• 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:
    Novel quinoxaline-di-N-oxide derivatives of the formula <IMAGE> are disclosed, wherein R represents a hydrogen atom, an alkyl group of 1 to 12 carbon atoms, a cyanoalkyl group containing 1 to 4 carbon atoms in the alkyl moiety or an allyl group, and A represents a straight-chain or branched alkylene bridge member containing 1 to 4 carbon atoms.
    公开号:SU890961A3
    申请号:SU772437355
    申请日:1977-01-10
    公开日:1981-12-15
    发明作者:ШМИД Вольфганг；Баслер Вальтер；Буркхардт Урс
    申请人:Циба-Гейги Аг (Фирма)；
    IPC主号:
    专利说明:

    (54) ANIMAL GROWTH AGENT
    This invention relates to growth stimulating agents for domestic and agricultural animals.
    A known agent l is for stimulating the growth of animals Bayo-n-ox, manufactured by Bayer and the following structural formula
    ABOUT
    t
    CO 1TN-С% -SE -OH
    eleven
    nri
    Hhh: #
     If CHj

    about
    However, the known tool is not effective enough.
    The purpose of the invention is to increase the efficiency of growth stimulation.
    To achieve this goal, the growth stimulating agent contains, as an active ingredient, quinoxalin di-H-oxide derivatives of the general formula
    where R is hydrogen, alkyl with 1-12 carbon atoms, cyanoalkyl with 1-4 carbon atoms in the alkyl part or alkyl, and A is a straight line or branched chain alkyl link with 1-4 carbon atoms in an amount of 0.001-10.0 wt. %
    In addition, the growth stimulating substance as a carrier contains kaolin, lime, alumina (alumina), ground shells of Bolus alba couches, aerosil, starch and lactose. ,
    ; Example. Compounds of formula T can be obtained according to the following scheme: base (amine)
    25
    V SKL-O S% CO - to - A - CH -
    about
     Yy
    . f sn,
    “3 o
    The synthesis is carried out in organic solvents that are inert with respect to components, such as alcohols, acetonitrile, dimethylformamide, tetrahydrofuran, dioxane, benzene, then luol or methyl cellosolve (ethylene glycol monomethyl ether), and preferably in methanol, when the reaction medium is as far as possible anhydrous.
    The reaction is carried out at 0-70 ° C, preferably at 30-50 ° C.
    The method is carried out in the presence of bases, which are amines, preferably primary, and also ammonia.
    The most optimal way to synthesize compounds of the formula T is that the acetic acetic acid amide of the formula FII in s1tu, which is obtained as a starting material at the preliminary stage of the reaction of aminonitrile with diketene, is reacted with a benzofuroxane of the formula I to obtain the desired compound of formula 1.
    Alternatively, the synthesis is carried out according to the following scheme:
    I 11 FCHONASO-SIP-SOOY -
    . N
    i i
    NN-A-SK
    about
    eo-w:
    x I A-SK
    . - w,
    about
    where R is C —C.-alkyl.
    The starting materials of the formula It for the preparation of the proposed compounds of the formula I, partially new, are partially known. They can be obtained from amines and diketenov scheme
    CHQ.
    I'm XX
    .0R
    H-N-A-ON-V
    -CHjCO-CHrj-CO-N -A1SC)
    The preparation of the starting compounds is carried out at a temperature from -15 ° C to, preferably from to 0 ° C. The reaction is carried out in organic solvents, in which alcohols such as ethanol or isopropanol and preferably methanol are used. The reaction should be carried out in an anhydrous environment.
    In other methods, the synthesis is carried out according to the scheme

    SN-UNPsOO ChnM-A-CN R
    (H)
    .
     - -oH t: ocH co-N-A-CH
    To obtain growth stimulating agents, the compound of formula I is mixed with an inert carrier, for example kaolin, lime, bauxite, ground shells of bolus shells, aerosil, starch or lactose. Growth stimulants may also contain some part of the normal feed for the corresponding animal species for which it is intended to be fed.
    The content of the compound of the formula D in the growth-promoting agent is 0.001-10.0% by weight, preferably 0.001-1.2% by weight.
