• 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 producing piperidinopropyl derivatives of the general formula: Chun 0-cng cH-ciV O WrO-B J, where R and Rj are hydrogen or a lower alkyl group; R is hydrogen, hydroxyl or benzyloxygrut; A is a group -NN-, a group is -NCR, where R / is hydrogen or lower alkyl, a group. Where Xg is a group -N-Rj-, where R is hydrogen or lower alkyl, UH.- group y with Z, where Z is oxygen or sulfur, B is pyridyl, benzimidazolinone or, if A is group X. then B is phenyl, possibly substituted by a lower alkyl or alkoxy group or their pharmacologically compatible halides, consisting of that the joint of the general formula (P) 1 0-CHg-CH-CH2-kGL-CH2-0-B JL vu - J. W, where R and Rj - have the indicated meanings; XH - amino or propylamino. the group is reacted with a compound of the general formula (111) Q S co L. C O, where L. L, hydrogen, lower alkyl, halogen; hydroxyl or halogen. to 4 S 00 H or with a compound of the general formula (lY) MeS H (/ S S, AlkO where Me is metal; AlkO is lower alkoxy, followed by cyclization of the resulting product, if necessary, by benzene of compound (J),
    公开号:SU1241987A3
    申请号:SU813241895
    申请日:1981-02-05
    公开日:1986-06-30
    发明作者:Фрибе Вальтер-Гунар；Михель Хельмут；Росс Карл-Хайнц；Видеманн Фритц；Шпонер Гисберт；Шауманн Вольфганг
    申请人:Берингер Маннхайм Гмбх (Фирма)；
    IPC主号:
    专利说明:

    where R is the hydroxy group, and the viscosity of the target product in the free pid
    or T; pkde pharmacologically sovmes- TJ-iMoro g halide.
    The invention relates to the production of new piperidine derivatives of the general formula
    B
    0-SN gSh-SNg
    Ш 7-0-В

    I1
    R2
    where R and IL can be the same or different-1I to mean a hydrogen atom or a lower alkyl group; - poo, R - hydrogen, hydroxyl
    or benzyloxygroup j A - group - group - -N-C-Ri, 5 where Ri is hydrogen or lower alkyl; the group X ,, -Ug 5 where X, is about 3 p ach e of r y and n p y N - K-, where Rj - is hydrogen or alkyl 5 U - about the group,., g. Z is oxygen or sulfur .; B - pyridyl, benzimittazolg understood or 5 if A - means the XE-U group, then B - phenyl, possibly substituted by a lower a.p-kilyl or alkoxy-strong group
    or their pharmacologically compatible first halides, possessing them; their vasoretic: iridescent action,
    The purpose of the invention is to develop a method based on a known method, a method of producing new compounds with valuable pharmacological properties, of enhanced action,
     The invention is illustrated by the following examples.
    Example 1. 4- (2-Oxy-3-) 4-phenoxymethylpiperidino (-propoxy) -2-benzimidazolinone hydrochloride.
    23.0 g of 2,3-diamino-1- (2-hydroxy-3-) -4-phenoxymethylpiperidino (-propoxy) benzyltrihydrochloride is dissolved in
    7
    600 ml of water. Phosgene is introduced into this solution over 40 minutes. Product G: RustallSap- sucked off ,. mixed with 500 ml of hot ethanol, treated with activated carbon and precipitated with 2, 5: i of ether. After repeated Hofi-recrystallization from ethanol and {oTiioij; e 4e :)) get 9.1 g
    (, 3Z from theory) hydrochloride with t, pl
     ; 44-46 C (, see Table 1).
