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    • 专利摘要:

    公开号:SU976846A3
    申请号:SU802882703
    申请日:1980-02-18
    公开日:1982-11-23
    发明作者:Вернер Скубала Вере；Радюхель Бернд；Форбрюгген Хельмут；Маннесманн Герда；Лозерт Вольфганг；Касальс Хорхе
    申请人:Шеринг Аг (Фирма)；
    IPC主号:
    专利说明:

    39 As a rule, heat treatment of compounds of the general formula P is carried out at 20-150 ° C, preferably at itO-120 ° C. As a rule, the esterification of the carboxy group of the compounds of the general formula II is carried out by treating the corresponding acid with a diazoalkane in an inertHONJ organic solvent, preferably diethyl ether. As a rule, the hydrolysis of the alkoxy group is carried out by acting on the corresponding ester of a solution of the base in an inert organic solvent, for example, a solution of potassium hydroxide in methanol. The azide of the general formula II, which is the starting compound for the production of the target products, is usually obtained from the corresponding known 9o-oxy derivative with protected 11- and 15-hydroxy groups, for example, tetrahydrofuranyl protection, conversion through Eo-tosylcoso-derivative and its treatment with potassium nitrite in dimethyl sulfoxide in the 9-hydroxy derivative with subsequent α-bysylation of the 9/3-hydroxy group, removal of the tetrahydrofuranyl protection and treatment with sodium azide in a polar aprotic solvent, preferably in hexdmethyltriamide . phosphoric acid. Example 1. (13E) - (11R, 13S) -11, 15-dioxy-3, 6-nitrilo-13-prostan-18-inova acid., Solution 365 mg (5z, 13E) - (9S, IIR 155) -9-azido-11,15-DIOXI-5,13-prostadiene-18-inoic acid in 30 ml of ethyl acetate is stirred for 27 h at 70-80 ° C under chromatographic chromatography on silica gel in the system methylene chloride-isopropanol ( 1: 1). 230 mg of the desired product are obtained in the form of a viscous oil. IR spectrum (CHC1e): Zb10, (broad),, 2862, 1720,, 1023, 1078, I975 The starting material was prepared as follows. A. Methyl ester (5z, 13E) - (95,11R, 15S) -11,15-bio- (tetrahydrofuren-2-yloxy) -9- (p-toluenesulfonyloxy) -5, T3prostadien-TV-inic acid. To a solution of 2 g of methyl ester (52, 13E) -95,11R, 155) -11,15-bio- (tetrahydrofuran-2-yloxy) -9-oxy-5,13-prostadiene-18-acid, obtained from the corresponding acid and ethereal solution of diazomethane, in k ml of pyridine. 1.38 g of para-toluenesulfonyl chloride is added at 0 ° C, stirred at room temperature for 6 hours and left at 5 ° C for 60 hours. Then the reaction mixture is diluted ether, shaken one after another with water, once with glacial sulfuric acid, once with water, once with a solution of sodium carbonate, twice with water, dried over Ulfat magnesium and evaporated in vacuo. 2, A5 g of the expected product are obtained in the form of a colorless oil. IR spectrum: 29 °, 2880, 1732, 1605, Y93, 1370, 1178 and 977 cm- B. Methyl ether (52.13E) - (9R, 11R, 1 5S) -1 1.15-bis- (tetrahydrofuran) 2-yloxy) -9-OXI-5,13-prostadi18-inoic acid. , To a solution of 2, L g of the obtained tosylate in 50 ml of dimethyl sulfoxide is added 5.1 g of potassium nitrite and stirred for kh G1ri 65 C. Then the solution is poured into a 20% solution of sodium chloride and extracted 5 times with 50 ml of a mixture pentane and ether (1: 1). The