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WO1994008964A1 - Derive de n-phenethylazepine et son utilisation - Google Patents

Derive de n-phenethylazepine et son utilisation Download PDF

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Publication number
WO1994008964A1
WO1994008964A1 PCT/JP1993/001435 JP9301435W WO9408964A1 WO 1994008964 A1 WO1994008964 A1 WO 1994008964A1 JP 9301435 W JP9301435 W JP 9301435W WO 9408964 A1 WO9408964 A1 WO 9408964A1
Authority
WO
WIPO (PCT)
Prior art keywords
azepine
azabicyclo
acid
compound
reaction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP1993/001435
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English (en)
Japanese (ja)
Inventor
Nobuyuki Takahashi
Daisuke Mochizuki
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Asahi Kasei Corp
Asahi Chemical Industry Co Ltd
Original Assignee
Asahi Chemical Industry Co Ltd
Asahi Kasei Kogyo KK
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Asahi Chemical Industry Co Ltd, Asahi Kasei Kogyo KK filed Critical Asahi Chemical Industry Co Ltd
Publication of WO1994008964A1 publication Critical patent/WO1994008964A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
    • C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
    • C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems

Definitions

  • the present invention relates to a novel azepine derivative having an activity of specifically binding to a sigma receptor ( ⁇ receptor) and a pharmaceutical use thereof.
  • ⁇ receptor sigma receptor
  • the present inventors have synthesized various compounds, and have searched extensively for their pharmacological actions.
  • the azepine derivative represented by the following general formula (1) has a high affinity to all receptors, It has been found that it shows almost no affinity for this receptor.
  • the present invention has been completed based on the above findings. That is, the present invention provides a compound represented by the general formula (1):
  • nitrogen-containing ring B is 3,3,5,5-tetramethylhexahydro-1H-azepine-11-yl, 3,3,5-trimethylhexahydro-1H-azepine-11-yl
  • R represents a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group or an amino group
  • A has 2 carbon atoms ⁇ 3 saturated or unsaturated alkylene groups
  • the present invention also provides a therapeutic agent for a disease associated with ⁇ -receptor, which comprises the formula (1) or a non-toxic salt thereof as an active ingredient.
  • the present invention provides a therapeutic agent for schizophrenia, which comprises the general formula (1) or a non-toxic salt thereof as an active ingredient.
  • the compound (1) of the present invention has, for example, the general formula (2)
  • A represents a saturated or unsaturated alkylene group having 2 to 3 carbon atoms
  • X represents a reactive organic sulfonyloxy group or a halogen atom.
  • the reactive derivative of the formula (3) is reacted in an inert organic solvent in the presence of a base.
  • R in the general formula (3) is a protected amino group, It can be obtained by removing a protecting group.
  • the compound represented by the general formula (2) is a known compound and represented by the following formulas (21) to (26).
  • 3,3,5,5-tetramethylhexahydro-1H-azepine (21) and 4,4-dimethylhexahydro-1H-azepine (22) are available from Tetrahedr 0 n, 37,107 1 9 8 1)
  • 9-azabicyclo [3.3.2] decane (25) can be synthesized from bicyclo [3.3.1] nonane-oneone in two steps. .
  • the sulfonyl derivative has the general formula (4)
  • a dry inert reaction solvent such as methylene chloride, methanesulfonyl chloride
  • a dry inert reaction solvent such as methylene chloride, methanesulfonyl chloride
  • the halogenated derivative of the reactive derivative (3) obtained by sulfonylation with p-toluenesulfonyl chloride or the like can be obtained by converting the alcohol (4) into a dry inert reaction solvent such as methylene chloride in thionyl chloride. It is obtained by halogenation with a halogenating agent such as.
  • the alcohol (4) is a known substance, for example, phenethyl alcohol, 0 (m or p) —fluorophenethyl alcohol, 0 (m or p) —chlorophenethyl alcohol, 0 (1 ⁇ ) Or p) — bromophenethyl alcohol, 0 (m or p) — ditrophenethyl alcohol, 0 (m or p) — protected amino phenyl alcohol, 3-phenylpropyl alcohol, 3 — [0 (m or p) —Fluorophenyl] propyl alcohol, 3— [0 (m or p) —chlorophenyl] propyl alcohol, 3— [0 (m or p) —bromophenyl] propyl alcohol, (m or p) — 2-butane phenyl) propyl alcohol, 3 — [0 (m or p) — protected amino phenyl] pulp alcohol, cinnamyl
