• 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:
    A pharmacologically active compound has the general formula in which R is a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; R, and R2, which can be different, represent a hydrogen atom, a hydroxyl group, an alkyl group, an alkoxy group, an arylalkyl group, or an arylalkoxy group, or can jointly represent an oxygen atom or a CHCOOR,' group where R1' is a hydrogen atom or an alkyl group; and R3 represents a hydrogen or halogen atom or an alkyl, NH2, NO2, NHCO-alkyl, NHCO-aryl, NHCONH-alkyl or NHCONH-aryl group. These compounds act on the central nervous system and have an anti-convulsant sedative activity.
    公开号:SU1301830A1
    申请号:SU833565650
    申请日:1983-03-14
    公开日:1987-04-07
    发明作者:Пестеллини Витторино；Челардони Марио；Джиолитти Алессандро；Вольтерра Джиованна；Фурио Мартино；Мели Альберто
    申请人:А.Менарини С.А.С. (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to new chemical compounds, namely, to derivatives 5j 6-dihydro-11-H-dibenzo b, e azepin-6-one of the general formula
    where R is hydrogen or methyl;
    when R j and R are hydrogen, R is hydroxy or ethoxy;
    when Rg is methyl and R is hydrogen, Rg is hydroxy;
    when R is NHCOCH, R and R together represent oxygen;
    After keeping at room temperature for 30 minutes, 2.5 ml of methyl iodide are added and the mixture is kept at room temperature.
    5 for 24 h, after which it. poured into water, the product is filtered off, dried and crystallized from ethanol to obtain a product with so pl. 199-201 ° C.
    PRI me R 3. 11-ethoxy-5-methyl- possessing an anticonvulsant activity of 5,6-dihydro-11H-dibenzo b, e azepin6-one.
    18 ml of thionyl chloride are added to 7.1 g of 11-hydroxy-5-methyl-5,6-dihydro-dibenzo b, e 1 azepin-6-one in 180 ml of chloroform and the mixture is left to stand at room temperature for 12 hours. After removing the solvent and excess thionyl chloride in
    stew.
    The aim of the invention is to search a number of 5,6-dihydro-11H-dibenzo b, el azepin-6-ones for new compounds that have valuable pharmacological properties, in particular, high anticonvulsant activity with low toxicity.
    Example 1. 5,11-dimethyl-11167, .. „g, there is a twisted product with so pl.
    hydroxy-5,6-dihydro-11H-dibenzo Lb, ej DA
    Azepin-6-on.i onir, r,
    1.20 g of sodium ethylate in 100 ml of an ab10 ml of methyl iodide. In 50 ml of anhydrous ethyl ether is added to 8.8 g of magnesium shavings in anhydrous ethyl ether at such a rate as to maintain a slow reflux.
    After the addition is complete, the mixture is kept for another 1 hour at refluxing, then Q is added with 10 g of 5-methyl-5,6-dihydro-1 1 H-dibenzo b, e3 azepin-6,11-dione dissolved in 100 ml of anhydrous THF. After boiling the mixture with
    Solvent ethanol is added little by little to 5.5 g of the previously obtained crude product in 56 ml of dioxane. 35 After boiling for 2 hours under reflux, the mixture is allowed to cool, the filtrate and the resulting product are evaporated to dryness and loaded into petroleum ether.
    The resulting product is crystallized from a mixture of hexane / cyclohexane (3: 1) and so on. is 98-100 C.
    Similarly obtained: 10-acetamido-5,6-dihydro-1 1 H-dibenzo b, e azepine ™ ° J, 6, n t „pl. 270-272-0; p-ethoxy-5, 6-dihydro-11H-dibenzo Cb, e az-PIN-6-OH; 5-methyl-11-hydroxy-5,6-dihydro-1 1H C b, e 1 azepin-6-one; 11-hydroxy-5, derived from ethanol to give the product, -11 and cr i -
    inn oloo,: 6-dihydro-11 N-dibenzo b, ej azepins m.p. 200-202 P.50 6-he.
    EXAMPLE 2: 5-methyl-10-acetam- dr-5,6-dihydro-11H-dibeiso 11L, e azepin-6, 11-dione.
    2 ml of acetic anhydride is added
    to 2.5 g of 10-amino-5,6-dihydro-11H-di-, 5 convulsively sedative. agents. benzo Lb, e3 azepine-6,11-dione (semi-when introduced into the body through the mouth, the proposed compounds show a higher anticonvulsant activity. They are poured into water, extracted with ethyl ether, the ether is removed under reduced pressure, and the product is crystalline. Biological activity. The proposed compounds are are of interest for pharmacology, especially in connection with their activity as an antichenne from 1-amino-anthraquinone according to the method of Sagolia and Palazzo Car. Chim 83,533,1953) in 50 ml of dioxane. After
    boil for 2 hours under reflux the mixture is evaporated almost to dryness under reduced pressure, then the residue is poured into water, filtered and
    dried to obtain 2 g of crude product.
