Staufosporine derivatives as inhibitors of receptor tyrosine kinase flt3 activity

FIELD: medicine; pharmacology.

SUBSTANCE: invention concerns application of N-[(9S,10R,11R,13R)-2,3,10,11,12,13-hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1H,9N-diindolo [1,2,3-gh:3', 2', 1'-lm] pyrrolo[3,4-j][1,7]benzodiasonine-11-yl]-N-methylbenzamide of formula or its salts for production of pharmaceutical composition intended for treatment of diseases associated with uncontrolled activity of receptor tyrosine kinase FLT3, pharmaceutical preparation and product, containing connection of formula (II).

EFFECT: high efficiency of treatment.

6 cl, 1 tbl, 2 ex

 

The text descriptions are given in facsimile form.

1. The use of N-[(9S,10R,11R,13R)-2,3,10,11,12,13-hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1H,N-vindaloo[1,2,3-gh:3',2',1'-lm]pyrrolo[3,4-j][1,7]benzodiazepin-11-yl]-N-methylbenzamide formula (VII)

or its salt to obtain a pharmaceutical composition intended for the treatment of diseases associated with uncontrolled activity of the receptor tyrosine kinase FLT3.

2. The use according to claim 1 for the treatment of leukemias and myelodysplastic syndromes.

3. The use according to claim 1 for the treatment of acute myeloid leukemia and myelodysplastic the x syndromes at high risk.

4. Pharmaceutical preparation for the treatment of leukemia, including N-[(9S,10R,11R,13R)-2,3,10,11,12,13-hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1H,N-vindaloo[1,2,3-gh:3',2',1'-lm]pyrrolo[3,4-j][1,7]benzodiazepin-11-yl]-N-methylbenzamide formula (VII) in an effective amount.

5. The product, including packaging material and N-[(9S,10R,11R,13R)-2,3,10,11,12,13-hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1H,N-vindaloo[1,2,3-gh:3',2',1'-lm]pyrrolo[3,4-j][1,7]benzodiazepin-11-yl]-N-methylbenzamide formula (VII) according to claim 1 or its pharmaceutically acceptable salts contained in the specified packaging material, and specified packaging material includes label instructions, in which it is reported that the compound of formula (VII) or its pharmaceutically acceptable salt should be introduced mammals suffering from diseases associated with uncontrolled activity of the receptor tyrosine kinase FLT3, in the amount of from 220 to 230 mg special treatment regimen for inhibiting the development of diseases associated with uncontrolled activity of the receptor tyrosine kinase FLT3.

6. The product according to claim 5, where the compound of formula VII is administered three times daily at a total dose of from 220 to 230 mg, and preferably at a dose of from 70 to 80 mg every introduction, for the treatment of leukemia, especially acute myeloid leukemia and myelodysplastic syndromes at high risk.

Priority items:

30.10.200 according to claims 1 to 4;

29.10.2002 on pp.5 and 6.



 

Same patents:

FIELD: medicine, oncology, hematology.

SUBSTANCE: method involves the complex using symptomatic, antibacterial, general tonic agents and nonspecific immunomodulating therapy. For this aim, lysozyme hydrochloride powder is given orally in the daily dose 500-1800 mg, 2 times per a day, every day for 20-30 days in combination with dosing sodium nucleinate in the daily dose 100-1500 mg, 2 times per a day, for 20-30 days by oral or sublingual route, and lactulose given orally in the dose 2.5-5 ml, 1-2 times per a day, every day for 10-30 days. Lysozyme hydrochloride is given 0.5-1 h before eating, sodium nucleinate is given after intake of lysozyme hydrochloride directly and lactulose is given 20-30 min before eating, or before eating immediately, or in 3-4 h after intake of lysozyme hydrochloride and sodium nucleinate. Method provides the complex correction of nonspecific resistance of body in patients suffering from leukosis and involving maintenance of immune homeostasis, plasma proteolysis, intestine microecology and reparative processes and improved tolerance of scheduled polychemotherapy.

