Pyridoxine derivatives with nonlinear optical properties

FIELD: chemistry.

SUBSTANCE: invention relates to pyridoxine derivatives of general formula

,

where R1-is a hydrogen atom or methyl, R2 is a hydrogen atom, methyl, linear, branched or cyclic alkyl or R1 and R2 together form a cyclic alkyl capable of powder second-harmonic generation (SHG).

EFFECT: invention can be used in laser technology and communication equipment.

1 cl, 1 tbl, 7 ex

 

The invention relates to the field of organic chemistry, organic substances that have the ability to powder second-harmonic generation (SHG), and represents a derivative of pyridoxine General formula I:

where R1represents a hydrogen atom or methyl, R2represents a hydrogen atom, methyl, linear or branched alkyl or cycloalkyl or R1and R2together form a cyclic alkyl, with the ability to powder second-harmonic generation (SHG).

The claimed technical solution relates to compounds with nonlinear optical properties, which are widely used in laser technology, means of communication, therefore, is currently undergoing active research in the field of creation of new, more efficient converters of laser radiation. The claimed compounds can be used to double the frequency of laser radiation.

To create materials with nonlinear optical properties are used as inorganic and organic compounds [Pat. US 5202891, IPC G02F 1/355. Nonlinear optical material / OREGON STATE. - Publ. - 13.04.1993; U.S. Pat. RF 2344208, IPC C30B 29/46. Nonlinear single crystal lithium chalcogenide / Institute of Geology and Mineralogy SB RAS. - Publ. - 20.01.2009; Pat. US 4181515, IPC C03B 37/023. Method of making dielectric optical waveguids / POST OFFICE. - Publ. - 01.01.1980; Pat. US 4077699, IPC C03B 37/014. Optical devices / POST OFFICE. - Publ. - 07.03.1978]. Special attention is paid to obtaining a polymer capable of generating second harmonic [U.S. Pat. RF 2369597, IPC C07C 255/65. Substituted 4-phenylazophenyl and polymers with nonlinear optical properties containing these fragments in the side and main chain of the polymer / GOU VPO Yaroslavl state technical University. - Publ. - 10.10.2009].

Currently in wide use in industry received the materials made from inorganic compounds. The main advantage of inorganic compounds is the ease of obtaining materials with nonlinear optical properties. It should be noted that the lack of inorganic compounds is their relatively low conversion of the powder SHG [US Pat 2004033038, IPC G02F 1/065. Method for producing non-linear optical organic crystal film / XU JIANJUN,; FAN BUNSEN,; REVEO, INC. - Publ. - 19.02.2004].

Unlike inorganic compounds some of the known organic materials have a higher conversion powder SHG, but low chemical resistance to laser radiation [Suresh, S.Review on theoretical aspect of nonlinear optics [Text] / S.Suresh, A.Ramanand, D.Jayaraman, P.Mani // Rev. Adv. Mater. Sci. - 2012. - V.30, N.2. - P.175-183].

So the analogue of the claimed compounds of meta-nitroaniline shows nelina what about the optical properties, but not resistant to the action of laser radiation and has a low conversion rate of the powder SHG.

The essence of the claimed technical solution is as follows. Derivatives of pyridoxine General formula (I)

where R1represents a hydrogen atom or methyl, R2represents a hydrogen atom, methyl, linear or branched alkyl or cycloalkyl or R1and R2together form a cyclic alkyl, with the ability to powder second-harmonic generation (SHG).

The objective of the claimed technical solution is to create a new organic compounds having a high conversion efficiency of the powder SHG and higher resistance to laser radiation.

The technical result of the claimed invention is to provide new compounds of General formula (I).

The problem is solved, and the specified technical result is achieved by obtaining the claimed new derivatives of pyridoxine formula (I):

The claimed compounds have a high conversion powder SHG compared with inorganic compounds (lithium Iodate, potassium dihydrophosphate)and organic compound (meta-nitroaniline). Important among what Stom the claimed compounds is their high stability under the action of laser radiation.

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".

Proposed in the present invention the compounds of formula (I) obtained according to the scheme below:

IIb) R1=CH3; R2=CH3IB) R1=CH3; R2=CH3
IIb) R1=R2=HIB) R1=R2=H
G) R1=H; R2=C2H5Iك) R1=H; R2=C2H5
D) R1=H; R2=CH2CH2CH3Ia) R1=H; R2=CH2CH2CH3
IIe) R1=H; R2=CH(CH3)2S) R1=H; R2=CH(CH3)2
I) R1=H; R2=CH(CH3)CH2CH3If R1=H; R2=CH(CH3)CH2CH3
S) R1=H; R2=C(CH3)3Z) R1=H; R2/sub> =C(CH3)3
I) Ri=H; R2=CH(CH3)C3H7AI) R1=H; R2=CH(CH3)C3H7
C) R1=H; R2=C7H15IK) R1=H; R2=C7H15
L) R1=H; R2=C8H17Il) R1=H; R2=C8H17
M) R1=H; R2=CH(CH3)C9H19Ei) R1=H; R2=CH(CH3)C9H19
N) R1=H; R2=cyclo-C6H11In) R1=H; R2=cyclo-C6H11
O) R1, R2=cyclo-C5H8O) R1, R2=cyclo-C5H8
P) R1, R2=cyclo-C6H10IR) R1, R2=cyclo-C6H10
R) R1, R2=cyclo-C7H12IP) R1, R2=cyclo-C7H12
IIC) R1=CH3; R2=C5H11IC) R1 =CH3; R2=C5H11
T) R1=CH3; R2=C8H17It) R1=CH3; R2=C8H17

Characteristics of the new compounds are given in the examples of specific performance. NMR spectra were recorded on a Bruker instrument" AVANCE 400 (400 MHz) and Varian Unity-300 (300 MHz). The chemical shift was determined relative to the signals of the residual protons of the deuterated solvents (1H and13C). Monitoring the progress of reactions and the purity of the compounds was performed by thin layer chromatography (hereinafter TLC) plates Sorbfil Plates.

Examples of specific performance of the claimed technical solution

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. The product was filtered, dried in air 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 M is C, 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, 1H); 7.74 (s, CH, 1H).

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 [Korytnyk, W.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 (6H, 2CH3), 2.38 (3H, CH3), 4.74 (2H, CH2), 4.86 (2H, CH2), 7.75 (1H, CH).

Example 3

A General method of obtaining semichronic acetals pyridoxine (IIB -, n) condensation in absolute dimethyl sulfoxide.

To a solution of hydrogen chloride (obtained from 10.5 g of calcium chloride and excess conc. sulfuric acid in 130 ml of absolute dimethyl sulfoxide doba is or 15 g (0.073 mol) of pyridoxine hydrochloride and 0.2 mol of carbonyl compounds. The reaction mass was heated 2 hours at 50-60°C. Then poured into a 30 ml aqueous solution of 14.5 g of sodium carbonate with stirring. The neutralized solution was converted into a vacuum to VAT residue 30 ml VAT residue in the flask was filled with 100 ml of ethyl acetate and unreacted pyridoxine filtered. The mother liquor was washed several times with water, dried and passed through a 1 cm layer of silica gel. Eluent-ethyl acetate. The eluate was evaporated and precrystallization from ethanol. The output of 40-70%.

