Derivatives intellipedia or their pharmaceutically acceptable salts

 

(57) Abstract:

Usage: as substances possessing anti-allergic action. The inventive product derivatives intellipedia General formula I, where R1is phenyl, substituted by substituents selected from the group consisting of lower alkyl, hydroxyl, protected hydroxyl, halogen or lower alkoxy; And the lowest alkylen Into the lower albaniles, or their pharmaceutically acceptable salts. The structure of f-crystals I: 6 C.p. f-crystals, 2 tab.

The invention relates to new derivatives of intellipedia General formula

where R1phenyl substituted by substituents selected from the group consisting of lower alkyl, hydroxyl, protected hydroxyl, halogen or lower alkoxy,

And lower alkylen,

In the lower albaniles, or their pharmaceutically acceptable salts which exhibit anti-allergic effect.

The aim of the invention is the creation of new compounds with more effective pharmacological effect with low toxicity.

P R I m e R 1. To a stirred mixture of 3-[3-methoxy-4-{(2-methoxyethoxy)methoxy} phenyl] -(E)-acrylic acid (1.75 g) and trailmen (1,81 ml) in dry N,N-dimethylformamide (10 ml) medlineta 30 min, to the reaction mixture slowly added to a solution of 1-(2-amino-ethyl)-4-(3-indolyl) piperidine (1.5 g) in dry N,N-dimethylformamide (10 ml) at -10aboutC. After stirring for 1 h at room temperature, the reaction mixture was poured into ice water (200 ml) and extracted with chloroform (100 ml). The extract is washed with saturated sodium chloride solution and dried in the presence of magnesium sulfate. The solution Argonauts and the residue subjected to column chromatography on silica gel (47 g) and eluted with a mixture of chloroform and methanol (10:1). Fractions containing the desired compound are combined and concentrated under reduced pressure to obtain a syrup 1-[2-[3-[3-methoxy-4-{ (2-methoxyethoxy)methoxy} phenyl]-(E)- propanolamine] -ethyl]-4-3-indolyl)piperidine (2.8 g).

NMR (DCl3, ): 1,6-3,3 (11H, m), 3,37 (3H, s), 3,55 (4H, m), 3,85 (2H, m) to 3.89 (3H, s), 5,32 (2H, s), 6.35mm (1H, d, J 15,0 Hz),6,52 (IH,Shir.c) the 6.9 to 7.8 (8H,m), EUR 7.57 (1H, d,J=15,0 Hz), of 8.25 (1H, Shir.C).

P R I m m e R 2. The following compounds were obtained by the method similar to that described in example 1.

(1) 1-[2-[5-[3-methoxy-4-{ (2-methoxyethoxy)methoxy} -phenyl]-(2E, 4E)-2,4-pentadienyl] ethyl] -4-(3-indolyl)piperidine (Nujol): 3300, 1660, 1260, 1092, 990, 744 cm-1< / BR>
NMR (CDCl3, ): 1,6-3,3 (11N, m) to 3.35 (3H, s),ptx2">

(2) 1-[3-[5-3-methoxy-4-{ (2-methoxyethoxy)methoxy} -phenyl] -(2E, 4E)-2,4-pentadienyl]Proline]-4-(3-indolyl)piperidine

NMR (CDCl3, 1.5 to 3.6V (15 NM, m) to 3.36 (3H, s), 3,6 (2H, m), a 3.87 (3H, s), a 3.87(3H, c) are 3.90 (2H, m), to 5.35 (2H, s), of 6.02 (1H, d, J 14.4 Hz), 6,6-7,9 (N, m), 8,55 (1H, s).

Mass: 547 (M+)

(3) 1-[4-[5-[3-methoxy-4-{ (2-methoxyethoxy)methoxy} -phenyl]-(2E, 4E)-2,4-pentadienyl]butyl]-4-(3-indolyl) piperidine

IR (Nujol): 3400, 3200 (W), 1650, 1377, 1260 cm-1.

NMR (DCl3, ): 1,3-3,4 (17H, m) to 3.33 (3H, s), 3,55 (2H, m), 3,80 (5H, Shir. C) at 5.27 (2H, s), 6,11 (1H, d, J 15,0 Hz), 6,5-8,0 (N, m) 9,23 (1H, s).

Mass: 561 (M+)

(4) 1-[2-{5-(3,4-acid)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl) piperidine

so pl. 196-198about(Recrystallization from ethanol)

IR (Nujol): 3280, 1640, 1610, 1590, 1550, 1510 cm-1,

NMR (DMSO-d6, ): 1.4 to 3.5 (13H, m), of 3.78 (3H, s), 3,81 (3H, s), x 6.15 (1H, d, J 15,0 Hz), 6,8-7,6 (11N, m), to 7.99 (1H, Shir.t), is 10.75 (1H, Shir.C).

Mass: 459 (M+), 213

Calculated C 73,18; H 7,24; N 9,14.

C28H33N3O3< / BR>
Found, C 73,84; H 7,42; N 8,72.

(5) 1-[2-{5-(3,4,5-trimethoxyphenyl)-(2E, 4E)-2,4-pentadienyl}ethyl] -4-(3-indolyl)piperidine

so pl. 86-100aboutWITH

IR (Nujol): 3250, 1650, 1610, 1680 cm-1.

NMR (DMSO-d6, ): 1,4-3,6 (13H, m), 3,70 (3H, s), 3,83 is isleno, C 69,23; H 7,31; N 8,35.

C29H35N3O4.3/4H2O.

Found, C 69,38; H 7,08; N 8,40.

(6) 1-[2-{ 3-(4-hydroxy-3-methoxyphenyl)-(E)-propanolamine} ethyl] -4- (3-indolyl)piperidine

so pl. 115-135aboutC.

IR (Nujol): 3300 (W), 1655, 1588, 1512 cm-1.

(7) 1-[2-{5-(4-hydroxy-3-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperidine

so pl. 115-131aboutC.

IR (Nujol): 3330 (W), 1660, 1377 cm-1.

(8) 1-[3-{5-(4-hydroxy-3-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl} propyl]-4-(3-indolyl)piperidine

so pl. 150-170aboutC.

IR (Nujol): 3400, 3200 (W), 1638, 1580 cm-1.

(9) 1-[4-{5-(4-hyroxy-3-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl} butyl]-4-(3-indolyl) piperidine, so pl. 150-170aboutC.

IR (Nujol): 3200 (Shir.), 1640, 1580, 1270, 720 cm-1.

(10) 1-[2-[5-[3,4-{Bis(2-methoxyethoxy)methoxy}phenyl]-(2E, 4E)-2,4-pentadienyl] ethyl]-4-(3-indolyl)-piperidine. This compound was used as the starting compound of example 7-(4) without purification.

(11) 1-[2-[5-[3,5-dimethoxy-4-{ (2-methoxyethoxy)methoxy} -phenyl] -(2E, 4E)-2,4-pentadienyl]ethyl]-4-(3-indolyl) piperidine.

