• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
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  • 引用文献
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  • 优先权
    • 专利摘要:
    A compound of the formula or its pharmaceutically acceptable salt: …<CHEM>… wherein… R<1> is hydrogen, lower alkyl or lower alkoxylphenyl,… R<2> is hydrogen or lower alkyl,… R<3> and R<5> are each hydrogen, or together to form a bond for getting a group of the formula: …<CHEM>… wherein R<4> and R<6> are each as defined below,… R<4> is lower alkyl,… R<6> is hydrogen or lower alkyl,… R<7> is hydrogen or a certain group, and… R<1><0> is hydrogen or lower alkyl which may have carboxy or esterified carboxy, processes for its preparation and pharmaceutical compositions containing it as an effective ingredient.
    公开号:SU1389678A3
    申请号:SU833678551
    申请日:1983-12-30
    公开日:1988-04-15
    发明作者:Окамото Масанори；Ивами Морита；Такасе Сигехиро；Утида Итсуо；Умехара Казуеси；Кохсака Масанобу；Иманака Хироси
    申请人:Фудзисава Фармасьютикал Ко,Лтд (Фирма)；
    IPC主号:
    专利说明:

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    R, RiR4 The invention relates to novel nitroaliphatic derivatives of the oxime of formula 2
    1 1-C-C-CH-C-R "t
    NOjRj (1)
    where R is hydrogen, lower alkyl or alkoxyphenyl;
    hydrogen or lower alkyl; lower alkyl;
    cyano, formylpiperazinecarboxylic, lower alkanoyl, lower alkyloxycarbonyl, cyan-alkanyloxy- (lower) -alkyl carbamoyl, lower alkylcarbamoyl, di- (lower) -alkylcarbamoyl, carboxy- (lower alkylcarbamoyl, benzylcarbamoyl, di-(lower) -alkylcarbamoyl, carboxy- (lower alkylcarbamoyl, benzylcarbamoyl) (1-carboxy-2-hydroxy) -pro-pylcarbamoyl or lower.
    which exhibit antithrombotic and antihypertensive effects and can be used in medicine ..
    The aim of the invention is to reveal new compounds in a series of nitroaliphatic oxime derivatives having a higher activity.
    Example 1. Sodium nitrite (60 g) is added to a solution of (E, E) -4-ethyl-2,4-hexadienamide (31.4 g) in 10% aqueous methanol (1500 ml) with stirring, the mixture acidified to pH 3.0 and stirred at room temperature for 15 minutes. More sodium nitrite (60 g) was added to the resulting reaction mixture. The mixture is acidified to pH 3.0 and then stirred at room temperature for 15 minutes. The resulting reaction mixture is extracted with ethyl acetate, crystallized from methanol, and (E) -4-ethyl-2-oxyimino-5-nitro-3-hexenamide (20 g) is obtained, m.p. 142 ° C.
    Example 2 Sodium nitrite is added to a solution of (E, E) -N-n-butyl-4-ETSH1-2,4-hexadienamide (3 g) in 10% aqueous methanol (300 ml). The resulting mixture is acidified to pH 3.0 and then stirred at room temperature for 15 minutes. An additional amount of sodium nitrite (7 g) was added to the resulting reaction mixture, the mixture was adjusted to pH 3, and then stirred at room temperature for 15 minutes. This pr










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    The procedure is repeated three times. The resulting reaction mixture was extracted twice with ethyl acetate (200 ml each). The extracts are combined, washed successively with water and brine, dried over magnesium sulfate, then evaporated to dryness to give an oil. This oil is purified by column chromatography on silica gel using chloroform containing 2% methanol as eluent to obtain NH-α-butyl-4-ethyl-2-oxyimino-5-nitro-3-hexeneamide (1.3 g) .
    NMR: f (CDCl1): 6.8 (IH, broad s), 6.1 (IH, s), 5.15 (IH, q, J 7 Hz), 3.5-3.2 (2H, m ), 2.12 (2H, k, J 7 Hz)., 1.72 (3N, d, J 7 Hz), 1.7-1.3 (4H, m), 1.1-0.9 (6H, m).
