Antibacterial compounds based on sulphanilic acid and pyridoxine

FIELD: chemistry.

SUBSTANCE: invention discloses a product of modification of sulphanilic acid, and specifically n-(1,5-dihydro-3-methyl-8-R1-8-R2-9-hydroxy-[1,3]dioxepino[5,6-c]pyridinyl-6-azo)phenylsulphonic acid and salt forms thereof of general formula I: , where R1, R2 are selected from a group comprising: a hydrogen atom, methyl, a linear or branched alkyl or R1 and R2 together form a spirocycloalkyl group. Compounds of formula (I) have antibacterial activity, are more efficient with respect to both gram-negative bacteria Proteus vulgaris, Pseudomonas aeroginosa and gram-positive bacteria Staphylococcus aureus, and can be used in medicine and veterinary.

EFFECT: improved properties.

1 cl, 1 tbl, 11 ex

 

The invention relates to synthetic biologically active substances heterocyclic series, having antimicrobial activity and representing the products modification of sulfanilic acid, namely n-(1,5-dihydro-3-methyl-8-R1-8-R2-9-hydroxy-[1,3]doxepin[5,6-C]pyridinyl-6-azo)vinylsulfonate and their salt forms of the General formula I

where R1, R2selected from the group of a hydrogen atom, methyl, linear, branched alkyl, or R1, R2, which together form spiratically group.

The compounds of formula (I) possess high antibacterial activity and the most effective against both gram-negative bacteria Proteus vulgaris, Pseudomonas aeroginosa, and gram-positive bacteria Staphylococcus aureus, and may find application in medicine and veterinary medicine.

Chemotherapeutic activity of sulfonamides was discovered in the early 30-ies. With infections caused by susceptible to them by microorganisms, sulfa drugs quite effective and relatively well tolerated, but some bacteria can be only of sulfa drugs [Mashkovsky PPM Medicines: 2 so [Text] / Medmaravis): New Wave, 2002]. However, because of the emergence of microbial strains resistant to existing the existing drugs, search for new, more effective analogues of sulfonamides, continues. A promising approach to solving this problem is the creation of safe and efficient systems of intracellular transport of active substances.

Many active substances are poorly overcome biological barriers due to the high hydrophilicity [O'shea R. Physicochemical Properties of Antibacterial Compounds: Implications for Drug Discovery [Text] / R.O'Shea, H.E.Moser // J. Med. Chem. - 2008. - V.51, N.10. - P.2871-2878], which negatively affects their antibacterial activity. In particular, sulfanilic acid in eight times more streptocide in experiments with immobilized enzymes [E.F. Gale The Molecular Basis of Antibiotic Action [Text] / E.F.Gale, E.Cundliffe, P.E.Reynolds, M.H.Richmond, .J.Waring. - London: Wiley & Sons, 1981. - 464 p.], but it does not show antibacterial activity due to low permeability through the cell membrane.

A number of compounds with antibacterial activity, known and among the derivatives of pyridoxine. It is known that 4-deoxypyridoxine and its esters possess antibacterial activity against Eimeria acervulina [Morisawa y, Kataoka M., Watanabe, T., Kitano n, Matsuzawa T. Studies on anticoccidial agents. 2. Synthesis and anticoccidial activity of pyridoxol analogs. // J. Med. Chem. - 1974. V.17, N.11. - P.1235-1237). Despite the low toxicity, antibacterial activity of the above compounds was low.

It should be noted that the above-described soybean is inane, according to the applicant, can be regarded as analogues to the claimed technical solution due to the fact that they do not coincide with the inventive compounds according to the chemical structure. The applicant has not identified the sources containing information about technical solutions, identical to the present invention, which allows to make a conclusion about its compliance with the criterion of "novelty".

The objective of the claimed technical solution is to create a new biologically active compounds with high antibacterial activity against both gram-negative bacteria Proteus vulgaris, Pseudomonas aeroginosa, and gram-positive bacteria Staphylococcus aureus.

The problem is solved by the synthesis of antimicrobial substances of General formula (I)

where R1, R2selected from the group of a hydrogen atom, methyl, linear, branched alkyl, or R1, R2, which together form spiratically group.

The claimed substances of General formula (I) can be used in neutral form or in the form of salts with cations of sodium, potassium, lithium, ammonium, magnesium, calcium or other pharmacologically acceptable cations.

The most similar chemical structure and purpose to the claimed antimicrobial substance are sulfanilic acid and antibacterial agents is streptocid, which were chosen as reference compounds for comparison of antibacterial activity.

The claimed substances showed high antibacterial activity against strains of Proteus vulgaris, Pseudomonas aeroginosa, Staphylococcus aureus, and may find application in medicine and veterinary medicine.

The applicant has not identified the sources, which would contain information about the impact of the distinctive features of invention achieved in the claimed technical solution the technical result. Specified a new property of the object determines, according to the applicant, according to the invention, the criterion of "inventive step", as it is not obvious to a person skilled in this technical field.

Proposed in the claimed technical solution of the compounds of formula (I) obtained according to the scheme below

Characteristics of the new compounds are given in the examples of specific performance.

Example 1. Synthesis of 1,5-dihydro-3,8-dimethyl-[1,3]doxepin[5,6-C]pyridin-9-ol (IIa).

Through a suspension of 20 g (0.096 mol) of piridoksingidrohlorid in 300 ml of acetic aldehyde, when cooled to 3-5°C and stirring, missed 22 g (0.603 mol) of hydrogen chloride. The resulting reaction mixture was stirred for 2 h, then the precipitate was filtered, washed with ether and neutralized to a 25%aqueous solution of potash. Product which was filtered, was air-dried and recrystallized from ethanol. The yield was 65%. TPL 186-186 .5°C (lit. 189.5-190°C [Pat. GB 1034483, C07D 213/67. A process for the manufacture of pyridine derivatives [Text] / ROCHE PRODUCTS LTD. - Publ. - 29.26.1966]), NMR1H (300 MHz, acetone-d6): δ 1.31 (d,3JHH=6 Hz, CH3, 3H); 2.36 (s, CH3, 3H); 4.73, 5.21 (AB,2JHH=-15.4 Hz, CH2); 4.74, 4.86 (AB,2JHH=-14.4 Hz, CH2); 5.05 (K3JHH=6 Hz, 1 H); 7.74 (s, CH, 1 H).