IR (Nujol): 3300, 1650, 1580, 1125, 990, 960, 845, 745 cm-1.

(12) 1-[3-[5-[3,5-di is P> IR (net): 3300, 3000, 2990, 1650, 1615, 1580, 1130, 990, 960, 850 cm-1.

(13) 1-[4-[5-[3,5-dimethoxy-4-{ (2-methoxyethoxy)methoxy} -phenyl] -(2E, 4E)-2,4-pentadienyl]butyl]-4-(3-indolyl) piperidine.

IR (net): 2900, 1650, 1580, 1550, 1120, 960, 860, 740 cm-1.

(14) 1-[2-[5-[4-{(2-methoxyethoxy)methoxy}-3, 5dimethylphenyl]-(2E, 4E)-2,4-pentadienyl]ethyl]-4-(3-indolyl) piperidine.

T square 163-164aboutC (recrystallized from ethyl acetate)

IR (Nujol): 3450, 3300, 1645, 1615, 990, 970 cm-1.

NMR (DMSO-d6, ): 1,5-2,3 (6N, m), 2,34 (6N, (C), 2,5-3,1 (7H, m) of 3.25 (3H, s), 3.5-inch, 3,8 (each 2H, m), of 5.05 (2H, s), x 6.15 (1H, d, J15 Hz), 6,8-in 7.7 (10H, m), 8,03 (1H, m) and 10.7 (1H, m).

Mass (m/e): 531 (M+), 213 (basic).

(15) 1-[2-[5-[3,5-Aminobutiramida-4-{ (2-methoxyethoxy)-methoxy}phenyl]-(2E, 4E)-2,4-pentadienyl]-ethyl]-4-(3-indolyl) piperidine

IR (pure): 1660, 1650, 1615, 970 cm-1.

(16) 1-[2-[5-[4-{(2-Methoxyethoxy)methoxy}-3-were]-(2E, 4E)-2,4-pentadienyl]ethyl]-4-(3-indolyl) piperidine.

So pl. 140-144aboutC.

IR (Nujol): 3470, 3280, 1640, 1610, 1595, 1000, 980 cm-1.

NMR (DCl3, ): 1,6-3,2 (13H, m), of 2.25 (3H, s) to 3.38 (3H, s), 3.6V, 3.8V( each 2H, m), 5,32 (2H, s), 5,96 (1H, d, J 15 Hz), 6,2-7,8 (11N, m) of 8.25 (1H, m).

Mass (m/e): 517 (M+), 213 (basic).

(17) 1-[2-[5-[3-Chloro-4-{ (2-3300, 1645, 1610, 1050, 990 cm-1.

NMR (DMSO-d6, ): 1,5-2,5 (6N, m), is 2.8-3.2 (7H, m), the 3.65 (3H, s), 3.6V, 3.8V (each 2H, m), of 5.39 (2H, s), 6,10 (1H, d, J 15 Hz), 6,8-7,9 (11N, m), with 8.05 (1H, m), is 10.75 (1H, m).

Mass (m/e): 537, 213 (basic).

(18) 1-[2-{5-(3,4-Dihydroxyphenyl)-(2E, 4E)-2,4-pentadienyl}ethyl] -4-(3-indolyl) piperidine.

IR (Nujol): 3400, 3350, 1650, 1585, 1520 cm-1.

Mass (m/e): 431 (M+), 213 (basic).

(19) 1-[2-{ 5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl) piperidine

IR (Nujol): 3420, 1665, 1650, 1620, 1590, 1530, 1515, 1120 cm-1.

Mass (m/e): 475 (M+), 213.

(20) 1-[4-{ 5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl}butyl]-4-(3-indolyl) piperidine

IR (Nujol): 3250, 1640,1600, 1540, 1510, 1130, 1110, 810 cm-1.

(21) 1-[3-{ 5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl}propyl]-4-(3-indolyl) piperidine

IR (Nujol): 3420, 1658, 1610, 1575, 1550, 1510, 1120 cm-1.

Mass (m/e): 489 (M+), 239, 233, 213 (basic), 197.

(22) 1-[2-{5-(4-Acetoxy-3-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperidine.

IR (Nujol): 3440, 3250, 1760, 1655, 1620, 1560, 1505 cm-1.

Mass (m/e): 487 (M+), 213 (basic).

(23) 1-[2-{5-(3-Methoxy-4-propionyloxy)-(2E, 4E)-2,4-pentadienoic +), 213 (basic).

(24) 1-[2-{ 5-(4-ethoxycarbonyl-3,5-acid)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl) piperidine.

IR (Nujol): 3360, 3300, 1750, 1640, 1590, 1130, 1000, 735 cm-1.

Mass (m/e): 547 (M+), 228, 213 (basic).

(25) 1-[4-{ 5-(4-Ethoxycarbonyl-3,5-acid)-(2E, 4E)-2,4-pentadienyl}butyl]-4-(3-indolyl) piperidine.

IR (Nujol): 3380, 3250, 1750, 1655, 1620, 1595, 1555, 1130, 1050, 1000, 735 cm-1.

Mass (m/e): 575 (M+), 531, 503, 285, 233, 213 (basic).

(26) 1-[2-{ 5-(4-hydroxy-3, 5dimethylphenyl)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl) piperidine.

IR (Nujol): 3300, 1640, 1590, 1545, 990, 860 cm-1.

Mass (m/e): 443 (M+), 213 (basic).

(27) 1-[2-{5-(4-Hydroxy-3,5-diisopropylphenyl)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl) piperidine.

IR (Nujol): 3400, 3300, 1650, 1630, 1585, 995, 870 cm-1.

Mass (m/e): 499 (M+), 226, 213 (basic).

(28) 1-[2-{ 5-(4-hydroxy-3-were)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperidine.

IR (Nujol): 3200, 1640, 1575, 1550, 1000 cm-1.

Mass (m/e): 429 (M+), 213 (basic).

(29) 1-[2-{ 5-(3-chloro-4-hydroxyphenyl)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperidine

IR (Nujol): 3420, 1650, 1590, 1000 cm-1.

Mass (m/e): 517 (M+), 213 (basic).

(31) 1-[2-[5-(3,5-the sodium dichloro-4-{(2-methoxyethoxy)methoxy}phenyl]-(2E, 4E)-2,4-pentadienyl]ethyl]-4-(3-indolyl) piperidine.

IR (pure): 1655, 1610, 995 cm-1.

(32) 1-[2-[5-[3-methoxy-2-{ (2-methoxyethoxy)methoxy}-phenyl]-(2E, 4E)-2,4-pentadienyl]ethyl]-4-(3-indolyl) piperidine.

IR (pure): 1650, 1610, 1000, 960 cm-1.

