Dibenzo(b,e) pyrano(3,2-b)-1-benzopyrylium salts and method of production thereof

 

(57) Abstract:

Compounds of General formula (I),

< / BR>
where R1is a hydrogen atom or halogen, C1-C6- alkyl, C1-C6- alkoxy or nitro group; R2is a hydrogen atom or halogen or allyl; R3is a hydrogen atom, a C1-C6- alkyl, C1-C6- alkoxy, di(C1-C6)alkylamino - or nitro-group; R4is a halogen atom; R5, R6- C1-C6- alkyl; high spectral characteristics and can be used as fluorescent dyes for aminomethylating fibers and films. Way to obtain is that 2-R4-5,5-R5,R6-cyclohexane-1,3-dione is administered in cooperation with salicylic aldehyde or substituted in the presence of perchloric acid and triethylorthoformate. Given: N; R1, R2, R3, R4, R5, R6; output (%); So square(oC); UV Spectrum (Lmax - E, nm) below. 2 S. p. f-crystals, 2 tab., 1 Il.

The invention relates to a previously undescribed dibenzo[b, e]pyrano[3,2-b]-1-benzopyrylium the perchlorate General formula (I),

< / BR>
where R1the atom of hydrogen or halogen, C1-C6alkyl, C1-C6alkoxy6alkyl, C1-C6alkoxy, di(C1-C6)alkyl-amino - or nitro-group;

R4halogen atom;

R5, R6C1-C6alkyl;

that exhibit fluorescent properties and can be used as fluorescent dyes for aminomethylating fibers and films, and the way they are received.

Known dibenzo[b, e]pyrano[3,2-b]-1-benzopyrylium salt of General formula (IIA,b),

< / BR>
where R1, R2the hydrogen atoms or halogen, C1-C6alkyl used as fluorescent dyes for dyeing aminomethylating fibers and films (DOS 2942931 (1980), BASF Erf. R. Schidt, V. Koch; C. A. 117065 (1980)).

The compound (II) we have Lmax(nm): 11a -549 (R2H, R1Br); 11b 552 (R1R2Br). The extinction coefficient (E) and the data of luminescence spectra (quantum yield) are not given.

The method of obtaining the compounds (IIA,b) lies in the interaction of sodium salt of 2-methyldienolone (IV), previously obtained by deprotonation of 2-methyldienolone (III) with sodium hydride in a nitrogen atmosphere atoC in excess of GMFA, further processing of butyllithium at 20oC, by heating with sodium salt of salicylic aldehydes VB>1R2H

The disadvantage of this method is a multi-stage process, the need for the first stage of the process in an inert atmosphere and at 0oC, the use of flammable reagents (sodium hydride, utility) and solvent (hexane), the use of a large number (up to 500 g per 5 g of the target product) hexadecapole, low yields of the target product (10-15%), inability to obtain compounds with R4= halogen-free, when administered in the reaction of the corresponding 2-galogenarenov, they decompose under the action of sodium hydride and/or utility, and do not give at the end of the reaction, the target product of the General formula I (where R4=halogen).

The aim of the invention are new compounds of a number of dibenzo[b,e]-pyrano [3,2-b]-1-benzopyrylium salts with high spectral characteristics, having in comparison with the known compounds of this series (DOS 2942931, (1980), BASF, Erf. R. Schmidt, V. Koch; C. A. 95, 117065 (1980) uptake of lmaxin the longer-wavelength region of the UV spectrum and a high coefficient of extinction, sufficient for use as fluorescent dyes for dyeing aminomethylating fibers and films similar to those used for these purposes are described compounds of General ,b according to the UV spectrum are: If - lmax555,6 nm; IIA lmax549,0 nm; 1H lmax558,0 nm; IIB lmax552,0 nm, respectively), as well as the way they are received.