    II p and mep 2, 4-- 2-Pivalorsh-- hydroxy - 3 (4 - phenoxymethylpiperidino) - -,: horn: .oxy j-2-oenzimidazolinone hydrochloride,
    5.0 g of 4- 2-hydroxy-3 - (, 4-phenoloxy-iyo.peeperid F o) -propoxy 1-2-benzimidazolinone (for preparation see Example 1) is added to 31e5 dg melted; and mixed with 6,., 28 pivalic anhydride anhydride; G: The mixture was stirred at room temperature for 5 days, then poured into 100 ml of ice-water, neutralized with diluted ammonia (1:10), 5 extracted, dichloromethane, dried over sodium sulfate and sugiasht. The residue was washed with ether, dissolved in alcohol and Laugh with 2N hydrochloric acid,
    After drying, they are subjected to over-); ristagiya from 20 ml of ethanol. According to 3 65 g. (56% of the theory) of conjugation with thi, 168-170 ° C,
    Example 3. A- 2 Oxy-3 - (- 4-Fensxymethylpiperidico) -propoxy - -6 5 7 - dimethyl - 2-benzimide.zolinongydroh.gorid.,
    Similarly, when 1-4u 1, 2,3-diamio-4, 5 - dimethyl-1 - 2 hydroxy - 3- (4-phenoxy-sime: peridvko) -proproxy | -benzene-trihydrochloro-oligomeric acid - her: tweak with Losgen. Output connector
    Nor is 24%, so pl. 270-275 C Used as the starting material 2 ,. Z-diamino-4 5-dimethyl- | 2-hydroxy 3 (4-phenoxy-etylpiperi
    3 1241 this) -propoxy-benzene trihydrochloride is obtained as follows: 15.9 g of 2-amino 1- (2,3-epoxyprop-hydroxy-A, 5-dimethyl-3-nitrobenzene and 2.8 g of 4-phenoxymethylpiperidine under reflux heated in 300 ml of ethanol for 5 hours.
    The cooled solution is added to 1.0 g of platinum oxide in 100 ml of ethanol, then hydrogenated at room Q temperature. After filtration, acidified with dilute hydrochloric acid and concentrated, the residue is placed in ethanol with water, treated with activated carbon and after concentration, 28.4 g (84% of theory) are obtained with mp, mp 144-148 ° C.
    In a similar way, a) 4- 2-hydroxy-3- 4- (4-carboxamidophenoxymethyl) -piperidino-propoxy-6,7- 2o-dimethyl-2-benzimidazolinone hydrochloride with a melting point of 311-313 C ( ethanol-water) and 29% yield from 2,3-diamino-1 - | 2-hydroxy-3- 4- (4-carboxamipophenoxymethyl) -piperidino-propoxy -4.5-25 dimethylbenzenethrihydrochloride and phosgene,
    Example 4 Analogously to Example 1, the compounds listed in Table 2.20 are prepared.
    Froze 4- {2-Hydroxy-3- 4- (2- methoxyphenoxymethyl) -piperidino-propoxy j-2-benzimidazoline thione hydrochloride.
    6.1 g of 2,3-diamino-1- 2-hydroxy-3-G4- (2-methoxyphenoxymethyl) -piperidino J- -propoxy and benzene trihydrochloride are mixed with 12.0 ml of 1N sodium methyl acetate solution and concentrated until dry. The residue is dissolved in 15 ml of ethanol and boiled under nitrogen for 2 hours with 2.1 g of potassium xanthate. 1.26 g (22% of theory) of the compound with melting point, 212-215 s, are obtained in the hot state of recrystallization from ethanol.
    Example 6. 4- | 2-Hydroxy-3- 4- - (3-methylf, enoxymethyl) -piperidino-J-propoxy -2-benzimidazolin-thihydrochloride.
    M.p. 236-237 C, from methanol is prepared analogously to example 5 from 2,3-diamino-1- {2-hydroxy-3-4- (3-methylphenoximemetl) -piperidino-propoxy J-benzo-a and potassium xanthate.
    Example 7. 4 p-hydroxy-3- (4-phenoxymethylpiperidino) -propoxy | - -7-methyl-3-propyl-2-benzimndazolone.
    40
    45
    55
    ,
    Q
    2 25
    20


    Q

    40
    45
    five
    987. four
    Analogously to Example 1, from 3-amino-1-2-hydroxy-3- (4-phenoxymethylpiperidino) - -propoxy-1-4-methyl-2-propylaminobenzentrihydrochloride and phosgene receive 54% of the compound, mp 234-235 ° C,
    The starting material required for this is prepared as follows: .15.0 g of 1–2-hydroxy-3- (4-phenoxymethylpiperidino) -propoxy-4-methyl-2,3-dinitrobenzene (see Example 4a) for 3, 5 hours, heated to boiling in 12 ml of N-propylamine. After cooling, 8.8 g (59% of theory) of crystalline is isolated, 1 - | 2-hydroxy-3- (4-phenoxymethyl-piperidipo) -propoxy-4-methyl-2-propylamino-3-nitrobenzene with m.p. 9 1-93 ° C.
