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WO1996005174A1 - Nouveau derive amine, procede pour le preparer et son utilisation comme antiarythmique - Google Patents

Nouveau derive amine, procede pour le preparer et son utilisation comme antiarythmique Download PDF

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Publication number
WO1996005174A1
WO1996005174A1 PCT/JP1995/001134 JP9501134W WO9605174A1 WO 1996005174 A1 WO1996005174 A1 WO 1996005174A1 JP 9501134 W JP9501134 W JP 9501134W WO 9605174 A1 WO9605174 A1 WO 9605174A1
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Prior art keywords
group
general formula
salt
compound
hydrogen atom
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PCT/JP1995/001134
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English (en)
Japanese (ja)
Inventor
You Sup Chung
Sung Dae Park
Lae Sung Kwon
Hong Sub Shin
Shigeru Tanabe
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C & C Research Labs
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C & C Research Labs
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Priority to AU26296/95A priority Critical patent/AU2629695A/en
Publication of WO1996005174A1 publication Critical patent/WO1996005174A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • Novel amine derivative its production method and use as antiarrhythmic agent
  • the present invention relates to amine derivatives useful as antiarrhythmic agents. More specifically, the present invention relates to an amine derivative represented by the following general formula (I) and a salt thereof, which can be usefully used as an antiarrhythmic agent having a blocking effect on a potassium channel.
  • an amine derivative represented by the following general formula (I) and a salt thereof which can be usefully used as an antiarrhythmic agent having a blocking effect on a potassium channel.
  • A is a general formula
  • R e represents a lower alkyl group or a hydroxy lower alkyl group, a is 0 or 1,
  • D is the formula - (CH 2) m -, one (CH 2) TM -0-, -CO- or single S0 2 - shows a group,
  • R 2 each independently represent a hydrogen atom, a halogen atom, a lower alkoxy group or a lower alkylsulfonylamino group,
  • R 3 represents a lower alkyl group
  • R 4 , R 5 , Re and R 7 each independently represent a hydrogen atom or a lower alkylsulfonylamino group
  • R represents a nitro group or a lower alkylsulfonylamino group
  • X represents a hydrogen atom or a halogen atom
  • n each represent an integer of 0 to 3.
  • the present invention includes a method for producing the amide derivative of the above general formula (I) and a salt thereof, and uses thereof as an antiarrhythmic agent.
  • Potassium channels one of the mechanisms that regulate systemic physiology, are distributed in whole body cell lines, including monocytes, myocardium, and so on. Are used for the treatment of various cardiovascular diseases, and are used, for example, as antidiabetic agents, antiarrhythmic agents and the like. Numerous compounds are known in the prior art for such a potassium channel blocker.
  • C for example, glibenclamide, an oral antidiabetic agent that blocks the potassium channel present in the cells of the tendon, is It has been reported that it blocks the ATP-dependent potassium channel of the kidney ⁇ one cell and thereby induces the release of insulin, thereby exerting a hypoglycemic effect, which is based on the sulfonylprea structure.
  • R 2 is hydrogen, nitro, halogen, d—C ⁇ alkyl or R 4 —0—,
  • R 4 is d—C 4 alkyl or phenyl, including the residue R 2 , R 5 and R 6 are hydrogen or the residue R 4 ,
  • R 7 represents residue R 1
  • n 0 or 1
  • m 1 or 2
  • n 1
  • the present inventors have searched various compound species for their ability to block the potassium channel and thereby their usefulness as an antiarrhythmic agent. As a result, the present inventors have identified a specific novel compound of the general formula (I) as defined above. Amine derivatives and their salts have few side effects and are strong It has been confirmed that a strong lithium channel blocking action is exhibited, and the present invention has been completed.
  • the present invention relates to a novel amine derivative of the general formula (I) and a salt thereof.