Example 2. Synthesis of 1,5-dihydro-3,3,8-trimethyl-[1,3]doxepin[5,6-C]pyridin-9-ol (IIB).

Through a suspension of 20 g (96 mmol) is dried in a water jet vacuum pump commercially available piridoksingidrohlorid (1) in 300 ml of acetone, cooled to 3-5°C and stirring was passed 22g (603 mmol) of hydrogen chloride. The resulting reaction mixture was stirred for 5 h, was kept for 20 h at room temperature, then the precipitate was filtered, washed with ether and neutralized to a 25%aqueous solution of potash. The product was filtered, dried in air and recrystallized from ethanol. Yield 17.9 g (yield 87%), TPL 184.5-186°C (lit. 184-185°C [W. Korytnyk A Seven-Membered Cyclic Ketal of Piridoxol [Text] / W.Korytnyk // J. Org. Chem. - 1962. - V.27, N.10. - P.3724-3726]). An NMR spectrum1H (DMSO-d6), δ, ppm: 1.44 (6N, 2CH3), 2.38 (3H, CH3), 4.74 (2H, CH2), 4.86 (2H, CH2), 7.75 (1H, CH)

Example 3. Synthesis of 1,5-dihydro-3-isopropyl-8-methyl-[1,3]dioxa is but[5,6-C]pyridin-9-ol (IIB).

To a solution of hydrogen chloride (obtained from 10.5 g (0.095 mol) of calcium chloride and excess conc. sulfuric acid) in 50 ml of absolute dimethyl sulfoxide was added 5 g (0.024 mol) of piridoksingidrohlorid and 0.048 mol samalanga aldehyde. The reaction mass was heated for 2 hours at 50-60°C. and Then poured into 30 ml of an aqueous solution of 14.5 g (0,136 mol) of sodium carbonate with stirring and neutralized with diluted solution of hydrogen chloride to pH 7. The precipitation was filtered, the mother liquor was dried under vacuum and the resulting oily mixture was washed with water. Not dissolved in the water mass was combined with the precipitate obtained after neutralization of the reaction mixture, and recrystallize from ethanol. Yield 62%. TPL 163.5-164°C (lit. 164-164 .5°C [Pat. FR 1384099, C07D 491/04. Procédé pour la préparation de dérivés de pyridine [Text] / Hoffmann La Roche. - Publ. - 04.01.1965]), NMR1H (300 MHz, acetone-d6): δ 1.31 (d,3JHH=6 Hz, CH3, 3H); 2.36 (s, CH3, 3 H); 4.73, 5.21 (AB,2JHH=-15.4 Hz, CH2); 4.74, 4.86 (AB,2JHH=-14.4 Hz, CH2); 5.05 (K3JHH=6 Hz, 1 H); 7.74 (s, CH, 1 H).

Example 4. Synthesis of 8-methyl-1,5-dihydrospiro[[1,3]doxepin[5,6-C]pyridine-3,1'-cyclohexane]-9-ol (G).

In a round bottom flask, equipped with a nozzle Dean-stark has prepared a suspension of 5 g (0.024 mol) of piridoksingidrohlorid, 1.34 g (to 0.007 mol) of the monohydrate of p-toluenesulfonic acid and 0.0 mole of cyclohexanone in 150 ml of benzene. The reaction mass was heated for 2 hours, then the solvent is kept in vacuum. To the mixture was added a solution of 0.32 g (0,008 mol) of sodium hydroxide in 100 ml of water and neutralized to pH 7 with diluted hydrochloric acid. Fallen oily precipitate was filtered, washed with water and with a mixture of acetone-heptane in the ratio of 1:1 and recrystallized from ethanol. TPL: 162-163°C (lit. 167-169°C [Pat. FR 1384099, C07D 491/04. Précédé pour la préparation de dérivés de pyridine [Text] / Hoffmann La Roche. - Publ. - 04.01.1965]), NMR1H (300 MHz, DMSO-d6): δ of 1.40 (m, CH22N); for 1.49 (m, 2CH2, 4H); 1,72 (m, 2CH2, 4H); 2,33 (s, CH3, 3H); 4,71 (s, CH22N); a 4.83 (s, CH2, 2H); 7,72 (s, CH, 1H), 8,83 (Usc, HE, 1H).

Example 5. Synthesis of 8-methyl-1,5-dihydrospiro[[1,3]doxepin[5,6-C]pyridine-3,1'-cyclopentane]-9-ol (Ia).

Synthesize and develop similar connection (G)using Cyclopentanone instead of cyclohexanone. TPL: 163-164°C, NMR1H (400 MHz, DMSO-d6): δ 1,63(m, 2CH2, 4H); is 1.81 (m, 2CH2, 4H); 2,28 (s, CH3, 3H); 4,63 (s, CH2, 2H); was 4.76 (s, CH2, 2H); 7,51 (s, CH, 1H).

Example 6. Synthesis of n-(1,5-dihydro-3,8-dimethyl-9-hydroxy-[1,3]doxepin[5,6-C]pyridinyl-6-azo)vinylsulfonate sodium salt (Ia).

In the flask to 50 ml of prepared solution diazocompounds of 0.005 mol sulfanilic acid, 0.35 g (0,005 mol) of sodium nitrite in 50 ml (0.01 mol) 0.2 N. hydrochloric acid at a temperature of 0-5°C. Separately prepared and a solution of 0.005 mole of the acetal IIA and 0.86 g (0.015 mol) of potassium hydroxide in 15 ml of water. To a solution of phenolate acetal is added dropwise with stirring and cooling to 0-5°C was added a solution of diazocompounds. The reaction mixture was stirred at room temperature for 30 minutes and neutralized with diluted hydrochloric acid to pH 7.5. The reaction mass was dried in vacuum to dryness, the product was recrystallized from ethanol. An output of 60%. Trasl. 225-226°C. NMR1H (400 MHz, DMSO-d6): δ 1.41 (d,3J=5.3 Hz, CH3, 3H); 2.32 (s, CH3, 3H); 4.65, 5.15 (AB Quartet,2J=-14.9 Hz, CH2, 2H); 5.11, 5.64 (AB Quartet,2J=-14.9 Hz, CH2, 2H); 5.19 (kV,3J=5.3 Hz, CH, 1H); 7.74 (s, s6H4, 4H). Calculated C16H15N3Na2O6S×H2O: 43.54; N, 3.88; N, 9.52. Found: 43.82; N, 3.28; N, 9.36.