(33) 1-[2-[5-[4-Methoxy-3-{ (2-methoxyethoxy)methoxy}-phenyl]-(2E, 4E)-2,4-pentadienyl]ethyl]-4-(3-indolyl) piperidine.

So pl. 135-136aboutC (recrystallized from ethyl acetate).

IR (Nujol): 3260, 1640, 1615, 1595, 1550, 1510 cm-1.

NMR (DMSO-d6, ): of 3.75 (3H, s), 5,23 (2H, s), 6,11 (1H, d, J 15 Hz), 6,7-7,6 (11N, m) of 7.96 (1H, t), is 10.7 (1H, Shir.).

Mass (m/e): 533, 445, 333, 213 (basic).

(34) 1-[2-[5-[3,5-di-tert-Butyl-2{(2-methoxyethoxy)-methoxy}phenyl]-(2E, 4E)-2,4-pentadienyl] -ethyl] -4-(3-indolyl) piperidine, so pl. 98-103aboutC (recrystallized from ethanol).

IR (Nujol): 3300, 1650, 1600, 970 cm-1.

NMR (DCl3, ): 1,42 (N, C), 1,6-2,3 (6N, m) of 2.53 (2H, t, J 7 Hz), and 2.8 (3H, m),(3H, (c) 3,5 (2H, m), 3,663,96 (each 2H, m), is 4.93 (2H, s), 5,95 (1H, d, J 15,5 Hz), 6,17 (1H, t like), and 6.6 to 7.7 (10H, m), and 8.2 (1H, s).

(35) 1-[2-{5-(3,5-di-tert-Butyl-4-g cm-1.

Mass (m/e): 527 (M+), 226, 213.

(36) 1-[2-{ 5-(3,5-the sodium dichloro-4-hydroxyphenyl)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl)-piperidine.

Mass (m/e): 485 (M+2), 483 (M+), 213 (basic).

(37) 1-[2-{5-(2-hydroxy-3-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperidine

IR (Nujol): 3400, 3240, 1650, 1605, 1600, 1530, 1090, 1005 cm-1.

Mass (m/e): 445 (M+), 226, 213 (basic).

(38) 1-[2-{5-(3-Hydroxy-4-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperidine.

IR (Nujol): 3350, 1650, 1615, 1590 cm-1.

Mass (m/e): 445 (M+), 213 (basic).

(39) 1-[2-[5-{3,4-bis(3-Ethoxycarbonyl)phenyl}-(2E, 4E)-2,4-pentadienyl]ethyl]-4-(3-indolyl piperidine

IR (Nujol): 3500, 3350, 1775, 1650, 1620, 1000 cm-1.

Mass (m/e): 529 (M+-46), 457, 285 (basic) 213.

P R I m e R 3. To a solution of 1-[2-[5-[3,5-di-tert-Butyl-4-{(2-methoxyethoxy)methoxy}phenyl]-(2E, 4E)-2,4-pentadienyl]ethyl]-4-(3-indolyl) piperidine (0.5 g) in methanol (5 ml) is added drop by drop methansulfonate acid (0,26 ml) at 18-25aboutC. After 2 h the reaction mixture using a 2n-sodium hydroxide is brought to pH 7.5, and then poured into saturated sodium bicarbonate solution (50 ml). The resulting precipitious with a mixture of chloroform and methanol (20:1). The fractions containing the desired compound are combined and concentrated under reduced pressure. The remainder recrystallized from 1,4-dioxane to obtain white crystals of the compound 1-[2{5-(3,5-di-tert-butyl-4-hydroxyphenyl)-(2E, 4E)-2,4-pentadienyl}-ethyl]-4-(3-indolyl) piperidine (0.28 g).

So pl. 108-115aboutWITH

IR (Nujol): 3550, 3300, 3230, 1650, 1610, 1590, 1000 cm-1.

NMR (CDCl3, ): 1,43 (N, C), 1,6-2,3 (6N, m) of 2.53 (2H, t, J 7 Hz), 2,7-3,2 (3H, m), of 3.45 (2H, m), 5,33 (1H, s), to 5.93 (1H, d, J 15,5 Hz), x 6.15 (1H, t like.), 6,65 to 7.7 (10H, m), 8,16 (1H, s).

Mass (m/e): 527 (M+), 226, 213.

P R I m e R 4. To the mixed solution 1-[2-[5-[3,5-dimethoxy-4-{(2-methoxyethoxy)methoxy}phenyl]-(2E, 4E)-2,4-pentadienyl]-ethyl]-4-(3-indolyl) piperidine (10.0 g) in methanol (100 ml) is slowly added methansulfonate acid (2.3 ml) at room temperature. After stirring for 2 h, the reaction mixture using a 2n-aqueous sodium hydroxide solution is brought to pH 7.2 and poured into a solution of 4.5 sodium bicarbonate in 500 ml of water. After stirring for 30 min, the resulting precipitate is collected by filtration and washed with 100 ml water. The residue is subjected to column chromatography on silica gel and eluted with a mixture of chloroform and myenecrolysis from ethanol to obtain 1-[2-{5-(4-hydroxy-3,5-acid)-(2E, 4E), pentadecanolide}ethyl]-4-(3-indolyl)piperidine (6.69 in).

So pl. 199-202aboutC.

IR (Nujol): 3420, 1665, 1650, 1620, 1590, 1530, 1515, 1120 cm-1.

NMR (DMSO-d6, ): 1.5 and 2.4 (7H, m), 2,7-3,5 (6N, m), 3,81 (6N, C), x 6.15 (1H, d, J 14 Hz), 6,8-7,8 (10H, m) 8,0 (1H, t), 8,68 (1H, m), is 10.75 (1H, s).

Mass (m/e): 475 (M+), 213.

Calculated C 70,71; H 6,99; N 8,83.

C28H33N3O4.

Found, C 70,34; H 6,56; N 8,65.

P R I m e R 5. The mixture 1-[3-[5-[3,5-dimethoxy-4-{(2-methoxyethoxy)methoxy} phenyl] -(2E, 4E)-2,4-pentadienyl] -propyl] -4-(3-indolyl) piperidine (1,67 g) and monohydrate p-toluenesulfonic acid (0.64 g) in methanol (33 ml) is heated in a flask with reflux condenser for 30 min in an inert atmosphere. After cooling to room temperature, the mixture is added drop by drop to the aqueous solution of sodium carbonate. The resulting powder substance is subjected to column chromatography on silica gel and eluted with a mixture of chloroform and methanol (10:1 vol.). The fractions containing the desired compound are combined and concentrated under reduced pressure. The obtained residue recrystallized from a mixture of ethanol and water (7: Ob.) to obtain 1-[3-{ 5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl}propyl CLASS="ptx2">

IR (Nujol): 3420, 1658, 1610, 1575, 1550, 1510, 1120 cm-1.