  • A is a general formula
  • R 8 represents a lower alkyl group or a hydroxy lower alkyl group
  • a is 0 or 1
  • D is formula one (CH 2) m -, one (CH 2) m -. 0- shows an CO- or SO 2 groups,
  • R 2 each independently represent a hydrogen atom, a halogen atom, a lower alkoxy group or a lower alkylsulfonylamino group
  • R 3 represents a lower alkyl group
  • R 4 , R 5 , Re and R 7 each independently represent a hydrogen atom or a lower alkylsulfonylamino group
  • R represents a two-terminal group or a lower alkylsulfonylamino group
  • X represents a hydrogen atom or a halogen atom
  • n and ⁇ represent an integer of 0 to 3.
  • a 5- or 6-membered heterocyclic ring containing a nitrogen atom is a group of a saturated or unsaturated 5- or 6-membered ring containing at least one nitrogen atom as a heteroatom and optionally containing an oxygen atom and a zeo atom.
  • Means for example, a pyrrolidinyl group, a pyrrolyl group, a pyrrolinyl group, an imidazolyl group, an imidazolidinyl group, a vilazolyl group, a vilazolidinyl group, a vilazolinyl group, a thiazolyl group, an isothiazolyl group, an oxazolyl group, an isoxoxazolyl group, a piperidinyl group, a piperidinyl group, a piperidinyl group.
  • Pyridyl group Pyridyl group, bilaridinyl group, pyrimidinyl group, pyridazinyl group, triazinyl group, thiadianyl group, morpholinyl group and the like. Desirable are a pyrrolidinyl group, a biperidinyl group, a piperazinyl group and the like.
  • the halogen atom means a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
  • the lower alkyl group means a linear or branched alkyl group having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such as a methyl group, an ethyl group, an n-propyl group, an i-propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group and the like.
  • the lower alkoxy group refers to a chained or branched alkoxy group having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such as a methoxy group, an ethoxyquin group, and n-propoxy group. Examples thereof include i-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy and t-butoxy.
  • a hydroxy lower alkyl group is a group in which any hydrogen atom of a lower alkyl group is substituted with at least one hydroxyl group.
  • a hydroxymethyl group a 1-hydroxyshethyl group, a 2-hydroquinethyl group, , 2-dihydroxyl, 1-hydroxypropyl, 2-hydroxypropyl, 3-hydroxypropyl, 1,2-dihydroxypropyl, 2,3-dihydroxypropyl, 1 , 2, 3-trihydroxypropyl group and the like.
  • the lower alkylsulfonylamino group means an alkylsulfonylamino group having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such as methylsulfonylamino group, ethylsulfonylamino group, and n-propylsulfonyl.
  • amino groups i one Puropirusu Ruhoniruamino group, n- butylsulfonyl ⁇ amino group, i over butylsulfonyl amino group, s- heptyl sulfonyl ⁇ amino group, t one-heptyl sulfonyl ⁇ amino Q that group, and the like
  • the compound of the general formula (I) according to the present invention has a strong power channel blocking action as an antiarrhythmic agent belonging to class III, and has a sustained action potential in cardiac muscle and conductive tissue. Prolong the period, thus increasing refractory to extra stimuli (pr ema turest imu li). They have effects on atria, ventricles and conductive tissue both in vitro and in vivo, and are therefore useful in the prevention and treatment of various types of ventricular and supraventricular arrhythmias, including atrial and ventricular fibrillation. is there. These compounds do not alter the rate at which the impulse is conducted and therefore have less tendency to promote or exacerbate arrhythmias than other currently used antiarrhythmic drugs (mostly Class I). In addition, there are few occurrences of neural side effects. Also, some of these compounds have some positive inotropic activity and are particularly useful in patients with impaired cardiac pump function. Desirable compounds of the general formula (I) of the present invention include:
  • ⁇ - is a general formula
  • A is the general formula ( CH 2) a
  • Ro Group showed heterocycles or nitrogen atom one or two to six-membered saturated containing the, wherein R 8 is Ci one C e-lower alkyl group or a hydroxy-C, shows an C e-lower alkyl group, a is 0 Or 1;
  • D is formula chromatography (CH 2) m -, one (CH 2) m - indicates the group, - 0-, One CO- or - S0 2
  • R 2 are each independently a hydrogen atom, a halogen atom, Ci one C e-lower alkoxy group or a C! A C ⁇ lower alkylsulfonylamino group;
  • RaiiCj-C 6 represents lower alkyl
  • R “R 5 , R e and R 7 each independently represent a hydrogen atom or d-C 6 lower alkylsulfonylamino group
  • R is nitro port groups or C, shows an C e lower alkylsulfonyl ⁇ amino group
  • X represents a hydrogen atom or a Hagen atom
  • n and n are compounds each representing an integer of 0 to 2.
