod for treatment of primary localized malignant neuroendocrinal tumours of pancreas head // 2625276
FIELD: medicine.SUBSTANCE: invention can find application in treatment of resectable malignant neuroendocrine tumours (NET) of the pancreas head (PH). 5-6 days before radical removal of the tumour, intraarterial oily chemoembolization of the pancreas head vessels is performed using 0.3 mg/kg of doxorubicin in 5-6 ml of lipidol. After surgical removal of the tumour, a dynamic observation of the patient by positron emission tomography (PET) of the whole body with radiopharmaceutical (RP) Ga-68 DOTATATE is performed. When its pathological accumulation in the form of a local recurrent tumour is revealed, it is removed. When NET metastasis is detected, it is either removed or intraarterial oily chemoembolization with doxorubicin in a dose of 0.5-0.7 mg/kg in 5-6 ml of lipidol is carried out, followed by dynamic observation of the patient by means of whole-body PET with Ga-68 DOTATATE. At that, Ga-68 DOTATATE is used at a dose of 1.5 MBq, but not less than 100 MBq per administration.EFFECT: method provides timely antitumor treatment and reduces the possibility of local recurrence.2 cl, 2 ex
ethod for treatment of malignant neuroendocrinal tumours of pancreas head with metastases in liver // 2625275
FIELD: medicine.SUBSTANCE: invention can find application in treatment of malignant neuroendocrine tumours (NET) of the pancreas head (PH). Prior to surgery to remove the primary tumour, selective intraarterial oily chemoembolization of the pancreas head vessels is performed using 0.3 mg/kg of doxorubicin in 6-7 ml of lipidol, of which 1/3 of doxorubicin and 3 ml of lipidol are administered super-selectively into the tumour vessels. Simultaneously, intraarterial oily chemoembolization of blood vessels feeding the liver and NET metastases is performed using 0.4 mg/kg of doxorubicin in 6-7 ml of lipidol. Then, during surgery to remove the primary tumour, radiofrequency ablation (RFA) is also performed in the presence of a single large metastatic lesion or multiple metastases in the liver. After surgery, intraarterial oily chemoembolization of liver metastases is performed, using doxorubicin at a dose of 0.5-0.7 mg/kg in 5-10 ml of lipidol until remission is achieved, under the control of PET with radiopharmaceutical (RP) Ga-68 DOTATATE. If pathological accumulation of RP is detected in the tumour bed at a local relapse or when distant NET metastases are detected, antitumor treatment is conducted. The primary tumour of the pancreas head is removed as a standard pancreatoduodenal resection in isolated neoplasms or in the form of an extended operation with resection of surrounding organs and main vessels, or in the form of extended lymphadenectomy with minimization or absence of surgical influence on intrahepatic metastases. Ga-68 DOTATATE is used at a dose of 1.5 MBq/kg, but not less than 100 MBq per administration.EFFECT: method provides minimization of surgical treatment traumatism at high treatment efficiency.3 cl, 2 ex
ethod for treatment of resectable primary locally advanced malignant neuroendocrinal tumours of pancreas head // 2625271
FIELD: medicine.SUBSTANCE: invention can find application in treatment of resectable primary locally advanced malignant neuroendocrine tumours (NET) of the pancreas head (PH). 5-6 days before radical removal of the tumour, intraarterial oily chemoembolization of the pancreas head vessels is performed using 0.3 mg/kg of doxorubicin in 6-7 ml of lipidol, of which 0.1 mg/kg of doxorubicin and 3 ml of lipidol are administered super-selectively into the tumour vessels. After surgical removal of the tumour, for at least 3 years, a dynamic observation of the patient under the control of positron emission tomography (PET) of the whole body with radiopharmaceutical (RP) Ga-68 DOTATATE is performed. When its pathological accumulation in the form of a local recurrent tumour is revealed, it is removed. When NET metastasis is detected, it is either removed or intraarterial oily chemoembolization with doxorubicin in a dose of 0.5-0.7 mg/kg in 5-6 ml of lipidol is carried out, followed by dynamic observation of the patient for at least 3 years by means of whole-body PET with Ga-68 DOTATATE. At that, Ga-68 DOTATATE is used at a dose of 1.5 MBq/kg, but not less than 100 MBq per administration.EFFECT: method ensures optimized treatment of this pathology, significantly reduces the possibility of local recurrence.2 cl, 2 ex
Vanilin derivatives with antitumour activity // 2624903
FIELD: pharmacology.SUBSTANCE: invention relates to the new antitumour agents based on vanillin derivatives of the general formula I I, where R=H, CH3 with high antitumour activity against breast cancer cells (MCF-7) and low toxicity.EFFECT: increased activity of agents.1 tbl, 3 ex