    With platinum oxide, this compound is added to the desired 3-α-amino-1-2-hydroxy-3- (4-phenoxymethyl-piperidino) -propoxy-4-methyl-2-propylaminobenzene. .-.
    EXAMPLE 8 4- 2-Oxy-3-J4- (4 -2 -2-benzimidazolino-nyloxymethyl) -pyrididino-propoxy-6-methylbenzotriazole hydrochloride.
    7.7 g of 2, 3-diamino-1- {2-hydroxy-3- 4- - (4-2-benzimidazolinonyl-oxyethyl) - piperidino-propoxy-5-methylbenzentrihydrochloride is dissolved in 45 ml of water and 17 ml of glacial acetic acid. The solution, cooled to O C, is mixed with 1, 0 g of sodium nitrate in 1.6 ml of water and stirred at room temperature for 1 hour. The solid precipitated product is removed and recrystallized from ethanol / ethyl acetate. 3.4 g (50% of theory) of the compound are obtained with t, pl. 227-230 C.
    The diamino compound. Applied in. the quality of the source material, obtained as follows.
    6.72 g of 2- (2,3-epoxy) 2-methyl-6-nitroaniline and 7.10 g of 4-2-benzimidazolinone oxymethylpiperidine are boiled in 200 ml of ethanol for 8 hours. The solution is added to 0.3 g of platinum dioxide in 100 ml of ethanol and hydrogenated at room temperature and normal pressure. It is filtered, acidified with hydrochloric acid in ether, and 7.7 g of 2,3-diamino-1- -42-hydroxy-3- 4- (4-2-benzimidazoline-onyloxymethyl) -piperidino-line is sucked off, Si1 - - 5-methylbenzenetrihydrochloride.
    Example 9. 4- 2-Oxy-3- 4- (2- -pyridyloxymethnl) -piperidino-propoxy-7-methylbenzimidazol hydrochloride,
    512
    18.0 g of 2, 3-di-sno-l- | 2-hydroxy-3-h- (2-pyridyloxymethyl) -piperidino-J -, -11-propr-x-4-methyl-bieiol-trihydrochloride are boiled in 60 ml of formic acid for 2 hours. Formic acid is completely distilled off, boiling: for 2 hours - in 60 ml of 2n. bleed with activated charcoal and thicken to dryness. The residue is crystallized from 160 ml of ethanol / 40 ml of methanol. 8.5 g (54% of theory) of the compound with t, nl are obtained. 188-190 Cp which can be converted by benzolyrovanium into the compound according to example 13.d
    Example 10. 4- | 2-Hydroxy-3-1A- (2-pyridyloxethetil) -piperidino - -propoxy -2-methylbenzimidazole hydrochloride.
    In 50 ml of glacial acetic acid, 9.6 g of 2,3-diamino-l- | 2 oxy-3-14-2 (2-hyridyloxymethyl. -Piperidine-but-propoxy} -6enzoltrigi doprochloride are boiled for 3 h
    After concentrating to a dry state, the partially formed 2-0-adylsyl compound ω1.1l in 50 ml of 2N hydrochloric acid for 2 hours at boiling. After clarification with the activated layer, they condense and crystallize from ethanol / ethyl acetate, Izolirzpot 2, 3 g (27% of theory) compound with t, silt, 166-169 s.
