9-aryl-6,8,20-trioxa-13-azapentacyclo[11,8,0,01,10,02,7014,19]heneicosa-9,14,16,18-tetraene-11,12,21-triones and method for production thereof

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 9-aryl-6,8,20-trioxa-13-azapentacyclo-[11.8.0.01,10.02,7.014,19]heneicosa-9,14,16,18-tetraene-11,12,21-triones (IIa-d), which includes reacting 3-aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones (Ia-d) with 3,4-dihydro-2H-pyran in a medium of an inert aprotic solvent, followed by separation of the end products. In general formula (I) Ar=Ph (a, d), C6H4Br-4 (b), C6H4OMe-4 (c), R=H (a-c), Cl (d).

EFFECT: obtaining 9-aryl-6,8,20-trioxa-13-azapentacyclo-[11,8,0,01,10,02,7,014,19]heneicosa-9,14,16,18-tetraene-11,12,21-triones.

2 cl, 1 tbl, 5 ex

 

The invention relates to the field of organic chemistry, namely to new individual compounds of the class 6,8,20-trioxa-13-isopentenyl[11.8.0.01,10.02,7.014,19]heneicosane and to method of their production, which can be used as starting materials for the synthesis of new heterocyclic systems.

Known structural analogue of the claimed compounds - ethyl 19-(trimethylsiloxy)-17-methoxy-14,15-diokso-5,7-dioxa-13-isopentenyl-[11.7.0.1,16.02,10.04,8]eicosa-2,4(8),9,18-tetraen-16-carboxylate obtained by the interaction of ethyl 2,3-diokso-2,3,5,6-tetrahydrooxazolo[1,2-α]-[1,3]dioxolo[4',5':4,5] benzo[C]Azin-1-carboxylate with 1-methoxy-3-(trimethylsiloxy)-1,3-butadiene carried out by exposing the reactants at a temperature of 130°C for 3 hours (T. Sano, J. Toda, N. Kashiwaba et al., Heterocycles, 1981, v. 16, No. 7, p.1151-1156).

The disadvantages of this method include the inability to obtain 9-aryl-6,8,20-trioxa-13-isopentenyl[11.8.0.01,10.02,7.014,19]heneicosan-9,14,16,18-tetraen-11,12,21-trions.

The object of the invention is to develop a simple method for the synthesis undescribed in the literature, 9-aryl-6,8,20-trioxa-13-isopentenyl[11.8.0.01,10.02,7.014,19]heneicosan-9,14,16,18-tetraen-11,12,21-trions.

The task is carried out by boiling 3-aroyl-1H-imidazo[2,1-C][1,4]benzoxazin-1,,4-trions (Ia-d) with 3,4-dihydro-2H-Piran in an inert aprotic solvent according to the following scheme:

The process is conducted at a temperature of 110°C, and the solvent used absolute toluene.

From the patent and technical literature were not identified ways to get the 9-aryl-6,8,20-trioxa-13-isopentenyl [11.8.0.01,10.02,7.014,19]-heneicosan-9,14,16,18-tetraen-11,12,21-trions, sharing similar characteristics with the claimed method, namely not used starting materials, the solvent in which the reaction takes place, on what basis can you conclude that the claimed technical solution the criteria of "novelty" and "inventive step".

The invention is illustrated by the following examples.

Example 1. 9-Phenyl-6,8,20-trioxa-13-isopentenyl-[11.8.0.01,10.02,7.014,19]heneicosan-9,14,16,18-tetraen-11,12,21-Tryon(IIA).

To a solution of 3.0 mmol of 3-benzoyl-1H-imidazo[2,1-C][1,4]benzoxazine-1,2,4-Tryon (Ia) in 20 ml of absolute toluene was added a solution of 4.5 mmol of 3,4-dihydro-2H-PYRAN in 5 ml of absolute toluene was boiled for 30 min, cooled, precipitated precipitate was filtered. Yield 32%, t a MP 299-300°C (decomp., toluene). The compound (IIA) C23H17NO6.

