• 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 aryl-ylalkenoic acids, in particular to the preparation of (E) -4- (4-acyloxyphenyl) -4- -oxo-2-butenoic acid of the general formula H-KC (0) 0-SbH4-C (0) ( 0) OH (BK), where R is methyl, ethyl, reducing the acidity of the stomach. The goal is to create more active substances of the specified class with low toxicity. The preparation of BC is carried out by the reaction of (E) -4- - (4-hydroxyphenyl) -4-oxo-2-butenes. Of an acid with acetic or propionic anhydride at 50-100 d. The cytoprotective effect of BC (according to the degree of gastric juice acidity) is 73-77% versus 17-47% for a known compound. 1 tab. CO oo with 00 tc with with CM
    公开号:SU1333233A3
    申请号:SU843783011
    申请日:1984-08-21
    公开日:1987-08-23
    发明作者:Бианки Марио；Барцаджи Фернандо
    申请人:Руссель-Юклаф (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to methods for producing new compounds of a number of unsaturated alkaline aromatic acids, namely, to a method for producing (E) -4 - (4-acyloxyphenyl) -4-oxo-2-butenoic acid of the general formula
    xooHrW w snson
    - II
    about
    where R is methyl, ethyl, and its pharmacological activity.
    The purpose of the invention is to obtain new compounds with valuable pharmacological properties with low toxicity.
    Example 1. (E) -4 - (. Hydroxy phenyl) -4-oxo-2-butenoic acid,
    At 50 ° C, a solution of b g (E) -4- (4-hydroxyphenyl) -4-oxo-2-5butenoic acid in 50 cm of acetic anhydride is heated for 1 h, cooled to room temperature, diluted with water, concentrated and then extracted with ethyl acetate. The organic layer is separated, dried and the solvent is evaporated. The residue is recrystallized in 70% ethanol and 4.5 g of the expected product are obtained. T, pl „154 ± 6 С, Calculated,%: ,, С 61.54; H 4.30,
    ,
    H 4.18.
    In the PMR spectrum 1 ,,, 15
    Found,%: C 61, 48;
    Hz for protons of a double bond, which proves the E configuration of a double bond.
    Example 2, (E) 4- (4-Propano-yloxyphenyl) 4-oxo-2-butenoic acid.
    B for 2 h at 100 ° C I heat a mixture of 2.5 g of (E) -4- (4-hydroxyphenyl) -4-oxobutene-2 oic acid; and 25 cm - propane anhydride. The excess of ai-hydride is evaporated, taken in Oenzo and evaporated to dryness. The residue is chromatographed on silica, an ether with a mixture of benzene - ethyl acetate and acetic acid (50: 50: 1). The product is crystallized in water and, after drying, 1.9 g of the expected product is obtained, mp. 140 ± 2 С
    Calculated,%: C 62.90 | H 4.37,
    C H,., 0Found,%: C 62.96; H 4.77.
    Pharmaceutical forms of poluagot as follows.
    Example 3 Preparing tablets containing the product of example 1 1CO mg excipient 300 mg.

    five
    ten
    15

    Components of the excipient: lactose, starch of grain bread, processed starch, rice starch, magnesium stearate, talc.
    Example 4. Preparations of a gel (gelatin capsules) containing the product of example 2 are 100 mg, excipient 300 mg. ,
    Components of excipient: talc, magnesium stearate, aerosil.
    Conduct pharmacological studies.
    Toxicity.
    A lethal dose of 50 (DLj) is evaluated after the administration of products through the mouth to mice. The following results are obtained, mg / kg: product of example 1 (product A) 350; the product of example 2 OQ (product B) 750; cimetidine N-ω-N-methyl-N. - (2- (5-methyl-1H-imide-azol-4-yl) methyl-Thio ethyl) guanidine (product C) 1000.
    Gastric anti-excretion 25 activity.