organic phase is washed 3 times with 50 ml of water, dried over magnesium sulphate and evaporated in vacuo. After chromatography of the residue on silica gel in the ether-pentane system (8: 2), 1-25 g of the expected product are obtained in the form of a colorless oil. IR spectrum: 3) 00, 2950, 1730, and 975 cm-1 V. Methyl ether (5z, 13E) - (9R, 11R, 155) -11,15-bis- (tetrahydrofu: wound-2-yloxy) -9- (p -toluenesulphonyloxy) -5,13-prostadiene-18-inoic acid. To a solution of 0.9 g of the 9 / alcohol obtained in 5 ml of pyridine, 622 mg of p-toluenesulfonyl chloride are added at 0 ° C and stirred for 21 hours at room temperature under argon. The solution is then diluted with ether and shaken in succession with Water, glacial sulfuric acid, water, sodium bicarbonate solution, three times with water, dried over magnesium sulfate and evaporated in vacuo. 1.09 g of tosylate is obtained as a colorless oil. IR spectrum: 2962, 1732, 1605, Y93, 137I and 975 cm 59 G, Methyl ether (5z, 13E) - (9R, 11R, 155) -11.15-DIOXI-9- (p-toluenesulfonyloxy) -5 , 13-prostadiene-18-invoy acid, 1.06 g obtained. tosylate is stirred for 20 hours with 30 ml of a mixture of acetic acid, water and tetrahydrofuran (65:35:10) under argon, evaporated in vacuo and the residue is separated by preparative thin layer chromatography with ether as a solvent. 85 mg of the compound are obtained in the form of a colorless oil. IR spectrum: Zb10, 29bZ, 2940 1730, 1603, 1363, 1178 and 975 cm-. D. Methyl ester (5z, 13E) - (9S, 11R, 15S) -9-azido-11,15-dioxy-5,13 prostadiene-18-inoic acid. A solution of 80 mg of the obtained diol in 1.6 ml of hexamethyltriamide of phosphoric acid is mixed with 10.8 mg of Asia and sodium, stirred for 6 hours at 0 ° C, mixed with 6 ml of 20% sodium chloride solution, extracted five times with a mixture of ether and pentane (3 : 1), the organic phase is shaken two times with 3 ml of water, dried over magnesium sulfate and evaporated in vacuo. After thin layer chromatography, the title compound is obtained as a homogeneous oil. IR spectrum:, 29bO, 2110, 1730 and 975 cm-L. E. (5z, 1hZR) - (Я5, 11R, 158) -9-azi to -11.15-DIOXI-5,13-prostadiene-18-acid . 70 mg of the obtained azide is mixed with 2 ml of a solution consisting of 50 mg of potassium hydroxide 3 with 1.65 ml of methanol and 0.35 ml of water, stirred for an hour at room temperature, then cooled to 5 ° C, under argon, acidified citric acid solution to pH 6, extracted three times with methylene chloride, washed the organic extract twice with water (5 ml each time), dried over magnesium sulfate and evaporated in vacuo. After chromatography of the residue on silica gel with ethyl acetate, 39 mg of the title compound are obtained as a colorless oil. . 1K-spectrum: j600,, (wide), 2110, 1715, 1605.and P p and m 2 p. (13E) -11R, 15S, 16RS) -11,15-Dioxy-1b-methyl-9o, 6-. .-nitrilo-13-prostan-18-inovic acid. 6 Solution, -520 mg (5z, 13E) - (9S, 1 1R, 15S, IbRS) -9-azido-11,15-Dioxy-1-methyl-5, 13-prostadiene-18-inoic acid in 50 ml of ethyl ether acetic acid is stirred for 26 hours at 70-80 ° C. under argon, evaporated in vacuo and the residue is chromatographed on silica gel in methylene chloride-isopropanol (1: 1). 