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WO2001066518A1 - E-ALCOOLS PHENYL-PROSTAGLANDINE φ-SUBSTITUES, PROCEDE DE PREPARATION ASSOCIE ET MEDICAMENTS RENFERMANT CES DERNIERS EN TANT QUE PRINCIPE ACTIF - Google Patents

E-ALCOOLS PHENYL-PROSTAGLANDINE φ-SUBSTITUES, PROCEDE DE PREPARATION ASSOCIE ET MEDICAMENTS RENFERMANT CES DERNIERS EN TANT QUE PRINCIPE ACTIF Download PDF

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Publication number
WO2001066518A1
WO2001066518A1 PCT/JP2001/001816 JP0101816W WO0166518A1 WO 2001066518 A1 WO2001066518 A1 WO 2001066518A1 JP 0101816 W JP0101816 W JP 0101816W WO 0166518 A1 WO0166518 A1 WO 0166518A1
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WO
WIPO (PCT)
Prior art keywords
alkyl
alkyloxy
alkylthio
phenyl
compound
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/JP2001/001816
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English (en)
Japanese (ja)
Inventor
Tohru Maruyama
Kaoru Kobayashi
Takayuki Maruyama
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.)
Ono Pharmaceutical Co Ltd
Original Assignee
Ono Pharmaceutical 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 Ono Pharmaceutical Co Ltd filed Critical Ono Pharmaceutical Co Ltd
Priority to AU2001241067A priority Critical patent/AU2001241067A1/en
Publication of WO2001066518A1 publication Critical patent/WO2001066518A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
    • C07C405/0008—Analogues having the carboxyl group in the side-chains replaced by other functional groups
    • C07C405/0016—Analogues having the carboxyl group in the side-chains replaced by other functional groups containing only hydroxy, etherified or esterified hydroxy groups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to ⁇ -substituted phenyl-prostaglandin E-alcohols. More specifically, the general formula (I)
  • Prostaglandin E 2 (abbreviated as PGE 2 ) is known as a metabolite in the arachidonic acid cascade and has cytoprotective effects, uterine contractions, painful effects, promotion of gastrointestinal peristalsis, It is known to have arousal action, gastric acid secretion inhibitory action, blood pressure lowering action, diuretic action and the like.
  • EP 4 receptor is involved in TNF-Q! Production suppression and IL-10 production enhancement Because it is believed, compounds that bind strongly to the EP 4 receptor, immune diseases (Suji ⁇ reduced lateral sclerosis (ALS), multiple sclerosis, Shiedaren syndrome, rheumatoid arthritis, systemic Eritomato one death, etc.
  • immune diseases Sudji ⁇ reduced lateral sclerosis (ALS), multiple sclerosis, Shiedaren syndrome, rheumatoid arthritis, systemic Eritomato one death, etc.
  • a a represents C 2-8 alkylene, C 2-8 alkenylene, C 1-4 alkylene-phenylene, or C 2-4 alkenylene-phenylene
  • R la is hydroxy, C L ⁇ 6 Arukiruokishi, C L ⁇ 6 Arukiruokishi - C L ⁇ 6 Arukiruokishi, HO- C 1 to 6 Arukiruokishi or wherein NR 6 a R 7a (wherein, R 6a and R 7a are independently a hydrogen atom or a C Represents 1-4 alkyl,) represents,
  • R 2a is oxo, halogen or a formula R 8a —COO— (where R 8a is a hydrogen atom C, C4 alkyl, phenyl or phenyl (C1-4 alkyl), C1-4 alkyloxy, H ⁇ C—C1-4 alkyl, C1-4 alkyloxy-carbonyl—C1-4 alkyl HOOC—C2-4 alkenyl, or C1-4alkyloxy-carbonyl C2-4alkenyl. ) Represents a group represented by
  • R 3a represents a hydrogen atom or hydroxy
  • R 4a represents C 1-4 alkylene
  • R 5a represents a phenyl group substituted with the following group:
  • R 2a is a group represented by the formula R 8a —C ⁇ —
  • R la is C 1-6 alkyloxy, C 1-6 alkyloxy_C 1-6 alkyloxy, or HO—C 1-6 It represents alkyloxy, and positions 8-9 represent a double bond.