  • Examples of the base used in the reaction of the amine (2) with the reactive derivative (3) include, for example, triethylamine, ethyldiisopropylamine, N, N-dimethylaniline, N-methylmorpholine, pyridine, Examples include tertiary organic bases such as N, N-dimethylaminopyridine and inorganic bases such as carbonates, hydrogencarbonates, hydroxides and hydrides of alkali metal and alkaline earth metal. Examples of the inert organic solvent include acetonitrile, benzene, acetone, tetrahydrofuran and the like, with acetonitrile being particularly preferred.
  • the above reaction is usually performed appropriately at the reflux temperature of the reaction solvent used.
  • the reaction time depends on the reaction temperature and the type of base. Since the progress of the reaction can be monitored by liquid chromatography or the like, the reaction may be appropriately terminated after the disappearance of compound (2). Although it cannot be generally specified, it is usually about 2 to 48 hours.
  • insoluble substances are filtered off, the solvent is concentrated, and the residue is concentrated, for example, using a mixture of pore-form and acetone as an eluent. Separation and purification can be performed by a known purification method such as chromatography.
  • the compound (1) of the present invention is, for example, a compound of the formula (5) with the amine (2)
  • R 2 represents a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group or a protected amino group
  • Y represents a saturated or unsaturated alkylene group having 1 to 2 carbon atoms.
  • R 2 in (5) is a protected amino group, it can be obtained by removing the protecting group of the amino group.
  • the aldehyde compound (5) is a known substance, for example, phenylacetaldehyde, 0 (m or p) -fluorophenylacetaldehyde, 0 (m or p) -cloth phenylacetaldehyde, 0 (m or p) — bromophenylacetaldehyde, 0 (m or p) — hydroxyphenylacetaldehyde, 0 (m or p) — ditrophenylacetaldehyde, 0 (m or p) monoprotected amino 2-Diacetaldehyde, 3-phenylpropionaldehyde, 3- [0 (m or p) -fluorophenyl] propionaldehyde, 3- [0 (m or p) -clothphenyl] propionaldehyde, 3-Co (m or p) —bromophenyl] propionaldehyde, 3— [0 (m or p) —Hy
  • Examples of the reducing agent used in the reaction between the amine (2) and the aldehyde compound (5) include, for example, sodium borohydride, sodium cyanoborohydride, Pd—C, and the like.
  • Examples of the inert organic solvent for the above reaction include alcohol-based organic solvents such as methanol.
  • the above reaction usually proceeds sufficiently at room temperature, and the reaction time depends on the type of reducing agent and the type of aldehyde (5). Since the reaction can be traced, the reaction may be appropriately terminated after the disappearance of the compound (2). Although it cannot be generally specified, it is usually about 2 to 48 hours.
  • the compound (1) of the present invention has the general formula (6)
  • R 3 represents a hydrogen atom, a halogen atom, a hydroxyl group or a protected amino group, and the nitrogen-containing rings B and Y have the same meanings as described above).
  • R 3 in the general formula (6) is a protected amino group, it can be obtained by removing the protecting group of the protected amino group.
  • the compound (6) is obtained by reacting the amine (2) with a compound represented by the general formula (7)
  • the carboxylic acid (7) is a known substance such as, for example, phenylacetic acid, 0 (m or p) -fluorophenylacetic acid, 0 (m or p) -clofen phenylic acid, 0 (m or p) —Bromophenylacetic acid, 0 (m or ⁇ ) —Hydroxyphenylacetic acid, 0 (m or p) —Protected aminophenylacetic acid, 3-Phenylpropionic acid, 3— [0 (m or p) —Fluorophenyl] propionic acid, 3 —
  • the above acylation reaction can be performed according to a known acylation reaction.
  • the reaction is carried out in the presence of a condensing agent.
  • the condensing agent include N, N'-dicyclohexyl carbodiimide, 1-ethyl-3- (3'-dimethylaminopropyl) carbodiimide, N-cyclohexyl-N '-(4-getyl Reagents such as carbodiimide compounds such as aminocyclohexyl) carposimid, diphenylphosphoryl azide, benzotriazolyl N-hydroxytris (dimethylamino) phosphonium hexafluorophosphoride, carbonyldiimidazole, N-methylformamide, N Amides such as N, N-dimethylformamide Reagents (so-called Vilsmeier reagents) formed by the reaction with halides such as
  • Examples of the reactive derivative of the carboxylic acid (7) include an acid halide, an acid anhydride, an acid azide, an active ester, and an active amide.
  • Preferred examples thereof include an acid chloride, an acid bromide, and the like.
  • Active esters such as enyl ester, pentachlorophenyl ester, 1-hydroxy-1H-pyridone, N-hydroxysuccinimide, N-hydroxysulfinimide ester, pyrazole, imidazole, dimethylvirazole, benzotriabul, etc. Active amide and the like.