380 mg of the title compound are obtained as a colorless oil. IR spectrum: 3600, (wide), 2H2, 286i, 1720,, 1025, 1РбО and 976 cm-. The starting material is prepared as follows. A. Methyl ether (5z., 13E) - (9S11R, 5S, 6RS) -11,15-bis- (tetrahydrofuran-2-yloxy) -1b-methyl-9- (p-toluenesulfonyloxy) -5,13-prostadiene - 13-inovoy acid. To a solution of 3.05 g of methyl ester (5z, 13E) - (9S, 11R, 15S, 16RS) 11, 15-bis- (tetrahydrofuran-2-yloxy) -9-oxy-1b-methyl-5,13-prostadiene -18-inoic acid (obtained from the corresponding acid with ethereal solution of diazomethane) in 6 ml of pyridine was added at 0 ° C with 2.15 g of p-toluenesulfonyl chloride, stirred for 6 hours at room temperature and then left for 60 hours at 5 ° WITH. The solution is then diluted with ether, agitated successively once with water, once with glacial sulfuric acid, once with water, once with sodium carbonate solution, twice with water, dried over magnesium sulfate and evaporated in vacuo. In this way, 3.7 g of tosylate are obtained as a colorless oil. IR spectrum: 12960.2878, 1733, 1b05. , 1370, 1178, and 975 cm. B. Methyl ether (5z, 13E) - (9R, 11R, 15S, 16RS) -11, 15-bic (tetrahydrofyran-2-yloxy) -9-oxy-Tb-methyl5, 13 - prostadiene-18-inic acid. 6.8 g of potassium nitrite is added to a solution of 3.6 g of the obtained thiozate in 70 ml of dimethyl sulfoxide and stirred at 65 ° C under argon. Then the solution is poured into a solution of sodium chloride and extracted five times with a mixture of pentane and ether (1: 1), 70 ml each time, the organic phase is washed three times with water. doi (60 ml), -. dried over sul-. with magnesium and evaporated in vacuo. After chromatography of the residue on silica gel in the ester-pentane system, Ch8: 2, 2.5 g of the expected product are obtained in the form of a colorless oil. IR spectrum: 2950, 1732, and 976 CM-l B, Methyl ether (5z, 13E ) - {9R, IIR, 15S, l6RS) -n, 5-bic- (tetrahydropyphan-2-yloxy) -l6-methyl-9 (p-tolysulphonyl xyloxy) -5,13-simple diene-18-inoic acid. A solution of 2.5 g of the obtained 9 / Lpita in 15 ml of pyridine is mixed with 1.7 p-toluenesulfonyl chloride at and left at room temperature for 2 hours. Then 0.5 ml of water is added to the n solution, left to stand for several hours. at room temperature, diluted with ether, shaken in succession with glacial 3% sulfuric acid, sodium bicarbonate solution and water, dried over magnesium sulphate and evaporated in vacuo. Get 3 g of 9p-tosylate in the form of oil. IR spectrum: 2955, 1735, 1b05, Y91370 and 975 cm. D. Methyl ether {5z, 13E) - (9R, 11R, 15S, 1bK $) - 11,15-Dioxy-1b-methyl-1b-methyl, -9- (p-toluenesulfonyl si) -5,13 prostag- 18-inic acid. 2.90 g of the 9p-tosylate obtained is stirred for 2 hours with 80 ml of a mixture of acetic acid, water and tetrahydrofuran (63:35:10), evaporated in vacuo and the residue is purified by chromatography on silica gel in hexane-ethyl acetate system. You get 1, JSC 11,15-DIOL in the form of a colorless oil. IR spectrum: 3600,, 2958, 173 1605, 1368 and 978 cm-g D. Methyl ether (Sz,, 13E) - (9S, 11R, 15S, l6RSl-9-a3MAO-n, 15-diox-16- Methyl 5, 13-prostadiene-18-inic acid. The resulting diol in 20 ml of phosphoric acid hexamethyltriamide and 130 mg of sodium azide is stirred for 6 hours, after which the solution is cooled, mixed with 100 ml of infused salt, extracted several times. a mixture of ether and pentane (3: 1), the organic phase is washed with water, dried over magnesium sulphate and evaporated in vacuo. (6.8 A 9-azido acid is obtained, and the viscous oil is obtained in the form of a viscous oil. IR spectrum: ZbOO, 2958, 2110 , 1735 and 978 cm. E. (52, 13E) - (9S, IIR, 135, 16RS) 19-azido-11, 15-dioxy-1b-methyl-5, 13.