• 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:
    Compounds of the formula …<IMAGE>… (the substituents are defined in the description) can be obtained by customary methods. The novel compounds are suitable as active substances for medicaments.
    公开号:SU1494867A3
    申请号:SU874202707
    申请日:1987-06-15
    公开日:1989-07-15
    发明作者:Шнейдер Клаус；Мерц Герберт；Соботта Райнер；Бауер Рудольф；Мирау Иоахим；Шингнитц Гюнтер
    申请人:Берингер Ингельгейм Кг (Фирма)；
    IPC主号:
    专利说明:

    It is heated under reflux for 2 hours, then it is poured onto ice and extracted with ethyl acetate. After drying, it crystallized out by concentration of 2- (4-methoxyphenylpropionyl) amino-6-oxo-tetrahydrobenzothiazole (17.5 g), which was dissolved in methanol without further purification and subjected to reductive amination with propylamine in the presence of further purification René nickel at a pressure of 5 bar and 60 ° C. After the catalyst is removed, the solvent is distilled off. The residue is crystallized from isopropyl ether.
    Output 12.5 g (63Z from theor.), So pl. bases 105-106 C (recrystallization from ethyl acetate), m.p. dihydrochloride 259-261 ° C
    B. Separation of the racemate.
    To a suspension of 9.3 g (0.025 mol) of the product obtained according to A in 200 ml of water was added 3.75 g (0.025 mol) of L - (+) - tartaric acid (with 20 H, 0). The mixture is heated under reflux for 15 minutes and filtered. The colorless crystals which separated out after 1 day were sucked off. This L - (+) - BHHHO- acid salt is recrystallized five times from 75 ml of water. Upon further recrystallization, the index no longer changes. 3 (, methanol) on the base.
    From pure L - (+) - tartaric acid salt, by adding concentrated ammonia, extract the base, which is extracted with ethyl acetate. After washing and drying with magnesium sulfate, the solvent is removed in vacuo. By treating ethereal hydrochloric acid, the (-) - enantiomer dihydrochloride crystallizes out.
    Output 0.9 g, so pl. 261-262 s, (, methanol).
    Biological testing.
    Determination of action against Parkinson's KPI Parkinson's disease.
    Based on the use of the neurotoxic cuifa (J-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), animal studies have been developed to study Parkinson's disease.
    Caused by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine in humans and monkeys is irreversible, the neurological picture of the disease is clinically
    five
    0
    5 0 5
    0
    five

    five
    Pathological, biochemical, and pharmacological phenomena are largely similar to idiopathic Parkinson's disease. The reason for this is that the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine selectively destroys that small group of dopaminergic nerve cells in the brain's Substantiia nigra that are destroyed by degenerative processes during natural Parkinson's disease. The clinical manifestation of the picture of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine disease can be demonstrated only on monkeys, which is likely due to the specific metabolism of 1-metsh4-4-phenyl-1,2, 3,6-tetrahydropyridine.
    The experiment using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, developed for rhesus, can be used to test the effectiveness of agents in the treatment of Parkinson's disease.
    1-Methyl-A-phenyl-1,2,3,6-tetrahydropyridine was given to monkeys for 3 days, daily 1 x 0.15 mg / kg intramuscularly, then they took a break for 3 days without giving medication, then for 3 days, they gave 1 x 0.30 - 0.40 mg / kg daily.
    The following symptoms were observed: the animals were akinetic, unable to take feed and water. Sometimes there are cataleptic conditions. Numbness appeared on the extremities, interrupted by passive movement of clonic convulsions. As a rule, even the strongest painful irritation did not cause arbitrary movements of the trunk and limbs.
    After intramuscular administration (50 µg / kg / of the proposed compound (as a racemate, (-) - enantiomer and dihydrochloride), the first voluntary movements were observed at intervals after several minutes, after which the motility was gradually normalized, due to which the animals were able to feed They were completely normal in the cells regarding vigilance and specific behavior for this monkey genus. Temporary lung was recorded as residual symptoms from time to time.
    trembling at rest and reduction of brute force.
    The effect of the proposed compound began to weaken after approximately 20 hours, after which the animals again showed symptoms of parkinsonism.
