• 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 concerns 6-methoxy-2-acetylnaphthalene oxime derivatives of the general formula <IMAGE> in which R1 and R2 each represent a lower alkyl radical, or form, in association with the nitrogen atom to which they are linked, a saturated heterocyclic group, and the acid addition salts thereof with physiologically acceptable acids. These derivatives have analgesic, antipyretic and anti-inflammatory activity and can be made up into pharmaceutical compositions in tablet, capsule, suppository and the like forms. The derivatives of the invention may be prepared by reacting the corresponding 2-acetyl-6-methoxynaphthalene oximes with an appropriate substituted halogeno-ethylamine.
    公开号:SU784763A3
    申请号:SU792792753
    申请日:1979-08-02
    公开日:1980-11-30
    发明作者:Эстеве-Субирана Антонио
    申请人:Провезан С.А. (Фирма)；
    IPC主号:
    专利说明:

    the presence of sodium hydride. As a result, the target product is isolated either as a free base or in hydrochloride. The latter is obtained by reacting the base with ethanol saturated with hydrohalic acid,. Example 1 Preparation of 6-methoxy-2-acetylnaphthalene-O- (2-dimethylaminoethyl) oxime. In a 500 ml Erlenmeyer flask equipped with a stirrer, a cooler and a dropping funnel with calcium chloride, 21.5 g (0.1 mol) of 2-acetyl-6-methoxy-naphthalene oxime, 2.5 g (0.1 mol) are added. sodium hydride and 200 ml of anhydrous dionne. The temperature of the reaction mixture is maintained at 3 hours, after which 0.11 mol of dimethylchloroethylamine is added to the reaction. The temperature of the reaction mixture is maintained at a level. 1Q ° C for 12 hours, after which the reaction mixture is cooled and poured into 2 liters of water. A precipitate is formed, which is filtered off and washed with distilled water. After recrystallization, for example, from Me C N of ethyl alcohol, b-methox -2-acetylnaphthalene-O- (2-dimethylaminoethyl) oxime is obtained as a free base, mp. 93-95 s. To obtain the corresponding hydrochloride, for example hydrochloride, the free base is reacted with ethanol, saturated with hydrohalic acid, for example hydrochloric acid, after which the residue is evaporated in vacuo. Recrystallization is then carried out, for example, from acetonitrile. The hydrochloride obtained in this way has m, pl. from 238 to, Examples 2-4. The same operations were carried out as in Example 1, using respectively substituted chloroethylamines, and I obtained, respectively, diethyl-substituted, pyrrolidino and piperidinoproducts. In tab. Table 1 lists the physico-chemical characteristics of these derivatives, in particular the recrystallization solvent, the melting point, and the characteristic peaks in the NMR spectra. An elemental analysis of these compounds is presented in Table. 2. -CHj-B Table
    . -S / 82-83 MeOH / HiO 220-221 CH CN61 P r and m replacement by
    (4H, m)
    from 8.2 to 7.2 (6H, m); 5.8 (2H, t); 4.25 (ЗН, s); 3.82 (2H, t); 3.65 (4H, m.); 3.8 (ЗН, s); 2.55 {6H, m) e ch. Nc e. Solvent C. — Internal standard: TMS, b, m-multiplet, C — singlet, T — triplet. Elemental analysis of the compounds obtained The analgesic activity of the derivatives of general formula D was determined in mice (males) weighing from 20 to 25 g. The test product was administered as a suspension in gum arabic, 5% orally, using an esophagus probe. The solution was administered in an amount of 25 ml / kg, and the concentration of the test product varied depending on the dose administered. Pain sensation in animals was caused by intraperitoneal administration of a solution of acetylcholine bromide in an amount; 0.2 ml-20 g, having a concentration of 0.32 mg / ml. 5 minutes before the test preparation was administered, groups of 5 mice were injected with acetylcholine, then injected; the test drug, followed by a secondary injection of acetylcholine after 20/40, 80, 120, and 160 minutes. In all cases, the number of convulsions was recorded per