  • the present inventors have now found that by converting the carboxylic acid moiety of the compound described in the earlier application to hydroxymethyl (alcohol), it is possible to increase the absorption into the living body, and to provide the present invention. completed.
  • the compound of the present invention represented by the general formula (I) is oxidized in a living body and changes to an active carboxylic acid.
  • the active carboxylic acid has strong binding activity to ⁇ - 4 , low binding activity to other prosnoid receptors including other sub-ives, and also has sufficient stability .
  • the present invention is a.
  • A represents C 2-8 alkylene, C 2-8 alkenylene, C 1-4 alkylene-1 phenylene, or C 2-4 alkenylene-1 phenylene,
  • R 1 represents a hydrogen atom, C1-6 alkyl, phenyl C1-6 alkyl, C2-6 alkanol, phenyl C2-6 alkanol,
  • R 2 represents an oxo or halogen atom
  • R 3 represents a hydrogen atom or a hydroxyl group
  • R 4 represents C 1-4 alkylene
  • R 5 represents a phenyl group substituted by the following groups:
  • C 1-4 alkyl in R 5 means methyl, ethyl, propyl, butyl and isomers thereof.
  • the C 1 to 4 alkylene in R 4 and A means methylene, E styrene, trimethylene, tetramethylene and isomers thereof.
  • C 2-8 alkylene represented by A means methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptane methylene, octamethylene and isomers thereof.
  • C 2-8 alkenylene represented by A has one or two double bonds in the group, and is vinylene, propenylene, butenylene, pentenylene, hexenylene Heptenylene, octenylene, pengenylene, hexogenenylene, heptagenylene, octenylene and isomers thereof.
  • C2-4 alkenylene in A means vinylene, propenylene, butenylene and isomers thereof.
  • the alkyl C 1 to 6 in R 1 means methyl, Echiru, propyl, heptyl, pentyl, hexyl and isomers thereof to.
  • C 2-6 alkanoyl in R 1 means acetyl, propanol, bushyl, pentanoyl, hexanoyl and isomers thereof.
  • C 2-4 alkenyl in R 5 is vinyl, probenyl, Butenyl and their isomers are meant.
  • C 2-4 alkynyl in R 5 means ethynyl, propynyl, butynyl and isomers thereof.
  • the C. 3 to 7 cycloalkyl in R 5 you cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, heptyl cyclohexane.
  • the halogen atom and ha in R 2 and R 5 mean fluorine, chlorine, bromine and iodine.
  • alkyl, alkenyl, alkynyl, alkylene and alkenylene include straight-chain and branched-chain ones.
  • isomers E, Z, cis, trans
  • Isomers R, S isomer, ⁇ , 3 isomers, enantiomers, diastereomers
  • optical isomers with optical activity D, L, d, 1 isomer
  • polar isomers by chromatographic separation highly polar isomers
  • Low polar compounds equilibrium compounds, compounds in any proportion thereof, and racemic mixtures are all included in the present invention.
  • the groups represented by are preferably the following (1) to (7)
  • the hydroxyl group at the 15-position preferably has an ⁇ -configuration.
  • the alkylene of R 4 is preferably methylene or methylmethylene.
  • the substituent of phenyl group in R 5 is 3-position, 3-position and is preferably a combination of 4-position of the combinations and the 3-position and 5-position.
  • the substituent of the phenyl group in R 5 includes: i) 1, 2 or 3 groups selected from an alkyloxyalkyl group, an alkenyloxyalkyl group and a phenyloxyalkyl group,
  • preferred compounds include the compounds described in Examples and the compounds shown below.