1,5-Dihydro-[1,3]doxepin-[5,6-C]-pyridin-9-ol (IIB). TPL 174-175°C. NMR1H (300 MHz, DMSO-d6): δ 2.36 (s, CH3, 3H); 4.78 (s, CH2, 2H); 4.91 (s, CH2, 2H); 4.96 (s, CH2, 2H); 7.80 (s, CH, 1H); 8.92 (s, OH, 1H).

1,5-Dihydro-3-ethyl-8-methyl-[1,3]doxepin[5,6-C]pyridin-9-ol (G). TPL 153°C, NMR1H. (300 MHz, DMSO-d6): δ 0.86 (t,3JNN=7.5 Hz, CH3., 3H); 1.58 (m, CH2., 2H); 2.34 (s, CH3, 3H); 4,65, 5.13 (AB,2J=15.3 Hz, CH2, 2H); 4,69, 4.77 (AB,2J=15,0, CH2, 2H); 4,81 (t3J=5.6 Hz, CH, 1H); of 7.75 (s, CH., 1H).

1,5-Dihydro-3-propyl-8-methyl-[1,3]doxepin[5,6-C]pyridin-9-ol (D). TPL 136°C, NMR1H (300 MHz, DMSO-d6): δ 0.89 (t,3JNN=7.4 Hz, CH3., 3H); 1.35 (m, CH2., 2H); and 1.56 (m, CH2, 2H); 2,35 (s, CH3., 3H); 4,68 5,13 (AB,2J=15.3 Hz, CH2., 2H); 4,73 4,79 (AB,2J=14,3, CH2., 2H); 4.92 in (t3J=5.5 Hz, CH., 1H) 7,80 (s, CH., 1H) to 8.94 (s, OH., 1H).

1,5-dihydro-isopropyl-8-methyl-[1,3]doxepin[5,6-C] pyridin-9-ol (IIE). TPL 163.5-164°C (lit. 164-164 .5°C [Pat. FR 1384099, C07D 491/04. Precédé pour la préparation de dérivés de pyridine [Text] / Hoffmann La Roche. - Publ. - 04.01.1965.]), NMR1H (300 MHz, acetone-d6): δ 1.31 (d,3JNN=6 Hz, CH3, 3H); 2.36 (s, CH3, 3H); 4.73, 5.21 (AB,2JNN=-15.4 Hz, CH2); 4.74, 4.86 (AB,2JNN=-14.4 Hz, CH2); 5.05 (K3JNN=6 Hz, 1H); 7.74 (s, CH, 1H).

1,5-Dihydro-3-(1-methylpropyl)-8-methyl-[1,3]doxepin[5,6-C]pyridin-9-ol (I). NMR1H (400 MHz, CDCl3): δ 0.82-0.90 (m,, 2CH3, 6H), 1.07-1.18 (m, CH2, 1H), 1.48-1.57 (m, CH2, 1H), 1.59-1.70 (m, CH, 1H), 2,36 (C., CH3, 3H), 4.66 (Shostakovich,3JNN=4.6 Hz,4JNN=-2,0 Hz, CH, 1H), 4.66, 5.18 (AB-square,2JNN=-16 Hz,4JNN=-2,0 Hz, CH2, 2H), 4.74, 4.79 (AB-square,2JNN=-16 Hz, CH2, 2H), 7.81 (C., CH, 1H), 8.97 (USS, OH, 1H).

1,5-Dihydro-3-tert-butyl-8-methyl-[1,3]doxepin-[5,6-C]-pyridin-9-ol (Z). TPL 178°C. NMR1H (300 MHz, DMSO-d6): δ 0.87 (s, 3, CH3, 9H); 2.37 (s, CH3, 3H); 4.66, 5.31 (AB,2JNN=-14.4 Hz, CH2); 4.51 (s, CH, 1H); 4.81 (d, CH2, 2H); 7.85 (s, CH, 1H); 8.99 (s, OH, 1H). Found, %: C, 65.75; H, 8.35; N, 5.85. C13H19NO3. Calculated, %: C at 65.80; H, 8.07; N, 5.90.

1,5-Dihydro-3-(1-methylbutyl)-8-methyl-[1,3]doxepin[5,6-C]pyridin-9-ol (I). NMR1H (400 MHz, CDCl3): δ of 0.91 (t,3J=7.5 Hz., CH3, 3H); 0.95 (d,3J=6.5 Hz., 2CH3, 6H); 1,07 (t,3J=6.5 Hz., CH3, 3H);1.12-1.68 (m, 4CH2, 8H); 1.76-1.85 (m, CH, 1H); 1.91-2.00 (m, CH, 1H); 2.40 (s, 2CH 3, 6H); 4.55 (s, CH2, 2H); 4.69 (d,3J=7.0 Hz., CH, 1H); 4.70, 4.89 (AB,2J=-14.4 Hz.,4JAH=1.8 Hz., CH2, 2H); 4.73, 5.31 (AB,2J=16.0 Hz,4JEN=1.8 Hz., CH2, 2H); 4.84 (DD,3J=4.0 Hz.,4J=1.8 Hz., CH, 1H); 4.99, 5.01 (AB,2J=-16.0 Hz., CH2, 2H); 8.99 (USS, 2OH, 2H); 7.76 (s, CH, 1H); 7.85 (s, CH, 1H).

1,5-Dihydro-3-cyclo-hexyl-8-methyl-[1,3]doxepin-[5,6-C]-pyridin-9-ol (N). NMR1H (400 MHz, DMSO-d6): δ 0.96-1.23 (m, CH, 2CH2, 5H); 1.50-1.76 (m, 3CH2, 6H); 2.37 (s, CH3, 3H); 4.59 (d,3J=6.0 Hz., CH, 1H); 4.64, 5.15 (AB,2JNN=-15.6 Hz, CH2); 4.72, 4.80 (AB,2JNN=-14.2 Hz, CH2); 7.81 (s, CH, 1H).

Example 4

The method of obtaining semichronic acetals pyridoxine (K-m, o-t) condensation in benzene with azeotropic distillation of water.

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 0.02 mol of carbonyl compound 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 recrystallize from ethanol. The output of 30-35%.

1,5-Dihydro-3-heptyl-8-methyl-[,3]doxepin[5,6-C]pyridin-9-ol (C). TPL 145°C, the NMR1H (400 MHz, DMSO-d6): δ 0,86 (t3J=7 Hz., CH3, 3H); 1,25 (m, CH2, 10H); of 1.57 (m, CH2, 2H); 2,35 (s, CH3, 3H); 4,66 5,14 (AB,2J=15 Hz., CH2, 2H); 4,71 4,77 (AB,2J=14 Hz, CH2, 2H); 4,89 (t3J=5.4 Hz, CH, 1H); 7,76 (s, CH, 1H).

1,5-Dihydro-3-octyl-8-methyl-[1,3]doxepin[5,6-C]pyridin-9-ol (L).

NMR1H (400 MHz, DMSO-d6): δ 0,86 (t3J=6.7 Hz., CH3, 3H); 1.24 (USS, 6CH2, 12H); 1.56 (m, CH2, 2H); 2.34 (s, CH3, 3H); 4.65 5.13 (AB,2J=-15.3 Hz., CH2, 2H); 4.71 4.77 (AB,2J=-14.1 Hz., CH2, 2H); 4,86 (t3J=5.4 Hz., CH, 1H); 7.74 (s, CH, 1H).

