Method for preparing 1,11-dialkyl-3,5-dihydrofuro-[2',3':3,4]-cyclohepta[c]isochromens

Invention relates to a novel method for preparing 14β-hydroxy-1,4-carbonate-desacetylbaccatin III and intermediate substances used in preparing new derivatives of taxane and possessing an antitumor activity. Method involves the following stages: a) protection of hydroxyls at positions 7 and 10 in 10-desacetylbaccatin III wherein R and R₁ are taken among hydrogen atom, (C₁-C₁₀)-alkyl or aryl, (C₁-C₁₀)-alkyl- or aryl-carbonyl, trichloroacetyl, (C₁-C₄)-trialkylsilyl; preferably, when R and R₁ are similar then they represent trichloroacetyl; when they are different then, preferably, R represents trichloroacetyl and R₁ represents acetyl; or R represents triethyl or trimethylsilyl and R₁ represents acetyl; b) two-stage oxidation to yield a derivative oxidized to carbonyl at position 13 and hydroxylated at position 14; c) carboxylation of vicinal hydroxyls at positions 1 and 14 to yield 1,14-carbonate derivative; d) reduction of carbonyl at position 13; e) removal of protective groups at positions 7 and 10. Also, invention relates to intermediate substances. Invention provides preparing intermediate substances used in synthesis of taxane.

Invention relates to a new pentacyclic compound derivative of taxane represented by the formula:

Invention relates to new bis-tetrahydrofuranbenzodioxolyl sulfonamide compounds of the formula (I): , its salts, stereoisomers and racemates that are effective inhibitors of protease activity. Also, invention relates to pharmaceutical preparations, methods for inhibition of retrovirus proteases, in particular, to resistant retrovirus proteases, to many drugs, methods for treatment and prophylaxis of infection or disease associated with retrovirus infection in mammals and to methods for inhibition of retrovirus replication. Invention provides preparing new derivatives of bis-tetrahydrofuranbenzodioxalyl sulfonamides eliciting the valuable pharmaceutical properties.

The invention relates to new derivatives epothilone formula I, where the bond indicated by a wavy line indicates that the bond “a” is either CIS-or TRANS-form; (I) R₂absent or represents oxygen; “a” denotes a single or double bond; “b” is absent or represents a simple bond; and “C” is absent or represents a simple bond, provided that when R₂denotes oxygen, then “b” and “C” both represent a simple bond and a represents a simple bond; if R₂no, the “b” and “C” both are absent and “a” represents a double bond; and if “a” represents a double bond, R₂“b” and “C” are absent; R₃denotes a radical selected from the group comprising hydrogen; (ness.)alkyl, especially methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl; -CH₂F; -CH₂-OH; R₄and R₅independently of one another denote hydrogen; R₁denotes a radical of the structure (a-d); (II) if R₃means (ness.)alkyl, especially methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl; -CH₂F; CH₂-HE; and other symbols except for the R₁have the values listed above in their characters except for the R₁have the above values, R₁can also represent a fragment of formula (j); or a salt of the compounds of formula I, if there is a salt-forming group

The invention relates to a method for producing 1,4:3,6-dianhydro-D-sorbitol, which is an intermediate in the production of lekarstvennyh drugs on the basis of its mono - or dinitropropane

The invention relates to a method for epoxidation prehiring of olefin, which includes the interaction prehiring of the olefin with oxygen source in the presence of salt catalyst

The invention relates to powder clarifier number sorbitol-xylitol-acetaline connections for clarification of a semicrystalline polyolefin resins and compositions based on it

The invention relates to a method of obtaining modified in the 16,17-position epothilones, according to which the protected position of 3.7 or unprotected epothilone a or b a) hydronaut double bond in position 16,17 or) double bond in position 16,17 spend epoxidation and, if necessary, the obtained epoxide reduced to the alcohol in position 16, to a method for epothilone-N-oxides, in which the protected position of 3.7 or unprotected epothilone And or transferred to N-oxide, the N-oxide optionally subjecting the reaction of Qatar; the method of obtaining modified in the C-19 position epothilones by metallizirovanaya in position C-19 secured or unsecured epothilone a or b, as well as to modified epothilones General formula I

The invention relates to new epothilone formula 1, where R=CH₃N

The invention relates to new substituted pyrazolylborate General formula (I) in which R¹-R⁶have the meanings given in the description of the invention

Invention relates to new bis-tetrahydrofuranbenzodioxolyl sulfonamide compounds of the formula (I): , its salts, stereoisomers and racemates that are effective inhibitors of protease activity. Also, invention relates to pharmaceutical preparations, methods for inhibition of retrovirus proteases, in particular, to resistant retrovirus proteases, to many drugs, methods for treatment and prophylaxis of infection or disease associated with retrovirus infection in mammals and to methods for inhibition of retrovirus replication. Invention provides preparing new derivatives of bis-tetrahydrofuranbenzodioxalyl sulfonamides eliciting the valuable pharmaceutical properties.

