WO1998037893A1 - Antagoniste du recepteur dopaminergique d4 - Google Patents

Antagoniste du recepteur dopaminergique d4 Download PDF

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Publication number
WO1998037893A1
WO1998037893A1 PCT/JP1998/000744 JP9800744W WO9837893A1 WO 1998037893 A1 WO1998037893 A1 WO 1998037893A1 JP 9800744 W JP9800744 W JP 9800744W WO 9837893 A1 WO9837893 A1 WO 9837893A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
optionally substituted
dopamine
formula
butyl
Prior art date
Application number
PCT/JP1998/000744
Other languages
English (en)
Japanese (ja)
Inventor
Yukihiro Ohno
Atsuyuki Kojima
Junko Wakabayashi
Rie Tagashira
Original Assignee
Sumitomo Pharmaceuticals Co., Ltd.
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 Sumitomo Pharmaceuticals Co., Ltd. filed Critical Sumitomo Pharmaceuticals Co., Ltd.
Priority to AU62306/98A priority Critical patent/AU6230698A/en
Publication of WO1998037893A1 publication Critical patent/WO1998037893A1/fr

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Classifications

    • 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
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • 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
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/58—[b]- or [c]-condensed
    • C07D209/72—4,7-Endo-alkylene-iso-indoles
    • C07D209/76—4,7-Endo-alkylene-iso-indoles with oxygen atoms in positions 1 and 3
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to dopamine D4 receptor antagonists containing imido derivatives and the like.
  • the dopamine D 4 receptor antagonist has selective and strong affinity for dopamine D 4 receptor, and is useful as a therapeutic drug for psychiatric disorders such as schizophrenia and Parkinson's disease. Background art
  • Clozapine is a typical example of a compound having selective affinity for the dopamine D4 receptor. Clozapine is classified as an atypical antipsychotic, has few extrapyramidal side effects, is effective for typical antipsychotics, is effective against negative symptoms, and appears when treating Parkinson's disease To improve the mental disorder caused by L-D0PA »Yaguchi Rare (P. ⁇ eeman, International Clinical Psychopharmaco 1 ogy (1995), 10 Suppl. 3, 5). The clinical utility of clozapine is said to be due to its selective affinity for dopamine D4 receptor over dopamine D2 receptor (G. Taubes , Science, 265, 1034 (1994)).
  • An object of the present invention is to find a drug capable of treating psychiatric disorders such as schizophrenia and Parkinson's disease by exhibiting selective antagonism to dopamine D4 receptor and having few side effects. It is in. Means to solve the problem
  • ⁇ represents a methylene group, a carbonyl group or a sulfonyl group.
  • RR 2 and R 3 represent a hydrocarbon ring which may be substituted by R 1 and R 2 together; 3 represents a hydrogen atom, or R 1 and R 3 together represent an optionally substituted hydrocarbon ring, R 2 represents a hydrogen atom, and ⁇ represents 0 or 1.
  • R 4 represents an optionally substituted phenyl group or an optionally substituted hydrocarbon ring group.
  • R 5 represents a hydrogen atom or a lower alkyl group.
  • W represents an optionally substituted lower alkylene group, an optionally substituted lower alkenylene group or an optionally substituted lower alkynylene group.
  • G represents a nitrogen atom or a methine group.
  • Ar is an optionally substituted phenyl group, an optionally substituted benzoyl group, an optionally substituted pyridyl group, an optionally substituted pyrimidyl group, an optionally substituted naphthyl group, an optionally substituted quinolyl group Represents an optionally substituted isoquinolyl group or an optionally substituted quinazolyl group.
  • Y represents a hydrogen atom, or — (CH 2 ) m _ (where m represents 1, 2 or 3; one of CH 2 — in the formula is replaced by an oxygen atom or a sulfur atom; And may be bonded to the ortho position of Ar at the other end. ]
  • a solid line with a broken line represents a single bond or a double bond.
  • E represents a lower alkylene group or an oxygen atom which may be substituted.
  • R 6 represents a hydrogen atom or a substituent. It is synonymous.
  • ring F represents a saturated or unsaturated cyclohexane ring or benzene ring.
  • R 6 and B have the same meanings as described above.
  • R 7 and R 8 independently represent a hydrogen atom or a substituent, or represent a saturated hydrocarbon ring which may be substituted together.
  • B has the same meaning as described above.
