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  • 专利说明
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    • 专利摘要:

    公开号:SU793390A3
    申请号:SU782664651
    申请日:1978-09-18
    公开日:1980-12-30
    发明作者:Крассо Анна；Кребс Эрнст-Петер
    申请人:Ф.Гоффманн-Ля Рош Унд Ко Аг (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a method for producing new imidazo derivatives
    la general formula 1 "4Vv, Ν Χ K 1 5 t 1-S-CH-X,. n IRwhere R,, Rg, R -g AND R4, everyone means 10 hydrogen or together with Rg and R3
    together with R4, each additional carbon-carbohydrate bond, η is the number 0 or 1, R ς is hydrogen or lower alkyl, and X is unsubstituted or monosubstituted with 15 lower alkyl 2-pyridinyl residue, 2-imidazolyl residue, 2-imidazolinyl residue, 2-thiazolyl residue, 4 (5) -imidazolyl residue, unsubstituted or one-to-one-fold substituted with lower alkyl, their salts, racemic mixtures, diastereoisomers or antipodes having biological activity.
    A known method for producing 2- (2-pyridylmethylsulfinyl) benzimidazole having the same properties by the interaction of the corresponding benzimidazole derivative with the corresponding mercaptan [1]. '3G
    The goal is achieved by the proposed method for producing compounds of the above formula I, which consists in the interaction of the compounds of formula I I
    R4 are as defined above, wherein R is the meaning and meanings, are reacted with a compound of formula III y′-cn-x, where Rg and X have the above meanings and Y are the meanings indicated below, one of the radicals Y and Y Is a mercapto group, and the other is a leaving group, with the formation of the target product, where η = 0 or with the oxidation of the obtained compound and isolation of the target product in free form and in the form of salt, racemic mixture or antipodes.
    Example 1. In a 250 ml sulfator flask equipped with a stirrer, thermometer, cooler and dropping funnel, 10.1 g of 1H-naphtha [2, 3-d] imidazole-2-thiol are suspended in 100 ml of alcohol. Then, a solution of 4.0 g of sodium dioxide in 50 ml of water is added dropwise, and a clear ’solution is formed. Then it is heated to the boiling point, 8.2 g of 2-chloromethylpyridining hydrochloride are added and refluxed overnight. Then the reaction mixture was evaporated, the residue was dissolved in 600 ml of ethyl acetate and 200 ml of water, and the ethyl acetate phase was washed twice with 200 ml of water, dried with sodium sulfate and evaporated in vacuo. The residue was recrystallized once from ethyl acetate-petroleum ether to give 2- [(2-pyridylmethyl) -thio] -1H-naphtha [2, 3-d] imidazole, 'm.p. 165167 ° C, the hydrochloride melts at 2 30231 ° C.
    Getting the source products.
    125.0 g of 2,3-dihydroxynaphthalene are suspended in 3.5 L (25%) and at 240 ° C (30 bar) N2 is shaken for 60 hours. The suspension is filtered on a suspension, washed with 1.5 L of water and then dissolved in 7 L of ethyl acetate. The ethyl acetate solution was extracted twice with 1 L of 3NNaOH and twice with 1 L of H2.0, dried over Na ^ SO ^, filtered on charcoal and the decolorized filtrate was evaporated in vacuo at 4 ° C. The residue was stirred with 400 ml of acetonitrile for 1 h at room temperature, filtered under suction and dried.
    128 g of the 2,3-diaminonaphthalene thus obtained are suspended in
    900 ml of ethanol. With vigorous stirring, 21.0 g of CPC in 160 ml of water are added dropwise. After stirring for ten minutes at room temperature, 71.6 g of carbon disulfide are added dropwise. The reaction mixture was stirred for 1 h at approximately 20 ° C, and then overnight at boiling point. After adding 91.0 g of KOH to 370 ml of water, everything goes into solution, filtered through a filter of 50 g of charcoal and 50 ml of water are diluted with filtrate. At an internal temperature of 60-70 ° C. and with stirring, 295 ml of glacial acetic acid in 295 ml of water are added dropwise. Then the suspension was stirred for another 1 h at the same temperature, then cooled in an ice bath and filtered on suction. The residue is washed first with 300 ml of water and then with 100 ml of ethanol. After drying in vacuo at 60 ° C., the crude product is heated to 158 ° C., suspended in 600 ml of dioxane at approximately 20 ° C., stirred for one hour and then filtered off under suction. The precipitate is washed alternately with 100 ml of dioxane and 300 ml of ester. After drying under vacuum at 60 ° C.,
    148.1 g of 1H-naphtha [2,3-d] imidazole-2-thiol; t. pl. 303-305 ° C.
