• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The invention relates to steroids, in particular, a process for the preparation of pregnane derivatives of the general formula (I): R2-CH / 2-C (0) -MOR, where R, H or formyl, OH or acetoxy, M is a group of the formula: X, - H or CH t ,, and the symbol is a single or double carbon-carbon bond that can be used as an intermediate in the synthesis of pharmacologically active steroids. The purpose of the invention is the creation of new intermediates for the synthesis of new active substances. The synthesis of the target compounds is carried out by the reaction of the androstane derivative of general formula (II): HO-MCsCCl with acetonitrile. The ester of general formula (III) obtained is X O-MC CC1, where M is cm Bbmie, X - N0, process conc. formic acid in the presence of a catalyst — O, 1 — 0.2 mol of silver nitrate (1+) per 1 mol of compound (III) and a basic solvent, such as 1-methyl-2-pyrrolidone. Then, if necessary, the 17-formyl ester is omitted and the C1 atom in the 21-position is replaced by the acetoxy group, after which it is also washed, if necessary. The invention allows to obtain the desired products in a simple manner. § SP 4 4 About co OJ
    公开号:SU1440351A3
    申请号:SU853949150
    申请日:1985-09-05
    公开日:1988-11-23
    发明作者:Хофмайстер Хельмут；Аннен Клаус；Лаурент Хенри；Вихерт Рудольф
    申请人:Шеринг Аг (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a new process for the preparation of pregan derivatives with the general formula
    five
    R is a hydrogen atom or a formyl group,
    X, is a hydrogen atom or methyl, R. is a chlorine atom, hydroxyl
    a group or acetoxy group; 20 - g means a single or double carbon-carbon bond,
    important intermediates in the synthesis of pharmacologically active steroids. .
    The purpose of the invention is to create a simple and effective method for producing targeted steroids of the general formula (I) "
    PRI me R 1.
    a7 K-suspension 5.7 g of 17 s-chloro-ethynyl-17-axi-4-androsten-3-one in 50 ml of acetic anhydride is added with 6.5 ml of fuming nitric acid. After 5 minutes, the cancer mixture was poured into ice-cold water containing methanol, the precipitated product was filtered off with suction, dissolved in ethyl acetate, washed with water and dried over sodium sulfate. 5.1 g of 17 ° were obtained (chloroethene -1-1 7 fi-nitroxy-A-and- rosten-3-one, mp 140 ° C (decomposition).
    b / 4.0 g 17o (-chlorethynyl-17 / b-nitroxy-4-androsten-3-she-dissolve in 10 ml of 1-meter-1-2-pyrrolidok. At the addition of 46 ml of concentrated formic acid and 200 mg of silver nitrate and allowed to stir at room temperature, the mixture is mixed into ice water after 8 hours. The precipitated product is precipitated, dissolved in acetic ether, washed with water and dried over sodium sulfate. chlorine-17-formyloxy-4-pregnen-3 ,, 20-dione, mp 204, OC
    Example 2. 1.6 g of 21-HLOR-17-β-formyloxy-4-pregnen-3, 20-dione at room temperature, ure stirred
    ten
    five
    20 ,
    thirty
    35
    40
    25
    ,

    440351, 2
    in a mixture of 60 ml of methanol and 9 ml of water with 500 mg of potassium bicarbonate. After 1 h, the reaction mixture was placed in ice water. The precipitated product is filtered off with suction, washed with water and dried over sodium sulfate. 1.3 g of 21-chloro-17-hydroxy-4-pregnen-3,20-dione are obtained. T. pl. 239 ,.
    Example 3. 1.0 g of 21-chloro-17-oxy-4-pregnen-3, 20-dione in 20 ml of dimethylformamide is stirred with 1.0 g of potassium acetate at. After 30 minutes, the reaction mixture was added to ice water, and the precipitated was removed. the product is dissolved in ethyl acetate and dried over sodium sulfate. 940 mg of 21-acetoxy-17-hydroxy-4-pregnen-3, 20-dione are obtained. Mp. 236 ,.
