Preparations for medical, dental, or toilet purposes (A61K)

A   Human necessities(308424)
A61K              Preparations for medical, dental, or toilet purposes (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms a61j0003000000; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles a61l)(51170)
A61K7 - (2074)
A61K37 - (206)
A61K43 - (6)

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
Oral care products, including zinc oxide and trimethylglycine // 2628540
FIELD: pharmacology.SUBSTANCE: group of inventions refers to oral care compositions, consisting of a mixture of zinc oxide and trimethylglycine (TMG), where the TMG is included into the composition in the form of hydrohalogenide, and zinc oxide and TMG form soluble complexes, selected from zinc-TMG-hydrohalogenide complexes, zinc-hydrohalogenide complexes and mixtures, where the hydrohalogenide is selected from hydrofluoride, hydrochloride and hydrobromide, as well as to a method for tooth enamel erosion treatment or mitigation, biofilm and bacterial plaque reduction, gingivitis reduction, tooth decay and cavities formation reduction, dentin hypersensitivity reduction, including application of such composition to the teeth, zinc oxide application together with the TMG in the form of hydrohalogenide during oral care composition production.EFFECT: creation of a complex, capable of yielding a solution which precipitates when diluted.15 cl, 4 ex, 6 tbl

Antimicrobial compositions of wide spectrum of action based on taurolidine and protamine combininations and medical devices containing such compositions // 2628539
FIELD: pharmacology.SUBSTANCE: group of inventions designed for antimicrobial treatment of implantable medical devices. The antimicrobial composition for antimicrobial coating application to medical devices contains about 50 to 99 wt % of taurolidine and about 1 to 50 wt % of protamine. For medical device coating, a medical device with at least one surface is provided and at least a portion of the said antimicrobial coating is applied to the surface. Polymeric resin which comprises the said composition is also provided for the manufacture of medical devices.EFFECT: antimicrobial composition effective against a wide range of microbes.80 cl, 2 dwg, 3 tbl, 4 ex

Composition including amlodipine and losartan having improved stability // 2628538
FIELD: pharmacology.SUBSTANCE: pharmaceutical composition for cardiovascular disorders prevention and treatment is described. The said composition comprises amlodipine besylate in an amount of 1.7 to 1.72 wt %, potassium losartan in an amount of 12.22 to 12.37 wt %, and propyl gallate in an amount of 0.01 wt %, based on the total weight of the composition. The said composition has the form of a two-layer pill having two separate layers consisting of an amlodipine layer containing amlodipine besylate and propyl gallate and a layer of losartan containing potassium losartan.EFFECT: improved composition stability in combination with simplicity of preparation.6 cl, 21 tbl, 2 dwg, 5 ex
Treatment of coagulation disease by administration of recombinant vwf // 2628537
FIELD: medicine.SUBSTANCE: group of inventions relates to a method of treating von Willebrand's disease or hemophilia A in a patient in need of treatment comprising administering to the patient a recombinant vWF (vWF) factor so that the half-life of factor VIII is prolonged compared to a patient administered vWF derived from blood plasma, where pFB is not modified with an aqueous soluble polymer. In this case, the pFB is a composition of high molecular weight PV multimers containing at least 20% of the PV emperors or higher-order multimers, with the rVB having a higher specific activity than the vWF derived from the blood plasma. The group of inventions also relates to a method for treating hemophilia A or vWF in a patient in need of treatment that includes administering to the patient a recombinant vWF (vWF) factor, wherein the half-life of FVIII is at least 1.5 times higher than the half-life of FVIII in the patient being treated Von Willebrand factor derived from blood plasma.EFFECT: increase in the half-life of FVIII in the treatment of von Willebrand disease or haemophilia A in the subject.29 cl, 5 ex, 22 dwg, 34 tbl

Production and application of bacterial histamine // 2628536
FIELD: medicine.SUBSTANCE: method for selecting a probiotic lactic bacterial strain for use in the local production of histamine in a mammal is provided. A product and composition for the local production of histamine in a mammal containing a lactic acid bacterial strain having an active histidine operon and capable of producing histamine is proposed for use in the treatment and/or prevention of inflammatory conditions.EFFECT: local production of histamine in a mammal by selecting certain strains of lactic acid bacteria.13 cl, 9 dwg, 2 tbl, 5 ex
External application means for chronic dermatosis treatment, and method for its production // 2628535
FIELD: medicine.SUBSTANCE: invention can be used as a preventive and therapeutic agent with anti-inflammatory and antibacterial properties, intended for external use, for treatment of all kinds of chronic dermatoses: dermatitis, neurodermatitis, furunculosis, eczema, fungal diseases, parasitic skin diseases, acne, and method for its production. The external agent for treatment of chronic dermatitis in the form of an aqueous suspension of mercuric monochloride is prepared by a process comprising premixing of powdered mercury monochloride with nitric acid at the following ratio of components, wt %: mercury monochloride 0.3-0.6; nitric acid 0.6-1.0, at a temperature of 70-90°C, stirring for 1 hour. Then the obtained solution is mixed with water of high mineralization from the "Belaya Gorka" mineral source to 100 wt %. At that, the pH of the obtained suspension is adjusted to 1-2 with nitric acid.EFFECT: increased efficiency of treatment.2 cl, 7 ex