    120 g of 2-hydroxymethylpyridine is stirred in 2 l of absolute benzene. At a temperature of 0-5 ° C, 100 ml of thionyl chloride are slowly added dropwise and the reaction mixture is stirred overnight at approximately 20 ° C. Then it is cooled to 0-5 ° C and filtered on the inside. The precipitate was dissolved in 1000 ml of ethanol in the hot state, filtered on charcoal and evaporated at 50 ° C. The residue was dissolved in 400 mp acetonitrile, stirred at room temperature for 1 h, and 2-chloromethylpyridin-Hse was filtered off under suction, mp. 121 123 ° C.
    Example 2. In a one-liter, four-necked round flask equipped with a stirrer, thermometer, dropping funnel and calcium chloride tube, 9.4 g of 2- [(2-pyridylmethyl) thio] -1H-naphtha [2, 3-d] imidazole in 250 mp are suspended methylene chloride. With vigorous stirring, a solution of 6.7 g of m-chloroperbenzoic acid in 150 ml of methylene chloride is added dropwise, while cooling with ice with methanol, and the mixture is stirred for another 5-7 hours at 0-5 ° C. Then it is washed to a neutral reaction 3 times with 100 ml sodium bicarbonate solution and two times with 200 ml sodium chloride solution, dried with sodium sulfate and evaporated in vacuo. The residue was recrystallized from 500 ml of toluene to give 2- [(2-pyridylmethyl) -sulfinyl] -1H-naphthyl G2, 3-d] imidazole, g . Mp. 145146 ° C.
    Example 3. 0.92 g of 2-chloro-1H-naphtha [2, 3-d] imidazole and 0.57 g of 2-mercaptomethylpyridine are heated in 15 ml of ethanol and 4.5 ml of 1N. caustic soda solution for 18 hours under reflux. 50 ml of water was added to the reaction solution, and a total of 50 mp ethyl acetate was extracted. The organic phases are washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated on a rotary evaporator to dryness. Crystallization from 50 ml of acetonitrile affords 0.68 g of 2- [(2-pyridylmethyl) thio] -1H-naphtha [2, 3-d [imidazole, 1 mp. 169-170 ° C.
    Getting the starting materials.
    16.2 g of 2-hydroxy-1H-naphtha [2, 3-d] imidazole is heated in 170 ml of phosphorus chloride for 3 hours under reflux. The reaction solution is concentrated, water is added and, through ammonia, it is brought to the main reaction. The residue after filtration under suction is chromatographed over 500 g of silica gel. Ethyl Acetic Acid Elute
    2.5 g of 2-chloro-1H-naphtha [2, 3-d] imidazole. After recrystallization from methanol, the product is obtained, so pl. less than 300 ° C.
    Example 4. 0.45 g of 2-methylthio-1H-naphtha [2,3-b] imidazole and 0.65 g of 2-mercaptomethylpyridine are heated in 10 ml of ethanol for 40 hours under reflux. 10 ml of water are added to the homogeneous solution and the precipitate formed is filtered off. Obtain 0.50 g of 2 - [(2-pyridylmethyl) tis1-1H-naphtha [2,3-0] imidazole, so pl. 170 ° C.
    Getting the starting materials.
    20.0 1H-naphtha [2, 3-d] imidazole-2-thiol and 4.0 g of sodium hydrochloride are heated in 150 ml of ethanol with 6.5 g of methyl iodide for one hour. fridge. The reaction solution was diluted with 500 ml of water and the precipitated product was filtered off under suction. Crystallization from dioxane afforded 12.0 g of 2-methyl-ethyl-1H-naphtha [2, 3-d]. Imidazole, m.p. 242-244 ° C.
