Novel 4-(azacycloalkyl)phthalonitriles and synthesis method thereof

FIELD: chemistry.

SUBSTANCE: invention relates to synthesis of novel 4-(azacycloalkyl)phthalonitriles. Novel 4-(azacycloalkyl)phthalonitriles of general formula

are obtained. The method of obtaining said compounds involves nucleophilic substitution of the bromine atom in 4-bromophthalonitrile (BPN) with N,N-cycloalkyleneamines.

.

The reaction takes place in the presence of a deprotonation agent K2CO3 and a catalytic complex Cul/dipyridyl formed in situ at temperature 90-95°C for 12 hours. Molar ratio of reactants BPN: amine: Cul: dipyridyl: K2CO3=1:1.2:0.1:0.1:1.5. After the reaction, the mixture is cooled and filtered. The filtered residue is washed with water and recrystallised.

EFFECT: obtaining novel 4-(azacycloalkyl)phthalonitriles using a method which is safe for this class of compounds.

2 cl, 4 ex

 

The invention relates to the field of production of new 4-(azacyclonol)phthalonitrile.

4-(azacyclonol)phthalonitrile can be used to obtain phthalocyanines [Shaposhnikov G.P., Maizlish V.E., Kulinich VP, Izv. Higher education institutions. Chemistry and chemical technology. 2005. T. VIP. S.; Shaposhnikov G.P., Maizlish V.E., " Izv. Higher education institutions. Chemistry and chemical technology. 2004. T. Vol.5. P.26], hexatriene [Siling S.A., Shamshin S.V., Grachev A.B., Tsiganova O.YU., Yuzhakov V.I., Abramov I.G., Smirnov A.V., Ivanovskii S.A., Vitukhnovsky A.G., Averjushkin A.S., Bui Chi Lap. // Oxidation Commun. 2000. Vol.4. P.481-494], 4-substituted phthalic acids and anhydrides.

The problem solved by the present invention is the obtaining of new 4-(azacyclonol)phthalonitrile.

Claimed 4-(azacyclonol)phthalonitrile General formula:

The claimed compounds are:

4-(1-Pyrrolidin-1-yl)phthalonitrile as:

4-(4-Phenylpiperazin-1-yl)phthalonitrile b:

4-[4-(4-Methoxyphenyl)piperazine-1-yl]phthalonitrile with:

4-(4-Benzhydrylpiperazine-1-yl)phthalonitrile d:

For compounds of this class with such substituents are known the following methods:

1. The method of obtaining 3 - and 4-dimethylaminoacetonitrile substitution of the nitro group to the corresponding 3 - and 4-nitrophthalonitrile (Micah is enko S.A.; Derkacheva V.M.; E.A. Lukyanets / J. General. Chemistry, 1981, 51, No 7, 1650-1657), lies in the nucleophilic substitution of the nitro group in the 3 - and 4-nitrophthalonitrile excess hydrochloric acid dimethylamine in DMF medium with addition as deproteinised agent calcined K2CO3when the temperature of the reaction mass 75-80°C for 1 hour. The selection of the product is carried out by cooling the reaction mixture and pouring in water, washing the precipitate with water, drying and chromatographytandem on aluminum oxide with benzene.

2. The method of obtaining 4-piperidinecarbonitrile substitution of the nitro group in 4-nitrophthalonitrile (ibid), lies in the nucleophilic substitution of the nitro group in 4-nitrophthalonitrile excess of piperidine in an environment of N-methylpyrrolidone adding as deproteinised agent calcined K2CO3when the temperature of the reaction mass 20°C for 1.5 hours. The selection of the product is carried out as in claim 1.

3. The method of obtaining 4-dimethylamino - 4-piperidinecarbonitrile substitution of bromine in the 4-bromptonville (BFN) (ibid), lies in the nucleophilic substitution of the bromine atom in the 4-bromptonville excess of the appropriate amine in DMF medium with addition as deproteinised agent calcined K2CO3when the boiling point of the reaction mixture for 3 hours. The selection of product PR is found as in claim 1.

4. The method of obtaining 4-morpholinomethyl substitution of bromine in BFN (ibid), lies in the nucleophilic substitution of the bromine atom in BFN morpholine in the environment of the research with the addition of as deproteinised agent calcined K2CO3when the boiling point of the reaction mixture for 3.5 hours. The selection of the product is carried out as in claim 1.

