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WO2002046146A1 - Derives d'acide carboxylique substitues - Google Patents

Derives d'acide carboxylique substitues Download PDF

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Publication number
WO2002046146A1
WO2002046146A1 PCT/JP2001/010563 JP0110563W WO0246146A1 WO 2002046146 A1 WO2002046146 A1 WO 2002046146A1 JP 0110563 W JP0110563 W JP 0110563W WO 0246146 A1 WO0246146 A1 WO 0246146A1
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WIPO (PCT)
Prior art keywords
group
carbon atoms
hydrogen atom
alkyl group
carboxylic acid
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Ceased
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PCT/JP2001/010563
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English (en)
Japanese (ja)
Inventor
Hiroyuki Miyachi
Yukie Takahashi
Kouji Murakami
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Kyorin Pharmaceutical Co Ltd
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Kyorin Pharmaceutical Co Ltd
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Priority to JP2002547885A priority Critical patent/JPWO2002046146A1/ja
Priority to AU2002222573A priority patent/AU2002222573A1/en
Publication of WO2002046146A1 publication Critical patent/WO2002046146A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C275/30—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups

Definitions

  • the present invention provides an agonist for human peroxisome proliferator-activated receptor (PPAR) agonist, particularly for human PPAR isoform, for metabolic diseases such as hyperlipidemia, obesity, and diabetes.
  • PPAR peroxisome proliferator-activated receptor
  • the present invention relates to a therapeutically effective substituted carboxylic acid derivative, an addition salt thereof, a production method thereof, and a pharmaceutical composition containing these compounds.
  • Peroxisome proliferator-activated receptor ⁇ is a ligand-dependent transcription factor that belongs to the nuclear family superfamily like steroid receptor, retinoid receptor, thyroid receptor, etc. Three isoforms ( ⁇ type, (5 (or ⁇ ) type, ⁇ type)) with different distributions have been identified in various animal species including humans (roc. Natl. Acad. Sci., 1992). Among them, PPAR is distributed in the liver and kidney, etc., which have high catabolism of fatty acids, and high expression is observed especially in the liver.
  • PPAR fatty acid metabolism and intracellular transport
  • genes involved in fatty acid metabolism and intracellular transport eg, acyl-CoA synthetase, fatty acid binding protein lipoprotein lipase
  • apolipoproteins involved in cholesterol and neutral lipid metabolism Controls gene expression (AI, AII, CIII, etc.).
  • PPAR (5 is ubiquitously expressed in various tissues in vivo, especially in neurons. At this time, the physiological significance of PPAR3 has not been fully elucidated.
  • PPARa is highly expressed in adipocytes. are involved in the minute of the fat cells Te (. es., 1996, ai , 907) o of PPAR in this manner Each isoform performs a specific function in a particular organ or tissue.
  • PPAR chick knockout mice exhibit hypertriglyceridemia and hypoglycemia with aging, and become obese mainly due to an increase in white adipocytes (Io 1998,, 29577, J. Clin. Invest., ⁇ ⁇ , ⁇ ⁇ ⁇ , 1083, Proc. Natl. Acad. Sci., 1999,, 747 3), PPARs have blood lipids (cholesterol and neutral lipids) and blood It is strongly suggested that it plays an important role in regulating the homeostasis and energy balance of Darcos.
  • fibrates have been widely used as drugs for treating hyperlipidemia, particularly for treating hypertriglyceridemia.
  • Activation of PPAR has been reported as a mechanism of action of this fibrinoid. Lipid. Res. A9, SI, 907).
  • fibrate drugs suppress the increase in body weight and adipose tissue weight in insulin resistant animal models and normalize the decreased glucose tolerance (J. Biol. Chem. ,?) 00, Ii, 16638 , Biochem .Biophys. Res. Com., 2000, m, 445) s P PAR has been shown to be involved in the improvement of Insurin resistance.
  • PPARs specifically bind to human ⁇ -ligand. If a compound capable of activating human PPARo: can be created, It is expected to be used as a medicament for the treatment of metabolic diseases caused by nism.
  • oxidation shea Tokuromu P- 450 in addition to LTB 4 is a metabolite of Arakidon acid HETE (hydroxycarboxylic Eiko satay Toraen acid ) Eicosanoids of the group, especially 8-HETE, 8-HEPE, etc. have been reported (/ »o ⁇ . ⁇ . ⁇ . ⁇ ⁇ ⁇ , ⁇ ., 312).
  • HETE hydroxycarboxylic Eiko satay Toraen acid
  • 8-HETE, 8-HEPE, etc. have been reported (/ »o ⁇ . ⁇ . ⁇ . ⁇ ⁇ , ⁇ ., 312).
  • these endogenous unsaturated fatty acid derivatives are metabolically and chemically unstable and cannot be used as a medicine.
  • JP-A-11-158144 as a -substituted phenylpropionic acid derivative having a hypoglycemic effect and a hypolipidemic effect
  • 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 group, a hydroxyl group or Represents an alkoxy group
  • R 1 represents a hydrogen atom or an alkyl group, etc., represents an alkyl group or a phenyl group, and represents a hydrogen atom, an alkyl group, an alkoxy group, or the like. It has been reported.
  • these compounds have a laid group at one part of the linking moiety. It differs from the compounds of the present invention in that they do not contain them and that they contain a lactam ring in the terminal substituent W, and it is described that these compounds have human ⁇ binding activity and transcriptional activation activity. Absent.