    Example 5. 0.165 g of 2- (methylsulfonyl) -1H-naphtha [2, 3-d] imidazole and 0.090 g of 2-mercaptomethylpyridine are heated under reflux in 5 ml of ethanol and 0.72 ml of 1 N. sodium hydroxide solution for 1 h. The reaction solution was concentrated and chromatographed on silica gel. Ethyl acetate was eluted with 0.050 g of 2- [(2-pyridylmethyl) thio] -1H-naphtha (2, 3-d] imidazole.
    Getting the starting materials.
    To 4.3 g of 2- (methylthio) -1H-naphtha [2, 3-d] imidaeol in 500 ml of methylene chloride, a solution of 4.2 g of m-chlorobenzoic acid in 100 ml of methylene chloride was added dropwise at 0-5 ° FROM. The reaction solution was stirred for 90 minutes at 0 ° C, washed twice with an aqueous solution of sodium chloride and once with a saturated solution of sodium chloride, dried with magnesium sulfate and concentrated in a rotary evaporator. Crystallization from acetonitrile affords 2.3 g of 2- (methylsulfinyl) -1H-naphtha [2,3-d] imidazole, m.p. 194 ° C.
    Example 6. 90.0 g of 1H-naphtha [2,3-0] imidazole-2-thiol in 200 ml of dimethyl formamide a is heated to a temperature of 95 ° C. To the homogeneous solution, 80.1 g of 2-chloromethyl-5-methylpyridining hydrochloride are added and incubated for 10 min at 95 ° C. After cooling to room temperature, 1 L of ether was mixed in and filtered off under suction. The residue is dissolved in 2 N. potassium bicarbonate solution and completely extracted with 2 l of methylene chloride. The organic phases are washed with saturated sodium chloride solution, dried with magnesium sulfate and then concentrated in a rotary evaporator. The residue was recrystallized from 2 L of alcohol. 106 g of 2- [(5-methyl-2-pyridyl) methylthio] -1H-naphtha [2, 3-d] imidazole are obtained, m.p. 185-186 C.
    Preparation of 2-chloromethyl-5-methylpyridining hydrochloride.
    11.5 2, B-dimethylpyridin-I-oxide in 5 ml of acetic acid is added dropwise to 18 ml of acetic anhydride, heated to 120 ° C. The reaction solution is refluxed for another 45 minutes, concentrated in a rotary evaporator and distilled off at 115 ° C (8 mmHg). 14.0 g of 2-acetoxymethyl-5-methylpyridine are obtained.
    14.0 g of 2-acetoxymethyl-5-methylpyridine is heated in solution from
    4.5 g of sodium hydroxide in 150 ml of water for 90 min under reflux. The cooled solution was saturated with sodium chloride and 100 ml of chloroform was fully extracted. The organic phases are washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated at 40 ° C (16 torr). The resulting oil was distilled at 12 ° C (8 mmHg) to give 8.7 g of 2-hydroxymethyl-5-methylpyridine.
    8.7 g of 2-hydroxymethyl-5-methylpyridine is added dropwise to 18 ml of thionic acid chloride at a reaction temperature of 0 to 10 ° C. The reaction solution is then stirred for 15 hours at room temperature and then concentrated in a rotary evaporator. The residue is treated with activated carbon in alcohol and crystallized from alcohol, ether. Obtain 11.5 g of 2-chloromethyl-5-methylpyridine hydrochloride, so pl. 145-146 ° C.
    PRI me R. 7. To 8.1 g of 1H-naphtha [2,3-d] imidazole-2-thiol in 80 ml of ethanol and 40 ml of water are added 3.2 g of sodium hydroxide and 7.2 g of 2-chloromethyl-4-methylpyridining hydrochloride, and refluxed for 2 hours. The reaction solution was concentrated and partitioned between water and ethyl acetate-tetrahydrofuran. The organic phases are washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated in a rotary evaporator. The oily residue is crystallized from toluene. 6.5 g of 2- [(4-methyl-2-pyridyl) methylthio] -1H-naphtha [2, 3-d] imidazole are obtained, m.p. 170172 ° C.
    Similarly, 2- ((6-methyl-2-pyridyl) methylthio] -1H-naphtha [2,3-d] imidazole is obtained, mp 119-120 ° C.