The method of obtaining the claimed aminophthalonitrile not described in literature, and to get them by any of these methods fail.

This object is achieved in that the connection data (scheme 1) are obtained by reaction of nucleophilic substitution of the bromine atom in BFN corresponding N,N-cyclooctylamine occurring in the presence of deproteinised agent K2CO3and formed in situ catalytic complex CuI/dipyridyl, when the molar ratio of the reagents BFN: Amin: CuI: dipyridil: K2CO3= 1:1.2:0.1:0.1:1.5, a temperature of 90-95°C for 12 hours. The selection of the target product is carried out after cooling and filtering the reaction mass from nerastvorim impurity and dilution of the filtrate with water.

The invention is illustrated by the following examples:

Examples 1-5 show an implementation of the present invention method for producing a 4-(azacyclonol)phthalonitrile using laboratory about what orogovenia.

Example 1. 4-Bromptonville obtained similarly [Abramov I.G., Smirnov A.V., Ivanovskii S.A., Abramova M.B. and Plachtinsky V.V. // Heterocycles. 2001, 55, 1161.].

4-(Pyrrolidin-1-yl)phthalonitrile as:

In a flask equipped with capillary for input of nitrogen, downloaded 4 cm3DMF, 0.3 g (1.45 mmol) BFN, 0.15 g (1.74 mmol) of pyrrolidine, 0.025 g (0.16 mmol) of α,α'-dipyridyl, 0.03 g (0.16 mmol), CuI 0.3 g (2,17 mmol) calcined K2CO3. The reaction mass in a stream of nitrogen was heated to 90-95°C and stirred at this temperature for 12 hours After the reaction mixture was cooled and was filtered. The filtrate was diluted 10 cm3water. The precipitation was filtered, washed with water and recrystallized from ethanol. The product yield is 0.19 g (67.7%) TPL 146-148°C. Range1H NMR1H (DMSO-d6) δ, ppm, J, Hz: 2.0 (4H, s), 3.35 (4H, s), 6.83 (1H, d, 8.9), 7.06 (1H, s), 7.66 (1H, d; 9.2). IR spectrum (KBr), cm-1: 2213, 1542 (CN), 1607, 1519 (Ph).

Examples 2-4. The substitution reaction is conducted analogously to example 1, except that the reagent is used phenylpiperazin b, 4-methoxyphenylpiperazine, 4-benzhydrylpiperazine d, respectively.

4-(4-Phenylpiperazin-1-yl)phthalonitrile b. Yield 0.21 g (50.3%), TPL 140-142°C. 1H Spectrum 1H NMR (DMSO-d6) δ, ppm, J, Hz): 3.30 (3H, s), 3.55 (8H, s), 6.89 (2H, s), 7.25 (2H, s), 7.35 (1H, d, 9.5), 7.65 (1H, s), 7.79 (1H, d, 8.8). IR spectrum (KBr), cm-1: 2217, 1547 (CN), 1597, 1509 (Ph), 1227 (-O-), 1031 (O-C), 824 (1,4-Ar).

4-[4-(4-Methoxyphenyl)piperazine-1-and the]phthalonitrile C. The product yield 0,239 g (51.9%), TPL 186-188°C. Range1H NMR1H (DMSO-d6) δ, ppm, j Hz): 3.30 (4H, s), 3.65 (4H, s), 6.83 (1H, t, 6.0), 6.99 (2H, d; 6.6), 7.20-7.30 (2H, m), 7.30-7.37 (1H, m), 7.61 (1H, s), 7.78 (1H, dd, 9.0, 4.8). IR spectrum (KBr), cm-1: 2217, 1548 (CN), 1595, 1496 (Ph).

(4-Benzhydrylpiperazine-1-yl)phthalonitrile d. The product yield 0,254 g (46.4%), TPL 83-86°C. Range1H NMR1H (DMSO-d6) δ, ppm, J, Hz): 2.44 (3H, s), 3.44 (4H, s), 4.32 (1H, s), 7.15-7.25 (3H, t, 7.1), 7.25-7.34 (4H, t, 7.6), 7.40-7.47 (4H, m), 7.48 (1H, d, 2.2), 7.73 (1H, d, 9.5). IR spectrum (KBr), cm-1: 2217, 1545 (CN), 1596, 1490 (Ph).