    2 g of the previously obtained crude product are suspended in 20 ml of N, N-dimethylformamide and 710 mg is added.
    sodium methoxide in 10 ml of methanol.
    After keeping at room temperature for 30 minutes, 2.5 ml of methyl iodide are added and the mixture is kept at room temperature.
    within 24 hours, followed by her. poured into water, the product is filtered off, dried and crystallized from ethanol to obtain a product with so pl. 199-201 ° C.
    167 convulsive sedative. agents.
    Biological activity. The proposed compounds are of interest for pharmacology, especially in connection with their activity as anti-acne.
    ness than valproate sodium. These compounds are characterized by this effect in dosages in which they do not have any side effects characteristic of sodium valproate.
    The mechanism of action of some of these compounds includes the GABA-ergic system by inhibiting nerve transmission associated with
    5. Natrium salt of 2-propiopentane acid.
    6.7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one.
    7.11-Ethoxy-5,6-dihydro-11H-DI-benzo b, e 1 azepin-6-one.
    8.5-Methyl-11-oxy-5,6-dihydro-11H-dibenzo b, e 1 azepin-6-one.
    9.11-Oxy-5,6-dihydro-11H-diben
    this pick. More specifically, dey-yo b, el azepin-6-one. The effect of compounds such as 5-methyl- From the data given in Table 1, 11-ethoxy-5,6-dihydro-11H-dibenzo b, e azepin-6-one and 1O-acetamido-5methyl-5, 6 -dihydro-11H-dibenzo b, e 1
    it can be seen that the products offered have an anticonvulsant effect with respect to MES and / or MET
    azepin-6,11-dione, approximately 10 times f5 or greater than the effect of the compared
    5. Natrium salt of 2-propiopentanoic acid.
    6.7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one.
    7.11-Ethoxy-5,6-dihydro-11H-DI-benzo b, e 1 azepin-6-one.
    8.5-Methyl-11-oxy-5,6-dihydro-11H-dibenzo b, e 1 azepin-6-one.
    9.11-Oxy-5,6-dihydro-11H-dibenzo b, el azepin-6-one. From the data given in table 1,
    it can be seen that the proposed products have an anticonvulsant action with respect to MES and / or MET (with comparable
    stronger than sodium valproate.
    products) (compounds 5 and 6), but when used in active doses, the proposed compounds have almost zero neurotoxicity, unlike
    moreover, this action is also longer.
    The compounds were tested on mice (Table 1) and rats (Table 2) using the method of the 20 compounds to be compared (tested, bam, separately indicated for odenki associated with weed), their antagonism against convulsions caused by MES.
    In experiments on mice and rats, it was found that the LDgp of the proposed compounds of 25 neneny exceeds or equal to 2000 mg / kg (for oral administration. For some of these products, antagonism is expressed even after 30 min
    after the introduction and duration of several parts of the compared products, owls.
    products demonstrate potency and potentiation of haloperidol-induced catalepsy.
    The results of the tests carried out on 35 ZO b, el azepin-6-one of the general formula on microscopes (Swiss albinos) are shown in Table 1.
    The results of tests conducted on rats (albino Spraque-Dowly), JO are given in table 2.
    In addition, as follows from the table. these compounds do not exacerbate catalepsy caused by the use of paloperio dol, i.e. they probably do not have a central anti-dopaminergic activity and, in general, they have a longer effect than the duration of the formula. Derivatives 5, b dihydro-11H-diben
    In the experiments using the following products.
    1.5,11-Dimethyl-11-hydroxy-5,6-dihydro-1 1 H-dibenzo b, eT azepin-6-one. 2. 5-Methyl-11-ethoxy-5,6-dihydro-11-H-dibenzoium, el azepin-6-one.
    3. 10-Acetamido-5-methyl-5,6-dihydro-1 1 H-dibenzo b, eZ azepin-6,11-dione
    A. 1O-Acetamido-5,6-dihydro-11H-dibenzo t b, e azepine-6,11-dione.
    products) (compounds 5 and 6), but when used in active doses, the proposed compounds have almost zero neurotoxicity, unlike
    comparable compounds (test- associated with stretch)
    comparable compounds (test- associated with stretch)
    In addition, as follows from Table 1, these compounds do not exacerbate catalepsy caused by the use of palopiolol, i.e. they probably do not possess central anti-dopaminergic activity and, in general, they have a longer duration of action compared to the duration of deiso b, el azepin-6-one of the general formula
    权利要求:
    Claims (1)
    [1]
    Claims of the Invention Derivatives 5, b dihydro-11H-diben Ri
    where RJ is hydrogen or methyl; when Rg and R are hydrogen, it is hydroxy or ethoxy;
    R ozn
    when Rj, methyl, and R - hydrogen, .. R, means hydroxy group;
    when R is NHCOCH, R, j and R. together represent oxygen;
    with anticonvulsant activity.