    Example 4
    a / 11.5 g (4.9 (11) -androstadiene-3,17-dione (US Patent No. 3441559, 1969) in 200 ml of dioxane are reacted with 20 ml of trimethyl ortoformate and 100 mg of p- toluenesulfonic acid. After 48 hours, 5 ml of pyridine was added to the solution, concentrated in vacuo, the residue was treated with ethyl acetate, washed with water and dried over sodium sulfate. After chromatography of the crude product with hexane-acetic gradients on silica gel, which contained 2% triethylamine, 9.2 g of 3-methoxy-3, 5.9 (II) -andprostate-pyrien-17-one, were isolated. Mp 153,.
    b / C 6 ml of 1,2-dichloroethylene in 100 ml of absolute ether at 0 ° C are added with 80 ml of a 1.5 M solution of methylillite (in ether). After 30 minutes, 6.3 g of 3-methoxy--2, -5.9 (11) -androstatryen-1 7-one is slowly added to 150 ml of absolute tetrahydrofuran. After 15 minutes, the reaction mixture is diluted with ether and carefully mixed with 50 ml of a saturated solution of aluminum chloride. The organic phase is washed to neutrality with 2N hydrochloric acid and water, dried over sodium sulfate, and concentrated in vacuo. The resulting crude product in 30 ml of acetone at room temperature is mixed with 0.3 ml of 70% perchloric acid. After 30 minutes, the reaction mixture was poured into ice water, the precipitated product was filtered off with suction, dissolved in ethyl acetate, washed with water and dried over sodium sulfate. After chromatography
    45
    50
    55
    ten
    20
    25
    thirty
    The crude product of silica gel with hexane-ethyl acetate gradients gives 6.0 g of 17 ° / -chlorethynyl-17-hydroxy-4.9 (11) -androstadien-3-eye. T. pl, 157 ,.
    in 5.7 g 17 ° -chloroethynyl 17-oxy-4.9 (11) -androstadiene-3-one, analogously to Example 1a, was reacted with nitric acid in acetic anhydride. After chromatography of the crude product on a silica gel with hexane-acetic ether-gradients, 4.8 g of 17 l -chlorethins 1-17 / 5-nitroxy-4,9 (11) androstadiene 15 3-one are obtained as a foam.
     g / 4.5 g 17e-chloroethyn-17-nitroxy-4.9 (11) -androstadiene-3-one is analogously introduced to the interaction in Example 16. 3.8 g of 21-chloro-17-formiroxy-4,9 (II) -pregnadien-3,20-dione are obtained. T. Sh1. 202.7 ° C.
    Example 5. 2.5 g of 21-chloro-17-β-forms 1Oxy-4,9 (II) pregnadien-3,20-dione are introduced into the reaction as in Example 2. 2.2 g of 21-chloro-17-hydroxy-4 are obtained. , 9 (11) -pregnadi-3,20-dione. T. pl. 236.9 ° C.
    Example 6. 1.5 g of 21-chloro-17-β-oxy-4,9 (II) -pregnadien-3,20-disn is reacted in the same way as in Example 3. 1.4 g of 21-acetoxy-SI-17 are obtained. -OXY-4,9 (II) -pregnadien-3,20-dione. T. pl. 234 ,.
    Example 7
    a / 1.5 g 21-acetoxy-17-hydroxy-4.9 (11) -pregnadaene-3,20-dione 40 ml of methanol is stirred with 15 ml of 0.2N. methanol solution of potassium hydroxide for 2 h at room temperature. The reaction mixture was added to ice water. The precipitated product is sucked off, dissolved in meth- etchton chloride, washed with water and dried over sodium sulfate. 1.2 g of 17,21-dioxy-4,9 (II) -pregnadien-3,20-dione are obtained. T. pl. 248.2 ° C.
    b / 20.0 g 17c (-chloroethenyl-17/5-hydroxy-4-androsten-3-one in 1 l of dioxane is stirred at 110 ° C together with 20.0 g of gg 2, 3-dichloro-5.6 -ditzian-p-benzoquinone. After 20 hours, dilute with methylene chloride, dilute with water and sodium bicarbonate solution and dry over sodium sulfate. The crude solution is chromatographed on silica gel with hexane-ethyl ether-gradients. Yield 14.7 g 17o-chloroethynyl-17 / -hydroxy-1,4-α-androstadien-3-one, mp 125.2 ° €.
    40
    35
    45
    5g
    .