The technical result consists in obtaining new 4-(azacyclonol)phthalonitrile not described for this class of compounds by method.

1. 4-(Azacyclonol)phthalonitrile General formula

2. Method of preparing compounds according to claim 1, consisting in carrying out reactions of nucleophilic substitution of the bromine atom in the 4-bromptonville (BON) the corresponding N,N-cyclooctylamine (scheme 2)occurring in the presence of deproteinised agent K2CO3and formed in situ catalytic complex CuI/dipyridyl, at a molar ratio of reagents BFN:Amin:CuI:dipyridil:K2CO3= 1:1,2:0,1:0,1:1,5, the temperature of 90-95°C for 12 h, followed by separation of the target product, cooling, filtering the reaction mass from nerastvorim impurity and dilution of the filtrate with water



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula in which Q together with carbon and nitrogen atoms whereto attached forms a 9-10-member bicyclic heterocycle, and R1 and R2, R3, R4, R5 and R6 are as specified in cl.1 of the patent claim, or to its enantiomers, or a mixture of its enantiomers, or to its pharmaceutically acceptable salt. Also, an invention refers to a method for activation of glucokinase activity in mammals, by introduction of the compound described above, to a method of treating the pathological conditions associated with glucokinase activity and impaired glucose tolerance by means of introduction of the compound of formula I, to a pharmaceutical composition on the basis of the presented compounds, and also to application of the compounds of formula I for preparing the pharmaceutical composition.

EFFECT: there are produced and described new compounds which are activators of glucokinase activity and can be used as therapeutic agents for preventing and treating impaired glucose tolerance, insulin-independent diabetes and obesity.

14 cl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: compound of formula pharmaceutically acceptable salt or solvate of a compound or salt (I), ring Q represents optionally substituted monocyclic or condensed (C6-C12)aryl or optionally substituted monocyclic or condensed heteroaryl where said substitutes are chosen from: halogen; (C1-C6)alkyl optionally substituted by 1-3 halogen atoms; (C1-C6)alkylsulphonyl; phenyl optionally substituted by 1 or 2 substitutes chosen from halogen, (C1-C6)alkyl which can be substituted by 1-3 halogen atoms, groups (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl optionally substituted by halogen; or oxo; Y1 represents a bond or -NR6-CO-, where R6 represents hydrogen, ring A represents optionally substituted a nonaromatic heterocyclyldiyl where said substitutes are chosen from (C1-C6)alkyl optionally substituted by groups hydroxy, (C1-C6)alkylamino, di(C1-C6)alkylamino, morpholino, (C1-C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl; cyano; (C3-C6)cycloalkyl; (C1-C6)alkoxy; (C1-C6)alkoxy(C1-C6)alkyl; phenyl; benzyl; benzyloxymethyl; thienyl; 4-8-members monocyclic nonaromatic heterocycle having 1 or 2 heteroatoms chosen from N or O, and optionally substituted by 1 or 2 substitutes chosen from (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and oxo; (C1-C6)alkylamino; di(C1-C6)alkylamino; a group of formula: -Y2Z'- represents a group of formula: [Formula 2] each R7 independently represents hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl, each of R8 and R9 independently represents hydrogen or (C1-C6)alkyl, n is equal to an integer 0 to 3, Z1 represents a bond, -O-, -S- or-NR9 - where R9 represents hydrogen, (C1-C6)alkyl, acyl or (C1-C6)alkylsulphonyl, ring B represents optionally substituted aromatic carbocyclediyl or optionally substituted aromatic heterocyclediyl where said substitutes are chosen from (C1-C6)alkyl, halogen, (C1-C6)alkoxy and oxo; Y3 represents a bond optionally substituted (C1-C6)alkylene or (C3-C6)cycloalylene, optionally interrupted -O- or optionally substituted (C2-C6)alkenylene where said substitutes are chosen from (C1-C6)alkyl, (C3-C6)cycloalkyl, halogen and (C1-C6)alkoxycarbonyl; Z2 represents COOR3; R3 represents hydrogen or (C1-C6)alkyl.

EFFECT: preparation of new compounds.

