• 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 provides compounds of the formula: wherein R1, R2 and R3, which can be the same or different, are each selected from hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxy, amino, hydroxy and nitro; R4 is hydrogen or alkyl of 1 to 7 carbon atoms; -X- is wherein R5 is hydrogen, hydroxy or-OR6, and R6 is alkyl of 1 to 7 carbon atoms or aryl of 6 to 10 carbon atoms; and their non-toxic pharmaceutically acceptable acid addition salts and mixtures thereof. Processes for the preparation and use of the subject compounds are described, as are novel pharmaceutical compositions comprising at least one of the subject compounds or their salts. The compounds and their non-toxic salts exhibit valuable pharmacological activity and are useful in the treatment of mammals, particularly as anti-hypertensive or anti-ulcer agents. Furthermore, they are useful as diuretic, sedative, analgesic, anti-inflammatory and tranquilizing agents.
    公开号:SU997607A3
    申请号:SU802959548
    申请日:1980-08-06
    公开日:1983-02-15
    发明作者:Йоханнес Карьялайнен Арто
    申请人:Фармос-Ихтюмя Ой (Фирма)；
    IPC主号:
    专利说明:

    (5) THE METHOD OF OBTAINING IMIDAZOLE DERIVATIVES AND / AND THEIR HYDROCHLORIDES ) MDVg (III) in the medium of dry tetrahydrofuran at 50-65 ° C with the isolation of the target product in free form or in the form of gyrochloride.  The examples show the NMR spectral chemical shifts (. bromine), the NMR spectrum is determined using a Perkin setup. Elmer K 2, which uses an external tetramethylsilone standard.  Letters 5, в, -t and denote a singlet, doublet, triplet, or multiplet, respectively.  The number of hydrogen atoms is determined in the form of the bond itself.  The compounds listed as bases are tested in deuterium methanol, acetone or chloroform, and the compounds listed as hydrochlorides are determined in dayte, rium oxide.  A mass spectrogram is obtained using a Perkin Elmer RMV setup using the direct entry system. Experiments are carried out at the minimum temperature necessary for evaporation of the compound in the form of a base.  In these examples, the strongest and most significant from the structural point of view, fragment-ions are given as t / 1 values.  In parentheses, the values of the fragmentation intensity are shown in comparison with the main peak.  Example 1  4- Alpha (2-methylphenyl) -oxymethylimidazole.  , 8 g of dry magnesium turning chips cover 100 ml of dry tetra hydrofuran (THF.  The mixture is heated to boiling point, and a solution of 2-bromotoluene is added to the mixture; In dry tetrahydrofuran, at a rate to maintain the mixture boiling under reflux.  The reaction mixture was heated under reflux for another 30 minutes, then about. cla) k give up and g-imidazaldehyde is gradually added in small portions.  After that, the mixture is boiled for h, cooled and about 100 are poured.  ml of cold water, which contains 20 ml of concentrated hydrochloric acid.  A portion of the tetrahydrofuran is distilled off to obtain a smaller volume and the tetrahydrofuran is replaced with water, then the mixture is washed twice with 1 0 ml portions of chloroform.  The aqueous layer is alkalinized by adding a solution of sodium hydroxide to it, bringing the pH to 8.  The precipitate formed is (watered with water and dried.  The crude product is recrystallized from a mixture of water and ethanol, resulting in a product with t. square  1BZ164 0.  Exit 80.  NMR spectrogram: 1.9 (s, 3N), A, 85 (s, 2H), 5.7 (s, 1H), 6.33 (s, 1H), 6.85 (t, 3N), 7 , 3 (t, 2H).  Mass spectrogram: 188 (37X) 171 (D), 170 (), 169 (10 () o), 155 (P%), (), (19o), 116 (19%), 115 (29), 97 (2}%), 95 (27), 91 (2U), 69 (26 °).  