Peptide-immunogen used in therapeutic vaccine for metastatic breast cancer treatment // 2624862
FIELD: medicine.SUBSTANCE: peptide immunogen is characterized by the amino acid sequence CKGPIVLDGVIKTQPHAAEK (SEQ ID NO: 1), identical to the amino acid sequences of the active site of the EGFR receptor, and contains a covalently bound carrier protein. It contains bovine serum albumin (BSA), or cationized bovine serum albumin, or ovalbumin or hemocyanin as the carrier protein.EFFECT: application of this invention allows preparation of an immunogen peptide used in a therapeutic vaccine for metastatic breast cancer treatment due to the high immunogenicity of the peptide, and for assurance of an immune response only to the protective epitopes of the target tumour markers that block the main pathways of tumour growth and metastasis.2 cl, 1 dwg, 1 tbl

Nuflein bisanhydrochloride, with cytotoxic activity related to human tumour cells // 2624861
FIELD: pharmacology.SUBSTANCE: invention is application of a Nuflein bisanhydrohydrodehyde chloride compound of formula I , which has selective cytotoxic activity on human cervical cancer cells. The invention allows application of a Nuflein bisanhydrohydrodehyde chloride compound preparation based on plant material for a new purpose.EFFECT: preparation has the lowest cytotoxic effect with respect to healthy cells.3 dwg, 2 tbl, 2 ex

Conjugates for integrin antagonist targeted delivery to cells, expressing lfa-1 // 2624732
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula wherein R1 is selected from compounds (1) (2) (3), which are used for the manufacture and delivery of conjugated groups, such as small molecules, peptides, nucleic acids, fluorescent groups and polymers crosslinked with antagonists of integrin LFA-1 for targeted delivery to cells expressing LFA-1.EFFECT: improved properties.21 cl, 6 dwg, 1 tbl, 10 ex

Conjugates for integrin antagonist targeted delivery to cells, expressing lfa-1 // 2624731
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula I wherein R1 is selected from the group consisting of formula (1), formula (2), formula (3), for the manufacture and delivery of conjugated molecules, such as small molecules, peptides, nucleic acids, fluorescent molecules and polymers that are associated with the integrin antagonists of VLA-4, target cells expressing VLA-4.EFFECT: improved properties of compounds.16 cl, 6 dwg, 5 tbl, 14 ex
ethod for treatment of inoperable asctic forms of ovarian cancer // 2624509
FIELD: medicine.SUBSTANCE: for treatment of inoperable ascitic forms of ovarian cancer, the patients with inoperable stage III-IV of ovarian cancer, receive an abdominal cavity drainage after ascitic fluid removal, then recombinant interferon gamma is injected intraperitoneally, 500 thous. IU on day 1, 1 million IU on days 2, 3, 5, previously dissolved in 20 ml of 0.9% saline, on day 4, a course of polychemotherapy is carried out according to the scheme: paclitaxel 175 mg/m2 IVFD, carboplatin (AUC 4-6) IVFD. 3 courses of immunochemotherapy are conducted with an interval of 21 days.EFFECT: method allows to neutralise the toxic reactions of chemotherapy with a significant decrease in the tumor size with appearance of its mobility, which allows to perform treatment as the full scope of surgical intervention.1 ex