-Prostadiene-18-inovaic acid. 200 mg of the obtained azide is treated with a solution of potassium hydroxide in methanol under conditions similar to that described in Example IE. The crude product is chromatographed on silica gel with ethyl acetate to give 150 mg of acid as a colorless oil. IR spectrum: ZbOO, 2952, 2110, 1710, 978 cm. (13E) - (nR, 15R) -11, 1 5 diox i-1b, 1b-dimethyl-9c b-nitrilo-1Z-prostolen-Tuinic acid. A solution of 300 mg (5z, 13E) - (9S, .P R, 15R) -9-aaido-11,15-dioxy-1b, 1b-dimethyl-5, 13-prostadiene-18-inoic acid in 25 MP ethyl ether acetic acid is heated at 70-75 ° C under argon. After distilling off the solvent in vacuo, the residue is chromatographed on silica gel in methylene chloride and 10-30 isopropanol to obtain 200 mg of the title compound as an oil. IR spectrum: 3tOO (wide), 2950, 2860.1715., 1020 and 978 cm. The source material is obtained as follows. A. Methyl ether (5z. 13E) - (9S, 11R, 15R) -11,15-bis- (tetrahydrofuran-2-yloxy) -16,1b-dimethyl-9 (p-toluenesulfenyloxy) -5,13-prostadiene - 1 8-inic acid. 3 g of methyl ester (5z, 13E) - (9S, P R, 1 5R) -11,15-bis- (tetrahydrofuran-2-yloxy) -16,1b-dimethyl-9-hydroxy-5, 13 Prostadien-18 α-Acidic acid (obtained from carbonic acid with an ethereal solution of diazomethane) is dissolved in 1 O ml of pyridine, mixed at 0 ° C with 2.09 g of p-toluenesulfonyl chloride, stirred for 48 hours at 5 ° C, after which the solution 0.5 l of water is added, stirred for several hours, diluted with 200 ml of ether and washed successively with glacial 10% sulfuric acid, sodium bicarbonate solution and water, dried over magnesium sulfate and evaporated in vacuo. teaching.Yu.T 4 g 9c) (- tosylate, which is used without additional purification in the next stage. IR spectrum: 29bO, 2868, 1735, .1602, 1360, 1175 and 975 cm-h. B. Methyl ether ((Z, 13E) - (9R, 11R, 1 5R) -11,15-bis- (tetrahydrofuren-2-yloxy) -16,1b-dimethyl-9-hydroxy-5, 13-prostadiene-18-inoic acid 3.8 g of the tosylate obtained and 7.6 g of potassium nitrite are mixed with 80 ml of dimethyl sulfoxide for hours, then diluted with a saturated solution of sodium chloride, extracted several times with a mixture of ether and pentane (1: 1), the organic phase is washed with a saturated solution of sodium chloride dried over sulfate magnesium and evaporated in vacuo. After chromatography on silica gel with a gradient of hexane and ethyl acetate, 1, 5 g of 9p alcohol is obtained as a colorless oil. IR spectrum:, 2950, 2860, 1735 and 980 cm-g V. Methyl ether (5z, 13E) -. (9R, P R, 1 5R) -11., 15-bis- (tetrahydrofur „-2-yloxy) -1b, 1b-dimethyl-9- (p-toluo sulfonyloxy) -5,13-prostadiene-18-inoic acid. A solution of T, 50 g of the obtained Er-spt in 10 ml of pyridine is mixed with 1, g of p-toluenesulfonyl chloride, stirred for 20 hours at room temperature, 0.2 ml of water is added and treated under conditions similar to that described in at the rate of ZA.