30 cl, 9 tbl, 944 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula [I-D1] or pharmaceutically acceptable salt thereof,

,

where each symbol is defined in the claim. The invention also relates to pharmaceutical compositions containing said compound and having HCV polymerase inhibiting activity.

EFFECT: disclosed compound exhibits anti-HCV activity, based on HCV polymerase inhibiting activity and is useful as an agent for preventing and treating hepatitis C.

32 cl, 497 tbl, 1129 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of benzene sulphonamide of formula (I), tautomeric and stereoisomeric forms and physiologically acceptable salts thereof: where X is O, S; R1 is H, halogen; R2 is H, halogen; halogen; R3 is NO2, CN; R4 is: ,

where R71 is H; R72 is H; Z1 is -[CH2]P-, where p = 2.

EFFECT: compounds have antagonistic activity towards CCR3, which enables for their use in making medicinal agents.

13 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the new compounds of formula (I): whereat R1 is -SO2NR102R103, -NR101SO2R104 or -COOR105 whereat R101 is hydrogen atom, R102 and R103 each independently represents hydrogen atom or C1-4 alkyl, R104 is C1-4 alkyl and R105 is hydrogen atom or C1-4 alkyl ; X is bond, -CH2- or -O-; Y is -CH2-; ring A and ring B, which are same or different, each independently is benzene, pyridine, pyrazol or piperidine which can have the following substituents: C1-4 alkyl or halogen; ring D is piperidine; R2 is whereat the arrow shows the position of the bond with the ring D; R51 is (1) hydrogen atom a, (2) C1-6alkyl, which can have the following substituents: (a) hydroxy, (b) methoxy, (c) cyano, (d) carboxy, (e) halogen, (f) methyl sulphonylamino, (g) C3-8cycloalkyl or phenyl, which can have the following substituents: methyl, halogen, hydroxy or methoxy, (h) thienyl, pyrazolyl, tetrahydropyranyl, thiazolyl, isooxalyl, imidazolyl, tetraazolyl, pyridyl, pyrimidinyl which can have the following substituents: methyl, trifluoromethyl or hydroxy, (3) C2-10alkenyl, (4) C2-10alkynyl, (5) phenyl which can have the following substituents: C1-4alkyl or halogen, or (6) pyridine or tetrahydropyran; R52 is (1) hydrogen atom a, (2) C1-6alkyl which can have the following substituents: (a) hydroxy, (b) methoxy, (c) carboxy, (d) C3-8cycloalkyl, (e) phenyl or (f) oxo, (3) C3-8cycloalkyl or phenyl which can have the following substituents: C1-4alkyl, hydroxy, cyano, oxo, carbamoyl, N-methyl aminocarbonyl, carboxy, halogen, methoxy, trifluoromethoxy, methythio, methylsulphonyl, acetylamino, dimethylamino, acetyl, tetraazolyl, trifluoromethyl or methylsulphonylamino (4) C3-10cycloalkenyl, (5) adamantyl, (6) thienyl, pyrazolyl, tetrahydropyranyl, isoxaazolyl, isothiazolyl, thiadiazolyl, piperidinyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, indolyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, dioxaindanyl, benzodioxaindanyl which can have the following substituents: C1-4alkyl, hydroxy, oxo, halogen, azido or trifluoromethyl or (7) benzyloxy groups; and R53 is hydrogen atom or C1-6alkyl; to its salts or its solvates. The invention refers also to the regulator CCR5, to the agent of prevention and/or treatment of HIV infection, immunological or inflammatory diseases, to the pharmaceutical composition, to the medicinal preparation, to the method of disease treatment or prevention as well as to the application of compound as in claim 1.

EFFECT: obtaining of new bioactive compounds possessing anti CCR5 receptor activity.

23 cl, 41 ex

FIELD: chemistry.

SUBSTANCE: inventive subject matter is compouns and their pharmaceutically acceptable salts which can be applied in prevention and treatment of diseases caused by HCV infection. Structural formulae of the compounds are presented in the claim.

EFFECT: obtaining anti-HCV medicine including the claimed compound or its pharmaceutically acceptable salt as active component.

2 cl, 100 ex

FIELD: medicine; cosmetology.