    HKV / CHCla), cm-: 3410, .- 3200, 2960, 2930, 2870, 1660, 1550, 1530, 1460, 2380, 1360, 1000.
    Example 3. K-Methyl-4-ethyl-2-oxyimino-5-nitro-Z-hexenamide (0.79 g) is obtained, as in Example 2, from (E, E) -H-methyl-4-ethyl -2,4-hexadienamide (1.5 g) and sodium nitrite (12 g).
    NMR f (COCl3): 7.0 (1H, broad s), 6.13 (1H, s), 5.17 (1H, q, J 7 Hz), 2.87 (ZN, d, J 5 Hz) , 2.12 (2H, q, J 7 Hz), 1.68 (3N, d, J 7 Hz), 0.97 (3N, t, J 7 Hz).
    IR V axCCHCls), cm0
    3400, 3200,
    5 2950, 2910, 2850, 1660, 1540, 1450, 1410, 1380, 1340, 1030, 980. I
    Example 4. 1-Formyl-4- (4-etsh12-oxyimino-5-nitro-3-hexeno-W1) -piperazine (0.6 g) is prepared, as in Example 2, from 1-formyl-4-t ( E, E) -4- -ethyl2,4-hexadienoyl piperazine (1.4 g) and sodium nitrite (12 g).
    IR, "y (СНС1з), 325.0, 3000, 2950, 2900, 1660, 1550, 1460, 1440, 5 1400, 1360, 1280, 1240, 1200, 1180, 1000.
    1550.
    Example 5. H- (4-Ethyl-2-hydroxyimino5-nitro-3-hexenoyl) glycine (300 mg) is prepared as in Example 2 from N- (E, E) -4-ethyl-2.4 -hexadienoyl-glycine (800 mg) and sodium nitrite (3 g).
    C NMR (CDCl3-CD, OD): 6.2 (1H, s), 5.25 (1H, q, J 7 Hz), 4.0 (2H, s), 2.17 (2H, q, J 7 Hz), 1.75 (2H, d, J 7 Hz), 1.0 (3N, t, J 7 Hz).
    IR,;, cm-:. 1720, 1670,
    Example 6, H-C-ETsh1-2-hydroxyimino-5-nitro-3-hexenoyl) piperidine (276 mg) is obtained, as in Example 2, from N- (E, E) -4-ethyl-2, 4-hexadienoyl with piperidine (500 mg) and sodium nitrite (4 g).
    NMR (CDCl 3): 6.13 (1H, s), 5.15. (1H, k, J 7 Hz), 3.65 (4FI, m), 2.27 (2H, k, J 7 Hz), 1.75 (ZN, d, J 7 Hz), 1.7 (6H , m), 1.05 (3N, t, J = 7 Hz).
    ten
    IR, 1630 ,. 1550,
    1450.
    Measure 2, from (E) -4- (E) - (4-methoxy benzylidene) -2-hexenamide (500 mg) and sodium nitrite (3 g).
    NMR s / (CBC1e): 7.40 (2H, d, J 8 Hz), 6.87 (2H, d, J 8 Hz), 6.86 (2H, m), 6.23 (1H, s) , 6.23 (1H, m), 5.90 (1H, s), 3.77 (ZN, s), 2.03 (2H, k, J 7 Hz), 0.97 (ZN, t, J 7 Hz).
    IR / „„ LSNS1z), cm-: 3550, 3420, 3000, 1695, 1620, 1560, 1365, 1260, 1040.
    Example 12. M- (4-ethyl-2-hydroxy- Example 7. N- (4-Ethyl-2-hydroxy-5-imino-5-nitro-3-hexenoyl) -4-amino-imino-5-nitro 3-hexenoyl) -b-threonine acid (100 mg) is obtained
    (180 mg) is obtained as in Example 2, from N- (E, E) -4-ethyl-2,4-hexadieno7-β-L-threonine (600 mg) and sodium nitrite (4 g). 20 sodium nitrite (2 g ).
