• 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:
    Hydrazine derivatives corresponding to the formula: <IMAGE> in which: X is a C1-C4 alkyl, the trifluoromethyl group or a halogen chosen from chlorine (in ortho or meta position), fluorine or bromine, R1 is a C1-C4 alkyl group; R2 denotes: - hydrogen, - a C3-C4 branched alkyl group, - a C1-C4 alkoxy, preferably ethoxy group, - a group of formula CR3R4R5 in which: R3 denotes an OR6, SR6 or NR7R8 group in which: R6 is hydrogen or a C1-C4 alkyl, R7 and R8 denote hydrogen, a C1-C4 alkyl group, a C2-C4 acyl group, a benzoyl group or else R7 and R8 together with the nitrogen atom to which they are bonded form a 5- or 6-membered heterocyclic group; R4 and R5 are identical and denote hydrogen or a C1-C4 alkyl group or else R4 is hydrogen and R5 denotes either a C1-C4 alkyl group optionally substituted by a hydroxyl group or a phenyl group, or else R3, R4 and R5 together with the carbon atom to which they are bonded form an amido group; - a phenyl group optionally substituted by a hydroxyl group; - a 5- or 6-membered heterocyclic group and the pharmaceutically acceptable salts of the said compounds.
    公开号:SU1672929A3
    申请号:SU884355707
    申请日:1988-05-13
    公开日:1991-08-23
    发明作者:Миок Марсель；Бинэ Пьер；Галон Эрве
    申请人:Ле Лаборатуар Мерам (Фирма)；
    IPC主号:
    专利说明:

    cuome. Hydrazide is isolated from M-acetyl-30 compounds:
    n n
    X / CH2-NH,
    with L
    4 HC1
    U sintraperitoneally 71 mg / kg LD5OpeR ° Ralno And mg / kg
    The antihypertensive activity of these two compounds, respectively, appears in doses of: 6.25 mg / kg orally. Gili 1 / 18e from 1.56 mg / kg orally 1/88 from.
    In contrast, in the rat, the antihypertensive activity of the HP of the compound of the invention indicated above is 2 mg / kg orally, or 1 / 485e of LD5
    Pharmacologists
    A. At the mouse.
    The molecule 1- (2-hydroxyisobutyroyl) -2- (1-o-chlorophenyl-1-ethylidene) -hydrazine: reduces the spontaneous mobility of the mouse (mg / kg intraperitoneal-HO) J antagonizes amphetamine hyper motility at 12.5 mg / kg intra- peritoneal; reduces the activity of the study (mg / kg intraper-C1 N
    0
    ABOUT
    LD to Intrapuritally 105 mg / kg LDbo orally 138 mg / kg
    toneally); has the consequence of motor non-coordination and hypothermia only with a strong dose (50 mg / kg) intraperitoneally); possesses analgesic activity; weak in the test with R.V.O., clearer with a heated plate (mg / kg intraperitoneally); strengthens sleep with barbiturates, starting with a dose of 12.5 mg / kg intraperitoneally.
    I
    The product is inactive in tests with yohimbin and apomorphine, and in a small degree of clarity modifies the test with oxo-tremorin in a strong dose.
    B. In the rat.
    1- (2-hydroxyisobutyroyl) -2- (1-o-chlorophenyl-1-ethylidene) -hydrazine is anti-inflammatory in the test with
    hypertonic properties, baths with sedatives, anal and anti-inflammatory, and at the same time have silence.
    权利要求:
    Claims (1)
    [1]
    Formula isobre Method of obtaining azin general formula
    17
    1672929
    ragenin (mg / kg intraperitoneally).
    In the cardiovascular plan, the molecule significantly increases the rhythm of the heart of a normal rat without modifying the blood pressure at a dose of 50 mg / kg intraperitoneally and significantly reduces the blood pressure of the spontaneously hypertensive gland (SHR) with a single administration, starting from very low doses to sedative and toxic doses (ED 1: 9 mg / kg intraperitoneally).
    Experiments on the introduction of oral sub- | with where X - o-C1 or m-Br; they confirm antihypertensive dey-R-C, -C4-alkyl; product: with the only introduction - R4 - group - CR3R4Ry; Dosing (mg / kg) with repeated administration after 5 days at a dose of 1.5 mg / kg.
    The frequency of contractions of the heart in the animal – jQ nugget does not change significantly under these experimental conditions.
    Pharmacological profile of 1- (2- hydroxyisobutyroyl) -2- (1-o-chlorophenyl-150
    Cnncn o
    R5 is the group ORg, SRg and
    R6 is hydrogen or R and RJ are the same, hydrogen is a C-C4 alkyl group or R. C, kil, which is substituted by an hydroxy group or Rj together with a carbon atom,
    R6 is hydrogen or C -C alkyl; R and RJ- are the same, hydrogen or C-C4 alkyl group or R. hydrogen and C, kil, which may be substituted by hydroxy group or Rj, R f and Rff together with the carbon atom to which
    thirty
    35
    ethylidene-hydrazine is co-25, they are attached, they form an amide group, such an antihypertonic substance, which also has sedative, anti-inflammatory and analgesic properties, but at doses higher than the current required for antihypertensive activity.
    The antihypertensive activity (SHR) of other compounds of the invention was also determined and compared to that of the known compounds (R) H) or alkyl compounds (R, -alkyl), which differ from the proposed compounds in their structural characteristics (X and P).
    In tab. 2 compounds are identified by an example number of their preparation and then each is followed by a compound or compounds used as a comparison, which have the same number, labeled with the index a, b.
    The results show that the compounds of formula (I) have antihypertensive activity.
