WO2002044129A1 - Dérivés d'acide carboxylique substitués - Google Patents

Dérivés d'acide carboxylique substitués

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Publication number
WO2002044129A1
WO2002044129A1 PCT/JP2001/010352 JP0110352W WO0244129A1 WO 2002044129 A1 WO2002044129 A1 WO 2002044129A1 JP 0110352 W JP0110352 W JP 0110352W WO 0244129 A1 WO0244129 A1 WO 0244129A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
carbon atoms
alkyl group
carboxylic acid
pharmaceutically acceptable
Prior art date
Application number
PCT/JP2001/010352
Other languages
English (en)
Japanese (ja)
Inventor
Hiroyuki Miyachi
Kouji Murakami
Original Assignee
Kyorin 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 Kyorin Pharmaceutical Co., Ltd. filed Critical Kyorin Pharmaceutical Co., Ltd.
Priority to JP2002546499A priority Critical patent/JPWO2002044129A1/ja
Priority to AU2002222549A priority patent/AU2002222549A1/en
Publication of WO2002044129A1 publication Critical patent/WO2002044129A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/84—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to a hypoperoxisomal proliferator-activated receptor (PPAR) agonist, particularly a hypolipidemic agent, particularly a hepatic lipid-lowering agent, and an arteriosclerosis agonizing agent against human PPAR isoform.
  • PPAR hypoperoxisomal proliferator-activated receptor
  • the present invention relates to a substituted carboxylic acid derivative and an addition salt thereof, which are effective as a therapeutic agent for metabolic diseases such as an inhibitor for progress, an antiobesity agent, and a therapeutic agent for diabetes, a method for producing the same, and a pharmaceutical composition containing these compounds.
  • PPAR hypoperoxisomal proliferator-activated receptor
  • Peroxisome proliferator-activated receptor is a ligand-dependent transcription factor that belongs to the nuclear superfamily, like the steroid receptor, retinoid receptor, and thyroid receptor. Three isoforms ( ⁇ -type, ( ⁇ (or ⁇ )-type, and ⁇ -type)) with different tissue distributions have been identified in various animal species including humans (Proc. Natl.
  • PPARs are distributed in the liver and kidney, etc., which have high fatty acid catabolism, and high expression is observed especially in the liver ( ⁇ 2 ⁇ ci / 2oc ⁇ 1995, JJil, 354). Correct the expression of genes related to intratransport (eg, acyl-CoA synthase, fatty acid binding protein lipoprotein lipase) and genes for apolipoprotein 1, 11, (] 111) related to cholesterol and neutral lipid metabolism. ⁇ Negative control. Is ubiquitously expressed in various tissues in the body, mainly in nerve cells. At this time, the physiological significance of PPAR5 is unknown. PPARa is highly expressed in adipocytes and is involved in adipocyte differentiation (. 1996, SI, 907). Thus, each isoform of PPAR performs a specific function in a specific organ or tissue.
  • PPARQ knockout mice exhibit hypertriglyceridemia and hypoglycemia with aging, and become obese mainly due to an increase in white fat cells ( ⁇ 1998, Natl. Acad. Sci., 1999, 747 3), PPARa is a major source of blood lipids (cholesterol and neutral lipids) and darcosyl chloride. It is strongly suggested that it plays an important role in regulating homeostasis and energy balance.
  • fibrate drugs have been widely used for the treatment of hyperlipidemia, especially for hypertriglyceridemia, but the activation of PPAR is considered as a mechanism of action of these fibrates. (Lipid. Res., 19%, SI, 907).
  • a fibrate-based drug suppresses the increase in body weight and adipose tissue weight in insulin-resistant animal models and normalizes decreased glucose tolerance in J. Biol. Chem., 2000, ⁇ , 16638, Biochem. Biophys. Res. Co, 2000, ⁇ , 445), has been shown to be involved in the improvement of insulin resistance.
  • fibrate drugs have a weak ⁇ activating effect, and their efficacy is far from satisfactory.
  • various side effects such as gastrointestinal disorders, rash, headache, hepatic dysfunction, renal dysfunction and gallstones have been reported for fibrate drugs. Non-specific effects are thought to be the cause, and the development of therapeutic drugs for metabolic diseases using specific mechanisms is desired.
  • W represents a (substituted) lactam ring
  • A represents an alkylene group or an alkylenoxy group
  • X represents 0, S, NH, CH 2
  • Y 1 represents an amino, hydroxyl, or alkoxy group.
  • R 1 represents ⁇ or an alkyl group, etc.
  • R 2 represents an alkyl group or a phenyl group
  • R 3 represents ⁇ , an alkyl group or an alkoxy group, etc.