    NMR (CDCl1-CDjOD): 6.2 (1H, s), NMR s / (CDC1 j-CD jOD): 6.2 (1H, s),
    5.3 (1H, q, J 7 Hz), 4.8-4.0 (2P, m), 2.2 (2H, q, J 7 Hz), 1.7 (3N, d, J 7 Hz), 1.3 (ZN, m), 1.0 (ZN, d, J 7 Hz).
    Example 8. N-Benzyl-4-ethyl--2-oxyimino-5-nitro-3-hexenamide- (340 mg) is prepared, as in Example 2, from (E, E) -N-benzyl-4-etyl- 2,4-hexadienamide (1 g) and sodium nitrite (4 g).
    NMR rf (SPSI-SVSOV): 7.3 pH, s).
    in the same manner as in Example 2, from L- (E, E) -4-ethyl-2,4-hexadieno1) -5-aminobutyric acid (270 mg) and
    5.2 (1H, m), 3.5 (2H, m), 2 „6-1.9 (6H, m), 1.75 (ZN, d, J 7 Hz), 1.0 (ZN, t, J 7 Hz).
    25
    thirty
    35
    45
    6.2 (1H, s), 5.2 (1H, d, J 7 Hz), 4.5 (2H, d, J 5 Hz), 2.18 (2H, k, J 7 Hz), 1, 8 (ZN, d, J 7 Hz), 1.0 (ZN, d, J 7 Hz).
    Example 9. 2-Oxyimino-4-methyl-5-nitro-3-hexenamide (180 mg) is prepared as in Example 2 from (E, E) -4-methyl-2,4-hexadienamide (200 mg) and Q sodium nitrite (1500 mg).
    NMR (D (SVZOO)): 6.22 (1H, s), 5.30 (1H, q, J 7 Hz), 1.68 (ZN, s), 1.68 (ZN, d, J 7 Hz) .
    IR (Nujol), cm: 3450, 3250, 2950, .1680, 1620, 1600, 1550, 1460, 1380, 1370, 1000.
    Example 10. 2-Oxyimino-4-methyl-5-nitro-Z-pentenamide (120 mg) is prepared as in Example 2 from (E) -4-methyl-2,4-pentadienamide (200 mg) and sodium nitrite (1500 mg).
    NMR c / (CHo, OD): 6.23 (1H, -c), 5.13 (2H, s), 2.07 (ZN, s).
    IR l1p, “(CHC1c iCM-: 3500, 3300, 2950, 1680, 1555; 1380.
    Example 11. 4-ethyl-2-oxime-5- (4-methoxyphenyl) -5-nitro-5-pentenamide (210 mg) is prepared as in
    55
    Example 13. 4-EHYL-2-OXIIHIMINO-5-methyl-5-nitro-3-hexenamide (740 mg) is prepared in the same manner as in Example 2 from (E) -4-ethyl-5- -methyl-2,4-hexadienamide (1 g) and sodium nitrite (6 g).
    NMR ((CBC1. -NW): 6.2 (1H, s), 2.15 (2H, q, J 7 Hz), 1.8 (6H, s), 0.95 (ZN, T, .J 7 Hz).
    IR l; „ah (Nujol), cm: 3450, 1650, 1590, 1540.
    Example 14. 4-EL-2-OXIIMINO-5-nitro-3-hexenitrile (3.9 g) is obtained in the same manner as in Example 2 from (E, E) -4-ethyl-2, 4-hexadienenitrile (3 g) and sodium nitrite (12 g).
    IR ", (СНС1з), cm-: 3550, 3250, 3000, 2250, 1640, 1550, 1460, 1390, 1360, 1040.
    Example 15. 4 ETHYL-2-OXYIMINO-5-nitro-3-hexenal (100 mg) is prepared in the same manner as in Example 2 from (E, E) -4-ethyl-2,4-hexa - dienal (0.3 g) and sodium nitrite (1.8 g).