  • the reaction using an acid halide or acid anhydride among the reactive derivatives in the above acylation reaction is preferably performed in the presence of a deoxidizing agent.
  • a deoxidizing agent include tertiary organic bases such as triethylamine, ethyldiisopropylamine, N, N-dimethylaniline, N-methylmorpholine, pyridine, and N, N-dimethylaminopyridine, and known inorganic bases. Is used.
  • the above acylation reaction is carried out in an organic solvent that does not adversely affect the reaction.
  • the organic solvent include chloroform, methylene chloride, tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, N, N-dimethylacetamide, acetone or a mixed solvent thereof is used.
  • the reaction temperature is not particularly limited, but usually proceeds sufficiently at room temperature.
  • the reaction time depends on the reaction temperature and the reaction solvent, and cannot be generally specified, but is usually about 2 to 30 hours.
  • the reaction solvent is a non-hydrophilic organic solvent
  • the reaction solution is washed with an alkaline aqueous solution, an acidic aqueous solution, or a saturated saline solution. After that, the organic layer is concentrated and the reaction solvent is hydrophilic.
  • the solvent is an organic solvent
  • the compound (6) can be obtained by distilling off the solvent, dissolving the residue in a non-hydrophilic organic solvent, and treating in the same manner as described above.
  • the compound (6) can be further purified by a known purification method such as silica gel column chromatography.
  • the carbonyl group of the compound (6) thus obtained is reduced to obtain the compound (1) of the present invention.
  • the compound (6) is hydrogenated in an inert organic solvent. It is carried out by refluxing in the presence of a reducing agent such as lithium aluminum, sodium aluminum hydride, sodium bis (2-methoxetoxy) aluminum hydride or borohydride.
  • a reducing agent such as lithium aluminum, sodium aluminum hydride, sodium bis (2-methoxetoxy) aluminum hydride or borohydride.
  • the inert organic solvent include tetrahydrofuran, getyl ether, 1,4-dioxane, toluene, and pyridin.
  • the reaction is carried out under heating, preferably at reflux.
  • the reaction time depends on the reaction temperature and the type of reducing agent, but the progress of the reaction can be monitored by thin-layer chromatography, high-performance liquid chromatography, etc.
  • the reaction may be terminated. Although it cannot be generally specified, it is usually about 15 minutes to 10 hours.
  • reaction solvent is a non-hydrophilic organic solvent
  • the reaction solution is washed with an alkaline aqueous solution, an acidic aqueous solution or a saturated saline solution, and then the organic layer is concentrated.
  • the reaction solvent is a hydrophilic organic solvent
  • the solvent is distilled off, the residue is dissolved in a non-hydrophilic organic solvent, and the mixture is treated in the same manner as above to obtain the desired compound (1). be able to.
  • the compound (1) of the present invention has the general formula (8)
  • the above reduction reaction is carried out in a mixed solvent of an alcoholic solvent such as methanol and an acid.
  • the catalyst is filtered off from the above reaction solution, the filtrate is concentrated, and the residue is treated with an organic solvent such as getyl ether, whereby the compound (1) of the present invention is collected in the form of an acid addition salt.
  • the acid addition salt may be used, if desired, by freeing the desired compound by a known method.
  • the target compound (1) thus obtained needs to be further purified, it can be purified by a known purification method such as silica gel column chromatography using a mixture of black form and acetone as eluent. can do.
  • the obtained compound (1) of the present invention can be converted into a pharmaceutically acceptable non-toxic salt thereof, if necessary.
  • salts include salts of inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid, acetic acid, propionic acid, tartaric acid, citric acid, glycolic acid, gluconic acid, succinic acid, malic acid, glutamic acid, aspartic acid, Examples thereof include acid addition salts with organic acids such as methanesulfonic acid, mandelic acid, ⁇ -toluenesulfonic acid, and maleic acid.
  • the compound (1) of the present invention or a non-toxic salt thereof as a medicament, it is necessary to formulate the compound and administer it orally or parenterally, such as by injection including infusion, in a dosage form of Depends on the age, weight, and symptoms of the recipient However, in general, it is about 0.1 to 100 mg per day per adult.
  • Examples of the dosage form for the formulation include tablets, pills, powders, granules, capsules, and injections.