Composition containing buffered lactic acid // 2628534
FIELD: pharmacology.SUBSTANCE: group of inventions refers to medicine, specifically to lubricating compositions containing buffered lactic acid with pH in the range of 3.0 to 6.5. The composition has an aqueous activity of 0.10 to 0.50 and the predetermined aqueous activity is obtained by drying.EFFECT: when the absorbent article contacts the skin or mucous membrane of the user, the friction between the absorbent article and the skin or mucosa decreases, the composition has a pH value in the range corresponding to acids that is close to the pH of skin or mucous membrane.13 cl, 9 dwg, 3 tbl, 1 ex
Anti-cellulite gel // 2628533
FIELD: cosmetology.SUBSTANCE: gel further contains pectin, hydrogenated castor oil, wheat germ oil, ginger essential oil, chlorella, propylene glycol extract of juniper, propylene glycol extract of horsetail, propylene glycol extract of horse chestnut, glycerin, preservative and water, the agent components are in a certain ratio, in wt %.EFFECT: increased tone and strengthening of blood vessel walls, lipid metabolism stimulation, surface smoothing, increased skin resilience and elasticity, cellulite elimination.1 tbl

New pyrimidine inhibitors of human adenovirus replication // 2628456
FIELD: pharmacology.SUBSTANCE: invention relates to new 5-aminouracil derivatives containing 4-(phenoxy) benzyl or ω-(phenoxy)alkyl substituent in the N1 position, corresponding to the general structural formula (I). Compounds represent a new class of anti-adenoviral agents of a non-nucleoside nature. In the general formula (I), X = CH or N; Y=(CH2)2, (CH2)3, (CH2)4 or C6H4; R1= H, R2= C6H or 3,5-Cl2C6H3; R1+R2= morpholino; R3=H, F or Cl.EFFECT: compounds have a selective antiviral effect against human adenoviruses and can be used for treatment of adenoviral infections.1 dwg, 3 tbl, 11 ex
ethod for heterotopic ossification surgical treatment with local neural simulation of spastic syndrome // 2628370
FIELD: medicine.SUBSTANCE: for surgical treatment of heterotopic ossification with local neural simulation of the patient spastic syndrome, preliminary multilayer spiral computerized tomography (CT) is used to ptovide spatial imaging of bone structures and ossificates. The method of magnetic resonance imaging reveals the ossificate soft tissue component which is not visualized by MSCT. Then the heterotopic ossificate maturity stage is determine by calcium-phosphorus metabolism indices - alkaline phosphatase, osteocalcin, and bone matrix formation marker PINP - N-terminal pro-peptide of type 1 procollagen in patient's venous blood. If the measured parameters of N-terminal propeptide of type 1 procollagen - PINP are less than 76 ng/ml, even in case of an isolated lesion of one elbow or knee joint, alkaline phosphatase level is in the range 40-150 U/l and osteocalcin level is within 11-46 ng/mL, completion of osteoid formation and mineralization with formation and maturation of newly formed cancellous bone is concluded. In this case, surgical ossificates removal from the affected joint is prescribed. At that, local neural simulation of spastic syndrom is performed prior to surgical removal of ossificates, until it a stable decrease to the level of 0 to 1 on Ashworth scale is reached. Next, surgical treatment is performed involving ossificate resection or removal of an adequate volume of heterogeneous bone to restore the functionally adequate range of motion in the affected joint.EFFECT: possibility of surgical treatment of heterotopic ossification in patients with spastic syndrome, minimizing the risk of complications during surgical treatment, and pathological process recurrence.3 cl, 5 ex

Combined vaccines for prevention of pigs viral infections // 2628313
FIELD: biotechnology.SUBSTANCE: inventions relate to vaccine compositions containing a vaccine against PRRSV (pig reproductive and respiratory syndrome virus) and the second vaccine against the pig virus that do not substantially interfere immunologically with each other. The vaccine against the second swine virus can be a vaccine against CSFV (classical swine fever virus) and/or PRV (pseudorabies virus). Methods for preparation of vaccines and formulations are also provided.EFFECT: vaccine compositions described herein impart protective immunity to pigs against reproductive and respiratory syndrome, classical swine fever and/or pseudorabism.44 cl, 40 dwg, 13 tbl, 25 ex