    NMR 1G (CBC1): 9.53 (1H, s), 6.03 (1H, s), 5.23 (1H, q, J 7 Hz), 2.15 (2H, j, J 7 Hz), 1.77 (ZN, d, J 7 Hz), 1.05 (ZN, t, J 7 Hz).
    IR) h), cm-: 3550, 3250, 3000, 1700, 1610, 1550, 1460, 1390, 1360, 1040.
    Example 16, ethyl 4-ethyl-2-oxyimino-5-nitro-3-gv-xenoate
    ten
     sodium nitrite (2 g).
    in the same manner as in Example 2, from L- (E, E) -4-ethyl-2,4-hexadieno1) -5-aminobutyric acid (270 mg) and
    NMR with / (CDC1 j-CD jOD): 6.2 (1H, s)
    5.2 (1H, m), 3.5 (2H, m), 2 „6-1.9 (6H, m), 1.75 (ZN, d, J 7 Hz), 1.0 (ZN, t, J 7 Hz).
    five
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    Example 13. 4-EHYL-2-OXIIHIMINO-5-methyl-5-nitro-3-hexenamide (740 mg) is prepared in the same manner as in Example 2 from (E) -4-ethyl-5- -methyl-2,4-hexadienamide (1 g) and sodium nitrite (6 g).
    NMR ((CBC1. -NW): 6.2 (1H, s), 2.15 (2H, q, J 7 Hz), 1.8 (6H, s), 0.95 (ZN, T, .J 7 Hz).
    IR l; „ah (Nujol), cm: 3450, 1650, 1590, 1540.
    Example 14. 4-EL-2-OXIIMINO-5-nitro-3-hexenitrile (3.9 g) is obtained in the same manner as in Example 2 from (E, E) -4-ethyl-2, 4-hexadienenitrile (3 g) and sodium nitrite (12 g).
    IR ", (СНС1з), cm-: 3550, 3250, 3000, 2250, 1640, 1550, 1460, 1390, 1360, 1040.
    Example 15. 4 ETHYL-2-OXYIMINO-5-nitro-3-hexenal (100 mg) is prepared in the same manner as in Example 2 from (E, E) -4-ethyl-2,4-hexa - dienal (0.3 g) and sodium nitrite (1.8 g).
    NMR 1G (CBC1): 9.53 (1H, s), 6.03 (1H, s), 5.23 (1H, q, J 7 Hz), 2.15 (2H, j, J 7 Hz), 1.77 (ZN, d, J 7 Hz), 1.05 (ZN, t, J 7 Hz).
    IR) h), cm-: 3550, 3250, 3000, 1700, 1610, 1550, 1460, 1390, 1360, 1040.
    Example 16, ethyl 4-ethyl-2-oxyimino-5-nitro-3-gv-xenoate
    (110 g) is obtained, as in Example 2, from ethyl- (E, E) -4-ethyl-2,4-hexadiatoate (0.3 g) and sodium nitrite (1.8 g).
    NMR J (CDCli): 10.3 (1H, broad s), 6.17 (1H, s), 5.23 (1H, q, J 7 Hz), 4.3 (2H, j, J 7 Hz) , 2.13 (2H, k, J 7 Hz), 1.73 (ZN, d, J 7 Hz), 1.33 (ZN, t, J 7 Hz), 1.0 (ZN, t, J 7 Hz ).
     IR p, ou (CHC1), cm-: 3570, 3250, 3000, 1725, 1555, 1390, 1030.
    Example 17. Methyl-2- (4-ethyl--2-oxyimino-5-nitro-3-hexenoylamino) acetic acid (120 mg) is obtained in the same manner as in example 2, from mets-1-2 G ( E, E) -4-ethyl-2,4-hexadieno-ylamino-acetate (0.3 g) and sodium nitrite (1.8 g).
    NMR cP (CBC1): 10.2 (1H, broad s), 7.42 (1H, broad c), 6.13 (1H, s), 5.2 (1H, q, J 7 Hz), 4, 12 (.1Н, д ,, а 6 Hz), 3.73 (ЗН, s), 2.12 (2Н к, J 7 Hz), 1.7 (ЗН, д, J 7 Hz), 0.97 (ZN, t, J 7 Hz).