Example 7. Synthesis of n-(1,5-dihydro-3,3,8-trimethyl-9-hydroxy-[1,3]doxepin[5,6-C]pyridinyl-6-azo)vinylsulfonate sodium salt (IB).

Synthesize and develop similarly to compound (Ia), using acetal IIB instead of compound IIA. Yield 70%. Trasl. 239-240°C. NMR1H (300 MHz, DMSO-d6): δ 1.51 (s, 2CH3, 6N); 2.25 (s, CH3, 3H); 4.79 (s, CH2, 2H); 5.32 (s, CH2, 2H); 7.69, 7.71 (AB Quartet,3J=8.94 Hz, C6H4, 4H). Calculated C17H17N3Na2O2S×2H2O: 43.13; N, 4.47; N, 8.80. Found: 42.03; N, 3.61; N, 8.50.

Example 8. Synthesis of n-(1,5-dihydro-3-isopropyl-8-methyl-9-hydroxy-[1,3]doxepin[5,6-C]pyridinyl-6-isopentylacetate sodium salt (Ie).

Synthesize and develop similarly to compound (Ia), using acetal IIB instead of compound IIa. Yield 70%. Trasl. 229-230°C. NMR1H (300 MHz, DMSO-d6): δ 1.02 (d,3J=6.8 Hz, CH3, 3H); 1.03 (d,3J=6.8 Hz, CH3, 3H); 2.00 (m, CH, 1H); 2.28 (s, CH3, 3H); 4.61 (d,3J=6.45 Hz, CH, 1H); 4.61, 5.74 (AB Quartet,2J=-14.47 Hz, CH2, 2H); 5.06, 5.20 (AB Quartet,2J=-of 14.56. Hz, CH2, 2H); 7.74 (s, C6H4, 4H). Calculated C18H19N3Na2O6S×2H2O: 44.35; H 4.76; N at 8.62. Found: %: 44.74; N, 4.13; N, 8.40.

Example 9. Synthesis of n-(8-methyl-9-hydroxy-1,5-dihydrospiro[[1,3]doxepin[5,6-C]pyridine-3,1'-cyclohexyl]-6-azo)vinylsulfonate sodium salt (Iك).

Synthesize and develop similarly to compound (Ia), using acetal G instead of compound IIa. Output: 38,5%. Trasl. 220°C, NMR1H (400 MHz, DMSO-d6): δ 1.41 (m, CH2, 2H); of 1.52 (m, 2CH2, 4H); to 1.75 (m, 2CH2, 4H); 2,22 (s, CH3, 3H); 4.75 V (s, CH2, 2H); 5.24 (s, CH22N); the 7.65 (s, SN, 4H).

Example 10. Synthesis of n-(8-methyl-9-hydroxy-1,5-dihydrospiro[[1,3]doxepin[5,6-C]pyridine-3,1'-cyclopentyl]-6-azo)phenylsulfonyl disodium salt (D).

Synthesize and develop similarly to compound (Ia), using acetal D instead of compound IIa. Yield: 41%, Trasl. 220°C, NMR1H (400 MHz, DMSO-d6): δ 1.77 in (m, 2CH2, 4H); of 1.85 (m, 2CH2, 4H); of 2.16 (s, CH3, 3H); 4,68 (who, CH2, 2H); 5,19 (s, CH22N); a 7.62 (s, SN, 4H).

Example 11. The methodology for the study of antibacterial activity.

Measurement of antimicrobial activity was carried out on strains of microorganisms: Proteus vulgaris, Pseudomonas aeroginosa, Escherichia coli, Staphylococcus aureus, which were isolated from physiological fluids of people suffering from infectious diseases. Cultivation of bacteria was carried out on a standard nutrient medium - mastopathy agar (MPA).

Antimicrobial activity was investigated during the incubation of the test strains in mesopatamia broth in the presence of test compounds. For 12-15 h before the experiment, the culture of sterile strains endured with beveled MPA in test tubes with 5 ml of BCH to obtain the "night of culture", which is further diluted to a concentration of cells in the environment of 0.01 opted (λ=600 nm). The resulting suspension was poured into the test tubes with the addition of the test substances dissolved in 50%aqueous solution of DMSO, final concentration of 10-5up to 10-2mg/ml, as control was used solvent. Incubation was led at 37°C for 6 and 12 h of the density Measurement was performed photometrically on the spectrophotometer SF-2000 at 600 nm. Expected percentage of inhibition of growth relative to control.

The most similar chemical structure and purpose to the declared the antimicrobial substance are sulfanilic acid and antibacterial drug streptocid, which were selected as reference (connection to compare the antibacterial activity of the compounds.

Table 1
The percentage of inhibition of growth of pathogenic bacteria tested substances (concentration 0.01 mg/ml) after different duration of cultivation
SampleP. vulgarisP. aeroginosaS. aureus
6 h12 hours6 h12 hours6 h12 hours
Ia7±48±217±215±43±24±3
1B50±635±462±451±793±585±6
Streptocide29±459±6 32±586±321±635±7
Sulfanilic acid10±311±56±37±419±412±4

From the presented data in table 1 it follows that the claimed compounds have antibacterial activity, in this connection 16 inhibits the growth of bacteria in 2-3 stronger than streptocide.

Derivatives sulfanilic acid, namely n-(1,5-dihydro-3-methyl-8-R1-8-R2-9-hydroxy-[1,3]doxepin[5,6-C]pyridinyl-6-azo)phenyl sulfonic acids and their salt forms, which have antibacterial activity of General formula I

where R1, R2selected from the group of a hydrogen atom, methyl, linear, branched alkyl, or R1and R2together form spiratically group.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are produced new diazepane substituted compounds representing various heterocyclic systems, including condensed, pharmaceutical compositions containing said compounds.

EFFECT: producing the compounds and compositions for preventing and treating neurological and mental disorders and diseases with involved orexin receptors.