Antibacterial composition for prevention or treatment of hospital infections (versions), bacteriophage stamps used to obtain such composition // 2628312
FIELD: biotechnology.SUBSTANCE: composition includes 7 strains of bacteriophage, each represented by a combination of bacterial phagolysates filtrates with lytic activity of at least 10-4 according to Appelman concerning test strains and isolated bacterial isolates, as well as target additives in an amount of 0.01±99.99 wt % of composition weight. At that, Staphylococcus aureus phagolysate filtrate obtained using the Staphylococcus aureus SCH1 bacteriophage strain, deposited in the collection of FBIS SSC PVB of Rospotrebnadzor under number Ph-105, Staphylococcus aureus phagolysate filtrate obtained using the Staphylococcus aureus SCH111 bacteriophage strain, deposited in the collection of FBIS SSC PVB of Rospotrebnadzor under number Ph-95, Klebsiella pneumoniae phagolysate filtrate, obtained using the Klebsiella pneumoniae KPV15 bacteriophage strain, deposited in the collection of FBIS SSC PVB of Rospotrebnadzor under number Ph-90, Klebsiella pneumoniae phagolysate filtrate, obtained using the Klebsiella pneumoniae KPV811 bacteriophage strain, deposited in the collection of FBIS SSC PVB of Rospotrebnadzor under number Ph-91, Pseudomonas aeruginosa phagolysate filtrate, obtained using the PA5 Pseudomonas aeruginosa bacteriophage strain, deposited in the collection of FBIS SSC PVB of Rospotrebnadzor under number Ph-88, Pseudomonas aeruginosa phagolysate filtrate, obtained using the Pseudomonas aeruginosa PA10 bacteriophage strain, deposited in the collection of FBIS SSC PVB of Rospotrebnadzor under number Ph-89, Acinetobacter baumannii, phagolysate filtrate, obtained using the Acinetobacter Baumannii AM24 bacteriophage strain, deposited in the collection of FBIS SSC PVB of Rospotrebnadzor under number Ph-106. The composition version also contains Acinetobacter baumannii phagolysate filtrate, obtained using the Acinetobacter baumannii AP22 bacteriophage strain, deposited in the collection of FBIS SSC PVB of Rospotrebnadzor under number Ph-42. The appropriate bacteriophage strains are also proposed. Nucleic acid molecules corresponding to the genome of the said bacteriophages are also proposed.EFFECT: expanded range of products containing highly selective natural antibacterial components as the main active ingredient, ensured biological stability and activity of bacteriophages in the agent composition, the composition has a low risk of toxic and side effects, allows to expand versions and methods of practical application of the agent containing bacteriophages, provides storage stability and application efficiency over a wide temperature range.28 cl, 1 dwg, 4 tbl, 24 ex

Single-chemical nucleic acid molecules for gene expression control // 2628311
FIELD: biotechnology.SUBSTANCE: invention relates to biochemistry, in particular to a single-stranded nucleic acid molecule that inhibits target gene expression. The said molecule in the order from the 5'-end to the 3'-end contains the 5'-end portion Xc, the linker portion Lx, the inner portion Z, the linker portion Ly and the 3'-end portion Yc. At that, the inner region Z consists of the inner 5'-end portion X that is complementary to the 5'-end portion Xc and the inner 3'-end portion Y that is complementary to the 3'-end portion Yc. At that, Z consists of 19-30 bases and contains a sequence that suppresses the target gene expression. Z-(Xc+Yc) from 0 to 4 bases, Xc from 1 to 11 bases and Yc from 1 to 11 bases. This invention also discloses a method, application and composition for target gene expression inhibition, method, use and pharmaceutical composition for treatment of a disease caused by an increase in target gene expression using the above-mentioned nucleic acid molecule and the use of such molecule to induce RNA interference.EFFECT: invention allows application of a single-stranded nucleic acid molecule for patients treatment, since it does not cause a side effect in the form of interferon induction.32 cl, 32 dwg, 7 tbl, 25 ex

ethod for recombinant polypeptide production // 2628310
FIELD: pharmacology.SUBSTANCE: method for antibody production, a method for production of a pharmaceutical preparation containing an antibody obtained by this method, a nucleic acid molecule, application of a vector containing such nucleic acid molecule, and application of a cell where the said nucleic acid molecule or vector is artificially introduced in the method for antibody production. This method for antibody production involves culturing a cell that expresses an antibody-enhancing sequence (APES) that has been artificially inserted into a cell and into which an exogenous DNA encoding the desired antibody was introduced to produce the desired antibody, and wherein APES is a nucleic acid molecule containing a nucleotide sequence that can bind to DNA or mRNA of NfkBia gene derived from a human, mouse, rat, or hamster by base pairing, and can suppress expression of the NfkBia gene.EFFECT: invention allows production of an antibody at a high level with suppression of NfkBia expression.16 cl, 29 dwg, 8 ex

Human antibodies to clostridium difficile toxins // 2628305
FIELD: biotechnology.SUBSTANCE: completely human antibodies that bind either to toxin A, or to toxin B Clostridium difficile, or both to toxin A and toxin B. Formulations containing these antibodies and methods for their application are also described. The antibodies of the present invention are useful for neutralisation of toxins from C. difficile, thus providing agents for treatment of disease and symptoms associated with C. difficile infection, including an agent for treatment of diarrhea or pseudomembranous colitis caused by C. difficile. Antibodies may also limit the severity and/or duration of the underlying disease or limit the amount, duration and/or severity of disease relapse or exacerbation due to the presence of C. difficile.EFFECT: antibodies of this invention may also be suitable for infection diagnosis.34 cl, 5 dwg, 10 tbl, 11 ex