Found, %: C, 68.58; H 4.24; N, 3.56.

Calculated, %: C, 68.48; H, 4.25; N, 3.47.

The compound (IIA) is a pale yellow crystalline solid, difficultly soluble in DMSO, DMF and in the usual organic solvents, insoluble in water and Elkanah. Mouth�Ichigo when stored under normal conditions.

In the IR spectrum of compound (IIA), filmed in the form of paste in vaseline oil, are the bands of stretching vibrations of lactone carbonyl group (C21=O in the field of 1785 cm-1, lactam carbonyl group (C12=O in the area of 1736 cm-1, ketonic carbonyl group C11=O in the field 1714 cm-1.

In the PMR spectrum of the compound (IIA), filmed in a solution of DMSO-d6except for the signals of the protons of the aliphatic substituents, aromatic rings and related groups, are present doublet methane group C7H when 5.74 M. D., a multiplet methane group2N, at 2.30 M. D.

Example 2. 9-(4-Bromophenyl)-6,8,20-trioxa-13-isopentenyl-[11.8.0.01,10.02,7.014,19]heneicosan-9,14,16,18-tetraen-11,12,21-Tryon (IIB).

To a solution of 3.0 mmol of 3-(4-bromobenzoyl)-1H-imidazo[2,1-C]-[1,4]benzoxazine-1,2,4-Tryon (IB) in 20 ml of absolute toluene was added a solution of 4.5 mmol of 3,4-dihydro-2H-PYRAN in 5 ml of absolute toluene was boiled for 10 min, cooled, precipitated precipitate was filtered. The yield of 20%, a MP 274-275°C (decomp., toluene). The compound (IIB) C23H16BrNO6.

Found, %: C, 57.36; H, 3.35; N, 2.95; Br 16.69.

Calculated, %: C, 57.28; H, 3.34; N, 2.90; Br 16.57.

The compound (IIB) is a pale yellow crystalline solid, sparingly soluble in DMSO, DMF and in the usual organic solvents, insoluble in water and Elkanah. Stable when stored under normal conditions.

In the IR spectrum of compound (IIB), filmed in the form of paste in vaseline oil, are the bands of stretching vibrations of lactone carbonyl group With21=O in the field of 1782 cm-1, lactam carbonyl group With12=O in the field 1738 cm-1, ketonic carbonyl group C11=O in the field 1705 cm-1.

In the PMR spectrum of the compound (IIB), filmed in a solution of DMSO-d6except for the signals of the protons of the aliphatic substituents, aromatic rings and their associated groups are present doublet methane group7N when 5.74 M. D., a multiplet methane group2H at 2.47 M. D.

Example 3. 9-(4-Methoxyphenyl)-6,8,20-trioxa-13-isopentenyl-[11.8.0.01,10.02,7.014,19]heneicosan-9,14,16,18-tetraen-11,12,21-Tryon (IIB).

To a solution of 3.0 mmol of 3-(4-methoxybenzoyl)-1H-imidazo[2,1-C]-[1,4]benzoxazine-1,2,4-Tryon (IB) in 20 ml of absolute toluene was added a solution of 4.5 mmol of 3,4-dihydro-2H-PYRAN in 5 ml of absolute toluene was boiled for 30 min, cooled, precipitated precipitate was filtered. Output 25%, t a MP 272-274°C (decomp., toluene). The compound (IIB) C24H19NO7.

Found, %: C, 66.59; H, 4.47; N, 3.30.

Calculated, %: C, 66.51; H 4.42; N, 3.23.

The compound (IIB) is a pale yellow crystalline solid, difficultly soluble in DMSO, DMF and in the usual organic solvents, insoluble in water and Elkanah. Stable when stored under normal conditions.

In the IR spectrum of compound (IIB), filmed in the form of paste in vaseline oil, are the bands of stretching vibrations of lactone carbonyl group With21=O in the area of 1780 cm-1, lactam carbonyl group With12=O in the field of 1737 cm-1, ketonic carbonyl group With11=O in the field 1699 cm-1.