13 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (I) or to their pharmaceutically acceptable salts, in which X is selected from group, consisting of-C(R1)2-, -O-, -S-, -S(O2)-, -NR1-; each R1 is independently selected from group consisting of H and alkyl; each of R2, R3 and R4 is independently selected from group consisting of (1) H, (2) alkyl, (3) -OR5, (4) alkylene-OR5, (5) -alkylene-R6, (6) -C(O)O-alkyl, (7) - alkylene-C(O)O-alkyl, (8) -alkylene-R8, (9) -NHR5, (10) -N(R5)2, (11) alkenyl, (12) -NH-R8, (13) -NH-CH(C(O)O(C1-C6)alkyl)-alkylene-O-alkyleneR6, (14)-NHCH(C(O)O(C1-C6)aalkyl)-alkylene-OH, (15) -NH-C(O)-alkenyl and (16) -N(C1-C6alkyl)C(O)-alkenyl; or R2 and R3 or R2 and R4 or R3 and R4 together with atoms with which they are bound, form condensed 3-7-member cycloalkyl or heterocycloalkyl ring, which represents non-aromatic monocyclic ring system, which contains in ring from about 5 to about 7 atoms, and one or several atoms in ring system represent atom of element, different from carbon, for instance, nitrogen or oxygen, and said condensed cycloalkyl or heterocycloalkyl ring is not substituted or is substituted with one or several groups L3 ; and on condition that if X represents -O-, and m equals 1, then, at least, one of R2, R3 or R4 is not H; each R5 is independently selected from group consisting of (1) H, (2) (C1-C6)alkyl, (3) hydroxy-substituted alkyl, (4) R6, (5) R7, (6) -C(O)-(C1-C6)alkyl, (7) -C(O)-(C1-C6)halogenalkyl, (8) -C(O)-R6, (9) -C(O)-R7, (10) -C(O)NH-(C1-C6)alkyl, (11) -C(O)N((C1-C6)alkyl)2, in which each alkyl group is selected independently, (12) -S(O)2-(C1-C6)alkyl, (13) -S(O)2-(C1-C6)halogenalkyl, (14) -S(O)2-R6, (15) -S(O)2-R7, (16) -S(O)2-R8, (17) -alkylene-C(O)-(C1-C6)alkyl, (18) -alkylene-C(O)-(C1-C6)halogen-alkyl, (19) -alkylene-C(O)-R6, (20) -alkylene-C(O)-R7, (21) -alkylene-S(O)2-(C1-C6)alkyl, (22) -alkylene-S(O)2-(C1-C6)halogenalkyl, (23) -alkylene-S(O)2-R6, (24) -alkylene-S(O)2-R7, (25) -alkylene-S(O)2-R8, (26) -alkylene-NHC(O)-(C1-C6)alkyl, (27) -alkylene-NHC(O)-(C1-C6)halogenalkyl, (28) alkylene-NHC(O)-R6, (29) -alkylene-NHC(O)-R7, (30) -alkylene-NHS(O)2-(C1-C6)alkyl, (31) -alkylene-NHS(O)2-(C1-C6)halogenalkyl, (32) -alkylene-NHS(O)2-R6, (33) -alkylene-NHS(O)2-R7, (34) -alkylene-N(alkyl)C(O)-(C1-C6)alkyl, (35) -alkylene-N(alkyl)C(O)-(C1-C6)halogenalkyl, (36) -alkylene-N(alkyl)C(O)-R6, (37) -alkylene-N(alkyl)C(O)-R7, (38) -alkylene-N(alkyl)S(O)2-(C1-Ce)alkyl, (39) -alkylene-N(alkyl)S(O)2-(C1-C6)halogen-alkyl, (40)-alkylene-N(alkyl)S(O)2-R6, (41) -alkylene-N(alkyl)S(O)2-R7, (42) -alkylene-C(O)-NH-(C1-C6)alkyl, (43) -alkylene-C(O)-NHR6, (44) -alkylene-C(O)-NHR7, (45) -alkylene-S(O)2NH-(C1-C6)alkyl, (46) -alkylene-S(O)2NH-R6, (47) -alkylene-S(O)2NH-R7 , (48) -alkylene-C(O)-N((C1-C6)alkyl)2, in which each alkyl group is selected independently, (49) -alkylene-C(O)-N(alkyl)-R6, (50) -alkylene-C(O)-N(alkylene)-R7, (51) -alkylene-S(O)2N((C1-C6)alkyl)2, in which each alkyl group is selected independently, (52) -alkylene-S(O)2N(alkyl)-R6, (53) -alkylene-S(O)2N(alkyl)-R7, (54) -alkylene-OH, (55) -alkylene-OC(O)-NH-alkyl, (56) -alkylene-OC(O)NH-R8, (57) -alkylene-CN, (58) -R8, (59) -alkylene-SH, (60) -alkylene-S(O)2-NH-R8, (61) -alkylene-S(O)2-alkylene-R6, (62) substituted with halogen alkylene, (63) -C(O)OR8, (64) -C(O)O(C1-C6)alkyl, (65) -C(O)R8, (66) -C(O)-alkylene-O-(C1-C6)alkyl, (67) -C(O)NH2, (68) -alkylene-O-(C1-C6)alkyl, (69) -alkylene-R8, (70) -S(O)2-halogen(C1-C6)alkyl, (71) hydroxy-substituted halogen(C1-C6)alkyl, (72) -alkylene-NH2, (73) -alkylene-NH-S(O)2-R8, (74) -alkylene-NH-C(O)-R8, (75) -alkylene-NH-C(O)O-(C1-C6)alkyl, (76) -alkylene-O-C(O)-(C1-C6)alkyl, (77) -alkylene-O-S(O)2-(C1-C6)alkyl, (78) -alkylene-R6 , (79) -alkylene-R7, (80) -alkylene-NH-C(O)NH-(C1-C6)alkyl, (81) -alkylene-N(S(O)2 halogen(C1-C6)alkyl)2, and each -S(O)2 halogen(C1-C6)alkyl fragment is selected independently, (82) -alkylene-N((C1-C6)alkyl)S(O)2-R8 , (83) -alkylene-OC(O)-N(alkyl)2, and each alkyl is selected independently, (84) -alkylene-NH-(C1-C6)alkyl, (85) -C(O)-alkylene-C(O)O-(C1-C6)alkyl, (86) -C(O)-C(O)-O-(C1-C6)alkyl, (87) -C(O)-alkylene-R6, (88) -C(O)-NH-R8, (89) -C(O)-NH-R6, (90) -C(O)-NH-alkylene-R6, (91) -C(O)-alkylene-NH-S(O)2-halogen(C1-C6)alkyl, (92) -C(O)-alkylene-NH-C(O)-O-(C1-C6)alkyl, (93) -C(O)-alkylene-NH2, (94) -C(O)-alkylene-NH-S(O)2-R8, (95) -C(O)-alkylene-NH-S(O)2-(C1-C6)alkyl, (96) -C(O)-alkylene-NH-C(O)-(C1-C6)alkyl, (97) -C(O)-alkylene-N(S(O)2(C1-C6)alkyl)2, and each -S(O)2(C1-C6)alkyl fragment is elected independently, (98) -C(O)-alkylene-NH-C(O)-NH-(C1-C6)alkyl, (99) -alkylene-O-R6, (100) -alkylene-R7, (101) -C(O)OH, (102) -alkylene-N(S(O)2(C1-C6)alkyl)2, (103) -alkylene-C(O)-O-(C1-C6)alkyl, (104) halogenalkyl, (105) halogen, (106) -alkylene-C(O)-NH2, (107) =N-O-(C1-C6)alkyl, (108) =N-O-alkylene-R6, (109) =N-O-alkenyl, (110) -N-O-R6, (111) =N-NH-S(O)2-R6, (112) alkenyl, (113) =R8, (114) -O-C(O)-R9, (115) -O-C(O)-(C1-C6)alkyl, (116)-CN, R6 is selected from group consisting of unsubstituted (C6-C14)aryl, (C6-C14)aryl, substituted with one or several groups L1, unsubstituted (C5-C14)heteroaryl and (C5-C14)heteroaryl, which represents aromatic monocyclic or bicyclic system, which contains in ring from about 5 to about 9 atoms, and one or several atoms in ring system represent atom of element, different from carbon, for instance, nitrogen, oxygen or sulphur, one or in combination, substituted with one or several groups L1; R7 is selected from group consisting of unsubstituted heterocycloalkyl and heterocycloalkyl which represents non-aromatic monocyclic system, which contains in ring from about 4 to about 6 atoms, and one or several atoms in ring system represent atom of element, different from carbon, for instance, nitrogen, oxygen substituted with one or several groups L2; R8 is selected from group consisting of unsubstituted cycloalkyl and cycloalkyl substituted with one or several groups L2; A8 is selected from group consisting of (a) unsubstituted aryl, (b) aryl substituted with one or several groups L1; each group L1 is independently selected fron group consisting of halogen, alkyl, -CN, -CF3, -O-(C1-C6)alkyl, -O-(halogen(C1-C6)alkyl), -alkylen-OH (-CH2OH); each group L2 is independently selected from group consisting of (a) -OH, (b) alkyl, (c) alkyl substituted with one or several groups -OH and (d) piperidyl; each group L3 is independently selected from group consisting of -CN, =O, R5 , -OR5 ; =N-R5 and -N(R5)2; n equals 0, 1, 2 or 3; and m equals 0, 1 or 2; and on condition that in composition of substituent -OR5 fragment R5 and oxygen atom, which it is bound with, do not form group -O-O-; and on condition that in composition of substituents -OR5, =N-R5 and -NHR5 R5 are not -CH2OH, -CH2NH2, -CH2NH-alkyl, -CH2NH-aryl or -C(O)OH. Invention also relates to pharmaceutical composition, as well as to application of one or several compounds by one of ii. 1-125.