EFFECT: improved method of treatment.

FIELD: medicine, oncology.

SUBSTANCE: invention relates to a method for chemotherapy of acute leucosis. Method involves isolation of blast cells and interphase cells from marrow puncture sample leukocyte fraction of blood of a patient subjected for chemotherapy. Then cells are deposited by centrifugation in medium 199 and their concentration is brought about to the level (2-3) x 106 cells/ml. Then isolated cells are incubated with each chemotherapeutic drug chosen from the following group: dexamethasone, cyclophosphanum, vincristine, teniposide, etoposide, citarabinum that are diluted preliminary with isotonic solution to the concentration 1:1000. Then cells treated with chemotherapeutic drugs are centrifuged repeatedly in medium 199 followed by carrying out the annexin test. In the schedule treatment drugs that showed the maximal percent of cells apoptosis are used. Method provides maximal decreasing adverse and toxic effects of chemotherapeutic drugs and to enhance apoptosis of tumor cells based on individual selection of chemotherapeutic drugs for a patient, to prolong remission period and to exclude using additional curative effects.

EFFECT: improved and enhanced method of chemotherapy.

2 ex

FIELD: organic chemistry, medicine, oncology, pharmacy, biochemistry.

SUBSTANCE: invention relates to amide derivative represented by the following formula [1]:

in any of the following cases (A) or (B), or its salt. In the case (A) R1 represents 5-7-membered saturated cyclic group comprising 1-2 nitrogen atoms as atom forming cycle (saturated cyclic amino-group can be substituted with 1-3 similar or different substitutes chosen from group consisting of (C1-C10)-alkyl, (C1-C10)-alkoxycarbonyl), mono-(C1-C10)-alkylamino- or di-(C1-C10)-alkylamino-group; R2 represents (C1-C10)-alkyl, halogen atom, halogen-(C1-C10)-alkyl, (C1-C10)-alkoxy-group, (C1-C10)-alkoxycarbonyl, nitro-group, mono-(C1-C10)-alkylcarbamoyl, di-(C1-C10)-alkylcarbamoyl or cyano-group; R3 represents hydrogen atom, halogen atom or (C1-C10)-alkoxy-group; Het1 represents any of the following formulae: [2] , [3] , [4] , [5] , [6] , [7] and [8] ; Het2 represents pyridyl, pyrimidinyl, pyrazinyl or 1,2-dihydropyridazinyl (wherein Het2 can be substituted with 1-3 similar or different substitutes chosen from halogen atom) but except for compound wherein R1 means (i) pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl and each of them can be substituted with 1-3 similar or different substitutes chosen from group consisting of alkyl, alkoxycarbonyl, halogen atom, halogenalkyl, hydroxyalkyl, amino-, monoalkylamino-, dialkylamino-group, carbamoyl, monoalkylcarbamoyl and dialkylcarbamoyl; (ii) monoalkylamino-group, or (iii) dialkylamino-group; Het1 means group of the formula [6], and Het2 means pyrazinyl or pyridyl and each of them can mean a substituted alkyl. In case the (B) R1 represents 4-methylpiperazin-1-yl, 1-pyrrolidinyl, piperidino-group, 4-ethylpiperazin-1-yl, 4-n-propylpiperazin-1-yl, cis-3,5-dimethylpiperazin-1-yl, morpholino-, dimethylamino- or diethylamino-group; R2 represents methyl, halogen atom, trifluoromethyl, methoxy-group, methoxycarbonyl, nitro-group, dimethylcarbamoyl or cyano-group; R3 represents hydrogen atom, bromine atom or methoxy-group; Het1 represents compound of the formula [6]; Het2 represents 3-pyridyl. Invention relates to a pharmaceutical composition possessing inhibitory activity with respect to BCR-ABL tyrosine kinase comprising amide derivative of the formula (I) or its salt as active component and a pharmaceutically acceptable nontoxic and inert carrier. Also, invention relates to BCR-ABL tyrosine kinase inhibitor, therapeutic agents comprising amide derivative of the formula (I) or its salt and, optionally, a pharmaceutically acceptable nontoxic and inert carrier used in treatment of chronic myelogenous leukemia, acute lymphoblast cell leukemia, acute myelogenous leukemia. Invention provides and proposes amide derivative inhibiting activity of BCR-ABL tyrosine kinase.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

8 cl, 2 tbl, 83 ex

FIELD: medicine, oncology, pharmacy.