Example 2  - | | Alpha (2,6-dimethylphenyl) is an oximethyl imidazole.  The procedure of Example 1 is repeated completely, but instead of 2-bromotoluene, 1-bromo-2,6-dimethylbenzene is used.  After recrystallization from ethanol, a product is obtained which starts at 1. 66-167 ° C, yield 85.  NMR spectrogram: 2.0 (s, 6I), ", 7 (s, 2H), 5.95 (s, 1H), 6.3 (s, 1H), 6.7 (s, 3N), 7 , 25 {s, 1H).  i Mass Spectrogram: 202 (60;).  187 / (k%), I8i (100%), 183 (96%), 169 (38%), 157 (), 156 (25%), 13.   (16), 133 (20), 115 (18), 105 (), 105 (18), 97 (32 °), 93 C + OSS), 191 (2k%), 77 (16%), 69 (60 °).  Example 3  - (Alpha-phenyl hydroxymethylimidazole.  The procedure of Example 1 is repeated completely, but bromobenzene is used instead of 2-bromotoluene.  The product obtained in isopropanol is converted into hydrochloride hydrochloride.  After recrystallization from isopropanol, hydrochloride is obtained, which melts at TZO-TZ;.  The yield is 78%.  5 NMR spectrogram (hydrochloride salt) 4.9 (S, 3N), 5.95 (S, 111), 7.2 (S, 1H), 7.  (S, 5H), Z, (S, 1H).  Mass spectrogram: 17 (11) 0%), 157 (22%), 156 (17%), 130 (25), 129 (), 10 (17%), 103 (1M), 102 (20%), 97 (86%), 96 (82%), 95 (89%), 91 (93%), 78 (26%), 77 (57%), B9 (86%), 68 (78%).  Example 4 4- Alpha (3-methyl phenyl hydroxymethylimidazole.  .  The procedure of Example 1 is repeated completely, but 3 bromotoluene is used.  1T. square  product is 120-122 ° C. Output 80%.  NMR spectrogram: 1.85 (S, ZN), 4.15 (S, 2H), 5.3 (S, 1H), 6, -35 (S, L), 6.75 (t, 4H), 7.2 (s, 1H).  Mass spectrogram: 188 (100%), 187 (29%), 171 (21%), 170 (), 144 (17%), 143 (40%), 115 (), 97463%), 96 (67% ), 95 (73%), 91 (33%), 69 (49%), 68 (51%).  Example 5  4- Alpha (4-methyl phenyl)} hydroxymethylimidazole.  The procedure of Example 1 is repeated, but 4-bromotoluene is used.  After recrystallization from a mixture of water with ethanol, the product melts at 11b-119 ° C.  Yield 72%.  NMR spectrogram: 2.25 (S, 3N) 5.6 (S, 2H), 5.75 (S, 1H), 6.75 (S, 1H), 7.2 (t, 5H).  Mass spectrogram: 188 (100%), 171 (36%), 170 (50%), 155 (), 143 (48%), 97 (49%), 96 (88%), 95 (98%) 91 (43%), 69 (56%), 68 (68%).  Example 6  4- Alpha 2,4-dimethylphenyl)} hydroxymethylimidazole.  The procedure of Example 1 is repeated completely, but -1-bromo-2,4-dimethylbenzene is used.  The crude product thus obtained is recrystallized. Slipped from a mixture of water with ethanol, the result is a purified product that melts at 115120 ° C.  Yield 81%.  NMR spectrogram: 2.0 (S, ZN), 2.1 (S, ZN), 4.95 (S, 2H), 5, Y (S, 1H), 6.95 (S, 1H), 6 , 8 (t, 2H) ,.  7.2 (t, 1H), 7. 4 (S, 1H).  Mass spectrogram: 202 (b2%), 185 (25%), 184 (100%), 183 (73%), 169 (39%), 157 (23%), 156 (), 133 (13%), 130 (13%), 115 (15%), 105 (11%), 97 (12%), 95 (44%), 91 (26%), 77 (14%), 69 (33%).  . .  07 And R and m 7.  4-alpha2,3-dimethylphenyl) 3-oxymethylimidazole.  The procedure of Example 1 is repeated completely, but using 1-Op () m-2,3-dimethylbenzene.  The melting point of the product obtained after recrystallization from a mixture of water with ethanol is 140-142 °.  Output.  NOL, NMR spectrogram: 1.75 (s ,. 3H), 1.85 (S, ZN), 4.75 (S, 2H), 5.65 (S, 1H), 6.25 (5, 1H), 6.85 (p, ZN), 7, 2 (S, 1H).  Example 8  4- Alpha (3,4-dimethylphenyl)} - hydroxymethylimidazole.  The procedure of Example 1 is repeated completely, but using 1-bromo-3,4-dimethylbenzene.  Yield 76%.  NMR spectrogram: 1.85 (S,), 4.8 (S, 2H), 5.4 (S, 1H), 6.6 (t, 4H), 7.2 (S, 1H).  Example 9  4- | Alpha (2-methoxyphenyl) oxymethyl1idazole.  The procedure of Example 1 is repeated completely, but 1-bromo-2-methoxybenzl is utilized.  In isopropanol, the product is converted to the hydrochloride with t. square  1b6-1b8 ° C.  