    0
    0
    five
    five
    in / 8.0 g of 17c / -chlorethynyl-17-oxy--1,4-androstadiene-3-one, as in Example 1a, was introduced into the interaction with nitric acid smoke. 6.8 g of 17a -chloroethynyl-17l-nitroxy--1,4-androstadiene-3-one were recovered. Foam.
    g / 2.6 g 17c-chloro-ethynyl-17 nitroxy-1,4-androstadiene-3-one is reacted in the same way as in Example 16. 1.8 g of 21-chloro-17-forms-1-hydroxy-1,4 are obtained. -pre gnadien-3,20-dione.
    Example 8. 1.2 g of 21-HLOR-17-β-formyloxy-1,4-pregnadien-3, 20-dione are reacted in the same way as in Example 2. 960 g of 21-chloro-17-OXY-1.4 are obtained. -pregnadien-3, 20-dione.
    Example 9. 820 mg of 21-chloro-17-y-oxy-1,4-pregnadien-3, 20-dione analogously to example 3 is converted into 21-acetoxy-17-OXI-1,4-pregnadien-3,20- dion. Yield 710 mg. T. pl. 215.8 ° C.
    0
    g
    0
    Example 10
    a / 16.0 g 17. (/ - chporethynyl-17-oxy-4.9 (II) -prednadien-3-one, analogously to Example 66, is introduced into the reaction with 2, 3-dsh-5,6-dicyan β-β-benzoquinone in dioxane. 9.8 g of 17c-chloroethenyl-17 /-hydroxy-1,4,9- (II) -a drostattien-3-one are obtained.
    6 / 8.6 g 17 (s-chloroethins 1-17 / s-oxy-5 -1 (11) -androstriatrien-3-one, as in Example 1a, is brought into contact with nitric acid smoke. 7.8 g of 17 ° are obtained ( -chlorethynyl-17 / -nitroxy-1,4,9 (11) -androstatrien-3-one.
    in / 6.5 g of 17-chlorostinyl-17/3-nitrooxy-1,4,9 (11) -androstriatene-3- -one is converted as in Example 16. 4.9 g of 21-chloro-17-form are obtained. - 5 miloxy-1,4,9 (11) -pregnatriene-3,20, -dione.
    Example 11. 3.2 g of 21-chloro-17-FORMILOXY-1,4,9 (11) -pregnatriene-3,20-dione analogously to example 2 is converted into 21-chloro-17-hydroxy-1,4,9 - (II) -predgnatin-3,20-dione. Exit 1 2.9 g. T. pl. 190 ,.
    Example 12. 1.2 g of 21-ChLOR-17 g-hydroxy-1,4,9 (II) -pregnatriene-3,20-diona is transformed as in Example 3. 980 mg of 21-acetoxy-17- are obtained. -oxy-1,4,9 (11) -pregnatriene-3,20-di. she is.
    Example13.
    a / Analogously to Example 4a 7.5 g of a 6 | / -metx-1-A, 9 (11) -androstadiene-3,17- -dione is converted into 3-methoxy-6-methyl-3,5,9 (11) -androstatrien-17-he, Exit 6.1,
    b / From 5.5 g of 3-methoxy-6-methyl- -3,5,9 (11) -androstatria-17. as in Example 4b, 5.1 g of i 17 / -chloroethish 1 -17 / 1-hydroxy- are obtained. 6o methyl -4.9 (11) -androstadien-3-one.
    in / 4.5 g 17 (X-chloroethenyl-17 3-hydroxy-6 in methyl-4.9 (II) -androstadiene-3- -one, as in Example 1a. Convert to 17g / -chloroetinsh1-17 / -neutroxy - -6 s -methyl-4.9 (II) -androstadien-3-one. Exit 3.8g.
    g / 2.9 g 17c -corethynyl-17/5-nitrooxy-6e -methyl-4, 9 (11) -androstadiene-3-one — as in Example 16, is converted into 21-chloro-17-formshoxy-6o ( - -methyl-4,9 (11) -pregnadien-3,20-dione. Output 2.1 g. Decomposition temperature 168-170 ° C,
    Example 14. Analogously to Example 2, 1.6 g of 21-chloro-17-formsh10ksi- -6o-methyl-4.9 (11) -pregnadien-3,20- -dione is transformed into 21-chloro-17 oxy-6c - methyl-4,9 (11) -lregnadiene-3,20-dion. 1.3g yield
    .Pr. Nme p 15. From 1.1 g of 21-chloro-17-hydroxy-6o-methyl-4.9 (11) -prednadien-3,20-dione, according to example 3, 870 mg of 21-hydroxy-17 -Oxy-6 "-methyl-4, 9 (11) -pregnadien-3,20- -dione.