ethod for mammoplasty // 2628238
FIELD: medicine.SUBSTANCE: mammary gland (MG) plasty with high ptosis or a stretched "dermal sheath" is performed. At that, Botox is injected into the large pectoral muscle 8-10 days before the operation and into the cavity in the large pectoral muscle base during the operation, prior to implant insertion. During the operation, the MG skin within the operating field is shrunk by exposure to laser radiation or ultrasound. Fibrin glue mixed with a solution of a nonpolarizing muscle relaxant is used, and the cavity is washed with an antibiotic solution before drying.EFFECT: method has a high aesthetic effect, ensures the stability of the mammary gland with the necessary shape, minimizes ptosis, excludes scars on the incision site.3 cl, 14 dwg, 3 tbl, 3 ex
Piperazino[1,2-a]indole-1-ones and [1,4] diazeptino[1,2-a]indole-1-one // 2628126
FIELD: medicine.SUBSTANCE: invention relates to application of compounds of general formula I .EFFECT: new compounds, as well as pharmaceutical compositions based thereon, are obtained, that can be used to treat schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorder, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction, Down's syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, and violations resulting from radiation therapy, chronic stress or abuse of neuroactive drugs, such as alcohol, opiates, methamphetamine, phencyclidine or cocaine.11 cl, 1 tbl, 46 ex

Cats calicivirus ashley virus strain for study of drug antiviral activity related to cats calicivirus // 2628096
FIELD: biotechnology.SUBSTANCE: ashley strain off cats calicivirus, deposited in FBIS SSC VB Vector under the number V-697 is obtain, having stable infectious activity, adapted to the transplanted cell cultures.EFFECT: strain can be used to study the antiviral activity of drugs against cats calicivirus.6 dwg, 4 ex

Rsv-specific binding molecules and means for their obtaining // 2628095
FIELD: biotechnology.SUBSTANCE: isolated antibody or a functional part thereof, capable of specifically binding the respiratory syncytial virus (RSV), is proposed. A nucleic acid molecule encoding the antibody is also provided. An expression vector and isolated cells comprising the said nucleic acid molecule for production of said antibody are described. In addition, the invention relates to a method for production of the said antibody, as well as to application of the said antibody in methods for RSV-related disorder treatment or prevention.EFFECT: invention allows to effectively bind RSV and can be used for RSV-related disorders therapy.27 cl, 16 dwg, 2 tbl, 5 ex

Antibodies, capable of specific connecting with her2 // 2628094
FIELD: biotechnology.SUBSTANCE: human epidermal growth factor 2 (HER2) receptor antibody is proposed, as well as pharmaceutical compositions comprising the said antibody for malignant tumour prevention and treatment and for apoptosis induction. In addition, a kit for malignant tumour diagnosing, comprising the said antibody, is provided.EFFECT: invention allows cancer cells destruction with significantly increased cytotoxicity when used in combination with trastuzumab and can be used for cancer therapy.11 cl, 27 dwg, 10 tbl, 15 ex
ethod for obtaining of msc-associated non-differentiated hemopoietic precursor cells with cd34+/cd133+ phenotype // 2628092
FIELD: biotechnology.SUBSTANCE: invention relates to production of cell cultures enriched with hematopoietic precursor cells with CD34+/CD133+ phenotype. The method includes preparation of a stromal sublayer, addition of an umbilical cord fraction, cultivation and selection. Multipotent stromal cells of adipose tissue (MSC) are obtained from the stromal-vascular fraction of adipose tissue, which are cultured at an O2 concentration of 5% in the environment. Mononuclear fraction of umbilical cord blood (MNF UB) is added to the MSC monolayer. After cocultivation, the undifferentiated hematopoietic precursors are selected from the mononuclear fraction of UB by adhesion to MSC at 20% O2, MSC is continued to be cultured with attached MNF UB for 96 hours at O2 concentration of 20% in the environment.EFFECT: invention allows to obtain a population enriched with undifferentiated hematopoietic umbilical cord blood precursors with this complex phenotype.9 dwg, 1 tbl, 1 ex

Immunocytocins combined therapy // 2628089
FIELD: pharmacology.SUBSTANCE: method for skin tumor treatment by TNF immunoconjugate single dose injectionα and IL-2 immunoconjugate single dose to tumor localization site, at that, injectable administration of TNF immunoconjugateα and IL-2 immunoconjugate is carried out simultaneously. TNF immunoconjugateα contains TNFα, bound to an antibody molecule that binds to the additional ED-B domain of the B-FN fibronectin splice isoform. The IL-2 immunoconjugate comprises IL-2, bound to an antibody molecule that binds to the additional ED-B domain of the B-FN fibronectin splice isoform. The invention also relates to compositions for skin tumor treatment comprising the said TNF immunoconjugateα and/or the said IL-2 immunoconjugate.EFFECT: invention provides for stimulation of complete destruction of large subcutaneous tumors with a single local administration of a combination of TNF immunoconjugateα and IL-2 immunoconjugate.42 cl, 4 dwg
Pyperidinyl naphthyluxic acids // 2628083
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula (I): , as well as to pharmaceutically acceptable salts, pharmaceutical compositions and application thereof.EFFECT: new compounds that are CRTH2 receptor antagonists have been obtained that can be useful for respiratory diseases treatment or prevention.20 cl, 2 tbl, 37 ex
Hinuclidine ethers of 1-azaheterocylic acetic acid as antimuscarine means, method for their production and their drug compositions // 2628082
FIELD: pharmacology.SUBSTANCE: invention relates to formula compounds, where A can be a single bond, a double bond, O, S, NR3, C(R3)R4, CO, C(O)N(R3), N(R3)C(O) and C(R3)-(CH2)-C(R4); m is an integer from 1 to 4; N is 0 or an integer from 1 to 4; R1 is selected from the group consisting of phenyl and 5-member heteroaryl containing one S heteroatom optionally substituted by one or more substituents selected from the group consisting of halogen atoms, (C1-C6)alkyl and (C1-C6)alkoxy; X is a physiologically acceptable anion; R2 is a group of the formula (Y), where p is 0 or an integer from 1 to 4; Q is 0 or an integer from 1 to 4; P is absent or selected from the group consisting of CO, N(R3)C(O) and C(O)N(R3); W is selected from the group consisting of H, (C1-C10)alkoxyl, phenyl, heteroaryl optionally substituted with one or more substituents selected from the group consisting of halogen atoms, OH, oxo (=O), CO2R3, (C1-C6)alkyl, (C1-C6)alkoxyl and phenyl; wherein heteroaryl is a mono- or bicyclic ring system having from 5 to 9 ring atoms and from 1 to 3 heteroatoms selected from N, O and S; R3 and R4 are independently selected from the group consisting of H, halogen atoms, CONH2, (C1-C6)alkyl, (C1-C6)alkanoyl and (C3-C8)cycloalkyl, as selective M3 receptor antagonists, to a method for their preparation, to compositions containing them, and to their therapeutic use for treatment of a respiratory disease such as asthma and chronic obstructive pulmonary disease (COPD).EFFECT: increased composition application efficiency.14 cl, 2 tbl, 34 ex