    Example 1 i, 4 - 2-exn-3- 4- (4 acetamidophenoxymethyl) -piperidino-T1-propoxy J-1-formylindoline,
    3.3 g 4-J 2-OXI-3-- 4- (4-aminophenoxymethyl) -piperidino-propoxy) formylindoline (preparation see, example 5b) is mixed with a mixture of 25 m of acetic anhydride B) and 25 ml of pyridine for 10 hours at room temperature, concentrated in vacuo and dissolved in water and dichloromethane. After neutralization with liaTi bicarbonate, the organic phase is distilled off and the resulting residue in methanol with sodium methylate solution is taken to the desired compound. Extraction by shaking between dichloromethane and water and evaporating the organic phase gives I, 0 g (27% of theory) of oxy-3-4- (4-acetamidrphenoxy-ethyl) -piperidino-propoxy | -1-form of chindoline with t .pl. (s; m, tabl, 3)
    Example 12, 4 | 2-hydroxy-3- 4- - (2-pyridyloxymethyl) -piperidino-propoxy -2-hydroxymethylindol benzoate.

    19876
    To a suspension of 1 g of lithium sodium hydride in 125 ml of abs. Tetrahydrofuran is added dropwise a solution of 4.6 g of 4- (2- -ox-3-4- (2-pyridyloxymethyl) -piperidino-propoxy 1-2-e Sicarbonylin-Dol current (g :: see, example 18 e) in 125 ml abs. tetrahydrofuran, stirred for 30 minutes, decomposed by cooling with a solution of sodium chloride g and a solution of 1 It, caustic n.tra, spray TAT; washed with tetrahydrofuran and thicken. After adding an equivalent amount of benzoic acid, is obtained from isopropanol, 4.0 g (74% of theory) of the compound with t, mp. 76-784 :.
    And p and mep 13, 4- | 2-Benzoilok (
    Si-3- 4- (2-pyridyloxymethyl) -piper i
    ;:; ino-propoxy-7-methyl-benzimide Q 3 o l H id p o X l o p ,,
    4.37 g 4- | 2-hydroxy-3-4- (2-pyridyl-scsime hydro) -piperidino -Gropoxy-methyl benzim1.dazole (preparation see, example 2), 19.5 g of benzoic acid
    j and 2jl2 g of benzoic acid anhydride) in a wok for 2 hours, is heated at boiling in 100 ml of benzene and 25 ml of dimethylformamide, After removing the solvent, the residue is placed in 100 ml of water,
    Q alkaline: with concentrated ammonia and extracted with chloroform, the chloroform phase is washed with water, dried with ethereal hydrochloric acid. After adding iso-hophopanol and ether, 21 g (41% of theory) of the compound crystallized with t.
    Example 14, 4- | 2-Benzoyloxy-3- - (2-pyridyloxymethyl) -piperi5
    0
    digo-triporfOKi: Mr. -Idr (5 chloride,
    si I-7 methylbenzimidazol20, O g 2, 3-diamino-1 - | 2-benzoyl-oxy-3- (2-pyridyloxymethyl) -piperchdino-J-prooxy-4-methylbenzoltrothylochloroide boils for 2 h with reflux in a 60 ml of formic acid, the formic acid is distilled off by half-boiling water, boiled for 2 hours: from 60 ml of 2N hydrochloric acid, lighten with activated charcoal and concentrates the cosiness to dryness. The residue is crystallized from 160 ml of ethanol, 40 ml of methanol,
    Obtain 7.8 g (50% of theory) Soyocinis-1 with t, pl, 178–81 s.
    The compounds obtained were tested for their vasodilator and / b-blocker; dragging activity. Since both properties cannot be investigated
    7 -
    In a separate experimental model, various pilot plants are selected.
    a) Test for vasodilator activity.
    The dilation of the blood vessels becomes noticeable due to a decrease in blood pressure. Rabbits were given for urethane anesthesia. For continuous measurement of arterial blood pressure in A, a femoral is implanted catheter. Blood pressure was measured using an electromechanical pressure transducer (Statham P23D). The pulses were recorded on a direct recording recorder and, after calibration, were determined using a mercury manometer.
    After determining the initial value, both carotid arteries (A.Caratis) were closed for 2 min and the blood pressure (CSE reflex) temporarily increased. Then, the test substance at the lowest dose of the test (0.125 mg / kg) was injected intravenously and later every 8 minutes again injected at a logarithmically increasing dosage (factor 2} test substances and the CSE again appeared (doses: 0.125, 0.125, 0.25 mg / kg).