  • these compounds have a carbonyl group under the linking moiety. It differs from the compound of the present invention in that it does not contain a mid group and that it contains a lactam ring in the terminal substituent W, and these compounds have human PPAR binding activity and transcription activation activity. The thing is not described.
  • a 1 represents an aryl group or a heterocyclic group which may have a substituent
  • Y 2 represents an alkylene chain having 1 to 5 carbon atoms
  • X 4 represents a bond, an oxygen atom or a sulfur atom.
  • W 1 represents a naphthylene ring, a quinoline ring, an indole ring, a benzisoxazole ring or a benzo [b] thiophene ring which may have a substituent; 4 represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms; X 5 represents an oxygen atom or a sulfur atom; and is an alkyl group having 1 to 8 carbon atoms which may have a substituent, an aralkyl group. Or represents an aryl group).
  • these compounds differ from the compounds of the present invention in that they do not contain a carbonyl group or an amide group in Y 2 and X 4 of the linking moiety and that W 1 bonded to the 3-position of propionic acid is a heterocyclic ring. It is not described that these compounds have different structures and that these compounds have human PPAR binding activity and transcriptional activation activity.
  • R represents a substituent represented by and D 2
  • ⁇ 1 represents an aromatic ring, a cycloalkyl group and a heteroaromatic ring
  • R 5 represents an alkyl group
  • R 4 represents a hydrogen atom or Represents an alkyl group, may be linked to a hydrogen atom or to form a double bond
  • ⁇ 7 is a carboxyl group, an acyl group, an alkoxycarbonyl group which may have a substituent, an alkyl group
  • R 8 represents an aryloxycarbonyl group, an aralkyloxycarbonyl group, a sorbamoyl group, the title R 8 or an OR 8 group
  • H 8 represents an optionally substituted alkyl group or an alkoxycarbonyl group.
  • R 9 represents a hydrogen atom, alkyl group, alkoxy carbonylation group
  • R 1 Q represents a hydrogen atom, an amino group, an alkoxy group, an alkyl group, Ariruokishi group and Ararukiruokishi group) Compounds have been reported.
  • these compounds also differ in structure from the compounds of the present invention in that the substituents on the benzene ring are di-substituted at the 1- and 4-positions, and these compounds also have human PPAR binding activity and transcriptional activation. No effect is stated.
  • A represents a hydrogen atom or a fluorine group
  • m represents an integer of 3 to 10
  • n represents an integer of 1 to 6
  • X represents a C0NH group or an NHC0 group
  • R represents a carboxy group.
  • these compounds do not have a substituent at the 2-position of propionic acid, and all of the R groups have a carbonyl group, so the structure is different from that of the compound of the present invention. No mention is made that it has a PPAR binding activity and a transcriptional activating effect.
  • R 1 represents a hydrogen atom, - 6 alkyl group, Ariru C 4 - 1Q alkyl, ⁇ aryl group, a carboxyl group, an alkoxy group, a carboxy C Q - fi alkyl Group, carboxy C Q - 6 alkoxy group, human Dorokishi _ 6 alkyl group, d_ 4 alkylsulfonyl C Q - 6 alkyl group, C Q - 4 Arukiruamino C.
  • Ra represents a 2-benzoxazolyl group or 2-pyridyl group
  • R b represents a methoxymethyl group or a trifluoromethyl group.
  • these compounds differ in structure from the compounds of the present invention in that the substituent on the benzene ring is a disubstituted derivative at the 1-position and 4-position, and further has a human PPAR binding activity and a transcription activating activity. The thing is not described.
  • X represents a hydrogen atom or a fluorine atom). Have been.
  • these compounds are different from the compound of the present invention in that they are phenoxyacetic acid derivatives, and the positional relationship of the substituents on the benzene ring is di-substituted at the 1-position and 4-position. Also, the transcriptional activation of PPAR is not satisfactory.
  • Atherosclerotic diseases such as ischemic heart disease
  • hyperlipidemia, diabetes mellitus and hypertension are considered as the main risk factors for this arteriosclerotic disease, and the presence of insulin resistance is considered to be important in the pathology. It is clear that obesity due to the accumulation of visceral fat is deeply involved. Therefore, there is a clinical need for the development of a therapeutic agent for metabolic diseases that is totally effective and highly safe for these diseases. Disclosure of the invention