1,5-Dihydro-3-(1-methyldecyl)-8-methyl-[1,3]doxepin[5,6-C]pyridin-9-ol (M). NMR1H (400 MHz, DMSO-d6): δ of 0.85 (t,3J=7.0 Hz., CH3, 3H); 0.85 (d,3J=6.5 Hz., CH3, 3H); 1.24 (USS, 7CH2, 14H); 1.32 (m, CH2, 1H); 1.46 (m, CH2, 1H); 1.68 (m, CH2, 2H); 2.35 (s, CH3, 3H); 4.65 (d,3J=5.26 Hz., CH, 1H); 4.66 5.18 (AB,2J=-15.2 Hz., CH2, 2H); 4.75 4.78 (AB,2J=14.2 Hz, CH2, 2H); 7.80 (s, CH, 1H).

8-Methyl-1,5-dihydrospiro[[1,3]doxepin[5,6-C]pyridine-3,1'-cyclopentane]-9-ol (A) 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).

8-Methyl-1,5-dihydrospiro[[1,3]doxepin[5,6-C]pyridine-3,1'-cyclohexane]-9-ol (P) TPL: 162-163°C, NMR1H (300 MHz, DMSO-d6): δ of 1.40 (m, CH2, 2H); for 1.49 (m, 2CH2, 4H); 1,72 (m, 2CH2, 4H); ,33 (C, CH3, 3H); 4,71 (s, CH2, 2H); a 4.83 (s, CH2, 2H); 7,72 (s, CH, 1H), 8,83 (USS, OH, 1H).

8-Methyl-1,5-dihydrospiro[[1,3]doxepin[5,6-C]pyridine-3,1'-Cycloheptane]-9-ol (R) NMR1H (400 MHz, CDCl3): δ of 1.37 to 1.47 (m, CH2, 1H), 1,49-of 1.65 (m, 4CH2, 7H), 1,66 of-1.83 (m, CH2, 1H), 1,84-2,03 (m, 2CH2, 3H), 2,32 (C., 3H, CH3), 4,73 (C., CH2, 1,3H), 4.75 in (C., CH2, 0,7H), equal to 4.97 (SD, CH2, 1,4H), 4,98 (C., CH2, 0,6H), to 7.61 (C., CH, 1H), 8,78 (USS, OH, 1H).

1,5-Dihydro-3-8-dimethyl-3-pentyl-[1,3]doxepin[5,6-C]pyridin-9-ol (IIC). NMR1H (400 MHz, CDCl3): δ 0,89 (that is,3JNN=6,5 Hz, CH3, 3H), 1,20-of 1.44 (m, 3CH2, 6H), 1,40 (C., CH3, 3H), 1,67 of-1.83 (m, CH2, 2H), 2,32 (C., CH3, 3H), 4,74, 4,77 (AB-square,2J=-16 Hz, CH2, 2H), 4.95 points, 4,99 (AB-square,2J=-18 Hz, CH2, 2H), 7,66 (C., CH, 1H), 8.34 per (USS, OH, 1H).

1,5-Dihydro-3-8-dimethyl-3-octyl-[1,3]doxepin[5,6-C]pyridin-9-ol (T). NMR1H (400 MHz, CDCl3): δ 0.87 for(that is,3JNN=6,9 Hz, CH3, 3H), 1,17-1,66 (USM, N, 6CH2), 1,41 (C., CH3, 3H), 1,63-to 1.87 (m, CH2, 2H), 2,34 (C., CH3, 3H), 4,74, 4,77 (AB-square,2JNN=-16 Hz, CH2, 2H), 4.95 points, to 4.98 (AB-square,2JNN=-17,2 Hz, CH2, 2H), 6,74 (USS, OH, 1H), 7,68 (C., CH, 1H).

Example 5.

A common technique to obtain 9-(2,4-dinitrophenoxy) derivatives acetals pyridoxine (Ia-t).

To a solution of 0.005 mol in 20 ml of ethanol is added 0.276 g of sodium methylate and the mixture evaporated to dryness. The dry residue was dissolved in 5 ml DIMET formamide. To the resulting solution was added dropwise with stirring a solution of 0.005 mole of 2,4-dinitrochlorobenzene in 3 ml of dimethylformamide. Maintained the reaction mass for 30 min at room temperature and then another 30 minutes while heating on a water bath. Next, the product was dropped off from the reaction mixture with water and after filtration was dried. The product was recrystallized from alcohol. The yield of 85-90%.

1,5-Dihydro-3,8-dimethyl-9-(2,4-dinitrophenoxy)-[1,3]doxepin[5,6-C]pyridine (Ia). TPL 189-189 .5°C. NMR1H (300 MHz, CDCl3): δ 1.37 (d,3JHH=5.2 Hz, CH3, 3H); 2.35 (s, CH3, 3H); 5.01,4.81 (AB,2JHH=-14.6 Hz, CH2); 4.37-5.06 (m, ush., CH2); 5.11 (K3JHH=5.2 Hz, 1H); 6.67-8.90 (m, ar., 3H); 8.31 (s, CH, 1H).

1,5-Dihydro-3,3,8-trimethyl-9-(2,4-dinitrophenoxy)-[1,3]doxepin[5,6-C]pyridine (IB). TPL 177.5-178°C. NMR1H (300 MHz, DMSO-d6): δ 1.38 (s, 2CH3, 6N); 2.25 (s, CH3, 3H); 4.63(s, CH2, 2H); 4.88 (s, CH2, 2H); 8.32 (s, CH, 1H), 6.89-8.94 (m, C6H3N2O4, 3H).

1,5-Dihydro-8-methyl-9-(2,4-dinitrophenoxy)-[1,3]doxepin[5,6-C]pyridine (Ie). TPL 148-149°C. NMR1H (400 MHz, CDCl3): δ 2,35 (C., CH3, 3H), 4,50 is 5.07 (m, CH22N,), 4,92 (C., CH2, 2H), 4,94 (C., CH2, 2H), 6,72 (doctor,3JHH=9,0 Hz, CH, 1H), 8,29 (C., CH, 1H), 8,32 (Shostakovich,3JHH=9,2 Hz,4JHH=-2,3 Hz, CH, 1H), 8,86 (doctor,4JHH=-2,3 Hz, CH, 1H).

1,5-Dihydro-3-ethyl-8-methyl-[1,3]-dioxano[5,6-C]-PI is one (Iك). TPL 112-114°C. NMR1H (400 MHz, CDCl3): δ 0,94(that is,3JHH=7,6 Hz, CH3, 3H), 1.69 in (m, CH2, 2H), 2,37 (C., CH3, 3H), 4,34-5.24 (USM, 2CH2, 4H), 4,82 (t,3JHH=5.5 Hz, CH, 1H), 6,74 (Usc, CH, 1H), 8,32 (C., CH, 1H), 8.34 per (Shostakovich,3JHH=9,0 Hz,4JHH=and 2.8 Hz, CH, 1H), 8,89 (d4JHH=and 2.8 Hz, CH, 1H).