- 2.1 g of 3-tosylate are obtained in the form of an oil. IR spectrum: 2960, 2860, 1735, 1b0 1365, 1175 and 980 cm-. . D. Methyl ester (5z, 13E.) - (9R, 11R, 1 5R) -11, 15-dirxy-1b, 1b-dimethyl-9- (p-toluenesulfonyloxy) -5,13-prostadiene-18-in acid. 2 g of the obtained 9A-tosylate to remove the tetrahydropyramine protection. Treat with acetic acid under conditions similar to those described in measure IF. After purification on silica gel with a gradient development of a mixture of hexane and ethyl acetate, 1.1 g of 11.15-diol are obtained in the form of an oil. IR spectrum: 3600, 2955, 1736 1601, 1360, 1175 and 978 cf D. Methyl ether (5z. 13E) - (9S, 11 R, 1 5R) -9-azido-11,15-dioxy-1b71 4610-dimethyl-5,13-prostadi-18-yno80y acid. A solution of 1.1 g of the obtained compound in 20 ml of hexamethyltriamide. phosphoric acid is heated with 150 mg of sodium azide g for 6 hours, diluted with 150 ml of a saturated solution of sodium chloride, shaken many times with a mixture of ether and pentane (3: 1), the organic phase is washed with water, dried over magnesium sulfate and evaporated in vacuo. The crude product is chromatographed on silica gel in the hexane-ethyl acetate system, and 700 mg of 9 ° C azide are obtained as an oil. IR spectrum: 3520, 290, 2110, 1735 and 978. E. (5Z. 13E) - (9S, 11R, 15R) -9-azido-11., 1 5-DIOXI-16,1b-dimethyl-5,13-prostadiene-18-yanoaic acid. 500 mg of the obtained compound are mixed in conditions similar to those described in Example IE. Obtain 00 mg of the desired product in the form of: colorless oil. IR spectrum: ZbOO, (wide), 2955, 2110, 1712 and 978 cm P e. (13E) -tHR, 15RS) -11, 15-doxy-15-methyl-9, 6-nitrilo-13-prost- 18-inovy acid. 200 mg (5z, 13E) - (9S, PC, 15RS) -9-azido-11, 15-dioxy-15-methyl-6 L3-prostadiene-18-inoic acid in 20 ml of ethyl acetate are heated for 2 h at 70 ° C. After distilling off the solvent, the residue is chromatographed on silica gel with a mixture of methylene chloride and 10-30% isopropanol to obtain 120 mg of the title compound as an oil. IR spectrum: ZbOO ,, 2950, 2845, 1712, 16/10 and 978 cm-. The starting material is prepared as follows. A. Methyl ester (5z, 13E) - (9S, 11R, 1 5RS) -11.15-bi.c- (tetrahydrofyran-2-yloxy) -1. P-9- (p-toluenesulfonyloxy) g 5.13-prostadiene-18-acid; i 2 g of (5z, 13E) - (9S, 11R, 15RS) methyl ester (11,1-bis- (tetra. Hydrofuran-2-yloxy) -9-hydroxy-15- Methyl 5, 13-prostadiene-18-inic acid (derived from carboxylic acid and diazomethane) is converted, under conditions similar to those described in Example 1A, to 2.3 g of 9-tosylate as an oil. .
    IR spectrum: 29 °, 2865, 1735, 1 ° 1365, 1175 and 975 cm-1
    B. Methyl ester of (5,13E) - (9R, 11R, 16RS) -11,15-bis- (tetrahydrofuran-2-yloxy) -9-oxide-15-methyl-5,13-prostadiene-18-INOH8OY acid .
    2.2 g of the tosylate obtained was added to the reaction with potassium nitrite under CONDITIONS similar to those described in Example 1b. 1.3 g of 9-alcohol are obtained as a colorless oil.
    IR spectrum: 3 1 0 2955, 1735 and 5) 78 cm-I
    B. Methyl ether (5z, 13E) - (9R, 11R, 15RS) -11,15-bis-tetrahydrofuran-2-yloxy-15-methyl-9- (p-toluenesulfonyloxy) -5,13-prostadiene-18- inoic acid
    Under conditions similar to those described in Example 1B, 1.7-g of 9 p-tosylate is obtained from 1.3 g of the obtained 9 alcohol in the form of an oil.