  • the compound of the present invention represented by the general formula (I) can be prepared by using ⁇ -, 3- or arcyclodextrin, or a mixture thereof, as described in JP-B-50-3362, JP-A-52-31404 or JP-A-61-52146. It can be converted to a dextrin clathrate inclusion compound by using the method described. Conversion to a cyclodextrin clathrate compound is advantageous when used as a drug because it increases stability and increases water solubility.
  • R 11 is a hydrogen atom, C 1-6 alkyl, phenyl—C 1-6 alkyl, C 2-6 alkanoyl, phenyl—C 2-6 alkanol, or protection of a hydroxyl group which is eliminated under acidic conditions. Represents a group,
  • R 31 represents a hydrogen atom or a hydroxyl group protected by a protecting group which is eliminated under acidic conditions
  • R 10 represents a protecting group for a hydroxyl group which is eliminated under acidic conditions
  • R 5 1 represents the same meaning as R 5, hydroxyl groups in the groups represented Te R 5 1 Niyotsu is assumed to be protected by protecting group which is eliminated under acidic conditions, and the other symbols before Symbol Has the same meaning as )
  • hydroxyl-protecting group examples include t-butyldimethylsilyl, triphenylmethyl, tetrahydropyran-2-yl and the like.
  • Hydrolysis under acidic conditions is known.
  • inorganic acids hydrochloric acid, hydrochloric acid, etc.
  • water-miscible organic solvents such as tetrahydrofuran, methanol, ethanol, dimethoxyethane, acetonitrile, or a mixed solvent thereof
  • the reaction is performed at a temperature of 0 to 5 O using phosphoric acid, hydrofluoric acid, hydrogen fluoride-pyridine, or an organic acid (acetic acid, tosylic acid or its hydrate, trichloroacetic acid, etc.).
  • the compound represented by the general formula (II) can be produced according to the following reaction schemes 1 or 2.
  • R 21 a halogen atom
  • R 12 C 1-6 alkyloxy
  • the other starting materials and reagents in the present invention are known per se or can be produced by known methods.
  • the reaction product is purified by conventional purification means, for example, distillation under normal pressure or reduced pressure, high performance liquid chromatography using silica gel or magnesium gayate, thin-layer chromatography, or color chromatography. It can be purified by a method such as column chromatography, washing, or recrystallization. Purification may be performed for each reaction, or may be performed after completion of several reactions.
  • conventional purification means for example, distillation under normal pressure or reduced pressure, high performance liquid chromatography using silica gel or magnesium gayate, thin-layer chromatography, or color chromatography. It can be purified by a method such as column chromatography, washing, or recrystallization. Purification may be performed for each reaction, or may be performed after completion of several reactions.
  • the compound of the present invention represented by the general formula (I) is oxidized in a living body and changes into carboxylic acid.
  • Carboxylic acid strongly binds to and acts on GE receptor, which is a subtype of PGE 2 receptor, as described in WO00 / 15608.
  • GE receptor which is a subtype of PGE 2 receptor, as described in WO00 / 15608.
  • LPS lipopolysaccharide
  • TNF tumor necrosis factor
  • the compound of the present invention (lmgZkg; alcohol form) was intravenously administered to male SD rats. After intravenous administration, the concentration of the compound in plasma and the concentration of the corresponding oxidized form, rubonic acid, were measured. The preparation of the administration solution was performed using a physiological saline solution containing 0.3% ethanol and 0.1% polysorbate 80 (registered trademark). The concentration was measured using a liquid chromatograph mass spectrometer (L CZM S ZM S).
  • the compound of the present invention represented by the general formula (I) is useful because it is oxidized in a living body to be converted into a carboxylic acid, and the carboxylic acid binds to a PGE 2 receptor and exhibits an action.