EFFECT: obtaining novel biologically active compounds possessing properties of γ-secretase inhibitor.

127 cl, 447 ex, 94 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I), and a salt or hydrate thereof:

,

in which R1 denotes a hydrogen atom; R2 denotes a hydrogen atom; R3 and R4 independently denote a hydrogen atom; R5 denotes a hydrogen atom or a fluorine atom; R6 and R7, together with carbon atoms to which they are bonded, form a 5- or 6-member cyclic structure, where the cyclic structure is a partial structure which, together with a pyrrolidine ring, forms a condensed cyclic (bicyclic) structure, the 5- or 6-member cyclic structure can contain an oxygen atom as a ring atom, R5 can be a methylene group which, together with R6, forms a 3-member condensed cyclic structure; and Q is a partial structure of formula (II):

,

in which R8 denotes a 1,2-cis-2-halogencyclopropyl group, a cyclopropyl group or a 6-amino-3,5-difluoropyridin-2-yl group; R9 denotes a hydrogen atom; R10 denotes a hydrogen atom; R11 denotes a hydrogen atom; XI denotes a fluorine or hydrogen atom; A1 denotes a nitrogen or partial structure of formula (III):

,

in which X2 is a methyl group, an ethyl group, a methoxy group or a chlorine atom, or X2 and R8, together with their coupling part of the parent skeleton, form a cyclic structure, such that Q denotes a partial structure of formula , in which Y0 denotes a methyl group or a pre-methyl group, and X1, R9, R10, R11 assume values given above. The invention also describes a medicinal agent based on said compound, having antibacterial activity, an antibacterial agent and a therapeutic agent for treating infections.

EFFECT: novel compounds are obtained and described, which have strong antibacterial activity not only on gram-negative bacteria, but gram-positive cocci as well, which have low sensitivity to quinolone antibacterial agents, and which demonstrate high safety and excellent pharmacokinetic properties.

18 cl, 61 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (11) given below and pharmaceutically acceptable salts thereof: chemical formula 1

in which: each of G1, G2, G3 and G8 independently denotes -N=, -CR1= or -C(-G9-X)=; one of G1, G2, G3 and G8 is-C(-G9-X)=; X is C1-6 alkyl (where C1-6 can be optionally substituted with a group selected from a halogen atom, hydroxy, cyano and -NR56R57), aryl, heterocycle (where the heterocycle denotes a 5-9-member saturated or unsaturated cyclic group containing one or more heteroatoms selected from nitrogen, oxygen and sulphur atoms, and can be a monocycle or condensed ring, and can be optionally substituted with a halogen atom, C1-6 alkyl; C1-6 alkoxy, R33R34NCS-, R3R4NCO-); G9 denotes a single bond, an oxygen atom, a sulphur atom, ring G6 denotes a divalent aryl group or divalent pyridyl group (where the divalent pyridyl group can be optionally substituted with a halogen atom); A is a group of formula (2) given below, or a group of formula (3) given below. Chemical formula 2