1,5-Dihydro-3-propyl-8-methyl-9-(2,4-dinitrophenoxy)-[1,3]doxepin[5,6-C]pyridine (Ia). TPL 119-120°C. NMR1H (400 MHz, CDCl3): δ 0,93 (that is,3JHH=7,2 Hz, CH3, 3H), of 1.40 (m, CH22N), of 1.64 (m, CH2, 2H), 2,37 (C., CH3, 3H), 4,29-5,20 (USM, 2CH2, 4H), 4,89 (that is,3JHH=5.7 Hz, CH, 1H), 6,74 (doctor,3JHH=8,5 Hz, CH, 1H), 8,31 (C., CH, 1H), 8,33 (Shostakovich,3JHH=8,5 Hz,4JHH=and 2.5 Hz, CH, 1H), 8,87 (doctor,4JHH=and 2.5 Hz, CH, 1H).

1,5-Dihydro-3-ISO-propyl-8-methyl-9-(2,4-dinitrophenoxy)-[1,3]doxepin[5,6-C]pyridine (S). NMR1H (400 MHz, CDCl3): δ 0,93 (doctor,3JHH=6,5 Hz, CH3, 3H), 0,96 (doctor,3JHH=6,8 Hz, CH3, 3H), 1,92 (ush S., CH, N), of 2.36 (SD, CH3, 3H), 4,33-5,17 (USM, 2CH2CH; 5H), 6.75 in (USS, CH, 1H), 8,32 (C., CH, 1H),8,33 (Shostakovich,3JHH=9,2 Hz4JHH=-2,7 Hz, CH, 1H), 8,89 (doctor,4JHH=-2,7 Hz, CH, 1H).

1,5-Dihydro-3-(1-methylpropyl)-8-methyl-9-(2,4-dinitrophenoxy)-[1,3]doxepin-[5,6-C]pyridine (If). TPL 133-134°C. NMR1H (400 MHz, CDCl3): δ 0.79, which is 0.99 (USM, 2CH3, 6H), 1.06 a is 1.23 (m, CH2, 1H), 1,48-to 1.63 (m, CH2, 1H), 1,68 (Usc, CH, 1H), 2,35 (s, CH3 , 3H), 4,55 (doctor,3JHH=5,1 Hz, CH, 1H), 4,30-of 5.29 (USM, 2CH2, 4H), 6,74 (Usc, CH, 1H), 8,30 (C., CH, 1H), 8.30 to-at 8.36 (USM, CH, 1H), 8,84-8,87 (m, CH, 1H).

1,5-Dihydro-3-tert-butyl-8-methyl-9-(2,4-dinitrophenoxy)-[1,3]doxepin[5,6-C]pyridine (Z). TPL 145-146°C. NMR1H (400 MHz, CDCl3): δ 0,87 (C., 3CH3, N), 2,34 (C., CH3, 3H), of 4.38 (SD, CH, 1H), 4,54-5,12 (USM, 2CH2, 4H), for 6.81 (Usc, CH, 1H), 8,29-at 8.36 (USM, CH, 1H), 8.34 per (C., CH, 1H), cent to 8.85 (doctor,4JHH=and 2.5 Hz, CH, 1H).

1,5-Dihydro-3-(1-methylbutyl)-8-methyl-9-(2,4-dinitrophenoxy)-[1,3]doxepin[5,6-C]pyridine (AI). TPL 96-97°C. NMR1H (400 MHz, CDCl3): δ 0,8-0,95 (m, 2CH3, 6N,), 1,02-1,56 (USM, 2CH2, 4H,), 1.77 in (USM, CH, 1H), 2,35 (s, CH3, 3H), 4,33-5.26 (USM, 2CH2, 4H), 4.53-in (USS, CH, 1H), 6,74 (Usc, CH, 1H), 8.30 to (s, CH, 1H), 8,32 (Shostakovich,3JHH=9,0 Hz,4JHH=-2,6 Hz, CH, 1H), 8,86 (doctor,4JHH=-2,6 Hz, CH, 1H).

1,5-Dihydro-3-heptyl-8-methyl-9-(2,4-dinitrophenoxy)-[1,3]doxepin [5,6-C] pyridine (VBE). TPL 104-105°C. NMR1H (400 MHz, CDCl3): δ 0.87 for (that is,3JHH=7,0, CH3, 3H), 1,2-a 1.44 (m, 5CH210H)of 1.66 (m, CH22N), of 2.38 (SD, CH3, 3H), 4,34 (USM, 2CH2, 4H), 4,88 (that is,3JHH=5.7 Hz, CH, 1H), 6,74 (doctor,3JHH=7,3 Hz, CH, 1H), 8,32 (C., CH, 1H), 8.34 per (Shostakovich,3JHH=7,3 Hz,4JHH=-2,4 Hz, CH, 1H), 8,88 (doctor,4JHH=-2,4 Hz, CH, 1H).

1,5-Dihydro-3-octyl-8-methyl-9-(2,4-dinitrophenoxy)-[1,3]-dioxano[5,6-C]pyridine (Il). TPL 110-111°C. NMR1H (400 MHz, CDCl3): δ 0,84 (.T.,3 JHH=6,8 Hz, CH3, 3H), 1,14-of 1.42 (m, 6CH2, N), and 1.63 (Usc, CH2, 2H), 2,34 (C., CH3, 3H), 4,33-5,23 (USM, 2CH2, 4H), a 4.86 (m, CH, 1H), 6.73 x (doctor,3JHH=6,1 Hz, CH, 1H), 8,29 (s, CH, 1H), 8,32 (Shostakovich,3JHH=6,1 Hz,4JHH=of-2.1 Hz, CH, 1H), cent to 8.85 (doctor,4JHH=of-2.1 Hz, CH, 1H).

1,5-Dihydro-3-(1-methyldecyl)-8-methyl-9-(2,4-dinitrophenoxy)-[1,3]-dioxano[5,6-C]pyridine (Ei). TPL 74-76°C. NMR1H (400 MHz, CDCl3): δ 0.79, which is 0,94 (USM, 2CH3, 6N), 1,01-1,56 (USM, 8CH2, 16H), at 1.73 (m, CH, 1H), 2,33 (C., CH3, 3H), or 4.31-5,07 (USM, 2CH2, 4H), 4.53-in (USS, CH, 1H), 6.73 x (Usc, CH, 1H), 8,28 (s, CH, 1H), 8,31 (Shostakovich,3JHH=9,0 Hz,4JHH=and 2.5 Hz, CH, 1H), cent to 8.85 (doctor,4JNN=-2,6 Hz, CH, 1H).

1,5-Dihydro-3-cyclo-hexyl-8-methyl-9-(2,4-dinitrophenoxy)-[1,3]-dioxano[5,6-C]pyridine (IR). TPL 102-103°C. NMR1H (400 MHz, CDCl3): δ 0,90-1.27mm (USM, 3CH2, 5H), 1,53-1,85 (USM, 3CH2, 6N), 2,35 (C., CH3, 3H), 4,32-to 5.21 (USM, 2CH2, 4H), 4,50 (doctor,3JHH=5.5 Hz, CH, 1H), 6.73 x (doctor,3JHH=7,0 Hz, CH, 1H), 8,29 (C., CH, 1H), 8,32 (Shostakovich,3JHH=7,0 Hz,4JHH=and 2.5 Hz, CH, 1H), 8,86 (doctor,4JHH=and 2.5 Hz, CH, 1H).