  • Ar is a phenyl group substituted with one or more lower alkoxy groups, or a 2-pyridyl group or a 2-pyrimidyl group.
  • a pharmaceutical composition for antagonizing dopamine D4 receptor comprising an imido derivative represented by the formula 1 or a pharmaceutically acceptable salt thereof, and
  • a use of an imid derivative represented by the formula 1 or a pharmaceutically acceptable salt thereof for producing a dopamine D4 receptor antagonist examples include a linear or branched group having 4 or less carbon atoms, and specific examples include methyl, ethyl, propyl, isopropyl, butyl, and isobutyl.
  • Examples of the lower alkylene group include linear or branched groups having 5 or less carbon atoms, and specific examples include methylene, ethylene, trimethylene, propylene, tetramethylene, pentamethylene, and 3-methyl-tetramethylene. No.
  • Examples of the lower alkenylene group include a linear or branched group having 2 to 5 carbon atoms, and specific examples include ethenylene, probenylene, 2-butenylene and the like.
  • Examples of the lower alkynylene group include a linear or branched group having 2 to 5 carbon atoms, and specific examples thereof include ethynylene, propynylene, and 2-pentynylene.
  • Examples of the lower alkoxy group include a linear or branched group having 4 or less carbon atoms, and specific examples include methoxy, ethoxy, propoxy, isopropoxy, butoxy, and isobutoxy.
  • halogen atom examples include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • halogen-substituted lower alkyl group examples include lower alkyl groups substituted with 1 to 5 halogen atoms, and specific examples include fluoromethyl, trifluoromethyl, 2-chloroethyl, 3-chloropropyl, and 3-chloropropyl. Bromo_2-fluorobutyl and the like.
  • Examples of the hydrocarbon ring in Z in Formula 1 include a hydrocarbon ring having 8 or less carbon atoms, and such a hydrocarbon ring may be bridged with a lower alkylene or an oxygen atom.
  • Examples of the hydrocarbon ring having 8 or less carbon atoms include cycloalkanes such as cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane and cyclooctane, cycloalkenes such as cyclopentene, cyclohexene and cycloheptene, and benzene ring And the like.
  • Examples of the hydrocarbon ring bridged by a lower alkylene group or an oxygen atom include a ring having 10 or less carbon atoms.
  • Y represents one (CH 2 ) m — (wherein, m represents 1, 2 or 3 and one —CH 2 in the formula may be substituted with an oxygen atom or a sulfur atom.)
  • bonding to the ortho position of Ar means that Y is bonded to the ortho position of the bonding position of Ar with G.
  • one (CH 2 ) m — for example, one CH 2 —, One CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, 110, one S—, _CH 20 —, one CH 2 CH 20 — and the like.
  • a preferred example of Ar in which Y is bonded to the ortho position is a phenyl group.
  • substituent in the phenyl group, benzoyl group, pyridyl group, pyrimidyl group, naphthyl group, quinoyl group, isoquinoyl group and quinazolyl group include, for example, hydroxyl group, lower alkyl group, lower alkoxy group, halogen atom, halogen-substituted lower alkyl group. And an amino group.
  • a hydroxyl group, a lower alkyl group, a lower alkoxy group, a halogen atom and the like are mentioned.
  • Preferred examples of W in Formula 1 include, for example, tetramethylene.
  • Preferred examples of Ar in the formula 1 include 2-pyrimidyl, 2-pyridyl, 3-lower alkoxy-2-pyridyl, 2-lower alkoxyphenyl, 2,6-di-lower alkoxyphenyl and the like.
  • Preferred compounds include the following compounds.
  • the above acceptable salts include acid addition salts with inorganic or organic acids, which are acceptable as pharmaceuticals.
  • the inorganic acid include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid and the like.
  • the organic acid include acetic acid, oxalic acid, citric acid, malic acid, tartaric acid, maleic acid, fumaric acid, methanesulfonic acid and the like.
  • the imid derivatives also include solvates such as hydrates.
  • the compound of the present invention can be produced by a known method. For example, it can be produced by the method described in the following patent publication.
  • it can be produced by reacting in the presence of a base by the following production method.
  • X represents a halogen atom.
  • the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof can be administered orally or parenterally. That is, it can be administered orally in the form of commonly used dosage forms such as tablets, capsules, sublingual tablets, syrups, suspensions and the like. Alternatively, liquid forms can be administered parenterally in the form of injections. It can also be administered rectally in the form of suppositories.