, chemical formula 3 , G4 is an oxygen atom or sulphur atom; G5 is an oxygen atom or sulphur atom; G7 is an oxygen atom, -CR42R43-, -CONR44-, -NR44CO, -NR45-, CR42R43NR45-, -S-, -NR44S(=O)2-; R1 is a hydrogen atom, a halogen atom, cyano, C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a halogen atom), carbamoyl or C2-7 alkynyl (where C2-7 alkynyl can be optionally substituted with C1-4 acyl); when G2 or G3 denotes -CR1=, then G8 is -C(-G9-X)=, and X is R3R4NCO-, R33R34NCS-; when G8 is -CR1=, then G3 denotes -C(-G9-X)=, and X is R3R4NCO, or R33R34NCS-; when G1 or G8 denotes -CR4 then G2 is -C(-G9-X)=, and X denotes R3R4NCO-, or R33R34NCS-; or when G2 is -CR1=, then G1 denotes -C(-G9-X)=, and X denotes R3R4NCO-, or R33R34NCS-; R1 can form a single bond or -CH2- with R4 or R34; R2 denotes hydroxy or C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a group selected from a halogen atom, hydroxy, C1-6 alkoxy, formyl and -CO2R50); R3, R4, R9 and R10 each independently denotes a hydrogen atom, C3-8 cycloalkyl or C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a group selected from cyano, a halogen atom, hydroxy, C1-6 alkoxy, -NR13R14, and CONR28R29); R6 and R7 each independently denotes a hydrogen atom, C1-6 alkoxy, C3-8 cycloalkyl or C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a group selected from cyano, halogen atom, hydroxy, C1-6 alkoxy, -NR13R14, and CONR28R29); R33 and R34 each independently denotes a hydrogen atom, C1-6 alkyl, the combination of R3 and R4 together with a nitrogen atom to which they are bonded can form a 5-6-member heterocyclic group containing at least one nitrogen atom (where the 5-6-member heterocyclic group which contains at least one nitrogen atom is a saturated or unsaturated heterocyclic group containing 5-6 atoms in the ring and which, in addition to one or more nitrogen atoms, can contain one or more heteroatoms selected from oxygen and sulphur atoms (where the 5-6-member heterocyclic group can be optionally condensed with a benzene ring); and which can be optionally substituted with a halogen atom or C1-6 alkyl; the combination of R6 and R7 together with the nitrogen atom to which they are bonded can form a 5-6-member heterocyclic group containing at least one nitrogen atom (where the 5-6-member heterocyclic group which contains at least one nitrogen atom is a saturated or unsaturated heterocyclic group containing 5-6 atoms in the ring and which, in addition to one or more nitrogen atoms, can contain one or more heteroatoms selected from oxygen and sulphur atoms (where the 5-6-member heterocyclic group can be optionally condensed with a benzene ring); and which can be optionally substituted with a halogen atom, C1-6 alkyl or an oxo group; R45 is a hydrogen atom, R13 and R14 each independently denotes a hydrogen atom, C1-6 alkyl or COR32; R56 and R57 each independently denotes a hydrogen atom or C1-6 alkyl, and R5, R8, R28, R29, R32, R42, R43, R44, and R50 each independently denotes a hydrogen atom or C1-6 alkyl. The invention also relates to a pharmaceutical composition, as well as to a medicinal agent for treating cell proliferative disorder.

EFFECT: obtaining novel biologically active compounds having inhibitory effect on cell proliferation.

15 cl, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of 5-(4-oxo-2-thioxo-1,3,4,5-tetrahydro-2H-chromeno [2,3-d] pyrimidin-5-yl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione of formula

, which involves reaction of thiobarbituric acid with salicylic aldehyde in ethyl alcohol medium with molar ratio of reagents equal to 1:1 at temperature 70-80°C for 30 minutes.

EFFECT: novel method for synthesis of said compounds with high output, which can be used as a intermediate product for preparing medicinal agents for treating Alzheimer's disease.

1 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I)

or pharmaceutically acceptable salts thereof, in which: R1, R2, R3, R4, A and E are as described in the claim, and to pharmaceutical composition containing said compounds, and a method of treating and application in order to treat conditions mediated by antagonistic activity towards acid pump, such as gastrointestinal diseases, gastrooesophageal diseases, gastrooesophageal reflux disease (GERD), laryngopharyngeal reflux disease, peptic ulcers, gastric ulcers, duodenal ulcers, NSAID- induced ulcers, gastritis, Helicobacter pylori infection, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, nonerosive reflux disease (NERD), viscerogenic pain, cancer, heartburn, nausea, oesophagitis, dysphagia, hypersalivation, disorders of the respiratory channel or asthma.

EFFECT: possibility of using compounds to treat different diseases.

9 cl, 1 tbl, 16 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 refers to compounds of the formula (I): , where R1 is C1-C8alkyl optionally substituted with one to three substitutes selected out of substitute group A; R2 is C1-C6alkyl or C1-C6alkoxyC1-C6alkyl; R3 is C1-C6alkyl or C1-C6alkoxy; or R2 and R3 together with adjoining carbon atoms form optionally substituted non-aromatic 5-10-member carbon ring; R4 is hydrogen; G is group represented by the formula: or the rest as provided in the invention claim; and to pharmaceutical composition, application of claimed compounds, and method of atopic dermatitis prevention or treatment.

EFFECT: novel compounds useful as atopic dermatitis treatment medication and antipruritic medicines.

24 cl, 75 ex, 290 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to benzopyran derivatives of formula or

or their pharmaceutically acceptable salts, where R1 and R2 independently represent a hydrogen atom or a C1-6alkyl group, R3 is a hydroxyl group, R4 is a hydrogen atom, m is an integer ranging from 1 to 4, n is an integer ranging from 0 to 4, V is a single bond, CR7R8 or NR9, R5 is a hydrogen atom, R6 is a hydrogen atom, C1-6alkyl group, C3-8cycloalkyl group, C3-8cycloalkenyl group, amino group, C1-6alkylamino group, C6-14aryl group, C2-9heteroaryl group or C2-9heterocyclic group, A is a 5- or 6-member ring condensed with a benzene ring, and the ring can contain an oxygen atom, a nitrogen atom or a sulphur atom numbering from 1 to 3 or separately, or combined, the number of unsaturated bonds in the ring equals 1, 2 or 3, including the unsaturated bond in the condensed benzene ring, carbon atoms in the ring can represent carbonyl or thiocarbonyl.

EFFECT: compounds can be used as antiarrhythmic agents.

47 cl, 1 tbl, 98 ex

FIELD: medicine.