NMR (DMSO-d6, ): 1.4 to 2.5 (N, m), 2,6-3,5 (6N, m), 3,79 (6N, (C), 6,10 (1H, d, J 15 Hz), 6,7-in 7.7 (10H, m), with 8.05 (1H, t like.), of 8.7 (1H, m), of 10.72 (1H, s).

Mass (m/e): 489 (M+), 239, 233, 213 (basic) 197.

Calculated C 71,14; H 7,20; N 8,58.

C29H35N3O4< / BR>
Found, C 70,79; H 7,12; N 8,57.

P R I m e R 6. The mixture 1-[2-[3-[3-methoxy-4{(2-methoxyethoxy)methoxy}-phenyl] -(E)-propanolamine] ethyl]-4-(3-indolyl)-piperidine (2 g) and monohydrate p-toluenesulfonic acid (1,05 g) in methanol (40 ml) is heated in a flask with reflux condenser for 30 min in an inert atmosphere. Then the solution Argonauts under reduced pressure, the residue is washed with water (100 ml) with sodium carbonate solution, the pH is brought to 10 and the resulting solution was extracted with ethyl acetate. The extract is washed with saturated sodium chloride solution and dried in the presence of magnesium sulfate. After removing the solution, the residue is subjected to column chromatography on silica gel (31 g) and eluted with a mixture of chloroform and methanol (8:1). The fractions containing the desired compound are combined and concentrated under reduced pressure to obtain 1-[2-{3-(4-hydroxy-3-methoxyphenyl)-(E)-propanolamine the

NMR (DMSO-d6, 1.5 to 3.6V (14N, m), 3,83 (3H, s), of 6.50 (1H, d, J 15,0 Hz), 6,7-7,7 (N, m), 7,83 (1H, Shir.t), 10,70 (1H, s).

Mass: 419 (M+), 213.

Calculated C 70,00; H 7,06; N 9,80.

C15H29N3O3.1/2H2O

Found, C 70,18; H 6,92; N 9,85.

P R I m e R 7. The following compounds were obtained by the method similar to that described in examples 3-6.

(1) 1-[2-{5-(4-Hydroxy-3-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperidine.

So pl. 115-131aboutC.

IR (Nujol): 3330 (W), 1660, 1377 cm-1.

NMR (DMSO-d6, 1.5 to 3.6V (13H, m), 3,82 (3H, s), 6,07 (1H, d, J 15,0 Hz), and 6.6 and 7.6 (8H, m), of 7.90 (1H, Shir.t) 9,20 (1H, s), is 10.68 (1H, s).

Mass: 445 (M+), 213.

Calculated C 71,34; H 7,10; N 9,24.

C27H31N3O3.1/2H2O

Found, C 71,15; H 6,87; N 9,19.

(2) 1-[3-{5-(4-Hydroxy-3-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl} propyl]-4-(3-indolyl)piperidine.

So pl. 150-170aboutC.

IR (Nujol): 3400, 3200 (W), 1638, 1580 cm-1.

NMR (DMSO-d6, ): 1,5-3,8 (15 NM, m), 3,86 (3H, s), 4,20 (1H, W), x 6.15 (1H, d, J 14,0 Hz), 6,6-7,8 (11N, m), compared to 8.26 (1H, Shir.C) was 10.82 (1H, s).

Calculated C 65,85; H 6,97; N 7,55.

C28H33N3O3.1/2CHClis oxyphenyl)-(2E, 4E)-2,4-pentadienyl} butyl]-4-(3-indolyl) piperidine

So pl. 150-170aboutC.

IR(Nujol):3200 (Shir.), 1640, 1580, 1270, 735 cm-1.

NMR (DMSO-d6, ): 1,2-3,7 (17H, m), of 3.80 (3H, s), 6,07 (1H, d J 15,0 Hz), 6,6-7,8 (11N, m), 8,10 (1H, s), a 9.25 (1H, s), was 10.82 (1H, s).

Mass: 473 (M+), 213

Calculated C 66,33; H 7,16; N 7,37.

C29H35N3O3.1/2CHCl3.1/2C2H5OC2H5.

Found, C 66,02; H 7,47; N 7,33.

(4) 1-[2-{ 5-(3,4-Dihydroxyphenyl)-(2E, 4E)-2,4-pentadienyl}ethyl] -4-(3-indolyl) piperidine.

So pl. 138-158aboutC (decomposition) (recrystallized from a mixture of ethanol and water (8:2 vol.)).

IR (Nujol): 3400, 3350, 1650, 1585, 1520 cm-1.

NMR (DMSO-d6, 1.5 to 3.6V (13H, m), to 7.93 (1H, m), of 10.73 (1H, Shir.).

Mass (m/e): 431 (M+), 213 (basic).

Calculated C 70,07; H 7,49; N 8,63.

C26H29N3O3.6/5 ethanol.

Found, C 69,77; H 7,39; N 8,67.

(5) 1-[4-{5-(4-Hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl}butyl]-4-(3-indolyl) piperidine

IR (Nujol): 3250, 1640, 1600, 1540, 1510, 1130, 1110, 810 cm-1.

(6) 1-[4-{ 5-(4-hydroxy-3, 5dimethylphenyl)-(2E, 4E)-2,4-pentadecanolide}ethyl]-4-(3-indolyl) piperidine

So pl. 125-135 mAabout(Rcris is B>6
, ): 1,4-2,4 (6N, m), 2,19 (6N, (C), of 2.6-3.2 (7H, m), 6,11 (1H, d, J 15 Hz), the 6.7 to 7.6 (10H, m), 7,95 (1H, m), was 10.82 (1H, m).

Mass (m/e): 443 (M+), 213 (basic).

Calculated C 71,92; H Of 7.69; N 8,99.

C28H33N3O2.4/3H2O.

Found, C 72,00; H Of 7.69; N 8,88.

(7) 1-[2-{5-(4-hydroxy-3,5-diisopropylphenyl)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl)piperidine

So pl. 110-120aboutC (recrystallized from a mixture of ethanol-water (8:2 by vol.).

IR (Nujol): 3400, 3300, 1650, 1630, 1585, 995, 870 cm-1.

NMR (DMSO-d6, ): 1.28 (in N, d, J 9 Hz), 1,5-2,4 (6N, m), 2.7-3.6V (N, m), 6,13 (1H, d, J= 15 Hz), of 6.8 to 7.6 (10H, m), 7,95 (1H, m), and 8.4 (1H, m), of 10.73 (1H, m).

Mass (m/e): 499 (M+), 226, 213 (basic).

Calculated C 74,24; H Of 8.37; N 8,11.

C32H41N3O2.H2O.

Found, 73,84; H 8,42; N 7,97;

(8) 1-[2-{ 5-(4-Hydroxy-3-were)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperidine

So pl. 138-141aboutC (recrystallized from a mixture of ethanol-water (8:2 by vol.).

IR (Nujol): 3200, 1640, 1575, 1550, 1000 cm-1.