  • A is the general formula Byeon (CH 2) a O-
  • D represents a group of the general formula — (CH 2 ) m —,-(CH 2 ) m — 0—, —CO— or —S 0 2 —,
  • R! And R 2 each independently represent a hydrogen atom, a chlorine atom, a methoxy group or a methylsulfonylamino group,
  • R 3 represents a methyl group
  • R 4 , R 5 , R 6 and R 7 each independently represent a hydrogen atom or a methylsulfonylamino group
  • R represents a two-terminal group or a methylsulfonylamino group
  • X represents a hydrogen atom, a chlorine atom or a fluorine atom
  • n and n are compounds showing an integer of 0 to 2.
  • the compound of the general formula (I) according to the present invention can further form a pharmaceutically acceptable salt.
  • pharmaceutically acceptable salts include acids which form non-toxic acid addition salts containing pharmaceutically acceptable anions, such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, Inorganic acids such as iodide hydrous acid, etc., and organic carboxylic acids such as tartaric acid, formic acid, citric acid, acetic acid, trichloroacetic acid or trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, etc.
  • pharmaceutically acceptable salts include acids which form non-toxic acid addition salts containing pharmaceutically acceptable anions, such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, Inorganic acids such as iodide hydrous acid, etc., and organic carboxylic acids such as tartaric acid, formic acid,
  • salts formed with sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid or naphthalenesulfonic acid.
  • Specific examples of such salts include hydrochloride, hydrobromide, hydroiodide, sulfate or hydrogensulfate, phosphate or hydrogenphosphate, acetate, maleate, fumarate Acid salt, lactate, tartrate, citrate, gluconate, benzoate, methanesulfonate, benzenesulfonate or p-toluenesulfonate.
  • the present invention further includes a process for producing the novel amine derivative of the above general formula (I) and a salt thereof.
  • the amine derivative of the general formula (I) and a salt thereof are (A) a compound of the following general formula (II) or a salt thereof with a compound of the following general formula (III) or Reacting with a salt thereof to produce a compound of the general formula (Ia) or a salt thereof,
  • Het represents a nitrogen atom-containing 6-membered hetero ring
  • R 8 represents a lower alkyl group or a hydroxy lower alkyl group, a is 0 or 1,
  • D represents a group of the general formula — (CH 2 ) m —, one (CH 2 ) m — 0—, one CO— or one S0 2 —,
  • Rt and R 2 each independently represent a halogen atom, a lower alkoxy group or a lower alkyl sulfonylamino group,
  • R 3 represents a lower alkyl group
  • R 4 , R 5 , Re and R 7 each independently represent a hydrogen atom or a lower alkylsulfonylamino group
  • R represents a nitro group or a lower alkylsulfonylamino group
  • X represents a hydrogen atom or a halogen atom
  • n each represent an integer of 0 to 3
  • L is a reactive leaving group, for example, a halogen atom such as a chlorine atom, a bromine atom, an iodine atom, an alkanesulfonyloxy group such as a methanesulfonyloxy group, a benzenesulfonyloxy group or a toluenesulfonyloxy group; Group.