SUBSTANCE: invention refers to new pyridine derivatives or to their pharmaceutically acceptable salts of general formula 1: wherein R1, R2, R3, R4, R5, R6 and R7 are independently chosen from the group including hydrogen atom, halogen, amino, C1-C6lower alkyl, C2-C6lower alkenyl, C1-C6lower alkoxy, C1-C10alkylamino, C4-C9cycloalkylamino, C4-C9heterocycloalkylamino, C1-C10aralkylamino, arylamino, acylamino, saturated heterocyclyl, acyloxy, aryl, heteroaryl, C1-C10aralkyl, aryloxy; X represents oxygen or sulphur atom; Y represents oxygen atom or N-R8, wherein R8 is chosen from the group including hydrogen atom; aforesaid aryl group is chosen from phenyl, naphthyl and condensed phenyl group; aforesaid heteroaryl and saturated heterocyclic groups represent pentagonal or hexagonal heterocyclic ring containing 1 to 2 heteroatoms chosen from oxygen, nitrogen and sulphur atom; or condensed heterocyclic ring; and aforesaid aryl and heteroaryl groups are those that 1 to 4 assistants chosen from group including halogen, C1-C6lower alkyl, C1-C6lower alkoxy are substituted. And specified compounds or their pharmaceutically acceptable salt of formula 1 are not compounds as follows 6-methyl-3,4-dihydro-pyrano[3,4-c]pyridin-1-one, 5-vinyl-3,4-dihydro-pyrano[3,4-c]pyridin-1-one, 6-methyl-8-furan-2-yl-3,4- dihydropyrano[3,4-c]pyridin-1-one, 3-tert-butyl-5,6,7,8-tetrahydro-[2,7]naphthyridine-8-one and dimethyl ether (3S)-6,8-dimethyl-1-oxo-1,2,3,4-tetrahydro-[2,7]naphthyridine-3,5-dicarboxylic acids.

EFFECT: compounds possess inhibitory action with respect to formation of cytokines involved in inflammatory reactions, can be used as a therapeutic agent for treatment of inflammatory diseases, immune diseases, chronic inflammations; it provides antiinflammatory and analgesic action.

21 cl, 7 tbl, 144 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to novel pyridyloxy derivatives or its pharmaceutically acceptable ester or a pharmaceutically acceptable salt of the mentioned derivatice or ester of general formula (I), wherein R represents a pyridyl group substituted by 1-3 groups independently specified in a group of substitutes A; the group of substitutes A represents a group comprising halogen atom, C1-C6 alkyl group and C1-C6 alkoxy group, and Me represents a methyl group. Also, the invention refers to specific compounds of formula (I), to a pharmaceutical composition and a receptor-γ activator/modulator on the basis of a compound of formula (I), to a method of treating and/or preventing a disease.

EFFECT: there are prepared novel pyridyloxy derivatives effective in treating the disease mediated by peroxisome proliferator activated receptor-γ (PPAR) γ.

37 cl, 2 tbl, 21 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new lipid compound of general formula , wherein n=0; R1 and R2 are identical or different, and may be specified in a group of substitutes consisting of a hydrogen atom, a C1-C7alkyl group, a halogen atom and a C1-C7alkoxy group; X represents COR3 or CH2OR4, wherein R3 is specified in a group consisting of hydrogen, hydroxy, C1-C7alkoxy and amino; and R4 is specified in a group consisting of hydrogen, C1-C7alkyl or C1-C7acyl, Y represents C9-C21 alkene with one or more double bonds in E- or Z-configurations with the chain Y being unsubstituted and containing a double bond in the ω-3 position; provided R1 and R2 cannot simultaneously represent a hydrogen atom.

EFFECT: invention refers to pharmaceutical compositions containing the lipid compounds which are used for treating and/or preventing the conditions related to high NFkB functions, treating and/or preventing an inflammatory disease or a condition, lower plasma insulin and/or blood glucose levels, treating insulin resistance, treating and/or preventing peripheral tissue insulin resistance and/or diabetic condition, eg type 2 diabetes mellitus.

45 cl, 1 tbl, 1 dwg, 31 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (1) and pharmaceutically acceptable salts thereof, which exhibit inhibitory activity on phospholipase A2 enzyme and therefore have prostaglandin and/or leucotriene production suppressing action. In formula X is a halogen atom, cyano group, C1-C3 alkyl group, which can be substituted with halogen atoms, C1-C3 alkoxy group or hydroxy group, C2-C4 alkenyl group, C1-C3 alkoxy group or hydroxy group; Y is a hydrogen atom or C1-C3 alkyl group; Z is C1-C3 alkyl group; G is selected from formulae and , where in formulae (G2) and (G5) R4 is a hydrogen atom or C1-C6 alkyl group which can be substituted with halogen atoms; D is -NR10C(O)-, -C(O)NR10-, -S(O)2NR10- or -N(R11)-; R10 is a hydrogen atom; R11 is a hydrogen atom or C1-C3 alkyl group; A is a single bond, C1-C6 alkylene, which can be substituted with a phenyl group, or C2-C4 alkenylene; Q is a phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, S, optionally substituted with a benzene ring; R5, R6 and R7 all or independently denote a hydrogen atom, a halogen atom, C1-C6 alkyl group which can be substituted with halogen atoms, C1-C6 alkoxy group which can be substituted with halogen atoms, phenyloxy group, phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, where said phenyl group and 5-6-member aromatic heterocyclic group can be substituted with a C1-C3 alkyl group which can be substituted with halogen atoms or a C1-C3 alkoxy group. The invention also relates to specific compounds, a medicinal agent, a pharmaceutical composition, a phospholipase A2 enzyme activity inhibitor and a treatment method.

EFFECT: improved method.

21 cl, 56 tbl, 561 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new N-aryl-2,3-diaroyl-8,10-dimethylpyrido[2',3':3,4]pyrazolo[1,5-α]pyrimidine-4-carboxamides of formula I possessing analgesic activity, and to a method for preparing them. In formula I Ar1=Ph, C6H4Me-4, C6H4OMe-4; Ar2-Ph, C6H4Me-4, C6H3(Me)2-2,5. The method for preparing said compounds consists in a reaction of 1-aryl-4,5-diaroyl-1H-pyrrol-2,3-diones with 3-amino-4,6-dimethyl-2H-pyrazolo[3,4-6]pyridine at temperature 108-110°C in an absolute toluene medium.

EFFECT: there are prepared the compounds possessing analgesic activity.