NMR (DMSO-d6, 1.5 to 3.6V (13H, m), of 2.20 (3H, s), 6,10 (1H, d, J 15 Hz), 6,7-7,7 (11 Hz, m), to 7.93 (1H, m), 9,65 (1H, m), of 10.73 (1H, m).

Mass (m/e): 429 (M+), 213 (basic).

Calculated C 71,73; H 7,47; N 9,29.

C27

So pl. 139-155aboutC (recrystallized from a mixture of ethanol-water).

IR (Nujol): 3420, 1650, 1590, 1000 cm-1.

NMR (DMSO-d6, ): 1,5-3,5 (13H, m), 6,12 (1H, d, J 15Hz), 6,7-7,7 (11N, m), 7,88 (1H, m) and 10.7 (1H, m).

Mass (m/e): 449 (M+), 213 (basic)

Calculated With 65,47; H 6,55; N 8,81.

C26H28Cl3N3O2.1,5 H2O.

Found, C 65,88; H 6,44; N 8,78.

(10) 1-[2-{ 5-(3,5-the sodium dichloro-4-hydroxyphenyl)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl) piperidine.

So pl. 165-175aboutC (recrystallized from N,N-dimethylformamide)

NMR (DMSO-d6, 1.5 to 3.6V (13H, m), 5,3 (1H, m), between 6.08 (1H, d, J 15 Hz), and 6.6 and 7.6 (10H, m), of 8.09 (1H, m), is 10.75 (1H, s)

Mass (m/e): 485 (M+2), 483 (M+), 213 (basic)

(11) 1-[2-{5-(2-hydroxy-3-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperidine.

So pl. 184-186aboutC (recrystallized from ethanol)

IR (Nujol): 3400, 3240, 1650, 1605, 1600, 1530, 1090, 1005 cm-1< / BR>
NMR (DMSO-d6, ): 1,4-3,6 (13H, m), of 3.78 (3H, s), 6,11(1H, d, J 15 Hz), 6,6-7,65 (11N, m), of 7.90 (1H, t like.), of 8.95 (1H, W), is 10.75 (1H, s).

Mass (m/e): 445 (M+), 226, 213 (basic).

(12) 1-[2-{5-(3-Hydroxy-4-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperid the

NMR (DMSO-d6, ): 1.4 to 3.5 (13H, m in), 3.75 (3H, s), 6,11 (1H, d, J 12 Hz), 6,6-7,7 (11N, m), to $ 7.91 (1H, t like.), 9,0 (1H, W), of 10.7 (1H, s).

Mass (m/e): 445 (M+), 213 (basic).

P R I m e R 8. To the mixture 1-[2-{5-(4-hydroxy-3-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl} ethyl] -4-(3-indolyl) piperidine (0,89 g), dry N-methylmorpholine (1.0 g) and dry N,N-dimethylformamide (10 ml) is slowly added acetylchloride (0.26 g) at 5-10aboutC. After stirring for 1 h, the reaction mixture is poured into water (50 ml) and stirred for 1 h the resulting precipitate is collected, washed with water and then recrystallized from a mixture of ethanol and water (7:3 vol.) to obtain 1-[2-{5-(4-acetoxy-3-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl) piperidine (0,22 g).

So pl. 101-105aboutC (recrystallized from a mixture of ethanol and water (8:2 by vol.)

IR (Nujol): 3440, 32500, 1760, 1655, 1620, 1560, 1505 cm-1.

NMR (DMSO-d6, ): 1,5-2,4 (6N, m), 2,24 (3H, s), 2,6-3,5 (7H, m), 3,81 (3H, s), of 6.20 (1H, d, J 15 Hz), 6,8-7,7 (11N, m), of 8.04 (1H, m), of 10.73 (1H, s)

Mass (m/e): 487 (M+), 213 (basic).

Calculated With 68,89; H 6,98; N 8,31.

C29H33N3O4.2H2O.

Found, 68,91; H 6,95; N 8,32.

P R I m e R 9. 1-[2-{5-(3-Methoxy-4-propionyloxy)-(2E, 4E)-2.4GHz-"ptx2">

So pl. 157-158aboutC (recrystallized from ethanol)

IR (Nujol):3430, 3250, 3060, 1750, 1655, 1620, 1560 cm-1.

NMR (DSO-d6, ):to 1.15 (3H, t, J 8 Hz), 1,5-2,4 (6N, m), 2,62 (2H, square J 8gts), 2,4-3,2 (5H, m) to 3.33 (2H, m), 3,82 (3H, s), from 6.22 (1H, d, J 15 Hz) and 6.9 to 7.7 (11N, m), with 8.05 (1H, m), is 10.75 (1H, s)

Mass (m/e): 501 (M+), 213 (basic).

Calculated C 69,34; H 7,18; N 8,09.

C30H35N3O4.H2O.

Found, C 69,19; H To 7.09; N 8,06.

P R I m e R 10. To the mixture 1-[2-{5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl} ethyl] -4-(3-indolyl) piperidine (1 g) and pyridine (10 ml) is slowly added acetylchloride (of 0.48 ml) at 5-10aboutC. After 1 h, the reaction mixture is poured into ice water and extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried in the presence of magnesium sulfate. Then the solution Argonauts and the residue subjected to column chromatography on silica gel and eluted with a mixture of chloroform with ethanol (10:1 vol.). The fractions containing the desired compound are combined and concentrated under reduced pressure. The residue is treated with a mixture of fumaric acid (83 g) with methanol (8 ml) and concentrated under reduced pressure to obtain white crystals. These cristati]-4-(3-indolyl) piperidine 1/2 fumarate (0.25 g).

So pl. 202-209aboutWITH

IR (Nujol): 3400, 1750, 1680, 1615, 1595, 1565 cm-1.

NMR (DMSO-d6, ): 1,6-of 2.15 (5H, m), 2,32 (3H, s), 2,2-3,6 (8H, m), 4,82 (6N, (C), to 6.22 (1H, d, J 14 Hz), only 6.64 (1H, s), 6,7-in 7.7 (10H, m), 8,29 (1H, m), is 10.75 (1H, s)

Mass (m/e): 517 (M+), 213 (basic).

Calculated C 63,77; H Of 6.68; N 6,97.

C30H35N3O5.1/2 fumarate.3/2H2O.

Found, C 63,57; H 6,44; N 6,95.

P R I m e R 11. 1-[2-{5-(3,5-Dimethoxy-4-propionyloxy)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperidine 1/2 of format was obtained by the method similar to that described in example 10.

So pl. 188-192aboutC (recrystallized from ethanol)

IR (Nujol): 3400, 1745, 1680, 1615, 1595, 1565 cm-1.