    Substances that, under these conditions, weaken the increase in blood pressure at CSE, are vasodilating. For test substances, a dose was calculated that reduces the CSE reflex by 30 mm Hg, st, (mm Hg)
    Since in each experiment the dose was tested until the animal died from toxic effects, it was possible to determine the lethal dose for each animal (lethal dose, LD). From igzdivrvdualnogo private LD. mmHg, the therapeutic index is calculated
    In some cases, it was not possible to determine the lethal dose, since the solubility limit was lower than
    9878 compatibility limit (indicated in the table, 4 is more).
    b) Test on-blocking by activity,
    Rabbits were fixed in wooden cages, heart rate in awake animals degenerated through point electrodes and read on a frequency counter (measurement time 15 s). First, intravenous mg / kg of isoprene was injected through the inferior vein, which increased the heart rate from approximately 200 beats / min to 330 beats / min. Then the test substances were administered intravenously in an increasing dosage (see method a) and the cardiac frequency after isoprenaline was again calculated. Inhibition of tachycardia from isoprenaline can be considered a blockade. The dose of the test substances has been determined, which limits by half the amount of isoprenaline tachycardia.
    The data from both experiments are shown in Table 4.
    Calculation of equally equivalent doses (DE 50mm. Mercury., See.) And private were made on a logarithmic basis of 4-6 separate experiments ,.
    The following compounds were tested.
     1a 4- (2-Oxy-3- 4- 12-benzimidazolinone hydrochloride;
    Example 1 in 4- | 2-hydroxy-3- 4- -proxy | -2-benzimidazolinone hydrochloride;
    Example 1e 4- | 2-hydroxy-3- 4- (2-pyri-dyloxymethyl) -piperidino-propoxy | -2-benzimidazolinone hydrochloride; g p
    Example 1g 4-2-hydroxy-3-14-J-propoxy-2-benzimidazo linr hydrochloride;
    Example 4a 4- | 2-hydroxy-3- (4-pheno-hydroxymethyl-piperidino) -7-methyl-2-benzimidazolino-hydrochloride.
    ) 4- | 2-Oxy-3-A- (2-methoxyphenoxymethyl) -piperidine-propox1 2- -benzimidazolinone hydrochloride
    s
    g
    2, 3-diamine - | 2-hydroxy- -3- | 4- (2-methoxyfenok-simethyl) -piperidine - -propoxy-benzenetrigidrochloride and phosgene
    )four-. | 2-hydroxy-3-A- (3-methylphenoxymethyl) - -, piperidine-propoxy | - -2-benzimidazolinone hydrochloride
    s
    g
    2, 3-diamino-1 | 2-hydroxy- -3- 4- (3-methylphenoxymethyl) -piperidine-propoxy 1-benzene trihydrochloride n phosgene
    ) (4-Phenoxymethyl-piperidino) -propoxy - -2-benzimidazolinone hydrochloride
    s
     2, 3-diamino-2-z- (4-phenoxymethylpiperidino) -propoxy 1-benzene trihydrochloride and phosgene
    d) 4-12-Oxy-3- (4-phenoxy-1-ethylpiperidino) -protinKCHj-6-methyl-2-benzimidazolinone hydrochloride
    Table 1
    162-164 (Methanol)
    40
    227-229 (Methanol)
    48
    257-258 (Methanol)
    31
    245-247
    one
    2, 3 diamino-1 -1 2-hydroxy-3- (4-phenoxymethylpiperidine) propoxy J-5-methyl benzene trihydrochloride and phosgene
    4- 2-hydroxy-3- (4-benoxy-methyl-piperidino) -propexy-6-tert-butyl-2-benzimidazolinone hydrochloride
    2, 3-diamino-1 - | 2-hydroxy-3- - (4-phenoxymethylpiperidino) -propoxy-5-tert-butylbenzene trihydrochloride and phosgene
    A- (2-Oxy-3- 4- (2-pyridyl-hydroxymethyl) -piperidino-propoxy -2-benzimidazolinone hydrochloride