    Dose, mg / kg body
    Protection,%, with MES through
    0.5 h
    4 h
    Protection,%, with MET in 0.5 h
    100
    50
    25
    200
    300
    600
    2.5
    five
    67,100
    50
    33
    100
    14
    48
    75 67
    Oh oh
    ten
    100 50 83 17 83
    100
     The test results after 1 h instead of 0.5 h.
    Table 2
    Pro- Dose Protection,%, with MET through
    Duct mg / kg / j1
    2 hours 5 hours 8 hours
    210071100100
    710079100100
    810010079100
    91007110086
    Compiled by I. Bocharova Editor. S.PekarTehred V.Kadar Corrector I.Erdeyi
    Order 1191/26 Circulation 372 Subscription
    VNIIPI USSR State Committee
    for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab., 4/5
    Production and printing company, Uzhgorod, st. Project, 4
    Table 1
    e%
    Strengthening of catalepsy caused by haloperidol after 0.5 h
    3
    3
    15
    65 45 65
    类似技术:
    公开号 | 公开日 | 专利标题
    US4098786A|1978-07-04|Benzodiazepin derivatives
    DE60016566T2|2005-12-15|TRIAZOLOPYRIDAZINE DERIVATIVES AS LIGANDS FOR GABA RECEPTORS
    EP0129128A2|1984-12-27|2-Pyrimidinyl-1-piperazine derivatives, process for their preparation and medicines containing them
    DE2609486C2|1988-11-03|
    EP0370236B1|1991-12-27|Indolocarbazole derivatives, processes for their preparation and their use as medicaments
    EP0075855B1|1985-12-27|7-bromo-5-|-1h-2,3-dihydro-1,4-benzodiazepines, method for their preparation, intermediates and pharmaceutical compositions containing them
    SU1301830A1|1987-04-07|Derivatives of 5,6-11h-dibenzo|-azepine-6-on possessing anticonvulsive activity
    BG64283B1|2004-08-31|DERIVATIVES OF 4-OXO-3,5-DIHYDRO-4H-PYRIDAZINO[4,5-b]INDOLE-1-ACETAMIDE, THEIR PREPARATION AND APPLICATION IN THERAPY
    DE3008904A1|1980-09-18|1-MERCAPTOACYLDIHYDROPYRAZOL-5-CARBONIC ACID DERIVATIVES AND THEIR SALTS WITH BASES, METHODS FOR THE PRODUCTION THEREOF AND THEIR USE IN THE TREATMENT OF HYPERTENSION
    DE1695698A1|1971-04-29|Novel benzothiazepine compounds and processes for their preparation
    SU936815A3|1982-06-15|Process for producing 4,1-benzoxazepines or their thia-analogs
    US3947408A|1976-03-30|Pyrrolo-benzodiazepines, method of preparation and method of use
    DE1695161A1|1970-12-10|Process for the preparation of benzodiazepine derivatives
    SK37394A3|1994-12-07|1,8-benzonaphthyridine derivatives, method of their preparation and compositions containing these derivatives
    EP0102602B1|1990-03-21|1,7-dihydro-pyrrolo|diazepin-2|-one derivatives, a process for preparing them and their use as anticonvulsant and antianxiety agents
    DE2712309A1|1977-11-17|AS-TRIAZINOBENZODIAZEPIN-1-ONE, BENZODIAZEPINE, THE METHOD OF MANUFACTURING IT AND THE MEDICINAL PRODUCTS CONTAINING THESE
    CA1194474A|1985-10-01|[1,2]-fused 1,4-benzodiazepine compounds, process for their preparation and compositions containingthem
    US3985732A|1976-10-12|1,2,3,11A-Tetrahydro-10-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5,11|-diones
    GB1596170A|1981-08-19|1,2,3,4,4a,10b-hexahydro-benz|isouqinolines
    US3947417A|1976-03-30|Triazolobenzodiazepine derivatives
    EP0118565A1|1984-09-19|1,4-methano-2-benzazepine derivatives
    EP0299345A2|1989-01-18|Dihydro-1,4-oxazino|quinolines, a process and intermediates for the preparation thereof and their use as medicaments