The objective is achieved by the compounds I, and also the fact that in the known method of producing compounds of the number of dibenzo[b,e]pyrano[3,2-b]-1-benzopirilievyh salts, including the interaction of substituted salicylic aldehydes with substituted 2-R4-5,5-R5, R6-cyclohexane-1,3-diones in the presence of perchloric acid, the difference is that as substituted salicylic aldehydes use of compounds of General formula VII, as a 2-R4-5,5-R5,R6-cyclohexane-1,3-diones use of compounds of General formula VI, and the process is conducted in the additional presence of triethylorthoformate.

The method of obtaining compounds 1A-m is that 2-R4-5,5-R5, R6-cyclohexane-1,3-dione of General formula VI, where R have the above values enter into interaction with substituted salicylic aldehydes of General formula VII, where R have the above values in the presence of perchloric acid and triethylorthoformate. The latter is taken in excess, sufficient to absorb the water produced in the reaction, and the water contained in perchloric acid.

Previously studied the combined effect of triethylorthoformate and perchloric acid in a mixture of o-oxybenzaldehyde and cyclic 1,3-diketones (in particular dimedone).

It is known that under the action of triethylorthoformate and perchloric acid on axially (VIII) are formed perchlorate 4-ethoxyphenyl (XI).

< / BR>
(Dorofeenko, N. Tkachenko Centuries Zhur.org.chem., 10,2188-2191, 1972).

Also studied the effect of triethylorthoformate and perchloric acid on the fatty-aromatic ketones number (X). Meanwhile, it is found that the reaction cannot be stopped at the stage of monoadduct ketone and triethylorthoformate (XI) and by condensation of two molecules of ketone with orthoevra formed 1,5-diketone (XII), in which the reaction cyclized in Pillay cation (XIII).

< / BR>
(Dorofeenko, N. Mezheritsky Centuries Olekhnovich E. P. Wasserman, A. L. Zhur.org.chem., 9, 395, 1973).

Not containing terminal methyl groups of the 1,3-diketones (XIV) under the action of triethylorthoformate and perchloric acid form cations 1,3-diethoxypropane (XV).

< / BR>
(Olekhnovich E. P. Of Corby I. C. Zhur.org.chem., 26, 213-214, 1990).

Below are examples of the preparation of compounds 1A-m constants (R1-R6, melting point, elemental analysis and spectral characteristics) are given in table.1 and 2.

Example 1. Getting perchlorate 6-bromo-13,13-dimethyl-13H(dibenzo [b,e]pyrano)[3,2-b] benzopyrene (1A). The reaction mixture is in the ratio of 2.2 g (0.001 mol) of 2-bromo-5,5-dimethylcyclohexane-1,3-dione (2-brandileone), 2.5 g (0.02 mol) of salicylic aldehyde, 20 ml triethylorthoformate and 1 ml of 70% perchloric acid was incubated for 1 h the crystals formed are filtered and washed on the filter with ethyl acetate (2 times 5 ml) and ether (2 x 5 ml). Yield: 4.8 g (55.1 per cent); T PL>300oC (from nitromethane; 310oC decomposition). The data of elemental analysis and spectral characteristics, see table.1.

Compounds 1B-g,e,W obtained without heating the reaction mixture analogously to compound 1A (example 1).

Example 2. Getting perchlorate 2,2-dinitro-6-bromo-13,13-dimethyl-13H(dibenzo[b,e]pyrano)[3,2-b] benzopyrene (1D).

To 2.2 g (0.01 mol) of 2-bromo-5,5-dimethylcyclohexane-1,3-dione and 3.4 g (0.02 mol) of p-nitrocellulose aldehyde is added 20 ml of triethylorthoformate, 1 ml of 70% perchloric acid and heated the reaction mixture before boiling (OSISA red-brown crystals are filtered. Washed on the filter with ethyl acetate and ether as in example 1. Yield: 2.0 g (54,5%); MP>300oC (from nitromethane).

Connection 1Z-m obtained by short-time heating of the reaction mixture before boiling (60oC) analogously to compound 1D (example 2).

All described compounds (1A-m) obtained with the yield 50-90%

All described compounds (1A-m) in solution in polar solvents (chloroform, nitromethane, acetonitrile, and others) have an intense orange-red fluorescence. Fluorescent characteristics (data UV spectra of compounds 1A-m, proving the use of compounds 1A-m as fluorescent dyes for aminomethylating fibers are given in table.2.