8-Methyl-9-(2,4-dinitrophenoxy)-1,5-dihydrospiro[[1,3]doxepin [5,6-C]pyridine-3,1'-cyclopentane] (A) TPL 172-173°C. NMR1H (400 MHz, CDCl3): δ of 1.62 and 1.75 (m, 2CH2, 4H,), 1,77-of 1.95 (m, 2CH2, 4H), 2,32 (C., CH3, 3H), 4,27-5,20 (USM, CH2, 2H), 4,85 (C., CH22N), of 6.71 (doctor,3JHH=9.4 Hz, CH, 1H), 8,24 (C., CH, 1H, 8,31 (Shostakovich,3JHH=9.4 Hz,4JHH=and 2.8 Hz, CH, 1H), cent to 8.85 (d,4JHH=and 2.8 Hz, CH, 1H).

8-Methyl-9-(2,4-dinitrophenoxy)-1,5-dihydrospiro[[1,3]doxepin[5,6-C]pyridine-3,1'-cyclohexane] (In) TPL 121-122°C. NMR1H (400MHz, CDCl3): δ of 1.42 (m, CH22N,), of 1.53 (m, 2CH2, 4H), 1,72 (m, 2CH2, 4H), 2,32 (s, CH3, 3H), 4,43-5,09 (m, CH22N,), 4,89 (C., CH22N,), of 6.71 (doctor,3JHH=remaining 9.08, CH, 1H), 8,24 (C., CH, 1H,), 8,31 (Shostakovich,3JHH=remaining 9.08,4JHH=-2,5, CH, 1H), 8,86 (doctor,4JHH=-2,5, CH, 1H).

8-Methyl-9-(2,4-dinitrophenoxy)-1,5-dihydrospiro[[1,3]doxepin[5,6-C]pyridine-3,1'-Cycloheptane] (IP) TPL to 140.5-141°C. NMR1H (400 MHz, CDCl3): δ 1,36-of 1.45 (m, CH2, 1H) 1,45-of 1.65 (m, 4CH2, 7H), 1,65-of 1.81 (m, CH2, 1H), 1,81 is 2.01 (m, 2CH2, 3H), 2,32 (C., CH3, 3H), of 4.44-5.09 (m, CH2, 2H), 4,87 (Usc, CH2, 2H), 6,72 (doctor,3JHH=9.1 Hz, CH, 1H), 8,23 (s, CH, 1H), 8,32 (Shostakovich,3JHH=9.1 Hz,,4JHH=-2,6 Hz, CH, 1H), 8,86 (doctor,4JNN=-2,4 Hz, CH, 1H).

1,5-Dihydro-3-pentyl-3,8-dimethyl-9-(2,4-dinitrophenoxy)-[1,3]-dioxano[5,6-C]pyridine (IC). NMR1H (400 MHz, CDCl3): δ 0.87 for (m, CH3, 3H), 1.18 to 1,62 (USM, 3CH2, 6N),to 1.38 (s, CH3, 3H), 1,72 (m, CH2, 2H), 2,32 (s, CH3, 3H), 4,42 is 5.07 (USM, CH22N), to 4.87 (s, CH2, 2H), 6,72 (doctor,3JHH=9,0 Hz, CH, 1H), 8,24 (C., CH, 1H), 8,32 (Shostakovich,3JHH=9,0 Hz,4JHH=and 2.5 Hz, CH, 1H), 8,87 (doctor,4JHH=and 2.5 Hz, CH, 1H).

1,5-Dihydro-3-octyl-3,8-dim the Teal-9-(2,4-dinitrophenoxy)-[1,3]-dioxano[5,6-C]pyridine (It). NMR1H (400 MHz, CDCl3): δ 0,86 (that is,3JHH=6,7, CH3, 3H,), 1,18 was 1.43 (m, 6CH2N), 1,39 (C., CH3, 3H), 4,42-5,04 (m, CH2, 2H), 4,88 (C., CH2, 2H), 6,72 (doctor,3JHH=9,2 Hz, CH, 1H), 8,25 (C., CH, 1H), 8,33 (Shostakovich,3JHH=9,2 Hz,4JHH=and 2.8 Hz, CH, 1H), 8,88 (doctor,4JHH=and 2.8 Hz, CH, 1H).

Example 6

The results of the study of nonlinear optical properties of the claimed compounds.

Studies were performed on a pulsed neodymium laser (1064 nm) with a frequency of 10 Hz, spot size of 2.5×1 mm, the Maximum energy density at the above spot size: 0.7 j/cm2. As reference compounds were used meta-nitroaniline and lithium Iodate. The results of the tests are presented in table 1.

Table 1.
The threshold value of the pump energy and the conversion of the powder SHG most active of these compounds.
ConnectionThe threshold value of the pump energy, mWThe conversion factor
IB260,65
IK72,46
Il440,038
Ei480,018
O310,069
In330,22
meta-nitroaniline190,24
the lithium Iodate190,40

From the presented data shows that the claimed compounds have the ability to powder SHG, while some of them have a much greater conversion of laser radiation than the meta-nitroaniline (increased up to 2.5 times) and lithium Iodate (gain up to 1.5 times).

Example 7

Investigation of the stability of the claimed compounds was performed on a neodymium laser (wavelength 1064 nm). The repetition rate of the pump pulses 12.5 Hz. The duration of the laser pulse ~10 NS. The average laser power of 430 mW. The energy of the laser pulses ~34.4 MJ. Pulsed laser radiation power of ~3.4 MW. The surface area of the laser radiation on the samples of ~1.15 j/cm2.

The results of the study the Oia showed in contrast to the reference meta-nitroaniline loss of conversion efficiency after irradiation of a sample IB within 100 not observed (m-nitroaniline for the same period of the exposition loses nearly 20%).

Derivatives of pyridoxine General formula (I)

where R1represents a hydrogen atom or methyl, R2represents a hydrogen atom, methyl, linear, branched alkyl or cycloalkyl or R1and R2together form a cyclic alkyl, with the ability to powder second-harmonic generation (SHG).



 

Same patents:

The invention relates to nonlinear optical crystal strontium to bellacourt, method of cultivation of nonlinear optical single crystals of Bellaterra and nonlinear optical device

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new compound, namely 1-(2-(4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluor-1,5-naphthyridin-2(1H)-one monohydrate which possess strong antibacterial activity. This compound is highly safe and applicable in the production of pharmaceutical preparations as a parent drug. What is furthermore described is a method for preparing 1-(2-(4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluor-1,5-naphthyridin-2(1H)-one monohydrate of formula 19 and methods for preparing intermediate compounds.

EFFECT: preparing the compounds possessing strong antibacterial activity.

8 cl, 1 tbl, 17 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to (aza)indole derivatives of formula

wherein the values T, X1-X3, R1, Q, Y, J are presented in clause 1 of the patent claim.

EFFECT: compounds possess xanthine oxidase inhibitory action that enables using it in a pharmaceutical composition for treating a disease specified in a group consisting of hyperuricemia, gouty tophus, gouty arthritis, renal diseases associated with hyperuricemia and nephrolithiasis.

19 cl, 62 tbl, 332 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to particular compounds, which demonstrate inhibiting activity with respect to ERK, whose structure formula is given in description, to their pharmaceutically acceptable salts, based on them pharmaceutical composition and their application for treatment of cancer, mediated by ERK activity.

EFFECT: obtaining compounds, which demonstrate inhibiting activity with respect to ERK.