    Growth-stimulating agents are usually admixed to, usually, in feed or in swill for domestic or agricultural animals, such as pigs, birds, or ruminants in such quantities as ready-made feed or swill. contain a compound of formula G in the amount of 1-500 h / ml. The following compounds are particularly suitable for the preparation of growth-promoting agents: 1,4-dioxido-3-methyl-quinoxaline (2) -N- (2-cyanoethyl) -amide carboxylic acid; 5 1,4-dioxido-3-methyl-quinox. bm (2) -M- (cyanomethyl) -amide of carbonic acid; I, 4-dioxido-3-metshl-1-xynoxaline (2) -N- (1-cyano-isopropyl-carboxylic acid amide; 1,4-dioxy to-3-methyl-xinoxaline (2) -N- (3-cyan progr) carboxylic acid-amide; 1,4-dioxido-3-metsht-quinoxaline ((4-cyanobutip) -amide carboxylic acid. EXAMPLE 2. By mixing. a compound of the formula D (1,4-dioxydio amide) 3-methylquinoxaline (2) -N- (2 -cyanoethyl) carboxylic acid) with Bolus alba and standard food, growth-enhancing agents of the following composition are obtained, by weight: a) Compound of formula T 0.15 Bolus alba 49.85 Standard food for homemade pigs, hogs or ruminants 150.0 b) Compound of formula I 0.30 Bolus alba44.70 Silicic acid 5.0 Standard feed for poultry, sweetened or ruminants 150.0 c) Compound of formula D 1.2 Bolus alba43.8 Silicic acid 5.0 Standard feed for poultry, pigs or ruminants 150.0 g ) The compound of formula I 2,4
     Numeric data in the form of averages. 1 kg of feed consumed per 1 kg gain weight. 14 Solus alba47,6 Standard feed for poultry, pigs or chewing gum 150.0 In preparing the proposed stimulating growth agents, the compound of the formula D is either directly mixed into the carrier or in the form of a solution, for example, in chloroform, nano-CNG on carriers. Then crushed to the desired particle size, for example, 5-10 microns. Thus, the resulting stimuli are. The growth-inhibiting agents are then processed to prepare finished feeds from 5800 parts by weight. standard feed or swill to obtain 6000 weight.h. finished feed or swill. Feed mixtures containing growth-stimulating agents which contain a) 25 ppm are obtained; b) 50 ppm; 200 ppm: g) 400 ppm Compounds of formula G. Example 3. To prove growth-stimulating activity, a group of 8 young pigs (4 each) were fed for 28 days with normal, containing 17.6% of crude protein and 3.4% of crude fiber with addition of 50 ppm amide I, 4-dioxido-3-mecIhioio cancanin (2) -N- (2-cyanostil) -carboxylic acid (example 1). At the beginning of the experiment, the average initial weight of the individual baseline aircraft is approximately 9 kg. At the end of the experiment, the hoppers are weighed separately and the feed consumption per group is determined. A parallel experiment of the same order of action was carried out with the use of feed without the active substance. The results of the control are presented in table. I. Table 1 Example 4. For the preparation of 1,4-dioxido-3-methyl-quinoxaline (2) -N- (2-cyanoethyl) -carboxylic acid amide in a solution of 23.8 g of amide M-2-cyanoethyl -acetoacetic acid in 8 ml of methanol was added 9.2 g of benzofuroxan in portions and then dried over KOH ammonia was passed through for two hours, and first, by any cooling, the temperature of the rapidly dyeing dark color was kept below A5 ° C. After cessation of the release of the reaction heat, the temperature of the reaction mixture is maintained at 4045 ° C and after completion of passing the ammonia is stirred for another 10-12 hours at this temperature. The reaction product is isolated in the form of beige colored crystals. Stir, suck on suction, rinse with chilled methanol. The resulting pure crystalline 1,4-dioxido-3-methylquinoscalin (2) -N- (2-cyanoethyl 1) -carboxylic acid amide melts at 198-199 ° C. It can be recrystallized from a mixture of dimethyl formamide with ethanol. Example 5: To obtain 1,4-dioxido-3-methyl-quinoxaline (2) (2-cyanoethyl) -carboxylic acid amide In a solution of 80 ml of methanol and 9.9 (jr of aminopropionitrile with stirring from -10 11.8 g of freshly distilled diketene is brought to room temperature and