    of
    )
    2, -3-diamino- {2-hydroxy-4- - (2-pyridyloxymethyl) - -piperidino-propoxy - -benzene trigi drochloride and phosgene
    4- (2-Oxy-3- 4- (2-benzimidazolinone-oxymethyl) -piperidino-propoxy 1-3-benzimidazolinone hydrochloride
    f
    2,3-diamino-1- | 2-hydroxy-3- - 14- (4-2-benzimidazolinonyl-hydroxymethyl) -piperidino-propoxy (-6 enzoltrigidrokhlo-. Read and phosgene
    4- | 2-hydroxy-3-1.4- (4-methyl) -2 - (- pyrimidyloxymethyl) - - piperidino-propoxy (-2- - benzimidazolinone hydrochloride 25
    of
    2,3-diamino-1 - | 2-hydroxy-3- - (4-methyl-2-pyrimidnl-β-oxymethyl) -piperidino-propoxy benzene trihydrochloride and phosgene
    24198712
    Continued table. one
    3 (Ethanol)
    261-262
    (Acetone)
    62
    195-197
    (Ethanol / methanol)
    20
    223-226. (Methanol / water)
    152-155
    (Ethanol / methanol)
    Name
    a) 4- | -Oxy-3- (4-fe, noxy-methylpiperidino) -propoxy-y-MeTHH-Z-eeHSHMHAaso linongohydrochloride
    of
    )
    2,3-diamino-2-hydroxy-3- (4-phenoxymethylpiperidino) -nponoKCHJ-4-methyl-benzene trihydrochloride and phosgene
    4- | 2-Oxy-3- 4- (2-methoxy-phenoxymethyl) -piperidino - -propoxy} -7-methyl-2-benzimidazolinone hydrohydrochloride
    of
    2, 3-diamino-1 | 2-ox1 - 3 - - 4- (2-methoxyphenoxymethyl.1) - piperidino-propoxy y-4- -methylbenzenetrighydrochlo-rd and phosgene
    c) 4- | 2- (xi-3- 4 - (2 me gsxy-4-methylphenoxymethyl) -im-peridino-propoxy-7-r-se-methyl-2 benzimidazolino-hydrochloride
    of
    2.3 diamino-1- 12-oxy-3i. , | M
    (2-methoxy-4-1methylphene oxymethyl-piperidino) - Propoxy-4 methylbe; 13OL trig drochloride and fost epa
    ) 4- 2-Oxy-3- j 4- (4-k arb oxy; a-MIDofenoc sym tyl) -piperid-HQJ-propoxy-7-methyl-2-baccimidazolinone hydrochloride 37
    of
    2,3-diamino-1 X Oxy-3-4-carbrxamidophenoxymethyl) piperidino-propok CAL-4-methylbenzenetrihydrochloride amorphous and phosgene
    Output
    from theory
    M.pl ,, c p 1solve.p
    272-274
    (Methanol)
    (Stanol / Acetic ester)
    248-250
    (And sonjion and Ioethanol /

    294-296 (Methanol / water)
    4- | 2-hydroxy-3- | 4- (4-aminophenoxymethyl) -piperidinej-nponoKcnj-l-formylindoline and methanesulfonic dichloride -blokirutcha and vasodilating, activity
    1120 280
    1673 4000
    In (4-phenoxymethylpiperidine) -propoxy-benzimidazole. .
    one . Compiled by I. Bocharova
    Editor M. Nedoluzhenko Tehred I.Popovich Proofreader L, Patay
    Order 3619/60. Circulation 379 - Subscription VNISHI of the USSR State Committee for Inventions and Discoveries 1 13035, -Moscow, Ж-35, Raushsk nab., 4/5
    Production and printing company, Uzhgorod, st. Project, 4
    Table 4
    16130 4000
    13
     1.4.3
    权利要求:
    Claims (1)
    [1]
    The method of obtaining piperidinopropyl derivatives of the general formula
    where and is a hydrogen or lower alkyl group;
    H - hydrogen, hydroxyl
    or benzyloxy;
    A - group-Ν-Ν-, group-K-C-K ^, where K.4 - hydrogen or lower alkyl, group X ^ -U ^, where X ^ group-I-Ku, where hydrogen or lower alkyl, Y ^. - group ** with - Ζ, where Ζ - oxygen or sulfur,
    B is pyridyl, benzimidazolinonyl or, if A is the group X 4 - X 2 , then B is phenyl, possibly substituted by a lower alkyl or alkoxy group
    or their pharmacologically compatible
    halide, consisting in the fact that the connection ^ General formula (P)
    0-SNg-CH-CH g- MGH-CH g O-B.