  • various carriers corresponding to these formulations for example, Oral preparations such as tablets, granules, and capsules include starch, lactose, sucrose, mannite, carboquin methylcellulose, corn starch, inorganic salts, and other excipients, starch, dextrin, gum arabic, gelatin, hydroxypropyl starch, and methylcellulose.
  • Binders such as sodium carboxymethylcellulose, hydroxypropylcellulose, crystalline cellulose, ethylcellulose, polyvinylpyrrolidone, macrogol, starch, hydroxypropyl starch, carboxypropylcellulose, sodium carboxymethylcellulose, hydrid Disintegrators such as roxypropylcellulose, sodium lauryl sulfate, soy lecithin, sucrose fatty acid esters, surfactants such as polysorbate 80, talc, wax, hydrogenated vegetable oil, sucrose fatty acid esters, magnesium stearate, magnesium stearate, Lubricants such as calcium stearate, fluidity promoters, flavoring agents, coloring agents, fragrances and the like can be used.
  • the compound (1) of the present invention or a nontoxic salt thereof can also be used as a suspending agent, emulsion, syrup, and elixir.
  • distilled water for injection physiological saline, aqueous glucose solution, vegetable oil for injection, propylene glycol, polyethylene glycol, and the like can be generally used as a diluent.
  • a bactericide, a preservative, a stabilizer, a tonicity agent, a soothing agent and the like may be added.
  • the membrane preparation (approximately 600 g protein content) and [3 H] 1, 3-di (2-Tris) grayed Anijin (DTG, manufactured by New Eng l and Nu cu lear Co.) (final concentration 3 nM) 25 °
  • the reaction was stopped for 60 minutes by suction filtration of the reaction mixture with a Kettman GFZC filter, and the reaction was measured with a radioactive scintillation counter adsorbed on the filter. The obtained value was regarded as the total binding amount.
  • the amount of non-specific binding (NB) was determined by adding 10 uM haloperidol and measuring in the same manner. In order to measure the binding amount of the sample, an appropriate concentration of the sample was added instead of haloperidol, and the measurement was performed in the same manner to obtain a measured value (DTB) in the sample.
  • the binding inhibition rate of the sample at a certain concentration was calculated by the following calculation method.
  • Ki IC 50 ⁇ [1 + (L) / Kd]
  • (L) is the concentration of the radioligand used in the experiment (3 nM)
  • Kd is the concentration (10.6 nM) indicating the affinity of the radioligand for the receptor
  • IC 50 is the receptor and radioligand Is the drug concentration that inhibits the binding to 50%.
  • Table 1 shows the results of measuring the binding ability of the compound of the present invention to the receptor.
  • the compound of the present invention has a high affinity for the receptor, shows almost no affinity for other receptors, and is particularly characteristic of receptors. Since it has a different affinity, it is effective for the treatment of diseases associated with ⁇ receptor, such as schizophrenia.
  • Tables 2 and 3 show the physical properties of the target compound obtained in each of Examples and Reference Examples by mass spectrometry (MS) or nuclear magnetic resonance spectrum (H-NMR).
  • MS mass spectrometry
  • H-NMR nuclear magnetic resonance spectrum
  • Example 4 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 4 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 7 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 8 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 8 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 9 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 10 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 10 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 1 2 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 1 2 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 13 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 13 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 14 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 14 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 15 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 15 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 16 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 16 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 17 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 19 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 20 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • Example 20 The product was treated in the same manner as in Example 1 to obtain a hydrochloride.
  • a tablet of 20 Omg per tablet having the following composition was obtained by dry tableting.

