• 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:
    Ergoline Esters I (R₁=H or CH₃; R₂=C₁-C₄ hydrocarbon; R₃=H or OCH₃; R₄=H or halogen; R₅=C₁-C₄ alkyl) and their pharmaceutically acceptable salts are active in the central nervous system level. A process for their preparation is also described. The ergoline esters and their salts can be used for the making of pharmaceutical compositions being effective against cerebral insufficiency and senile dementia.
    公开号:SU1549482A3
    申请号:SU874202582
    申请日:1987-05-19
    公开日:1990-03-07
    发明作者:Темперилли Альдемио；Май Роберто；Мантегани Серджио；Брамбилла Энцо
    申请人:Фармиталиа Карло Эрба С.П.А. (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a method for producing a new ergoline derivative of the general formula 1
    where Rd is C 4 -C 4 alkyl having valuable pharmacological properties.
    A method of obtaining a new ergoline derivative of the general formula 1 zaklyu2 (54) METHOD FOR PRODUCING ERGOLINE DERIVATIVE (57) The invention relates to ergoline derivatives, in particular the production of 10-methoxy-1,6-dimethyl-8) 5- (1-C | -C 4 alkyl -1,4-dihydro-3-pyridylcarbonyloxymethyl) -ergolins, which have activity against the central nervous system and can be used to treat metabolic vascular cerebral disorders. The goal is the creation of new active substances of the specified class. Their synthesis led recovery ergoline quaternary halide salt with sodium dithionite in a weakly basic aqueous solution at 5-25 C. The novel compounds have low toxicity (LDjo>
    > 800 mg / kg) and can be used for the intended purpose. 1 tab.
    arises in the restoration of the quaternary salt of ergoline of general formula II
    ΟΗ 3 θ £ © s
    CH 2 -0-С0- <О> -X χΝ-СНз
    SU .... 1549482 AZ where R <takes the indicated values and & represents the halide anion.
    Sodium dithionite is used as a reducing agent.
    The reaction is carried out in a weak basic aqueous solution at 5-25 ° C for a period of 1-12 hours, preferably for 3 hours. Ergoline esters obtained by the proposed method and their pharmaceutically acceptable salts have significant pharmacological activity on level of the central nervous system and can be used to treat metabolic vascular cerebral disorders. ·
    PRI me R 1. 10-methoxy-1,6-dimethyl-8 ^ - (1-methyl-1,4-dihydro-3-py-15 Ridylcarbonyloxymethyl) ergoline 1,
    To a solution of 4.42 g of 10-methoxy-1,6dimethyl-8 ^ (3-pyridylcarbonyloxymethyl) ergoline hydrochloride in 50 ml of dimethylformamide was added 25 ml of methyl-20 ioid and the resulting mixture was stirred for 5 hours at 50'’C. The yellow product which separated out was separated by filtration! And washed with dimethylformamide to give 5.5 g of a quaternary salt, so pl. 25 187-189 ° C.
    To a solution of 4.67 g of the obtained salt in 300 ml of deaerated 50% aqueous acetone, cooled to 5 ° C., 6.78 g of sodium bicarbonate and 3Q 13.9 g of sodium dithionate are added. The resulting mixture was stirred for 3 hours at room temperature. After dilution with water, the separated product is separated by filtration. 35
    The crude product is several times re-crystallized from aqueous acetone to give I g of the title compound, mp 128-130’C.
    Example 2. Biological tests. The compound obtained in Example 1 showed indicative acute toxicity (LD So ) in excess of 800 mg / kg (p / o, in mice).
    In addition, the compound obtained in Example 45 1 was tested at a dose of 20 mg / kg p / o in rats with observation of an electroencephalographic effect (EEG). The data are presented in the table.
    EEG showed increased and long-lasting effects of the modification.
    The test compounds were administered at a dose of 20 mg / kg by mouth to groups of rats of eight animals each and changes (increase and continuation) in the electroencephalograms were determined and compared with those of nicergoline, taking the changes in electroencephalograms as 100
    Acute toxicity (LD TO ) of compounds was determined in mice, increasing the dose of administration and examination was carried out on the seventh day after treatment. The results of ps ^ indicate that the proposed compounds are classified as low-toxic compounds.