  • the present inventors focused on the specific role of such a human PPAR for the purpose of creating a structurally novel drug having high efficacy and safety as a therapeutic drug for metabolic diseases, and conducted intensive research. As a result, the present inventors have found that the novel substituted carboxylic acid derivative represented by the following general formula (1) has excellent human PPARa binding activity and transcription activating effect, and completed the present invention.
  • the present invention relates to the general formula (1)
  • n 0, 1 or 2
  • IU 0 or 2
  • hydrogen Atom or a lower alkyl group having 1 to 10 carbon atoms and when n is 1, represents a lower alkyl group having 1 to 10 carbon atoms.
  • It relates to salts and hydrates thereof.
  • the salts of the compound represented by the general formula (1) in the present invention are conventional ones, and include metal salts such as alkali metal salts (eg, sodium salt, calcium salt, lithium salt, etc.), Pharmaceutically acceptable salts such as alkaline earth metal salts (for example, calcium salt, magnesium salt, etc.) and aluminum salts.
  • metal salts such as alkali metal salts (eg, sodium salt, calcium salt, lithium salt, etc.)
  • Pharmaceutically acceptable salts such as alkaline earth metal salts (for example, calcium salt, magnesium salt, etc.) and aluminum salts.
  • the compound represented by the general formula (1) in the present invention may include an optical isomer based on a substituted carboxylic acid moiety.
  • compounds obtained in the course of synthesis of the compound represented by the general formula (1) include a mixture of geometric isomers. All such isomers and mixtures thereof are included within the scope of the present invention.
  • Each optical isomer can be produced by a stereoselective synthesis method. They are also obtained by separating the diastereomeric ester derivative oxazolidinone derivative obtained by reacting with an optically active alcohol derivative or an optically active oxazolidinone derivative by fractional crystallization or a method of chromatography and then hydrolyzing it. It can also be manufactured. Further, they can be produced by a technique of mouth chromatography using a chiral support.
  • the “lower alkyl group having 1 to 10 carbon atoms” refers to a linear or branched one having 1 to 10 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl and the like. No.
  • the compound represented by the above general formula (1) can be produced, for example, by the following method (Scheme 1). 4th process
  • ⁇ represents 0, 1 or 2
  • R represents a hydrogen atom or a lower alkyl group having 1 to 10 carbon atoms when ⁇ is 0 or 2
  • the substituted carboxylic acid derivative represented by the following formula] or its ester, its pharmaceutically acceptable salt and its hydrate are benzyl 2-methoxy-5-formylbenzoate (2)
  • the compound can be produced by hydrolyzing 1 part of C00H (fourth step).
  • the Wittig reaction or Horner-Eimons reaction in the first step is carried out in a solvent such as tetrahydrofuran, toluene, dioxane or ⁇ -dimethylformamide, and as a base, an alkali metal such as sodium hydride. It is possible to use hydrides, organometallic compounds such as butyllithium, metal amides such as lithium diisopropylamide, and metal alkoxides such as sodium methoxide cadmium-butoxide.
  • the reaction can be carried out at a reaction temperature of -20 ° C to 150 ° C, preferably at 0 ° C to 50 ° C.
  • the reduction reaction in the second step is carried out in a solvent such as ethanol, methanol, tetrahydrofuran, ethyl acetate, and -dimethylformamide in the presence of a metal catalyst such as palladium-supported activated carbon, platinum-supported activated carbon, platinum oxide, and alumina supported on mouth.98. It can be implemented at 1 kPa to 491 kPa.
  • the reaction can be carried out at a reaction temperature of 0 ° C to 100 ° C, preferably at room temperature to 80 ° C.
  • the condensation reaction in the third step can be carried out by leaving the carboxyl group as it is or by converting it into a reactive derivative.
  • Examples of the “reactive group for carboxyl group” include acid chlorides, acid bromides, acid anhydrides, carbonimidazoles, and the like.
  • an alkali metal hydride such as sodium hydride or sodium hydroxide is used as a base.
  • Al-like metal hydroxide such as Pum It can be carried out in the presence or absence of an alkali metal carbonate such as potassium carbonate, or an organic base such as pyridine or triethylamine.
