Analogs of himbacin, their using and pharmaceutical composition based on thereof possessing property of thrombin receptor antagonist

Invention describes derivatives of benzonaphthoazulene of the formula (I): wherein X represents oxygen (O) or sulfur (S) atom; Y and Z mean hydrogen atom; groups of the formula or the formula mean structures of formulae ; R¹ represents compound of the formula (II): wherein R² and R³ can represent simultaneously and independently of one another hydrogen atom (H), (C₁-C₄)-alkyl, or in common with nitrogen atom (N) they mean heterocycle chosen from morpholinyl, piperidinyl or pyrrolidinyl; n means a whole number from 0 to 3; m means a whole number 1; Q₁ and Q₂ represent independently of one another oxygen atom or group of the formula: wherein y₁ and y₂ represent independently of one another hydrogen atom or (C₁-C₄)-alkyl. Also, invention describes derivatives of benzonaphthoazulene of the formula (Ia) given in the invention description and differing from compounds of the formula (I) wherein R¹ represents (C₁-C₇)-alkyl substituted with hydroxyl or (C₁-C₇)-alkyloxycarbonyl. Compounds of the formula (I) inhibit producing TNF-α, and compounds of the formula (Ia) are intermediate substances used in synthesis of compounds of the formula (I). Also, invention describes using compounds of the formula (Ia) wherein R¹ means CO₂Et, CH₂OH for preparing compounds of the formula (I), and using compounds of the formula (I) for preparing pharmaceutical compositions designated for inhibition of production of TNF-α.

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 diazacycloalkanes of the general formula (I): wherein G¹ represents condensed polycyclic group. Compounds are selective and strong acting agonists of oxytocin and can useful in treatment of erectile dysfunction. Also, invention describes a pharmaceutical composition based on compounds of the formula (I) and their using in manufacturing the pharmaceutical composition.

Invention relates to compounds of general formula 1 (G¹ is group of general formulae 2 G¹ is group of general formulae ; meanings of the rest substituents are as described in specification) or pharmaceutically acceptable salts thereof and use thereof in srug production. Said compounds are useful in treatment of male and female sexual disorders.

Invention relates to new amide-type carboxamide derivatives of formula [1] , wherein X represents -N= or -CH= group; R¹ represents halogen atom, lower alkyl and a like; R¹ represents -CO-R²¹-R²² (meanings of R²¹ and R²² are as defined in claim 1); Y¹ and Y² are independently halogen atom, lower alkyl, lower alcoxy group, and a like; ring A represents phenyl and a like; or pharmaceutically acceptable salts thereof. Said derivatives are useful as FXa inhibitors. Also disclosed are pharmaceutical composition based on abovementioned compounds and uses thereof.

Invention relates to pharmaceutical compositions possessing inhibitory effect with respect to MC2R-receptors, for preparing medicinal preparations as tablets, granules, capsules, suspensions, solutions or injections placed into pharmaceutically acceptable package. As active substance the composition comprises azaheterocyclic compound of general formulas (1.1.1) , (1.2.1) or (1.3.1) , wherein R¹ in the general formula (1.1.1) represents substituted alkyl, aryl, heteroaryl, heterocyclyl, or R¹ in the general formula (1.2.1) represents a substitute of amino-group chosen from hydrogen atom or possibly substituted lower alkyl or lower acyl; each R², R³ and R⁴ represents independently of one another a substitute of cyclic system chosen from hydrogen atom, azaheterocyclyl, possibly substituted lower alkyl, possibly substituted hydroxy-group, carboxy-group, cycloalkyl; or R³ and R⁴ in common with carbon atoms to which they are bound form azaheterocycle, or R¹ in common with nitrogen atom to which it is bound, and R³ and R⁴ in common with carbon atoms to which they are bound form azaheterocycle through R¹, R³ and R⁴; R¹⁸ and R¹⁹ represent independently of one another substitutes of amino-group chosen from hydrogen atom or lower alkyl substituted with azaheterocycle as their racemates, optically active isomers or their pharmaceutically acceptable salts and/or hydrates; R²⁰ and R²¹ in common with nitrogen atom to which they are bound form possibly substituted azaheterocycle. Also, invention relates to a method for preparing a pharmaceutical composition and using compounds and compositions for preparing medicinal preparations and for treatment or prophylaxis of diseases associated with enhanced activation of adrenocorticotropic hormone for compounds of general formulas (1.1.1), (1.2.1) and (1.3.1), and for using compounds for experimental investigations of indicated processes in vitro or in vivo also.