NMR (DMSO-d6, ): of 1.13 (3H, t, J 7 Hz), 1,6-2,2 (3H, m), 2,2-3,7 (N, m), 3,81 (6N, (C), 6,21 (1H, d, J 15 Hz), 6,62 (1H, s), of 6.8 to 7.6 (10H, m), and 8.3 (1H, m), 10,78 (1H, s)

Mass (m/e): 531 (M+), 213 (basic)

Calculated C 64,27; H 6,86; N For 6.81.

C31H37N3O5.1/2 fumarate.3/2H2O.

Found, C 64,17; H Is 6.78; N Is 6.78.

P R I m e R 12. To the mixture 1-[2-{5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl)piperidine (1.19 g), triethylamine (1,74 ml) and dry N,N-dimethylformamide (12 ml) is slowly added to the mixture ethylchloride the 5-acid)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl) piperidine (0.74 g).

So pl. 90-98aboutC (recrystallized from a mixture of ethanol-water (8:2 by vol.).

IR (Nujol): 3360, 3300, 1750, 1640, 1590, 1130, 1000, 735 cm-1.

NMR (DMSO-d6, ): of 1.28 (3H, t, J 8 Hz), 1,5-3,6 (13H, m), 3,81 (6N, C) to 4.23 (2H, square J8 Hz), 6,21 (1H, d, J 15 Hz), 6,8-in 7.7 (10H, m), with 8.05 (1H, m), 10,71 (1H, s).

Mass (m/e): 547 (M+), 228, 213 (basic)

Calculated C 62,82; H 6,14; N 7,09.

C31H37N3O6.2,5 H2O.

Found, C 62,74; H 6,93; N 7,05.

P R I m e p 13. The following compounds obtained by the method similar to that described in example 13.

(1) 1-[4-{5-(4-Ethoxycarbonylmethoxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl}butyl]-4-(3-indolyl) piperidine.

So pl. 90-98aboutC (recrystallized from a mixture of ethanol-water (8:2 by vol.)

IR (Nujol): 3380, 3250, 1750, 1655, 1620, 1595, 1555, 1130, 1050, 1000, 735 cm-1.

NMR (DMSO-d6, ): of 1.27 (3H, t, J 8 Hz), 1,4-3,7 (17H, m), 3.72 points 6N, m), 3.72 points 6N, C) to 4.23 (2H, square J 8 Hz), of 6.20 (1H, d, J 15 Hz), 6,8-of 7.75 (10H, m), 8,10 (1H, m), of 10.76 (1H, s).

Mass (m/e): 575 (M+), 531, 503, 285, 233, 213 (basic).

Calculated C 67,01; H 7,81; N 6,52.

C33H41N3O6.3/2 ethanol.

Found, C 66,39; H 7,74; N 6,52.

(2) 1-[4-{5-(3,5-DimetokaC (recrystallized from acetonitrile).

IR (Nujol): 3250, 2650, 2500, 1760, 1650, 1595, 1130, 1010, 850, 750 cm-1.

NMR (CDCl3, ): of 1.29 (3H, t, J 8 Hz), 2,65 (2H, square J 8 Hz), 1,5-3,7 (17H, m), 3,80 (6N, (C), 6.35mm (1H, d, J 15 Hz), and 6.6 to 7.7 (10H, m), and 7.9 (1H, m), 9,05 (1H, m), and 11.3 (1H, m).

Mass (m/e): 559 (M+), 503, 233, 213 (basic)

(3) 1-[2-[5-{ 3,4-bis(ethoxycarbonyl)phenyl} -(2E, 4E)-2,4-pentadienyl]ethyl]-4-(3-indolyl) piperidine.

So pl. 135-137aboutC (recrystallized from a mixture of water and ethanol).

IR (Nujol): 3500, 3350, 1775, 1650, 1620, 1000 cm-1.

NMR (DMSO-d6, ): 1,30 (6N, t, J 8 Hz), 1,3-3,5 (13H, m), 4,30 (4H, square J 8 Hz), and 6.25 (1H, d, J 15 Hz), 6,6-7,7 (11N, m), 8,08 (1H, m), of 10.73 (1H, s).

Mass (m/e): 529 (M+-46), 457, 285 (basic), 213.

P R I m e R 14. To the mixture 1-[2-{5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperidine (2.0 g), triethylamine (2.9 ml) and dry N,N-dimethylformamide (20 ml) is slowly added to a solution of acetochlor (0.5 g) and methylene chloride (1.0 ml) in 5aboutC. After 1 h the reaction mixture was poured into water (200 ml) and stirred for 1 h the resulting precipitate is collected, washed with water and dried at room temperature. Then, this precipitate chromatographies on silica gel (60 g) and buyumlari reduced pressure. The remainder recrystallised of ethyl acetate, the resulting light yellow crystals 1-[2-{5-(4-acetoxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl) piperidine (1.35 g).

So pl. 169-172aboutWITH

IR (Nujol): 3380, 3320, 1755, 1650, 1620, 1595, 990, 745 cm-1.

NMR (CDCl3, 1.5 to 3.6V (13H, m), 2,32 (3H, s), 3,82 (6N, C) 6,0 (1H, d, J 15 Hz), 6,34 (1H, m), 6,7-in 7.7 (10H, m), 8,32 (1H, m)

Mass (m/e): 517 (M+), 213 (basic).

Calculated C To 69.61; H 6,82; N 8,12.

C30H35N3O5.

Found, C 69,35; H 6,82; N 8,02.

P R I m e R 15. To a stirred mixture of 5 [3,5-dimethoxy-4-{(2-methoxyethoxy)methoxy}phenyl]-(2E, 4E)-2,4-pentadienoic acid (1.35 g) and triethylamine (1,17 ml) in dry N,N-dimethylformamide (8 ml) is slowly added diphenylphosphoryl (0.97 g)- 10-(-15)aboutWith in an inert atmosphere. After stirring for 1 h, the reaction mixture at the same temperature slowly added a solution of 1-(2-amino-ethyl)-4-(3-indolyl) piperidine (0.97 g) in dry N, N-dimethylformamide (8 ml). After stirring for 40 min at the same temperature, the reaction mixture is poured into ice water (160 ml) and extracted with ethyl acetate. The extract is washed with saturated sodium chloride solution and dried in ethoxyethoxy)methoxy} phenyl]-(2E, 4E)-2,4-pentadienyl]ethyl]-4-(3-indolyl) piperidine (1.97 g).

IR (Nujol): 3300, 1650, 1610, 1580, 1125, 990, 960, 845, 745 cm-1.

P R I m e R 16. To a hot solution of citric acid hydrate (2.65 g) in a mixture of water and ethanol (4:6.about 50 ml) was added 1-2-{5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl) piperidine (6.0 g), and then added a mixture of water with ethanol (4:6, by vol./about. 50 ml). The resulting mixture was stirred for 6 hours at ambient temperature and the resulting precipitate was collected by filtration. The residue was washed with a mixture of water with ethanol and dried to obtain 1-[2-{5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperidineacetate (7.2 g).