    Example 8. To 8 g of 1H-naphtha [2, 3-d] 2-thiol in 80 ml of ethanol was added 6.4 g in 40 ml of water at 0 ° C. and then, with stirring, 8.72 g of rac was added dropwise. -2- (1-chloroethyl) -pyridine in 40 ml of ethanol. After 12 hours at reflux, the solution was evaporated in vacuo and the residue was again taken up in ethyl acetate-water. From 11.5 g of crude product, after purification on silica gel and crystallization from tilatse7 ^ '7 93 390 6.0 theta obtained. g rac-2- [1- (2-pyridyl) ethylthio] -1H-naphtha [2,3-c1] -imidazole, 'm.p. 129-133 ° C.
    The optical cleavage of the racemates is carried out by means of (-I-) or (-) -di-0,0-p-toluoyl tartaric acid (D1TTA) in ethyl acetate-toluene (1: 1).
    Example 9. 10.0 g of 111-naphtha [2,3-d] imidazole-2-thiol and 9.6 g of 2-chloromethyl-5-ethylpyridining hydrochloride are heated in 200 ml of ethanol and 100 ml of 1N. caustic soda solution for 2 hours under reflux. The reaction solution was concentrated in a rotary evaporator, dissolved in 250 ml of water and extracted three times with 100 ml of ethyl acetate. The organic phases are washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated to dryness. Crystallization from acetonitrile affords 8.2 g of 2- [(5-ethyl-2-pyridyl) methylthio] -1H-naphtha [2, 3-d] imidazole, m.p. 156-157 S.
    Π p and measure 10. To 4.09 g of 5,6,7,8-tetrahydro-1H-naphtha [2, 3-d] imidazole-2-thiol in 50 ml of ethanol add 2.24 g of potassium hydroxide in 10 ml of water, then 3.28 g of 2-chloromethylpyridylhydro ~ chloride in 20 ml of ethanol. After 12 hours at reflux, the solution was evaporated in vacuo and the residue was taken up in ethyl acetate and water. Chilled to 0 ° C and concentrated to approximately 50 ml ethyl acetate phase gives 4.8 g of crystals, 'so pl. 95-97 ° C, which, after recrystallization, give 4.15 g of 5,6,7,8-tetrahydro-2-C2-pyridylmethyl) thio] -1H-naphtha G2, Z-d] imidazole, m.p. 98101 ° C.
    Getting the starting materials.
    To a solution of 16.2 g of 5,6,7,8-tetrahydro-2,3-diaminonaphthalene in 100 ml of isopropanol and 20 ml of ethanol, 6.16 g of potassium hydroxide dissolved in 20 ml of water are added dropwise first at 0 ° C. then 7.3 mp carbon disulfide. After 2 hours at reflux, the pH is adjusted to 3-4 with glacial acetic acid and the settled white crystals are filtered under suction at 0 ° C. The crystals are dissolved in 200 ml of isopropanol, the solution is boiled for half an hour under reflux, and at b ° С it is filtered off under suction. 17.8 g of .5,6,7,8-tetrahydro-1H-naphtha [2,3-d] imidazole-2-thiol are obtained, m.p. 282 ~ 289 ° C.
    Example 11. To 3.2 g of 2 - [(5-etilg-2-pyridyl) methylthio J-lH-naphtha [2, 3-d] imidazole is added dropwise in 200 ml of methylene chloride, at a reaction temperature of 0- 5 ° C, a solution of 1.7 g of m-chloroperbenzoic acid in 50 ml of methylene chloride. The reaction solution was stirred for 3 hours at 0 then Q C 'twice washed with potassium bicarbonate solution i'odin' times, saturated sodium chloride solution and then concentrated to dryness. The green residue is treated with activated carbon in acetonitrile methanol and a mixture of solvents crystallizes from it. 2.1 g of 2- [(5-ethyl-2g-pyridyl) methylsulfinyl] -1H-naphtho [2, 3-d / imidazole, m.p. 11 7 ° C.
    Example 12. 1.1 g of 2-hydroxymethylthiazole is dissolved in 50 ml of chloroform and stirred with 0.82 ml of thionyl chloride for 2 hours at 20 ° C ; then refluxed for 30 minutes. After evaporation in vacuo at 40 ° C, the residue was dissolved in 20 ml of ethanol and the solution was again evaporated.
