• 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:
    A new synthesis of auranofin comprising reacting 2,3,4,6-tetra-O-acetyl- alpha -D-glucopyranosyl bromide with triethylphosphinegold(I) chloride and sodium or potassiumsulfide. Auranofin is an antiarthritic pharmaceutical compound. Auranofin is an orally active therapeutic agent which is useful in man as an antiarthritic.
    公开号:SU795486A3
    申请号:SU782607697
    申请日:1978-04-20
    公开日:1981-01-07
    发明作者:Тейлор Хилл Дэвид；Моут Саттон Блэйн；Лантос Иван
    申请人:Смитклайн Корпорейшн (Фирма)；
    IPC主号:
    专利说明:

    one
    The invention relates to an improved method for the preparation of auranofin / which is an active therapeutic anti-arthritis agent used to treat humans.
    A known method for producing aura-. finite, which is that S (2,
    3,4,6-tetra-0-acetylglycopyranosyl), thiopseudourea hydrobromide is dissolved in water together with potassium carbonate, after which it is reacted with gold triethylphosphine in ethanol, in the cold (-10 ° C) according to the following scheme:
    2,3,4, B.-tetra-0-acetylglucopyranosyl of the General formula
    (D
    where Ac is an acetyl group, and the y-atom of bromine is reacted with sodium or potassium sulfide and triethylphosphine gold chloride in a two-phase solvent system consisting of a halogenated hydrocarbon and water. The most preferred option is to use methylene chloride as the halogenated g of levodrod and starting compound of formula (i), where; about (.- brom.
    The reaction is most conveniently carried out by the interaction of approximately equimolar amounts of the 2,3,4,6 tetra-0-acetyl-1 reactive ester; -0-glucopyranosyl, a reactive triethylphosphine gold halide and sodium or potassium sulphide.
    The reaction conditions are not critical, but it is most advisable to carry out the reaction at about room temperature with stirring for 0.5-6 hours until the reaction is complete. Reflux heating can be used, but it does not provide significant advantages, and if high boiling point solvents are used, the reaction temperature should be limited to about 75 ° C.
    The reaction product is prepared by conventional methods. For example, the organic layer is separated, washed and evaporated to give the desired crude auranofine, which is then purified by chromatography or fractional crystallization.
    Example. A mixture of 1.2 g. . (5 mol) sodium sulfide monohydrate in 20 ml of water is added to a mixture of 2.0 g (5 mol) of 2,3,4,6-tetra-Oacetyl-.o-D-glucopyranosyl bromide and 1.7 g (5 mol) triethylphosphine gold in 20 ml of chloroform and 20 ml of water. . After stirring at room temperature for 1 hour, the layer is divided. The chloroform layer is washed, dried over magnesium sulfate, filtered, and the filtrate is evaporated under reduced pressure, to give an oily crude auranofin. It is passed through an aluminum column (Belma) with a chloroform applied as eluent to obtain solid auranofine, which is then recrystallized from a mixture of ethanol and water. A white solid is obtained, mp. 9925
    .
    . j, {1% methanol), 52.4. The yield of 96% product is 2.75 g.
    Replacing potassium sulphide gives a similar product. with Chloroform may be replaced with methylene chloride.
    EXAMPLE 2 Chloroform solution (25 ml) - 1.0 g (1.5 mol) of bis (triethylphosphine) gold 3-sulphide obtained by reacting sodium sulphide with two molar equivalents of triethylphosphine chloride in a mixture of chloroform and water, and 0 , 6 g (1.5 mol) 2,3,4 / 6-tetra-O-acetyl glucopyranosyl bromide is stirred at room temperature 5 for 48 hours. The solvent is removed under reduced pressure. The residue is purified over silica gel using benzene and ether (0-5Q% ll
    The resulting product is crystallized from a mixture of methanol and water and get: auranofin, so pl. 109-111 С fei J. (1% methanol) - 53.3. The yield of 100% product is 0.8 g.
