• 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:
    Novel compounds of the general formula I <CHEM> processes for its preparation, pharmaceutical compositions containing such compounds as the active ingredient and the use of the compounds in medicine, especially for use in inhibiting gastric acid secretion and in the treatment of gastrointestinal inflammatory deseases. R<1> represents aryl, cycloalkyl or an adamantyl group. R<2> represents hydrogen, alkyl, alkoxy or halogen. R<3> represents hydrogen, alkyl, phenalkyl or a cykloalkyl-alkyl group. R<4> and R<5> represents hydrogen or alkyl. R<6> represents hydrogen, alkyl, aryl or a hydroxylgroup when n= 1-6 or an amino when n=O. A representents an alkylene, optionally connected to, or interrupted by an optionally substituted heteroatom selected from O,S and NR. n is 0-6.
    公开号:SU1597100A3
    申请号:SU874203542
    申请日:1987-10-26
    公开日:1990-09-30
    发明作者:Биргитта Бривинг Карин；Оге Ингемар Карлссон Стиг；Леннарт Линдберг Пер；Хиллеви Маттссон Анни；Петер НОРДБЕРГ Матс；Морган Габриель Валльмарк Бьерн
    申请人:Актиеболагет Хессле (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a process for the preparation of new benzimidazole derivatives, which are anti-ulcer agents and can be used in the prevention of peptic ulcers.
    The purpose of the invention is the synthesis of new benzimidazole derivatives, possessing new activity for this range of compounds i.
    Example 1. Getting 4-benzyloxybenzimidazole.
    A mixture of 1.6 g (0.0073 mol) W-benzi. Pepoxy-1, 2-diaminobenzene and 2.6 g (0.057 mol) of formic acid was heated to a temperature of 5–5 h. Degree. Then the reaction mixture was cooled, dissolved. in methylene chloride, washed with a 10% solution of sodium carbonate, dried () and evaporated to dryness in vacuo. The residue was ca. 10 recrystallized from acetonitria and obtained 0.75 g (46%) of the compound, mp. 165-167 C.
    Example 2 Preparation of 4-benzyoxy-1, 2-dimethylbenzimidazole and 7-15 benzyloxy-1,2-dimethylbenzimidazole.
    To a mixture of 0.5 g (0.021 mol) A-benzyloxy-2-methylbenzimidazole, 0.71 g (0.021 mol) of tetrabutylammonium bisulfate and 0.48 g (0.003 mol) 20
    methyl iodide in 30 ml of methylene chloride dropwise with stirring
    0.17 g (0.0042 mol) of NaOH in 30 ml was added. This mixture was heated to
    reflux temperature 2 h. After 25 cooling, the organic layer was separated, volatiles were removed at low pressure and an oil was obtained,
    which is suspended in ethyl
    ether, filtered tetrabutylammo, 30 niyodid and remove volatile substances. Chromatography on sipicagel and elution at a ratio of methylene chloride to methanol (10: 1) yielded 0.24 g (0.00095 mol), yield 45%, isomeric product 4-benzox Oxy-1, 2-dimethylbenzimidazole and 7-benzyloxy -1, 2-dimethylbenzimidazole, t, pl. 100-101 ° C.
    Compounds 1-12 listed in the dO table were prepared according to the method of Example 1.
    Example 1a Preparation of 3-beisyloxy-1, 2-diaminobenzene (intermediate product),
    I g of skeletal nickel hydrogenation catalyst was added to a solution of 3-benzyloxy-, 2-dinitrobenzene (2 g, 0.0073 mol) in 300 ml of ethanol and the mixture was hydrated at room temperature and atmospheric pressure until the absorption of hydrogen ceased (30 min) . The colorless solution was filtered (celite), evaporated in vacuo to dryness and the compound obtained as an unstable oil (1.6 g), which was immediately used for the next step (see Example I).
    All the compounds obtained have low toxicity.
    Inhibition of in vitro acid secretion in isolated rabbit gastric glands.
    The method of analysis.
    Preparation of the gastric gland, I Isolated rabbit gastric glands were prepared in a known manner. This method includes the vascular perfusion of the rabbit stomach through the gastric arteries, scraping and scaling the separated gastric mucosa and digesting with collagenase for 60-90 minutes. The gastric glands are then collected and filtered through nylon fabric to remove coarse fragments. After that, the gastric glands are incubated in an environment containing, mm: NaCl 132.4, KC1 5.4; 5.0; 1.0; MgS04. 1.2; CaClz 1.0; glucose 10; 1 mg / ml rabbit albumin, pH 7.4.
    Measurement of acid secretion.
    Acid secretion in isolated gland preparations was measured by measuring the absorption of aminopyrin, labeled, inside the glands in a known manner. Accumulation of aminopyrine in the glands indicates the secretion of gastric acid inside the gland. The standard medium contained 10 M of aminopyrine -. After incubation, the glands were centrifuged, the supernatant was removed, and the glands were dried, weighed, and dissolved in Soluene-350. Samples of the supernatant and glands were calculated separately by a scintillation counter. The accumulation of aminopyrin C in the glands was counted.
    The protocol of the experiment.
    The glands were incubated for
    (-
    60 min in the presence of 5x16 M histamine and the test compound. The free base of the test compound was dissolved in methanol. The final concentration of methanol in the incubation medium was 1%, which did not affect the ratio of aminopyrine accumulation. An inhibitory concentration is given for each test compound.
    ():
    Compound 1SMM /
    4-Benzsh1oxy2-ethylbenzimidazole9
    5-Benzyloxy2-methylbenzimidazole
    A- (p-Chlorobenzyloxy) -2-methyl
    benzimidazole
    4- (p-Fluorobenzyloxy) -2-methylbenzimidazole
    2-Methyl-4-phenylethoxybenzimidazole
    9 (see tab.1)
    10 (see tab.1)
    权利要求:
    Claims (1)
    [1]
    and compounds of the invention. A method for the preparation of benzimidazole derivatives of the general formula I RI-AV -. (CR RsbReV 2 I where R, is a substituted or unsubstituted aryl or cycloalkyl group with 3-8 carbon atoms in an unsubstituted cyclic group; RJ, is hydrogen; P. a is hydrogen, LOW alkyp; n is an integer 0-2 {
    hydrogen;
    I: hydrogen;
    hydrogen, a substituted or unsubstituted aryl group or, when n 1, a hydroxyl group, or, when n o, an amino group;
    Alkylene, optionally bound or interrupted by an optionally substituted heteroatom selected from O and NR, in which Rg is hydrogen, phenylalkyl with 1-4 carbon atoms in the alkyl group, provided that when p O,
    Table R and R are all hydrogen, then the group A-R is not 7-benzylamino, different from the fact that the compound of the formula </ BR> </ RTI> where R and R ,, interact, has the indicated values. with a compound of the general formula R6 (CR4R6-) fiCOR7, where R (, Rr-s Rg is as previously defined; R- is a leaving group, with isolation of the target product.
    table 2
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    同族专利:
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    HU196971B|1989-02-28|
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    KR880005092A|1988-06-28|
    DK555387D0|1987-10-23|
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    DD264433A5|1989-02-01|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    SE8604566A|SE8604566D0|1986-10-27|1986-10-27|NOVEL COMPUNDS|
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