    A solution of 1.91 g of 1H-naphtha [2, 3-d] imidazole-2 thiol in 50 ml of ethanol, 2.14 g of potassium hydroxide and 10 ml of water is added to the obtained crystals of chloromethylthiazole hydrochloride, and heated under reflux for two hours . The solvent is removed in vacuo and the residue is treated with ethyl acetate - water. After double crystallization from acetonitrile, 1.3 g of 2- [(2-thiazolylmethyl) thio -1H-naphtho [2, 3-d / imidazole, m.p. 153157 ° C.
    Example 13. 1.0 g of 1H-naphtha j / 2, 3-d] imidazole-2-thiol and 0.8 g of 2-chloromethylimidazole hydrochloride are heated in 20 ml of dimethylformamide for an hour and a half to 90 ° C. The precipitate formed is filtered off, washed with a small amount of acetonitrile and dissolved in 2N. sodium carbonate solution. The aqueous phases are extracted 3 times with 30 ml ethyl acetate. The organic phases are washed with saturated sodium chloride solution, dried with magnesium sulfate and then concentrated. The residue was recrystallized from 150 ml of acetonitrile. Obtain 1.50 ml of 2- [(imidazol-2-ylmethyl) thio / -1H-naphtha [2, 3-d] imidazole, so pl. 172 ° C.
    Example 14. 10.0 g of 1H-naphtha [2, 3-d] imidazole-2-thiol and 8.0 g of 2-chloromethylimidazoline-hydrochloride are heated in 50 ml of dimethylformamide for 3 hours to 90 ° C. After cooling to room temperature, dilute in 200 ml of toluene. The residue is filtered off under suction, washed well with toluene and crystallized from 700 ml of methanol with the addition of 300 ml of ether. 10.3 g of 2- [(2-imidazolin-2-ylmethyl) -thio] -1H-naphtha [2, 3-d] imidazole dihydrochloride are obtained, m.p. 227-228 ° C.
    Example 15. To 2.5 g of 2- (1-hydroxyethyl) -thiazole is added, in 50 ml of absolute chloroform, 2.38 g of thionyl chloride in 10 ml of chloroform at OS, and stirred for one hour at 0 ° C, 30 min at 20 ° C and 1 h with reflux. After removal of the solvent in vacuo, the residue was dissolved in 20 ml of ethanol, and the solution9 was evaporated again. a mixture of 4.0 g of 1H-naphtha [2, 3-d] imidazole-2-thiol, 80 ml of ethanol, 4.48 g of potassium hydroxide and ml of water was added to the remaining oil and refluxed for 12 hours. After evaporation in in vacuo, the residue was dissolved in 300 ml of water and extracted three times with 200 ml of methylene chloride. Evaporated to dryness, the organic phases crystallize from benzene. After double recrystallization from benzene, 1.8 g of 2 [1- (2-thiazolyl) -ethylthio] -1H-naphthyl [2, 3-d] imidazole are obtained, m.p. 18418b ° C.
    PRI me R 16. 2.85 g of 5,6,7,8-tetrahydro-1H-naphthyl [2, 3-d] imidaeol-2-thiol are boiled at reflux temperature together with 50 ml of ethanol for 12 hours, 2, 24 g of potassium hydroxide, 10 ml of water and 2.5 g of 2-chloromethyl-5-methylpyridine, then evaporated in vacuum and processed with methylene chloride - water.
    From 4.8 g of the residue after recrystallization from 80 ml of acetonitrile, 3.78 g of 5,6,7,8-tetrahydro-2- [(5-methyl-2-pyridyl) methylthio] -1H-naphtha are obtained [2, 3 -d] imidazole, 'm.p. 135-136 ° C.
    5,6,7,8-tetrahydro-2- [1- (2-pyridyl) ethylthio] -1H-naphtha G2, 3-d] imidazole, m.p. 124 125 ° C.
    PRI me R 17. To 3.05 g of 2- [(5-methyl-2-pyridyl) methylthio] -1H-naphtha [2,3-d] imidazole and 3.0 g of potassium carbonate in 300 ml of chloride 1.725 g of m-chloroperbenzoic acid in 50 ml of methylene chloride are added at 0-5 ° C. Then it is stirred for 30 min at 0 ° С, washed with an aqueous sodium bicarbonate solution and saturated sodium chloride solution, dried with magnesium sulfate and evaporated at 40 ° С. The residue is recrystallized twice. from acetonitrile. Obtain 1.6 g of 2 [(5-methyl-2-pyridyl) methyl] sulfonyl-1H-naphtha [2, 3-d] imidaeol, ‘mp. 181 ° C.