New derivative of 3-(4-(benzyloxy)phenyl)hex-4-ine acid, method for its production and pharmaceutical composition for metabolic disease prevention and treatment including it as effective ingredient // 2628077
FIELD: pharmacology.SUBSTANCE: invention relates to a compound represented by formula 1, its optical isomer or a pharmaceutically acceptable salt thereof: [Formula 1] , as well as to methods for its preparation and a pharmaceutical composition based on it.EFFECT: new connections are obtained, with the ability to activate the GPR40 enzyme, suitable for use for metabolic disease prevention or treatment.10 cl, 7 tbl, 77 ex, 2 dwg
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
ethod for obtaining of antigen for determination of antibrucellar immunity // 2627897
FIELD: medicine.SUBSTANCE: method comprises culturing a brucella culture in a liquid nutrient medium, followed by desired product isolation. Cultivation is carried out at a temperature of 39-40 for 18-24 hours, followed by an increase in temperature to 45-50 within 6-10 hours and an increase in temperature to 60 degrees for 1-2 hours, followed by separation of the bacmass and antigen isolation from the culture medium.EFFECT: use of this method allows to obtain the brucella antigen, by means of which it is possible to carry out objective monitoring of immunity level induced in animals in response to the introduction of antibrucellar vaccines.2 cl, 4 tbl, 36 ex

