• 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 method of obtaining the derivatives, nortropanol of the general formula (1) At-X-CHj-CHj-CHj-M is a radical of the formula where Ar is fVR, I I. , where R is hydrogen, fluorine, bromine, thyl or methoxy; X - radicals .CO, CH-CM, sn.one, NCH-QHF, R or with form where under the arms where with, ty, lennom or -NH-; - hydrogen, 4-fluoro, 4-chloro, 4-trifluoromethyl, 3-trifluoromethyl, 3-triftoEcchetl-4-chloro, 4-methyl or 4-methoxy, their salts, o tl and h and y y and it, that the compound of the common mule R has the indicated values, is reacted with an alkyl dim compound of the general formula III-A-X-CH-CHj-CH Ar has the indicated values; halogen or alkylbenzenesulfonyloxy has the meaning indicated for radical X or means the group as follows, in case of removal of ethylene ketal, and the yield of the desired product in free form, or as a salt. .
    公开号:SU1042617A3
    申请号:SU813355198
    申请日:1981-11-24
    公开日:1983-09-15
    发明作者:Лангбейн Адольф；Мерц Герберт；Соботта Райнер；Бауер Рудольф；Михаэль Иенневейн Ханс；Мирау Йоахим
    申请人:К.Х.Берингер Зон (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a process for the preparation of new derivatives of northol of the general formula CH, -CHO-CHO-1 1. i. B. . . .jr- where Ar is the radical of FoO and the .JO. - hydrogen, fluorine, bromine, meth or methoxy, X - radicals WITH,: CH-SYa, or -O-, -SR - hydrogen, 4-fluoro, 4-chloro, 4-tr fluoromethyl, 3-trifluoromethyl, 3 fluoromethyl- 4-chloro, 4-methyl, or, 4-methoxy, or their salts, which have valuable macologic properties. A known method for the alkylation of a piperidinyl-4-ol derivative. with an aroyl alkyl halide in an inert organic solvent. In some cases, the process is accelerated with heating T |. The purpose of the invention is to obtain nthropanol derivatives that have improved pharmacological properties. This goal is achieved by the method based on the well-known method 1, combined with the general formula where R has the indicated values, is reacted with an alkylating compound of the general formula Ar - CHj , - CHj - CH, - At fTl where Ar - has the indicated values Y -. halogen and: pi alkylbenzenesul fonyloxy; has the meaning indicated for the radical or means groups, followed, if necessary, by removal of ethylene ketal, and precipitating the desired product in a free form or in salt form. The reaction can be carried out in the absence or presence of an inert solvent, such as, for example, chlorophor, toluene, ethanol, nitromethane, tetrahydrofuran, dimethylformamide. It is advisable to carry out the reaction when heated. Adding a catalytic to a molar amount of potassium or sodium iodide has a positive effect on the course of the reaction. Example. 8- (4-P-fluorophenyl-4-oxobutyl) -3- (4-chlorophenyl) -3-nortropanol hydrochloride. A mixture of 27.4 g (0.1 mol) of 3- (4-chlorophenyl) -3-nortropanol hydrochloride, 26.9 g (0.1 mol) of 4-chloro-4-fluorophenylbutyrene, 25.4 g ethylene ketal, 25.4 g (0, 3 mol of sodium sodium carbonate and 5 g of potassium iodide in 250 ml of dimethylformamide are stirred and heated to 100 ° C for 5 hours. Then the solvent is removed in a rotary evaporator at 70 ° C. The residue is taken up in 200 ml of ethyl ester of acetic acid, washed twice with water in a quantity of 100 ml and concentrated. The residue is dissolved in a mixture of 500 ml of 2N. hydrochloric acid and 500 ml of ethanol. The hydrochloric acid solution is heated to 50 ° C. for 30 minutes. After cooling, it is concentrated. The residue is made alkaline with 50 ml of concentrated ammonia with ice cooling and shaken three times with methylene chloride in an amount of 100 ml each. The resulting organic phase is dried over sodium sulfate and filtered on 10 g of silica gel, followed by concentration in a rotary evaporator. "The residue is dissolved in 50 ml of ethanol and first 0.1 mol of ethanolic acid is added, and then ether, so that the resulting turbidity immediately disappears . 