So pl. 140-142aboutC.

IR (nuol): 3600, 3370, 3300, 1745, 1645 cm-1.

NMR (DMCO-d6, ): 1,78 is 2.1 (4H, multiplet), is 2.8-3.2 (5H, multiplet), 3,33-3,62 (4H, multiplet), 3,80 (6N, singlet), 6,11 (1H, doublet, J 14,8 Hz), 6,8-of 7.25 (8H, multiplet), was 7.36 (1H, doublet, J 7.9 Hz), to 7.61 (1H, doublet, J 7.5 Hz), 8,35 (1H, broad), 10,86 (1H, broad singlet).

P R I m e R 17. The mixture 1-[2-{5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl} ethyl] -4-(3-indolyl-piperidine (7.0 g), fumaric acid (1,708 g) and methanol (200 ml) was heated from the reverse was built in the th temperature. The resulting precipitate was collected by filtration, washed with methanol (10 ml) and dried with education 1-[2-{ 5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl} ethyl]- 4-(3-indolyl)piperidine fumarata (7,58 g).

So pl. 138-140aboutC.

IR (nuol): 3400-3150, 1700, 1645 cm-1.

NMR (DMSO-d6,) of 1.75 and 2.1 (4H, multiplet), of 2.5-3.0 (5H, multiplet), 3,15-3,5 (4H, multiplet), 3,80 (6N, singlet), 6,09 (1H, doublet J 14,8 Hz), 6,60 (2H, singlet), 6,77-to 7.15 (8H, multiplet), 7,33 (1H, doublet, J 7.8 Hz), to 7.59 (1H, doublet, J 7.4 Hz), scored 8.38 (1H, triplet-like), was 10.82 (1H, broad singlet).

P R I m e R 18. The following compounds were obtained according to the method similar to the method of example 17.

(1) 1-[2-{5-(4-Hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl) piperidine (-)-tartrate (51 UMG received from 1-[2-{5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl) piperidine (0.5 g) and (-)wine kizilot (158 g).

So pl. 144-147aboutC (decomp.)

IR (nuol): 3450-3150, 1710, 1645, 1600 cm-1.

NMR (DMSO-d6, ): 1,75-2,10 (4H, multiplet), of 2.5-3.0 (5H, multiplet), 3,2-3,5 (4H, multiplet), 3,80 (6N, singlet), 4,14 (2H, singlet), 6,10 (1H, doublet, J 14,8 Hz), 6,8-7,26 (8H, multiplet), 7,34 (1H, doublet, J7,8 Hz), to 7.59 (1H, doublet, J 7.4 Hz), a 8.34 (1H, triplet-the ethyl] -4-(3-indolyl) piperidine succinate (0.25 g) was obtained from 1-[2-{5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl}ethyl]-4-(3-indolyl) piperidine (0.5 g) and succinic acid (124 mg).

So pl. 95-105aboutC (decomp.)

IR (nuol): 3400-3100, 1720, 1650, 1590 cm-1.

NMR (DMSO-d6, ): 1,61-2,12 (4H, multiplet), 2,17-2,22 (2H, multiplet), is 2.40 (4H, singlet), 2,5-2,6 (2H, multiplet), 2,7-2,9 (1H, multiplet), a 3.0-3,17 (2H, multiplet), 3,23-of 3.42 (2H, multiplet), 3,80 (6N, singlet), 6,10 (1H, doublet, J 14,8 Hz), 6,78-of 7.25 (8H, multiplet), 7,33 (1H, doublet, J7,8 Hz), 7,55 (1H, doublet, J 7.4 Hz), 8,07 (1H, triplet-like), 10,78 (1H, broad singlet).

P R I m e R 19. To a hot solution of (+)-tartaric acid (2,21 g) in a mixture of ethanol and water (9:1, vol/about. 200 ml) was added 1-[2-{5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl} ethyl] -4-(3-indolyl) piperidine (7.0 g) in the bubbling system with gaseous nitrogen. After that the system was added a mixture of ethanol and water (9:1, vol/about. 80 ml), the mixture was heated under reflux for 5 minutes and then was stirred for 3 hours at ambient temperature. The resulting precipitate was collected by filtration, washed with a mixture of ethanol-water (9:1, vol/about./20 ml) and dried in obtaining 1-[2-{5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl-amino}ethyl]-4-(3-indolyl) piperidine (+)tartrate (8,18 g).

So pl. 142-146about<5-3,0 (5H, multiplet), 3,17-3,5 (4H, multiplet), 3,80 (6N, singlet), of 4.13 (2H, singlet), 6,10 (1H, doublet, J 14,8 Hz), 6,8-7,26 (8H, multiplet), 7,34 (1H, doublet, J7,8 Hz), 7,58 (1H, doublet, J 7.5 Hz), 8,30 (1H, triplet-like), was 10.82 (1H, broad singlet).

P R I m e R 20. 1-[2-{5-(4-Hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl} ethyl] -4-(3-indolyl) piperidine (4.5 g) was dissolved in a mixture of methanol (90 ml), 1 N. hydrochloric acid (to 18.9 ml) and water (to 19.8 ml) and added dropwise at room temperature was added water. The precipitate was collected by filtration, washed with ethanol (9 ml) and dried to obtain 1-[2-{ 5-(4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl} ethyl]- 4-(3-indolyl)piperidine hydrochloride (4.30 m).

So pl. 155aboutC.

IR (nuol): 3350, 2650, 1640, 1620 cm-1.

NMR (DMSO-d6, ): 2,0-2,3 (4H, multiplet), of 3.0 to 3.3 (5H, multiplet), 3,5-of 3.75 (4H, multiplet), 3,80 (6N, singlet), 6,13 (1H, doublet, J 14,8 Hz), 6,8-7,4 (N, multiplet), of 7.69 (1H, doublet, J 7.7 Hz), 8,67 (1H, multiplet), 8,72 (1H, singlet), or 10.60 (1H, broad singlet), of 10.93 (1H, singlet).

To illustrate the use of the considered compounds (1) listed below are the pharmacological test data of some representative compounds (1).

Test 1.

Antagon is in turn supported by male Guinea pigs of the species Hartley weight 305-400, These animals were sensitized by intravenous injection of 0.5 ml/animal rabbit anticorodal to egg albumin protein/PCA titer antibodies 4000). After 24 h, animals were placed separately in a plastic chamber with a volume of 5.3 liters In each camera was introduced in the form of an aerosol using a conventional spray 5% solution of egg albumin protein with a rate of 0.16 ml/min for 2 minutes For 30 minutes before spraying a solution of egg albumin protein was administered orally the test compound in various concentrations. For evaluation used a number of Guinea pigs, surviving for at least 2 h after injection of antigen in each of the input concentration of the test compounds. Preventive action to anaphylaxis was estimated as the ratio of the number of surviving Guinea pigs to the number of pigs used in the group.