    Example 16
    a / 12.5 g of 3/5-hydroxy-B-homo-5-androstan-17c-it, as in Example 4b, is reacted with lithium chloroacetylide. After chromatography of the crude product on silica gel with hexane-acetone gradients, 8.9 g of 17 ° are obtained (-chlorethynyl-B-gomo-5-androstene-3 / 3.17a / 5-diol.
    b / From a solution of 10.0 g of 17α-chloro-ethynyl-B-homo-5-androsten-3 / 3-, 7af, -diol in 300 ml of toluene and 50 mp of cyclohexanone, about 5 ml of solvent are distilled off. With further distillation of the solvent, 4.0 g of aluminum triiso-propylate in 30 ml of toluene are added. After 1.5 hours, 50.0 g of potassium sodium tartrate in 70 ml of water are slowly added and the mixture is stirred for 30 minutes at reflux temperature. After cooling, the solution is diluted with acetic acid.

    -

    4-40351
    ether, preserve the organic phase multiple times with water and dry over
    sodium sulfate. After chromatography
    g fi the crude product on silica gel with hexane-acetone-gradient n-get 8.4 g of 17ao-chloroethenyl-17a / -oxy-D-homo-4-andprostan-3-one. in / 8.3 g 17a (/ - chloroethenyl-17a / i-o-10-C-B-homo-4-androsten-3-one, as in Example 1a, is converted into chloroetinine-17a-nitroxy-1) homo-4 - Androsten-3-he. Exit 6.7 g
    g / 6.3 g 17ac / -chloroethynyl-17a / -nit15 rooxy-B-homo-4-androsten-3-one is converted as in Example 16. 4.3 g of 21-chloro-17ac | (-formal 1-hydroxy) are added. -B-homo-4-pregnen-3,20-dione Example 17. 3.8 g of 21-chloro 20 -17ao-formyloxy-B-homo-4-pregnen-1 -3,20-dione analogously to example 2 is converted into 21 -chloro-17a / -oxy-B-homo-4-pregnen-3,20-dione. Yield 3.1 g. Example 18. 2.4g21-chloro25 -17 ao / -oKCH-D-homo-4 -pregnen-3,20-β-dione, analogously to example 3, is converted into 21-acetoxy-17ao (α-hydroxy-B-homo-4-pregnen-3,20-dione. Yield 2.1 g. Example 19.
    30 a / K 5.0 g 17 (/ - chlorethin 1-17 p-oxy-4-androsten-3-one in 25 ml of pyridine at 0 ° C, 3.4 ml of trifluoroacetic anhydride are added. After 30-NIN the reaction mixture contribute to
    35 hydrochloric acid mixture of ice water. The precipitated product is removed by suction, washed with water and dried. By hardly combining the crude product on silica gel using hexane / ethyl acetate gradients, 4.1 g of 17 / -chlorethyn-17 / -trifluorocetoxy-4-androsten-3-one are obtained. T. pl.
    139 ° C.
    b / 3.5 g 17o / -chloro-ethynyl-11/3-trifluoroacetoxy-4-androsten-3-she is stirred in 30 ml of concentrated formic acid and 6 ml of 1-methyl-2-pyrrolidone with 300 mg of silver nitrite at 60 ° C. After 6 hours, the reaction mixture was added to ice water. The precipitated product is removed by suction, washed with water and dried. After chromatography of the crude product on silica gel with a mixture of hexane and acetic acid, 1.3 g of 2 1-chloro-1 7-formyloxy-4-pregnen-3,20-dione are obtained. T. pl. 201.5 s.