In the PMR spectrum of the compound (IIB), filmed in a solution of DMSO-d6except for the signals of the protons of the aliphatic substituents, aromatic rings and their associated groups are present doublet methane group7N when 5.71 M. D., a multiplet methane group2H at 2.44 M. D.

Example 4. 9-Phenyl-16-chloro-6,8,20-trioxa-13-isopentenyl-[11.8.0.01,10.02,7.014,19]heneicosan-9,14,16,18-tetraen-11,12,21-Tryon (IIG).

To a solution of 3.0 mmol of 3-benzoyl-8-chloro-1H-imidazo[2,1-C]-[1,4]benzoxazine-1,2,4-Tryon (1 g) in 20 ml of absolute toluene was added a solution of 4.5 mmol of 3,4-dihydro-2H-PYRAN in 5 ml of absolute toluene was boiled for 15 min, cooled, precipitated precipitate was filtered. The yield of 24%, t a MP 277-278°C(sec., toluene). Compound (IIG)23N16ClO6.

Found, %: C 63.15; H 3.61; N, 3.22; Cl 8.15.

Calculated, %: C 63.09; H 3.68; N, 3.20; Cl 8.10.

Compound (IIG) is a pale yellow crystalline solid, difficultly soluble in DMSO, DMF and in the usual organic solvents, insoluble in water and Elkanah. Stable when stored under normal conditions�H.

In the IR spectrum of compound (IIG), filmed in the form of paste in vaseline oil, are the bands of stretching vibrations of lactone carbonyl group With21=O in the field of 1785 cm-1, lactam carbonyl group With12=O in the area of 1736 cm-1, ketonic carbonyl group With11=O in the field 1714 cm-1.

In the PMR spectrum of the compound (IIG), filmed in a solution of DMSO-d6except for the signals of the protons of the aliphatic substituents, aromatic rings and their associated groups are the doublet retinovoy group C16H 5.73, M. D., a multiplet of retinovoy group17N2at 2.54 M. D.

The proposed method is easy to implement, one-step and allows you to get undescribed in the literature, 9-aryl-6,8,20-trioxa-13-isopentenyl[11.8.0.01,10.02,7.014,19]heneicosan-9,14,16,18-tetraen-11,12,21-trions (IIA-g), which can be used as starting materials for the synthesis of heterocyclic systems and in pharmacology as potential drugs.

Example 5. Pharmacologic study of 9-aryl-6,8,20-trioxa-13-isopentenyl[11.8.0.01,10.02,7.014,19]heneicosan-9,14,16,18-tetraen-11,12,21-trions (IIA-g) in the presence of analgesic activity.

Analgesic activity of compounds (IIA-g) relative to the dipyrone was determined by the method of thermal irritation "hot plates�and" Eddie and Leimbach on outbred mice weighing 18-22 grams (N. B. Eddy, Leimbarh D. J.-Pharmacol & Exper. Gher. 1953, 385-393). Statistical processing of the experimental data was performed using t student test (M. L. Belenky, Elements of quantitative evaluation of the pharmacological effect. - 2nd ed. - L., 1963. - p. 152). The effect was considered significant at p<0,05.

Studies have shown (see table) that the compounds (IIA, b, g) have an analgesic activity. Data on pharmacological activity of analogues of the claimed compounds available in the literature.

Table
The analgesic activity of compounds (IIA, b, g)
No. connectionDose, mg/kgBeing defensive reflex via
2 hours2.5 hours
IIa50,/b16,42±2,19
IIb50,/b19,84±2,22
IIG50,/b15,92±1,10
Control 2% of krahm. mucus50,/b8,95±0,7810,75±1,63
Metamizole sodium93 (U50) [2]16,33±3,02

1. A method of obtaining a 9-aryl-6,8,20-trioxa-13-isopentenyl-[11.8.0.01,10.02,7.014,19]heneicosan-9,14,16,18-tetraen-11,12,21-trions (IIa-g), characterized in that 3-aroyl-1H-imidazo[2,1-c][1,4]benzoxazine-1,2,4-trions (Ia-g) is subjected to interaction with 3,4-dihydro-2H-Piran in an inert aprotic solvent, followed by separation of the target products:

where Ar=Ph (a, d), C6H4Br-4 (b), S6N4OMe-4 (C), R=N (a-b), Cl (g).