SUBSTANCE: invention contains antiperspirant, continuous phase and structure-forming agent containing cyclic depeptide derivative, method of production thereof, method of hidropoiesis prevention or reduction, derivative of cyclic depeptide and gel base for antiperspirant.

EFFECT: compositions have higher activity.

46 cl, 10 tbl, 6 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compositions and methods for treatment of depressive disorder in subject using the therapeutically effective dose of agonist(s) of delta-receptors of the general formula: wherein Ar1 represents a 6-membered carbocyclic aromatic ring with a substitute Y at its carbon atom wherein Y represents carboxamide of the formula: CONR9R10 wherein both R9 and R10 represent ethyl group; Z is chosen from group consisting of hydrogen atom (H), -OH and alkoxy-group; Ar2 represents a 6-membered carbocyclic aromatic ring with a substitute X at its carbon atom wherein X represents H, or pharmaceutically acceptable ester or salt of such compound. Invention provides antidepressant effect in a patient in using indicated compounds in lower doses as compared with the known agonists of delta-receptors showing the related chemical structure with compounds proposed.

EFFECT: improved method of treatment, enhanced and valuable medicinal properties of compounds.

17 cl, 1 tbl, 21 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compounds of formula I , wherein G is carbon or nitrogen atom; A is i) phenyl substituted with any from -COOH, -CONH2, COOCH3, -CN, -NH2 or -COCH3; ii) naphthyl, benzophuranyl, and quinolinyl; and iii) formulae , , .

Compounds of present invention are useful in particular in pain treatment.

EFFECT: new agents for pain treatment.

58 ex

FIELD: organic chemistry.

SUBSTANCE: claimed method includes reaction of C60-fullerene with 1,2-diaminepropane in presence of Cp2TiCl2 as catalyst in toluene medium at room temperature (approximately 20°C) for 44-52 hours. Yield of target product is 73-90 %. Compound of present invention is useful as chelating agent, sorbent, biologically active compound and for production of new materials with desired electronic, magnetic and optical properties. .

EFFECT: new compound; method of increased yield and selectivity.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general structural formula:

or to pharmaceutically acceptable salts, where Z denotes -O- or -CH2- or -CH2-CH2-; X1 denotes a covalent bond or -O-; Y1 denotes a covalent bond or C1-C10 alkylene, provided that Y1 is a covalent bond only when X1 denotes a covalent bond; R1 denotes a) (C3-C7)cycloalkyl or b) phenyl or heteroaryl, which is a monovalent heteroatomatic monocyclic radical ring containing 1-2 heteroatoms, independently selected from nitrogen and sulphur, possibly substituted with 1-3 groups, independently selected from fluorine, chlorine, bromine, (C1-C6)alkyl or (C1-C6)-alkoxy; R2 denotes -OC(O)(NH2), -OC(O)(NHR9), -NHC(O)OR9, -C(O)R9, -C(O)(NH2), -C(O)(NHR9) or -NHC(O)H, where R9 denotes a linear or branched C1-C5 alkyl or a linear or branched (C1-C5)alkoxyalkyl; R3 denotes H, C1-C5 alkyl, -NHC(O)R10 or OH, where R10 denotes C1-C3 alkyl, provided that when R3 denotes -OH, X1 is not O and R2-Y1-X1 is not -OC(O)(NH2), -OC(O)(NHR9), -NHC(O)OR9 or -NHC(O)H; -Q denotes

, where N and N are bonded by bonds denoted by a wavy line; R4 denotes H; R5 and R6 independently denote: a) H, (C1-C10)alkyl, (C4-C10)cycloalkylalkyl, hydroxylated (C4-C10)cycloalkylalkyl, halo(C4-C10)cycloalkylalkyl, (C1-C2)alkyl(C4-C10)cycloakylalkyl, (C4-C10)bicycloalkyl(C1-C3)alkyl, (C1-C5)alkoxy(C1-C5)alkyl; or a saturated heterocyclyl(C1-C3)alkyl, where the saturated heterocyclic ring is selected from 5-, 6- or 7-member heterocyclic rings which contain 1 heteroatom independently selected from N and O; or b) phenyl(C1-C2)alkyl, phenoxymethyl, each of which is possibly with 1-3 groups independently selected from fluorine, chlorine, (C1-C3)alkyl, (C1-C3)alkoxy; provided that both R5 and R6 are not H; G denotes NH2 or NHR7; R7 denotes (C1-C6)alkyl; or R5 and R7 together denote -CH2, -(CH2)2 or -(CH2)3, possibly substituted with 1-2 groups independently selected from (C1-C8)-alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C2)alkyl or (C1-C8)alkoxy. The invention also relates to compounds selected from the group, pharmaceutical compositions, a method for antagonising one or more aspartate proteases, as well as methods of treating aspartate protease-mediated disorders.