    According to another embodiment, it is possible to add 5 bromide in chloroform to the mixture of chloroform and water used to prepare bis-sulfide without separating the sulfide.
    权利要求:
    Claims (3)
    [1]
    1. The method of obtaining auranofina (G
    CHjOAc
    (P
    5AoR (SdN5),
    -4 ASO SLA
    where Ac is an acetyl group, by reacting a reactive derivative of 2,3,4,6-tetra-O-acetyl glucopyranosyl with gold triethylphosphine chloride and an alkali metal salt, characterized in that / to simplify the process as a derivative 2,3,4, 6-tetra0-acetyl-glucopyranosyl use a compound of the formula
    (0)
    where Ac means an acetyl group, and a y-atom of bromine, as an alkali metal salt, sodium or potassium sulfide and the process is carried out in a two-phase solvent system consisting of a halogenated hydrocarbon and water.
    E 795486
    [2]
    2. The method according to claim 1, 1 and 2 of the formula CHO use the compound and with the fact that as a halogen, where y is cL - bromine,
    Nated hydrocarbons are used by sources of information emathia,
    methylene chloride. injected during examination
    [3]
    3. The method according to claim 1, about tl and cha u-1. US patent No. 3635945,
    1d and with the fact that in quality koesedi-kl. 260-210, publ. 1972 (prototype),
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    同族专利:
    公开号 | 公开日
    NO146328B|1982-06-01|
    SE7804208L|1978-10-22|
    DK163978A|1978-10-22|
    IL54528D0|1978-07-31|
    DK150858C|1987-12-07|
    IT1094084B|1985-07-26|
    FR2387996A1|1978-11-17|
    DK150858B|1987-07-06|
    FI781155A|1978-10-22|
    AR215695A1|1979-10-31|
    IE780753L|1978-10-21|
    PL206281A1|1979-03-12|
    ATA274678A|1980-08-15|
    PL111162B1|1980-08-30|
    YU39417B|1984-12-31|
    NO146328C|1982-09-08|
    DD136745A5|1979-07-25|
    CH633561A5|1982-12-15|
    US4131732A|1978-12-26|
    SE444568B|1986-04-21|
    IE47046B1|1983-12-14|
    FR2387996B1|1980-08-01|
    FI64165B|1983-06-30|
    AT361507B|1981-03-10|
    IT7822402D0|1978-04-17|
    FI64165C|1983-10-10|
    PT67904A|1978-05-01|
    CS194843B2|1979-12-31|
    BG28716A3|1980-06-16|
    NO781391L|1978-10-24|
    ES468938A1|1978-12-16|
    YU95478A|1982-10-31|
    PT67904B|1979-10-15|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    BE757672A|1969-10-28|1971-04-19|Smith Kline French Lab|1-beta-D-glucopyranosides auro-trialcoylphosphine complexes|
    DK129847C|1969-10-28|1975-05-12|Smith Kline French Lab|
    DK135897C|1969-10-28|1977-12-12|Smith Kline & French Laboratories|US4301152A|1979-10-26|1981-11-17|Merck & Co., Inc.|Immunologic adjuvant|
    US5527779A|1988-03-23|1996-06-18|Top Gold Pty Limited|Topically applied gold organic complex|
    NZ228367A|1988-03-23|1992-02-25|Smithkline Beecham Corp|Topical composition containing a gold compound for treating inflammatory conditions|
    CN1057092C|1997-10-31|2000-10-04|昆明贵金属研究所|Preparation of Anranofin|
    EP2627322B1|2010-10-12|2017-08-02|The U.S.A. as represented by the Secretary, Department of Health and Human Services|Methods of treating giardiasis|
    EP3253214A1|2015-02-06|2017-12-13|Auspherix Limited|Methods for the inhibition and dispersal of biofilms using auranofin|
    WO2016124936A1|2015-02-06|2016-08-11|Auspherix Limited|Inhibition of microbial persister cells|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US05/789,603|US4131732A|1977-04-21|1977-04-21|Method for preparing auranofin|
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