injection of acetylcholine for 5 minutes. Analgesic activity was calculated according to the following formula: I. 100 - () (1-Hp / I - inhibited pain sensations after T minutes; HO - number of seizures before the introduction of the product; H - number of seizures after T of the min after the introduction of the product. For for determining the 50% analgesic dose (YES-50), different doses of each product were administered. For each of these doses, the I, values were calculated for a time of 20, 40, 80, 120, and 160 minutes. effect, was taken as the average of the obtained 5 values And for each of the doses. Then Table 3 shows the dose corresponding to the analgesic cog effects as a function of the logarithm 2. The resulting curve was determined to be 50% analgesic dose, i.e. a dose corresponding to 50% analgesic effect. Table 3 shows the results obtained for the derivatives according to examples 1-4. Acute toxicity. The value of the p-toxic toxicity was determined by oral administration on doses weighing from 20. to 25 g for grupps of 6 animals, while several doses were administered exponentially. The observation time was 72 4.50% lethal dose (LD-50) was graphically on a logarithmic graph. In tab. 3 summarizes the results. obtained for the derivatives of examples 1-4. Table 3 6-Methoxy-2-acetylnaphthapin-0- (2-di-methylaminoethyl} oxime, hydrochloride salt 40 336 2 6-Methoxy-2-acetylnaphthalene-0- (2-diethylaminoestil) oxime, hydrochloride salt 17,5 490 6-Methoxy-2-acetylnaphthalene-0- (2-pyrrolidineeth l) -oxime, sol noxyl salt 35 1394 b-Methoxy 2-acetylnaphthalene-0- (2-piperidinoethyl) -oxim, solo acid salt 22 254
    权利要求:
    Claims (3)
    [1]
    Claim
    1. The method of obtaining derivatives
    6-methoxy-2-acetylnaphthyloxime of the general formula
    100
    1.5
    [2]
    2.5
    0.2
    1.8 compositions can be used, for example, for various pain phenomena, 35 For brain phenomena, for migraines, for toothache, for neuralgia, for menstrual phenomena, for inflammatory rheumatism, for arthritic phenomena, for fever, for runny nose, with flu and seasonal infectious diseases.
    CHjO where smoke is a lower alkyl radical containing from 1 to 4 carbon atoms or, together with the nitrogen atom to which they are attached, form a saturated heterocyclic group, or their hydrochlorides, characterized in that they carry out the reaction of 2-acetyl-6-methoxynaphthyloxy total the formulas ft 2 ^ are each. For use in the treatment of humans, the proposed dose of the compounds according to the invention is within the range. from about 100 to 500 mg / day when taken, for example, in the form of tablets, gelatin capsules or suppositories. Three common galenical formulas for the 50 derivatives of the invention are given below as examples. Example of tablet formulations}
    I
    CH 3 0 with substituted haloethylamine of the general formula mg:
    [3]
    6-Methoxy-2-acetylnaphthalene-0- (2-pyrrolidinoethyl) oxime, hydrochloric acid salt 100
    Amidon 50
    X-CH g -CH g -Ή 1 and where X is a halogen atom, a R ^ h R each represents a specified value, and the target product is isolated in the form of a base or corresponding hydrochloride.
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3963778A|1965-11-10|1976-06-15|Bayer Aktiengesellschaft|Basic oximes and their preparation|
    US3937841A|1967-04-05|1976-02-10|U.S. Philips Corporation|Treatment of depression|JPS58156006U|1982-04-13|1983-10-18|
    JPS61192912U|1985-05-25|1986-12-01|
    JPH0525285Y2|1987-01-12|1993-06-25|
    JPS63173814U|1987-05-02|1988-11-11|
    CA2584311C|2004-10-26|2010-09-14|Sigma-Aldrich Co.|Synthesis of amino acid, n-carboxyanhydrides|
    GB2435830A|2006-03-09|2007-09-12|Del Dr Esteve S A Spain Lab|Oxime ether compounds for the treatment of conditions associated with food uptake|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    FR7822836A|FR2432506B1|1978-08-02|1978-08-02|
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