    IR spectrum: 2960, 2880, 1735, 1601.1370, 1175 and 978 cm-L
    G. Methyl ester (5z. 1.3E) - {9R, 11R, 15RS) -11,15-dioxy-15-methyl-9- (p-toluenesulfonyloxy) - 5,13-prostadiene-18-inoic acid.
    Under conditions similar to those described in Example 1G, 1.7 g of the obtained material is obtained from 1 g of P, 15-diol as a colorless oil.
    IR spectrum: ZbOO, 29bO, 173 1601, 1365, 1178 and 975. cM-t
    D. Methyl ester (5z., 13E) - (9R, 11R, 15RS) -9-azido-11,15-dioxy-15-methyl-5, 13-prostadiene-18-inoic acid.
    1 g of the obtained compound is reacted with sodium azide under conditions similar to Example IE. 600 mg of 9-azido compound are obtained as a colorless oil.
    IR spectrum: ZbOO, 2955, 2110,
    1735 and 975 cM-i.
    .. E. (5z, 13E) - (9S, 11R, 15RS) -9-azido-i1, 15-Dioxy-15-methyl-5,13-prostadiene-18-inovic acid. about 600 mg of the obtained compound
    is washed under conditions similar to those described in Example IE. 500 mg of carboxylic acid is obtained in the form of an oil.
    IR spectrum: ZbOO, (broad), 2560, 2110, 1710 and: 975 cm--.
    PRI me R 5. Methyl ether (13E) - (1 1R, 1 3 $) - 11,1b-dioxy-9o -,
    6-nitrilo-13-prostan-18-inic acid. .
    A solution of 150 mg of (13E) - (11R, 155) -11, 1 5-dioxy-9o1, 6-nitrile) -13-prostogen-18-inoic acid in 10 ml of methylene chloride is mixed at -10 ° C and added dropwise the ethereal solution of diazomethane until the yellow color remains, is evaporated in vacuo, and the residue is purified by preparative: thin-layer chromatography on silica gel plates in an ethyl acetate-methanol system (9: 1). 120 mg of the title compound are obtained as a colorless oil.
    IR spectrum:, 29bO, 1735, and 978 cm.
    PRI me R 6. Methyl ester (13E) - (nR, 15S, l6RS) -11,15-dioxy-1b-methyl-9, 6-nitrile-13-prosta-18-inic acid.
    Under conditions analogous to those described in Example 5, they are obtained from (13E) - (11R, 15S, 16RS) -11,15-dioxy-1b-methyl-9o, 6-nitrile-13-prostane-18-inoic acid ( example 2) the target compound in the form of oil.
    IR spectrum:, 2955, 1735, and 978 cm
    PRI me R 7. Methyl ester (13E) - (nR, 1 5R) -11,1 5-dioxy-16,16-dimethyl-9o, 6-nitrilo-13-prostogen-18-inoic acid.
    Under conditions similar to those of opium, in example 5, from (13E) - (11R, 15R) -1 1, 1 5-Dioxy-1b, 1b-dimethyl-9o, 6-nitrile-13-prostane-18-inova acids (Example 3) give the title compound as an oil.
    IR spectrum:, 2955, 1735.1640 and 975 cm-.
    EXAMPLE 8 Methyl Ester (13E) - (nR, 1 5RS) -11, 1 5-Dioxy-15-methyl-90., 6-nitrile-13-prostogen-18-inoic acid.
    under conditions similar to those described in Example 5, from (13E) - (11R, 15RS -11.1, 5-dioxy-15-methyl-9c, 6-nitrilo-13-prostogen-18-inoic acid (example)) compound in the form of oil.
    IR spectrum:, 2955, 1735, and 978 cm.
    Example 9. Tris- (hydroxymethyl) -aminomethane salt (13E) - (11R, 1 5S, 16RS) -11.1 5-dioxy-1b-methyl-9o (, 6-nitrile-13-prostogen-18-inoic acid .
