• 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 present invention relates to new compounds of general Formula I and physiologically acceptable salts thereof wherein A and B stand for oxygen or -CH₂ group with the proviso that if A stands for oxygen, then B stands for -CH₂ group and R stands for hydrogen, if A represents a -CH₂ group, then B stands for oxygen, R stands for a -CH₂-Q group wherein Q stands for hydrogen, pyrrolidino, piperidino or morpholino and a process for the preparation thereof and pharmaceutical compositions containing as active ingredient a compound of the general Formula (I) or a physiologically acceptable salt thereof.
    公开号:SU1598878A3
    申请号:SU884356751
    申请日:1988-10-31
    公开日:1990-10-07
    发明作者:Корбонитш Деже；Хейа Гергели；Сомор Мария；Минкер Эмиль
    申请人:Хиноин Дьедьсер Еш Ведьесети Термекек Дьяра Рт (Инопредприятие)；
    IPC主号:
    专利说明:

    This invention relates to a process for the preparation of a new xanthine.tin derivative having a biological active nose. and which can be used in medicine.
    The purpose of the invention is a method for producing a new xanthine derivative having a higher proto-crocage activity and less toxicity.
    Example 1: Inject 16, 6 g of 3-methylxanthine and 32.6 ml of a 10% sodium hydroxide solution to give a solution that soon crystallizes. Water is distilled off under reduced pressure, and traces of it are removed by azeotropic distillation with toluene. The residue is suspended in 250 ml of dimethylformamide, after which 16.7 g of 2-bromomethyl-1,3-dioxolane and 0.5 g of potassium iodide are added to the suspension and the mixture is kept for 12 hours at 110-118 C. After this solvent is distilled off under reduced pressure, and the residue is mixed with 100 ml of water, distilled in vacuum and washed with water. After recrystallization from propanol, 17.0 g (68%) of 2- (3-methylxanthine-7) methyl -1,3-dioxolane of the formula Q are obtained.
    vr ™
      °
    about nn
    SNS
    (I)
    O1
    - X
    eo
    36

    s

    M.p. 277-279 C. Mass: H-NMR (DMCOd), MD: ZN NCH,); 3.85 (S, 4H
    / O-BUT
    -sn-
    M 252, 3.4 (S.
    O-CH.
    4.4-4.45 (d, 2R - CH -); 5.1 5, 25 (t, 1H - sleep); 8.0 (S, 1H-8CH)
    11.15 (s, 1H, NH).
    The advantage of the new compound 1 is its low toxicity. For comparison, codeine hydrochloride and 2- (theophyllin-7-yl) methyl | - 1,3-dioxolane were used in biological tests. Antitussive activity was determined by the method described. According to this method, the test compound was administered orally and the time after which the coughing caused by 15% citric acid aerosol was determined was determined.
    Guinea pigs (females and males) weighing 300–350 g were placed in a 3000 ml plexiglas case for inhalations and 15% citric acid solution was sprayed in it (droplet diameter 0.4–5 µm). About the defeat of the respiratory system was judged by the number of cough stupas for 10 min. Thereafter, the test compounds in the form of a 0.5% suspension in methylcellulose were injected into the stomach through a tube. According to the literature data, control compounds, used as protivokashalevnyh drugs, administered orally in an amount of 100 mg / kg. Therefore, screening tests were performed at this dose.
    The test results for compound I and the known analogues are listed in the table (dose: 100 mg / kg, oral administration).
    From the table it can be seen that hydrochloric, codeine tiepe3 1 h after administration, shows the greatest activity in relation to the cessation of coughs. It is followed by dioxolane of formula I.
    After 4 h after administration, Compound I exhibits significantly more


    cortical activity than comparative compounds. The antitask activity of Compound I was investigated in various doses for different periods of time. It was found that already oral doses of 25 mg / kg have a rather strong and long-lasting antitussive.
    act. Unlike Chloride
    Prenatal codeine Compound I does not cause respiratory depression in functional respiratory tests on guinea pigs and rabbits and at the same time has a beneficial effect on the bronchopulmonary system. Respiratory depression and bronchial activity restriction caused by codeine, histamine and acetylcholine can be reduced (in proportion to the dose) using a compound of formula I.
    The compound has low toxicity. Its toxicity can be illustrated by experiments on muscles. According to these experiments, in the case of a compound of formula I and 2- (teofillin-7-yl) meti-JI 3-1, 3-dioxalan, 9 out of 12 mice died after they were orally administered a dose of 1000 mg / kg. In the case of hydrochloric codeine, the same dose caused 100% mortality.
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method for preparing 2- (3-methyl-xanthinyl-7) methyl 3-1,3-dioxalane of formula
    four
    SNS
    characterized in that 3-methylxanthine is reacted with dioxolane of the general formula
    ABOUT
     J
    Q
    where X is .chromium or bromine, in the presence of a base.
    Known:
    (Theophylline-7-yl) methyl J-dioxolane hydrochloride codeine
    18.5 59.8
    47.3 48.2
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    引用文献:
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    IT1113122B|1978-04-06|1986-01-20|Abc Ist Biolog Chem Spa|PHARMACEUTICAL COMPOSITION WITH ANTIBROCOSPASTIC AND ANTITOSSE ACTIVITIES|
    IT1195267B|1980-04-15|1988-10-12|Abc Ist Biolog Chem Spa|THEOFILLINMETHYLSOXANANIC DERIVATIVES, PROCEDURE FOR THEIR PREPARATION AND RELATED PHARMACEUTICAL COMPOSITIONS|
    HU190377B|1982-03-12|1986-08-28|Chinoin Gyogyszer Es Vegyeszet|Process for preparing theophyllinyl-alkyl-oxadiazoles|
    HU197574B|1986-10-09|1989-04-28|Chinoin Gyogyszer Es Vegyeszet|Process for production of derivatives of 3,7-dihydro-3-methil-7-//1,2,4-oxadiasole/-3-il/alkylenil/-1h-purin-2,6-dion and medical compositions containing these substances|US6350753B1|1988-04-11|2002-02-26|Biochem Pharma Inc.|2-Substituted-4-substituted-1,3-dioxolanes and use thereof|
    US5041449A|1988-04-11|1991-08-20|Iaf Biochem International, Inc.|4--substituted-1,3-dioxolanes useful for treatment of retroviral infections|
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    US5270315A|1988-04-11|1993-12-14|Biochem Pharma Inc.|4--substituted-1,3-dioxlanes|
    DE3929864A1|1989-09-08|1991-03-14|Nordmark Arzneimittel Gmbh|METHOD FOR PRODUCING THEOPHYLLIN PELLETS|
    HU206884B|1990-11-22|1993-01-28|Chinoin Gyogyszer Es Vegyeszet|Process for producing purin derivatives and pharmaceutical compositions containing them|
    US5288721A|1992-09-22|1994-02-22|Cell Therapeutics, Inc.|Substituted epoxyalkyl xanthines|
    DK1140937T3|1998-12-23|2004-03-22|Shire Biochem Inc|Antiviral nucleoside analogues|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    HU874905A|HU198933B|1987-11-02|1987-11-02|Process for producing new xanthine derivatives and pharmaceutical compositions comprising same as active ingredient|
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