• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
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  • 引用文献
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  • 优先权
    • 专利摘要:
    A method for producing benztriazole derivatives of the general formula (I) N wherein R is C-Cj alkyl, a cyclopropyl group, and an alkyl group with 1 to 3 carbon atoms. substituted by pyridyl or phenyl, unsubstituted or substituted. hydroxyl, one or two methoxy groups or an amino group and two halogen atoms, an alkyl group with 2-4 carbon atoms, a substituted at the terminus of hydroxyl, phenyl, substituted by a halogen atom, a methoxyphenylsulfonyl group, alkanoyl group with 1 6 carbon atoms, unsubstituted or I substituted by phenyl, methoxyphenyl or cyclohexyl (L scrap; Rj C-C alkyl, characterized in that the compound of general formula (II) is xNH where R and R- have the indicated values Vey with an inorganic or organic nitrite followed by isolation of the desired product. SU ,,,. 1179927 A (51) 4 C 07 D 249/18 // A 61 K 31/41 taenia., l ..
    公开号:SU1179927A3
    申请号:SU823463049
    申请日:1982-07-14
    公开日:1985-09-15
    发明作者:Хауэль Норберт；Аустель Фолькхард；Гейдер Иоахим；Рейффен Манфред；Дидерен Вилли；Хаарманн Вальтер
    申请人:Др Карл Томэ Гмбх (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a method of producing new benztriazole derivatives having pharmacological activity, in particular, to a method for preparing benztriazole derivatives of the general formula
    .
    where R is C -Ca-alkyl, a cyclopropyl group, an alkyl group with 1-3 carbon atoms, substituted by pyridyl or phenyl, unsubstituted or substituted by hydroxyl, one or two methoxy groups or an amino group and two halogen atoms, an alkyl group with 2-4 atoms carbon, substituted at the end by hydroxyl, phenyl, substituted by halogen atom, methoxyphenylsulfonyl group, alkanoyl group with 1-6 carbon atoms, unsubstituted or substituted by phenyl, methoxyphenyl or cyclohexyl; R- - C-C, -alkyl,
    possessing property to lower blood pressure.
    The aim of the invention is to obtain new benztriazole derivatives having improved antihypertensive properties.
    Example 1. 5-methyl-6- (1-benzyl benztriazole-3-yl) -4,5-dihydro-3 (2H) -pyridazinone (1a).
    9 g (29.2 mol) of 5-methyl-6- (3-amino-4-benzylaminophenyl) -4,5-dihydro-3 (2H) -pyridazinb are dissolved in 200 ml of half-concentrated hydrochloric acid. With stirring, a solution of 4.13 g (60 mmol) of sodium nitrite in 40 ml of water is slowly added dropwise. Continue stirring the reaction mixture for another 5 hours at room temperature, then the reaction product is sucked off and recrystallized from acetone. Yield 6.5 g (69.6%). T. pl. 160-162 C.
    Calculated,%: C 67.70; H 5.37; N 21.93.
    CieHt7% 0
    Found,%: C 67.52; H 5.45;
    N 21.56.
    Example 2. 5-methyl-6- (l-benzylbenztriazol-5 -yl) -4,5-dihydro-3 (2H) -pyridazinone (la).
    1 g (3.24 mmol) of 5-methyl-6- (3-amino-4-benzylaminophenyl) -4,5-dihydro-3 (2H) -pyridazinone is dissolved in a mixture of 100 ml of dioxane and O, 1 g of trichloroacetic acid acid. When 0.52 g (5 mmol) of tert-butyl nitrite is added with stirring. The mixture is stirred at 15-20 ° C for 2 hours. Then the solvent is evaporated under vacuum, the residue is triturated with water, sucked off and the crude product thus obtained is recrystallized five times. acetone.
    Yield 0.21 g (20.3%), m.p. 158161 C.
    Calculated,%: C 67.70; H 5.37; N 21.93.