    5,6,7,8-tetrahydro-2- [(2-pyridylmethyl) -sulfonyl--1H-naphtha [2,3-0] imidazole, 'm.p. 155156 S.
    Example 18. To 8.0 g of 1H-Naft ^ 2,3-8] imidazole ~ 2-thiol and 20 ml of dimethylformamide , 6.7 g of 4-chloromethyl-5-methylimidazole hydrochloride are added at 90 ° C. After 10 minutes, cool to room temperature and add ether. The precipitate is distilled off under suction and recrystallized from water — ethanol. 6.5 g of 2 £ (5-methylimidazol-4-yl) methylthio] -1H-naphtha [2, 3-d] imidazole dihydrochloride are obtained; so pl. 265-267 ° C.
    Example 19. To 6.2 g of 5,6,7,8-tetrahydro-2- [1- (2-pyridyl) ethylthio] -1H-naphtha [2, 3-d] imidazole in 50 ml of methylene chloride are added h at 0 ° C, 35 ml of a 10% solution of m-chloroperbenzoic acid. After stirring for 3 hours at 0 ° C, the precipitated material is washed in the suction, suspended with acetonitrile, again washed in the suction, washed with ether and then with petroleum ether. Obtain 2.7 g of 5,6,7,8-tetrahydro-2- [1- (2-pyridyl) ethylsulfonyl -1H-naphtha [2, 3-d] imidazole, so pl. 152153 ° C.
    Similarly receive:
    5,6,7,8-tetrahydro-2- [(5-methyl-2-pyridyl) methyl] -sulAonyl -1H-naphth [2, 3-d] imidazole, mp 188189 ° C.
    2- [1- (2-pyridyl) ethylsulfonyl 15 -1H-naphtha [2, 3-d] imidazole; t. pl. 172173 ° C.
    权利要求:
    Claims (1)
    [1]
    1. The GDR patent number 122534, cl. C 07 D 235/28, published 1976.
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    同族专利:
    公开号 | 公开日
    IT7827861D0|1978-09-19|
    AU3981778A|1980-03-20|
    BR7806148A|1979-04-17|
    NL7809529A|1979-03-21|
    ATA673378A|1982-01-15|
    PL209693A1|1979-06-04|
    US4248880A|1981-02-03|
    DD138210A5|1979-10-17|
    PH16342A|1983-09-05|
    MC1213A1|1979-05-18|
    JPS5459274A|1979-05-12|
    FI782847A|1979-03-20|
    NO783155L|1979-03-20|
    GR73069B|1984-01-30|
    ES473451A1|1979-05-01|
    EP0001279A1|1979-04-04|
    FR2403340B1|1981-02-13|
    MTP835B|1979-11-14|
    FR2403340A1|1979-04-13|
    AU519711B2|1981-12-17|
    NO149962C|1984-07-25|
    FI64365C|1983-11-10|
    AR224350A1|1981-11-30|
    SE7809792L|1979-03-20|
    PT68573A|1978-10-01|
    IL55557D0|1978-12-17|
    AT368152B|1982-09-27|
    PL114494B1|1981-01-31|
    IT1098858B|1985-09-18|
    IE47363B1|1984-03-07|
    GB2004281A|1979-03-28|
    DE2840591A1|1979-03-29|
    NZ188405A|1981-03-16|
    HU176111B|1980-12-28|
    IL55557A|1982-02-28|
    BG28708A3|1980-06-16|
    US4182766A|1980-01-08|
    IE781878L|1979-03-19|
    EP0001279B1|1981-09-30|
    GB2004281B|1982-03-10|
    DK406578A|1979-03-20|
    CA1106849A|1981-08-11|
    IN148930B|1981-07-25|
    FI64365B|1983-07-29|
    OA06054A|1981-06-30|
    NO149962B|1984-04-16|
    YU216778A|1983-01-21|
    RO75258A|1980-11-30|
    EG13530A|1981-12-31|
    DE2861237D1|1981-12-10|
    引用文献:
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    LU78140|1977-09-19|
    CH814978|1978-07-28|
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