    where K, and K. 3 - have the indicated meanings;
    XH - amino or propylamino. Group,
    subjected to interaction with the compound of the General formula (111)
    C = O,
    Memory "1241987 AZ
    where is hydrogen, lower alkyl, halogen;
    · Hydroxyl or halogen, or with a compound of the general formula (ΪΥ)
    Meuse
    C = 8,
    /
    A1kO
    where Me -. metal;
    A1CO - lower alkoxy,
    with the subsequent cyclization of the resulting product, if necessary, by benzene a compound (X),
    '241987
    where ~ hydroxy group, and by excision - or in the form of a pharmacologically co-mixture of the product in the free form of thymic halide.
    αέ.
    .
    类似技术:
    公开号 | 公开日 | 专利标题
    SU1241987A3|1986-06-30|Method of producing piperidinopropyl derivatives or their pharmaceutically compatible halides
    SU862826A3|1981-09-07|Method of preparing phthalazine derivatives or their salts with pharmacetically accepted salts
    SU1331426A3|1987-08-15|Method of production of carbostyryl derivatives
    US4675319A|1987-06-23|Antianaphylactic and antibronchospastic piperazinyl-|carboxamides, compositions and use
    DE3906920A1|1989-09-14|PIPERAZINE DERIVATIVES OR SALTS, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL AGENTS, CONTAINING THE SAME AS THE ACTIVE SUBSTANCE
    HU196990B|1989-02-28|Process for producing piperazine derivatives with antiarrhythmic effect and pharmaceuticals comprising same
    CA1114379A|1981-12-15|Piperidino-phthalazines
    FR2667317A1|1992-04-03|2-AMINOPYRIMIDINE-4-CARBOXAMIDE DERIVATIVES, THEIR PREPARATION AND THERAPEUTIC USE THEREOF
    US4578481A|1986-03-25|Pyrrolacetic amides having antiinflammatory activity
    US4472411A|1984-09-18|1,4-Dihydropyridine derivatives and use as vasodilators
    US5258397A|1993-11-02|3-Isoxazoyl derivatives endowed with anticonvulsant activity, procedure for their preparation and their pharmaceutical compositions
    FI91634B|1994-04-15|A process for the preparation of therapeutically useful 1,4-dihydropyridine derivatives
    US3120540A|1964-02-04|Bis |-4-piperidinol alkanoates
    CA1086740A|1980-09-30|Piperidinopropyl derivatives and the preparation thereof
    HU203234B|1991-06-28|Process for producing new, multiply oxygenated labdane derivatives and pharmaceutical compositions comprising such compounds as active ingredient
    US4937242A|1990-06-26|1,4-dihydropyridine derivatives and pharmaceutical composition thereof
    BRPI0110184B1|2015-12-29|pyridine-1-oxide derivative, and process for its transformation into pharmaceutically effective compounds
    US4515944A|1985-05-07|1,5-Diphenyl-2-haloalkylpyrazolin-3-one intermediates
    RU2081872C1|1997-06-20|Dihydropyridine derivatives, mixture of their isomers, individual isomers or their physiologically tolerantable salts, methods of their synthesis, intermediate compounds and method of their synthesis
    DE2737630C2|1987-11-05|
    US3141019A|1964-07-14|Chaohj
    KR870001681B1|1987-09-22|Process for preparation of hydantoin derivatives
    DE3424586A1|1986-01-09|3-AMINOCARBONYLMETHOXY-5-PHENYL-PYRAZOLE COMPOUNDS AND METHOD FOR THE PRODUCTION THEREOF, AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
    DK154083B|1988-10-10|METHOD OF ANALOGY FOR THE PREPARATION OF HALOGENIC VINCAMO DERIVATIVES OR OPTIC ACTIVE ISOMERS OR ACID ADDITION SALTS THEREOF