  • reaction When the reaction is carried out in the form of a carboxylic acid, the reaction is carried out in the presence of a condensing agent in a solvent such as methylene chloride, chloroform, dioxane, or ⁇ -dimethylformamide. Can be performed in the presence or absence of a condensing agent in a solvent such as methylene chloride, chloroform, dioxane, or ⁇ -dimethylformamide. Can be performed in the presence or absence of
  • Examples of the condensing agent include dicyclohexylcarbodiimide, tri [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride, getyl cyanophosphate, azide diphenylphosphate, carbonyldiimidazole and the like.
  • Can be Examples of the base include alkali metal hydroxides such as sodium hydroxide, alkali metal carbonates such as potassium carbonate, and organic bases such as pyridine and triethylamine.
  • Examples of the additives include -hydroxybenzotriazole, -hydroxysuccinimide ⁇ 3,4-dihydroxy-3-hydroxy-4-oxo-1,2,3-benzotriazine and the like. No. The reaction can be carried out at a reaction temperature of -20 ° C to 100 ° C, preferably 0 ° C to 50 ° C.
  • the hydrolysis reaction in the fourth step can be performed under alkaline conditions.
  • the alkaline conditions lithium hydroxide, sodium hydroxide, potassium hydroxide, etc. are used.
  • the reaction can be carried out at a temperature of 0 ° C to 80 ° C, preferably at room temperature to 60 ° C.
  • Examples of the dosage form of the novel compound of the present invention include solid compositions, liquid compositions and other compositions for oral administration, and injections, external preparations and suppositories for parenteral administration.
  • Solid compositions for oral administration include tablets, pills, capsules, powders, granules and the like.
  • Liquid compositions for oral administration include pharmaceutically acceptable emulsions, mouthwashes and the like.
  • Other compositions for oral administration include sp Laying agents are included.
  • Injections for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions.
  • reaction solution was washed with a 10% aqueous solution of citric acid, a 0.5 mol / L aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride, and then anhydrous sodium sulfate. Dried and concentrated. The residue was purified by silica gel chromatography (eluent ⁇ -hexane: ethyl acetate 2: 3 v / v) to give 770 mg (85%) of the title compound as a colorless oil. I got it.
  • reaction solution is washed successively with a 10% aqueous solution of citric acid, a 0.5 mol / L aqueous solution of sodium hydrogen carbonate, and saturated saline, dried over anhydrous sodium sulfate and concentrated. 800 mg of the condensate was obtained quantitatively.
  • the obtained condensate (550 mg, 1.30 mmol) was mixed with 2 mol / L sodium hydroxide aqueous solution (5fflL) and methanol (30 mL), and the mixture was stirred at 60 ° C for 4 hours.
  • the reaction solution was concentrated under reduced pressure, and the residue was dissolved in water and acidified with diluted hydrochloric acid.
  • the DNA-binding domain of yeast transcription factor and the ligand-binding domain of human PPAR were added to CH0 cells cultured in Dulbecco's modified Eagle's medium (FCS / DMEM) containing 10% defatted bovine serum Biocheittistry, 1993, ⁇ l , 5598), a receptor plasmid expressing the fusion protein and its repo overnight plasmid (STRATAGENE), and an internal standard, such as MYCHIKELCIFFERASE Plasmid (PR0MEGA), were not available in Lipofectamine. Cotransfection was performed in serum. Thereafter, the test compound was added in 10% SFCS / DMEM, and 24 hours later, both luciferase activities were measured, and corrected using an internal standard.
  • FCS / DMEM Dulbecco's modified Eagle's medium
  • STRATAGENE a receptor plasmid expressing the fusion protein and its repo overnight plasmid
  • PR0MEGA MYCHIKELCIFF
  • Table 5 shows the results. From these results, it was shown that the compound of the present invention has a strong transcriptional activating effect on the receptor for activating the hyperperoxisome proliferator. (Table 5) Example Transcriptional activation
  • the substituted carboxylic acid derivatives of the present invention are a group of novel compounds having an excellent PPAR transcription activating effect.
  • these compounds of the present invention have a strong agonistic activity against PPAR, the above-mentioned lipid-lowering drugs, especially drugs for lowering lipids in the liver, drugs for suppressing the progression of arteriosclerosis, anti-obesity drugs, drugs for treating diabetes, etc. It is a compound that is effective as a drug for treating metabolic diseases.

