• 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 method of producing pyridylallylamine derivatives of the general formula; moreover, if X is a bromine atom, it is not in position 4; P-1 or 2, or their salts with acids, or mixtures of tjt / e-itrams-isomers, or individual individual isomers, characterized in that the compound of the general formula (L, where R, X and P have the indicated meanings, is dehydrated with the following isolation of the target product in free form or in the form of a salt with an acid or in the form of mixtures of tetra and isomers or individual isomers 4; & H o-a ai
    公开号:SU1149875A3
    申请号:SU823419750
    申请日:1982-04-13
    公开日:1985-04-07
    发明作者:Хегберг Томас；Де Паумес Томас；Бертил Росс Сванте；Бенгт Иоган Ульфф Карл
    申请人:Астра Лэкемедель Актиеболаг (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to the preparation of new pyridyllylamine derivatives of the general formula CHCHNMS R hydrogen atom, methyl; a halogen atom in any position of the phenyl, and, if the atom is bromine, it is not in position 4; n - 1 or 2, or their salts with acids, or mixtures and w-isomers, or individual isomers possessing anti-depressive activity, and can be used in medicine. Pyridylallyl amine derivatives, in particular 3- (4-bromophenyl) are known. -I methyl (NI, N-dimethyl) -3- (Z-pyridine allylamine, possessing antidepressant activity 1. A known method for producing derivative allylamines by dehydration of 3-hydroxypropylamine derivatives in concentrated sulfuric acid upon Heating | Y. Purpose of the Invention - obtaining new pyridylallyl derivatives or their salts with acids, or mixtures of tijuc and Trans-isomers, or individual isomers with increased ant depressive activity. The goal is achieved by the method of producing pyridylallylamine derivatives of general formula 1 or their salts with acids, or mixtures of hydroxy and trans-isomers, or individual isomers, a compound of the general formula M. ". (" hL / I. HE where R, X and and have the indicated meanings, is subjected to dehydration followed by chi B1 separation of the target product in the free form of S1I as an acid salt, or as mixtures and trans isomers, or individual isomers. EXAMPLE 1. Oxalate (5;) - 3 (3-chlorophenyl) -K, M-dimethyl-3- (3-pyridinn) allylamine. A solution of 4.45 g (15 mmol) of 3- (3 chlorophenyl) -H, N-dimethyl-3-hydroxy-3 (3-pyridyl) -propylamine in 5 ml of glacial acetic acid and 3.3 ml of concentrated sulfuric acid is heated with reflux for 1 hour. After cooling, 25 ml of water are added and the pH of the mixture is adjusted to 9.5 by the addition of concentrated ammonia solution. The mixture is extracted with ether. The ether phase is evaporated and evaporated. 3.6 g (88%) of brown oil are obtained, which, according to the data of liquid chromatography, contains isomers 2 and E in a ratio of 72:28. The base is dissolved in 20 ml of acetone and then one equivalent of oxalic acid in acetone is added. The precipitated product is recrystallized from ethanol. Obtain 2.5 g (46%) of the desired product in the form of white crystals, so pl. 171174С. Example 2. Oxalate (E) -3 (4-chlorophenyl) -I-methyl-3- (3-pyridsh1) allylamine. Repeat 1 with the difference that 3- (4 chlorophene) -N-methyl-3-hydroxy-3- (3-pyridsh1) -propylamine is subjected to dehydration. The resulting mixture of isomers and E is threefold diluted with a mixture of ethyl acetate, methanol and triethylamine (2t: 4: 1) on silica gel tiles (0.2 mm; 20x20 cm). The fraction containing E isomer is collected and washed with a mixture of methanol and dichloromethane. After evaporation of the solvent, isomer E is obtained in the form of an oil. UV spectrum: (0.1 M NSB) "max: 219; 235 (shoulder). Yield 18%. Analogously to Examples 1 and 2, the following are prepared. . Oxalate 3- (4-chlorofensh1) -N, -N Dimethyl-3-f3-pyridyl) allylamine as isomer 2, so pl. 164 -, yield 42%. 2. Oxalate 3- (4-chlorophenyl) -Mtipy-3- (3-pyridyl) -allylamine as Z isomer, so pl. 203-204s (from a mixture of ethanol with water 3: 1); vrsod 45%. .3, Oxalate 3- (4-fluorophenp) -M, K dimethyl-3 (3-pyridyl) -allylamine, so pl. 15t-155c; yield 58%. 4.Oxalate 3- (4-fluorophenyl) -Mtipy-3- (3-pyridyl) -allylamine, so pl. 196-198 ° C; yield 55%. 5. Oksalat 3- (2-bromophenyl) -M, Mdimetil-Z- (Z-pyridyl) -allylamine in the form of isomer E, so pl. 148-149 ° C; yield 15%. 6. Oksalat 3- (2-bromophenyl) -I-metsh1-3- (3-pyridyl) -allilanine as E isomer, so pl. 200-202 С; yield 16%. 7.Oxalate 3- (3-bromofensh1) -Mamethyl-3- (3-pyrndyl) -allylamine & isomer 2, m.p. 198-199®C; yield 38%. 8.Oxalate 3 (2,4-dichlorophenyl) M, N-dimethyl-3- {3-1-tridyl) -allylamine as E isomer, mp. 167-169 ° C; yield 16.5%. 