    / .14
    Example 20
    a / K 5.0 g 17o-chloroethynyl-17/3-oxy-4-androsten-3-one in 30 ml of pyridine, 3.5 ml of trichloroacetic anhydride are added dropwise. After 15 minutes, the reaction mixture was added to an ice-water mixture containing sulfuric acid. The precipitated product is treated with acetic ether. Chromatography of the crude product on silica gel using hexane with ethyl acetate gives 4.8 g of 17 ° -chlorethin1-17-trichloroacetoxy-4-androsten-3-one. T. pl. 173 ° C (decomposition).
    b / 1.4 g 17o-chloro-ethynyl-11/3-trichloroacetox-4-androsten-3-one (as described in Example 18) in concentrated formic acid and 1-methyl-2-pyrrolidone are reacted with silver nitrate. After chromatography of the crude product on silica gel with hexane with ethyl acetate, 630 mg of 21-chloro-17-formyloxy-4-pregnen-3,20-dion are obtained. T. pl. 202 ..
    Thus, using the described method, it is possible to synthesize the target products by essentially
    by.
    权利要求:
    Claims (1)
    [1]
    1. The method of obtaining derivatives of pregnane with the general formula CIOHL
    . -
    Oh oh

    where R is a hydrogen atom, or formyl X. is a hydrogen atom or methyl
    eight
    7 chlorine atom, hydroxyl group or acetoxy group, means a single or double carbon-carbon bond,
    characterized in that the derivative of androstan is common
    Nl
    with-
    about
    X
    are esterified with acetylnitrate to form a total ester
    formulas
     , 20
    25
    thirty
    where X. has the indicated meanings


    35
    X-, - nitro group,
    which is then treated with concentrated formic acid in the presence of 0.1-0.2 mol of silver nitrate (Ij per 1 mol of compound (III) and the main solvent, such as 1-methyl-2-pyrrolidone, as catalyst, then, if necessary, The 17-form ester is washed and the chlorine atom in the 21-position is replaced by an acetoxy group, after which it is also washed if necessary.
    类似技术:
    公开号 | 公开日 | 专利标题
    US4061661A|1977-12-06|Δ9| -5α-20-KETO STEROIDS AND PROCESS FOR THEIR PRODUCTION
    SU1440351A3|1988-11-23|Method of producing derivatives of pregnane
    US3993675A|1976-11-23|Process for the preparation of 1α,25-dihydroxycholecalciferol
    EP0326340B1|1993-12-08|Improvement in the synthesis of 6-methylene derivatives of androsta-1,4-diene-3,17-dione
    AU775831B2|2004-08-19|Process for preparing 17alpha-acetoxy-11beta-|phenyl)-21- methoxy-19-norpregna-4,9-diene-3,20-dione, intermediates useful in the process, and processes for preparing such intermediates
    CA1159049A|1983-12-20|Process for the preparation of 6-halo-pregnanes
    US3682983A|1972-08-08|Preparation of {66 {11 {11 -17 ethinyl steroids
    US4119625A|1978-10-10|Process for the manufacture of steroid carboxylic acids and the esters thereof
    SU517263A3|1976-06-05|The method of obtaining d-homosteroids
    Wendler et al.1956|The Structure and Synthesis of D-Homosteroids1
    US4102908A|1978-07-25|Process for the preparation of pregnane derivatives
    Parish et al.1980|Inhibitors of sterol biosynthesis. Synthesis of 9. alpha.-fluoro-3. beta.-hydroxy-5. alpha.-cholest-8 |-en-15-one and related compounds
    Bowers et al.1959|Steroids. CX. 1 Studies in Nitro Steroids |. 1 A New Route to 6-Nitro Steroid Hormones. 6α-Nitro-17α-acetoxyprogesterone and 6α-Nitrocortisone2
    US4031080A|1977-06-21|16-Alpha-methyl-17 alpha-bromo-1,4-pregnadiene-21-ol-3,20-dione-derivatives
    US4145346A|1979-03-20|Preparation of 3β-hydroxy-27-norcholest-5-ene-25-one and intermediates thereof
