• 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 invention relates to heterocyclic compounds and in particular to the preparation of substituted 2-fenilgeksagidro-1,2,4 - triazin-3,5-diones of formula wherein R @ 1, phenoxy, mono- or di-substituted alkylthio, alkylsulfinyl, alkylsulfonyl, or C 1 -C 6 alkylgroup, or phenylthio radical, substituted by chlorine R 2 is a lower C 1 -C 6 alkyl or benzoyl radical having coccidiostatic activity. The purpose of the invention is to develop a method for producing more active compounds. Obtaining the target compounds are alkylation or acylation, respectively, IN - unsubstituted 2-phenylhexahydro-1,2,4-triazin-3,5-dione. 2 tab.
    公开号:SU1517760A3
    申请号:SU864028140
    申请日:1986-09-05
    公开日:1989-10-23
    发明作者:Реснер Манфред；Ретер Вольфганг
    申请人:Хехст Аг (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a method for producing substituted 2-phenylhexa-hydro-1,2,4-triazin-3, 5-diones of the general formula
    where P, is phenoxy, single or double alkylthio, alkylsulfonyl, alkylsulfonyl or
    A C, -C-alkyl group, or a phenylthio radical substituted by chlorine,
    R is a lower C —C-alkyl or benzoyl radical,
    with coccidiostatic activity.
    The purpose of the invention is to develop a method for obtaining new 1,2,4-triazine derivatives, which are more active and stable than the known structural analogues of a similar effect.
    ate

    ot

    cm
    Example 1.2-3,5-Dichloro-β-D- (4-methylsulphonylphenoxy) phenyl 3-1-methyl hexahydro-1,2,4-triaine-3, 5-dione. .
    1 g of 5-dichloro-4- (A-methylsulfo-nylphenoxy) phenyl-hexahydro-1, 2,4-triazine-3,5-dione is heated in 1 O ml of N-methyl pyrrolidone with 10 ml of methyl iodide for 4 and then, after the addition of another 10 ml of methyl iodide, another 3 hours to 140–160 ° C. After cooling, the reaction mixture was rusted with water, resulting in the release of a slowly hardening oily liquid, which was recrystallized from methanol with the addition of activated carbon Melting point of the obtained product .223 s.
    NMR spectrum (270 mG c, DMSO-dg, tetramethylsilane as an internal standard) S, ppm: -N -CH, 2.7 (s). -N -SI 3.9 (s).
    PRI mery 2-5. In a similar way, using the appropriately substituted hexahydroCh, 2,4-triazine-3,5-diones as the starting compounds, by means of alkylation, the compounds of the formula I additionally alkylated to the 1st position, shown in Table 1, are obtained by alkylation.
    Example 6. 1-Lcetyl-2-3, 5-dichloro-4- (4-methylsulfonylphenoxy) phenyl-hexahydro-1,2,4-triazin-3, 5-dion.
    2 g of 5-dichloro-4- (4-methylsulfonylphenoxy) phenyl 3-hexahydro-1, 2, 4-triazine-3, 5-dione are suspended in 10 MP of acetic anhydride and to the resulting suspension is added dropwise 1 ml of concentrated sulfuric acid. The sauce is then slightly heated and the starting material goes into solution. The solution is stirred for 2-3 hours at room temperature and then water is added to it with stirring.
    The resulting product is filtered off with suction, washed with water, dried and recrystallized from a small amount of glacial acetic acid, m.p. 267 ° C. NMR spectrum (0 MHz, DMSO-dg, | tetra methylsilane as an internal standard) S, ppm: -N -COCH, 2.1 (s), -N -CPi 4,6 Oirpky d, LP signal).
    J
    Q 5
    0
    5 jq 35
    before . DZ
    P
    Example 7. In a similar way, using the 2-substituted hexahydro-1, 2,4-triazine-3,5-dione as the starting product, by acylation, a compound of formula 1 additionally acylated at position 1 is obtained
    where R, - 4-CFjS-C6H40 -,
    i.p.
    Example 8. 2-t3,5-Dichloro-4- (4-methylsulfonylphenoxy) phenyl - -hexahydro-J 2 4-triazine-3,5-dione.