ethod of production of a combined antihelmint tablet with a symbiotic treatment for treatment of a small cattle // 2627893
FIELD: veterinary medicine.SUBSTANCE: invention is a method for producing a combined anthelmintic tablet with a symbiotic for treating small cattle containing a first and second layer comprising the steps of: adding a first powder mixture to a mould plate. Mentioned first powder mixture contains a pharmaceutically active substance and a binder, a second powder mixture is added to said mould plate. Mentioned second powder blend comprises a binder and the composition of mentioned second powder blend is different from the composition of mentioned first powder mixture, the first powder mixture and the second powder blend are pressed on said plate of the mould to form a tablet form and subjected to said tableted form with radio frequency emission for a period of Time sufficient to activate said binder within said tablet mould to fuse mentioned tableted Th form into said tablet, such that the density of mentioned tablet is less than about 0.8 g/cm3, characterized in that a bacterial concentrate is prepared for the preparation of the first powder mixture comprising a bifidobacterium adolescentis B-1 and Lactobacillus acidophilus LH-1 consortium with a titre of 108-1010 CFU/g sorbed on a carrier in a ratio of 1:1:12, which Is concentrated by filtration or centrifugation to a suspension containing 5 billion bacteria per ml, followed by mixing them in equal volumes. As the carrier, flour or bran is used at the rate of 12 parts of the support per part of a mixture of concentrated cultures, and then the obtained dry powder mass is mixed with lactulose, and to obtain the second powder mixture, ivermectin, praziquantel and at least one pharmaceutically acceptable excipient microcrystalline cellulose MCC is used, then the substances ivermectin, praziquantel and excipient are mixed in dry kind. The components in the tablet are in a certain ratio in wt %.EFFECT: invention provides high anthelmintic activity, intensification of treatment and prevention of a number of helminthic invasions, nonspecific correction of the immune response of the animal organism, normalization of hepatoprotective and reparative liver functions.6 ex, 1 tbl, 1 dwg
Transdermal device, including porous microparticles // 2627869
FIELD: medicine.SUBSTANCE: group of inventions refers to a transdermal device comprising porous microparticles that are capable of containing nicotine as an active ingredient. The device is used as a medicine, in particular, in case of smoking refusal. The invention also relates to a method for manufacture of a transdermal device comprising porous microparticles carrying the active ingredient.EFFECT: device exhibits improved cohesive properties, in particular reduces the risk of leakage, and reduces the amount of matrix remaining on the skin after patch removal.17 cl, 4 dwg, 7 tbl, 5 ex
Hemostatic sponge (versions) // 2627855
FIELD: medicine.SUBSTANCE: invention is a hemostatic sponge containing a base and iron salts as an active substance, characterized by the base and active substance being freeze-dried, while the sponge contains sodium alginate as the base, and iron sulfate as the active ingredient, the components in the sponge are in a certain ratio in the final aqueous solution, in the volume of 1 litre in %.EFFECT: expanded assortment of hemostatic sponges with pronounced hemostatic action and exclusion of direct adverse effect of the active substance on the wound surface and surrounding tissues due to the pharmacological form of the sponge.4 cl, 37 ex
ethod for active molecules extraction from natural resins and their application // 2627848
FIELD: biotechnology.SUBSTANCE: according to the invention, a method for active molecules extraction from a plant substrate comprises the step of the said substrate contacting with an extraction liquid. This extraction liquid contains: an extraction gas in the gaseous state at a temperature of 23°C and a pressure of 1 atm (101.325 kPa), and an extraction solvent in a liquid state comprising or consisting of acetic acid alone or mixed with at least one of water and primary aliphatic alcohol having the formula (V) R-OH, wherein R is a C1-C10 alkyl group, preferably C1-C5, wherein the said extraction gas is selected from the group consisting of helium, neon, argon, krypton, xenon, carbon dioxide and nitrogen, or mixtures thereof; wherein the said extraction gas is introduced into the said extraction solvent at a concentration of 0.1 to 10 vol % relative to 100 parts by weight of the extraction solvent. Active molecules extraction from plant substrate. Extract application for preparation of a food composition for internal use. Extract application for preparation of a food supplement for internal use. Extract application for preparation of a nutraceutical composition for internal use. Extract application for preparation of a pharmaceutical product for external or internal use.EFFECT: method allows to obtain an extract with a high yield of biologically active substances, to avoid chemical destruction of extracted molecules or modification of the original chemical structure.13 cl, 1 dwg, 10 tbl, 10 ex
Estrogen components for application in neurological disorders treatment // 2627846
FIELD: pharmacology.SUBSTANCE: use of estetrol for treatment of brain damage in the hippocampus is proposed.EFFECT: estetrol reduces the early loss of gray matter and stimulates neuro- and vasculogenesis after perinatal or neonatal asphyxia.5 cl, 16 dwg
ethod for obtaining suspensional form of a ruled decellularized extracellular matrix // 2627844
FIELD: pharmacology.SUBSTANCE: method includes separating the cleaned extracellular matrix layers from the cleaned, extruding the layers, fractionating the powder and suspending the selected fraction of the purified extracellular matrix particles in a liquid medium by alternating the mixing and dispersing cycles of the particles in a liquid medium with a predominant mixing time at a temperature that does not induce denaturation of the collagen, and degassing the resulting particle suspension.EFFECT: method of the invention provides for the preparation of a suspension form of a decellularized extracellular matrix with an adjustable size of its structural components, the use of which allows for the injection of injections into the desired region without incision and easily filling the open wound defect of various tissues.12 cl, 6 dwg, 1 tbl
Dental materials based on monomers, able to disconnect on request // 2627843
FIELD: pharmacology.SUBSTANCE: dental restorative material is proposed containing a thermolabile polymerizable compound of formula II: where Z1 and Z2 each independently represents a polymerizable group selected from vinyl groups, CH2=CR1-CO-O- and CH2=CR1-CO-NR2-, or a linking group selected from -Si(OR)3, -COOH, -O-PO (OH)2, -PO (OH)2, -SO2OH and -SH, wherein at least one Z1 or Z2 is a polymerizable group. Q1 in each case is independently absent or is A (m+1)-valent linear or branched aliphatic C1-C20-radical that can be interrupted by -O-, -S-, -CO-O-, -O-CO-, -CO-NR3-, -NR3-CO-, -O-CO-NR3-, -NR3-CO-O- or -NR3-CO-NR3-. Q2 in each case is independently absent or is a (n+1)-valent linear or branched aliphatic C1-C20-radical, which can be interrupted by -O-, -S-, -CO-O-, -O-CO-, -CO-NR3-, -NR3-CO-, -O-CO-NR3-, -NR3-CO-O- or -NR3-CO-NR3-. R, R1, R2 and R3 each independently is H or a C1-C7 alkyl radical; R4 - H or a C1-C10 alkyl radical; R5 - H, a C1-C5 alkyl radical, F or CN; R6 - H, a C1-C5 alkyl radical, F or CN. m and n are each independently 1, 2 or 3. It is also proposed to use the aforementioned compound of formula II for preparation of dental restorative material.EFFECT: using of the group of inventions provides adhesive dental restorative materials that are polymerized, show good adhesion to the substrate, in particular, to the structure of a tooth or dental ceramics, and capable of disconnection from the substrate when heated, and that, therefore, are particularly suitable for production of adhesives or composite cements that are capable of separation on requested.17 cl, 11 ex, 2 tbl