SUBSTANCE: invention proposes a pharmaceutical composition that contains compounds of chlorogenic acid isolated from Piper betel leaves extract or from any other part of plant Piper betel and a pharmaceutically acceptable excipient. Invention provides enhanced effectiveness of treatment of such diseases as acute and chronic myeloid leucosis and lymphoid leucosis and absence of its effect on normal cells. Invention can be used in treatment of patients suffering from acute and chronic myeloid and lymphoid leucosis.

EFFECT: enhanced and valuable medicinal properties of pharmaceutical composition.

32 cl, 4 tbl, 4 dwg, 11 ex

FIELD: organic chemistry, pharmacy, veterinary science.

SUBSTANCE: invention relates to compound comprising 1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridine-4-amine or pharmaceutically acceptable salt of this compound and pharmaceutical composition used for stimulation of biosynthesis of cytokine based on abovementioned compound Also, invention claims a method for stimulation of biosynthesis of cytokines in animal body involving administration in animal body of above described compound or its salt. Invention provides preparing a novel compound possessing useful biological properties.

EFFECT: valuable biological properties of compound and pharmaceutical composition.

3 cl, 12 tbl, 213 ex

FIELD: medicine, peptides.

SUBSTANCE: invention relates to osteogenic growth oligopeptides used as stimulators of hemopoiesis. Invention proposes using an oligopeptide of molecular mass in the range from 200 to 1000 Da, comprising one of the following sequence: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly used in preparing a pharmaceutical composition and enhancing mobilization of hemopoietic stem cells from many differentiation line into peripheral blood, in particular, CD34-positive hemopoietic stem cells. Advantage of the invention involves expanding field in using oligopeptides used in stimulation of hemopoiesis.

EFFECT: enhanced and valuable properties of oligopeptides.

34 cl, 2 tbl, 7 dwg, 4 ex

FIELD: oncology.

SUBSTANCE: invention characterizes compositions, their employment, and embodiments of a method of treatment of B-cellular lymphomas, leucosis, and other malignant tumors CD40+. Principal active therapeutical agent is anti-CD40L antibody or another CD40L antagonist inhibiting CD40-CD40L intermediate. In combination or composition with indicated CD40L antagonist any one or several of the following components can be additionally used: anti-CD20 antibody, a chemotherapeutical agent or a combination thereof, and radiotherapy.

EFFECT: enhanced mechanisms of apoptosis of tumor CD40+ cells due to sensitization of these earlier destruction-resistant cells.

88 cl, 4 dwg, 6 tbl, 8 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I)

or their pharmaceutically acceptable salts or esters hydrolyzing in vivo and possessing activity inhibiting the cellular cycle and selective with respect to CDK-2, CDK-4 and CDK-6. Compounds can be used in cancer treatment. In the formula (I) R1 represents halogen atom, amino-group, (C1-C)-alkyl, (C1-C6)-alkoxy-group; p = 0-4 wherein values R1 can be similar or different; R2 represents sulfamoyl or group Ra-Rb-; q = 0-2 wherein values R2 can be similar or different and wherein p + q = 0-5; R3 represents halogen atom or cyano-group; n = 0-2 wherein values R3 can be similar or different; R4 represents hydrogen atom, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl, phenyl or heterocyclic group bound with carbon atom wherein R4 can be optionally substituted at carbon atom with one or some groups Rd; R5 and R6 are chosen independently from hydrogen, halogen atom, (C1-C)-alkyl, (C2-C6)-alkenyl or (C3-C8)-cycloalkyl wherein R5 and R6 can be substituted at carbon atom independently of one another with one or some groups Re; Ra is chosen from (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkyl-(C1-C6)-alkyl, phenyl, heterocyclic group, phenyl-(C1-C)-alkyl or (heterocyclic group)-(C1-C6)-alkyl wherein Ra can be substituted optionally at carbon atom with one or some groups Rg and wherein if indicated heterocyclic group comprises residue -NH- then its nitrogen atom can be optionally substituted with group chosen from the group Rh; Rb represents -N(Rm)C(O)-, -C(O)N(Rm)-, -S(O)r-, -OC(O)N(Rm)SO2-, -SO2N(Rm)- or -N(Rm)SO2- wherein Rm represents hydrogen atom or (C1-C6)-alkyl, and r = 1-2. Also, invention relates to methods for synthesis of these compounds, a pharmaceutical composition, method for inhibition and using these compounds.

EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical compositions.

24 cl, 3 sch, 166 ex

FIELD: organic chemistry, vitamins, medicine, pharmacy.

SUBSTANCE: invention relates to a new compound of the formula (I): wherein X means hydrogen atom or hydroxy group; R1 and R2 that can be similar or different mean hydrogen atom, (C1-C4)-alkyl; R3 means hydrogen atom, methyl group, fluorine or chlorine atom. Also, invention relates to its esters able to hydrolysis in vivo in combination with pharmaceutically acceptable acids. Also, invention relates to a pharmaceutical composition eliciting the inhibitory activity with respect to proliferation and promoting differentiation of cells and comprising the effective dose of compound of the formula (I) in common with pharmaceutically acceptable carriers and/or excipients. Also, invention relates to applying compound of the formula (I) for preparing a medicine used in treatment and prophylaxis of disease characterizing by abnormal differentiation of cells and/or proliferation of cells.

EFFECT: valuable medicinal properties of compounds.

13 cl, 3 sch, 3 tbl, 6 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new inhibitors of farnesyltransferase of the formula (I):

wherein R1 means hydrogen atom (H), group of the formula R5C(O)- wherein R5 means phenyl, pyridyl or N-methylpiperidine; R2 means hydrogen atom (H), isopropyl, cyclopentyl or N-methyltetrahydropyridyl; R3 means hydrogen atom (H), halogen atom; R4 means hydrogen atom (H), halogen atom; L means -CH2-Z- wherein Z means NH; Y means sulfur atom (S), S(O) or S(O)2; or its salt. Compounds of the formula (I) inhibit activity of enzyme, farnesyl(protein)transferase, that allows their using in pharmaceutical composition in cancer treatment.

EFFECT: valuable medicinal properties of inhibitors.

18 cl, 3 tbl, 3 sch, 6 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: compound of formula [I]: is described, where the ring A represents halogen substituted benzene ring; the ring B represents benzene ring substituted with two lower, 1 to 4 carbon atoms, alcoxy-groups; the ring C represents benzene ring or five-member aromatic heterocyclic ring, that may be optionally substituted with substitute as follows: carboxyl group, C1-4-alkyl group, C2-7-alkanoiloxy-C1-6-alkyl group, phenyl-C1-4-alkyl group, phenyl group, optionally substituted with carboxyl group, or oxo-group; R1 represents C1-6-alkyl group, optionally substituted with hydroxyl group, that optionally substituted with C2-20-alkanoil or C1-7-alkyl group; X1a represents bound or C1-6-alkylen, optionally substituted with hydroxyl or oxo-group; X1b represents bound or C1-6-alkylen, optionally substituted with hydroxyl or oxo-group; X2 represents bound, -O- or -S- ; X3 represents bound or group, formed by one hydrogen atom elimination from either straight or branched chain C1-7-alkyl, or C2-6-alkenyl group, that optionally substituted with hydroxyl or oxo-group; and Y represents optionally etherified carboxyl group; or its salt. Benzoxazepin derivatives production method, medicine based on them, and their application are also described.

EFFECT: novel compounds have high lipids-decreasing effect and are helpful as hyperlipidemia prevention and treatment medicine.