Yield 72%.  NMR special procedure (hydrochloride salt): 3.65 (S, 3N), 4.7 (S,; H), 6.1 (1H), 7.1 (t, 5H), 8.5 (S, 1H).   PRI me R 10.  4-Sulf (3-methoxyphenyl) oxymethylimidazole.  The procedure of Example 1 is repeated completely, but using 1-bromo-3-methoxybenzene.  After recrystallization from a mixture of water and ethanol, the melting point of the product is 9b-97s.  75% yield.  NMR spectrogram: (S, ZI), 5.1 (S, 2H), 5.75 (S, 1H), 7.0 (ch, 5H), 7.55 (S, 1H).  Example 11  4-alpha 4-methoxyphenyl l)} hydroxymethylimidazole.  The procedure of Example 1 is repeated completely, but using 1-bromo-4-method | sibenzene.  The product is cooled at 127-129 C.  75% yield.  NMR spectrogram: 3.7 (S, ZN), 5.25 (S, 2H), 5.75 (S, 1H), 7.1 (t, 5H), 7.55 (S, 1H).  Example 12  4-AlfL4-chlorophenyl) oxymethylimidazole.  The procedure of Example 1 is repeated completely, but using 1-bromo-4-chlorobenzene.  After the redraw. Talization from a mixture of water with ethanol melts the product at.  Yield 68%.  NMR spectrogram: +, 75 (S, 2H), 5.45 (S IH).  6.5 (s, ih).  7 0 (S, H), 7.25 (S, IH).  Example 13  4- Alpha (2-ethylphenyl) oxymethylimidazole.  The procedure of Example 1 is repeated completely, but using 1-bromo-2-ethylbenzene.  After recrystallization from a mixture of water and ethanol, the product melts at 139 H2C, Pyhod 701.  NMR spectrogram: 1.1 (t, 3N), 2.65 (q, 2H), 5.05 (S, 2H), 6.05 {S W), 6.65 (S, 1H). 17.3 (t, k), 7.55 (5, 1H).  Example I.  (; , 4,6-trimethylphenyl) oxymethylimidazole.  The procedure of Example 1 is repeated completely, but bromomesylene is used. After recrystallization from the mixture. Water with ethanol melts the product at 186-188 ° C.  Exit 85.  NMR spectrogram: 1.95 (S, 9I), k, 6 (S, 2H), 5.95 (5, 1H), 6.3 (s, 1H), 6.5 (5, 2H), 7 , 25 (5, 1H).  Example 15- 5 Methyl-α-Half (2,6-dimethylphenyl) oxymethylimidazole.  The procedure of Example 1 is repeated completely, but instead of 2-bromotoluene and -imidazolald guide, 1-6 ppm-2,6-dimethyl (5 benzene and 5 methyl-A-imidazolaldehyde, respectively) are used.  After recrystallization from a mixture of water with ethanol, the melting point of the free base is:. 77 278с.  T, pl.  hydrochloride exceeds 300 ° C.  Yield 65%.  NMR spectrogram (hydrochloride salt): 1.7 (5, 3N), 2.2 (S, B11), i, 7 (B, 3N), 6, i (S, IH), 7.1 (S, 3H), 8.65 (5, IH).  Example 16  5 Methyl - - (alpha-phenyl) oxymethylimidazole.  The procedure of Example 15 is repeated completely, but bromobenzene is used instead of 1-bromo-2,6-dimethylbenzene.  After recrystallization from water and ethanol, the product melts at.  Yield 79%.  NMR spectrogram: 1.75 (S, 3N), 9 (S, 2H), 5.55 (9, 1H), 7, (t, 6H).  Example 17  5-Methyl- - (2-methylbenzoyl) imidazole.  C, 9 g of dry magnesium lathe shavings close 50 kp of dry tetrahydrofuran.  The mixture is heated to boiling point and a solution of 3 g of 2-bromo-toluene in 50 ml of dry tetrahydrofuran is added dropwise to it at such a rate as to ensure uniformity of the reaction.  After this, the reaction mixture is kitted under reflux for 30 minutes until the magnesium turning chips are completely reacted.  Next, the reaction mixture is cooled to and 20 g of methyl 5-methyl-imidazolecarboxylic acid methyl ester are added in small portions.  The mixture is then refluxed for another 2 hours, the solvent is distilled off to half the original volume.  Then the mixture is cooled and poured into 300 ml of cold water containing 15 ml of concentrated sulfuric acid with simultaneous stirring for 15 minutes, after which the mixture is filtered; The pH value of the oyltrate is adjusted and the solution is subjected to triple extraction treatment with 30 ml portions of chloroform.  