2. A method according to claim 1, characterized in that the solvent used absolute toluene.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to 7R-substituted tris[1,2,5]oxadiazolo[3,4-b:3',4'-d:3",4"-f]-azepine derivatives of general formula (1) , where R denotes H, an NH2 group, an alkyl substitute: methyl, a substituted alkyl substitute: 2-hydroxyethyl, benzyl, furfuryl, tetrahydrofurfuryl, homoveratryl. The compounds are obtained by reacting 3,4-bis(4-nitrofurazan-3-yl)furazan with a compound, respectively selected from: ammonia, hydrazine, a compound containing a primary amine group: methylamine, 2-hydroxyethylamine, benzylamine, furfurylamine, tetrahydrofurfurylamine, homoveratrylamine. The technical result is 7R-substituted tris[1,2,5]oxadiazolo[3,4-b:3',4'-d:3",4"-f]-azepine derivatives, which are suitable as a component of explosive compounds, solid rocket propellants and energy compounds for different purposes, used at high temperatures.

EFFECT: high output.

2 cl, 1 dwg, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of obtaining a polymer conjugate of an indolocarbazole compound of formula (I), where R1, R2, R3, W1 and W2 represent hydrogen, X represents methoxy-polyethyleneglycol. The method includes the interaction of a polymer compound of formula (II) with an indolocarbazole compound of formula (III), where Y stands for a methoxygroup. The nvention also relates to a polymer conjugate of formula (I), a pharmaceutical composition, containing the conjugate of formula (I) as an active ingredient, and to the application of the polymer conjugate of formula (I).

EFFECT: obtaining the polymer conjugate of the formula with a high output, the polymer conjugate of the formula for treatment of skin pathologies and HMGB1-associated pathologies.

48 cl, 7 dwg, 7 tbl, 15 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to conjugates of Disorazol with cell adhesion molecules, such as peptides, proteins, hormones, blood proteins, and methods for preparing conjugates.

EFFECT: conjugates of Disorazol may be used as drug preparations for treating various tumours.

19 cl, 17 dwg, 2 tbl, 17 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel crystalline polymorphous forms of the rifaximin antibiotic (INN) known as rifaximin δ and rifaximin ε. The invention also relates to a method for synthesis of such polymorphs, which is realised through hot dissolution of crude rifaximin in ethanol and crystallisation of the product, which is induced by adding water at temperature of approximately 50°C and is carried out for approximately 4-36 hours, with subsequent drying at controlled conditions until attaining given content of water in the end product. Novel polymorphs have properties which enable to control rifaximin absorption when used as an antibiotic. The invention also relates to pharmaceutical compositions containing the novel polymorphous forms of rifaximin.

EFFECT: obtaining novel polymorphous forms of rifaximin.

20 cl, 2 tbl, 3 ex, 2 dwg

Organic compounds // 2394038

FIELD: medicine.

SUBSTANCE: new crystal form II N-benzoilstaurosporin is described, as well as pharmaceutical composition containing it, inhibiting protein kinase C; ways of obtaining crystalline form of compounds, and the use of crystal form of II N-benzoilstaurosporin for treatment neoplastic diseases. Crystalline form of II N-benzoilstaurosporin is a stable form of N-benzoilstaurosporin with low hygroscopicity.

EFFECT: suitability in pharmaceutical compositions.

21 cl, 2 tbl, 4 dwg, 16 ex

FIELD: medicine.