20 cl, 168 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the new compounds presented by the following formula (I), or to the pharmaceutically acceptable salts: , where R1 and R2 represent substitutes, adjoining with each other and with two carbonic atoms, to each of which they are adjoined forming the group presented by the following formula: 1) , or

2) , , , , , , , , or

3) or

4) , , or

where hydrogen atom in each cyclic group can be substituted bi 1-4 substitutes selected fro the following group of substitutes B1, R3 represents hydrogen atom or methyl group; and R6 represents substitute selected from the following group of A1 substitutes, the group of A1 substitutes: (1) hydrogen atom, (2) C1-C6 alkoxy group; substitute B1 group: (1) hydrogen atom, (2) hydroxyl group, (3) oxo group, (4) C1-C6 alkanoyl group, (5) C3-C8 cycloalkyl group, (6) C1-C6 alkyl group (where C1-C6 alkyl group can be substituted by C1-C6 alkoxy group), (7) C1-C6 alkoxy group, (8) C1-C6 alkoxyimino group, (9) C5-C6 cycloalkyl group, derived by two C1-C3 alkyl groups joined to the same carbonic atom with hydrogen atom and the carbons. The invention is also relates to the pharmaceutical composition.

EFFECT: production of the new biologically active compounds and pharmaceutical compositions on their basis having inhibitor potency towards to serotonine1A receptor.

34 cl, 73 ex, 12 tbl, 4 dwg

FIELD: chemistry.

SUBSTANCE: claim describes benzoxazepinone derivatives of formula : wherein R1 represents hydrogen, C1-C6 alkoxy, halogen or NR'R", n is 1 or 2, R', R" independently from each other represents hydrogen or C1-C6 alkyl; R2 represents hydrogen, C1-C6 alkyl -(CH2)m-C3-C7-cycloalkyl, -(CH2)m-phenyl or -(CH2)m-O-C1-C6 alkyl; m is 0.1 or 2; R3 represents C1-C6 alkyl,-(CH2)m-C(O)O-C1-C6 alkyl, C3-C7 cycloalkyl or -(CH2)m-phenyl which is unsubstituted or substituted by one or two substituents, selected from the group consisting of halogen, trifluoromethyl, -NR'R", nitro and -SO2NH2, or represents -C3-C7 -cycloalkyl, unsubstituted or substituted by phenyl, or is -(CR′R″)o-heterocyclyl, selected from the group consisting of tetrahydropyran-4-yl, pyridin-3-yl, indol-3-yl optionally substituted by halogen or C1-C6 alkoxy group, or thiophen-2-yl, furan-2-yl, NH-pyridin-2-yl optionally substituted by nitro group or benzoimidazol-2-yl, 2-oxo-tetrahydrofuran, and benzo[1,3]dioxol-5-yl and represents -tetrahydro-naphthalen-1-yl, -CHR′-naphthalen-2-yl, -fluoren-9-yl, -(CH2)o-S-lower alkyl, -(CH2)o-S-benzyl, -(CH2)o-C(O)NH2, -(CH2)oNR′R″, -CH[C(O)NH2]-(CH2)o-phenyl, -(CH2)o-CF3, or -(CH2)o-CR′R″-CH2-NR′R″; and o is 1 or 2; or their pharmaceutically suitable acid addition salts, excluding: phenetylamide 4-benzyl-3-oxo-2,3,4,5-tetrahydro-benzo[f][1,4]-oxazepine-5-carboxylic acid, butylamide 4-benzyl-3-oxo-2,3,4,5-tetrahydro-benzo[f][1,4]-oxazepine-5-carboxylic acid, phenetylamide 4-cyclohexyl-3-oxo-2,3,4,5-tetrahydro-benzo[f][1,4]-oxazepine-5-carboxylic acid, butylamide 4-cyclohexyl-3-oxo-2,3,4,5-tetrahydro-benzo[f][1,4]-oxazepine-5-carboxylic acid. The pharmaceutical on basis of the compounds of formula I aimed at the treatment of Alzheimer's disease is described.