Invention relates to a new pentacyclic compound derivative of taxane represented by the formula:

Invention relates to a novel method for preparing 14β-hydroxy-1,4-carbonate-desacetylbaccatin III and intermediate substances used in preparing new derivatives of taxane and possessing an antitumor activity. Method involves the following stages: a) protection of hydroxyls at positions 7 and 10 in 10-desacetylbaccatin III wherein R and R₁ are taken among hydrogen atom, (C₁-C₁₀)-alkyl or aryl, (C₁-C₁₀)-alkyl- or aryl-carbonyl, trichloroacetyl, (C₁-C₄)-trialkylsilyl; preferably, when R and R₁ are similar then they represent trichloroacetyl; when they are different then, preferably, R represents trichloroacetyl and R₁ represents acetyl; or R represents triethyl or trimethylsilyl and R₁ represents acetyl; b) two-stage oxidation to yield a derivative oxidized to carbonyl at position 13 and hydroxylated at position 14; c) carboxylation of vicinal hydroxyls at positions 1 and 14 to yield 1,14-carbonate derivative; d) reduction of carbonyl at position 13; e) removal of protective groups at positions 7 and 10. Also, invention relates to intermediate substances. Invention provides preparing intermediate substances used in synthesis of taxane.

Invention relates to a method for synthesis of new compounds, namely, 1,11-dialkyl-3,5-dihydrofuro-[2',3':3,4]-cyclohepta[c]isochromens of the formula: (Ia-f): wherein (Ia): R means hydrogen atom (H); R₁ means hydrogen atom (H); (Ib): R means bromine atom (Br); R₁ means hydrogen atom (H); (Ic): R means chlorine atom (Cl); R₁ means hydrogen atom (H); (Id): R means hydrogen atom (H); R₁ means bromine atom (Br): (Ie): R means hydrogen atom (H); R₁ means chlorine atom (Cl); (If): R means methoxy-group (-OCH₃); R₁ means hydrogen atom. Method involves formation of condensed tetracyclic system as result of the successive recyclization reactions of furan ring of derivatives of 2-bis-(5-methyl-2-furylmethyl)phenylmethanol and the secondary cyclization of formed isochromen ketone in boiling of solution containing derivatives of 2-bis-(5-methyl-2-furylmethyl)phenylmethanol of the formula: in ethanol medium in the presence of hydrogen chloride alcoholic solution for 15-40 min. Invention provides synthesis of new derivatives of isochromens possessing the potential anti-inflammatory activity.

Invention relates to a novel crystalline form of (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-acetoxy-2-benzoyloxy-9,10-[(1S)-2-(dimethylamino)ethylideneoxy]-5,20-epoxy-1-hydroxytax-11-ene-13-yl-(2R,3S)-3-(tert.-butoxycarbonylamino)-3-(3-fluoro-2-pyridyl)-2-hydroxypropionate that shows the diffraction picture of roentgen rays in powder with characteristic peaks at diffraction angles (θ)= 6.2^o, 10.3^o, 10.7, 11.4^o and 12.0, and a method for its preparing. Method involves carrying out the crystallization step by using organic solvent chosen from group consisting of ketone type solvent, nitrile solvent type and their mixture, or mixture of said solvent and water. Also, invention relates to an antitumor agent based on the prepared crystalline form. Invention provides the stable quality of a medicinal agent based on its lower hygroscopicity.

