• 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 compound of the formula <IMAGE> and non-toxic, pharmacologically acceptable acid addition salts thereof. The compound as well as its salts are useful as bradycardiacs.
    公开号:SU812175A3
    申请号:SU792721602
    申请日:1979-02-09
    公开日:1981-03-07
    发明作者:Штеле Гельмут；Кеппе Герберт；Куммер Вернер；Хефке Вольфганг；Гайда Вольфрам；Пихлер Лудвиг
    申请人:К.Х.Берингер Зон (Фирма)；
    IPC主号:
    专利说明:

    us Thioureas are then converted into isothiourea salt by alkyl alkyl. From these kislotnoaddi tive compounds with bases are obtained the corresponding isothiourea Predlagaelale 2-fenilimynoimidaeolidi us the general formula (I) by the usual method can be converted into their physiologically tolerable acid addition salts for salt formation are suitable acid such as hydrochloric, bromistovodoro to, hydroiodic, hydrofluoric, sulfuric , phosphorus, nitric, acetic, propionic, oil, caprone, sherianova, oxalic, little new, amber, mgsheiieva, furarorova, dairy, viina lemon, block, benzo yna, p-hydroxybenzoic, p-aminobenzoic, phthalic, brown, salicylic, ascorbic, methanesulfonic acid, 8-chlorophyllin, etc. The new 2-phenyliminoimidazrelidins of the general formush (1) and their acid-additive salts impart valuable therapeutic properties. They act strongly bradyka and therefore are suitable for the treatment of coronary diseases. The effect on heart rate was investigated in rabbits and bunks. The compounds of formula (I) can be administered enteric or parenterally. The dosage is between about 0.1 and 80 mg, preferably between 0.5 and 30 mg. Example 1. Hydrochloride 2- (2,6-dibrom-4-oxymethylphenyl Limo) -imidazolidine. 35.5 g (0.0335 mol) of 2- (2,6-dibromo-4-oxmmethylphenyl) -S-methyl-iothiouroni iodide with 7.5 ml of ethylene diamine in 75 ml of butanol are boiled under reflux for 8 hours and the organic the solvent is evaporated in vacuo. The residue is dissolved in 2N. The HC, the aqueous solution, is extracted with ether (the ether extracts are removed). The aqueous phase is alkalinized 2 n. NaOH and fractionally extracted with ethyl acetate. The homogeneous fractions are concentrated in vacuo, the residue is dissolved in methanol, the hydrochloric acid is acidified to form a congo-acid reaction, and the clear solution is mixed with ether. The amorphous solution is filtered off with suction and washed with ether. After drying, a yield of 1.6 g is obtained (5.6% of theory), mp. 267268 ° C, K, 0.6, eluate; 50 hours of benzene, 40 hours. dioxane, 5 parts of ethanol and 5 parts of concentrated aqueous. Silica gel carrier, manifestation of potassium iodoplatinate. The required 2,6-dibromo-4-6ximethylaniline as the starting material is obtained by brominating 4-aminobenzoic acid methyl ester and reducing the intermediate by lithium aluminum hydride. Example 2. Hydrochloride 2- (4-ami no-3,5-dibromo n nimo) imidaeolidine. 30.35 g (0.065 mol) of 2- (4-amino-3,5-dibromophenyl) -S-methyl. Isothiouronium hydroiodide together with 6.5 ml of ethylene diamine in 65 ml of methanol is heated under reflux for 10 hours. The methanol is then evaporated in vacuo and the viscous residue is dissolved in methanol. The solution is filtered and alkalinized with 50% KOH by adding ice. This releases an imidazolidine base which, after stirring with ether, crystallizes, m.p. bases 203-205 s, yield, 3.58 g (16.5% of theory). To obtain the salt, the base is dissolved in a small amount, acidified with HCE to obtain a congo-acidic reaction, followed by simple precipitation with ether. After isolation and drying, a yield of 3.20 g (13.3% of theory) is obtained, m.p. 234236 0, R. 0.4, eluate: 50 hours of benzene, 40 hours of dioxane, 5 parts of ethanol and 5 hours of concentrated. The carrier is silica gel, an ultraviolet ray, potassium iodoplatinate., Example 3. 2- (3-methyl-mercaptophenylimino) -imidazolidine hydrobromide. 42.5 g (0.125 mol of 2- (3-methyl mercapto-phenyl) -S-methyl-isothiuronium iodide in 125 ml of CHjOH together with 12.5 ml of ethylene diamine are heated under reflux for 6 hours and then the reaction mixture is concentrated in vacuo to dryness. Mass, the residue in a small amount of CH, .OH, is precipitated with 50% KOH, ice is added. The free base is again dissolved in 2N HCR and extracted with ether. The acidic extracts are removed, then alkalinized and fractionally extracted with ether. the ether extracts are combined, dried with KgSO4, and purified over active carbon. The ganic phase is brought to a congo-acidic reaction with 65% IV g. A white, amorphous powder is obtained, and after separation and drying, a yield of 6 g (16.7% of theory) is obtained, mp 147-148s , Rp 0.3, eluate: 50 parts of benzene, 40 parts of dioxane, 5 parts of ethanol and 5 parts of concentrated. Ultraviolet ray, potassium iodine platinate. Similarly, the following compounds of general formula (I) can be obtained (melting point if there are no other marks, refers to hydrobromides) listed in the table.
    权利要求:
    Claims (1)
    [1]
    Claims.