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

Abstract

L'invention concerne un composé répondant à la formule général (I) ou bien un sel non toxique de celui-ci, ainsi qu'un remède contenant ledit composé comme ingrédient actif, destiné au traitement de maladies dans lesquelles le récepteur sigma joue un rôle. Dans ladite formule (I), le cycle azotique B représente 3,3,5,5-tétraméthylhexahydro-1H-azépine-1-yle, 3,3,5-triméthylhexahydro-1H-azépine-1-yle, 4,4-diméthylhexahydro-1H-azépine-1-yle, 1,3,3-triméthyl-6-azabicyclo[3.2.1]octan-6-yle, 9-azabicyclo[3.3.2]décan-9-cyle ou bien 3-azabicyclo[3.2.2]nonan-3-yle; R représente hydrogène, halogène, hydroxy, nitro ou amino; et A représente alkylène C2-C3 saturé ou non saturé. Ledit composé et le sel non toxique de celui-ci présentent une haute affinité spécifique pour le récepteur sigma et presque aucune activité pour les autres récepteurs, ce qui permet de l'utiliser pour traiter des maladies dans lesquelles le récepteur sigma joue un rôle, maladies telles que la schizophrénie.
PCT/JP1993/001435 1992-10-16 1993-10-06 Derive de n-phenethylazepine et son utilisation Ceased WO1994008964A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP4/278281 1992-10-16
JP27828192 1992-10-16

Publications (1)

Publication Number Publication Date
WO1994008964A1 true WO1994008964A1 (fr) 1994-04-28

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PCT/JP1993/001435 Ceased WO1994008964A1 (fr) 1992-10-16 1993-10-06 Derive de n-phenethylazepine et son utilisation

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003080046A1 (fr) * 2002-03-21 2003-10-02 Merz Pharma Gmbh & Co. Kgaa Derives azabicycliques, azatricycliques et azaspirocycliques d'aminocyclohexanes comme antagonistes des recepteurs de nmda, des recepteurs de 5ht3 et des recepteurs nicotiniques neuronaux
WO2005035534A1 (fr) * 2003-10-08 2005-04-21 Ono Pharmaceutical Co., Ltd. Composes a anneau bicyclique heterocyclique et a anneau tricyclique heterocyclique et medicaments les contenant

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2626880A1 (fr) * 1988-02-10 1989-08-11 Lafon Labor Derives n-substitues de 2-amino-1-phenylpropanone, procede de preparation et utilisation en therapeutique
JPH01316369A (ja) * 1988-02-10 1989-12-21 Lab L Lafon Sa １―（４―アミノフェニル）―２―ヘキサメチレイミノプロパノン

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2626880A1 (fr) * 1988-02-10 1989-08-11 Lafon Labor Derives n-substitues de 2-amino-1-phenylpropanone, procede de preparation et utilisation en therapeutique
JPH01316369A (ja) * 1988-02-10 1989-12-21 Lab L Lafon Sa １―（４―アミノフェニル）―２―ヘキサメチレイミノプロパノン

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACT, Vol. 92, No. 19, (1980), Abstract No. 163771r; & FR,A,2 626 880 (Laboratoire L. Laton, Fr.), 11 August 1989. *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003080046A1 (fr) * 2002-03-21 2003-10-02 Merz Pharma Gmbh & Co. Kgaa Derives azabicycliques, azatricycliques et azaspirocycliques d'aminocyclohexanes comme antagonistes des recepteurs de nmda, des recepteurs de 5ht3 et des recepteurs nicotiniques neuronaux
US7022729B2 (en) 2002-03-21 2006-04-04 Merz Pharma Gmbh & Co. Kgaa Azabicyclic, azatricyclic and azaspirocyclic derivatives of aminocyclohexane NMDA, 5HT3, and neuronal nicotinic receptor antagonists
US7238703B2 (en) 2002-03-21 2007-07-03 Merz Pharma Gmbh & Co. Kgaa Azabicyclic, azatricyclic and azaspirocyclic derivatives of aminocyclohexane NMDA, 5HT3, and neuronal nicotinic receptor antagonists
WO2005035534A1 (fr) * 2003-10-08 2005-04-21 Ono Pharmaceutical Co., Ltd. Composes a anneau bicyclique heterocyclique et a anneau tricyclique heterocyclique et medicaments les contenant

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