    10 g of 2- (3,5-dichloro-4-ethylsul-Fonylphenoxy) phenyl 3-1,2,4-triazine-3,5- (2H, 4H) -dione is dissolved in 150 ml of hot ice of acetic acid, mixed the resulting solution with 10 g of zinc dust and boil for 2 hours under reflux. The hot reaction mixture is then filtered and the residue containing zinc is boiled three times with 50 ml of glacial acetic acid. The combined solutions are evaporated under reduced pressure, mixed with water, and a precipitate is sucked off. The solid residue is recrystallized from methanol with the addition of activated carbon, so pl. 240 C (with decomposition),
    NMR spectrum (60 MHz, / MCO-dg, TeT- ramethylsilane D as an internal standard) S, ppm: -N H-SNg. 6.53 (triplet, Hz), to n-CH 3.7 (c, I 8 Hz), 3.2 Co.
    Example 11, 5-Dichloro-4- (4-methylthiophenoxy) phenyl-hexahydro-1, 2,4-triazine-3, 5-dione.
    20 g, 5-dichloro-4- (4-methylthiophenoxy) -phenyl -, 2,4-triazin-3, 5- - (2H, 4H) -dione is dissolved in 200 ml of hot glacial acetic acid, added 25 g of tin chloride with 2 molecules of water of crystallization and 100 ml of concentrated hydrochloric acid are added to the resulting solution and the mixture is boiled for 4 hours under reflux. After cooling the reaction mixture, the precipitated product is precipitated, washed with water until neutral and recrystallized from 2-methoxyethanol, m.p. 239 ° C.
    NMR spectrum (60 MHz, DMSO-dg, tetramethylsilane as an internal standard) S, ppm: -N H-CHt
    (6.53 triplet, I 8 Hz), -N H-CH 3.7 (c, I 8 Hz), CHjS - 2.43 (s),
    Coccidiostatic effect on Eimeria tenella.
    Chickens (4–50 pieces / dose) weighing 35–40 g were orally infected with the Eimeria tenella gastric probe. The control group (8–30 qt of t) received the same infectious dose as the group that was given medication (dose of 3.5–10 societies per chicken).
    The test preparations of formula (I) were mixed in a mixer with a feed of usual composition. The feed prepared in this way was given chickens there over the course of the whole experiment in sufficient quantity. For control, the behavior of ordinary chickens (8–50), i.e. uninfected chickens in which feed but drugs were injected. The duration of the experiment was approximately 10 days.
    In the case of compounds according to examples 7 at a dosage of 100 ppm. (in terms of feed) no signs of cocciosis were observed in chickens that received feed with medication (bloody feces, high social status, intestinal upset).
    Conventional feedstuffs can be used as carriers. The active substance of the formula (I) is in this case introduced into the feed in an amount of 0.1-300, preferably 0.5-50 ppm. Compared with the known aralkyl-hexahydrotriazines, which are active only when they are in feed or drinking water, 70-200 ppm, the proposed compounds of formula (I) and their salts are active at the indicated low concentrations and at the same time time is well tolerated by animals.
    The dosages at which the treated plants survive without any signs of coccidosis are shown in Table 2.
    5177606
    In addition, the compounds of formula (I) are highly stable, in particular under the conditions of action on light and air.
    Since the proposed compounds for the control of coccyodia are administered as mixtures with feed, the stability of these compounds in mixtures is of great importance, especially when stored in open form and in daylight.