stirred for the next 2 hours while stirring. Now a solution of N-2-cyanoethyl acetoacetic acid amide is added in portions of 19.2 g of benzofuroxane and then For 8 hours, dried 18% KOH ammonia is passed through, and first, by any cooling, the temperature quickly becomes colored in t The color of the solution is maintained below 45 C. After the evolution of the reaction heat has ceased, the temperature of the reaction mixture is maintained at 40-45 ° C and after passing the ammonia, stirring is continued at this temperature for another 1012 hours. The reaction product is isolated in the form of beige crystals. The resulting pure, crystalline 1,4-dioxido-3-methyl-quinoxaline (2) -N- (2-cyano-eth. p) -carboxylic acid amide is melted at 198-199 ° C. It can be recrystallized from a mixture of dimethylformamide with ethanol. PRI D MER 6. The preparation of N-cyanomethylamide acetoacetic acid consists in the fact that 92 g of freshly distilled diketene is also added dropwise with stirring from -10 ° to 0 ° C into a solution of 400 ml of methanol and .56 g of freshly distilled aminoacetonitrile. room temperature and stir for another 2 hours at 35 ° C in a water bath. The solvent is distilled off on a rotary evaporator and the solid residue is suspended in cooled ether. After suction, a colorless, crystalline acetoacetic acid N-cyanomethylamide is obtained in its pure form. 63-65 ° C. In tab. 2; the compounds obtained are obtained analogously to the method described in examples 3 and 4. Table 2
    - {sn) ,, sn, 1 1
    12- (CHj) -CH3-CH, j-CH
    13-CH | j-CH CH ij-CH (j-CH, j14H-CH (CHi 15- (cn) j-CHj-CIi-CH, P p and M ep 7a. Animals: a piglet weighing approximately 11 kg (by sex they do not differ.) - Food: single food No. 513 CRA. Test substances: 1.Active substance A (example 3) amide 1,4-dioxido-3-metschinoxapine (2) -I- (2-cyanoetch1) - carboxylic acid; 2.Active substance B (Bayo-n-ox - (1,4-dioxido-3-methylquinoxaoline amide (2) - (2 -hydroxyethyl) -carboxylic acid. 4 groups of each of 4 experimental animals for 49 days calving
    221,100 2.18. 100 348 256 116 1.86 85 376 239 108 1.99 91 358
     Average daily weight gain (in grams)
    ""
    The ratio of feed consumption to weight gain.
    890961JO
    Continued table. 2
      1.558
    197-198 n 1,566
    100 2.08 100 108 1.90 91 103. 2.01 97 feed I 513 CRA supplemented with 25 ppm active substances A or B. The weight of the animals is recorded at the beginning and at the end of the period for comparison, as well as after 28 days, and feed consumption is determined in equal intervals. For control, a parallel experiment is carried out according to an equal prescription when using the same feed without the addition of the active substance. The test results are shown in Table. 3. Table 3
    1189096
    PRI me R 76. Petals: Piglets with a weight of about 10 kg (divided by sex). Feed for 56 days of unit feed No. 513 CRA, then unit feed K 539 CRA. Test 5 substances: similar to the first experience.
    4 groups (2 9) of each of the 4 experimental animals are fed for 140 days once the feed with K 513 CRA and K 539 CRA with the addition of Q Research Institute 25 ppm of active substance A or B. The weight of the animals is registered at the beginning
    Control 349 100 2.20 100 523 100 2.75 100
    The active substance A 381 109 2-, 02 92 553 106 2.61 95
    Active substance B 360 103 2.12 96 533 102 2.7.0 98
    Average daily weight gain (in grams) The ratio of feed consumption to weight gain.
    513 CRA barley ... 34.0
    corn13,0
    barley flake 5.0
    oat flakes 5.0
    wheat bran22,0
    soy meal (44) 9.0
    yeast1.0
    fish meal5.0
    kir3, o
    Ca-carbonate, I
    bone meal0.5
    513 CRA monocalcium phosphate 0.5
    1J2.
    and at the end of the test run, as well as intermediately after 56 days of running the test, and the feed consumption is determined in a group way at equal intervals. For control, a parallel experiment is carried out according to the same regulations and when using the same food, but without the addition of active substances.