2-carboxamide cycloamino urea derivatives in combination with hsp90 inhibitors for treating proliferative diseases // 2624493
FIELD: pharmacology.SUBSTANCE: proposed: a pharmaceutical combination for treating melanoma comprising: (a) 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl) pyridin-4-yl] thiazol-2-yl}amide) (S)-pyrrolidine-1,2-dicarboxylic acid (compound A) or its pharmaceutically acceptable salt; and (b), at least, one Hsp90 inhibitor, representing ethylamide 5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethyl-phenyl) isoxazole-3-carboxylic acid (AUY922) or its pharmaceutically acceptable salt; the use of the said combination for manufacturing drugs to treat melanoma and corresponding method for treating melanoma.EFFECT: synergistic effect of the compound combinations in reducing the tumour volume.4 cl, 9 dwg, 2 tbl, 6 ex
ethod of treatment of luminal subtype of breast cancer n1 in postmenopausal period // 2624370
FIELD: medicine.SUBSTANCE: for the treatment of the luminal subtype of breast cancer N1 in the postmenopausal period, estrogen receptors are determined, the total diameter of metastases D in axillary lymph nodes and the average number of metastatic cells K whose nuclei express estrogen receptors in them. If identifying 2≤D<10 mm and the value of K exceeding 1%, radiotherapy is carried out according to the chosen treatment regimen, and after its completion, combined administration of tamoxifen and a nonselective beta-blocker is carried out daily in therapeutic doses for 1-5 years. If D≥10 mm is detected and at a value of K≥33% consistently perform adjuvant chemotherapy with simultaneous subcutaneous administration of fragin at a daily dose of 2500 ME daily, then radiotherapy is performed according to the chosen treatment regimen, and then hormone therapy with aromatase inhibitor is carried out for 5-7 years. If D≥10 mm is detected and with a value of K<33%, concurrent chemoradiotherapy and hormone therapy are performed, concomitantly with chemotherapy subcutaneous injection of fragmine at a dose of 5000 ME daily, and as an hormone inhibitor, an aromatase inhibitor is used for 7-10 years.EFFECT: method provides an opportunity to undergo a shorter period of treatment, in some cases to preserve the ability to work during it, to save the patient from possible complications while ensuring high effectiveness of therapy.3 ex
ethod for selective chemoembolization of pancreatic malignant tumors // 2624323
FIELD: medicine.SUBSTANCE: for selective chemoembolization of pancreatic tumours, a diagnostic catheter is placed in the proximal part of the gastroduodenal artery by a pre-inserted conductor. A conductor with a diameter of 0.014-0.018 inches is directed into the right gastro-omental artery for redistributory embolization, along which distally relative to the place of arteries divergence, providing blood supply to the tumour, a balloon catheter, with diameter corresponding to the right gastro-omental artery diameter in this segment, is introduced. The balloon is inflated until the blood flow on the right gastro-omental artery ceases completely. Further, diagnostic angiography of the gastroduodenal artery is performed through the diagnostic catheter. When blood flow is stopped on the right gastro-omental artery, chemoembolizate is injected through the diagnostic catheter.EFFECT: reduced procedure duration, reduced radiation load on the patient and intervention cost.2 cl, 1 ex

"antibody-drug" conjugates // 2624141
FIELD: biotechnology.SUBSTANCE: conjugate for the 5T4 antibody or its antigen-binding fragment with monomethylauristatin F (MMAF), coupled through maleimidocaproyl; and a pharmaceutically acceptable salt thereof. Furthermore, a pharmaceutical composition is considered, a method of 5T4-positive cancer treatment and invention-based conjugate application for the drug manufacture. The method for conjugate production is described. According to this invention, the conjugate is at least 100 times less toxic than the 5T4 antibody conjugate with calicheamicin.EFFECT: possibility of conjugate application for therapy.17 cl, 17 tbl, 9 ex

