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 showing antinociceptive activity and method for producing it

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

 

The invention relates to the field of organic chemistry, to develop a method of synthesis of hard-substituted dimethyl ester of 9-oxo-1,6-dioxaspiro[4.4]non-3,7-diene-3,4-dicarboxylic acids, namely dimethyl ether 2-[(2-methylphenyl)imino]-9-oxo-7-phenyl-8-(3-phenyl-2-chinoxalin)-1,6-dioxaspiro[4.4]non-3,7-diene-3,4-dicarboxylic acid of the formula (1)

exhibiting antinociceptive activity, which can find application in medicine as a drug. As a benchmark comparison of the biological activity was taken Metamizole sodium [M. D. Mashkovsky. Medicines. - M.: New wave, 2010. - P. 164].

Known structural analogue of the claimed compounds - dimethyl ether 5'-(cyclohexylamino)-4,6-dimethyl-3-oxaspiro[benzofuran-2(3H), 2'(5'H)furan]-3',4,-dicarboxylic acid (2) obtained three-component synthesis of 4,6-dimethylbenzofuran-2,3-dione, cyclohexyldiamine and dimethyl ether acetylenedicarboxylic acid [A. A. Esmaeili, Vesalipoor H. Reaction of Isocyanides, Diakyl Acetylenedicarboxylates, and α-KetoLactones: Unexpected Participation of an Esters Carbonyl Group in the Isocyanide-Based Three-Component Reaction / Synthesis, 2009. No. 10. P. 1635-1638]. Biological activity structural analog unknown.

The structural analog synthesis is carried out according to the following scheme:

The disadvantages of this method-prototype �tositsa the inability to obtain dimethyl ether 2-[(2-methylphenyl)imino]-9-oxo-7-phenyl-8-(3-phenyl-2-chinoxalin)-1,6-dioxaspiro[4.4]non-3,7-diene-3,4-dicarboxylic acid.

The object of this invention is to develop a method of synthesis of previously undescribed dimethyl ether 2-[(2-methylphenyl)imino]-9-oxo-7-phenyl-8-(3-phenyl-2-chinoxalin)-1,6-dioxaspiro[4.4]non-3,7-diene-3,4-dicarboxylic acid (1) showing antinociceptive effect and has a lower toxicity than the known medicines.

The task is carried out by three-component synthesis of 4-(3-phenylindolin-2-yl)-5-phenylfuro-2,3 dione, dimethyl ether acetylenedicarboxylic acid and o-methylphenylacetonitrile scheme

The technical result - expanding Arsenal of means of influence on a living organism.

The invention is illustrated by the following examples.

Example 1. The preparation of the compound (1). A solution of 1.1 mmol of o-methylphenyl of isocyanide in 10 ml of absolute 1,2-dichloroethane was cooled to -10°C, was dripped a solution of 1 mmol of 4-(3-phenylindolin-2-yl)-5-phenylfuro-2,3-dione and 1.1 mmol of dimethyl ether acetylenedicarboxylic acid in 10 ml of absolute 1,2-dichloroethane, cooled to -10°C. the Mixture was stirred at room temperature for 2 hours. The solvent was removed, the residue was erased from ethanol, recrystallized from ethyl alcohol. The yield was 0.54 g (84%). TPL=145-147°C. Found, %: C, 71.50; H, 4.35; N, 6.66. C38H27N3O7. Calculated, %: C 7.58; H 4.27; N, 6.59. The IR spectrum (FSM 1201, vaseline oil, ν, cm-1): 1752 (CO2Me), 1736 (CO2Me), 1723 (C=O), 1687 (C=N). The NMR spectrum1H (Varian Mercury 300 (300 MHz), DMSO-d6, GMDS, δ, M. D.): 2.13 (3H, CH3), 3.85 (3H, CH3O), 3.99 (3H, CH3O), 7.05-8.22 m (18H, 2C6H4+2C6H5). Mass spectrum, m/z (IRel., %): 637 (100) [M]+.

The resulting compound (1) is a yellow crystalline substance insoluble in water, hexane, sparingly soluble in ethyl alcohol, easily soluble in DMSO and chloroform.