The combined chloroform extracts are washed with water and evaporated to dryness.  The residue that contains the crude product is converted to ethanol in hydrochloride in ethanol.  After recrystallization from ethanol, the hydrochloride melts at 289-29I C.  5-Methyl - - (2-methylbenzoyl -1 H-imidazole is isolated from the hydrochloride in water containing sodium hydroxide.  The product melts at lb-1b-6 ° C.  Exit 88 /,;, NMR spectrum, program (hydrochloride salt): 2.0 (S, 3N), 2.15 (S,: G), ", 75 (S, 2H), 7.3 (S, kH}, B, 8 {S, 1H).  Mass spectrogram: 200 (33), 185 (), 172 (15%), 171 (lf%), 119 (), 110 (), 91 ().  Example 18  5 Methyl - - (2,6-dimethylbenzoyl imidazole.  The procedure of Example k is repeated completely, but using 1-bromo-2,6-dimethylbenzene instead of 2-bromotoluene.  The melting point of the hydrochloride is 268-27l.  The melting point of the base, which is liberated from hydrochloride in water, is 179-181 ° C.  Yield 92%.  NMR spectrogram (hydrochloride coj. b): 1.9 (5, ZN), 2.01 (S,: t), 2.07 (5, ZN), k, 7 (5, 2H), 7.15 (ZN), 8.9 (S, 1H).  The isomeric compounds of the formula T, their non-toxic pharmaceutically acceptable acidic adducts, or mixtures thereof 9 are administered into the body by garenrently, intravenously or orally.  3cxJ) eKtivny amount, the derivative is used in combination with a pharmaceutically acceptable excipient. An effective amount means an amount that allows one to achieve a ground effect, does not cause () and side effects and depends on the route of administration of the organism, the type of mammal, the conditions of administration, etc. d. and also on the structure of the derivative.  One of the effective anti-hypertonic derivatives is t-C 2,6-dimethylbenzene-imidazole, the daily dosage of which is 0.01-0.05 mg / kg animal weight.  Pharmaceutical excipients (carriers), which are used in a combination of 20 scientific research institutes with the proposed derivatives - -), are solid or hidk materials, the choice of which depends on the method of administration into the body.  So, a class of solid fillers (carriers include lactose, sucrose, chole. 1Tin and agar, and a class of liquid fillers (carriers include water syrup, peanut and olive oil or other fillers.  The combination of the derivative with a filler is given in any acceptable form, in particular the form of a tablet, capsule, suppository, solution, emulsion and powder.  The antihypertensive properties of the proposed imidazole derivatives are defined as follows.  Sprague-Devley rats of normal weight are anesthetized with urethane.  Thereafter, the femoral artery is connected to a blood pressure transducer with a polyethylene tube.  The test compound is then injected into the femoral vein and the blood pressure and pulse rate is recorded using a recording device.  Antihypertensive properties are also determined on Okamoto-Aoki rats with spontaneous hypertension (GLC. The test compound is administered orally to the body via a tube directly into the stomach.  Blood pressure is measured on the tail according to the indirect bloodless method. .  The prophylactic effect of the compounds of Formula 1 on the formation of sludge is determined as follows.  7 Sprague-Devley females, 10 years old, each weighing 200-250 g each, are not fed overnight.  The animals are then divided into two groups.  Rats of the first group are given orally 20 kg / kg of indomethacin, and rats of the other group are given the test compound intraperitoneally at the same time as indomethacin.  After the expiration of A h, animals are sucked and the anti-ulcer action is determined by counting the stars and comparing the data obtained in animals that receive the test compound and in animals that are given only indomethacin.  