  • a halogen atom such as a chlorine atom, a bromine atom, an iodine atom
  • an alkanesulfonyloxy group such as a methanesulfonyloxy group, a benzenesulfonyloxy group or a toluenesulfonyloxy group
  • a compound of the general formula ( ⁇ ) or a salt thereof is reacted with a compound of the general formula (III) or a salt thereof, and A is represented by the general formula- (CH 2) a J ⁇
  • the compound of the general formula (I), ie, the compound of the general formula (la) or a salt thereof can be produced.
  • the reaction of Method A can be desirably performed in an organic solvent, generally in the presence or absence of a water-soluble base.
  • the organic solvent used in this reaction is not particularly limited as long as it does not adversely affect the reaction, and is preferably an alcohol solvent such as methanol or ethanol, a halogenated hydrocarbon solvent such as chloroform, methylene chloride, or the like.
  • the reaction can be carried out using dimethyl sulfoxide, dimethylformamide, acetone or the like.
  • This reaction can be further carried out in the presence of an acid acceptor, particularly when the reactive leaving group L is a halogen atom, that is, a chlorine atom, a bromine atom or an iodine atom, and the reaction is carried out in the presence of an acid acceptor. It may be advantageous.
  • the reaction is carried out in the presence of a water-soluble base
  • examples of the water-soluble base include pyridine, triethylamine, potassium carbonate, potassium bicarbonate, potassium iodide, sodium methoxide, 1,8-diazabicyclo [5.4. [0]
  • Usual water-soluble bases such as Ndeco 7-ene (DBU) can be desirably used.
  • the reaction of the method A can be carried out in a relatively wide temperature range, it is generally carried out at room temperature to elevated temperature, preferably at the flow temperature of the solvent used or at a temperature of 50 to 150 ° C.
  • the reaction is generally carried out for 0.5 to 24 hours, preferably for 1 to 15 hours.
  • the reaction product can be separated and purified by a post-treatment method common in the art, if necessary, for example, a method such as column chromatography or recrystallization.
  • a compound of the general formula (IV) or a salt thereof is reacted with a compound of the general formula (V) or a salt thereof, and A is a nitrogen-containing 6-membered heterocyclic ring such as piperidino or piperazino.
  • a compound of the general formula (I) representing a group, that is, a compound of the general formula (lb) or a salt thereof can be produced.
  • reaction of this method B is carried out under substantially the same reaction conditions as in the above method A.
  • the reaction product can be separated and purified by a post-treatment method common in the art, if necessary, for example, a method such as column chromatography or recrystallization.
  • the amide derivative of the general formula (I) and the pharmaceutically acceptable salt thereof according to the present invention have a strong potassium channel blocking action, and are used as a useful antiarrhythmic agent for beds. be able to.
  • the present invention further provides an antiarrhythmic agent composition comprising as a active ingredient a novel amine derivative of the general formula (I) or a pharmaceutically acceptable salt thereof.
  • Pharmaceutical compositions according to the invention may furthermore be prepared in the customary pharmaceutical field using customary pharmaceutically acceptable carriers by customary methods, such as tablets, capsules, troches, solutions, suspensions and the like. Suspensions and other preparations for oral administration, solutions for injection or suspensions, or dry powders for immediate use that are reconstituted with distilled water for injection at the time of injection It can be formulated into an injection.
  • Carriers used for such purposes are conventional in the pharmaceutical field, for example, in the case of formulations for oral administration, binders, lubricants, disintegrants, excipients, solubilizers, dispersants Agents, stabilizing agents, suspending agents, dyes, fragrances, etc.
  • binders binders, lubricants, disintegrants, excipients, solubilizers, dispersants Agents, stabilizing agents, suspending agents, dyes, fragrances, etc.
  • solubilizers solubilizers, dispersants Agents, stabilizing agents, suspending agents, dyes, fragrances, etc.