    The test results are shown in Table. 4. Compositions of feed are given in table. five
    Table 4
    Table 5
    Continued table. five
    权利要求:
    Claims (2)
    [1]
    Claim
    I. Growth-stimulating agent for animals containing an active substance and a carrier, characterized in that, in order to increase its effectiveness, it contains, as an active substance, quinoxaline -1- di-I-oxide derivatives of the general formula about f soya a
    X x sn
    1 3 about .40 bridges of quantity R — hydrogen, alkyl with 1-12 carbon atoms, cyanoalkyl with 1-4 carbon atoms in the alkyl part or allyl, and an A-straight or branched alkyl unit with 1-4 carbon atoms at a value of 0.001- 10.0 wt.%.
    [2]
    2. The vehicle, as the main carrier, contains kaolin lime, alumina (aluminum oxide), ground shells of Bolus alba shells, aerosil, starch and lactose.
    1, in that it
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    同族专利:
    公开号 | 公开日
    BR7700355A|1977-09-20|
    FR2338935A1|1977-08-19|
    DE2701707C2|1986-05-22|
    NL7700581A|1977-07-22|
    EG13191A|1980-12-31|
    DK20277A|1977-07-21|
    US4092415A|1978-05-30|
    SE7700529L|1977-07-21|
    CA1108143A|1981-09-01|
    DE2701707A1|1977-07-21|
    MY8400251A|1984-12-31|
    JPS5289683A|1977-07-27|
    GB1569034A|1980-06-11|
    SE427928B|1983-05-24|
    IL51292A|1981-06-29|
    HK41283A|1983-10-21|
    FR2338935B1|1979-03-23|
    AU515192B2|1981-03-19|
    YU153482A|1982-10-31|
    IL51292D0|1977-03-31|
    YU13577A|1982-10-31|
    JPS6135985B2|1986-08-15|
    DK141509C|1980-09-29|
    NZ183118A|1979-12-11|
    YU39221B|1984-08-31|
    ES455158A1|1978-04-01|
    YU40081B|1985-06-30|
    KE3289A|1983-06-17|
    DK141509B|1980-04-08|
    AU2144377A|1978-07-27|
    SG28883G|1984-04-19|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    RU2578485C2|2010-12-20|2016-03-27|ДСМ АйПи АССЕТС Б.В.|Application of nitroxy-organic molecules in forage to reduce release of methane by ruminants and/or to increase productivity in ruminants|
    RU2615390C2|2012-03-26|2017-04-04|ДСМ АйПи АССЕТС Б.В.|Application of para-nitroammophosphate in forage to reduce ruminants' methane emissions|DE1670935C3|1967-10-04|1975-12-04|Bayer Ag, 5090 Leverkusen|2-Methyl-3-carboxamidoquinoxaline-1,4-dl-N-oxides, a process for their preparation and antibacterial agents containing these compounds|
    GB1223720A|1968-10-30|1971-03-03|Ici Ltd|Growth promotion|
    US3635972A|1969-07-22|1972-01-18|Pfizer|3-methyl-2-quinoxalinecarboxamidedi-n-oxides|IT7869686D0|1978-11-24|1978-11-24|Loranze Torino A|PROCEDURE FOR PREPARATION OF 2METHYL 3 BIDROXYETHYL CARBAMOLLCHINOXALINE I.4 OF PURE N OXIDE AND OTHER COMPOUNDS SIMILAR TO IT|
    US4418063A|1978-12-19|1983-11-29|Ciba-Geigy Corporation|Growth promoting quinoxaline-di-N-oxide carboxamides|
    US4254120A|1978-12-19|1981-03-03|Ciba-Geigy Corporation|Growth promoting quinoxaline-di-N-oxide carboxamides|
    DE3133888A1|1981-08-27|1983-03-10|Bayer Ag|ACTIVE COMBINATION OF KITASAMYCIN AND CHINOXALIN-DI-N-OXIDES|
    JPH06701B2|1983-12-01|1994-01-05|旭化成工業株式会社|Veterinary composition|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    CH63476A|CH627174A5|1976-01-20|1976-01-20|Process for the preparation of quinoxaline di-N-oxide derivatives|
    CH1492076|1976-11-26|
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