4 cl, 1 dwg, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to tricyclic spiro-derivatives of formula (I') wherein: R1 means H, C1-C6-alkyl, C1-C6-alkoxy, halogen-C1-C6-alkyl, halogen-C1-C6-alkoxy, halogen; m is equal to 0-4; R2 means A; A means , : n is equal to 1-4; R4 means C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C6-C10-aryl, 5, 6-member heteroaryl containing one, two and three heteroatoms independently specified in N, O, S, which may be condensed with a benzene ring; R4 may be substituted by one or more groups R6; R6 means C1-C6-alkyl, C1-C6-alkoxy, C6-C10-aryl, C6-C10-aryl-C1-C6-alkyl, C3-C8-cycloalkyl, CN, halogen, aminocarbonyl, C1-C6-acylamino, C1-C6-alkylsulphonyl, trihalogen-C1-C6-alkyl, -O-phenyl wherein phenyl may be substituted by one or two substituted specified in halogen, C1-C6-alkoxy; R7 means H, and C1-C6-alkyl; R means B; B means: , n is equal to 1-4; R5 means COOH, tetrazole; X means CH2, NH; Y means C(O); Z means C(O); as well as its geometric isomers, optically active forms, such as enantiomers, diastereomers, its racemate forms, or its pharmaceutically acceptable salts.

EFFECT: compounds are used for treating and/or preventing allergic diseases, inflammatory dermatoses and other diseases with an inflammatory component.

23 cl, 3 tbl, 125 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to dimethyl 4-acyl-1-hydroxy-3-methyl-7-oxo-6-phenyl-2,6-diazabicyclo[3.2.1]oct-3-ene-5,8-dicarboxylates of formula wherein Ar=Ph, C6H4Me-4, C6H4OMe-4, C6H4C1-4, C6H4Br-4; R=Me, Ph, as well as to a method for preparing them by setting a benzene solution of 1-aryl-4,5-bis(methoxycarbonyl)-1H-pyrrol-2,3-dions and 4-aminopent-3-en-2-one or 3-amino-1-phenylbut-2-en-1-one at room temperature.

EFFECT: compounds may be used as raw products for synthesis of new heterocyclic systems in pharmacology as potential drug preparations possessing analgesic activity.

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new imidazo[4,5-b]pyrazine derivatives of general formula or to its pharmaceutically acceptable salt wherein: R1 represents either aryl unsubstituted or substituted by one of the groups: halogen, hydoxyl, C1-6alkyl, C1-6alkoxyl, NH2, NHC1-6alkyl, N(C1-6alkyl)2, NHC1-6alkylC1-6alkoxy, C1-6alkylhydroxy, -C(O)NH2, -C(O)OC1-6alkyl, -C(O)NH C1-6alkyl, cyano, carboxy, heteroaryl and heterocycloalkyl; or heteroaryl unsubstituted or substituted by one of the groups: C1-6alkoxy, hydroxy, -C1-6alkyl, NH2 and NHC1-6alkyl; heterocycloalkyl unsubstituted or substituted by one group =O; and R2 represents H; unsubstituted C3-4alkyl; C1-4alkyl substituted by C5-6cycloalkyl unsubstituted or substituted by one group specified in amino, hydroxyl, C1-6alkoxy, or heterocycloalkyl unsubstituted or substituted by 1-2 groups specified in =O, C1-6alkyl; or C5-6cycloalkyl substituted by one group specified in hydroxyl, C1-6alkoxyl, C1-6alkylC1-6alkoxy, C1-6alkylhydroxy, CONH2; or substituted ir unsubstituted heterocycloalkyl; wherein aryl represents an aromatic structure consisting of 6-10 carbon atoms containing one ring or two condensed rings; wherein heteroaryl represents a 5-10-member aryl ring system containing 1-2 heteroatoms specified in nitrogen, oxygen and sulphur; wherein heterocycloalkyl represents a 5-9-member nonaromatic cycloalkyl wherein 1-2 heteroatoms specified in nitrogen and oxygen; provided the compound does not represent 1,3-dihydro-5-phenyl-2H-imidazo[4,5-b]pyrazin-2-one. Also, the invention refers to the specific imidazo[4,5-b]pyrazine derivatives, to a based pharmaceutical composition, to a method of treating or preventing cancer, inflammatory conditions, immunological diseases, metabolic conditions, and to a method of kinase inhibition in a cell expressing said kinase.

EFFECT: there are produced new imidazo[4,5-b]pyrazine derivatives showing effective biological properties.

17 cl, 2 tbl, 210 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new derivatives of ((phenyl)imidazolyl)methylheteroaryl of formula wherein A represents pyridyl or thienyl having 0 or 1 substitute; B represents phenyl having 0, 1 or 2 substitutes; wherein each substitute independently represents alkyl having 1 to 8 carbon atoms, -F, -Cl, -Br or -CF3. Also, the invention refers to the use of the declared compounds for the purpose of preparing a therapeutic agent, a pharmaceutical composition on the basis of the declared compounds, and to a kit containing the pharmaceutical composition above.

EFFECT: there are prepared new derivatives of ((phenyl)imidazolyl)methylheteroaryl effective in pain management.

10 cl, 1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to cyclohexane derivatives presented by general formula wherein the substitute A is a group of general formula or wherein the radicals and symbols are presented in the patent claim. The compounds of formula (I) possess strong analgesic action both on nociceptive pain, and on neuropathic pain, and to a lesser degree side effects. Their pharmaceutical use is also described.

EFFECT: cyclohexane derivative and its pharmaceutical use is presented.

17 cl, 42 tbl, 7 dwg, 177 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new compound that is N-[3-(4-ntirophenylamino)-indol-2-ylmethylene]aminoguanidine hydrochloride of formula (2) or its pharmaceutically acceptable salt which shows systemic anti-inflammatory and chondroprotective action, and shows no side effects.

EFFECT: what is presented is the biologically active compound which shows systemic anti-inflammatory and chondroprotective action, and shows no side effects.

3 cl, 1 dwg, 4 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a pharmaceutical composition for local application containing a therapeutic compound of an immune response modifier, sterilisation-resistant and applicable for local application immediately on tissue regions with skin damages wherein said composition is sterilised by electron-beam irradiation, and the therapeutic compound represents 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinoline-4-amine (imiquimod). Also, the invention refers to a packed composition for local application containing a packing material and said pharmaceutical composition.

EFFECT: invention provides the sterilisation-resistant pharmaceutical composition.

26 cl, 5 tbl, 1 ex

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