Example 2. Acute toxicity of compound (1). Acute toxicity (LD50mg/ml) compound (1) was studied on white mice (females) weighing 16-18 g by a single intraperitoneal injection. The animals were observed for 10 days, fixing the behavior, the intensity and nature of physical activity, the presence and nature of seizures, coordination of movements, the tone of the skeletal muscles, response to tactile, auditory and visual stimuli, the frequency and depth of respiratory movements, heart rhythm, the condition of the hair and skin, the color of the visible mucous membranes, the consumption of food and water, change of body weight.

Calculated acute toxicity, following the recommendations of the state pharmacological Committee for the study of General toxic action of biologically active substances[Methodical recommendations for study of General toxic effect of pharmacological agents. Approved. 25.12.97./ Vestn. pharmacop. Committee. - 1998. - No. 1. - P. 27-32.].

For the studied compounds (1) LD50is >1500 mg/kg. According to the classification of the toxicity of preparations of compound (1) refer to the V class is practically non-toxic drugs [Izmerov N. F., Sanok I. V., Sidorov, K. K. Settings toxicometric industrial poisons. - M.: Medicine, 1977. - P. 196], whereas sodium metamizol

Example 3. Antinociceptive activity of compound (1)

Evaluation of antinociceptive (analgesic) activity of compound 1 was studied in outbred mice weighing 18-22 grams method "acetic cramps". The test substance was administered at a dose of 25 mg/kg, I/p) as a suspension in 2% starch mucus 30 minutes before in b/W the introduction of a 0.75% solution of acetic acid (0.1 ml/10 gram body weight). In the next 15 minutes after injection was counting the number of writhing for each animal. Reducing the number of writhing in animals compared with the control group was an indicator of analgesic activity of substances. Antinociceptive activity was expressed as percent decrease in the number of acetic writhing in the experimental animals compared to control groups. Each connection was tested with 6 animals.

Statistical processing of the experimental data was performed using t student test [Belenky M. L. Elements of kolichestvo�the second evaluation of the pharmacological effect. - 2nd ed. - L., 1963. - P. 152]. The effect was considered significant at p<0,05.

Example 4. Antinociceptive activity of compound (1).

Antinociceptive activity of compound (1) was studied in outbred mice weighing 18-22 g with test "hot plate" [Radell Z. O., Selitto J. J. A method for measurement of analgesic activity on inflamed tissue. // Arch. Intermat. Pharmacodun. Et ther. 1957. - Vol.11. - No. 4 - S. 409-419].

The investigated compound was administered intraperitoneally in a 2% starch mucilage in the dose of 50 mg/kg at 0.5 h before placing the animals on a heated to 53.5°C metal plate. Indicator of pain sensitivity served as the duration of stay of the animal on the hot plate until the licking of the hind paws, measured in seconds. As ethanol comparison of analgesic activity taken Metamizole sodium [M. D. Mashkovsky. Medicines.- M.: New wave, 2010. - P. 164]. The test results are shown in the table.

Table 1
Antinociceptive activity of compounds (1) according to the methods of the "hot plate" and "acetic cramps"
№ p/pThe cipher of connectionsDose mg/kg route of administration in a/b"Hot plate" "Acetic cramps"
Being defensive reflex after 120 min.The number of writhing% reduction in writhing to the controlActivity %
1Control 2% of krahm., mucus5010,10±1,32
2525,20±2,32100
2Metamizole sodium93 (U50)16,33±3,02 p<0,1
55To 10.06±1,38The 42.657,9
315031,00±3,36 p<0,05
25 11,60±1,5046,0353,97

As the table shows, the inventive compound (1) exhibits a pronounced antinociceptive activity, is practically non-toxic. Therefore, the claimed compound (1) may find application in medical practice as analgesic drugs.

1. Dimethyl ether 2-[(2-methylphenyl)imino]-9-oxo-7-phenyl-8-(3-phenyl-2-chinoxalin)-1,6-dioxaspiro[4.4]non-3,7-diene-3,4-dicarboxylic acid of the formula (1)

possess antinociceptive activity.

