• 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:
    3-[4-(2'-Pyridyl)-piperazin-1-yl]-1-(3,4,5-trimethoxybenzoyloxy)-propane or a pharmaceutically acceptable acid-addition salt thereof in a composition with anti-arrhythmic activity.
    公开号:SU862825A3
    申请号:SU792719250
    申请日:1979-02-05
    公开日:1981-09-07
    发明作者:Молнар Арпад；Фелфельди Карой；Барток Михай；Карпати Эгон；Спорни Ласло
    申请人:Рихтер Гедеон Ведьесети Дьяр Рт (Инопредприятие)；
    IPC主号:
    专利说明:

    The invention relates to a method for producing a new 3- [4- (2 pyridyl) piperazin-1-yl] -1 -
    - (3,4,5-trimethoxybenzoyloxy) propane or its dihydrochloride, which may find application in the pharmaceutical industry.
    The interaction of piperazine with halogenated H] is known.
    The purpose of the invention. - obtaining a new derivative of pyridcl-piperazine or its dihydrochloride, which have valuable pharmacological properties.
    This is achieved by the method of obtaining 3- (4-
    - (2 g- pyridyl) piperazin-1-yl] -1- (3,4,5-trimethoxybenzoyloxy) propane or di hydrochloride, which consists in the fact that 4- (2'-pyridyl) piperazine is introduced into interaction with 1- (3,4,5- trimeths of sibenzoyloc si) - 3-gal ogenpropane, and the obtained target product is isolated in free form or in the form of dihydrochloride.
    This reaction is carried out in a solvent. incompatible with an aliphatic ketone or alcohol, with 1–5 carbon atoms, or in a hydrocarbon, or in derivatives of a series of benzene, for example, in benzene, toluene, or xylene, at elevated temperature, it is advisable at the boiling point of the reaction mixture. The resulting product can be isolated from the reaction mixture, for example, by extraction. The product can be purified 5 , and under certain conditions, it can be converted into the acid addition salt in the resulting reaction mixture and isolated in this form.
    The reaction product obtained as the free base] θ ния by reaction with an acid is converted into the corresponding acid addition salt. Inorganic or organic salts giving physiologically compatible salts are changed for this purpose: slots, U, for example, hydrohalic acids, such as hydrochloric acid, hydrogen bromide or iodide, sulfuric acid, phosphoric acids, acetic, propionic, butyric, maleic, fumaronic, citric, malic tartaric acid and the like In therapy, new compounds and their acid addition salts are primarily administered orally or intravenously. The daily dose is about 1-10 mg / kg, especially 3-7 mg / kg of body weight; as a single oral or intravenous dose, depending on the severity of the patient's condition, approximately 1.0-3.0 mg / kg of biologically active substance can be administered.
    The resulting new compound or its acid addition salts to formulate drugs are mixed with solid or liquid pharmaceutical bases and / or with conventional pharmaceutical excipients and converted into suitable dosage forms. As the bases used, for example, water, gelatin, milk sugar, starches, talc, magnesium stearate, petroleum jelly, gum arabic, vegetable oils, polyethylene glycols and t. The preparations may contain various auxiliary substances, for example, stabilizers, preservatives, wetting agents, emulsifiers that improve the taste of the substance.
    PRI me R 1. 3.3 g (0.02 mol) of 4- (2 * -pyridyl) piperazine, 6.4 g (0.022 mol) of 1- (3,4,5-trimethoxy-benzoyloxy) -3-chloropropane and 3.1 g of anhydrous potassium carbonate in 30 ml of xylene with stirring are refluxed for 20 hours. Then the reaction mixture is cooled to room temperature, mixed with 30 ml of benzene and washed with water. After phase separation, the organic phase is dried, filtered and the filtrate is saturated under cooling with gaseous hydrogen chloride. The precipitate obtained is filtered off, dried and recrystallized from a mixture of ethanol and water. Obtain 5.0 g (51% of theory) of 3- (4/2-pyridyl) piperazin-1-yl / -1- (3,4,5-trimethoxybenzoyloxy) propane dihydrochloride, so pl. 200-201 ° C. g Found,%: C 54.05; H, 6.32; CI 14.62.
    C 22 Hji Cl 2 Ν3Ο5
    Calculated,%: C 54.10; H 5.40; CI 14.52 ° The base of the compound is so pl. 82-85 C. Found,% 'C 63.35; H, 7.25; N, 10.30. C22H29N3OS
    Calculated,%: C 63.70; H 7.04; N, 10.11
    PRI me R 2. To obtain medicinal tablets containing as biologically active substances 3- [4- (2'-pyridyl) piperazin-1-yl] -1 (3,4,5-trimethoxybenzoyloxy) 5 - propane dihydrochloride, the following substances are used, g:
    Biologically active substance30
    Talcum 9
    Magnesium Stearate3
    Polyvinylpyrrolidone6
    Potato starch 84
    Lactose168
    The biologically active substance is mixed with lactose and one part of potato starch15 is small, the mixture is moistened with an aqueous solution of polyvinylpyrrolidoya and granulated. The dried granulate is then mixed with talc, magnesium stearate and the rest of the starch and compressed to 1000 tablets containing 3.0 mg of biologically active substance each ..
    Target products have antiarrhythmic activity.