  • immune diseases Sudji ⁇ reduced lateral sclerosis (ALS), multiple sclerosis, Shiedaren syndrome, rheumatoid arthritis, systemic Eritomato autoimmune diseases such as one death, Rejection after organ transplantation
  • asthma bone dysplasia, neuronal cell death, lung injury, liver injury, acute hepatitis, nephritis, renal failure, high blood pressure, myocardial ischemia, systemic inflammatory response syndrome, sepsis, hemophagocytosis Syndrome, macrophage activation syndrome, Still (Sti 11) disease, Kawasaki disease, burn, generalized granuloma, ulcerative colitis, Crohn's disease, hypercytosis during dialysis,
  • the oxidized carboxylic acid is represented by E Those binding to subtype other than P 4 is weak, because they do not express other effects, there can be a few side effects drugs.
  • the compound of the present invention represented by the general formula (I) or a cyclodextrin inclusion compound thereof is used for the above purpose, it is usually administered systemically or locally, orally or parenterally.
  • the dosage varies depending on the age, body weight, symptoms, therapeutic effect, administration method, treatment time, etc., but it is usually from 1 g to 100 mg per day per adult, once to several times per day. It is administered orally or parenterally (preferably intravenously) once to several times a day in the range of Olg to 1 Omg per adult per dose. It is continuously administered intravenously for 1 to 24 hours a day.
  • a dose smaller than the above-mentioned dose may be sufficient in some cases, or administration outside the range may be necessary.
  • the compound of the present invention When the compound of the present invention is administered, it is used as a solid composition, a liquid composition and other compositions for oral administration, an injection for parenteral administration, an external preparation, a suppository and the like.
  • Solid compositions for oral administration include tablets, pills, capsules, powders, granules and the like.
  • Capsules include hard capsules and soft capsules.
  • the one or more active substances comprise at least one inert diluent, such as lactose, mannitol, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinyl. It is mixed with pyrrolidone and magnesium aluminate metasilicate.
  • composition may be formulated according to standard procedures with additives other than inert diluents, such as stearyl.
  • a lubricant such as magnesium phosphate, a disintegrant such as calcium cellulose glycolate, and a solubilizing agent such as glutamic acid or aspartic acid may be contained.
  • Tablets or pills may be coated with a film of gastric or enteric substance such as sucrose, gelatin, hydroxypropylcellulose, hydroxypropylcellulose phthalate, if necessary, or with two or more layers. Is also good.
  • capsules of absorbable materials such as gelatin.
  • Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, syrups, elixirs and the like.
  • the one or more active substances are contained in commonly used inert diluents (eg, purified water, ethanol).
  • the composition may contain, in addition to the inert diluent, adjuvants such as wetting agents and suspending agents, sweetening agents, flavoring agents, fragrances, and preservatives.
  • compositions for oral administration include sprays which contain one or more active substances and are formulated in a manner known per se.
  • This composition contains, in addition to the inert diluent, a stabilizer such as sodium bisulfite to provide isotonicity, an isotonic agent such as sodium chloride, sodium citrate or citrate. It may be.
  • a stabilizer such as sodium bisulfite to provide isotonicity
  • an isotonic agent such as sodium chloride, sodium citrate or citrate. It may be.
  • the method for producing the spray is described in detail in, for example, US Pat. Nos. 2,868,691 and 3,095,355.
  • Injections for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions.
  • Aqueous solutions and suspensions include, for example, distilled water for injection and physiological saline.
  • Non-aqueous solutions and suspensions include, for example, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, alcohols such as ethanol, and polysorbate 80 (registered trademark).
  • Such compositions may also contain adjuvants such as preserving, wetting, emulsifying, dispersing, stabilizing, and solubilizing agents (eg, glutamic acid, aspartic acid).
  • compositions for parenteral administration include topical solutions, ointments, liniments, suppositories for rectal administration, and vaginal administration containing one or more active substances and formulated in a conventional manner Pessaries etc. are included.
  • Ac represents an acetyl group
  • Me represents a methyl group
  • THP represents a tetrahydropyran-2-yl group
  • TBS represents a t-butyldimethylsilyl group.
  • the solvent in kakkoko indicated by the chromatographic separation and TLC indicates the elution solvent or developing solvent used, and the ratio indicates the volume ratio.
  • the solvent in kakkoko shown in the NMR section indicates the solvent used for the measurement.