Thus the compounds I are obtained with a higher yield (50-90%) and a more simple way than the method of obtaining the compounds II, which in turn can also be obtained by the proposed method. Compounds 1A-m have sufficiently high fluorescence characteristics, sufficient for the use of these compounds as fluorescent dyes for dyeing aminomethylating fibers. Compound 1K is allyl derivative, such phosphors.

1. Dibenzo(b,e) pyrano(3,2-C) -benzopyrylium salt of General formula I

< / BR>
where R1the atom of hydrogen or halogen, WITH1WITH6- alkyl, C1WITH6alkoxy or nitro-group;

R2a hydrogen atom or halogen or allyl, R3a hydrogen atom, a C1WITH6alkyl, C1WITH6alkoxy, di(C1WITH6)alkylamino - or nitro-group;

R4halogen atom;

R5and R6WITH1WITH6alkyl.

2. The method of obtaining dibenzo(b,e)pyrano(3,2-C) 1-benzopirilievyh salts of General formula I

< / BR>
where R1the atom of hydrogen or halogen, WITH1WITH6- alkyl, C1WITH6alkoxy or nitro-group;

R2a hydrogen atom or halogen or allyl;

R3a hydrogen atom, a C1WITH6alkyl, C1- C6alkoxy, di(C1WITH6)alkylamino - or nitro-group;

R4halogen atom;

R5and R6WITH1WITH6alkyl,

characterized in that 2-R4-5,5-R5,R6-cyclohexane-1,3 - dione of the formula VI

< / BR>
where R4, R5and R6have the above values,

subjected to interaction with salicylic aldehyde or replaced by the General formula VII

< / BR>
where R is ormita.

 

Same patents:

The invention relates to a new method of obtaining the previously described connections of a number of dibenzo[b, e]pyrano[3,2-b]-1-benzopirilievyh salts of General formula (I),

< / BR>
where X 0;

R1a hydrogen atom;

R2-R4the atom of hydrogen or halogen, C1-C6alkyl or C1-C6alkoxygroup, the nitro-group;

R5, R6, R7the atom of hydrogen or C1-C6alkyl,

that exhibit fluorescent properties and are used as dyes for dyeing films and aminomethylating fibers (DOS 2942931 (1980), BASF, Erf

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: 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.

EFFECT: valuable medicinal properties of compound and composition, improved treatment method.

16 cl, 2 dwg, 3 tbl

FIELD: organic chemistry, medicine, oncology, pharmacy.

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

wherein R1 represents dimethylaminomethyl group or morpholinomethyl group; R2 represents halogen atom or alkoxy-group comprising from 1 to 6 carbon atoms, or its salt eliciting an antitumor effect, and to a medicine agent based on its. Invention provides preparing new derivatives of taxane eliciting the valuable biological effect.

EFFECT: valuable medicinal properties of compound.

13 cl, 1 dwg, 4 tbl, 16 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: 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.

EFFECT: improved preparing method.

8 cl, 8 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: 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.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds.

1 cl, 2 tbl, 5 ex

FIELD: organic chemistry of natural compounds, medicine, oncology.

SUBSTANCE: 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)= 6.2o, 10.3o, 10.7, 11.4o 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.

EFFECT: improved and valuable properties of compounds.

8 cl, 5 ex

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

SUBSTANCE: 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.

EFFECT: improved isolating method.

12 cl, 2 ex

FIELD: organic chemistry, medicine, gynecology.

SUBSTANCE: 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.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

25 cl, 7 tbl, 171 ex

FIELD: organic chemistry, medicine, endocrinology.

SUBSTANCE: 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.

EFFECT: valuable medicinal properties of compounds.

11 cl, 41 tbl, 243 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: organic chemistry, medicine, pharmacy.

SUBSTANCE: 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=CR12a(CH2)n5 wherein n4 and n5 = 0-2 independently; R12 and R12a 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.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

10 cl, 11 tbl, 9 ex

Up!