    After intramuscular administration of a known tetrahydrobenzothiazole derivative of 2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazole, at the same concentration as the proposed derivative (50 µg / kg),
    action with the same efficiency, but its weakening began after about 6 hours.
    The proposed tetrahydrobenzothiazole derivative belongs to the category of low-toxic substances.
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method of obtaining 2- (4-methoxyphenylpropionyl) amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazole of the formula
    N-xx СНзО -) - СН2-СН2-СО-ЗНЛ ХД
    In the form of a racemate or (-) - enantiomer or its acid addition salt, characterized in that
    СНзОн (about -СНгСН, -CO-ш4 СХо
    is reacted with the n-propyl product in the form of the racemate or (-) - amine in the presence of the reducing agent of the enantiomer or their acid addition, followed by separation of the target salt.
    NH
    Sleep
    2- (4-methoxyphenylpropionyl) amino-6-oxo-tetrahydrobenzothiazole of formula
    类似技术:
    公开号 | 公开日 | 专利标题
    DE69535315T2|2007-06-28|1-AMINOINDANDERIVATE AND COMPOSITIONS HEREVON
    DE2851435A1|1979-06-13|SUBSTITUTED AMIDE DERIVATIVES OF L- AND DL-PHENYLGLYCINE, PROCESS FOR THEIR MANUFACTURING AND MEDICINAL PRODUCTS CONTAINING THESE DERIVATIVES
    SU1494867A3|1989-07-15|Method of producing 2-|amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazol as racemate or |-enantiomer or its acid-additive salt
    AT6687U1|2004-02-25|METHOD FOR SEPARATING TAMSULOSIN AND RELATED COMPOUNDS AND COMPOSITIONS
    DE69813228T2|2004-02-19|ALIFATIC PROPARGYLAMINE AS A CELLULAR RESCUE
    FR2625678A1|1989-07-13|Anorexigenic agents based on N-|benzamides or -thiobenzamides
    DE2362754A1|1974-07-11|CYCLOPROPYLMETHYLAMINES, THE PROCESS FOR THEIR PRODUCTION AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
    CH639639A5|1983-11-30|Alpha-fluoromethyl-alpha-amino-alkanoic acids and their esters
    JP5923499B2|2016-05-24|Synthesis and use of kinase inhibitors
    FR2827288A1|2003-01-17|NOVEL OCTAHYDRO-2H-PYRIDO [1,2-A] PYRAZINE DERIVATIVES, PROCESS FOR PREPARING THEM AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
    EP0280603A1|1988-08-31|Absolute S confirmation enantiomers of amide derivatives of 3-aminoquinuclidine, process for their preparation and their therapeutical use
    MXPA06006522A|2006-08-23|A process for the resolution of nefopam.
    EP0022017B1|1982-05-05|Derivatives of 2-benzoyl-4-nitro anilides, their preparation and their use as medicines
    FR2534915A1|1984-04-27|New 2-|morpholine derivatives, their therapeutic use and process for preparing them
    HU178220B|1982-03-28|Process for producing quaternery ammonium-salts
    CN1172908C|2004-10-27|N-substituted benzyl or phenyl aromatic amide compound and its use
    DE60026161T2|2006-11-16|AMIDINE DERIVATIVES, THEIR PREPARATION AND USE AS MEDICAMENTS
    EP0158545B1|1987-04-22|[Alpha-|-benzylthio]-acetic-acid derivatives, process for their preparation and their therapeutic use
    US20100312010A1|2010-12-09| Process for the Preparation of |-Pregabalin
    DE19908539A1|2000-08-31|Polycyclic 2-amino-dihydrothiazole systems, processes for their preparation and their use as medicines
    TW201039813A|2010-11-16|Derivatives of aminocyclobutane or aminocyclobutene, their method of preparation and their use as medicinal products