9. Ocalate of 3- (2,4-dichlorophenyl) -H-me yl-3- (3-pyridyl) -alshamin in the form of E isomer, t.q. 203-205 С; yield t7%. 10. Oksalat 3- (4-iodfennl) -M, N-dimesh1-3- (3-pyridyl) -allylamine in the form of isomer Z, so pl. 170-173 ° С (from a mixture of ethanol and propyl ether); yield 38%. I 11. Oxalate 3- (3-bromophenyl) -M, H dimethyl-3t- (3-pyridyl) allnlamine in n de isomer 2, so pl. 162-163 ° C from a mixture of ethanol and isopropyl ether yield 40%. Example 3. Maleate (1 (;) - 3- (4chloro-fesch) -Y, N-dimethyl-3- (E-pyridyl) -allylamine. A solution of 4.4 g (15 Nyul) 3- (4-chloro phenyl) -H, H-dimethyl-3-hydroxy-3- (3-pyriD1sh) -Allysmi a in 5 ml of glacial acetic acid and 3.3 MP of concentrated hydrochloric acid is heated under reflux for 1 h. After cooling, a solution of 25 MP of water is added to the solution, alkalinized (with a concentration of 9.0) and concentrated with ammonium solution and extracted with ether. following equivalent and maleic acid in ethanol .. The precipitate is filtered and recrystallized from diisopropyl ether and this cola. 1.64 g (34%) of pure is obtained
    product with so pl. 114-116 S.
    renaline than the famous, pharmacological experiments. Experimentally, it is impossible to cause depression in animals. Biochemical and pharmacological methods should be used to determine the possible suppressive depression of the activity of new compounds. One of them gives good results in relation to potential depressive activity. The method is reduced to determining the decrease in absorption of C-5-hydroxytryptamine (C-5-HT) and H-norepinephrine (H-MA) in brain media after application of the test compound in vivo and in vitro. The inhibition of the absorption of C-5-HT and H-NA in vivo and in vitro has been investigated. blown compounds are administered intraperitoneally half an hour before the animals are killed. The midbrain is cut and incubated in a mixture consisting of 1x10M C-5-HT, 1x10 M in HN A, 5.6 mmol of glucose, 5x10 M pargyline, 1.1 mm JOL of ascorbic acid, and 1.3x10 M sodium salt of ethylene oxide-tetra-acetic acid in 2 ml of Krebs-Henseleit buffer 25 mg of brain slices (pH 7.4). Incubate for 5 minutes with 5 minutes preincubation. Then the compounds indicated in the table are added. The sections were dissolved in Soluene and the amount of absorbed radioactive amines was determined by liquid scintillation. A dose giving a 50% reduction in the active Ml C-5-HT and H-NA absorption (ED) is graphically determined from the dose-response curve. Active uptake is defined as part of the radioactive uptake that is inhibited by a high concentration of cocaine. In in vitro experiments, midbrain sections were pre-incubated for 5 minutes in solution of the test compound and then incubated in the manner described. The concentration of the test compound is determined, giving a 50% reduction in C-5-HT and H-NA (EC) absorption. As can be seen in the table, the suggested compounds are a bo active inhibitor of the neuronal absorption of 5-oxytriptamine and norad
    权利要求:
    Claims (2)
    [1]
    A method of producing pyridylallylamine derivatives of the general formula wherein, if X is a bromine atom, it is not in position 4;
    P-1 or 2, or their salts with acids, or mixtures
    Lp-itrans-isomers, or individual isomers, characterized in that the compound is of the general formula / I
    OH CbfeCH.N
    [2]
    2 g where S, X and O have the indicated meanings, are subjected to dehydration with the subsequent isolation of the target product in free form or as a salt with acid or as a mixture of cis and trans isomers or individual isomers.
    where R is a hydrogen atom, methyl;
    X is a halogen atom in any position of phenyl,
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    同族专利:
    公开号 | 公开日
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    PL232731A1|1982-08-16|
    FI812196L|1981-07-10|
    PL227849A1|1981-12-23|
    SU1149874A3|1985-04-07|
    GR72129B|1983-09-16|
    DK300781A|1981-07-07|
    PL232732A1|1982-08-16|
    WO1981001407A1|1981-05-28|
    AU538087B2|1984-07-26|
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    引用文献:
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    SE409706B|1976-05-21|1979-09-03|Astra Pharma Prod|PROCEDURE FOR PREPARING N, N-DIMETHYL-3- -3-3 -ALLYLAMINE DIHYDROCHLORIDE MONOHYDRATE|
    SE418399B|1976-05-21|1981-05-25|Astra Laekemedel Ab|PROCEDURE FOR THE PREPARATION OF N, N-DIMETHYL-3- -3- ALLYLAMINE|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    SE7909514A|SE7909514L|1979-11-16|1979-11-16|NEW HALOPHENYL-PYRIDYL-ALLYLAMINE DERIVATIVES|
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