• 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 new benzo-as-triazine derivatives of the formulae (I) and (Ia) and pharmaceutically acceptable acid addition salts thereof, <IMAGE> (I) <IMAGE> (Ia) wherein R1 and R2 each represent hydrogen, a C1-20 alkylcarbonyl group, a phenylcarbonyl or phenyl-(C1-4 alkyl)-carbonyl group having optionally one or more halogen, hydroxy or C1-3 alkoxy substituents which may be the same or different, furthermore a pyridylcarbonyl, a pyrazinylcarbonyl, a furylcarbonyl, a chloroacetyl or a C1-4 alkoxycarbonyl group, or R1 and R2 may form, together with the adjacent nitrogen atoms, a pyrazole ring having optionally a C1-6 alkyl substituent in position 4, with the proviso that one of R1 and R2 is always different from hydrogen, R3 stands for hydrogen, mercapto group, a C1-4 alkylmercapto group, amino group, a C1-4 alkylamino group, a piperazino group having optionally an N-alkyl or 2-pyridyl substituent, a morpholino group or a piperidino group, and R4 stands for hydrogen, halogen, C1-4 alkyl or C1-4 alkoxy group. The compounds of the formulae (I) and (Ia) are prepared by acylating the respective 2,4,5-unsubstituted 4,5-dihydro-benzo-as-triazine derivatives. The new compounds of the formulae (I) and (Ia) possess analgesic, antiphlogistic and narcosis-potentiating effects.
    公开号:SU1234401A1
    申请号:SU823393298
    申请日:1982-02-18
    公开日:1986-05-30
    发明作者:Хайош Дьердь；Мешшмер Андраш；Бенко Пал；Петец Луиза；Герег Петер；Кошоцки Иболиа
    申请人:Эдьт Дьедьсерведьесети Дьяр (Инопредприятие)；
    IPC主号:
    专利说明:

    This invention relates to organic synthesis, in particular to new benzo-av-triazine derivatives of the general formula
    (I)
    where a), j-aneTRn; R, -H;
    b) R-R, -propionyl;
    Rj-w;
    c) R-propionyl;
    CL-Cs-H;
    d) R-R2-propionyl; Rj-methylthio,
    which are used as pharmaceuticals.
    The purpose of the invention is to obtain benzo-az-triazine derivatives with a different pharmaceutical action than known structural analogues.
    Example 1, Preparation of 4,5-di-acetyl-4,5-dihydro-8-triazolo- (3,4- -c) -benzo-a8-triazine (1a).
    7.0 g (0.04 mol) of 4,5-dihydro-3-triazolo (3,4-c) -benzo-a8-triazine is heated for 6 hours to boil in a mixture of 35 ml of glacial acetic acid and 35 ml of acetic anhydride. The reaction mixture is cooled, the product is precipitated with sfir, the filtrate is. Obtain 9.4 g of the desired product (yield 91%), so pl. 186-188 ° C.
    Elemental analysis: calculated - N 27.2%; found N 26.95%. Molecular mass of 257 (according to mass spectrometry),
    Example 2. Preparation of 4,5-dipropionyl-4,5-dihydro-8-triazolo- (3,4-с) -benzo-a5-triazine (16)
    A mixture of 4.0 g (0.023 mol) of 4,5-di-hydro-3-triazolo- (3,4-c) -benzo-a5-triazine and 50 ml of propionic anhydride is heated for 1 hour at 120–125 ° С . The reaction mixture is cooled, the target product is precipitated with ether, filtered. The yield of 3.5 g (67%), so pl. 192-193 p.
    Elemental analysis: calculated - N 30.5%; found N 30.15%. Molecules p per mass 229 (according to mass spectrometry data).
    Example 3. Preparation of 5-propiono-4,5-dihydro-8-triaol-3,4-c-benzo-az-triazine (1c).
     g (0.017 mol) of 4,5-dipropionyl-4,5-dihydro-5-triazolo- (3,4-c) -benzo-av-triazine is treated with 50 ml of 5% sodium hydroxide solution. The solution is clarified, filtered, the filtrate is acidified with acetic acid, and the colorless precipitated precipitate is filtered off. Obtain 4.5 g (63%) of the desired product, so pl. 244 C.
    Analysis: calculated N 30.60%; found N 30.45%. Molecular weight 229 (based on mass spectrum).