  • Reference example 1 The solvent in kakkoko shown in the NMR section indicates the solvent used for the measurement.
  • the reaction solution was cooled with ice, a saturated aqueous solution of sodium hydrogen carbonate and ethyl acetate were added, and the mixture was separated.
  • the aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with water and saturated saline, dried, and concentrated under reduced pressure.
  • the residue is subjected to silica gel column chromatography (hexane-ethyl acetate to ethyl acetate). The title compound having the following physical data was obtained.
  • the 16 position of these compounds is racemic and the ⁇ / 3 at position 15 is undetermined.
  • Position 16 of this compound is racemic, and position 3 of position 15 is undecided.
  • Formulation Example 1 The following components were mixed in a conventional manner, and the mixture was tableted to give 100 tablets each containing 0.5 mg of the active ingredient.
  • the solution is sterilized by the conventional method, filled into vials by lm 1 and freeze-dried by the conventional method, and 100 vials containing 0.2 mg of the active ingredient in one vial I got

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne des E-alcools phényl-prostaglandine φ-substitués de formule générale (I) dans laquelle chaque symbole est défini dans la description. En raison de leur forte liaison aux récepteurs PGE2 (en particulier, le sous-type EP4) d'acides carboxyliques formés par oxydation in vivo, les composés de formule générale (I) sont spécialement utiles pour la prévention et/ou le traitement de maladies telles que des maladies immunes, l'asthme, des défaillances ostéogénétiques, des lésions pulmonaires et hépatiques, l'hépatite aiguë, l'insuffisance rénale, l'hypertension, l'ischémie du myocarde, le syndrome de réaction inflammatoire généralisée et la septicémie et sont également efficaces contre des maladies associées avec des troubles du sommeil et l'agglutination plaquettaire.
PCT/JP2001/001816 2000-03-09 2001-03-08 E-ALCOOLS PHENYL-PROSTAGLANDINE φ-SUBSTITUES, PROCEDE DE PREPARATION ASSOCIE ET MEDICAMENTS RENFERMANT CES DERNIERS EN TANT QUE PRINCIPE ACTIF Ceased WO2001066518A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001241067A AU2001241067A1 (en) 2000-03-09 2001-03-08 Omega-substituted phenyl-prostaglandin e-alcohols, process for producing the same and drugs containing the same as the active ingredient

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2000064707 2000-03-09
JP2000-64707 2000-03-09

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WO2001066518A1 true WO2001066518A1 (fr) 2001-09-13

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005533043A (ja) * 2002-06-10 2005-11-04 アプライド リサーチ システムズ エーアールエス ホールディング ナームロゼ フェンノートシャップ プロスタグランジン作動薬としてのγラクタムおよびその使用
JP2008533107A (ja) * 2005-03-17 2008-08-21 プロイェクト、デ、ビオメディシナ、シーマ、ソシエダッド、リミターダ 自己免疫疾患および／または移植拒絶反応の予防および／または治療における５’−メチルチオアデノシン（ｍｔａ）の使用
US20150329518A1 (en) * 2014-05-15 2015-11-19 Allergan, Inc. Therapeutic prostaglandin receptor agonists
WO2017195762A1 (fr) * 2016-05-09 2017-11-16 旭硝子株式会社 Nouveau dérivé de prostaglandine

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2523676A1 (de) * 1975-05-26 1976-12-16 Schering Ag Neue prostanderivate und verfahren zu ihrer herstellung