Abstract

L'invention concerne des dérivés d'acide carboxylique substitués qui se lient au récepteur humain α activé par les proliférateurs de peroxysome (PPARα) en tant que ligands dudit récepteur et qui activent ledit récepteur afin de réduire les lipides, de prévenir l'artériosclérose, de lutter contre l'obésité, de provoquer un effet hypoglycémique, etc. L'invention concerne également un procédé de production desdits dérivés. L'invention concerne plus particulièrement des dérivés d'acide carboxylique substitués représentés par la formule générale suivante (1), des esters, des sels pharmaceutiquement acceptables et des hydrates desdits dérivés, ainsi qu'un procédé de production desdits composés. Dans la formule générale (1), n vaut 0, 1 ou 2 ; et R représente hydrogène ou alkyle inférieur C1-10 si n vaut 0 ou 2 ou alkyle inférieur C1-10 si n vaut 1.
PCT/JP2001/010352 2000-11-29 2001-11-28 Dérivés d'acide carboxylique substitués WO2002044129A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2002546499A JPWO2002044129A1 (ja) 2000-11-29 2001-11-28 置換カルボン酸誘導体
AU2002222549A AU2002222549A1 (en) 2000-11-29 2001-11-28 Substituted carboxylic acid derivatives

Applications Claiming Priority (2)

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JP2000-363676 2000-11-29
JP2000363676 2000-11-29

Publications (1)

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WO2002044129A1 true WO2002044129A1 (fr) 2002-06-06

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006503915A (ja) * 2002-10-21 2006-02-02 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ 置換テトラリンおよびインダンを用いたｘ症候群の治療
JP2006503917A (ja) * 2002-10-21 2006-02-02 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ 置換テトラリンおよびインダンそしてこれらの使用
JP2006503916A (ja) * 2002-10-21 2006-02-02 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ 置換テトラリンおよびインダン
JP2007001912A (ja) * 2005-06-22 2007-01-11 Univ Of Tokyo 置換フェニルプロピオン酸誘導体

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000256194A (ja) * 1999-01-06 2000-09-19 Mitsui Chemicals Inc 核内レセプタ作動薬およびその効果増強剤
WO2000075103A1 (fr) * 1999-06-09 2000-12-14 Kyorin Pharmaceutical Co., Ltd. DERIVES D'ACIDE PHENYLPROPIONIQUE SUBSTITUES COMME AGONISTES DU RECEPTEUR HUMAIN ACTIVE DE LA PROLIFERATION DES PEROXYSOMES (PPAR) $g(a)
WO2001025181A1 (fr) * 1999-10-01 2001-04-12 Eisai Co., Ltd. Derives d'acide carboxylique et medicaments les contenant

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000256194A (ja) * 1999-01-06 2000-09-19 Mitsui Chemicals Inc 核内レセプタ作動薬およびその効果増強剤
WO2000075103A1 (fr) * 1999-06-09 2000-12-14 Kyorin Pharmaceutical Co., Ltd. DERIVES D'ACIDE PHENYLPROPIONIQUE SUBSTITUES COMME AGONISTES DU RECEPTEUR HUMAIN ACTIVE DE LA PROLIFERATION DES PEROXYSOMES (PPAR) $g(a)
WO2001025181A1 (fr) * 1999-10-01 2001-04-12 Eisai Co., Ltd. Derives d'acide carboxylique et medicaments les contenant

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006503915A (ja) * 2002-10-21 2006-02-02 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ 置換テトラリンおよびインダンを用いたｘ症候群の治療
JP2006503917A (ja) * 2002-10-21 2006-02-02 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ 置換テトラリンおよびインダンそしてこれらの使用
JP2006503916A (ja) * 2002-10-21 2006-02-02 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ 置換テトラリンおよびインダン
JP2007001912A (ja) * 2005-06-22 2007-01-11 Univ Of Tokyo 置換フェニルプロピオン酸誘導体

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AU2002222549A1 (en) 2002-06-11

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