    权利要求:
    Claims (1)
    [1]
    Claim
    A method for producing an ergoline derivative of the general formula 1 wherein R 4 is C 4 -Cc-alkyl, characterized in that the 'compound of the general formula wherein R 4 has the indicated meaning;
    X - anion is a halide, is subjected to reduction with sodium dithionite in a weakly essentially aqueous solution at 5 to -25 C.
    Compound Cartical activation Toxicity LD So p / o Increase Duration Famous Nicergoline 100 100 800 mg / kg The proposed (for example 1) FCE 24154 140 126 800 mg / kg
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    同族专利:
    公开号 | 公开日
    FI872174A0|1987-05-18|
    JPS62294682A|1987-12-22|
    JPH0723375B2|1995-03-15|
    GB8612366D0|1986-06-25|
    IL82556D0|1987-11-30|
    AT82287T|1992-11-15|
    KR870011134A|1987-12-21|
    NZ220341A|1989-06-28|
    PT84897A|1987-06-01|
    ES2052512T3|1994-07-16|
    IE871291L|1987-11-21|
    EP0249761A2|1987-12-23|
    IL82556A|1991-06-10|
    FI85142B|1991-11-29|
    PT84897B|1990-02-08|
    FI872174A|1987-11-22|
    DE3782548T2|1993-04-22|
    DE3782548D1|1992-12-17|
    HU196069B|1988-09-28|
    KR950006866B1|1995-06-23|
    HUT44542A|1988-03-28|
    IE60655B1|1994-08-10|
    DK254687A|1987-11-22|
    AU7316887A|1987-11-26|
    EP0249761B1|1992-11-11|
    US4785001A|1988-11-15|
    DK254687D0|1987-05-19|
    GR3006298T3|1993-06-21|
    FI85142C|1992-03-10|
    EP0249761A3|1989-05-10|
    DK169818B1|1995-03-06|
    CA1292224C|1991-11-19|
    ZA873592B|1987-11-12|
    AU588109B2|1989-09-07|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3879554A|1970-03-20|1975-04-22|Farmaceutici Italia|Use of 1,6-dimethyl-8-{62 --10 {60 -methoxyergoline in treating cerebral and peripheral metabolic vascular disorders|
    DE2330912C3|1972-06-22|1979-01-11|Societa Farmaceutici Italia S.P.A., Mailand |Process for the preparation of bromergoline compounds|
    US4057635A|1973-05-23|1977-11-08|Simes Societa Italiana Medicinali E Sintetici S.P.A.|Carbamates of ergolines and therapeutic compositions therewith|
    US4199579A|1975-03-14|1980-04-22|Siphar S. A.|Carbamates of 2-haloergolines and 2-haloergolenes and process for the preparation thereof|
    YU39278B|1976-12-22|1984-10-31|Lek Tovarna Farmacevtskih|Process for preparing 5-bromo nicotinic acid esters|HU193782B|1985-06-21|1987-11-30|Richter Gedeon Vegyeszet|Process for producing 2-halogeno-nicergoline derivatives and acid additional salts thereof|
    GB8615471D0|1986-06-25|1986-07-30|Erba Farmitalia|T-butyl ergoline derivatives|
    DK0628042T3|1992-12-24|2001-11-12|Pharmacia & Upjohn Spa|Serotoninergic ergoline derivatives|
    GB9407637D0|1994-04-18|1994-06-08|Erba Carlo Spa|Serotoninergic abeo-ergoline derivatives|
    GB9603226D0|1996-02-15|1996-04-17|Pharmacia Spa|Heterocyclyl-ergoline derivatives|
    US6060483A|1996-06-27|2000-05-09|Pharmacia & Upjohn S.P.A.|Antineurodegenerative ergoline derivatives|
    DE10018834A1|2000-04-15|2001-10-25|Lohmann Therapie Syst Lts|Transdermal or transmucosal pharmaceutical dosage form for treatment of nicotine dependence or smoking withdrawal contains nicotine compound or substitute and CNS active compound|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB868612366A|GB8612366D0|1986-05-21|1986-05-21|Ergoline esters|
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