5 cl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof: (I) where R1, R2 and R3, which are identical or different, denote H, lower alkyl; R4, R5, R6, R7 and R8, which are identical or different, denote H, lower alkyl, halogen, nitro, -X-OR0, -X-NR10R11, -X-NR0C(O)R10, -X-O-halogen lower alkyl, -X-O-X-phenyl; or R6 and R7 are combined to form -O-lower alkylene-O-; R, which is identical or different, denotes H, lower alkyl; R10, R11, which are identical or different, denote H, lower alkyl; X, which is identical or different, denotes a bond, lower alkylene.

EFFECT: compounds exhibit type 5 17βHSD inhibiting activity, which enables their use in producing a pharmaceutical composition and in a method of inhibiting type 5 17βHSD.

15 cl, 11 tbl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to substituted pyrazolopyrimidines derivatives of formula , wherein Y1, Y2, Y3, Y4 represent N or C-, wherein at least, two groups of Y1-Y4 represent carbon atom, R1 represents chlorine or bromine, R2-R7 represent, e.g. hydrogen, methyl or ethyl; and R10 and R11 independently represent, e.g. hydrogen or C1-C6alkyl, their optical isomers and pharmaceutically acceptable salts. Also, the invention refers to using said compounds for treating and preventing a number of acute and chronic mGluR5 related neurological disorders, such as, e.g. pains of various character, dyskinesia, Parkinson's disease, anxiety disorder, Alzheimer's disease and others, a pharmaceutical composition containing specified compounds and methods for preparing them.

EFFECT: compounds are strong mGluR5 modulators.

21 cl, 2 tbl, 274 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel cyclohexylamine derivatives of formula (I), having inhibiting properties towards at least one monoamine transporter, such as serotonin transporter, dopamine transporter or norepinephrine transporter, or a combination of two or more transporters. The compounds can be used to treat and/or prevent central nervous system disorders such as pain, depression, anxiety, schizophrenia, sleep disorder etc. In formula (I) , n equals 0 or 1; s equals 1, 2 or 3, m equals a whole number from 0 to 12; Ar is

or where Y and Z are (i) both halogen; or (ii) one of Y and Z is CF3 or OCF3 and the other is hydrogen; Y1, Z1, Y2 and Z2 each independently denotes H or a halogen; each X independently denotes H, halogen, CF3, OR5, (C1-C4)alkyl, optionally substituted with halogen or OH, or NR6R7; each R1 and R2 independently denotes H or (C1-C6)alkyl; and each R3 and R4 independently denotes H or (C1-C9)alkyl optionally substituted with OH; where each R5 independently denotes H, (C1-C4)alkyl or phenyl; and each R6 and R7 independently denotes H or (C1-C4)alkyl; where at least two of R1, R2, R3, R4 and X together with atoms to which they are bonded are optionally bonded to form a 5-6-member ring, where the 5-6-member ring is selected from: a) R3 and R4 together with a nitrogen atom to which they are bonded optionally form a pyrrolidine, piperidine, piperazine or morpholine ring, which is optionally substituted with (C1-C4)alkyl; b) when R3 is H or lower alkyl, X and R4 together with atoms to which they are bonded optionally form a 1,3-oxazine ring; c) two X substitutes together with a carbon atom to which they are bonded optionally form a 1,3-dioxolane ring; and d) when R1 and R3 denote hydrogen, R2 and R4 together with atoms to which they are bonded optionally form a 5- or 6-member saturated heterocyclic ring containing one nitrogen atom.

EFFECT: high efficiency of using the compounds.

29 cl, 36 dwg, 11 tbl, 6 ex

FIELD: pharmacology.

SUBSTANCE: invention relates to novel compounds - tetrahydronaphthyridine derivatives of formula (I) or their pharmaceutically acceptable salts, where R1 represents C1-6alkoxycarbonyl group optionally substituted with 1-5 substituents, etc; R2 represents C1-6alkyl group; R3 represents hydrogen or and all; R4 represents C1-4alkylene group; R5 represents optionally substituted unsaturated 5-8-member heterocyclic group containing 1-4 heteroatoms independently selected from oxygen and nitrogen atoms; R6, R7 and R8 represent independently hydrogen atom, hydroxygroup, cyanogroup, C1-6alkyl group, C1-6alkoxygroup, mono- or di- C1-6alkylcarbamoyl group or mono- or di- C1-6alkylaminogroup, optionally substituted with 1-6 substituents independently selected from halogen atom, C1-6alkoxygroup and aminogroup; R10 represents optionally substituted with 1-2 substituents phenyl group; which possess inhibiting activity with respect to cholesteryl ester transfer protein (CETP).

EFFECT: novel tetrahydronaphthyridine derivatives and method of obtaining them.

12 cl, 408 ex, 38 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to new derivatives of benzodiazine of the formula (1), which possess properties of inhibiting proliferative action and can be used during treatment of hyper-proliferative diseases like cancer. In formula (I) G1 and G2 each independently representing a halogen; X1 -R1 selected C1-C6-alkoxy, X2 represents a simple bond; Q1 represents a non-aromatic saturated 3-7-member monocyclic heterocyclic ring with 1 circular heteroatom of nitrogen and not necessarily 1 or 2 heteroatoms, selected from nitrogen, oxygen and sulphur, where Q1 does not necessarily have 1, 2 or 3 substitute groups, which can be similar or different , selected from cyano, carbamoyl, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkylthio, C1-C6-alkyl-sulfinyl C1-C6-alkyl-sulfonyl, N-C1-C6-alkyl-carbamoyl N,N-di-[C1-C6-alkyl]carbamoyl, C1-C6-alkanoyl, sulfamoyl, N-C1-C6-alkyl-sulfamoyl, N,N-di-[C1-C6-alkyl-]sulfamoyl, carbamoyl C1-C6-alkyl, N-C1-C6-alkyl-carbamoylC1-C6-alkyl, N,N-di-[C1-C6-alkyl]carbamoylC1-C6-alkyl, sulfamoylC1-C6-alkyl, N-C1-C6-alkyl-sulfamoylC1-C6-alkyl, N,N-di-[C1-C6-alkyl]sulfamoylC1-C6-alkyl, C1-C6-alkanoylC1-C6-alkyl, or from the group with the formula: Q2 -X3-, where X3 represents CO and Q2 represents a non-aromatic saturated 3-7-member monocyclic heterocyclic ring with 1 circular nitrogen heteroatom and not necessarily 1 or 2 heteroatoms, selected from nitrogen and sulphur, and where. Q2 does not necessarily have 1, 2 or 3 substitute groups, which can be similar or different, selected from halogens, C1-C4-alkyl, and where any C1-C6-alkyl and C2-C6-alkaloid groups within the limits of Q1 does not necessarily have one or more substitute groups, which can be similar or different, selected from hydroxy and C1-C6-alkyl and/or not necessarily a substitute selected from cyano, C1-C6-alkoxy, C2-C6-alkanoxy and NRaRb, where Ra represents hydrogen or C1-C4-alkyl and Rb represents hydrogen or C1-C4-alkyl, or Ra and Rb together with a nitrogen atom, to which they are attached, they form a 4-, 5- or 6- member non-aromatic saturated monocyclic heterocyclic ring with 1 circular heteroatom of nitrogen and not necessarily 1 or 2 heteroatoms, selected from nitrogen, oxygen and sulphur, which not necessarily have 1 or 2 substitutes, which can be similar or different, on the available carbon atom, and selected from halogens and C1-C3-alkilenedioxy.

