• 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 the method of preparation of N-glycosyl compounds of anthracyclin antibiotics of formula I <IMAGE> I where R1 is the hydrogen atom or hydroxylic group, whereas R2 is the residue of a mono- or oligosaccharide of a series of aldeses and ketoses or the derivatives reacted with the amine group of the antibiotic. The invention depends upon the reaction of the antibiotic, which is converted into the form of base, in an organic solvent by treatment with molar excess of the saccharide or its derivative at temperature from 20 DEG up to 60 DEG C., for several hours, in the presence of a catalyst, under continuous stirring. The product is precipitated from the reaction mixture upon the addition of a nonpolar solvent and subsequently is purified by known methods.
    公开号:SU1054352A1
    申请号:SU802954187
    申请日:1980-07-30
    公开日:1983-11-15
    发明作者:Янина Стэфаньска Барбара；Станислав Фальковски Льэонард；Боровски Эдвард
    申请人:Политехника Гданьска (Инопредприятие)；
    IPC主号:
    专利说明:

    M
    The invention relates to new daunorubition products of the formula I Oo, where R is deoxyfructosyl, glucosyl deoxyketoarabinosyl, deoxy-4-cij-D-glucopyranosyl, exhibiting antibiotic activity, and which can be used in medicine. The most similar in structure and exhibiting properties to the compounds of formula 1 is daunorubicin of formula II No. Х HoV exhibiting the antibiotic properties of Cl 3. The purpose of the invention is to search for new compounds exhibiting antibiotic activity, expanding the arsenal of means lively body. The goal is achieved by the properties of the compounds of formula I, showing antibiotic activity. The proposed compounds are obtained by synthesis based on the known reaction of hydroxide-containing compounds with amino containing compounds G2 and are closed in the reaction of daunorubicin as a base with a carbohydrate component in dimethylacetamide in the presence of acetic acid. EXAMPLE 1 0.58 g of daunorubicin as hydrochloride is dissolved in 2 ml of water, a two-fold molar excess of imidazole is added and the extract is extracted with 25 ml of a mixture of chloroform and methyl alcohol in a ratio of 10: 0, 5. The extract is dried with anhydrous sodium sulfate, filtered and evaporated under reduced pressure at 15-20 ° C. the resulting daunorubicin as a base is dissolved in 3 ml of dimethylacetamide, 0.3 g of glucose and 0.003 ml of acetic acid are added and mixed at 35 ° C for 12 hours. After completion of the regression, 150 ml of ethyl ether are added, the precipitate is centrifuged, washed several times with 5 ml of chloroform, and the remaining precipitate is purified by column chromatography — on Sephadexe consisting of methanol: chloroform 5: 1. After the solution thickens with ethyl alcohol, it is precipitated with K- ( 1-deoxy-fructose-1-yl) daunorubicin, washed with ethyl alcohol and dried under reduced pressure. Received O, 56g of the derivative indicated above, which is 80% of the theory. So pl, with a decomposition of 183 ° C. Example 2. About, 53 g of daunorubicin as a base and 0.3 g of glucose are dissolved in 3 ml of dimethylformamide and mixed at 35 ° C for 12 hours. After completion of the reaction, 150 g of ethyl ether are added, the precipitate is centrifuged, washed several times 5 ml of chloroform, and the rest of the residue is purified by the method of column chromatography on Sephadexe HNoH composition of chloroform: methanol 5: 1. After the solution is thickened by the addition of ethyl ether, H - (- glucose-1-yl) -daunoru is precipitated, bicin, which is washed with ethyl ether and dried under reduced pressure. 0.45 g of the derivative mentioned above was obtained, which constitutes 60% of the theory. Example 3. About, 53 g of daunorubicin and 0.3 g of ribose are dissolved in 3 ml of dimethylacetamide, 0.03 ml of acetic acid is added and mixed for 12 hours. Then proceed as in example 1. 0.5 g of I-O {1-deoxyketoarabinos-1 (yl) daunorubicin, which is 70% of the theory. Melting point with decomposition of 170-173 ° C. Example 4.0.53 g of daunorubicin in the form of an alkali and 0.75 g of maltose are dissolved in 5 ml of dimethylacetamide, 0.1 ml of acetic acid is added and stirred for 16 hours at 35 ° C. After completion of the reaction, 100 ml of ethyl ether are added. The precipitate obtained is separated in a centrifuge and purified according to the method of column chromatography on Sefeshex JIX-20 in methanol. Concentration of the solution is then performed and N- (1-deso1 (CI-4-) -D-gJ-succinyl (α-fructos-1-yl) rubidomycin in an amount of 0.8 g is precipitated with ethyl ether in an amount of 50% of theory. , pl. with decomposition of 187-189 C. The obtained derivatives have anti-neoplastic activity against leukemia L 1210. The biological activity of daunorubicin and its derivatives with respect to mouse leukemia L 1210 is given in the table.
     T / C denotes the ratio of the average lifetime of the treated mice to the group of untreated myaea (10 pieces).
    The studies were performed by inoculating 10 LF in the amount of 10 CDF cells on day zero in mice of the breed of CDF leukemia cells. The drug was administered to the pharmacy daily for 5 days.
    The data show that the novel compounds of formula 1 are not inferior in biological activity to the known antibiotic daunorubicin.
    权利要求:
    Claims (2)
    [1]
    | -Glycosyl derivatives of daunorubicin formula
    where nd is deoxyfructosyl, glucosyl, deoxyketoarabnnosyl, deoxy-4-c1-B-glucopyranoyl-fructosyl, exhibiting antibiotic activity.
    SL
    with
    SP
    Yu
    >
    one
    1054352
    [2]
    2
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    同族专利:
    公开号 | 公开日
    JPS5663994A|1981-05-30|
    DK305880A|1981-04-18|
    DE3028148C2|1984-10-25|
    BE884318A|1980-11-03|
    PL219049A1|1981-05-08|
    FI67708C|1985-05-10|
    PL124284B1|1983-01-31|
    SU1011051A3|1983-04-07|
    GB2060609A|1981-05-07|
    FI802332A|1981-04-18|
    DE3028148A1|1981-04-30|
    GB2060609B|1984-09-05|
    FR2473524B1|1983-06-03|
    FR2473524A1|1981-07-17|
    US4351937A|1982-09-28|
    JPS5914479B2|1984-04-04|
    FI67708B|1985-01-31|
    SE8005099L|1981-04-18|
    引用文献:
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    JPS5438103B2|1976-08-16|1979-11-19|
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    GB2007645B|1977-10-17|1982-05-12|Stanford Res Inst Int|Benzyl anthracyclines and pharmaceutical compositions containing them|CH648327A5|1980-10-16|1985-03-15|Hoffmann La Roche|ANTHRACYCLINE.|
    JPH0479355B2|1985-06-24|1992-12-15|Microbial Chem Res Found|
    US4863739A|1987-05-19|1989-09-05|Board Of Regents, The University Of Texas System|Liposome compositions of anthracycline derivatives|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    PL1979219049A|PL124284B1|1979-10-17|1979-10-17|Process for preparing n-glycosyl derivatives of antibiotics from anthracyclines group|
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