    IR dx (CHCl3), cm-: 3570, 3400, 3000, 1740, 1680, 1555, 1440, 1390, 1230.
    EXAMPLE 18 1-Acetoxy-4-ethyl-2-oxyimino-5-nitro-3-hexene (60 mg) is obtained in the same manner as in Example 2 from (E, E) - 1-ace-toxi-4-ethyl-2,4-hexadiene (0.3 g) and sodium nitrite (1.8 g).
    IR l) „o (.,), Cm-: 3600, 3300. 3000, 1740, 1550, 1390, 1220.
    Example 19. Hydroxylamine hydrochloride (60 mg) is added to a solution of N-tert-butyl-4-ethyl-5-nitro-2-oxovensamide (100 mg) in a mixture of chloroform (1.5 ml) and methanol (1 ml). The resulting the mixture is stirred at room temperature overnight
    The reaction mixture is evaporated and the residue is diluted with ethyl acetate. The resulting solution is washed successively with water and brine, dried over magnesium sulfate and then evaporated to dryness. The resulting oil is purified using a male white rabbit male (weighing 2.5–3 kg) to collect blood from the arteries of the middle ear. Blood coagulation is prevented by adding 1 volume I of 3.8% sodium citrate to 9 volumes of blood. Platelet-rich plasma (BTP) is obtained with a thin-layer chromatography (diluted with blood centrifugation with spruce benzene - ethyl acetate 10: 1). H-tert-butyl-4-ethyl-2-hydroxyimino-5-nitrohexanamide (47 mg) is obtained.
    1300 rpm for 10 minutes at 10 ° C. BTP is diluted with platelet-poor plasma, which is obtained by additional centrifuging blood at 3000 rpm for 10 minutes. The number of platelets in the BTP used in the aggregation study, fYa (NMNR): 9.1 (1H, broad s), 55 6.7 (1H, broad s), 4.55 (1H, m), 2.8 -2.4 (ЗН, m), 1.7-1.2 (14Н, m) 0.9 (ЗН, m).
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    IR at „с.х (СНС1э), cm-: 3600, 3410, 3300, 3000, 1670, 1630, 1550, 1530, 1400, 1240, 1000.
    Example 20. 4-ethyl-2-oxime-i-5-nitrohexanamide (15 mg) is obtained in the same manner as in example 14, from 4-ethyl-5-nitro-2-oxohexane-amide (20 mg) and hydroxylamine hydrochloride (14 mg).
    NMR / (CDCl 2): 9.0 OlH, broad c), 6.7 (1H, broad c), 5.6 (1H, broad c), 4.55 (1H, m), 2.8-2 , 4 (ZN, m), 1.7-1.2 (5H, m), 0.9 (ZN, m).
    IR-JmaxCCHCl 3), cm-: 3550, 3425, 3300, 3000, 1690, 1555, 1400, 1000.
    Example 21. 4-Ethyl-2-hydroxyimino-3-methyl-5-nitro-3-hexenamide (170 mg) is obtained in the same manner as in Example 2 from (E, E) -4-ethyl- -3-methyl-2,4-hexadienamide (400 mg) and sodium nitrite (1600 mg).
    NMR (CDjOD): 5.68 (1H, q, J 7 Hz), 2.00 (2H, q, J 7 Hz), 1.92 (ZN, s), 1.66 (ZN, d, J 7 Hz), 0.90 (3N, t, J = 7 Hz).
    IR „„ x (Nujol), cm-: 3500, 3290, 3240, 3170, 1670, 1600, 1555.
    Example 22. N, N-Dimethyl-4-ethyl-2-oxyimino-5-nitro-3-gwxen-g amide (203 mg) is obtained in the same manner as in example 2 from (E, .E) - -N, H-dimeglyl-2,4-hexadienamide (0.3 g) and sodium nitrite (1.8 g).