Invention relates to a method for isolation of epotilons used in medicine in treatment of cancer diseases. Method for desorption of epotilons A, B, D and/or E from synthetic resin is based on using low-polar or nonpolar solvent chosen from the group comprising (lower)-alkyl halides and aromatic solvents, or mixture of two or more amount of such solvents wherein prefix "(lower)" means that radical comprises up to 7 carbon atoms. Used aromatic solvent is chosen from the group including naphthalene, benzene or naphthalene and benzene substituted with one or some substitutes chosen from the following group: (lower)-alkyl, (lower)-alkoxy-group, halogen atom, nitro-group and (lower)-alkoxy-(lower)-alkyl wherein prefix "(lower)" means that radical comprises up to 7 carbon atoms. Solvent is removed to the required level but up to preparing a dry residue preferably. If necessary, residue is dissolved in mixture alcohol/hydrocarbon in the corresponding volume ratio. Alcoholic phase is evaporated until dry and then alcoholic extract is crystallized from mixture alcohol and hydrocarbon. Then formed crystallized product is dissolved in mixture nitrile/water but preferably in mixture acetonitrile/water taken in the ratio = 2:3 (vol./vol.). Formed solution is applied on column (if necessary, after separation for some distillates) for preparative chromatography in reversed phase followed by elution with mixture nitrile/water, removing nitrile and extraction of an aqueous phase with ester. Ester extract is evaporated and formed product is subjected for crystallization. Method for preparing epotilons A, B, D and/or E from resin or reaction mixture involves the following steps: (a) desorption of epotilons with low-polar or nonpolar solvent chosen from the group including (lower)-alkyl halides and aromatic solvents, or mixture of two or more amount of such solvents being the desorption step can be repeated up to achievement of the more complete desorption; (b) removal of solvent used in desorption from formed solutions by evaporation; (c) optional crystallization of epotilon(s) after desorption and first of all for crystallization of epotilon B by addition of mixture of alcohol with hydrocarbon and the following evaporation of alcoholic phase until dry and crystallization of epotilon B from the corresponding mixture of solvents; (d) (obligatory step) separation of epotilons by method of chromatography in reversed phase and the following dissolving a residue obtained in previous step in suitable solvent, elution with mixture nitrile/water and removing nitrile from epotilon-containing fractions by evaporation. If necessary, water remained with epotilon is extracted with ester followed by evaporation of epotilon-containing ester phase until dry; (e) optional purification by adsorption chromatography method, and final recrystallization of purified epotilon from corresponding solvents or mixture of solvents. If necessary, in this process between each step formed solutions or suspensions are concentrated, and/or liquid or solid components are separated of one another. Separation of epotilons A and B is carried out by chromatography method based on a mobile layer modeling. Invention provides simplifying methods for preparing large amounts of epotilons for satisfying requirement in these agents.

Invention relates to novel tetracyclic heterocompounds of the formula (I): wherein X, Y, Z, R¹ - R⁴, n and m has values given in the invention description and used as selective modulating agents for estrogen receptors. Also, invention relates to a method for synthesis of these compounds and pharmaceutical compositions comprising thereof, and their using in treatment and/or prophylaxis of disorders mediated by one or more estrogen receptors. Proposed compounds are useful in treatment and/or prophylaxis of disorders associated with depleting estrogen and comprising such disorders as rush of blood, vaginal dryness, osteopenia and osteoporosis, hormone-dependent cancer and hyperplasia of breast, endometrium, uterus cervix and prostate, endometriosis, uterus fibroma, osteoarthritis that can be used as contraceptive agents both separately and in combination with progestogen or progestogenous antagonist.

Invention relates to novel compounds representing C-glycoside derivatives and their salts of the formula: wherein ring A represents (1) benzene ring; (2) five- or six-membered monocyclic heteroaryl ring comprising 1, 2 or 4 heteroatoms chosen from nitrogen (N) and sulfur (S) atoms but with exception of tetrazoles, or (3) unsaturated nine-membered bicyclic heterocycle comprising 1 heteroatom representing oxygen atom (O); ring B represents (1) unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (2) saturated or unsaturated five- or six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (3) unsaturated nine-membered bicyclic carbocycle, or (4) benzene ring; X represents a bond or lower alkylene wherein values for ring A, ring B and X correlate so manner that (1) when ring A represents benzene ring then ring B is not benzene ring, or (2) when ring A represents benzene ring and ring B represents unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O and comprising benzene ring or unsaturated nine-membered bicyclic carbocycle comprising benzene ring then X is bound to ring B in moiety distinct from benzene ring comprised in ring B; each among R¹-R⁴ represents separately hydrogen atom, -C(=O)-lower alkyl or lower alkylene-aryl; each R⁵-R¹¹ represents separately hydrogen atom, lower alkyl, halogen atom, -OH, =O, -NH₂, halogen-substituted lower alkyl-sulfonyl, phenyl, saturated six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N and O, lower alkylene-OH, lower alkyl, -COOH, -CN, -C(=O)-O-lower alkyl, -O-lower alkyl, -O-cycloalkyl, -O-lower alkylene-OH, -O-lower alkylene-O-lower alkyl, -O-lower alkylene-COOH, -O-lower alkylene-C(=O)-O-lower alkyl, -O-lower alkylene-C(=O)-NH₂, -O-lower alkylene-C(=O)-N-(lower alkyl)₂, -O-lower alkylene-CH(OH)-CH₂(OH), -O-lower alkylene-NH, -O-lower alkylene-NH-lower alkyl, -O-lower alkylene-N-(lower alkyl)₂, -O-lower alkylene-NH-C(=O)-lower alkyl, -NH-lower alkyl, -N-(lower alkyl)₂, -NH-lower alkylene-OH or NH-C(=O)-lower alkyl. Indicated derivatives can be used as inhibitor of co-transporter of Na⁺-glucose and especially as a therapeutic and/or prophylactic agent in diabetes mellitus, such as insulin-dependent diabetes mellitus (diabetes mellitus 1 type) and non-insulin-dependent diabetes mellitus (diabetes mellitus 2 type), and in diseases associated with diabetes mellitus, such as insulin-resistant diseases and obesity.