Pharmaceutical composition for cancer treatment and prevention // 2624049
FIELD: pharmacology.SUBSTANCE: invention relates to an antibody or a binding fragment thereof, wherein the antibody or a binding fragment thereof specifically binds CAPRIN-1 protein and has immunological reactivity to CAPRIN-1 protein, its encoding DNA, and also to a pharmaceutical composition for treatment or prevention of cancer, expressing CAPRIN-1, and to a conjugate capable of specifically binding CAPRIN-1 protein. A method of treatment or prevention of cancer expressing CAPRIN-1 using the aforementioned antibody or fragment thereof and to a pharmaceutical combination for treatment or prevention of cancer expressing CAPRIN-1, comprising the aforementioned pharmaceutical composition and a pharmaceutical composition comprising an antitumor agent, are described as well.EFFECT: invention enables efficient treatment or prevention of cancer expressing CAPRIN-1.8 cl, 7 ex

Homodimer protein construction // 2624041
FIELD: biotechnology.SUBSTANCE: invention relates to a nucleic acid molecule which encodes an amino acid chain capable of forming a dimeric protein and to the said dimeric protein. The said dimeric protein is used as a vaccine. It contains two identical amino acid chains, each containing a targeting group - humanα MIP1 - and an antigenic group connected by the motif for dimerization. This invention also discloses a pharmaceutical composition and a vaccine against the malignancy, comprising the said dimeric protein or nucleic acid molecule and a host cell and a method for production of the said dimeric protein. Due to human MIP1 application as the targeting group toα deliver the antigen to antigen presenting cells, this invention allows to produce a vaccines inducing the antigen-specific CD8+T-cell response.EFFECT: possibility of obtaining a vaccine.92 cl, 9 dwg, 1 ex

Drugs for cancer treatment and/or prevention // 2624029
FIELD: pharmacology.SUBSTANCE: invention relates to a medicament for treatment or prevention of cancer expressing the CAPRIN-1 protein. A method for treatment or prevention of cancer expressing the CAPRIN-1 protein is also disclosed.EFFECT: invention effectively treats CAPRIN-1 mediated cancer.10 cl, 10 dwg, 1 tbl, 7 ex

Integrin antagonist conjugates for targeted delivery to cells expressing alpha-v-beta-3 // 2623441
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula for application in the manufacture and delivery of conjugated molecules, such as low molecular compounds, peptides, nucleic acids, fluorescent molecules and polymers, which are connected with the integrin antagonists of alpha-V-beta-3, to target the cells expressing alpha-V-beta-3.EFFECT: improved properties.17 cl, 10 dwg, 1 tbl, 14 ex
ethod of obtaining a block copolymer // 2623426
FIELD: chemistry.SUBSTANCE: block copolymer has the following formula (1): ,where R1 is a hydrogen atom or a (C1-C5) alkyl group; R2 is a (C1-C5) alkylene group; R3 is a methylene or ethylene group; R4 represents a hydrogen atom or a (C1-C4) acyl group; R5 is a hydroxyl group, an aryl (C1-C8) alkoxy group which may have a substituent, or -N (R6) -CO-NHR7, where R6 and R7 may be the same or different and each represents a cyclic (C3-C6) An alkyl group or a (C1-C5) alkyl group which may be substituted with a tertiary amino group; N is 20-500; M is 2-200; But is 0-100; B is 0-100, provided that the sum of a and b is greater than or equal to 1 and not more than m; The fraction of the R5 group representing the hydroxyl group is 0-5% of m; proportion of the R5 group representing an aryl (C1-C8) alkoxy group which may have a substituent is 10-80% of m; The fraction of the R5 group representing -N (R6) -CO-NHR7 is 11-30% of m. The process for preparing the block copolymer is that the compound of the formula (2) is reacted, wherein R1, R2, R3, R4, n are as defined above; x is 0-100, y is 0-100, the sum of x and y is 2-200, with aryl (C1-C8) alkyl alcohol, and a carbodiimide-based compound in an amount of 2(x+y) equivalents or more relative to the amount of carboxyl Groups in the compound of formula (2). The reaction is carried out in a solvent at a temperature of 15-30°C for 2-48 hours.EFFECT: invention allows to maintain the process in a single reactor, reduce manufacturing period and reduce the quantity of solvent.4 cl, 1 tbl, 6 ex
 
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