SUBSTANCE: invention refers to a compound of the formula , where R1 and R2 are different independent groups and are selected from the group consisting of OR3 and N (R3') (R3"); or R1 and R2 are different groups connected through a single bond and selected from the group consisting of O and NR3; R3, R3', and R3" are independently selected from the group consisting of H, phenyl, substituted phenyl, where substituents are independently selected from the group consisting of C1-C6 alkyl, halogen; R4 and R4': (a) independently selected from the group consisting of H, OH, a group of the formula ; R5, R6, and R7 are independently selected from the group consisting of OCH3; R8 and R9 are joined by (i) a single bond and represent CH2 or (ii) double bond and are CH; R15 are selected from the group consisting of C=O; n is equal to 2. The invention also refers to method for obtaining these compounds.

EFFECT: obtaining new compounds which can be used in medicine as neurodefensive and neurogenerative, antiproliferative and anti-inflammatory drugs.

43 cl, 7 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: regioselective synthesis of complex rapamycin 42-ether (CCI-779) involves: (a) acylation of 31-silyl rapamycin ether by compound of formula HOOC.CR7R8R9 or its combined anhydride, where: R7 is hydrogen, alkyl with 1-6 carbon atoms, alkenyl with 2-7 carbon atoms, alkinyl with 2-7 carbon atoms, -(CR12R13)fOR10, -CF3, -F or -CO2R10; R10 is hydrogen, alkyl with 1-6 carbon atoms, alkenyl with 2-7 carbon atoms, alkinyl with 2-7 carbon atoms, triphenylmethyl, benzyl, alcoxymethyl with 2-7 carbon atoms, chloroethyl or tetrahydropyranyl; R8 and R9 together form X; X is 2-phenyl-1,3,2-dioxaborinane-5-yl or 2-phenyl-1,3,2-dioxaborinane-4-yl, where phenyl can be optionally substituted; R12 and R13 each is independently hydrogen, alkyl with 1-6 carbon atoms, alkenyl with 2-7 carbon atoms, alkinyl with 2-7 carbon atoms, trifluormethyl or -F; and f=0-6; to obtain 42-ether boronate of 31-silyl rapamycin ether; (b) selective hydrolysis of 42-ether boronate of 31-silyl rapamycin ether in moderately acid environment to obtain rapamycin 42-ether boronate; and (c) diol treatment of rapamycin 42-etherboronate to obtain complex rapamycine 42-ether. Invention also claims new intermediate products applicable in this method.

EFFECT: application as antitumour medication.

48 cl, 3 ex

FIELD: organic chemistry, biochemistry.

SUBSTANCE: invention relates to some new macroheterocyclic compounds that can act as selective inhibitors of kinase or double kinase. Invention describes compounds of the following formulae: formula (Ia1), formula (Ib1), formula (If1), formula (Ii1), and formula (Ij1) wherein values R2, R4 and R5 are chosen by the dependent manner as given in the invention claim. Invention provides preparing new compounds possessing valuable biological properties.

EFFECT: valuable biological properties of compounds.

5 cl, 3 tbl, 22 ex

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

FIELD: chemistry.

SUBSTANCE: invention refers to a new compound, namely to 2-[(2-methylphenyl)imino]-9-oxo-7-phenyl-8-(3-phenyl-2-quinoxalinyl)-1,6-dioxaspiro[4,4]none-3,7-diene-3,4-dicarboxylic acid dimethyl ester of formula possessing antinociceptive activity, and a method for producing it consisting in synthesis of 4-(3-phenylquinoxalin-2-yl)-5-phenylfurane-2,3-dione, acetylene dicarboxylic acid dimethyl ester and o-methylphenylisonitrile.

EFFECT: preparing the new compound.

2 cl, 1 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound, represented by the following formula

,

or its pharmaceutically acceptable salt. In claimed formula each symbol has values, determined in formula of invention. Versions of formula [I] compound and particular compounds are also objects of invention. In addition, invention relates to pharmaceutical composition, ITK inhibitor and means for treatment or prevention of inflammatory diseases, allergic diseases, autoimmune diseases, transplant rejection and other diseases and methods of treating said diseases.

EFFECT: claimed compounds inhibit induced T-cellular kinase (ITK).

32 cl, 86 tbl, 387 ex

FIELD: medicine.

SUBSTANCE: application of a compound of the general formula 1 or its spatial isomers as analgesic means is claimed.