24.5 g of the title compound are obtained, which is 56% of the theoretical yield. Melting point: 244 ° C. Calculated: C 63.01; H 5.98; SL 16.18; to 4.33; N 3.22. Cj HjjClFNO HC1 (molecular weight: 438.36) Found: p. 62.88; H 5.64; e 15.76; F 4.28; N 2.91. Similarly, compounds of the formulas are prepared. G-X- (CH2), F listed in the table. The new compounds of general formula (1) show a typical picture of the action of neuroleptic drugs and are therefore planned for use as a sedative (sedative) agent and tranquilizer for neutralizing the central nervous system. In comparison with similar structure, which also has a neuroleptic effect, halo peridol 1- (3-P-fluorobenzoylpropyl) -4-P-chlorophenyl-4g-hydroxypiperidine3 new compounds show a more favorable profile of action. The described compounds were investigated by experiment conducted on api-morphine using B. Costall et al. It was found that they exhibit a strong aproscleroan activity, which is many times greater than the effect of haloperidol. According to the level of technology can be expected. These properties can have a neuroleptic effect on humans, “Conclusions regarding adverse events, such as sedatatsiya or impaired motocordination, were made on the basis of the following research materials: motility studies on the basis of THSvensson HG.Thleme, the study showed that using compounds exhibit sedation. action A test of determination of the ataxia action by means of a rotating one. Rods (Rotarod) by N.W.Dunham T.s.Miya, allows us to conclude that the substances used cause mobility disorders. In particular, the side effects of the proposed compounds are more: favorable results than the comparative substance haloperidol. To determine the biochemical characteristics of the proposed compounds, studies were conducted on rats. Thus, the proposed substances were studied experimentally by determining the effect of ZN-spiroperidol and preparative synaptosome samples from the brain of rats (Stratium). The test used dp-labeled 8- 3- (p -fluorobenoyloyl) -propyl} -1 -1-phenyl-1,3,8-triazaspyrot4, 5 decan-4-one according to I.Greese D.R.Burt and S.H.Snyder. Compared to galrperidol, the test substances have many times better contact effects and are thus potent antipsychotic agents. In addition, studies have been carried out to determine the adotinergic and about -adrevolitic properties using tritiated hydrochloride (2, b -dimethoxy-phenoxy} -ethyl-am-: but-methyl-beisodiszhsansa- "c-adrenergic antagonist. the test showed that the proposed compounds were found in comparison with haloperidol in MNOCH times 14 times higher than the properties. Studies on muscovite-anti-cholinergic contact action Conducted on a test using marked trityl04 3-quinuclidi nid-benzylate by lamanura and S.H.Snyder. The described compounds showed partly stronger actiholinergic contact properties than haloperidol. Taki; 1 way, the proposed method allows to obtain new derivatives of nortropaiol, with improved properties compared to haloperidol.
    Continued table
    Table continuation
    权利要求:
    Claims (1)
    [1]
    A method of obtaining derivatives of nortropanol of the general formula (1) where Ar
    is a radical of the formula or
    - hydrogen, fluorine, bromine, methyl or methoxy; .
    - radicals> CO, 5CH-CH,> CH-OH,
    -S- or -ΝΗ-;
    R is hydrogen, 4-fluoro, 4-chloro, 4-trifluoromethyl, 3-trifluoromethyl, 3-trifluoromethyl-4-chloro, 4-methyl or 4-methoxy, or their salts, exc. js so that, the connection is common
    IT . where R has the indicated meanings, is reacted with an alkylating compound of the general formula III
    Ar-X'-CH 2 —CH 2 —CH 2 —Ύ wherein Ar has the indicated meanings; Υ - halogen or alkylbenzenesulfonyloxy group, and X 4 has the meaning indicated for the radical X or means a group
    Λ
    H ^ C — CH g 'followed by, if necessary, removal of ethylene ketal and isolation of the target product in free form, or in the form of a salt. .
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    引用文献:
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    法律状态:
    优先权:
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