    SU615863A3|1978-07-15|Method of obtaining derivatives of pregnanolic acid
    US4150044A|1979-04-17|Process for the manufacture of 17α-hydroxy-21-acetoxy-progesterone
    US4145357A|1979-03-20|Steroid derivatives and process for preparing the same
    JPH0776231B2|1995-08-16|Process for producing 17α-ethynyl-17β-hydroxy-18-methyl-4,15-estradien-3-one
    US4116978A|1978-09-26|D-homo oxasteroids
    US2915535A|1959-12-01|Process and intermediates to produce substituted 4-bromo-21-acetoxy-pregnane-3, 20-dione compounds
    US3096350A|1963-07-02|6, 16alpha-dimethyl-delta1, 4, 6-pregnatriene-17alpha-ol-3, 20-dione and esters thereof
    US3945997A|1976-03-23|Steroidal bicyclic dioxanes
    Scott et al.1974|C |‐Methylation of Steroidal Synthesis Intermediate BCD‐Tricyclic 9‐En‐5‐ones
    US3087941A|1963-04-30|17alpha-bromo-6-methyl-pregnane derivatives
    同族专利:
    公开号 | 公开日
    FI853560A0|1985-09-17|
    DE3571441D1|1989-08-17|
    AT44532T|1989-07-15|
    CA1260929A|1989-09-26|
    CS250695B2|1987-05-14|
    US4956482A|1990-09-11|
    EP0181442B1|1989-07-12|
    JPS61129197A|1986-06-17|
    PL255391A1|1986-07-15|
    GR852241B|1986-01-17|
    FI853560L|1986-03-18|
    DK420985A|1986-03-18|
    ES546995A0|1986-03-16|
    EP0181442A1|1986-05-21|
    DD238387A5|1986-08-20|
    DK420985D0|1985-09-17|
    ES8604987A1|1986-03-16|
    HU194905B|1988-03-28|
    HUT38951A|1986-07-28|
    JPH0710877B2|1995-02-08|
    DE3434448A1|1986-03-27|
    US4708823A|1987-11-24|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3067214A|1960-04-20|1962-12-04|Merck & Co Inc|Haloethisterone compounds|
    DE2625306C2|1976-06-02|1978-06-15|Schering Ag, 1000 Berlin Und 4619 Bergkamen|Process for the preparation of pregnane derivatives|
    HU185797B|1981-04-16|1985-03-28|Richter Gedeon Vegyeszet|Process for producing 3-oxo-17-alpha-ethinyl-17beta-trifluoroacetoxy-gonane derivatives|
    EP0063368B1|1981-04-16|1984-07-25|Richter Gedeon Vegyeszeti Gyar R.T.|Process for the preparation of pregn-4-ene-3,20-dione derivatives and 17-alpha-ethynyl-17-beta-trifluoroacetoxy-gon-4-ene-3-one derivatives, and pharmaceutical compositions containing the latter compounds|
    HU183397B|1981-04-16|1984-04-28|Richter Gedeon Vegyeszet|Process for preparing 17alpha-hydroxy-pregn-4-ene-3,20-dione derivatives|
    US4342702A|1981-05-18|1982-08-03|The Upjohn Company|Metallated halogenated acetylene corticoid synthesis|
    DE3315324A1|1983-04-25|1984-10-31|Schering AG, 1000 Berlin und 4709 Bergkamen|METHOD FOR PRODUCING 17 - -ETHINYL-17SS-OR STEROIDS|JPH05501115A|1990-03-27|1993-03-04|
    AP141A|1990-04-25|1991-08-25|Richter Gedeon Vegyeszet|Novel steroid doils.|
    WO1995030684A1|1994-05-09|1995-11-16|Pharmacia & Upjohn Company|SYNTHESIS OF 17β-CYANO-3-ETHOXY-17α-HYDROXY-6-METHYLANDROSTA-3,5,9-TRIENE|
    JPH10191658A|1996-01-09|1998-07-21|Nikon Corp|Vibration actuator|
    US5879711A|1997-11-07|1999-03-09|Sequeira; Joel A.|Stable antiandrogenic gel composition|
    US6696592B2|2001-05-22|2004-02-24|Nicox-S.A.|Methods of making 21-[4′-benzoate] corticosteroid derivatives and intermediates useful in the synthesis thereof|
    CN103833814A|2014-03-06|2014-06-04|浙江仙居君业药业有限公司|Preparation method of 17hydroxy-pregnane-4-alkene-3,20-diketone-21-acetic ester|
    CN105017364A|2015-07-06|2015-11-04|湖南新合新生物医药有限公司|Methylprednisolone intermediate, preparation method therefor and application thereof|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19843434448|DE3434448A1|1984-09-17|1984-09-17|METHOD FOR PRODUCING PREGNAN DERIVATIVES|
    [返回顶部]