    IR) n, ah (CHC1 e), cm: 3570, 3250, 3000, 1640, 1550, 1380.
    Compounds obtained in accordance with the proposed method are tested for pharmacological activity.
    The inhibitory activity against platelet aggregation of rabbit blood is determined as follows.
    Platelet aggregation.
    Blood from the middle ear arteries is collected from male white rabbit individuals (weighing 2.5–3 kg). Blood coagulation is prevented by adding 1 volume I of 3.8% sodium citrate to 9 volumes of blood. Platelet-rich plasma (BTP) is obtained by centrifuging blood with
    by centrifuging blood with a
    1300 rpm for 10 minutes at 10 ° C. BTP is diluted with platelet-poor plasma, which is obtained by additional centrifuging blood at 3000 rpm for 10 minutes. The number of platelets in the BTP used in the aggregation study is 4, platelets / mm. The study was carried out using platelet aggregating agents in a SIENKO double specimen aggregometer (DP-247 E) at 37 ° C, using 0.3 ml of BTP mixture and agents in a cylindrical glass cuvette with constant stirring using a magnetic stirring rod. Platelet aggregation is determined turbidimetrically by recording changes in light transmission of BTP during the aggregation process. The activity of the inhibitors is expressed in terms of ICI, i.e. at concentrations required to slow down platelet aggregation by 50%. Collagen is used in an amount of 2-20 µg / ml for FGTs, sufficient to cause a response that is 80-90% of the maximum obtained. Arachidonic acid is used at a final concentration of 5 μM. Similarly, the final concentration of ada-nosine diphosphate (ADP) is usually chosen 1-5 μM in order to cause 25 oxygen (95% O, 5%. CO,) solution of approximately 75% aggregation from maxi-Tyrode of the following composition, mm g / l): minimal. Thrombin is used in a final concentration of 0.3 B / ml.
    NaCl 137 (8); KC1 2.7 (0.2), -2H, 0 1.8 (0.264); MgCli-6H, 0 1.02
    (0.208); NaHCO, 1.1., 9 (1); NaH P04-2H. these agents that cause aggregate - d 0,42 (0,066); glucose 5.55. thrombocytes, IR ,, „Tissue compounds are stretched for 90 minutes,
    then they are poured over Tyroid's solution
    (10 ml / min) norepinephrine-saline
    So when using
    Example 1 is µg / ml:
    Collagen 0.07
    Thrombin 0.15
    ADP0.15
    Arahidonova
    acid 0.75
    When using thrombin caused platelet aggregation, IR compounds obtained by the proposed method; as well as a known compound of the formula
    with a solution (0.6 µg / ml) (0.5 ml / min), which increases tissue stretching by 500 mg. Changes in tissue stretching are measured isometrically using a Force Displacement Sensor connected to a multiplier.
    The vasodilating effect is expressed as the dose of each compound, causing a 50% decrease in tissue tension ().
    40
    m-he
    M02-CH2-CH-CH2-C-
    leaving µg / ml: Compounds according to an example
    20.15
    30.3
    40.3
    50.15
    60,15
    70.3
    80.15
    100.3
    110.3
    12 0.75
    141.5
    153.0
    160.07
    170.15
    180.15 Known compound 8.0
    Test of vasodilator action.
    The vasodilating effect of aliphatic nitro compounds (1) is determined by the method of pouring. This method is as follows.
    Male Sprague-Dowle rats aged 8–10 weeks are slaughtered with a blow to the head and the cervical aorta is quickly isolated. After the adipose tissue is removed from the aorta, spiral strips (2 mm wide and 50 mm long) are cut, which are immersed by stretching 1 g into a 30 ml organic bath containing warm (37 ° C) liquid;
    solution (0.6 µg / ml) (0.5 ml / min), g, which increases the stretching of tissues by 500 mg. Changes in tissue stretching are measured isometrically using a Force Displacement Sensor connected to a multiplier.
    The vasodilating effect is expressed as the dose of each compound, causing a 50% decrease in tissue tension ().