2. A method of producing dimethyl ether 2-[(2-methylphenyl)imino]-9-oxo-7-phenyl-8-(3-phenyl-2-chinoxalin)-1,6-dioxaspiro[4.4]non-3,7-diene-3,4-dicarboxylic acid (1)

harakterizuetsya the fact that carry out the three-component synthesis of 4-(3-phenylindolin-2-yl)-5-phenylfuro-2,3-dione, dimethyl ether acetylenedicarboxylic acid and o-methylphenylacetonitrile.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to dispiro 1,2,4-trioxolanes of formula: , where values of R are given in claim 1.

EFFECT: disclosed compounds unexpectedly enable to treat malaria with a single dose and provide preventive action against malaria and bilharzia.

17 cl, 6 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compound with spirochiral carbon base, or its pharmaceutically acceptable salt of general formula 1 , where W represents CO or CHO(C=O)CH3; X represents N3 or OR2; R2 represents hydrogen, linear or branched alkyl C1~C8 or Y represents O; Z represents simple bond or O; R3 represents linear or branched alkyl C1~C8 or alkenyl C2~C8, and M and N represent, each independently, hydrogen, OH or are absent; carbon atom, bound with M or N forms simple bond or double bond with other carbon atoms, and number of double bonds constitutes one or less for each of carbon atoms. Invention relates to method of obtaining and pharmaceutical compositions.

EFFECT: compound with spirochiral carbon base possesses excellent activity of osteoblast differentiation, activity of inhibiting mast cells and activity of inhibiting synthesis of fatty acids in liver that is why compound will play leading role in treatment of steoporosis, fatty liver dystrophy and obesity.

13 cl, 6 ex, 5 tbl, 17 dwg

FIELD: chemistry.

SUBSTANCE: present invention relates to a sterile aqueous solution of fluorescein for angiography and a method of obtaining fluorescein with special impurity content. The disclosed solution contains 10-25 wt % fluorescein in form of a sodium salt, where the only impurity of resorcinol and fluorescein-related compounds with molecular weight of 258, 284, 346, 332, 424, 374 and 738 is present in amount of not more than 0.1 wt % fluorescein, or the total amount of said impurities is not more than 0.6 wt % fluorescein, and where content of chloride is less than 0.25 wt % fluorescein. Fluorescein with said nature of impurities is obtained by conducting deacetylation of commercial-grade fluorescein with an acetic anhydride as a reagent and a solvent to obtain O,O'-diacetyl fluorescein with purity of 99.7%; after basic hydrolysis of which activated carbon is added; filtered; ethanol is added to the filtrate until achieving ethanol-to-water ratio of 2:1; pH of the solution is brought to a value of 1.0-2.5 by adding HCl solution while cooling for 2-4 hours; the precipitate is filtered, washed with water and ethanol and dried.

EFFECT: fluorescein obtained using the method disclosed herein is slightly coloured, reduces hypertonicity of the solution for injection obtained therefrom, and also has low content of impurities which can be toxic or non-fluorescent.

7 cl, 20 dwg, 10 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: compound has general formula (where R1 and R3 are identical or different, and each denotes a hydrogen atom or C1-6alkyl; R2 denotes, for example, 5,5-dimethyl-1,3-dioxan-2-yl, 5,7-dioxaspiro[2.5]oct-6-yl, 1,5,9-trioxaspiro [5.5]undec-3-yl, 2,2-dimethyl-1,3-dioxan-5-yl etc; R4, R5, R6 and R7 each denotes a hydrogen atom, a halogen atom, C1-6 alkyl, C1-6 halogenalkyl, C1-6 alkoxy, C1-6 halogenalkoxy etc, and W1 denotes a single bond, methylene or ethylene, or salt thereof.

EFFECT: compound has excellent inhibiting activity towards secretion of gastric hydrochloric acid and more effectively in preserving inhibiting activity towards secretion of gastric hydrochloric acid, can maintain pH in the stomach for a long period of time, is safe and has acceptable physical and chemical resistance.

40 cl, 4 tbl, 97 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted cycloalkene derivatives of formula (I) in which X and Y are a group, in which X and Y together with a carbon atom on ring B to which they are bonded form a ring A, X and Y together represent a ring B substitute, or each of X and Y is a hydrogen atom.

EFFECT: invention relates to a medicinal agent based on the said compounds, which has inhibitory effect on intracellular signal transduction or cell activation induced by an endotoxin.