  • the above-mentioned appropriate dosage form is produced by mixing the compound represented by the formula 1 or a pharmaceutically acceptable salt thereof with an acceptable usual carrier, excipient, binder, stabilizer and the like. can do. When used as an injection, an acceptable buffer, solubilizing agent, isotonic agent and the like can be added.
  • the dose and frequency of administration of the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof will vary depending on the symptom-age, body weight, dosage form, etc.
  • the dose of 1-500 mg, preferably 5-100 mg for oral administration, and 0.1-100 mg, preferably 0.3-50 mg for intravenous injection, in one or several divided doses Can be.
  • the activity of the compound was determined using a D4 receptor membrane preparation prepared from CHO-K1 cells transfected with human D receptor cDNA according to the method described in Nature, 610-614 (1991), etc.
  • the inhibition rate of the radioligand [3 ⁇ 4] -spiperone against the binding reaction to the D4 receptor membrane standard by a predetermined concentration of the test compound was determined.
  • Table 1 shows the binding activity of the compounds as Ki values.
  • the activity of the compound was determined using a D2 receptor membrane preparation prepared from CH0-K1 cells transfected with human D2 receptor cDNA according to the method described in Nature, 610-614 (1991).
  • the inhibitory rate of the radioligand [3 ⁇ 4] -spiperone to the binding reaction to the D2 receptor membrane standard by the test compound at a predetermined concentration was determined.
  • Table 1 shows the binding activity of the compounds as Ki values.
  • the activity of the compound was determined using a cell suspension of CHO-K1 cells transfected with human D4 receptor cDNA according to the method described in J. Neurochem., 65, 1157-1165 (1995).
  • the inhibitory rate of dopamine (0.3 mM) in the presence of forskolin (10) against the cyclic-AMP (c-AMP) production inhibitory effect in the presence of forskolin (10) was determined.
  • the inhibitory activity of compound 1 was IC 5 .
  • the value was 300 nM.
  • Ground tandospirone citrate, lactose, corn starch and carmellose Calcium is put into a fluidized bed granulator, granulated by spraying an aqueous solution of polyvinyl alcohol (partially saponified), and granulated to produce granules.
  • Magnesium stearate is added to the granules, mixed, and tabletted to form tablets.
  • the tablet is sprayed with a coating solution prepared from hydroxypropyl methylcellulose 2910, concentrated glycerin, yellow iron sesquioxide (only for 5 mg tablets), titanium oxide, carnaupa wax, and purified water.
  • a coating solution prepared from hydroxypropyl methylcellulose 2910, concentrated glycerin, yellow iron sesquioxide (only for 5 mg tablets), titanium oxide, carnaupa wax, and purified water.
  • Pulverized product of tandospirone citrate, lactose, corn starch and low-substituted hydroxypropylcellulose are charged into a fluidized bed granulator, and granulated by spraying with an aqueous solution of povidone (K value 30). To produce granules.
  • Magnesium stearate is added to the granules, mixed, and tabletted to form tablets.
  • This tablet was prepared from hydroxypropyl methylcellulose 2910, concentrated glycerin, yellow iron sesquioxide (only for 5 mg tablets), titanium oxide and purified water. Coating solution by spraying, to produce a film-coated tablets (
  • a milled product of tandospirone citrate, lactose, and corn starch are mixed, and a corn starch aqueous solution is heated and gelatinized, added, kneaded, extruded, dried, and sized to produce fine granules.
  • Formulation Example 8 A milled product of tandospirone citrate, lactose, and corn starch are mixed, and a corn starch aqueous solution is heated and gelatinized, added, kneaded, extruded, dried, and sized to produce fine granules.
  • Pulverized product of tandospirone citrate, lactose, and corn starch are mixed, an aqueous solution of polyvinyl alcohol (partially saponified) is added, kneaded, extruded, sized with a marmalizer, and dried to produce granules.
  • the obtained granules are put into a fluidized bed coating machine and sprayed with a coating liquid consisting of ethyl cellulose, hydroxypropyl methylcellulose 2910, methylene chloride and ethanol to obtain persistent granules.
  • a coating liquid consisting of ethyl cellulose, hydroxypropyl methylcellulose 2910, methylene chloride and ethanol to obtain persistent granules.