Diuretic activity is studied in rats by urine collection at 0–5 h after intraperitoneal administration of the compounds.  Prior to testing, animals were not fed overnight and immediately before injection they were given 10 ml of water orally.  . The sedative effect of the proposed compounds evaluated as follows.  After the intramuscular administration of the test compounds to the males at the age of 1-5 days.  (two animals for each dosage monitor the duration of their sleep.  The duration of sleep under the action of barbiturate is studied in mice.  The test compound was intraperitoneally administered 30 minutes before the intraperitoneal administration of centobarbititurate mice (at a dosage of 60 mg / kgJ.  The spontaneous mobility of mice and rats is determined using an Animexatiosity measuring instrument.  Test compounds were administered intraperitoneally 30 minutes before imeination for 2 minutes.  Anilgetic effect is determined as follows.  but} .  Test with painful cramps.  The test compounds and the brine are given orally to the rats, and after 5 minutes they are injected intraperitoneally with 1 (ill 1% acetic acid).  Then, 25 min fs xs the amount of pain writhing.  BL Testing with a hot plate. Intraperitoneally the males are injected into the males and the test compounds or raspos are introduced and after 30 minutes the holding time is recorded on a plate heated to 55 C.  The results obtained are correlated with the results with saline.  The anti-inflammatory effect is determined by the degree of suppression of edema caused by carrageenan in rats that are tested by compounds.  The traction action is determined according to the Irwin netting method in rats.  They study the sedator and cataleptic effects and the effect on pyshechny tone.  The tranquilizing effect (tpmming effect) on cattle.  The compound being injected intramuscularly is introduced to cattle cattle, mainly to chicks (130,200 kg).  They are followed by n; 1) people for 3 hours, studying their vital functions, the reaction to pain and touching their hands, muscle tone, sleep and so on. P.  The most pronounced tranquilized state of the animal includes the ability to maintain a good posture and coordination with minimal avoidance reactions (5% stimulators and hand touches).  Acute toxicity was determined on female mice of NMfU species at the age of 7 months. whose weight is g. Test compounds are administered intravenously.  Some of the pharmacological properties of the proposed compounds are as follows.  When studying blood pressure in anesthetized rats of normal weight, it was established that t-2,6-dimethyl-benzene / imidazole induces an understanding of blood pressure already in dosage.  ; 1 µg / kg intravenously, and LD is kO mg / kg.  At a dosage of 3 µg / kg (intravenous administration, a decrease in blood pressure is observed, and at a dosage of 10 µg / kg, a decrease in blood pressure is 30%, a decrease in the pulse rate is 12%, the duration of the compound is 50 minutes, after which the measurement is stopped.  Because of the intravenous injection into the body, the LD50 value is 40 mg / kg, it can be concluded that the therapeutic dosage range for such a compound is shear.  When determining the antihypertensive effect of this compound on awake rats of a CAG, it was established that a decrease in blood pressure on oral administration of 205 at a dose of 300 µg / i / kg is noted after h.  When determining the anti-ulcer effect of this compound, it was established that a dosage of 5 µg / kg when administered intravenously prevents the formation of ul.  