DE2715838A1 (de) * 1977-04-05 1978-10-19 Schering Ag Neue prostanderivate und verfahren zu ihrer herstellung
WO1994006433A1 (fr) * 1992-09-21 1994-03-31 Allergan, Inc. Derives non-acides de 2-cycloalkyle ou d'arylalkyle d'acide heptanoique de cyclopentane en tant qu'agents therapeutiques
WO1996010407A1 (fr) * 1994-09-30 1996-04-11 Alcon Laboratories, Inc. Utilisation de derives de la 9-desoxy prostaglandine pour traiter le glaucome
WO1997030710A1 (fr) * 1996-02-22 1997-08-28 Vision Pharmaceuticals L.P. Composes non acides d'acide cyclopentyle heptanoique et leurs derives 2-cycloalkyle ou arylalkyle utilisables comme agents therapeutiques
WO2000015608A1 (fr) * 1998-09-14 2000-03-23 Ono Pharmaceutical Co., Ltd. Derives e de phenyl-prostaglandine a substitution-φ et medicaments les contenant comme ingredient actif
WO2001017957A1 (fr) * 1999-09-06 2001-03-15 Taisho Pharmaceutical Co., Ltd. Analogues de la prostaglandine e

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2523676A1 (de) * 1975-05-26 1976-12-16 Schering Ag Neue prostanderivate und verfahren zu ihrer herstellung
DE2715838A1 (de) * 1977-04-05 1978-10-19 Schering Ag Neue prostanderivate und verfahren zu ihrer herstellung
WO1994006433A1 (fr) * 1992-09-21 1994-03-31 Allergan, Inc. Derives non-acides de 2-cycloalkyle ou d'arylalkyle d'acide heptanoique de cyclopentane en tant qu'agents therapeutiques
WO1996010407A1 (fr) * 1994-09-30 1996-04-11 Alcon Laboratories, Inc. Utilisation de derives de la 9-desoxy prostaglandine pour traiter le glaucome
WO1997030710A1 (fr) * 1996-02-22 1997-08-28 Vision Pharmaceuticals L.P. Composes non acides d'acide cyclopentyle heptanoique et leurs derives 2-cycloalkyle ou arylalkyle utilisables comme agents therapeutiques
WO2000015608A1 (fr) * 1998-09-14 2000-03-23 Ono Pharmaceutical Co., Ltd. Derives e de phenyl-prostaglandine a substitution-φ et medicaments les contenant comme ingredient actif
WO2001017957A1 (fr) * 1999-09-06 2001-03-15 Taisho Pharmaceutical Co., Ltd. Analogues de la prostaglandine e

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005533043A (ja) * 2002-06-10 2005-11-04 アプライド リサーチ システムズ エーアールエス ホールディング ナームロゼ フェンノートシャップ プロスタグランジン作動薬としてのγラクタムおよびその使用
JP4754820B2 (ja) * 2002-06-10 2011-08-24 メルク セローノ ソシエテ アノニム プロスタグランジン作動薬としてのγラクタムおよびその使用
JP2008533107A (ja) * 2005-03-17 2008-08-21 プロイェクト、デ、ビオメディシナ、シーマ、ソシエダッド、リミターダ 自己免疫疾患および／または移植拒絶反応の予防および／または治療における５’−メチルチオアデノシン（ｍｔａ）の使用
US20150329518A1 (en) * 2014-05-15 2015-11-19 Allergan, Inc. Therapeutic prostaglandin receptor agonists
US9394273B2 (en) * 2014-05-15 2016-07-19 Allergan, Inc. Therapeutic prostaglandin receptor agonists
WO2017195762A1 (fr) * 2016-05-09 2017-11-16 旭硝子株式会社 Nouveau dérivé de prostaglandine
KR20190005172A (ko) * 2016-05-09 2019-01-15 에이지씨 가부시키가이샤 신규 프로스타글란딘 유도체
JPWO2017195762A1 (ja) * 2016-05-09 2019-03-14 Ａｇｃ株式会社 新規なプロスタグランジン誘導体
US10494338B2 (en) 2016-05-09 2019-12-03 AGC Inc. Prostaglandin derivative
JP2020109096A (ja) * 2016-05-09 2020-07-16 Ａｇｃ株式会社 新規なプロスタグランジン誘導体
AU2017264102B2 (en) * 2016-05-09 2020-09-24 AGC Inc. Novel prostaglandin derivative
KR102532836B1 (ko) 2016-05-09 2023-05-15 에이지씨 가부시키가이샤 신규 프로스타글란딘 유도체

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