    SU1473710A3|1989-04-15|Method of producing thickoketene derivatives of piperidine or their acid-additive salts
    EP0066762B1|1985-11-21|1,7-dihydro-pyrrolo|diazepin-2|-one derivatives
    US3968230A|1976-07-06|Compositions containing benzodiazepindiones and method of use
    同族专利:
    公开号 | 公开日
    EP0089322A1|1983-09-21|
    PL252303A1|1985-12-17|
    YU63083A|1989-08-31|
    DE3217236C2|1994-04-14|
    ES520577A0|1984-10-01|
    AU562360B2|1987-06-11|
    EP0089322B1|1987-06-16|
    GB2116539A|1983-09-28|
    JPS58180471A|1983-10-21|
    JPH0480027B2|1992-12-17|
    DK158722B|1990-07-09|
    PL241018A1|1985-07-16|
    PT76372A|1983-04-01|
    GR78455B|1984-09-27|
    IT1207417B|1989-05-17|
    PT76372B|1985-12-05|
    DK86483A|1983-09-16|
    DK86483D0|1983-02-24|
    IT8209356D0|1982-03-15|
    HU189671B|1986-07-28|
    NO830877L|1983-09-16|
    CA1226282A|1987-09-01|
    MX156434A|1988-08-22|
    ZA831473B|1983-11-30|
    AU1243183A|1983-09-22|
    PL140327B1|1987-04-30|
    ES8407479A1|1984-10-01|
    IE54859B1|1990-02-28|
    DE3217236A1|1983-09-15|
    DD209452A5|1984-05-09|
    IE830542L|1983-09-15|
    AT27816T|1987-07-15|
    GB2116539B|1986-04-30|
    US4551451A|1985-11-05|
    DK158722C|1990-12-03|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3084155A|1963-04-02|Derivatives of dibenzo |
    GB972082A|1961-06-07|1964-10-07|Koninklijke Pharma Fab Nv|Dihydrodibenzazepinones|
    GB1062573A|1963-10-29|1967-03-22|Colgate Palmolive Co|Morphanthridine derivatives,and processes of preparing the same|
    DE1545856A1|1965-09-10|1969-11-27|Bayer Ag|Process for the preparation of basic substituted derivatives of 5,6-dihydro-dibenz- [b, e] -azepine-6,11-dione-11-oxime|
    DE1568217A1|1966-12-16|1970-01-02|Boehringer Mannheim Gmbh|Process for the preparation of tricyclic derivatives of acetamide|
    JPS4934996B1|1969-05-06|1974-09-19|
    CH569731A5|1972-04-04|1975-11-28|Wander Ag Dr A|
    CH577975A5|1972-10-20|1976-07-30|Sandoz Ag|
    DE2361467A1|1973-12-10|1975-06-19|Thiemann Chem Pharm Fab|1-AMINO-5,6-DIHYDRO-MORPHANTHRIDINE 5,11-DIONE COMPOUNDS AND MEDICINAL PRODUCTS CONTAINING SUCH COMPOUNDS|
    CH601287A5|1975-08-06|1978-07-14|Sandoz Ag|
    DE2918778A1|1979-05-10|1980-11-20|Basf Ag|6-SUBSTITUTED 11-ALKYLENE MORPHANTRIDINE|
    DE2918832A1|1979-05-10|1980-11-20|Basf Ag|5,6-DIHYDRO-11-ALKYLENE-MORPHANTRIDINE-6-ONE|
    DE3113094A1|1981-04-01|1982-10-21|Basf Ag, 6700 Ludwigshafen|5,6-DIHYDRO-11-ALKYLENE-MORPHANTRIDIN-6-ONE, THEIR PRODUCTION AND MEDICINAL PRODUCTS CONTAINING THEM|JPH0665664B2|1985-01-18|1994-08-24|大塚製薬株式会社|Morphoanthridine derivative|
    IT1233715B|1989-07-14|1992-04-14|Menarini Farma Ind|USE IN THERAPY OF 10-AMINO-5,6 DIIDRO-11H = DIBENZOAZEPINA-6,11-DIONE AND DERIVATIVES, WHICH USEFUL DRUGS FOR THE TREATMENT OF URINARY INCONTINENCE|
    DE4138853A1|1991-11-27|1993-06-03|Bayer Ag|5,6-DIHYDRO-DIBENZAZEPINE-6,11-DION-11-OXIME|
    WO1993020695A1|1992-04-14|1993-10-28|Sphinx Pharmaceuticals Corporation|Polyhydroxylated dibenzazepines as protein kinase c inhibitors|
    JP2001514253A|1997-09-04|2001-09-11|スミスクライン・ビーチャム・コーポレイション|Integrin receptor antagonist|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    IT8209356A|IT1207417B|1982-03-15|1982-03-15|AZEPINA-6-ONE WITH ACTIVITIES TRICYCLIC COMPOUNDS DERIVED FROM PHARMACOLOGICAL, AND PROCEDURES OF 5,6-DIHYDRO-11H-DIBENZORELATED MANUFACTURE|
    [返回顶部]