EFFECT: compounds have high efficiency, low toxicity, can be applied in medicine.

4 tbl 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

possessing properties of binding with delta opioid receptors. In formula I R1 is selected from the group, consisting of phenyl, pyridinyl and thiazolyl, with R1 being optionally substituted with one or two substituents, independently selected from the group, consisting of C1-4alkoxy, fluorine atom, chlorine atom, bromine atom and cyanogroup; in addition, R1 is optionally substituted with di(C1-4alkyl)aminocarbonyl; Y represents O, S, H3, vinyl, ethinyl or S(O); R2 represents a substituent, selected from the group, consisting of hydrogen, C1-4alkyl, C1-4alkoxy, C1-4alkylthio, fluorine atom, chlorine atom, bromine atom and hydroxy; Ra represents hydrogen or methyl; R3 is selected from the group, consisting of pyrrolidin-2-ylmethyl; pyrrolidin-3-ylmethyl; piperidin-2-ylmethyl, piperidin-3-ylmethyl, piperidin-4-ylmethyl, piperidin-2-ylethyl, piperidin-3-ylethyl, piperidin-4-ylethyl, pyridine-4-yl-(C1-2)alkyl, azetidin-3-ylmethyl; morpholin-2-ylmethyl, morpholin-3-ylmethyl, imidazolylmethyl, thiazolylmethyl, (amino)-C3-6cycloalkyl, 3-hydroxy-2-aminopropyl, 8-azabicyclo[3.2.1]octanyl, 1-azabicyclo[2.2.2]octanyl, guanidinylethyl, 4-(imidazol-1-yl)phenylmethyl, 2-(methylamino)ethyl, 2-diethylaminoethyl, 4-diethylaminobut-2-yl, piperidin-3-yl, piperidin-4-yl and pyrrolidin-3-yl; with piperidin-3-yl being optionally substituted on a carbon atom with phenyl; with pyrrolidin-2-yl in pyrrolidin-2-yl-methyl, pyrrolidin-3-yl, piperidin-3-yl and piperidin-4-yl being optionally substituted on a nitrogen atom with methyl, phenylmethyl, phenethyl or methylcarbonyl.

EFFECT: compounds can be used in the treatment of pain, induced by diseases or conditions, such as osteoarthritis, rheumatoid arthritis, migraine, burn, fibromyalgia, cystitis, rhinitis, neuropathic pain, idiopathic neuralgia, toothache, etc.

24 cl, 3 tbl, 19 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to pharmaceutical industry, namely to composition for treating skin ageing. Composition for treating signs of skin ageing, increase of cytikin IL-1α secretion, contains: NF-kB inhibitor, selected from the group, consisting of substituted resorcinols, (E)-3-(4-methylphenylsulphonyl)-2-propenenitrile, tetrahydrokurkuminoids, extracts of Paulownia tomentosa wood, as well as their combinations, and anti-inflammatory compound, which is not NF-kB inhibitor. Composition for treating signs of skin ageing, increase of cytokine IL-1α, containing NF-kB inhibitor, selected from the group, consisting of substituted resorcinols, and anti-inflammatory compound (versions).

EFFECT: compositions are effective for treating signs of skin ageing.

4 cl, 9 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention aims at pharmaceutical compositions containing a number of microparticles with taste masking, containing high-/low-dose therapeutic agents, at dosage forms containing the above pharmaceutical compositions (such as orally dispersible tablets), and at methods for producing these pharmaceutical compositions and dosage forms.

EFFECT: dosage forms containing the pharmaceutical compositions according to the invention represent the improved homogenous mixtures of the high-dose and low-dose therapeutic agents, which enable controlling the release rate of the therapeutic agent from particles by various ways, as well as flexible correction of dosages when administering the combinations of the therapeutic agents, eg in pain management.