Invention relates to novel 4-phenyl-substituted tetrahydroisoquinolines of the formulae: (IA) , (IB) , (IIA) , (IIB) , (IIIA) and (IIIC) wherein values X and R¹-R⁷ are given in the invention description. Proposed compounds show selective binding of neurotransmitters and therefore they can be used in treatment of different neurological or psychological disorders, for example, ADHD. Also, invention relates to a pharmaceutical composition based on proposed compounds and to a method for treatment.

Invention relates to novel compounds of the formula (I): and their pharmaceutically acceptable salts possessing properties of inhibitors of protein kinase p38. In the formula (I) A means nitrogen atom (N) or -CH; R¹ means hydrogen atom, alkyl or aralkyl; R² means (C₁-C₆)-alkyl, hydroxy-(C₁-C₆)-alkyl, (R'')₂NCO-alkylene- (wherein each R'' means independently hydrogen atom or (C₁-C₆)-alkyl), (C₃-C₇)-cycloalkyl substituted optionally with hydroxy-group, 6-membered heterocyclyl comprising nitrogen, oxygen or sulfur atom or its oxides as heteroatoms and wherein nitrogen-containing heterocyclyl can be substituted with (C₁-C₄)-alkylsulfonyl group, optionally substituted phenyl wherein substitutes are chosen from halogen atoms and lower alkoxy-group; X means oxygen atom (O), -NR³ or sulfur atom (S) wherein R³ means (C₁-C₆)-alkyl or phenyl; Y means a chemical bond, O, C(=O), -CH(OR'), -CHR' or S wherein R' means hydrogen atom; R means phenyl optionally substituted with one or some substitutes chosen from halogen atoms, lower alkyl and lower alkoxy-group. Proposed compounds can be used, for example, in treatment of inflammatory diseases, among them intestine disease, Alzheimer's disease, Crohn's disease, cerebrospinal sclerosis, asthma and can be used in development of viral diseases also.

Invention relates to derivatives of thieno[2,3-d]pyrimidine of the general formula (I): or their pharmaceutically acceptable salts wherein R1 and R2 in common with nitrogen atom to which they are added form a ring comprising from 2 to 6 carbon atoms and optionally comprising one or more heteroatoms chosen from nitrogen (N), oxygen (O) and/or sulfur (S) atoms. Proposed compounds possess ability to activate both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and can be used in therapy in aims for regulating fertility. Also, invention describes a pharmaceutical composition based on compounds of the formula (I).

Invention relates to compounds of the formula (1): wherein each R¹ and R² represents independently (C₁-C₆)-alkyl, (C₃-C₆)-alkenyl, (C₃-C₆)-cycloalkyl-(C₁-C₃)-alkyl or (C₃-C₆)-cycloalkyl wherein each of them can be substituted possibly with halogen atom in the amount from 1 to 3; R³ represents isoxyzolydine-2-ylcarbonyl or tetrahydroisoxazine-2-ylcarbonyl wherein each ring is substituted possibly with one hydroxy-group; Q represents -CO- or -C(R⁴)(R⁵)- (wherein R⁴ represents hydrogen atom or (C₁-C₄)-alkyl, and R⁵ represents hydrogen atom or hydroxy-group); Ar represents 5-10-membered aromatic ring system wherein up to 4 ring atoms can be represented by heteroatoms chosen independently from nitrogen, oxygen and sulfur atoms and wherein this ring system is substituted possibly with one or more substitute. Proposed compounds can be used for modulation of autoimmune disease. Also, invention describes methods for synthesis of compounds of the formula (1) and pharmaceutical composition based on compounds of the formula (1).

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 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 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 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 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 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 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

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.