EFFECT: production of the new compounds, benzoxazepinone derivatives having useful biological properties.

26 cl, 196 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel azaheterocycles of the general formula (I): possessing inhibitory effect on activity of tyrosine kinase and can be used in treatment of different diseases mediated by these receptors. In compound of the general formula (1) W represents azaheterocycle comprising 6-13 atoms that can be optionally annelated with at least one (C5-C7)-carbocycle and/or possibly annelated with heterocycle comprising 4-10 atoms in ring and comprising at least one heteroatom chosen from oxygen (O), sulfur (S) or nitrogen (N) atom; Ra1 represents a substitute of amino group but not hydrogen atom, such as substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-10-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; Rb represents carbamoyl group -C(O)NHRa wherein Ra represents a substitute of amino group but not hydrogen atom, such as possibly substituted alkyl, possibly substituted aryl, possibly substituted 5-10-membered heterocyclyc comprising at least one heteroatom chosen from O, S or N; Rc represents a substitute of cyclic system, such as possibly substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-6-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; or Rb and Rc form in common aminocyanomethylene group [(=C(NH2)CN], or their pharmaceutically acceptable salts. Also, invention relates to methods for synthesis of these compounds (variants), a pharmaceutical composition, combinatory and focused libraries.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved methods for synthesis and preparing.

35 cl, 16 sch, 13 tbl, 43 ex

FIELD: medicine.

SUBSTANCE: drugs contain H-SGK kinase having lysine substituted by arginine in position 127.

EFFECT: enhanced effectiveness in treating states for which sodium channel and/or Na+, K+, 2Cl- cocarrier activity is to be reduced.

2 cl, 6 dwg

FIELD: organic chemistry.

SUBSTANCE: invention relates to derivatives of general formula I , wherein R1, R2 and R3 are independently H or C1-C4-alkyl; Ar is condensed thiophene or pyridine ring optionally substituted with one or more substituents selected from C1-C4-alkyl, C1-C4-alkyloxy, C1-C4-alkyloxy(C1-C4)-alkyl, CF3, halogen, nitro, cyano, NR4R5 NR4COR6 and CONR4R5 (R4 and R5 are independently H or C1-C4-alkyl; or R4 and R5 together with adjacent nitrogen atom form 5- or 6-membered saturated heterocyclic ring; R6 is C1-C4-alkyl): A is residue of 4-7-membered saturated heterocyclic ring optionally containing nictogen atom and optiomally substituted with 1-3 substituents selected from C1-C4-alkyl, C1-C4-alkyloxy, hydroxyl, halogen, and alkoxy; and pharmaceutical composition based on the same; with the proviso, that compound of formula I wherein A represents condensed [3,2-f]pyridine ring; each R1, R2 and R3 represents H, and A represents (CH2)3. Also described are application of abovementioned derivatives, pharmaceutical composition enhancing of synaptic response mediated with AMPA receptors in CNS based on the same, and method for treatment of neurological diseases or mental disorders.

EFFECT: new compounds with value biological properties.