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; R^a ₁ 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; R^b represents carbamoyl group -C(O)NHR^a wherein R^a 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; R^c 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 R^b and R^c 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.

Invention relates to heterocycle-substituted tricyclic compounds of the formula (I): or their pharmaceutically acceptable salts wherein R means hydrogen atom; R¹ and R² are chosen independently from group comprising hydrogen atom or alkyl comprising 1-6 carbon atoms; R³ means hydrogen atom; n₁ and n₂ = 0-3 independently under condition that they both do not mean 0; Het means pyridyl wherein pyridyl is added to B through cyclic carbon atom and it comprises from 1 to 4 substitutes (W) chosen independently from group comprising -NR⁴R⁵, -NHCOR²⁶, -NHSO₂R¹⁶; R²¹ means aryl and R²¹ means heteroaryl wherein heteroaryl represents furyl, thienyl, pyridyl, thiazolyl, pyrrolidinyl, azethidinyl; R⁴ and R⁵ mean hydrogen atom or alkyl comprising 1-6 carbon atoms, or R⁴ and R⁵ mean in common -(CH₂)₃-, -(CH₂)₄-, -(CH₂)₅- or -(CH₂)₂NR⁷-(CH₂)₂- wherein R⁷ means hydrogen atom or alkyl comprising 1-6 carbon atoms; R⁸, R, R¹⁰ and R¹¹ mean hydrogen atom; B means -(CH₂)_n4CR¹²=CR^12a(CH₂)_n5 wherein n₄ and n₅ = 0-2 independently; R¹² and R^12a are chosen independently from group comprising hydrogen atom or alkyl comprising 1-6 carbon atoms; R²¹ means from 1 to 3 substitutes chosen independently from group comprising hydrogen atom, trifluoromethyl, trifluoromethoxy, halogen atom, cyano, alkyl comprising 1-6 carbon atoms, alkoxy group comprising 1-6 carbon atoms, or -CR²⁹(=NOR²⁸); R²² means -COR²³, -S(O)R³¹, -S(O)₂R³¹ or -COOR²⁷; R²³ means cycloalkyl comprising 3-7 carbon atoms, (C₃-C₇)-cycloalkyl-(C₁-C₆)-alkyl, cycloalkyl comprising 3-7 carbon atoms containing from 1 to 3 substitutes chosen from group comprising halogen atom, (C₁-C₃)-alkoxy-(C₁-C₃)-alkyl, hydroxy group and alkoxy group comprising 1-6 carbon atoms, aryl, aryl-(C₂-C₆)-alkyl; R²⁷ means alkyl comprising 1-6 carbon atoms, phenyl or benzyl; R²⁸ and R²⁹ are chosen independently from group comprising hydrogen atom or alkyl comprising 1-6 carbon atoms; R³¹ means alkyl comprising 1-6 carbon atoms, halogenalkyl comprising 1-6 carbon atoms, aryl, aryl-(C₁-C₆)-alkyl. Also, invention relates to pharmaceutical compositions containing these substances and their using for preparing a drug used in treatment of thrombosis, atherosclerosis, restenosis, hypertension, stenocardia, arrhythmia, heart failure and cancer.