    权利要求:
    Claims (2)
    [1]
    For an oral or intravenous dose of 38, depending on the severity of the patient’s condition, about 1.0-3.0 mg / kg of biologically active substance can be administered. The resulting compound or its salts of acid to form drugs are shifted with solid or liquid pharmaceutical bases and / or with conventional pharmaceutical auxiliaries and converted into a useful dosage form. As bases, for example, water, gelatin, milk sugar, starches, talc, magnesium stearate, vaseline, gum arabic, vegetable oils, polyethylene glycols, and tl are used. Preparations may contain various adjuvants, for example, stabilizers, preservatives, wetting agents, emulsifiers, taste-improving substances. EXAMPLE 1 3.3 g (0.02 mol) 4- {2-mirvdi-0-liperazine, 6.4 g (0.022 mol) b (ZD, 5-trimethoxy-benzoyloxy) -3- chloropropane and 3.1 anhydrous potassium carbonate in 30 ml of xylene while being transferred) the al is boiled under reflux for 20 hours. In the same way, the reaction mixture is cooled to room temperature, shifted from 30 ml of benzene and washed with water. After separation of the phases, the organic phase cjTiiaT is filtered and the filtrate is saturated with cooling with gaseous hydrogen chloride. The precipitate obtained is filtered, and the residue is recrystallized from ethanol / water. Obtain 5.0 g (51% of theory) 3- 4/2-pyridyl) -piperazine-b / 1- (3,4,5-trimegoxybenzoyl oxy) -propane dihydrochloride, so pl. 200–201 ° C. Found,%: C 54.05; H 6.32; From 14.62. CjjHsiCljNsOs Calculated,%: C 54.10; H 5.40; C1 14.52 The base of the compound is m. Pl. 82-8 5 C Found,%: C 63.35; H 7.25; N 10.30. CajHieNjOs Calculated,%: C 63.70; H 7.04; N 10,11 PRI me R
    [2]
    2. For the preparation of medicinal tablets containing 3- 4- (2-pyridyl) -sterazin-1-yl-1- (3,4,5-trimethoxybenzoyloxy) dihydrochloride as a biologically active substance, the following substances are used, g: Biologically active substance30 Talc9 Stearate m of polyvipshparrolidoy6 Potato starch84 Lactose168 The biologically active substance is shifted with lactose and one part of potato starch, the mixture is moistened with an aqueous solution of polyvinylpyrroldone and granulated. The dried granulate is then mixed with talc, magnesium stearate and the rest of the starch, pressed to 10 (10 tablets containing 3 mg mg of biologically active substance each. Target products have antiarrhythmic activity. Formula 1) (3- (4- (2. pnridyl) -sterazin-1-yl-1- (3,4,5-trimethoxybenzonloxy si) propane or its dihydrochloride, which means that 4- (2-pyridsh1) piperazine is reacted with 1- (3 , 4,5-trimethoxybenzoyloxy) -3-halogenpropan obtained target product The product is isolated in free form or as the dihydrochloride. Sources of information received note in the examination 1. Heterocyclic compounds. Ed. Elderfild. vol. 6, 1960, p. 347.
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    同族专利:
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    NL7802031A|1978-08-29|
    IN149333B|1981-10-24|
    DE2807169A1|1978-09-14|
    AU3355178A|1979-08-30|
    ZA781018B|1979-01-31|
    AU514106B2|1981-01-22|
    US4196206A|1980-04-01|
    AR215290A1|1979-09-28|
    SU718010A3|1980-02-25|
    PT67703B|1979-09-20|
    SE7801949L|1978-08-26|
    GB1569084A|1980-06-11|
    SE429863B|1983-10-03|
    FI66350C|1984-10-10|
    ATA127878A|1980-08-15|
    NO147837C|1983-06-22|
    NO780635L|1978-08-28|
    FI780624A|1978-08-26|
    HU173380B|1979-04-28|
    BE864296A|1978-06-16|
    FR2381760B1|1982-09-17|
    NO147837B|1983-03-14|
    JPS53105486A|1978-09-13|
    FR2381760A1|1978-09-22|
    CH635337A5|1983-03-31|
    ES467224A1|1978-11-16|
    IL54038A|1981-06-29|
    GR64159B|1980-02-05|
    PT67703A|1978-03-01|
    YU40278A|1982-10-31|
    AT361488B|1981-03-10|
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US2958694A|1959-06-22|1960-11-01|Janssen Paul Adriaan Jan|1--4- piperazines|
    DE1670360A1|1966-07-02|1970-10-29|Cassella Farbwerke Mainkur Ag|Process for the preparation of derivatives of piperazine|
    JPS5210877B2|1972-11-08|1977-03-26|
    US4038279A|1972-12-23|1977-07-26|Boehringer Ingelheim Gmbh|N-aryl-n'--piperazines and salts thereof|US4367335A|1981-08-03|1983-01-04|Mead Johnson & Company|Thiazolidinylalkylene piperazine derivatives|
    JPH0338875Y2|1983-06-09|1991-08-15|
    IT1191845B|1986-01-20|1988-03-23|Dompe Farmaceutici Spa|PHARMACOLOGICALLY ACTIVE ALCHYLOLS|
    JPH03104641U|1990-01-30|1991-10-30|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    HU77RI617A|HU173380B|1977-02-25|1977-02-25|Process for producing new pyridyl-piperazine derivatives and acid additional salts thereof|
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