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    5 Method for Producing Substituted 2-Phenyl Hexahydro-1, 2,4-Triazin-3,5-Diones of the General Formula
    20
    C1
    25
    0
    Where
    R is phenoxy, mono- or doubly substituted alkylthio, alkylsulphin-, alkyl. sulfonyl- or C -Cg-atnkilgrytIy, or phenylthio-radical, substituted by chlorine, is lower C, -C-alkyl or benzoyl radical,
    5 characterized in that, a compound of the general formula is alkliruyut or acylated
    R
    40
    45
    C1
    where R, has the indicated meanings,
    Table 1
    Example R, RZ Melting Point,
    , S-CgH ol-CH, 204
    3 4-CH SO-CgH o3-CH, 228
    , -4 - CHjS-C4l, 0 CH, 226
    5t -Cl-CglV S -CHj. 195
    table 2
    Active Connection by
    dosage, ppm example
    2.51, 2, 5
    57
    204
    503
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    同族专利:
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE2149645A1|1970-10-07|1972-09-14|Pfizer|2-Phenyl-as-triazine-3.5- -diones and the use of these compounds for combating coccidiosis|
    GB1448696A|1973-05-29|1976-09-08|Pfizer|2-phqnyl-astriazine-3,4-2h,4h-diones|
    DE2722537A1|1977-05-18|1978-11-23|Hoechst Ag|SUBSTITUTED 2-PHENYL-1,2,4-TRIAZINE-3,5- -DIONE, METHOD FOR THE PRODUCTION THEREOF AND THEIR CONTAINING COCCIDIOSTATIC AGENTS|
    IL62151A|1981-02-18|1984-10-31|Abic B M|Hexahydro-1,2,4-triazine-3,5-dione derivatives,their preparation and feed compositions,drinking water and pharmaceutical compositions containing said derivatives|
    DE3408924A1|1984-03-12|1985-09-26|Hoechst Ag, 6230 Frankfurt|SUBSTITUTED 2-PHENYL-HEXAHYDRO-1,2,4-TRIAZINE-3,5-DIONE, METHOD FOR THE PRODUCTION THEREOF, MEANS CONTAINING IT AND THEIR USE|
    CA1244024A|1984-08-01|1988-11-01|Gustaaf M. Boeckx|.alpha.- ARYL-4--YL)BENZENEACETONITRILES|BR8602556A|1984-06-12|1987-02-03|Fmc Corp|HERBICIDE COMPOUND; HERBICIDE COMPOSITION AND PROCESS TO CONTROL THE GROWTH OF UNWANTED PLANTS|
    DE3814323A1|1988-04-28|1989-11-09|Hoechst Ag|WATER-SOLUBLE PREPARATIONS BY COCCIDIOSTATICA|
    GB8810185D0|1988-04-29|1988-06-02|Glaxo Group Ltd|Chemical compounds|
    CN1044905A|1989-02-16|1990-08-29|赫彻斯特股份公司|Fish and entomophagous parasite worm antagonist|
    CA2012004A1|1989-03-15|1990-09-15|Frank Ellis|Chemical compounds|
    DE4030042A1|1990-05-17|1991-11-21|Bayer Ag|USE OF SUBSTITUTED 1,2,4-TRIAZINDIONES|
    EP0476439A1|1990-09-18|1992-03-25|Bayer Ag|Substituted 1,2,4-triazindiones, method for their preparation, intermdiates for it and their use|
    DE4120138A1|1991-06-19|1992-12-24|Bayer Ag|SUBSTITUTED HEXAHYDRO-1,2,4-TRIAZINDIONES, METHOD FOR THE PRODUCTION THEREOF, INTERMEDIATE PRODUCTS THEREOF AND THEIR USE|
    US5994355A|1993-10-15|1999-11-30|Takeda Chemical Industries, Ltd.|1, 2, 4-Triazin-3-one derivatives, production and use thereof|
    US5436243A|1993-11-17|1995-07-25|Research Triangle Institute Duke University|Aminoanthraquinone derivatives to combat multidrug resistance|
    US5985875A|1996-08-30|1999-11-16|Takeda Chemical Industries, Ltd.|1,2,4-triazine-3, 5-dione derivatives, their production and use thereof|
    US6294536B1|1997-08-29|2001-09-25|Takeda Schering-Plough Animal Health K.K.|Triazine derivatives, their production and use|
    DK2385938T3|2009-01-12|2015-04-27|Pfizer Ltd|Sulfonamidderivater|
    EP2590972B1|2010-07-09|2015-01-21|Pfizer Limited|N-sulfonylbenzamides as inhibitors of voltage-gated sodium channels|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19853531919|DE3531919A1|1985-09-07|1985-09-07|SUBSTITUTED 2-PHENYL-HEXAHYDRO-1,2,4-TRIAZINE-3,5-DIONE, METHOD FOR THE PRODUCTION THEREOF, MEANS CONTAINING IT AND THEIR USE|
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