  • the pharmaceutical preparation thus produced can be administered orally or parenterally, for example, intravenously, intramuscularly or subcutaneously.
  • the administration dose can be varied depending on the patient's condition, body weight, age and the like. 1) to 60 mg per kg) is divided into 1 to 3 divided doses.
  • Example 1 (Optical activity) Production of 1-3- [N- (3,4-dimethoxyfunetyl) -1-N-methylamino] -1- (4-nitrobenzyl) piperidine dihydrochloride (1) ( ⁇ ) —3—Hydroxypiperidine (10.1 g, 99.9 mmol) is dissolved in 400 ml of acetone, and (1 S) — (+) — 30.2 g (130 mmol) of 10-camphorsulfonic acid is dissolved in acetone. It was mixed with a solution dissolved in 40 Om1, stirred at room temperature for 14 hours, and stored in a refrigerator for about 12 days.
  • the extract is washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, and then distilled under reduced pressure to give the target compound, 3-hydroxy (11-nitrobenzyl) piperidine, in the form of a pale yellow foil 10. 7 g were obtained.
  • Example 5 (Optical activity) Production of 1-3- [N- (3,4-Dimethoxyphenethyl) -1-N-ethylamino] 1-12- (412nitrobenzyl) piperidine dihydrochloride (1) 5 g (27.5 mimol) of 3,4-dimethyphenethyl alcohol and 7.66 ml (55 mimol) of triethylamine are added to 5 Om 1 of methylene chloride and then added to this mixture. At 0 ° C., 3.18 ml (41.3 mmol) of methanesulfonyl chloride was gradually added, and the mixture was stirred at room temperature for 3 hours.
  • E— 4031 4 '— [[1- [2- (6-methyl-12-pyridyl) ethyl] -14-piperidyl] carbonyl] methanesulfonylanilide
  • the compound of the present invention exhibits a 3HzZ1Hz ratio that is several times higher than that of the E-4031 compound already developed as an antiarrhythmic agent. It shows that it is an excellent antiarrhythmic agent that has improved the proarrhythmic effect due to reverse 'youth dependency'.
  • Action potential extension for papillary muscles isolated from guinea pigs
  • the right ventricular papillary muscle of a male guinea pig weighing 400-600 g is removed and was fixed to an organ bus made by the company.
  • electrical stimulation frequency: 1 Hz or 3 Hz, oscillation width: 2 ms ec, voltage: ⁇ value x 1.5
  • 3M KC The action potential duration (APD 90 ) was measured using a glass microelectrode (20-30 ⁇ ) charged with one solution.
  • the compound of the present invention exhibits a 3% / 1% ratio which is several times higher than that of the E-4031 compound which has been already developed as an antiarrhythmic agent. It can be seen that this is an excellent antiarrhythmic drug that has improved the 7 roalismic effect due to a certain reverse use dependency (reverseused ep end en cy).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

L'invention concerne un nouveau dérivé amine représenté par la formule générale (I) ou un sel de cette amine. Ces composés sont utiles comme antiarythmiques. Dans la formule (I), le groupe de la formule (a) a la formule développée (b) ou (c); A représente -NR8-(CH2)a-(hétérocycle azoté à 5 ou 6 éléments)- ou un hétérocycle azoté à 6 éléments, où R8 représente un alkyle inférieur ou un alkyle inférieur hydroxylé et a représente 0 ou 1; D représente -(CH2)m-, -(CH2)m-O-, -CO- ou -SO2-; R1 et R2 représentent chacun indépendamment un hydrogène, un halogène, un alcoxy inférieur ou un alkylsulfonylamino; R3 représente un alkyle inférieur; R4, R5, R6 et R7 représentent chacun d'une manière indépendante un hydrogène ou un alkyl(inférieur)sulfonylamino; R représente un nitro ou un alkyl(inférieur)sulfonylamino; X représente un hydrogène ou un halogène; et m et n représentent chacun 0, 1, 2 ou 3.