For compound 4-12-methylbenzyl) imidazole, the LD value of which is 25 mg / kg when administered intravenously to the mouse, a decrease in blood pressure is observed at a dosage of 0.5 mg / kg (intravenously at 10% within 30 minutes after injections and prevention of ulceration at a dosage of 5 µg / kg (pintribroshinno).  When the compound was tested (alpha (2,6-dimethylphenium 11) -oxymethylimidazole, LD value. which when administered intravenously is.  125 mg / kg for a mouse, a decrease in blood pressure at a dosage of 300 µg / kg was noted, and when administered orally to CGS rats at a dosage of 3 mg / kg, blood pressure decreased by 20% 3 hours after administration.  At a dosage of 5 mg / kg, this compound prevents the formation of sv completely, and at a dosage of 0.5 mg / kg it partially.  When tested - (.  2-methylphenyl} J hydroxyethylimidazole, the LD value, which when administered intravenously to mice is 1 Bg / kg, does not show a decrease in blood pressure.  At a dosage of 5 mg / kg, it completely prevents the formation of scum, and at a dosage of 0.5 mg / kg - partially.  In the test of 5 methyl-4-2,6-dimethylbenzyl imidazole, the LD value of which when administered intravenously to mice is 27 mg / kg, an antihypertensive effect is not observed.  At a dosage of 0.5 mg / kg, this compound prevents the formation of sc or partially, and at a dosage of 5 mg / (sg, completely.  I When testing (2,6-dimethylbenzoyl imidazole, the LD value of which when administered intravenously is 100 mg / kg for mice, a slight antihypertensive effect is detected, at a dosage of 20 mg / kg it completely prevents irritation () and 10 mg / kg partially.  Tests of it-fafa (2,6-dimethylphenyl) ethoxymethylimidazole, LD value. Which, when administered intravenously to mice, is 45 mg / kg, it has shown that it exhibits a weak antihypertensive effect, 139, and in the dosage of 5 mg / kg, it completely prevents sporulation, and at a dose of 0.5 g / kg - partially.  In you.  1 is shown with: compounds exhibiting an antihypertensive effect.  In tab.  2 shows compounds with a high therapeutic profile for treating ulcerative diseases.  7; I In tab.  3 shows compounds with a diuretic effect.  in tab.   shows compounds with a sedative effect.  In tab.  5 shows compounds with analgesic action.  In tab.  6 shows compounds with anti-inflammatory effects.  In tab.  7 shows compounds with a tranquilizing effect.  Table 1
    k- (2,6-dimethylbenzyl) imidazole
    - (2,3-Dime tilbenzyl) them (2,6-Dimethylbenzyl) imidazole
    - (2,3-dimethylbenzyl) imidazole
    C- (2, -Dimethylbenzyl) imidazole
    A- (2-Ethylbenzyl) imidazole k- (2-Methylbenzyl) imiddzol C- (3-Methylbenzyl) imidazole
    0,003
    0.00.3-0.1
    Table 2
    8,000
    0,005
    7,000
    0,005
    15
    997607 16
    Continued table. 2
    17
    Compound
    t- (2, -Dimethylbenzyl) imidazole
    - (2,3-dimethylbenzyl) imidazole
     3-Methylbenzyl) imidazrel
    | - {2,., 6-Trimethylbenzyl) imidazole
    - (2-Ethylbenzyl) imidazole - (3-Methoxybenzyl) imidazo C- (2-Chlorobenzyl) imidazole
    - Alfa (2,3 dimethylphenyl) hydroxymethylimidazole
    k- Alpha (2-methoxyphenyl) hydroxymethylimidazole
    5-Methyl- {2,6-dimethylbenzyl) -imidazole
    997607.18
    Table
    Dose, mg / kg 0.3-1.0 {3-10 j 30-60
    + - i19
    - Alpha 2-methoxyphenyl oxymethyl imidazole
     SLP-3-methoxyphenyl) oxymethylimidazole
    - alpha-methoxyphenyl)
    oxymethyl imidazole
     -tAlfa 2,6-dimethylphenyl) methoxymethylimidazole
     - Alpha 2,6-dimethylphenyl) ethoxymethylimidazole
    5-Methyl - "- {2-methylbenzyl) imidazole
    5-Methyl-4-alpha (2,6-dimethylphenium / 1) 3-oxymethylimidazole
    Note: GP-test with a hot plate,
    BC - tested with painful cramps.