Abstract

L'invention concerne un dérivé imide représenté par la formule générale (1), dans laquelle Z est représenté par la formule (2) (où B représente un groupe carbonyle ou similaire; pour R?1, R2 et R3, R1 et R2¿ se combinent de façon à former un noyau hydrocarbure éventuellement substitué, avec R3 représentant un atome d'hydrogène, ou bien R1 et R3 se combinent de façon à former un noyau hydrocarbure éventuellement substitué, avec R2 représentant un atome d'hydrogène; et n est 0 ou 1), ou un groupe représenté par R?4CO-NR5 (où R4¿ représente un groupe phényle éventuellement substitué ou similaire; et R5 représente un atome d'hydrogène ou un groupe alkyle inférieur); W représente un groupe alkylène inférieur éventuellement substitué ou similaire; G représente un atome d'azote ou un groupe méthine; Ar représente un groupe pyrimidyle éventuellement substitué ou similaire; et Y représente un atome d'hydrogène ou (CH¿2?)m (où m est 1, 2 ou 3), l'autre extrémité étant éventuellement fixée sur la position o de Ar; ou un sel pharmaceutiquement acceptable dudit dérivé. Ces dérivés et leurs sels, qui sont des antagonistes du récepteur dopaminergique D4, ne provoquent pas le syndrome extra-pyramidal associé à l'antagonisme du récepteur D2 et sont utiles comme agents thérapeutiques dans les troubles mentaux tels que ceux de la schizophrénie dans son état négatif, etc., ou ceux liés à la L-dopa durant le traitement de la maladie de Parkinson.
PCT/JP1998/000744 1997-02-26 1998-02-23 Antagoniste du recepteur dopaminergique d4 WO1998037893A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU62306/98A AU6230698A (en) 1997-02-26 1998-02-23 Dopamine d4 receptor antagonist

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP9/59809 1997-02-26
JP5980997 1997-02-26

Publications (1)

Publication Number Publication Date
WO1998037893A1 true WO1998037893A1 (fr) 1998-09-03

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Application Number Title Priority Date Filing Date
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AU (1) AU6230698A (fr)
WO (1) WO1998037893A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002020533A2 (fr) * 2000-09-07 2002-03-14 Abbott Laboratories Composes de benzoxazine alpha-1 adrenergique
WO2002055495A1 (fr) * 2001-01-15 2002-07-18 Glaxo Group Limited Derives aryle de piperidine comme inducteurs de l'expression du recepteur ldl
WO2002055497A1 (fr) * 2001-01-15 2002-07-18 Glaxo Group Limited Derives d'arylepiperidine utilises comme inducteurs d'expression de ldl
EP1495000A1 (fr) * 2002-04-08 2005-01-12 Ranbaxy Laboratories, Ltd. Derives d'alpha, omega-dicarboximide utiles en tant qu'inhibiteurs uroselectifs de l'adreno-recepteur a1a
US6914064B2 (en) 2000-11-30 2005-07-05 Ranbaxy Laboratories Limited 1,4-Disubstituted piperazine derivatives useful as uro-selective α1-adrenoceptor blockers
JP2005531571A (ja) * 2002-05-23 2005-10-20 アボット・ラボラトリーズ 性機能不全の治療に有用なアセトアミド類およびベンズアミド類
JP2016516829A (ja) * 2013-04-23 2016-06-09 ラボラトリオス・デル・ドクトル・エステベ・ソシエダッド・アノニマ ピラジノ［１，２−ａ］インドール化合物、その調製および医薬としての使用
WO2020235587A1 (fr) * 2019-05-21 2020-11-26 国立大学法人富山大学 Dérivé de tandospirone

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS56138170A (en) * 1980-02-25 1981-10-28 Ayerst Mckenna & Harrison 2-(1-piperazinyl)-2,4,6-cycloheptatriene-1-one derivative
JPH04208263A (ja) * 1990-01-02 1992-07-29 Fujisawa Pharmaceut Co Ltd インドール誘導体およびそれらの製造法
JPH04230362A (ja) * 1990-07-10 1992-08-19 Adir 新規なピペリジン、テトラヒドロピリジンおよびピロリジン誘導体およびこれらを含有する製薬組成物
WO1995030659A1 (fr) * 1994-05-10 1995-11-16 Warner-Lambert Company Derives de benzimidazoles et d'imidazopyridines, leur preparation et leur utilisation comme agents dopaminergiques hautement selectifs vis-a-vis des recepteurs d3 de la dopamine
WO1996014297A1 (fr) * 1994-11-04 1996-05-17 Sumitomo Pharmaceuticals Company, Limited Nouveaux derives de lactame
WO1997010229A1 (fr) * 1995-09-13 1997-03-20 Neurogen Corporation Nouveaux n-aminoalkylfluorenecarboxamides; nouvelle classe de ligands specifiques de sous-types de recepteurs dopaminergiques
WO1997034884A1 (fr) * 1996-03-21 1997-09-25 Neurogen Corporation Nouveaux n-aminoalkyl-2-anthracenecarboxamides; nouveaux ligands specifiques de sous-type de recepteur de dopamine
WO1997038989A1 (fr) * 1996-04-18 1997-10-23 Neurogen Corporation N-aminoalkyl-2-anthraquinonecarboxamides; nouveaux ligands specifiques de sous-types de recepteurs de la dopamine
JPH09291033A (ja) * 1995-12-11 1997-11-11 Inst Natl Sante & Rech Med <Inserm> 新規な２−ナフタミド誘導体とその治療への応用