PCT/JP1995/001134 1994-08-16 1995-06-07 Nouveau derive amine, procede pour le preparer et son utilisation comme antiarythmique Ceased WO1996005174A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU26296/95A AU2629695A (en) 1994-08-16 1995-06-07 Novel amine derivative, process for producing the same, and use thereof as antiarrhythmic

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP19249994 1994-08-16
JP6/192499 1994-08-16

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WO1996005174A1 true WO1996005174A1 (fr) 1996-02-22

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003055321A (ja) * 2001-08-09 2003-02-26 Taiho Yakuhin Kogyo Kk ベンジルアミン誘導体の製造法
WO2003068236A1 (fr) * 2002-02-18 2003-08-21 Glaxo Group Limited Derives de piperidine et de piperazine possedant une affinite pour les recepteurs de type 5ht-1
WO2004009549A3 (fr) * 2002-07-18 2004-06-03 Actelion Pharmaceuticals Ltd Piperidines utiles pour traiter des maladies du systeme nerveux central
JP2010532382A (ja) * 2007-06-29 2010-10-07 エモリー・ユニバーシテイ 神経保護のためのｎｍｄａ受容体拮抗薬
JP2013014607A (ja) * 2009-05-06 2013-01-24 Merck Sharp & Dohme Corp 腎髄質外部カリウムチャネルの阻害剤

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JPS62281858A (ja) * 1986-02-26 1987-12-07 Eisai Co Ltd ピペリジン誘導体及びその類縁誘導体
JPS6452756A (en) * 1987-08-24 1989-02-28 Eisai Co Ltd Piperdine derivative and remedy and preventive for arrhythmia containing said derivative
JPH04290878A (ja) * 1990-12-05 1992-10-15 Ciba Geigy Ag 置換ｎ−ベンゾイル−ｎ′−（２−フェニルエチル）ピペラジン
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JPS62281858A (ja) * 1986-02-26 1987-12-07 Eisai Co Ltd ピペリジン誘導体及びその類縁誘導体
JPS6452756A (en) * 1987-08-24 1989-02-28 Eisai Co Ltd Piperdine derivative and remedy and preventive for arrhythmia containing said derivative
JPH05500660A (ja) * 1989-09-15 1993-02-12 シエーリング　アクチエンゲゼルシヤフト ２―置換―１（４）―アリールピペラジンおよびその製造方法
JPH04356462A (ja) * 1990-03-28 1992-12-10 Du Pont Merck Pharmaceut Co 向精神薬または植物の真菌殺菌剤としてのピペリジンエーテル誘導体
JPH04290878A (ja) * 1990-12-05 1992-10-15 Ciba Geigy Ag 置換ｎ−ベンゾイル−ｎ′−（２−フェニルエチル）ピペラジン

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INDIAN J. CHEM., Sect. B, 20B(8), 680-2 (1981). *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003055321A (ja) * 2001-08-09 2003-02-26 Taiho Yakuhin Kogyo Kk ベンジルアミン誘導体の製造法
WO2003068236A1 (fr) * 2002-02-18 2003-08-21 Glaxo Group Limited Derives de piperidine et de piperazine possedant une affinite pour les recepteurs de type 5ht-1
WO2004009549A3 (fr) * 2002-07-18 2004-06-03 Actelion Pharmaceuticals Ltd Piperidines utiles pour traiter des maladies du systeme nerveux central
JP2010532382A (ja) * 2007-06-29 2010-10-07 エモリー・ユニバーシテイ 神経保護のためのｎｍｄａ受容体拮抗薬
US9079852B2 (en) 2007-06-29 2015-07-14 Emory University NMDA receptor antagonists for neuroprotection
JP2013014607A (ja) * 2009-05-06 2013-01-24 Merck Sharp & Dohme Corp 腎髄質外部カリウムチャネルの阻害剤

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KR960007560A (ko) 1996-03-22

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