    Thus, the proposed method allows to obtain compounds of general
    40
    a pu, or pharmaceutically compatible salts, characterized in that the hydrazine hydrate is reacted with an ester of the general formula
    R2-COOR,
    where R is lower alkyl;
    Rg has the indicated meanings, followed by the reaction of the resulting acylhydrazine with the general formula
    HN-NH-C-R,
    2 q 2 O
    where R4 is as defined, with aryl alkyl ketone of the general formula
    South
    Ј-R, O
    50
    where X and R have the indicated meanings, followed by isolation of the target product or translation into a pharmaceutically compatible salt.
    Formulas (I) that exhibit anti-18
    hypertonic properties combined with sedative, analgesic and anti-inflammatory properties, and at the same time have low toxicity.
    The invention The method of producing hydro-azine derivatives of the general formula
    .Q
    C N-N-CR3
    n o
    where X is o-C1 or m-Br; R is C, -C4-alkyl; R4 - group - CR3R4Ry;
    R5 is the group ORg, SRg or
    R6 is hydrogen or C -C alkyl; R and RJ- are the same, hydrogen or C-C4 alkyl group or R. hydrogen and C, kil, which may be substituted by hydroxy group or Rj, R f and Rff together with the carbon atom to which
    they are attached to form amidogroup
    they are attached to form amido group
    a pu, or pharmaceutically compatible salts, characterized in that the hydrazine hydrate is reacted with an ester of the general formula
    R2-COOR,
    where R is lower alkyl;
    Rg has the indicated meanings, followed by the reaction of the resulting acylhydrazine with the general formula
    HN-NH-C-R,
    2 q 2 O
    where R4 is as defined, with aryl alkyl ketone of the general formula
    South
    Ј-R, O
    where X and R have the indicated meanings, followed by isolation of the target product or translation into a pharmaceutically compatible salt.
    21
    1672929
    22 Continuation of table 1
    table 2
    Inactive 490 I.P,
    150 I.P.
    660 I.P.
    433 I.P,
    227 I.P.

    240 I.P. 300
    583 I0P. 200 I.P. 477 I.P. 143 I.P. 360 I.P. 400 I.P. 400 I.P. 400 I.P.
    2J5
    O.R. - oral
    1672929
    26 Continuation of table 2
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    同族专利:
    公开号 | 公开日
    TNSN88045A1|1990-07-10|
    FR2615188A1|1988-11-18|
    EP0294258A1|1988-12-07|
    CN88102858A|1988-12-14|
    DK265788D0|1988-05-13|
    NZ224617A|1991-02-26|
    FI882267A0|1988-05-13|
    FR2615188B1|1989-11-17|
    AU1613488A|1988-11-17|
    ZA883301B|1988-11-14|
    JPS6463561A|1989-03-09|
    NO882030L|1988-11-15|
    NO882030D0|1988-05-10|
    KR880013881A|1988-12-22|
    FI882267A|1988-11-15|
    DK265788A|1988-11-15|
    OA08734A|1989-03-31|
    MA21273A1|1988-12-31|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3654294A|1967-07-27|1972-04-04|R & L Molecular Research Ltd|Certain isothiazolylacetylenemercaptides|
    US3708591A|1970-03-18|1973-01-02|Rohm & Haas|Certain formylhydrazones used as aphicides|
    US3753680A|1970-05-14|1973-08-21|Stauffer Chemical Co|Arylidene semicarbazones and their utility as herbicides|
    DD107255A1|1973-06-14|1974-07-20|
    US3867425A|1974-01-09|1975-02-18|American Cyanamid Co|Substituted benzyl carbazic acid esters|
    JPS5459326A|1977-10-18|1979-05-12|Nissan Chem Ind Ltd|Insecticide|
    FR2457288A2|1978-09-12|1980-12-19|Rhone Poulenc Agrochimie|NOVEL OXADIAZOLINE-1,3,4-ONE-5 DERIVATIVES, THEIR PREPARATION AND INSECTICIDE COMPOSITIONS CONTAINING THEM|
    HU190795B|1982-05-04|1986-11-28|Egyt Gyogyszervegyeszeti Gyar,Hu|Process for producing carbazinic derivatives and compositions containing them for increasing weight yield|
    DE3624349A1|1986-07-17|1988-01-28|Schering Ag|SUBSTITUTED HYDRAZONE, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS A PEST CONTROL|US5623072A|1994-10-11|1997-04-22|Monsanto Company|3-phenylpyridazines, herbicidal compositions and uses thereof|
    KR100736838B1|2001-05-03|2007-07-10|씨제이 주식회사|Novel catechol N-methylhydrazide derivatives and process for preparation thereof|
    KR100866285B1|2002-09-06|2008-10-31|씨제이제일제당 |Novel catechol hydrazide derivatives and process for preparation thereof|
    DE10346913A1|2003-10-09|2005-05-04|Merck Patent Gmbh|acylhydrazone|
    CN100355748C|2004-09-20|2007-12-19|中国人民解放军军事医学科学院毒物药物研究所|Aromatic hydrazide kind compound and its use in preparation of immune inhibitor|
    JP2010518008A|2007-02-02|2010-05-27|レッドポイントバイオコーポレイション|TRPM5 inhibitors that modulate insulin and GLP-1 release|
    JP5759893B2|2008-08-05|2015-08-05|オメロス コーポレーション|PDE10 inhibitors and related compositions and methods|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    FR8706801A|FR2615188B1|1987-05-14|1987-05-14|HYDRAZINE DERIVATIVES, PROCESS FOR OBTAINING SAME AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME|
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