EFFECT: obtaining new derivatives benzodiazine, which possess properties of inhibiting proliferative action and can be used during the treatment of hyper-proliferative diseases such as cancer

27 cl, 73 ex

FIELD: chemistry.

SUBSTANCE: in general formula (I) , R1 represents similar or different 2 groups, each of which is selected from group consisting of C1-3alkyl, or when R1 are two adjacent groups, two groups R1, taken together, can form saturated or unsaturated 5- or 6-member cyclic group, which can have 1 or 2 oxygens as heteroatom; X represents oxygen or sulphur; values of other radicals are given in invention formula.

EFFECT: increase of composition efficiency.

16 cl, 11 tbl, 31 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted derivatives of noscapine of the general formula (1) or its racemates, optical isomers, or their pharmaceutically acceptable salts and/or hydrates possessing anticarcinogenic activity, and to a pharmaceutical composition as tablets, capsules or injection formulations placed into pharmaceutically acceptable package, ant to methods for their synthesis, and to a method for inhibition of proliferation by their using. In compounds of the formula (1) R1 represents a substitute of amino-group chosen from alkyl; R2 represents a substitute of cyclic system chosen from possibly substituted alkyl wherein substitutes are chosen from possibly substituted amino-group or azaheterocycle comprising possibly oxygen (O), sulfur (S) or nitrogen (N) atoms as an additional heteroatom, and added to alkyl group by nitrogen atom, possibly substituted aryl possibly substituted and possibly condensed heteroaryl comprising at least one heteroatom chosen from nitrogen, sulfur and oxygen atoms, possibly substituted sulfamoyl. Except for, invention relates to 3-(9-iodo-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]-dioxolo-[4,5-g]-isoquinoline-5-yl)-6,7-dimethoxy-3H-isobenzofuran-1-one, 3-(9-chloromethyl-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]-dioxolo-[4,5-g]-isoquinoline-5-yl)-6,7-dimethoxy-3H-isobenzofuran-1-one, 5-(4,5-dimethoxy-3-oxo-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]-dioxolo-[4,5-g]-isoquinoline-9-carbaldehyde (or -9-carbonitrile, or -9-sulfonyl chloride, or -9-carboxylic acid) and 3-(9-methoxymethyl-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]-dioxolo-[4,5-g]-isoquinoline-5-yl)-6,7-dimethoxy-3H-isobenzofuran-1-one, and method for their synthesis. Also, invention relates to combinatory and focused libraries.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds and pharmaceutical composition.

20 cl, 5 tbl, 9 ex

FIELD: organic chemical, pharmaceuticals.

SUBSTANCE: invention relates to new compounds having JAK3 kinase inhibitor activity, methods for production thereof, intermediates, and pharmaceutical composition containing the same. In particular disclosed are aromatic 6,7-disubstituted 3-quinolinecarboxamide derivatives of formula I and pharmaceutically acceptable salts thereof useful in production of drugs for treatment of diseases mediated with JAK3. In formula n = 0 or 1; X represents NR3 or O; Ar is selected from phenyl, tetrahydronaphthenyl, indolyl, pyrasolyl, dihydroindenyl, 1-oxo-2,3-dihydroindenyl or indasolyl, wherein each residue may be substituted with one or more groups selected from halogen, hydroxy, cyano, C1-C8-alkoxy, CO2R8, CONR9R10 C1-C8-alkyl-O-C1-C8-alkyl, etc., wherein R-groups are independently hydrogen atom or C1-C8-alkyl; meanings of other substitutes are as define in description.

EFFECT: new compounds having value biological properties.

17 cl, 222 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel amino- and hydroxy-derivatives of phenyl-3-aminomethylquinolone-2 of the general formula (1):

wherein R1, R2, R3 and R4 are independently similar or different and R1 is chosen from hydrogen atom (H), Alk, OAlk; R2 is chosen from H, Alk, OAlk, -OCF3; R3 is chosen from H, Alk, OAlk, -SCH3; R4 is chosen from H. Alk, OAlk, or R2 and R3 are chosen from -(CH2)3, -OCH2O-, -OCH2CH2O-; R5 means H or Alk; R6, R7 and R9 mean H; R8 is chosen independently from the following substitutes:

wherein n = 1, 2, 3; Het represents furan; R represents hydrogen atom or alkyl. In case of hydroxy-derivatives at least one among R6, R7, R8 or R9 is -OH and other represent H. Also, invention relates to methods for synthesis of these compounds and to a pharmaceutical composition based on these compounds inhibiting activity of NO-synthase. Invention provides preparing novel compounds and pharmaceutical compositions based on thereof in aims for treatment of diseases associated with hyperactivity of phagocytizing cells, for example, rheumatic arthritis, asthma and others.

EFFECT: improved preparing method, valuable medicinal and biochemical properties of compounds and pharmaceutical composition.

32 cl, 1 tbl, 132 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted derivatives of noscapine of the general formula (1) or its racemates, optical isomers, or their pharmaceutically acceptable salts and/or hydrates possessing anticarcinogenic activity, and to a pharmaceutical composition as tablets, capsules or injection formulations placed into pharmaceutically acceptable package, ant to methods for their synthesis, and to a method for inhibition of proliferation by their using. In compounds of the formula (1) R1 represents a substitute of amino-group chosen from alkyl; R2 represents a substitute of cyclic system chosen from possibly substituted alkyl wherein substitutes are chosen from possibly substituted amino-group or azaheterocycle comprising possibly oxygen (O), sulfur (S) or nitrogen (N) atoms as an additional heteroatom, and added to alkyl group by nitrogen atom, possibly substituted aryl possibly substituted and possibly condensed heteroaryl comprising at least one heteroatom chosen from nitrogen, sulfur and oxygen atoms, possibly substituted sulfamoyl. Except for, invention relates to 3-(9-iodo-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]-dioxolo-[4,5-g]-isoquinoline-5-yl)-6,7-dimethoxy-3H-isobenzofuran-1-one, 3-(9-chloromethyl-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]-dioxolo-[4,5-g]-isoquinoline-5-yl)-6,7-dimethoxy-3H-isobenzofuran-1-one, 5-(4,5-dimethoxy-3-oxo-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]-dioxolo-[4,5-g]-isoquinoline-9-carbaldehyde (or -9-carbonitrile, or -9-sulfonyl chloride, or -9-carboxylic acid) and 3-(9-methoxymethyl-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]-dioxolo-[4,5-g]-isoquinoline-5-yl)-6,7-dimethoxy-3H-isobenzofuran-1-one, and method for their synthesis. Also, invention relates to combinatory and focused libraries.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds and pharmaceutical composition.

20 cl, 5 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: in general formula (I) , R1 represents similar or different 2 groups, each of which is selected from group consisting of C1-3alkyl, or when R1 are two adjacent groups, two groups R1, taken together, can form saturated or unsaturated 5- or 6-member cyclic group, which can have 1 or 2 oxygens as heteroatom; X represents oxygen or sulphur; values of other radicals are given in invention formula.

EFFECT: increase of composition efficiency.