    997607
    20 Continued table. five
    2.5
    ABOUT
    ++
    BE
    +
    13
    0.6
    ++
    “H
    thirty
    100
    13
    21
    - (2, -Dimethylbenzyl) -imidase t - (3-Methylbenzyl) imidazole
    "- Alpha (2,3 Dimethylphenyl) J hydroxymethyl imdazole
    4- Alpha (2-methylphenyl)} - hydroxymethylimidazole
    t-f Alpha (3 methylphenyl)) hydroxymethylimidazole
    4- | Alpha ("-methylphenyl Zoxymethylimidazole
     - Alpha (2-ethylphenyl | hydroxymethylMIDazole
    - Alpha (2-methoxyphenyl) 3 okeimethylimidazole
     pfa (3-methoxyphenyl) hydroxymethylimidazole
    4- Alpha (2,6-dimethylphenyl) methoxymethylimidazole
    4- Alpha {2,6-dimethylphenyl) ethoxyMethylimidazole
    - (A-Methylbenzoyl) imidazole
    - eJil - - (2-methylbenzyl) imidazole
    5-Methyl + Half (2,6-dimethylphenyl Loxy methylimidazole
    B-Methyl-alpha (2-methylphenyl Zo KS imimeti da 3 ol
    5-Methyl - «- (2-methylbenzyl) imidazole.
    Dosage 100 mg / kg (by mouth).
    99760722
    Table
    ++
    ++
    + f
    23
    (2,3 Dimethylbenzyl) imidaeol
    "- (2-Chlorobenzyl) imidazole
    - (2,4., 6-Trimethylbenzyl) imidazole
    (2,6-Dimethyl21,
    E97607
    . T a 6 l. And c a
    0.1-n0, 1 +
    0.1 +
    权利要求:
    Claims (1)
    [1]
    Claim
    A method of obtaining imidazole derivatives of the general formula where R * H, CH—, Cj.Hj or OCH—; K. "N, CH ,, or OCH ^; R * = H, C1, CH ^ or 0CH 3 ;
    Id and R g are the same or different, and mean H or CH ^;
    Y = -СК- 1 , -СИ, - ““ - С -, moreover, if R = R = R “R. = H and R, or СН 5 1 2. b 4 f then
    OH about
    I .11
    Y "-CH ~ -W-C *, or their hydrochlorides, characterized in that the compound of General formula
    HE ♦ | means CHO for the cases Ύ = - - ^ o 'or -COOCH.J, for the cases Y = ~ C f, they are reacted with the corresponding phenyl magnesium bromide of the general formula
    $ 4 in dry tetrahydrofuran medium at 50-65 ° C with the isolation of the target product $ 0 mt in free form or in the form of hydrochloride.
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    同族专利:
    公开号 | 公开日
    BG60426B2|1995-03-31|
    DK157491C|1990-06-25|
    HU184809B|1984-10-29|
    EP0024829A1|1981-03-11|
    ZA804787B|1981-07-29|
    US4443466A|1984-04-17|
    SU1014472A3|1983-04-23|
    UA5559A1|1994-12-28|
    HK68587A|1987-10-02|
    NO153220C|1986-02-05|
    DK157491B|1990-01-15|
    NO802352L|1981-02-09|
    DE3067618D1|1984-05-30|
    DK630586A|1986-12-29|
    AU6107180A|1981-02-12|
    AT7226T|1984-05-15|
    CA1154780A|1983-10-04|
    AU518569B2|1981-10-08|
    DK338580A|1981-02-08|
    DK630586D0|1986-12-29|
    IE50080B1|1986-02-05|
    NZ194536A|1983-06-17|
    NO153220B|1985-10-28|
    IE801626L|1981-02-07|
    IL60723A|1985-02-28|
    FI802404A|1981-02-08|
    JPS624387B2|1987-01-30|
    SG34987G|1988-03-04|
    DK155794B|1989-05-16|
    EP0024829B1|1984-04-25|
    DD152548A1|1981-12-02|
    JPS5632463A|1981-04-01|
    DK155794C|1989-11-06|
    FI70709C|1986-10-06|
    FI70709B|1986-06-26|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US6457579A| true| 1979-08-07|1979-08-07|LV920312A| LV5060A3|1980-08-06|1992-12-17|Method of obtaining imidazole derivatives or their hydrochlorides|
    LTRP762A| LT2215B|1979-08-07|1993-07-07|IMPORTANT BUDGET FOR IMIDAZOL OR HIDROCHLORIDE|
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