31 cl, 4 dwg, 12 tbl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of the general formula

,

wherein R1/R2 independently represent hydrogen, (CR2)o-C3-7 cycloalkyl optionally substituted by a lower alkyl or hydroxy, or represent a lower alkyl or tetrahydropyranyl, and o represents 0 or 1; and R can be identical or different, and represent hydrogen or a lower alkyl; or R1 and R2 can form together with a N atom to which they are attached, a heterocycloalkyl group specified in a group consisting of pyrrolidinyl, piperidinyl, 3-aza-bicyclo[3.1.0]hex-3-yl or 2-aza-bicyclo[3.1.0]hex-2-yl which are optionally substituted by hydroxy; R3 represents an S-lower alkyl, lower alkyl, lower alkoxy or C3-7 cycloalkyl; R3′ represents hydrogen, a lower alkyl substituted by a halogen, lower alkyl or lower alkoxy; R4 represents a lower alkyl substituted by a halogen; X represents -O- or -CH2-; X' represents -O- or -CH2-; provided one of X or X' always represent -O- and the other represents -CH2-; or a pharmaceutically acceptable acid-additive mixture, a racemic mixture, or a respective enantiomer and/or an optical isomer.

EFFECT: compounds of the general formula (I) are good inhibitors of glycine transporter 1 (GlyT-1) and hence can be used for treating schizophrenia and other neurological conditions, including pain.

13 cl, 1 tbl, 63 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel N-containing heteroaryl derivatives of formula I or II or their pharmaceutically acceptable salts, which possess properties of JAK kinase, in particular JAK3, and can be applied for treating such diseases as asthma and chronic obstructive pulmonary disease (COPD). In formulae A represents carbon and B represents nitrogen or A represents nitrogen and B represents carbon; W represents CH or N; R1 and R2, independently represent hydrogen, C1-4alkyl, halogenC1-4alkyl, -CN; R3 represents C1-4alkyl, R9-C1-4alkyl, Cy1, where Cy1 is optionally substituted with one or several substituents R10; R4 represents hydrogen, C1-4alkyl, R12R7N-C0alkyl, where one of R7 and R12 represents hydrogen, and the other represents C1-4alkyl or group R13, which is selected from C1-5alkyl, Cy2-C0alkyl; R5 represents hydrogen; R6 represents hydrogen, C1-4alkyl, C1-4alkoxyC1-4alkyl, hydroxyC1-4alkyl, R12R7N-C1-4alkyl, R16CO-C0alkyl, Cy1; R7 represents hydrogen or C1-4alkyl; R9 represents halogen, -CN, -CONR7R12, -COR13, CO2R12, -OR12, -SO2R13, -SO2NR7R12, -NR7R12, -NR7COR12; R10 represents C1-4alkyl or R9-C0-4alkyl; R11 represents C1-4alkyl, halogen, -CN, -NR7R14; R12 represents hydrogen or R13; R13 represents C1-5alkyl, hydroxyC1-4alkyl, cyanoC1-4alkyl, Cy2-C0alkyl or R14R7N-C1-4alkyl; where Cy2 is optionally substituted with one or several constituents R11; R14 represents hydrogen or C1-4alkyl; R16 represents C1-4alkyl, halogenC1-4alkyl, C1-4alkoxyC1-4alkyl, hydroxyC1-4alkyl or cyanoC1-4alkyl; Cy1 represents monocyclic carbocyclic unsaturated or saturated ring, selected from C3-C6cycloalkyl, phenyl, or saturated monocyclic 4-6-membered heterocyclic ring, containing from 1 to 2 heteroatoms, selected from N and S, or partially unsaturated 10-membered bicyclic heterocyclic ring, containing oxygen atom as heteroatom, which can be substituted with group R11, where said ring is bound with the remaining part of molecule via any available C atom, and where one or several ring C or S atoms are optionally oxidised with formation of CO or SO2; and Cy2 represents monocyclic carbocyclic unsaturated ring, selected from C3-C6cycloalkyl, or aromatic monocyclic 4-6-membered heterocyclic ring, containing from 1 to 2 heteroatoms, selected from N and S, or unsaturated 10-membered bicyclic heterocyclic ring, containing oxygen atom as heteroatom, which can be substituted with group R11, where said ring is bound with the remaining part of molecule via any available atom C or N.