Test connection 1-[2-[5-(4-Hydroxy-3-methoxyphenyl)-(2E,4E)-2,4-pentadienyl] aminoethyl] -4-benzy troxipide (hereinafter indicated as the test compound (A));

< / BR>
(A)

1-[2-[5-(4-Hydroxy-3-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl]aminoethyl]-4-(3-indolyl) piperidine (hereinafter indicated as the test compound (1));

< / BR>
(1)

1-[2-[5-(4-hydroxy-3,5-R>
< / BR>
(2)

1-[2-[5-(4-acetoxy-3-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl]aminoethyl] -4-(3-indoyl) piperidine (hereinafter indicated as the test compound (3));

< / BR>
(3)

1-[2-[5-(4-ethoxycarbonyl-3,5-acid-(2E, 4E)-2,4-pentadienyl] aminoethyl] -4-(3-indolyl) piperidine (hereinafter indicated as the test compound (4));

< / BR>
(4)

1-[2-[5-(4-hydroxy-3, 5dimethylphenyl)-(2E, 4E)-2,4-pentadienyl]aminoethyl] -4-(3-indolyl) piperidine (hereinafter indicated as the test compound (5));

< / BR>
(5)

1-[2-[5-(4-hydroxy-3,5-diisopropylphenyl)-(2E, 4E)-2,4-pentadienyl]aminoethyl] -4-(3-indolyl) piperidine (hereinafter indicated as the test compound (6));

< / BR>
(6)

1-[2-[5-(3-chloro-4 oksifenil)-(2E, 4E)- 2,4 - pentadienyl]aminoethyl]-4-(3-indolyl) piperidine (hereinafter indicated as the test compound (7));

< / BR>
(7) 1-[2-[3-(4-hydroxy-3-methoxyphenyl)-(E)-propenyl] aminoethyl]-4-(3-indolyl) piperidine (hereinafter indicated as the test compound (8));

< / BR>
(8)

1-[4-[5-(4-hydroxy-3-methoxyphenyl)-(2E, 4E)-2,4-pentadienyl]aminobutyl]-4-(3-indolyl) piperidine (hereinafter indicated as the test compound (9));

< / BR>
(9)

1-[2-{ 5-(4-acetoxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl)-piperidine Association 11).

The test results are given in table. 1.

Test 2.

Countering slow-reacting substance (SRS-A).

From rats, which was introduced glycogen were collected cells of peritoneal exudate shown then in a concentration of 1 x 107KML/ml with Tyrode solution. One milliliter of cell suspension were incubated in the presence of indomethacin (10 mg/ml) and test compounds at each concentration for 10 min, and then for 10 min in the presence of CA++ionophore (A, 1 mg/ml). The supernatant was collected by centrifugation and SRS-a activity was determined on the basis of contractility of the ileum isolated Guinea-pigs in the presence mepyramine, atropine and methysergide.

Below are the results of testing, expressed as 50% inhibitory concentration for the synthesis of SRS-a or secreting cells of peritoneal exudate.

The results are given in table. 2.

For a more detailed illustration of the invention listed below are compositions and examples of their production.

1. Derivatives intellipedia General formula

< / BR>
where R1phenyl substituted by substituents selected rd alkylen;

In the lower albaniles;

or their pharmaceutically acceptable salts.

2. Connection 1, wherein R1phenyl, substituted lower alkyl, hydroxyl, lower alkoxy(lower alkoxy)lower alkoxyl, acyloxy-, halogen or lower alkoxy.

3. Connection 2, wherein R1phenyl, substituted lower alkyl, hydroxyl, lower alkanoyloxy or lower alkoxycarbonylmethyl, halogen or lower alkoxy.

4. Connection on p. 3, wherein R1phenyl, substituted mono - or dihydroxy and mono - or di(lower)alkoxy.

5. Connection on p. 4, which is a 1-[2-{5- (4-hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl} ethyl] -4-(3-indolyl)piperidine.

6. Connection on p. 4, which represents an acid additive salt 1-[2-{ 5-(4-hydroxy-3,5-acid)- (2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl)-piperidine.

7. Connection on p. 6, representing 1-[2-{5-(4- hydroxy-3,5-acid)-(2E, 4E)-2,4-pentadienyl} ethyl]-4-(3-indolyl)piperidine citrate.

 

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FIELD: medicine, neurology.

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55 cl, 29 ex, 11 tbl

FIELD: medicine.

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FIELD: medicine, phthisiology.

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2 ex

FIELD: medicine; physiotherapy.

SUBSTANCE: two to here days after surgical operation, vibration massage is made by means of vibration apparatus on thorax area of root of lung being opposite to that one which was subject to operation. Vibration massage is made daily at frequency of 90-100 Hz and amplitude of 0,4-0,5 mm during 3-5 minutes for 13-14 days. Starting from the fourth f the fifth day after operation, when both drainages are removed from post-resection pleural cavity, electric-vibration acupressure is made in parallel on skin covers all around total area of thorax by means of massaging device. Vibration-acupressure is made daily at the second part of day after I-II row chemical preparations are given to patient. Frequency of procedure is 35-40 Hz and amplitude 0,5-0,6 mm. Duration of influence is increased gradually from 3 to 13-14 minutes during 11-12 days.

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2 ex, 3 tbl

FIELD: organic chemistry, medicine, pharmacy.

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53 cl, 78 tbl, 17 ex

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Biocidal gel // 2305544

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2 tbl, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

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wherein R1 means hydrogen or halogen; R2 means hydrogen, halogen atom, (lower)-alkyl or (lower)-alkoxy-group; R3 means halogen atom, trifluoromethyl group, (lower)-alkoxy-group or (lower)-alkyl; R4/R4' mean independently hydrogen atom or (lower)-alkyl; R5 means (lower)-alkyl, (lower)-alkoxy-group, amino-group, hydroxyl group, hydroxy-(lower)-alkyl, -(CH2)n-piperazinyl substituted optionally with lower alkyl, -(CH)n-morpholinyl, -(CH2)n+1-imidazolyl, -O-(CH2)n+1-morpholinyl, -O-(CH2)n+1-piperidinyl, (lower)-alkylsulfanyl, (lower)-alkylsulfonyl, benzylamino-group, -NH-(CH2)n+1N(R4'')2, -(CH2)n-NH-(CH2)n+1N(R4'')2, -(CH2)n+1N(R4'')2 or -O-(CH2)n+1N(R4'')2 wherein R4'' means hydrogen atom or (lower)-alkyl; R6 means hydrogen atom; R2 and R6 or R1 and R6 in common with two ring carbon atoms can represent -CH=CH-CH=CH- under condition that n for R1 is 1; n means independently 0-2; X means -C(O)N(R4'')- or -N(R4'')C(O)-. Also, invention relates to a pharmaceutical composition.

EFFECT: valuable medicinal properties of compounds.

15 cl, 4 sch, 86 ex

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