    Males of rats weighing about 200 g and 1 p-1 food E. Food for 48 hours, but with an unlimited amount of 8% glucose solution, -50, tie the pylorus slightly anesthetized with ether, and after the end of the operation, inject doses, and the animal control, - a 0.5% solution of carboxymethylcellulose by an intraduodenal route, followed by an abdominal incision.
    After 3 hours, the animals are sacrificed and their stomach is taken out after ligation of the esophagus. The gastric juice is centrifuged. The volume is measured and the total acidity is determined by dosing to pH 7 with a help of 0.01 n per 100 µl of gastric juice. caustic soda,
     The percentage change in acidity (total) gastric secretions is calculated in relation to the results obtained in control animals.
    The results obtained are presented in the table.
    35
    40
    50
    Cytocystic action. After 6 hours of starvation, female rats weighing 200 g are placed in individual cages and are deprived of food and water for another 18 hours. Rats are treated in groups of 10 individuals in oral doses with products in specified doses
    and after 1 h, the following necrotic agents are orally administered: pure ethanol, HC1, 0.6 N, NaOH, 0.2 N (8). After i h, the animals are injected with ether and their stomachs are opened. Check the gastric mucosa under a microscope, calculate and assess the damage. For each stomach, calculate the total damage indicator by adding the values of each damage according to the following scheme: 1 - for less than 0.5 mm; 2 - 0.5–1.5 mm thick; 3 - Zva 1.5-3 mm; 4 - name more than 3 mm.
    formula of invention
    The method of obtaining (E) -4- (4-acyloxy-1) -4-70 x co-2-butenoic acid of the general formula
    RCOO- (O) -C CH. SNC,
    about
    Editor P. Geresi
    Compiled by A. Evstigneev Tehred L. Serdyukova
    Order 3853/58 Circulation 371 Subscription
    VNIIPI USSR State Committee
    for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab., 4/5
    Production and printing company, Uzhgorod, UL. Project, 4
    where R is methyl, ethyl, characterized in that. (E) -4- (4-hydroxyphenyl) -4-oxo-2-butenoic acid is reacted with acetic or propionic anhydride at 50-100 C.
    Corrector n. King
    权利要求:
    Claims (1)
    [1]
    Claim
    The method of obtaining (E) -4- (4-acyloxyphenyl) -4-toxo-2-butenoic acid of the General formula
    RCOO-ZoV-C sn = snsoon, '' II о
    A 10 77 0.6 fifty IN 10 73 0.6 56 20 FROM fifty 17 12.5 18 200 47 fifty 14
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    同族专利:
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    引用文献:
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    GB588108A|1944-10-23|1947-05-14|Roche Products Ltd|Manufacture of bacteriostatic substances|
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    DE1282644C2|1962-09-08|1969-07-17|
    DE2047806A1|1970-09-29|1972-04-06|Dr Karl Thomae GmbH, 7950 Biberach|3-aroyl-acrylic acids - pharmaceutical intermediates prepd from acetophenones and glyoxylic acid derivs|
    DE2103749A1|1971-01-27|1972-08-10|Dr. Karl Thomae GmbH, 7951 Biberach|3-acyl-acrylic acids prepn - from a ketone and glyoxylic acid |
    DE2116293A1|1971-04-02|1972-10-19|Cassella Farbwerke Mainkur Ag, 6000 Frankfurt|Ketone derivatives and processes for their preparation|
    US3753997A|1971-06-07|1973-08-21|A Ash|Trifluoromethly substituted-2,6-diphenyl-4-pyridyl carbinolamine antimalarials|
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    FR2270856B1|1974-01-17|1978-07-21|Screen|
    US3940404A|1974-03-06|1976-02-24|The United States Of America As Represented By The Secretary Of The Army|2-Substituted phenyl-6-trifluoromethyl-4-pyridyl-carbinolamines|
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    IT1210582B|1981-10-22|1989-09-14|Roussel Maestretti Spa|4-FENYL-4-OSSOBUTEN-2-OICO ACID DERIVATIVES EQUIPPED WITH PHARMACOLOGICAL PROPERTIES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM|
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    法律状态:
    优先权:
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