eans for left ventricle diastolic function improvement // 2627842
FIELD: pharmacology.SUBSTANCE: application of 4-[(2-{(2R)-2-((1E,3S)-4-(4-fluorophenyl)-3-hydroxy-1-buten-1-yl]-5-oxo-1-pyrrolidinyl}ethyl)thio]butanoic acid, or a salt thereof, of its clathrate complex with cyclodextrin for preparation of means 1) for treatment of diastolic heart failure and/or symptom alleviation; 2) for heart failure treatment, at which the diastolic function is weakened; 3) for left ventricle diastolic function improvement; 4) for left ventricle expansion improvement; 5) for left ventricle selective diastolic function improvement; 6) for diastolic functional insufficiency treatment or improvement; 7) for diastolic dysfunction treatment or improvement.EFFECT: agent improves diastolic function of the left ventricle itself, without dependence on diuretic influence or vasodilator effect, controls the pathological state of diastolic functional insufficiency and prevents relapse, can prevent dyspnea and death caused by a pathological condition, the agent can alleviate diastolic functional failure for which an effective therapeutic method has not been established.10 cl, 3 dwg, 5 tbl, 2 ex

Combination of chekpoint-kinase 1 inhibitors and wee 1 kinase inhibitors // 2627841
FIELD: biotechnology.SUBSTANCE: to inhibit cell proliferation and initiation of apoptosis in human a CHK1 inhibitor is used which is (R)-N-(4-(3-aminopiperidin-1-yl)-5-brom-1H-pyrrol[2,3-b]pyridin-3-yl)isobutyramide, in combination with WEE1 inhibitor, which is MK-1775.EFFECT: group of inventions provides a dosage regimen, which is the minimum amount to achieve a given biological effect without side effects.4 cl, 9 dwg, 6 ex
Antiperspirant products with protein content and antipresspirant salts // 2627840
FIELD: cosmetology.SUBSTANCE: antiperspirant composition contains a protein and antiperspirant salt in combination with a cosmetically acceptable carrier. The antiperspirant salt is a complex of X zinc chloride, where X is lysine or arginine. To reduce sweating, reduce body odor and kill bacteria, an effective amount of the noted antiperspirant composition is applied to the skin.EFFECT: increased antibacterial efficacy, excluding irritating effect on the skin, increased effectiveness of reducing sweating and body odor.23 cl, 4 tbl, 4 ex
ethod of producing nanocapules of l-arginine // 2627819
FIELD: nanotechnology.SUBSTANCE: method is characterized in that L-arginine is slowly added to a suspension of carrageenan in butyl alcohol in the presence of 0.01 E472c preparation as a surfactant with stirring at 1300 rpm. Then 5 ml of hexane are poured, the resulting suspension of the nanocapsules is filtered off and dried at room temperature. The mass ratio core: the shell is 1:3 or 1:1.EFFECT: simplification and acceleration of the process of obtaining nanocapsules.3 ex
ethod for tubular bone defects plastic in patients with chronic osteomyelitis // 2627815
FIELD: medicine.SUBSTANCE: sanation of the osteomyelitis focus, plastic of the bone cavity by platelet-enriched autoplasm and biomaterial are performed. At that, prior to plastic surgery, a thin needle is rotated in various directions to provide revascularizing osteoperforation of the bone cavity walls along the edge of which the bioplastic membrane "Collost" is fixed with transossal sutures, without tightening the threads. The intact autologous muscle tissue is taken, which is ground to the state of muscle mince. It is mixed with the platelet-enriched autoplasma and densely placed in the bone cavity, which is sealed with the bioplastic membrane "Collost", tightening the threads of the transossal sutures.EFFECT: method allows to ensure sealing of the plastic area of tubular bones defects in patients with chronic osteomyelitis, to create optimal conditions for reparative processes of bone tissue.1 ex
ethod for chronic wounds treatment // 2627814
FIELD: medicine.SUBSTANCE: pre-sanitized wound is covered with a bioplastic membrane "Collost", fixing it with separate nodal sutures at a distance of 0.3 mm from each other. Near the upper edge of the wound, a subclavian catheter is installed, the tube of which is up to 1 mm and length is up to 150 mm . This tube is pre-perforated and inserted under the membrane through the upper edge of the wound. The membrane is covered with an antiseptic dressing so that the head with the subclavian catheter plug remains above it for daily single administration of platelet-enriched plasma, which is obtained by taking 20 ml of blood from the peripheral vein, which is centrifuged for 15 minutes at 4000 revolutions. Then, the liquid part of plasma is placed in a sterile tube without a stabiliser and is centrifuged at 3500 rpm for 15 minutes to obtain platelet-enriched plasma with a volume of up to 2 ml, which is injected through the subclavian catheter no later than 10 minutes after its production. The antiseptic bandage on the wound is replaced once in 5-7 days.EFFECT: method allows to increase the effectiveness of chronic wounds local treatment, reduce trauma, simplify wound treatment and care.1 ex

9-benzyl-2-biphenylimidazo[1,2-a]benzimidazole and pharmaceutically acceptable salts thereof that express properties of destroyers of transversal cross-links of glycosylated proteins // 2627769
FIELD: pharmacology.SUBSTANCE: invention relates to new 9-benzyl-2-biphenylimidazo[1,2-a]benzimidazole (I) and pharmaceutically acceptable salts thereof.EFFECT: imidazobenzimidazole derivatives having the property of destroyers of transversal cross-links of glycosylated proteins.3 cl, 2 dwg, 1 tbl, 1 ex