16 cl, 11 tbl, 31 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new derivatives of benzodiazine of the formula (1), which possess properties of inhibiting proliferative action and can be used during treatment of hyper-proliferative diseases like cancer. In formula (I) G1 and G2 each independently representing a halogen; X1 -R1 selected C1-C6-alkoxy, X2 represents a simple bond; Q1 represents a non-aromatic saturated 3-7-member monocyclic heterocyclic ring with 1 circular heteroatom of nitrogen and not necessarily 1 or 2 heteroatoms, selected from nitrogen, oxygen and sulphur, where Q1 does not necessarily have 1, 2 or 3 substitute groups, which can be similar or different , selected from cyano, carbamoyl, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkylthio, C1-C6-alkyl-sulfinyl C1-C6-alkyl-sulfonyl, N-C1-C6-alkyl-carbamoyl N,N-di-[C1-C6-alkyl]carbamoyl, C1-C6-alkanoyl, sulfamoyl, N-C1-C6-alkyl-sulfamoyl, N,N-di-[C1-C6-alkyl-]sulfamoyl, carbamoyl C1-C6-alkyl, N-C1-C6-alkyl-carbamoylC1-C6-alkyl, N,N-di-[C1-C6-alkyl]carbamoylC1-C6-alkyl, sulfamoylC1-C6-alkyl, N-C1-C6-alkyl-sulfamoylC1-C6-alkyl, N,N-di-[C1-C6-alkyl]sulfamoylC1-C6-alkyl, C1-C6-alkanoylC1-C6-alkyl, or from the group with the formula: Q2 -X3-, where X3 represents CO and Q2 represents a non-aromatic saturated 3-7-member monocyclic heterocyclic ring with 1 circular nitrogen heteroatom and not necessarily 1 or 2 heteroatoms, selected from nitrogen and sulphur, and where. Q2 does not necessarily have 1, 2 or 3 substitute groups, which can be similar or different, selected from halogens, C1-C4-alkyl, and where any C1-C6-alkyl and C2-C6-alkaloid groups within the limits of Q1 does not necessarily have one or more substitute groups, which can be similar or different, selected from hydroxy and C1-C6-alkyl and/or not necessarily a substitute selected from cyano, C1-C6-alkoxy, C2-C6-alkanoxy and NRaRb, where Ra represents hydrogen or C1-C4-alkyl and Rb represents hydrogen or C1-C4-alkyl, or Ra and Rb together with a nitrogen atom, to which they are attached, they form a 4-, 5- or 6- member non-aromatic saturated monocyclic heterocyclic ring with 1 circular heteroatom of nitrogen and not necessarily 1 or 2 heteroatoms, selected from nitrogen, oxygen and sulphur, which not necessarily have 1 or 2 substitutes, which can be similar or different, on the available carbon atom, and selected from halogens and C1-C3-alkilenedioxy.

EFFECT: obtaining new derivatives benzodiazine, which possess properties of inhibiting proliferative action and can be used during the treatment of hyper-proliferative diseases such as cancer

27 cl, 73 ex

FIELD: pharmacology.

SUBSTANCE: invention relates to novel compounds - tetrahydronaphthyridine derivatives of formula (I) or their pharmaceutically acceptable salts, where R1 represents C1-6alkoxycarbonyl group optionally substituted with 1-5 substituents, etc; R2 represents C1-6alkyl group; R3 represents hydrogen or and all; R4 represents C1-4alkylene group; R5 represents optionally substituted unsaturated 5-8-member heterocyclic group containing 1-4 heteroatoms independently selected from oxygen and nitrogen atoms; R6, R7 and R8 represent independently hydrogen atom, hydroxygroup, cyanogroup, C1-6alkyl group, C1-6alkoxygroup, mono- or di- C1-6alkylcarbamoyl group or mono- or di- C1-6alkylaminogroup, optionally substituted with 1-6 substituents independently selected from halogen atom, C1-6alkoxygroup and aminogroup; R10 represents optionally substituted with 1-2 substituents phenyl group; which possess inhibiting activity with respect to cholesteryl ester transfer protein (CETP).

EFFECT: novel tetrahydronaphthyridine derivatives and method of obtaining them.

12 cl, 408 ex, 38 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel cyclohexylamine derivatives of formula (I), having inhibiting properties towards at least one monoamine transporter, such as serotonin transporter, dopamine transporter or norepinephrine transporter, or a combination of two or more transporters. The compounds can be used to treat and/or prevent central nervous system disorders such as pain, depression, anxiety, schizophrenia, sleep disorder etc. In formula (I) , n equals 0 or 1; s equals 1, 2 or 3, m equals a whole number from 0 to 12; Ar is

or where Y and Z are (i) both halogen; or (ii) one of Y and Z is CF3 or OCF3 and the other is hydrogen; Y1, Z1, Y2 and Z2 each independently denotes H or a halogen; each X independently denotes H, halogen, CF3, OR5, (C1-C4)alkyl, optionally substituted with halogen or OH, or NR6R7; each R1 and R2 independently denotes H or (C1-C6)alkyl; and each R3 and R4 independently denotes H or (C1-C9)alkyl optionally substituted with OH; where each R5 independently denotes H, (C1-C4)alkyl or phenyl; and each R6 and R7 independently denotes H or (C1-C4)alkyl; where at least two of R1, R2, R3, R4 and X together with atoms to which they are bonded are optionally bonded to form a 5-6-member ring, where the 5-6-member ring is selected from: a) R3 and R4 together with a nitrogen atom to which they are bonded optionally form a pyrrolidine, piperidine, piperazine or morpholine ring, which is optionally substituted with (C1-C4)alkyl; b) when R3 is H or lower alkyl, X and R4 together with atoms to which they are bonded optionally form a 1,3-oxazine ring; c) two X substitutes together with a carbon atom to which they are bonded optionally form a 1,3-dioxolane ring; and d) when R1 and R3 denote hydrogen, R2 and R4 together with atoms to which they are bonded optionally form a 5- or 6-member saturated heterocyclic ring containing one nitrogen atom.

EFFECT: high efficiency of using the compounds.

29 cl, 36 dwg, 11 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to substituted pyrazolopyrimidines derivatives of formula , wherein Y1, Y2, Y3, Y4 represent N or C-, wherein at least, two groups of Y1-Y4 represent carbon atom, R1 represents chlorine or bromine, R2-R7 represent, e.g. hydrogen, methyl or ethyl; and R10 and R11 independently represent, e.g. hydrogen or C1-C6alkyl, their optical isomers and pharmaceutically acceptable salts. Also, the invention refers to using said compounds for treating and preventing a number of acute and chronic mGluR5 related neurological disorders, such as, e.g. pains of various character, dyskinesia, Parkinson's disease, anxiety disorder, Alzheimer's disease and others, a pharmaceutical composition containing specified compounds and methods for preparing them.

EFFECT: compounds are strong mGluR5 modulators.

21 cl, 2 tbl, 274 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof: (I) where R1, R2 and R3, which are identical or different, denote H, lower alkyl; R4, R5, R6, R7 and R8, which are identical or different, denote H, lower alkyl, halogen, nitro, -X-OR0, -X-NR10R11, -X-NR0C(O)R10, -X-O-halogen lower alkyl, -X-O-X-phenyl; or R6 and R7 are combined to form -O-lower alkylene-O-; R, which is identical or different, denotes H, lower alkyl; R10, R11, which are identical or different, denote H, lower alkyl; X, which is identical or different, denotes a bond, lower alkylene.

EFFECT: compounds exhibit type 5 17βHSD inhibiting activity, which enables their use in producing a pharmaceutical composition and in a method of inhibiting type 5 17βHSD.

15 cl, 11 tbl, 13 ex

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