EFFECT: obtaining novel heteroaryl derivatives.

27 cl, 41 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula I, possessing ability of binding with delta-opioid receptors. In formula R1 is selected from the group, consisting of i) phenyl, optionally substituted with one-two substituents, independently selected from the group, consisting of C1-4alkyl, C1-4alcoxy, C1-4alkylthio, hydroxyl, di(C1-4alkyl), aminocarbonyl, chlorine and fluorine, in such a way that only one di(C1-4alkyl)aminocarbonyl is present; ii) naphthyl; iii) pyridinyl, optionally substituted with one substituent, selected from the group, consisting of C1-4alkyl, C1-4alcoxy, C1-4alkylthio, hydroxy, fluorine, chlorine and cyano; iv) pyrimidin-5-yl; v) furanyl; vi) thienyl; vii) 5-oxo-4,5-dihydro-[1,2,4]oxodiazol-3-yl; and viii) di(C1-2alkyl)aminocarbonyl; Y represents ethyl, vinyl or bond; or Y represents O, when R1 represents optionally substituted phenyl, where substituent represents C1-4alcoxy; R2 represents phenyl, optionally substituted with one-two substituents, independently selected from the group, consisting of C1-4alkyl, C1-4alcoxy, fluorine, chlorine and cyano, trifluoromethoxy and hydroxy; or R2 represents phenyl, substituted with one aminocarbonyl, di(C1-4alkyl)aminocarbonyl, C1-4alcoxycarbonyl or carboxysubstituent; R3 is selected from the group, consisting of i) 3-aminocyclohexyl; ii) 4-aminocyclohexyl; iii) piperidin-3-yl; iv) piperidin-4-yl; v) pyrrolodin-2-yl-methyl, in which pyrrolodin-2-yl is optionally substituted by 3-rd or 4-th position with one or two fluorine-substituents; vi) azetidin-3-yl; vii) 2-(N-methylamino)ethyl; viii) 3-hydroxy-2-aminopropyl; ix) piperidin-3-yl-methyl; x) 1-azabicyclo[2.2.2]octan-3-yl; and xi) 8-azabicyclo[3.2.1]octan-3-yl; or R3 together with Ra and nitrogen atom, which they both are bound to, form piperazinyl, optionally substituted with 4-C1-4alkyl; Ra represents hydrogen, 2-(N-methylamino)ethyl or C1-2alkyl, optionally substituted with azetidin-3-yl.

EFFECT: compounds can be used in treatment of pain in the range from medium to strong, caused by diseases or conditions, such as osteoarthritis, migraine, burn, fibromyalgia, cystitis, rhenite, neuropathic pain, idiopathic neuralgia, toothache, etc.

21 cl, 4 tbl, 26 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to substituted phenylureas and phenylamides of formula in which X stands for CR3 or N, where R3 stands for H; C1-10alkyl, saturated or unsaturated, branched or non-branched, non-substituted; or CF3; A stands for N or CR5b; R1 stands for substructure , which has the formula, given below. The other radicals and symbols have the values, given in the invention formula. The invention also relates to methods of obtaining formula (If) compounds, to pharmaceutical compositions, containing the said compounds, as well as to the application of the said compositions for the preparation of the pharmaceutical compositions.

EFFECT: formula (If) compounds possess activity with respect to the vanilloid receptor of I subtype (receptor VR1/TRPV1).

7 cl, 1 tbl, 147 ex

FIELD: medicine.

SUBSTANCE: invention refers to a method of treating tuberculosis with multiple drug resistance characterised by prescribing a combination of six anti-tuberculosis preparations in the intensive phase of chemotherapy and five preparations - in the phase of the 20-month therapy continuation, wherein the intensive phase duration makes at least 8 months until obtaining four negative culture results every month in tuberculosis with multiple drug resistance and until obtaining two negative culture results in all other cases of tuberculosis with multiple drug resistance, the phase of the therapy continuation makes 12 months.

EFFECT: higher clinical effectiveness.

1 tbl, 9 ex

Up!