• 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:
    NEW MATERIAL:The compound of formula I [Ar<1> is group of formula II (X<1> and X<2> are H, nitro, Cl or trifluoromethyl) or formula III; R<1>-R<6> are H or 1-3C alkyl; A is 1-6C alkylene; Ar<2> and Ar<3> are (substituted)phenyl; l and m are 0-3], its salt and their solvates. EXAMPLE:5-( 2,2-Dimethylpropylene-dioxy-phosphinyl )-2,6-dimethyl-4-(3-nitrophe nyl)-3-carboxylic acid 2-(N,N-diphenyl)-aminoethyl ester. USE:Remedy for circulatory diseases such as stenocardia, cerebral circulation disorder and hypertension. PREPARATION:An alpha-acetylstyryl-phosphonate derivative of formula IV is made to react with a 3-aminocrotonic acid derivative of formula V in an inert solvent (e.g. methanol) preferably at 60-140 deg.C for 5-20hr.
    公开号:SU1586519A3
    申请号:SU874203193
    申请日:1987-08-14
    公开日:1990-08-15
    发明作者:Киетомо Сето；Сакуя Танака；Риозо Сакода；Тозинори Сакаи；Юкинори МАСУДА
    申请人:Ниссан Кемикал Индастриз, Лтд (Фирма)；
    IPC主号:
    专利说明:

    h table
    20 20
    27.8 41.2 4230.6
    40.7 41.2 32.912.3
    eleven
    1586519
    HCl-salt (compound I)
    HCl-salt (compound II)

    Compound
    Action on vascular smooth muscle
    The time of pre-incubation with the test compound pA, h
    12 Table 2

     800
    LD
    GO
    200
    Table3
    one
    .
    Table 4
    23.1
    43.5 80.2
    Table 5
    Table 6
    权利要求:
    Claims (1)
    [1]
    Claim
    A method for producing a propylene glycol ester of a substituted 1,4-dihydropyridyl-5-phosphonic acid of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein the propylene glycol ether of a substituted ethenphosphonic acid of the formula
    CH 3 Οθ η <) P s = si <3 sn / '- n I. υ C (O) CH 3 is reacted with a substituted 3-aminocrotonic acid ester of the formula
    C 6 11 5 / C = C1SO -С11пСН 9 K <
    30 CH CH r -C 6 H 5 are prepared unity orally
    25 mp / kg 0.9% NaCl solution. Then, each rat was placed in a metabolic envelope (to collect 35 metabolic products) and urine was collected over 10 hours. Urinary electrolytes (Na + ) were measured using a plasma promo-. 'pa (FPF-3A), The test results are presented in table.6. 40 and the desired product is isolated in the form of ether or converted into a pharmaceutically acceptable salt or solvate thereof.
    Priority by signs:
    01/23/86 when receiving the ester or its pharmaceutically acceptable salt.
    11.25.86 upon receipt of the solvate.
    • h table!
    Test compound Dose mg / kg Antihypertensive effect, decrease (%) after, h 2 4 6 1 8 HC1 salt (compounds I) 20 27.8 41.2 42 30.6 HC1 salt (compounds II) 20 40.7 41.2 32.9 12.3
    eleven
    table 2
    Test subject Dose, Mortality DC £ 4 , mg / kg compound mg / kg HC1 salt 200 0/5 5O4 ^ DD 50 <800 (connect- 318 0/5 I) 504 2/5800 4./5 HC1 salt 200 5/5 LD G0 <200 (connection- 318 5/5 II) 504 5/5800 5/5 - ’·
    Table 3
    Compound
    Effects on vascular smooth muscle
    Pre-incubation time with test compound pA ^, i
    1 I 3I 6 HCl salt (with unity I)8.63 9.17 9.33 Nifedipine8.60 - - Hydrochloride cardipina9.689.70
    Table 4
    Compound Heart rate Contraction force Dose, M % Reduction Dose, M Decline, 2 HCl salt (connect- I) 10 ' 911.623.1 Hydrochloride 10'' 60,4nicardipine . W 311.3 10 ' 743.5 10'" 50,0 ίο- 480.2
    Table 5
    Subjects Dose mg / kg Test compounds animals HCl salt (compound I) Nicardipine HydrochlorideDead animals / test animals Dead animals / test animals
    Mouse strain
    ma ddY 300 0/3 0/3 424 0/3. 1/3 600 0/3. 3/3 SD strain rats 600 0/5 2/5 1200 0/5 2/5 2400 0/5 2/5
    Tableb Test compoundUrinary Na Content, mEq / Rat Dose mg / kg Urine volume, ml / rat Control4.7 0.73 HCl salt 10 7.9 1, 02 (compound I) 20 15.3 1.25 Furosemide 20 7.7 1, 02
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    同族专利:
    公开号 | 公开日
    UA5590A1|1994-12-28|
    JPH0699458B2|1994-12-07|
    JPS63233992A|1988-09-29|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    JPH0365351B2|1983-03-04|1991-10-11|
    JPH0379359B2|1983-09-26|1991-12-18|Nissan Chemical Ind Ltd|
    JPH0259835B2|1984-04-19|1990-12-13|Nippon Shinyaku Co Ltd|
    JPH0655751B2|1986-01-22|1994-07-27|日産化学工業株式会社|Dihydropyridinephosphonic acid cyclic ester|
    JPH054396A|1991-06-28|1993-01-14|Nec Home Electron Ltd|Printer|NZ542681A|2003-03-28|2009-01-31|Nissan Chemical Ind Ltd|T-type calcium channel blockers comprising optically active 1,4-dihydropyridines|
    EP1676852B1|2003-10-01|2011-10-05|Nissan Chemical Industries, Ltd.|Process for producing optically active dihydropyridinephosphonic ester|
    TW200528107A|2003-11-25|2005-09-01|Nissan Chemical Ind Ltd|T-type calcium channel inhibitor|
    AU2008248188A1|2007-05-02|2008-11-13|Tau Therapeutics Llc|Dihydropyridine derivative for treating cancer or a pre-cancerous condition and other conditions|
    法律状态:
    优先权:
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    JP1275586|1986-01-23|
    JP28015986|1986-11-25|LTRP307A| LT2138B|1986-01-23|1993-01-27|OF THE PROPOSAL FOR THE RECEIVING OF THE PROPILENGLICOL-ETHYL ACID OF THE 1,4-DIHYDRROPYRID-5-PHOSPHONE OR OF ITS PHARMACEUTICAL-USED SALTS OR SOLVENT|
    LV930112A| LV5271A3|1986-01-23|1993-02-09|Substitution for the replacement of the substituted 1,4-dihydropyridyl-5-phosphonyl-propyleneglycerol or the pharmaceutically acceptable salt or solvate thereof|
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