    EDGD of the tested compounds is equal to μg:
    0
    five
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    five
    The proposed connection example
    10.05
    20.20
    30.10 40.1
    52.0
    60.5
    75
    80.1
    90.05
    10.0.25
    110.05
    12 14 15 16 17 18
    2.5
    0.25
    0.025
    0.01
    0.1
    0.025
    0.25
    nineteen
    Known compound 1.0
    Antihypertensive activity in animal testing.
    8-week-old Sprague-Dowley rats are anesthetized with urethane (0.7 g / kg intraperitoneally). Blood pressure is determined in the femoral artery using a sensor connected to the Biophysiograph 180 system (manufactured by Sanya Sokuki Co., Co., Ltd.). A cannula is inserted into the femoral vein for administration of the test compound of Example 1. The compound is dissolved in saline and injected at a dose of 0.2 ml.
    At 100 µg / kg of the compound, a maximum pressure drop of 40 mm Hg is achieved, the duration of the hypotensive effect is 4 minutes; at 10 µg / kg of the test compound, the maximum pressure drop is 4 mm Hg, duration - 1.5 min
    Determination of toxicity.
    The experimental animal is a mouse. Method of administration - intraperitoneal injection of the compound of Example 1 at a dose of 500 mg / kg. The compound is non-toxic.
    Thus, the compounds obtained by the proposed method have a higher activity than the structural analogue. Indicated
    compounds include toxic compounds
    the group is small
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method of obtaining nitroaliphatic DERIVATIVES of the oxime of the general formula
    TSiOH
    II
    RI-C-C CH-C-Rrt
    R CC R
    N0 "3
    where R is hydrogen, lower alkyl or lower alkoxyphenyl; hydrogen or lower alkyl; lower alkyl;
    cyano, formylpiperazinecarbonyl, lower alkanoyl, lower alkyloxycarbonyl, lower alkanoyloxy- (lower) - -alkyl, carbamyl, lower alkylcarbamoyl, di- (lower) - -alkylcarbamoyl, carboxy- - (lower) alkylcarbamoyl- - dincarbonyl. i (1-carboxy--2-hydroxy) propylcarbamoyl or lower alkoxycarbonyl (lower U-alkylcarbamoyl), characterized in that
    Vg
    R.-C C-CH CH-Rti 1 I
    Cs
     listed above.
    Where
    or its salt is reacted with nitrogen trioxide, obtained from a nitrous acid salt, such as sodium nitrite in the presence of an acid.
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    SU1480760A3|1989-05-15|Method of producing arythrodiol-5-yl-alkenic acid
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    同族专利:
    公开号 | 公开日
    AU2174483A|1984-07-05|
    DK607783D0|1983-12-30|
    PH19042A|1985-12-11|
    JPH0219822B2|1990-05-07|
    IE56312B1|1991-06-19|
    NO158379C|1988-08-31|
    US4863926A|1989-09-05|
    ES8504682A1|1985-05-01|
    JPH02160750A|1990-06-20|
    US4767768A|1988-08-30|
    FI834702A|1984-07-01|
    CA1231949A|1988-01-26|
    FI834702A0|1983-12-21|
    IE832788L|1984-06-30|
    DK607783A|1984-07-01|
    NO834884L|1984-07-02|
    FI78904C|1989-10-10|
    FI78904B|1989-06-30|
    EP0113106B1|1986-05-14|
    ES528561A0|1985-05-01|
    US4778804A|1988-10-18|
    EP0113106A1|1984-07-11|
    JPH0417944B2|1992-03-26|
    KR910006761B1|1991-09-02|
    AU560980B2|1987-04-30|
    HU200747B|1990-08-28|
    DE3363550D1|1986-06-19|
    ZA838831B|1984-07-25|
    GR79553B|1984-10-30|
    AT19773T|1986-05-15|
    JPS59152366A|1984-08-31|
    NO158379B|1988-05-24|
    KR840007579A|1984-12-08|
    US4782088A|1988-11-01|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB8237068|1982-12-31|
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