7 cl, 1 tbl, 12 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of benzoxazepine and describes derivative of benzoxazepine of the general formula (I): wherein X represents -CO or -SO2; R1, R2, R3 and R4 are chosen independently from hydrogen atom (H), (C1-C4)-alkyl, (C1-C4)-alkoxy-group, (C1-C4)-alkyloxy-(C1-C4)-alkyl, -CF3, halogen atom, nitro-group, cyano-group, -NR8R9, -NR8COR10 and -CONR8R9; R5, R6 and R7 represent independently hydrogen atom (H) or (C1-C4)-alkyl; R8 and R9 represent independently hydrogen atom (H) or (C1-C4)-alkyl; or R8 and R9 in common with nitrogen atom to which they are bound form 5- or 6-membered saturated heterocyclic ring comprising optionally the additional heteroatom chosen from oxygen atom (O), sulfur atom (S) or the group -NR11; R10 represents (C1-C4)-alkyl; R11 represents (C1-C4)-alkyl; A represents residue of 4-7-membered saturated heterocyclic ring comprising optionally oxygen atom wherein ring is substituted optionally with 1-3 substitutes chosen from (C1-C4)-alkyl, (C1-C4)-alkoxy-, hydroxy-group, halogen atom and oxo-group, or to its pharmaceutically acceptable salt under condition that compounds of the formula (I) are excluded wherein X represents -CO, and each among R1-R7 represents hydrogen atom (H), and A represents -(CH2)3 or -(CH2)4; compounds of the formula (I) wherein X represents -CO; R1 represents hydrogen atom (H); R2 represents methyl (CH3); each among R3-R7 represents hydrogen atom (H), and A represents -(CH2)3; compounds of the formula (I) wherein X represents -CO; R1 and R2 represent hydrogen atom (H); R3 represents methyl; each among R4-R7 represents hydrogen atom (H), and A represents -(CH2)3; compounds of the formula (I) wherein X represents -CO; each among R1-R3 represents hydrogen atom (H); R4 represents methyl; each among R5-R7 represents hydrogen atom (H), and A represents -(CH2)3, and compounds of the formula (I) wherein X represents -CO; each among R1-R4 represents hydrogen atom (H); R5 represents methyl; R6 and R7 represent hydrogen atom (H), and A represents -(CH2)3. Also, invention describes pharmaceutical compositions comprising indicated derivatives and using these benzoxazepine derivatives in treatment of neurological diseases and psychotic disorders sensitive to enhancing responses mediated by AMPA receptors in the central nervous system. Invention provides preparing new compounds possessing the useful biological properties.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

8 cl, 1 tbl, 31 ex

FIELD: medicine.

SUBSTANCE: invention proposes a method for inhibition of chorionic neovascularization. Method involves irradiation of undesirable novel vascular reticulum in combination with photosensitive agent (porphyrine) and an anti-angiogenic agent taken among antagonist of phospholipase A2, inhibitor of complex kappa B, inhibitor of the growth hormone, inhibitor of insulin-like growth factor-1, inhibitor of cyclooxygenase II, inhibitor of protein kinase C (stautosporin PKC 412) and inhibitor of angiotensin II. The claimed combined treatment provides potentiation of effect of adjunctive photodynamic therapy in combination with enhanced safety.

EFFECT: improved treatment method.

7 cl

FIELD: chemical-pharmaceutical industry, medicine, pharmacy.

SUBSTANCE: invention relates to a spontaneously dispersing composition comprising N-benzoylstaurosporin, a hydrophilic component, a lipophilic component and a surface-active substance taken in the definite ratio of components. Also, invention relates to a method for treatment of the patient needing administration of N-benzoylstautosporin as a component of the spontaneously dispersing composition. The composition possesses the enhanced level of biological availability or diminished variability of the biological availability levels and effectiveness.

EFFECT: improved and valuable properties of composition.

13 cl, 3 dwg, 2 tbl, 5 ex

Derivative to-a // 2205184
The invention relates to new derivatives of K-a (a derivative of indolocarbazole), which are represented by the General formula 1, as well as to a method for improving the functioning and/or increase the survival of cholinergic neurons and the way to improve cell survival at risk of death because of the compounds of formula 1 inhibit production of interleukin-2 and have immunosuppressive activity

FIELD: chemical-pharmaceutical industry, medicine, pharmacy.

SUBSTANCE: invention relates to a spontaneously dispersing composition comprising N-benzoylstaurosporin, a hydrophilic component, a lipophilic component and a surface-active substance taken in the definite ratio of components. Also, invention relates to a method for treatment of the patient needing administration of N-benzoylstautosporin as a component of the spontaneously dispersing composition. The composition possesses the enhanced level of biological availability or diminished variability of the biological availability levels and effectiveness.

EFFECT: improved and valuable properties of composition.

13 cl, 3 dwg, 2 tbl, 5 ex

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