EFFECT: obtaining novel biologically active compounds having activity towards rennin.

35 cl, 33 ex, 4 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of general formula (I) or to their pharmaceutically acceptable salts exhibiting CCR2B antagonist activity, and to a based pharmaceutical composition. (I) where P represents phenyl optionally substituted by 1 or 2 substitutes independently selected from halogen, C1-4alkyl, cyano, trifluoromethyl, C1-4alkoxy and trifluormethylthio, and R2 has the values specified in the patent claim.

EFFECT: preparation of new compounds of general formula (I) or their pharmaceutically acceptable salts exhibiting CCR2B antagonist activity.

16 cl, 340 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to cyclic derivatives of aminobenzoic acid and to their pharmaceutically acceptable salts of general formula , in which ring Ar is a phenyl group, a 5-member aromatic heterocyclic group containing 1-2 heteroatoms selected from nitrogen, sulphur and oxygen, or a benzothiazolyl group; where the said groups can have 1-2 substitutes selected from a group comprising lower alkyl; a phenyl group; a phenyl group substituted with 1-2 halogens; a phenyl group substituted with a lower alkoxy group; a phenyl group substituted with a halogen-substituted lower alkyl group; a phenoxy group substituted with a halogen; a halogen; Z is an oxygen atom or -(CH2)-n (where n equals 0, 1 or 2); Y is C1-C4 alkylene, C2-C4 alkenylene or general formula (2) -T-A-U- (2) in which T is a single bond, C1-C4 alkylene or C2-C4 alkenylene; U is single bond, C1-C4 alkylene; values of the rest of radicals are given in the formula of invention.

EFFECT: obtaining a PPARα, agonist which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid, and an agent which reduces the level of lipids which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid.

12 cl, 16 tbl, 184 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel bioisosteres of actinonin of general formula (I) , as well as to pharmaceutically acceptable salts thereof and pharmaceutical compositions based on said compounds, with peptide deformylase (PDF) inhibitory activity, as well as to use of the compounds or pharmaceutical compositions based on said compounds to prepare medicinal agents. In general formula (I) R1 is a hydrogen atom, R2 is a hydrogen atom, (C1-C6)alkyl residue, hetero(C1-C6)alkylphenyl residue, where the heteroatom is sulphur, R3 is a hydrogen atom, R4 is (C1-C6)alkyl residue, (C3-C7)cycloalkyl residue, R6 is a hydrogen atom, n is 1, 2 or 3. Values of substitute R5 are given in the formula of invention.

EFFECT: new compounds have useful biological activity.

8 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to methods of producing formula I compounds and their salts, , where R1 is H or F; and Boc is tert-butoxycarbonyl. These compounds are useful as intermediate products during production of tryptase inhibitors.

EFFECT: invention also relates to intermediate products, which can be used when producing said compounds, as well as to methods of producing such intermediate products and their use in production of said compounds.

20 cl, 7 ex

FIELD: medicine.

SUBSTANCE: invention relates to amidines of formula (I) and to their derivatives, methods for making thereof and pharmaceutical compositions containing amidines of formula (I). According to said invention, amidines are applicable for inhibition of IL-8 induced chemotactic factor, and can be applied to produce medicine agents for treating psoriasis, ulcerative colitis, melanoma, chronic obstructive pulmonary disease (COPD), bullous pemphigoid, rheumatoid arthritis, idiopathic fibrosis, glomerulonephritis and for preventing and treating injuries caused by ischemia and reperfusion.

EFFECT: higher clinical effectiveness.