    Found,%: C 67.23; H 5.28; N 22,10.
    Example 3. Example 1 is repeated with the difference that the reaction is carried out in 4 n medium. sulfuric acid. Thus receive 6.6 g (70.6%) of the product with so pl. 160-162 ° C. Example 4. Example 1 is repeated with the difference that the reaction is carried out in glacial acetic acid. This gives 6.45 g (69.1%) of the product with so pl. 160-162 C. Analogously to examples 1-4 receive
    the following benztriazole derivatives: 5-methyl-6 (1-p-methoxybenzoylbenztriazol-5-yl) -4,5-dihydro-3 (2H) -pyridazinone (16).
    The output of 61.3%, so pl. 220-225 ° C. Calculated,%: C, 62.80; H 4.72; N 19.27.
    Found,%: C 62.98; H 4.84;
    N 19.37.
    5-methyl-6 - (. 1 -cyclohexanoylbenztriazol-5-yl) -4,5-dihydro-3 (2H) -pyridazinone (1c). Output 76.3%, t. Pl. 218-221 ° C.
    Calculated,%: C 63.70; H 6.24; N 20.63.
    Found,%: C 64.13; H 6.11; N 20.45.
    5-methyl-6- (1-eopropylbenzotriazol-5-yl) -4,5-dihydro-3 (2H) -pyridazinone (1 g).
    Yield 51.3%, mp. 185-187C.
    Calculated,%: C, 61.98; H 6.32; N 25.81.
    ,, NjO
    Found,%: C 62.03; H 6.26; N 25.69.
    5-methyl-6- (1-ethylbenztriazol-3-yl) -4,5-dihydro-3 (2H) -pyridazinone (1d).
    Yield 29.5%, m.p. 189-192 C.
    Calculated,%: C 60.69; H 5.88; N 27.22.
    C, 3H, jNjO
    Found,%: C 60.60; H 5.86; N 27.41.
    5-methyl-6- (l-p-methoxybenzylbenztriazol-5 -yl) -4,5-dihydro-3 (2H) -pyridazinone (1e).
    Yield 14.3%, m.p. 157-159 C. Calculated,%: C 65.32; H 5.48; N 20.04.
    С „Н ,, Nj02
    Found,%: C 65.40; H 5.55; N 20.01.
    5-methyl-6- (1 -metsh1benztriazol-5 - -yl) -4,5-dihydro-3 (2H) -pyridazinone. (1g).
    Yield 29.4%, m.p. 223-224 0.
    Calculated,%: C 59.25; H 5.39; N 28.79.
    Found,%: C 59.13; H 5.60; N 29.28.
    5-methyl-6- (l-p-fluorophenylbenztriazol-5-yl) -4,5-dihydro-3 (2H) -pyridazinone (1h).
    Yield 58%, so pl. 250C.
    Calculated,%: C 63.14; H 4.36; N 21.66.
    C-fvH ,, NjOF
    Found,%: C 63.20; H 4.51; N 21.59.
    5-methyl-6- 1- (3,4-dimethoxybenzyl) -benztriazol-5-ylJ-4,5-dihydro-3 (2H) -pyridazinone (1i).
    Yield 52.5%, m.p. 197-200s.
    Calculated,%: C H 5.58; N 18.40.
    .NfOj
    Found,%: C 63.37; H 5.46; N 18.29. 5-metsh1-6- l- (2-picolsh1) -benztri1799274
    Azole-5 -ylJ-4,5-dihydro-3 (2H) -pyridazinone (1k).
    The output of 39.7%, so pl. 95-97 p. Calculated,%: C 63.74; H 5.03; 5 N 26.24.
    Ci7 "f" N.O
    Found,%: C 63.04; H 5.43;
    N 26.93.
    5-methyl-6-C1 - (3-picolyl) -benztri0 azole-5, 5-dihydro-3 (2H) -pyridazinone (1 l).
    The output of 39.8%, so pl. 202-204С.