    DD290136A5|1991-05-23|USE OF 2,7-DIAMINO-1,2,3,4-TETRAHYDRONAPHTHALINES AS DRUGS, NEW 2,7-DIAMINO-1,2,3,4-TETRAHYDRONAPHTHALINES, AND METHOD OF PREPARING THEM
    US3903165A|1975-09-02|Ethynylaryl amines and processes for their preparation
    DE2710504A1|1977-09-15|METHOD FOR MANUFACTURING OPTICALLY ACTIVE PHENYLGLYCINE
    RU2015960C1|1994-07-15|Process for preparing phenylkylamines or salts of these compounds
    同族专利:
    公开号 | 公开日
    FI872719A0|1987-06-18|
    PT85100B|1994-10-31|
    ZA874470B|1989-02-22|
    UA8032A1|1995-12-26|
    NO167978B|1991-09-23|
    FI88297C|1993-04-26|
    DD259623A5|1988-08-31|
    FI872719A|1987-12-22|
    EP0251077A1|1988-01-07|
    CS451187A3|1992-05-13|
    CA1322372C|1993-09-21|
    AT70060T|1991-12-15|
    IE871633L|1987-12-21|
    HU204042B|1991-11-28|
    HUT47091A|1989-01-30|
    DK313587A|1987-12-22|
    KR950004000B1|1995-04-22|
    IL82925D0|1987-12-20|
    JPS6317872A|1988-01-25|
    DE3774942D1|1992-01-16|
    NZ220800A|1989-12-21|
    DE3620813A1|1987-12-23|
    EP0251077B1|1991-12-04|
    PL266361A1|1988-10-13|
    FI88297B|1993-01-15|
    NO872574D0|1987-06-19|
    NO167978C|1992-01-02|
    KR880000415A|1988-03-25|
    DK313587D0|1987-06-19|
    PL150292B1|1990-05-31|
    CS276376B6|1992-05-13|
    PH24207A|1990-04-10|
    AU7457887A|1987-12-24|
    PT85100A|1988-07-01|
    IE60676B1|1994-08-10|
    AU593357B2|1990-02-08|
    NO872574L|1987-12-22|
    GR3003656T3|1993-03-16|
    DK168437B1|1994-03-28|
    ES2040226T3|1993-10-16|
    US4981862A|1991-01-01|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE1923677A1|1969-05-09|1970-11-19|Bayer Ag|2,6-diaminobenzothiazole derivatives|
    DE2136233A1|1971-07-20|1973-02-01|Riedel De Haen Ag|Virustatic tetrahydro-benzthiazoles - active against both rna and dna viruses|
    FR2406635B1|1977-10-24|1980-06-27|Logeais Labor Jacques|
    FR2459239B1|1979-06-20|1982-09-10|Logeais Labor Jacques|
    AT45735T|1984-12-22|1989-09-15|Thomae Gmbh Dr K|TETRAHYDRO-BENZTHIAZOLE, THEIR PRODUCTION AND THEIR USE AS AN INTERMEDIATE PRODUCT OR AS A MEDICINAL PRODUCT.|
    DE3447075A1|1984-12-22|1986-07-03|Dr. Karl Thomae Gmbh, 7950 Biberach|Tetrahydrobenzothiazoles, their preparation and their use as intermediates or as medicaments|
    ZA864626B|1985-06-24|1988-02-24|Lilly Co Eli|Dialkylaminotetrahydrobenzothiazoles and oxazoles|FR2731619A1|1995-03-14|1996-09-20|Logeais Labor Jacques|PHARMACEUTICAL COMPOSITIONS CONTAINING L-ETRABAMINE, USES THEREOF AND PREPARATION METHODS|
    ES2187249B1|2000-09-18|2004-09-16|Synthon Bv|PROCEDURE FOR THE PREPARATION OF 2-AMINO-6-AMINO-4,5,6,7-TETRAHYDROBENZOTIAZOLES.|
    GB0221513D0|2002-09-17|2002-10-23|Generics Uk Ltd|Novel compounds and processes|
    KR100715203B1|2003-12-19|2007-05-07|주식회사 코오롱|Polyester spunbonded nonwoven fabrics for air filter and preparation method thereof|
    ITMI20060044A1|2006-01-13|2007-07-14|Dipharma Spa|SUMMARY OF INTERMEDIATES PR PREPARATION OF PRAMIPEXOL|
    GB0721333D0|2007-10-31|2007-12-12|Motac Neuroscience Ltd|Medicaments|
    CN108084115B|2017-12-28|2020-03-17|上海博志研新药物技术有限公司|Preparation method of pramipexole dihydrochloride and intermediate thereof|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19863620813|DE3620813A1|1986-06-21|1986-06-21|NEW TETRAHYDRO-BENZOTHIAZOLES, THEIR PRODUCTION AND USE|
    [返回顶部]