    CA1227209A|1987-09-22|Polymethoxybenzyl piperazine derivatives
    同族专利:
    公开号 | 公开日
    AU529849B2|1983-06-23|
    IL59351D0|1980-05-30|
    SU1021342A3|1983-05-30|
    FI800407A|1980-08-17|
    CA1115703A|1982-01-05|
    HU184238B|1984-07-30|
    AU5540980A|1980-08-21|
    DD149069A5|1981-06-24|
    DE2905876A1|1980-08-28|
    CS226021B2|1984-03-19|
    EP0014928A1|1980-09-03|
    DE3060353D1|1982-06-24|
    ZA80787B|1981-03-25|
    FI66370B|1984-06-29|
    ES8102719A1|1981-02-16|
    FI66370C|1984-10-10|
    US4288442A|1981-09-08|
    CS226008B2|1984-03-19|
    JPS55113777A|1980-09-02|
    ES488401A0|1981-02-16|
    DK65780A|1980-08-17|
    IL59351A|1984-01-31|
    AT968T|1982-05-15|
    EP0014928B1|1982-05-05|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE255000C|
    US4126688A|1976-05-17|1978-11-21|Janssen Pharmaceutica N.V.|Antiemetic 1--piperidine derivatives|
    DE2550001A1|1975-11-07|1977-05-12|Boehringer Mannheim Gmbh|NEW INDOL DERIVATIVES AND PROCESS FOR THEIR PRODUCTION|
    DE2701794A1|1976-01-21|1977-07-28|Ciba Geigy Ag|OXIGENATED N-ARYL DIAZACYCLES|
    US4146630A|1976-11-12|1979-03-27|Boehringer Mannheim Gmbh|Blood pressure lowering and adrenergic β-receptor inhibiting 3--propyl-phenyl ethers|
    US4200641A|1976-12-21|1980-04-29|Janssen Pharmaceutica, N.V.|1-[-alkyl]-4-diarylmethoxy piperidine derivatives|
    DE2737630C2|1977-08-20|1987-11-05|Boehringer Mannheim Gmbh, 6800 Mannheim, De|DE2901336A1|1979-01-15|1980-07-24|Boehringer Mannheim Gmbh|NEW ARYLETHERS, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS|
    SE8003277L|1979-05-04|1980-11-05|Continental Pharma|BENZIMIDAZOLE DERIVATIVES, THEIR PREPARATION AND USE, AND COMPOSITIONS CONTAINING THESE DERIVATIVES|
    DE3200304A1|1981-01-16|1982-08-26|Sandoz-Patent-GmbH, 7850 Lörrach|3-AMINOPROPOXYARYL DERIVATIVES, THEIR PRODUCTION AND MEDICINAL PRODUCTS CONTAINING THEM|
    DE3209271A1|1982-03-13|1983-09-15|Boehringer Mannheim Gmbh, 6800 Mannheim|BICYCLIC PHENOLETHERS, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS|
    ZA848275B|1983-12-28|1985-08-28|Degussa|New piridine-2-ethers or pyridine-2-thioethers having a nitrogen-containing cycloaliphatic ring|
    US5231184A|1987-11-23|1993-07-27|Janssen Pharmaceutica N.V.|Pridazinamine derivatives|
    DE3839743A1|1988-11-25|1990-05-31|Hoechst Ag|METHOD FOR PRODUCING BENZIMIDAZOLONES|
    US5082847A|1990-07-18|1992-01-21|SyntexInc.|Carbostyril compounds connected via an oxyalkyl group with a piperidine ring and having pharmaceutical utility|
    US5614523A|1995-01-17|1997-03-25|Eli Lilly And Company|Compounds having effects on serotonin-related systems|
    US5627196A|1995-01-17|1997-05-06|Eli Lilly And Company|Compounds having effects on serotonin-related systems|
    US5789402A|1995-01-17|1998-08-04|Eli Lilly Company|Compounds having effects on serotonin-related systems|
    US5576321A|1995-01-17|1996-11-19|Eli Lilly And Company|Compounds having effects on serotonin-related systems|
    US5741789A|1995-01-17|1998-04-21|Eli Lilly And Company|Compounds having effects on serotonin-related systems|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19792905876|DE2905876A1|1979-02-16|1979-02-16|NEW PIPERIDINOPROPYL DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS|
    [返回顶部]