21 cl, 3 tbl, 191 ex

FIELD: organic chemistry, insecticides.

SUBSTANCE: invention relates to compounds of formula I , wherein W is halogen, C1-C6-alkyl, C1-C6-alkoxy, C1-C4-haloalkyl or C1-C4-haloalkoxy; X is hydrogen, halogen, C1-C6-alkyl; Y is hydrogen, halogen, C1-C6-alkyl, C1-C4-haloalkyl, C1-C4-haloalcoxy or cyano; Z is hydrogen, halogen, etc.; G is halogen or nitro; meanings of the other substituents are as defined in specification. Also disclosed are methods for production of said compounds by interaction compounds of formula II with halogenation agents in presence of solvent and optionally of radical initiator of with fumed nitric acid in presence of solvent.

EFFECT: new compounds with insecticide activity.

17 cl, 20 tbl, 114 ex

FIELD: color-forming compositions and recording material.

SUBSTANCE: claimed composition includes developer containing urea-urethane compound and colorless or light colored leuco dye. Recording material based on this composition also is proposed.

EFFECT: color-forming compositions with improved image conservation ability and increased image intensity.

21 cl, 14 tbl, 153 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, pharmaceutics.

SUBSTANCE: invention relates to a novel compound of formula

(I)

or its pharmaceutically acceptable salt, possessing properties of the IKKβ and TNFα inhibitor. The compound can be used with an additional therapeutic agent, selected from vincristine, camptothecin hydrochloride (CPT-11), lefunomid, dexamethasone and TNFα. Preferable are compounds of formula (I), corresponding to 2-{5-chloro-2-[(1R,2R)-2-hydroxycyclopentylamino]pyrimidin-4-yl}-N-cyclopropyl-1H-indole-4-carboxamide and 2-{5-chloro-2-[(1R,2S)-2-hydroxycyclopentylamino]pyrimidin-4-yl}-N-cyclopropyl-1H-indole-4-carboxamide.

EFFECT: compound can be applied in the treatment of inflammatory diseases such as rheumatoid arthritis, chronic obstructive lung disease, bronchial asthma, multiple sclerosis and intestinal inflammatory diseases, or cancer diseases, such as multiple myeloma, colon cancer, pancreas cancer and ovary cancer, by IKKβ inhibition.

30 cl, 4 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to a new derivative of anthrafurandione of formula I or its pharmaceutically acceptable salts possessing high antitumour effect and activity on tumours resistant to other drug preparations. Besides, the invention refers to antitumour pharmaceutical compositions containing the compound of formula I, a pharmacologically acceptable carrier and one or mode excipients specified in co-solvents, solubilisers, filling agents, emulsifiers, preserving agents, antioxidants, buffer compounds, substances for maintaining isotonicity.

EFFECT: effective use of anthrafurandione, as it possesses high storage stability as a lyophilisate, and as a solution, and also other improved characteristics, including solubility, efficacy and acceptability.

10 cl, 6 tbl, 13 ex

FIELD: biotechnologies.

SUBSTANCE: invention relates to new heterogeneous ring compounds containing a pentatomic rings, condensed with other nuclei, only with one atom of oxygen as a heteroatom, namely to derivants of acetamid N-((1S)-1',2',3'-trimethoxy-6,7-dihydro-1H-benzo[5',6':5,4]cyclohepta-[3,2-f]benzofuran-1-il) with the general formula 1 , where R - substituent, R=Ph, pyridine-2-il, CH2OH, CH(CH3)OH, CH2CH2OH, CH2OAc, (CH2)8CO2Me or CH2N(CH2CH3)2, and also to their application as an active component of antitumoral medicinal preparation.

EFFECT: increase of activity with inhibition of proliferation of the tumour cells.

10 cl, 3 dwg, 8 ex

FIELD: chemistry.

SUBSTANCE: invention provides benzylidene furanone derivatives of (+)-usnic acid of formula 6-13 as anti-tumour agents. The compounds exhibit cytotoxic activity with respect to tumour cell lines CEM-13, U-937, MT-4.

EFFECT: high activity.

2 dwg, 3 tbl, 8 ex

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