2-acetyl-6-(2-(2-(4-brombenzylidene)hydrazinyl)thiazol-4-yl)-3,7,9-trihydroxy-8,9b-dimethyldiobenzo[b,d]furan-1(9bh)-oh, with inhibiting action on humen tyrosyl-dna-phosphodiesterase 1 // 2627764
FIELD: biotechnology.SUBSTANCE: compound is 2-acetyl-6-(2-(2-(4-bromobenzylidene)hydrazinyl)thiazol-4-yl)-3,7,9-trihydroxy-8,9b-dimethyldibenzo[b,d]furan-1(9bH)-one of formula . The compound of the invention shows the ability to inhibit the action of the human tyrosyl-DNA-phosphodiesterase 1 (Tdp1) enzyme.EFFECT: derivative of usnic acid as a human tyrosyl-DNA phosphodiesterase 1 enzym inhibitor and an increased inhibitory effect on the Tdp1 enzyme.2 dwg, 3 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
Gpr40 agonists // 2627703
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula (I), wherein ring A is an optionally substituted phenyl group, wherein the optional substituent is fluorine or methoxy; ring B is an optionally substituted phenyl group, wherein the optional substituent is selected from methoxy, 1 or 2 fluorine atoms, -CH2CN, -O-CH2-C3cycloalkyl, isopropoxy; isoxazole (which may be substituted with 1 or 2 methyl groups), -O-CH2-CN and -O-CH2-C(O)OH; X is a bond or -CH2O-; Y is -CH2O-; Z is a bond or -(CR5R6)-; L is -CO2H; R1 is OR7; R2 is a ring, selected from the group consisting of C3-C12 cycloalkyl, C6aryl-condensedC3-C6 cycloalkyl, and optionally substituted C6 aryl, each possible substituent being selected from methyl, fluoro, methoxy, cyano and methanesulfonyl; each R3, R4, R5 and R6 is independently selected from the group consisting of H, CN, OH, CONH2, C1-C12 alkyl, C2-C12 alkynyl, C6 aryl and optionally substituted C1-C18 heteroaryl selected from isoxazole, wherein the isoxazole may be substituted with 1 or 2 methyl groups, or any two of R3, R4, R5 and R6 together with the atoms to which they are attached, can form an optionally substituted C3 cycloalkyl or a double bond between the atoms to which they are attached; R7 is selected from the group consisting of H, optionally substituted C1-C12 alkyl, where possible substituents are selected from 3 fluorine atoms or -N(CH3)2 or phenyl, C2-C12 alkenyl, C3-C12 cycloalkyl and C6 aryl; r is 1; or a pharmaceutically acceptable salt thereof. The compounds of formula (I) of the invention are intended for manufacture of a pharmaceutical composition or a medicament for diabetes treatment.EFFECT: GPR40 activating connections.30 cl, 3 tbl, 124 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
Sulfonamide compounds and their use as tnap inhibitors // 2627701
FIELD: chemistry.SUBSTANCE: invention relates to compounds of Formula I: wherein: Y1 is a bond and Y2 is -N(R6)-; L1 and L2 are each a bond; X1 is =N- or =C(R2)-; X2 is =N- or =C(R3)-; R1 and R4 are independently selected from the group consisting of -F, -Cl, -Br, -CN, -C(O)N(R7)-R8, -C(O)-O-R9, methyl, -OMe, -OCF3, optionally substituted phenyl and optionally substituted 5- or 6-membered heteroaryl; R2, R3 and R5 are hydrogen; R6 is hydrogen; R7 is hydrogen and R8 is selected from hydrogen, optionally substituted C1-C4 alkyl, optionally substituted C3-C6 cycloalkyl or optionally substituted phenyl; either R7 and R8 together with the nitrogen atom to which they are attached form an optionally substituted heterocycloamino which is an optionally substituted pyrrolidine, an optionally substituted piperidine, an optionally substituted morpholine or an optionally substituted piperazine; R9 is selected from hydrogen, optionally substituted C1-C4 alkyl, optionally substituted C3-C6 cycloalkyl or optionally substituted phenyl; A is selected from the group consisting of -C(O)-N(R7)-R8 or -C(O)-O-R9, or A is , R12 and R13 are independently selected from the group consisting of hydrogen, halogen, -CN, -OH, -C(O)-O-R19, optionally substituted C1-C4 alkyl, optionally substituted C3-C6 cycloalkyl optionally substituted with C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, optionally substituted phenyl and optionally substituted 5- or 6-membered heteroaryl, R19 is selected from the group consisting of hydrogen, optionally substituted C1-C4 lkila, C1-C4 haloalkyl, optionally substituted C3-C6 cycloalkyl and optionally substituted phenyl; and R15 represents hydrogen or C1-C4 alkyl; Wherein the substituted group is substituted by -CO2H, nitrile, hydroxyl, C1-C4 alkyl, C1-C4 alkoxy, phenyl, C3-C6 cycloalkyl or diC1-C4 alkylamine, which modulate TNAP activity.EFFECT: improved properties of compounds.14 cl, 1 tbl, 12 ex
 
2551055.
Up!