7 cl, 6 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds satisfying general formula (I): where: R1 stands for direct or branched (C1-C7)alkyl, X stands for hydrogen atom, R2 stands for the group chosen from naphthalenyl, pyridinyl, isoquinoleinyl, thienyl, imidazolyl, benzothienyl, benzimidazolyl, indolyl, benzotriazolyl and optionally substituted with one or more substitutes chosen from halogen atoms and following groups: (C1-C4)alkyls, thio(C1-C4)alkyls or phenyls, optionally substituted with one or more substitutes chosen from halogen atoms or trifluoromethyl, as free base or additive salt with acid. Additionally, the invention concerns medical product, pharmaceutical composition, and application.

EFFECT: production of new biologically active compounds active to specific inhibitors of glycine glyt 1 and/or glyt 2 carriers.

6 cl, 3 ex, 1 tbl

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to piperidine- and piperazine-substituted N-hydroxyformamides of the general formula (I) or their pharmaceutically acceptable salts wherein B represents phenyl group monosubstituted at 3- or 4-position with halogen atom or trifluoromethyl group or bisubstituted at 3- and 4-position with halogen atom (that can be similar or distinct); or B represents 2-pyridyl or 2-pyridyloxy-group monosubstituted at 4-, 5- or 6-position with halogen atom, trifluoromethyl group, cyano-group or (C1-C4)-alkyl; or B represents 4-pyrimidinyl group possibly substituted with halogen atom or (C1-C4)-alkyl at 6-position; X represents carbon or nitrogen atom; R1 represents trimethyl-1-hydantoin-(C2-C4)-alkyl or trimethyl-3-hydantoin-(C2-C4)-alkyl group; or R1 represents phenyl or (C2-C4)-alkylphenyl monosubstituted at 3- or 4-position with halogen atom, trifluoromethyl group, thio-group, (C1-C3)-alkyl or (C1-C3)-alkoxy-group; or R1 represents phenyl-SO2NH-(C2-C4)-alkyl; or R1 represents 2-pyridyl or 2-pyridyl-(C2-C4)-alkyl; or R1 represents 3-pyridyl or 3-pyridyl-(C2-C4)-alkyl; or R1 represents 2-pyrimidine-SCH2CH2; or R1 represents 2- or 4-pyrimidinyl-(C2-C4)-alkyl possibly monosubstituted with one of the following substitutes: halogen atom, trifluoromethyl, (C1-C3)-alkyl, (C1-C3)-alkoxy-group, 2-pyrazinyl possibly substituted with halogen atom, or 2-pyrazinyl-(C2-C4)-alkyl possibly substituted with halogen atom. Also, invention describes a method for synthesis (variants) of compounds of the formula (I) and a pharmaceutical composition. Compounds can be used as inhibitors of metalloproteinases and useful in such morbidity states as inflammatory and allergic ones.

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical compositions.

12 cl, 1 tbl, 10 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivative of benzene or its salt of the formula (I): wherein X1 means -C(=O)-NR5-, -NR5-C(=O)-; X2 means -NR6-C(=O)-, -NR6-CH2-; R1 means halogen atom, lower alkyl or lower alkoxy-group; R2 and R3 mean hydrogen or halogen atom; R4 means hydrogen atom, -SO3H- or sugar residue; ring A represents benzene or pyridine ring; ring B represents piperidine ring, and a pharmaceutical composition based on thereof. Proposed compounds possess anti-coagulating effect based on inhibition of blood coagulation activated factor X that are useful as anti-coagulants or prophylactic agents against diseases caused by thrombosis and embolism.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

5 cl, 9 tbl, 38 ex

The invention relates to new piperidine derivative of formula (I)

< / BR>
where X represents the group< / BR>
Ar represents phenyl, one-deputizing or disubstituted by a halogen atom or (C1-C3)alkyl, R1represents a chlorine atom, a bromine atom, (C1-C3)alkyl or trifluoromethyl, R2represents a group-CR3R4СОNR5R6, R3and R4represent identical radicals selected from methyl, ethyl, n-propyl or n-butyl, or R3and R4together with the carbon atom form a (C3-C6)cycloalkyl, R5and R6represent hydrogen, (C1-C3)alkyl or together with the nitrogen atom form a 4-morpholinyl, or their salts, solvate or hydrate

Iap inhibitors // 2425838

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

, which can inhibit binding of protein Smac with apoptosis protein inhibitor (IAP).

EFFECT: improved properties of the inhibitor.

4 cl, 198 ex

Up!