    权利要求:
    Claims (1)
    [1]
    Claim
    A method of obtaining derivatives of prostacyclin of the general formula where RW or with I ! * 3 hydrogen atom or lower alkyl; oxymethylene -1,1-ethylene atoms of hydrogen hydrogens alkyl, their salts, about t and h in that the compound of the general formula 'or 1-hydroxy group;
    or lower
    40 “where are the arterial and coronary vessels and, thereby, lowering the systemic blood pressure without decreasing at the same time- 4! but systolic blood volume and coronary blood flow, inhibition of platelet accumulation and suppression of bronchospasm, inhibition of gastric acid secretion, S • antiallergic properties, decreased pulmonary vascular resistance and pulmonary blood pressure, increased renal and cerebral blood flow. In addition, they possess 5ί antiproliferative properties: mi.
    VNIIIPI Order 9026/80 Branch of PPP Patent, g.
    in in 3 n n
    S-SzS-CH 3
    R ^. 'R ^ M RjMW have the indicated meaning, are subjected to heat treatment in an inert organic solvent, for example ethyl acetate, optionally saponified with an alkoxy group or esterified with a carboxy group and the desired product is isolated in free form or in the form of its salt.
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    同族专利:
    公开号 | 公开日
    AU540077B2|1984-11-01|
    CA1155114A|1983-10-11|
    IE800326L|1980-08-20|
    DE3063231D1|1983-07-07|
    AT3420T|1983-06-15|
    DK154294B|1988-10-31|
    IL59434A|1984-07-31|
    IE49406B1|1985-10-02|
    EP0015227B1|1983-05-18|
    IL59434D0|1980-05-30|
    JPS6248668B2|1987-10-15|
    US4315013A|1982-02-09|
    AU5574980A|1980-08-28|
    JPS55122759A|1980-09-20|
    DK71680A|1980-08-21|
    DE2907118A1|1980-09-04|
    CS216217B2|1982-10-29|
    DK154294C|1989-07-03|
    HU183114B|1984-04-28|
    EP0015227A1|1980-09-03|
    ES488775A1|1980-09-16|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE2118686A1|1970-04-20|1971-11-11|The Upjohn Co., Kalamazoo, Mich. |Prostaglandin compounds and processes for their preparation|
    CA1018970A|1972-10-27|1977-10-11|American Home Products Corporation|15-substituted prostanoic acids|
    GB1458315A|1974-04-22|1976-12-15|Ici Ltd|Prostanoic acid derivatives|
    US4097489A|1977-06-17|1978-06-27|The Upjohn Company|9-Deoxy-9α,6-nitrilo or 6,9α-imino-PGF compounds|
    US4211706A|1978-10-13|1980-07-08|The Upjohn Company|9-Deoxy-9α,6-nitrilo or 6,9α-imino-17,18-didehydro-PGF compounds|US4294759A|1979-11-15|1981-10-13|The Upjohn Company|Structural analogues of 5,6,-dihydro PG1|
    DE3107100A1|1981-02-20|1982-09-09|Schering Ag, 1000 Berlin Und 4619 Bergkamen|AZAPROSTACYCLINE, METHOD FOR THEIR PRODUCTION AND THEIR PHARMACEUTICAL USE|
    EP0063538B1|1981-04-13|1986-08-06|Schering Aktiengesellschaft|Prostaglandins and prostacyclins, their preparations and pharmaceutical applications|
    JPH0443053B2|1984-07-23|1992-07-15|Dainippon Seiyaku Kk|
    DE3708537A1|1987-03-13|1988-09-22|Schering Ag|6-OXOPROSTAGLANDIN-E DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND THEIR PHARMACEUTICAL USE|
    ES2747259T3|2006-03-09|2020-03-10|Salix Pharmaceuticals Inc|Anti-rectal preparation of rifaximin|
    RU2012126084A|2009-11-23|2013-12-27|Сипла Лимитед|FOAM COMPOSITION FOR LOCAL USE|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19792907118|DE2907118A1|1979-02-20|1979-02-20|NEW PROSTACYCLINE DERIVATIVES AND METHOD FOR THE PRODUCTION THEREOF|
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