    Example 4. Preparation of 1-methylthio-4,5-dipropionyl-4,5-dihydro-8-triazo- (3,4-c) -benzo-az-triazine (1 g).,
    10.0 g (0.046 mol) of 1-methylthio-3-triazolo- (3,4-c) -benzo-az-triazine and 12 g (0.068 mol) of sodium dithionite are suspended in 100 ml of water. 20 ml of Zanol is added to the suspension. The precipitate formed is cold filtered for 30 minutes. The obtained 1-methyl type-4, 5-dihydro-5-triazolo- (3,4-c) -benzo-a8-triazine (7.2 g, 71%) under argon at 120 ° C is stirred for 2 hours at 65 ml of propionic anhydride. The reaction mixture is evaporated and the residue is crystallized from a mixture of methylene chloride and petroleum ether. Obtain 8 g (80%) of the desired product, so pl. .
    Analysis: Calculated N 21.13%; found - N 21.02%. Molecular weight is 331 (according to mass spectrum data).
    The toxicity of the compounds of general formula I was determined orally. The corresponding values are given below:
    45
    50
    Test compound, 1a 16
    IB 1g
    Meprobamate Paracetamol 55 Phenylbutazone
    Ace tilsalicylic acid
    mg / kg
    VET 2000 1750
    1000 1 100 510 1000 1500
    31
    The analgesic effect of the compounds of general formula I was determined on the basis of acetic acid Writhing test. After applying 0.4 ml of a 0.5% aqueous solution of acetic acid, the Writhing reaction was calculated and the Writhing number obtained within 5 min after treatment was expressed as a percentage of the control value. Before using acetic acid for 1 hour, the animals were orally treated with a test substance or drug base.
    The results are summarized in table. 1 (analgesic effect).
    Table 1
    16 IB
    200 175
    10 10
    The anti-inflammatory (edematous) effect was tested on rats, 0.1 ml of 1% Carragenin solution was injected into the sole of the hind limb of the animal. The volume of the paw was measured with a mercury plethysmometer before and 3 hours after the administration of the inflammatory substance. The preceding 30% inhibition doses are summarized in Table. 2 (anti-inflammatory effect).
    Editor I. Kishtulints
    Order 2951/29 Circulation 379
    VNIIPI USSR State Committee
    for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab., D. / 5
    Production and printing company, Uzhgorod, st. Project, 4
    table 2
    Potentiated anesthesia action was determined in mice according to the Kaeggaard method.
    The test results are summarized in table. 3 (hexobarbitol potentiated narcotic effect).
    iT Blitz 3
    35
    before
    Compiled by Y. Head
    Tehred L. Serdyukova Proofreader S. Shekmar
    Subscription
    权利要求:
    Claims (3)
    [1]
    DERIVATIVES OF BENZO-AB-TRIAZIN, MANIFESTING AN ANESTHESIS ANNOIDING ACTION (57) 1Benzo-az-triazine derivatives of the general formula f where a) -R 2 is acetyl;
    R 3 is H;
    b) R —R.-propionyl;
    R1-H;
    c) R, -propionyl; R 2 —R 3 —H;
    d) R 7 -R 2 propionyl; Rj-methylthio, showing anesthesia-enhancing effect.
    [2]
    2. Derivatives of benzo-av-triazine of the formula 1a, 1c, exhibiting enhancing anesthesia and anti-inflammatory effect.
    [3]
    3. Derivatives of benzo-av-triazine of the formula 16, 1B, 1 g, showing increasing anesthesia and analgesic effect.
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    引用文献:
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    US3933816A|1974-09-12|1976-01-20|The Upjohn Company|3--7-substituted-3,5-dihydro-as-triazino[4,3-a][1,5]benzodiazepines|
    US4017492A|1976-04-02|1977-04-12|The Upjohn Company|As-triazinobenzodiazepin-1-ones|US5175287A|1986-09-25|1992-12-29|S R I International|Process for preparing 1,2,4-benzotriazine oxides|
    US5616584A|1986-09-25|1997-04-01|Sri International|1,2,4-benzotriazine oxides as radiosensitizers and selective cytotoxic agents|
    WO2000034278A1|1998-12-04|2000-06-15|Toray Industries, Inc.|Triazolo derivatives and chemokine inhibitors containing the same as the active ingredient|
    US6833454B1|2003-01-15|2004-12-21|The United States Of America As Represented By The Secretary Of The Navy|Chemical compounds containing bistriazine structures and methods thereof|
    EP1502918A1|2003-07-31|2005-02-02|Bayer CropScience GmbH|The use of fused ring-1,2,4-benzotriazine derivatives as herbicides or plant growth regulators for the control of undesired plants or vegetation, compounds and compositions thereof, and processes for their preparation|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    HU79EE2646A|HU179158B|1979-04-11|1979-04-11|Process for producing triasolo-benzo-asimetrical-triasine derivatives|
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