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS56138170A (en) * 1980-02-25 1981-10-28 Ayerst Mckenna & Harrison 2-(1-piperazinyl)-2,4,6-cycloheptatriene-1-one derivative
JPH04208263A (ja) * 1990-01-02 1992-07-29 Fujisawa Pharmaceut Co Ltd インドール誘導体およびそれらの製造法
JPH04230362A (ja) * 1990-07-10 1992-08-19 Adir 新規なピペリジン、テトラヒドロピリジンおよびピロリジン誘導体およびこれらを含有する製薬組成物
WO1995030659A1 (fr) * 1994-05-10 1995-11-16 Warner-Lambert Company Derives de benzimidazoles et d'imidazopyridines, leur preparation et leur utilisation comme agents dopaminergiques hautement selectifs vis-a-vis des recepteurs d3 de la dopamine
WO1996014297A1 (fr) * 1994-11-04 1996-05-17 Sumitomo Pharmaceuticals Company, Limited Nouveaux derives de lactame
WO1997010229A1 (fr) * 1995-09-13 1997-03-20 Neurogen Corporation Nouveaux n-aminoalkylfluorenecarboxamides; nouvelle classe de ligands specifiques de sous-types de recepteurs dopaminergiques
JPH09291033A (ja) * 1995-12-11 1997-11-11 Inst Natl Sante & Rech Med <Inserm> 新規な２−ナフタミド誘導体とその治療への応用
WO1997034884A1 (fr) * 1996-03-21 1997-09-25 Neurogen Corporation Nouveaux n-aminoalkyl-2-anthracenecarboxamides; nouveaux ligands specifiques de sous-type de recepteur de dopamine
WO1997038989A1 (fr) * 1996-04-18 1997-10-23 Neurogen Corporation N-aminoalkyl-2-anthraquinonecarboxamides; nouveaux ligands specifiques de sous-types de recepteurs de la dopamine

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KOEK W. et al., J. PHARMACOL. EXP. THER., (1993), 267(1), p. 181-91. *
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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002020533A2 (fr) * 2000-09-07 2002-03-14 Abbott Laboratories Composes de benzoxazine alpha-1 adrenergique
WO2002020533A3 (fr) * 2000-09-07 2002-08-22 Abbott Lab Composes de benzoxazine alpha-1 adrenergique
US6914064B2 (en) 2000-11-30 2005-07-05 Ranbaxy Laboratories Limited 1,4-Disubstituted piperazine derivatives useful as uro-selective α1-adrenoceptor blockers
WO2002055495A1 (fr) * 2001-01-15 2002-07-18 Glaxo Group Limited Derives aryle de piperidine comme inducteurs de l'expression du recepteur ldl
WO2002055497A1 (fr) * 2001-01-15 2002-07-18 Glaxo Group Limited Derives d'arylepiperidine utilises comme inducteurs d'expression de ldl
EP1495000A1 (fr) * 2002-04-08 2005-01-12 Ranbaxy Laboratories, Ltd. Derives d'alpha, omega-dicarboximide utiles en tant qu'inhibiteurs uroselectifs de l'adreno-recepteur a1a
EP1495000A4 (fr) * 2002-04-08 2005-10-05 Ranbaxy Lab Ltd Derives d'alpha, omega-dicarboximide utiles en tant qu'inhibiteurs uroselectifs de l'adreno-recepteur a1a
JP2005531571A (ja) * 2002-05-23 2005-10-20 アボット・ラボラトリーズ 性機能不全の治療に有用なアセトアミド類およびベンズアミド類
JP2016516829A (ja) * 2013-04-23 2016-06-09 ラボラトリオス・デル・ドクトル・エステベ・ソシエダッド・アノニマ ピラジノ［１，２−ａ］インドール化合物、その調製および医薬としての使用
WO2020235587A1 (fr) * 2019-05-21 2020-11-26 国立大学法人富山大学 Dérivé de tandospirone

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