    Calculated,%: C 63.74; H 5.03; N 26.24. t5
    Found,%: C 63.95; H 5.14; N 26.39.
    5-methyl-6- (1-cyclopropyl-isoethnazol-5 -yl) -4,5-dihydro-3 (2H) -pyri20 dazinone (1m).
    The output of 39.5%, so pl. 219-22GS.
    Calculated,%: C, 62.44; H 5.61; N 26.00.
    С Н N0
    25Found,%: C, 62.91; H 5.61;
    N 26.44.
    5-methyl-6- l- (2-hydroxyethyl) -benztriazol-5-yl T-5-dihydro-3 (2H) -pyridazinone GHn). 30 Output 26%, so pl. 182-183 S.
    Calculated,%: C 57.13; H 5.53; N 25.63.
    C jH jNjOj.
    Found: C 57.00, H 5.50; N 25.60.
    , 35
    5-methyl-6- (1-p-hydroxybenzylbenztriazol-5-yl) 4.5 dihydro-3 (2H) is pyridazinone (1o).
    Yield 26.9%, mp. 193-195С. 40 Calculated,%: C 64.47; H 5.11; N 20.88.
    ,, nj02
    Found,%: C 64.48; H 5.22; N 21.16.
    5 5-methyl-6- (1-p-methoxyphenylsulfonylbenztriazol-5 -yl) -4,5-dihydro-3 (2H) -pyridazinone (In),
    Exit 337 ,, m. Pl. 170-173 S.
    Calculated,%: C 54.12; H 4.29; 50 N 17.53; S 8.03.
    Found,%: C 54.20; H 4.38; N 17.85; S 8.13.
    5-methyl-6-Cl- (3,5-dichloro-D-amino55 benzyl) -benztriazol-5, 5-dihydro-3 (2H) -pyridazinone (1p).
    Yield 10.5%, m.p. 250-252 0.
    -methyl-6- (l -n-hexanoylbenztriaol-5 -yl) -4,5-dihydro 3 (2H) -pyridazinone (1c). t. nji. NU-NE C. Yield 55.5%, C 62.37; H 6.47; Calculated,%; N 21.39. C ,, H2, Ny02 Found,%: C 62.43; H 6.42; N21.38.10 Determination of a decrease in blood pressure and a positive inotropic effect. Experiments were carried out on anesthetized cats (narcotic drugs: 5 drugs: 40 mg / kg sodium salt pentobarbital, intraperitoneally). Animal breathing is spontaneous, arterial blood pressure is measured in the abdominal aorta. To determine the positive effect, the pressure in the left ventricle of the heart is measured, and the contractility parameter dp / dt, y (; is determined using an analogue differentiator. Compound 1 (a-c) is injected into the femoral vein. The physiological is used as a solvent. salt solution. Each 30 compounds are given to at least three cats at a dose of 0.1 mg-kg. The duration of action of compounds 1 (a-c) is in each case at least 45 minutes.35
    权利要求:
    Claims (1)
    [1]
    METHOD FOR PRODUCING BENZTRIAZOLE DERIVATIVES of the general formula (I) where R 1 is a C 1 ~ C 3 -alkyl, a cyclopropyl group, an alkyl group with 1-3 carbon atoms, substituted with pyridyl or phenyl, unsubstituted or substituted with .hydroxyl, one or two methoxy groups or an amino group and two halogen atoms, an alkyl group with 2-4 carbon atoms, substituted at the end with hydroxyl, phenyl substituted with a halogen atom, methoxyphenylsulfonyl group, alkanoyl group with 1-6 carbon atoms, unsubstituted or substituted with phenyl, methoxyphenyl or cyclo eksilom;
    Rj is C ^ -C ^ -alkyl, characterized in that the compound of the general formula (II) wherein Rj and имеют have the indicated meanings, are reacted with inorganic or organic nitrite, followed by isolation of the target product.
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    优先权:
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