    The method of obtaining substituted 2-phenyliminoimidazolidines of the general formula
     J
    tl)
    II
    c-I H
    where R is 2 bromo-4,5-dirxyphenyl, 3-chloro-4-hydroxyphenyl, 4-bromo-2,5-. dioxyphenyl, 3,5-dioxyphenyl 5-chloro-2,4-dioxyphenyl ,. 3 hydroxy-4-methylphenyl, 2,6-dibrrm-4-hydroxymethylphenyl, 3-5-dibromo-4-aminophenyl, 3-methylmercaptophenyl, 3,4,5-trioxyphenyl or 3-bromo-4-fluorophenyl. radicals ,.
    or salts thereof, characterized in that the compound of the general formula .3-R
    ./
    (AND)
    NH
    where R has the indicated meanings, R is a hydrogen atom or an alkyl group with up to 4 carbon atoms,
    or its salts undergo interaction.
    VIS with ethylenediamine or its salts
    with the subsequent selection of the target
    product in free form or as
    spout
    Information sources,
    B9 accepted attention during examination 1. Belgium patent 623305,
    cl. C 07 D, pub. 1963.
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    同族专利:
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    SE7901405L|1979-08-18|
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    US4250186A|1981-02-10|
    AU519356B2|1981-11-26|
    IE48073B1|1984-09-19|
    FR2417502A1|1979-09-14|
    CS207774B2|1981-08-31|
    CH640230A5|1983-12-30|
    RO81504A|1983-04-29|
    NO151239C|1985-03-06|
    FI69301C|1986-01-10|
    FI69301B|1985-09-30|
    PL115759B1|1981-04-30|
    DD142048A5|1980-06-04|
    GR67626B|1981-09-01|
    GB2014575A|1979-08-30|
    FR2417502B1|1981-06-26|
    YU36779A|1983-04-30|
    PL213475A1|1980-03-10|
    FI790510A|1979-08-18|
    DE2806775A1|1979-08-30|
    NO151239B|1984-11-26|
    AT370093B|1983-02-25|
    ES477784A1|1980-04-01|
    ATA101579A|1982-07-15|
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    CA1115717A|1982-01-05|
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    LU80924A1|1980-04-21|
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US2938038A|1960-05-24|X-dihydroxyphenylamino |
    US2899426A|1959-08-11|Synthesis of l |
    FR1211341A|1955-12-19|1960-03-15|A Wander Dr|Process for the preparation of 2-amino-imidazolines|
    US3595961A|1965-10-01|1971-07-27|Boehringer Sohn Ingelheim|Hypotensive compositions containing 2- - 1,3 -diazacyclopentenes- and methods of using the same|
    DE1670274A1|1966-10-31|1970-07-16|Boehringer Sohn Ingelheim|New process for the preparation of 2-arylamino-1,3-diazacycloalkenene |
    AT285599B|1968-06-21|1970-11-10|Boehringer Sohn Ingelheim|Process for the preparation of new trisubstituted 2-arylaminoimidazolines and their salts|
    DE2446758C3|1974-10-01|1979-01-04|C.H. Boehringer Sohn, 6507 Ingelheim|2- -imidazolidine, its acid addition salts, processes for the preparation of these compounds and their use in combating hypertension|
    DE2523103C3|1975-05-24|1979-11-29|C.H. Boehringer Sohn, 6507 Ingelheim|Substituted 2- [N-Progargyl-N- amino] -imidazoline- ^), their acid addition salts, processes for their preparation and their use|
    DE2630060C2|1976-07-03|1984-04-19|C.H. Boehringer Sohn, 6507 Ingelheim|2- -imidazolidine, its acid addition salts, medicaments containing them and processes for their preparation|DE2854659A1|1978-12-18|1980-07-10|Boehringer Sohn Ingelheim|NEW 3,4-DISUBSTITUTED 2-PHENYLIMINO IMIDAZOLIDINES, THEIR ACID ADDITION SALTS, THE MEDICINAL PRODUCTS CONTAINING THEM AND METHOD FOR THE PRODUCTION THEREOF|
    DE3168754D1|1980-07-09|1985-03-21|Beecham Group Plc|Clonidine derivatives useful in the treatment of diarrhoea|
    EP0070084A3|1981-04-24|1983-02-16|Beecham Group Plc|Imidazoline derivatives|
    US4515800A|1981-11-20|1985-05-07|Icilio Cavero|Method of lowering intraocular pressure using phenylimino-imidazoles|
    CA1201066A|1981-11-20|1986-02-25|Alcon Laboratories, Inc.|N-¬3,5-dichloro-4--phenyl|-acetamide solutions for loweringintraocular pressure|
    US4461904A|1981-11-20|1984-07-24|Alcon Laboratories, Inc.|2--imidazolines|
    US4517199A|1981-11-20|1985-05-14|Alcon Laboratories, Inc.|Method for lowering intraocular pressure using phenylimino-imidazoles|
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    FR2521140B1|1982-02-05|1984-03-16|Synthelabo|
    GB2137191A|1983-02-28|1984-10-03|Sumitomo Chemical Co|Fungicidal N-phenylimidates|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19782806775|DE2806775A1|1978-02-17|1978-02-17|NEW SUBSTITUTED 2-PHENYLIMINO IMIDAZOLIDINE THEIR ACID ADDITION SALTS, MEDICINAL PRODUCTS CONTAINING THEM AND METHOD FOR THE PRODUCTION THEREOF|
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