  • 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
  • R 4 is hydrogen
  • X represents an atom or an alkyl group having 1 to 8 carbon atoms
  • X 5 represents an oxygen atom or a sulfur atom
  • R 5 represents an alkyl group having 1 to 8 carbon atoms which may have a substituent;
  • Or represents an aryl group).
  • these compounds have a different structure from the compounds of the present invention in that they do not contain a peridot group in Y 2 and X 4 of the linking moiety and are heterocyclic rings bonded to the 3-position of propionic acid. It is not described that these compounds have a human PPARa binding activity and a transcription activating effect.
  • R 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
  • beta 7 is a carboxyl group
  • Ashiru group which may have a substituent alkoxycarbonyl group
  • an alkyl represents an aryl group, an aryloxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl group, a group and an OR 8 group
  • R 8 represents an optionally substituted aryl group or an alkoxycarbonyl group.
  • R 9 represents a group
  • R 9 represents a hydrogen atom
  • Al kill group represents an alkoxycarbonyl two Le group
  • R 1 Q is represented by a hydrogen atom, an amino group, an alkoxy group, an alkyl group, Ariruokishi group and Ararukiruokishi group) Compounds have been reported .
  • these compounds differ in structure from the compounds of the present invention in that the linkage between the H-containing side chain moiety and the benzene ring is limited to oxygen atoms, and these compounds have a human PPAR binding activity, It is not described that it has a transcription activating effect.
  • A represents a hydrogen atom or a fluoro 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.
  • Compounds represented by a lower alkyl group or a carboxy lower alkylcarbamoyl group (where A represents a phenyl group and R represents a carboxy lower alkyl carbamoyl lower alkyl group) have been reported.
  • R 1 is a hydrogen atom, an alkyl group, an aryl C 4 _ 1 Q alkyl group, an aryl group, a carboxyl group, a 6 alkoxy group, a carboxy C Q _ 6 alkyl Group, forces Rupokishi C Q - 6 alkoxy group, human Dorokishi CH alkyl group, ( ⁇ _ 4 alkylsulfonyl C Q - 6 alkyl group, C 4 Arukiruamino C Q - 6 alkyl group, Ariru Co- 1 () Arukiruamino C 0 _ 6 alkyl groups, C 2 - 1 () Ashiruami Bruno C Q _ 6 alkyl group, (4 carboalkoxy C Q _ 6 alkyl or halogen atoms, the same or different hydrogen atom, androgenic atom, human de port hexyl group, CH alkoxy group, Ariru Co- 4 alkyl group, Ari Le C Q Q _ 6
  • Ra represents a 2-benzoxazolyl group or a 2-pyridyl group
  • Rb represents a methoxymethyl group or a trifluoromethyl group
  • Atherosclerotic diseases such as ischemic heart disease
  • hyperlipidemia, diabetes, and hypertension are considered to be the main risk factors for this arteriosclerotic disease, and the presence of insulin resistance is considered to be important in the pathology. It has been shown that obesity due to fat accumulation 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 have focused on the specific role of such a human PPAR for the purpose of creating a structurally novel drug that is highly effective and safe as a therapeutic drug for metabolic diseases, and conducted extensive research.
  • 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 activity, and completed the present invention. That is, the present invention relates to the general formula (1)
  • R 1 represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms
  • R 2 represents a hydrogen atom or a lower alkoxy group having 1 to 4 carbon atoms
  • R 4 represents a hydrogen atom, a trifluoromethyl group, a lower alkoxy group having 1 to 4 carbon atoms, a halogen atom, or an unsubstituted or substituted
  • R 5 represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms
  • n represents an integer of 0 to 3
  • the substitution position of the carboxylic acid residue is represented by R 2 Para to the substituent or para to the (CH 2 ) n substituent]], a pharmaceutically acceptable salt thereof, and a hydrate 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 process of synthesizing 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 can also be produced by reacting an optically active alcohol derivative or an optically active oxazolidinone derivative with a diastereomeric ester derivative ⁇ oxazolidinone derivative obtained by fractional crystallization or chromatography. . Further, they can be produced by a technique of mouth chromatography using a chiral support.
  • a lower alkyl group having 1 to 4 carbon atoms means a straight chain such as methyl, ethyl, propyl, isopropyl and butyl Or branched ones having 1 to 4 carbon atoms.
  • lower alkoxy group having 1 to 4 carbon atoms includes straight or branched ones having 1 to 4 carbon atoms such as methoxy group, ethoxy group, propoxy group, isopropoxy group and butoxy group.
  • alkyl group having 1 to 10 carbon atoms includes those having 1 to 10 carbon atoms that are linear or branched such as methyl, ethyl, propyl, isopropyl, heptyl, and decyl.
  • Substituents allowed in the “unsubstituted or optionally substituted phenoxy group” represent a lower alkoxy group having 1 to 4 carbon atoms or a halogen atom.
  • Halogen atom includes a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
  • R 3 is a hydrogen atom
  • n is 0, and the carboxylic acid moiety is in the para position of R 2 in the general formulas (la ′ and la).
  • Certain compounds can be produced, for example, by the following method (Scheme 1).
  • ⁇ 1 represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms
  • R 2 represents a hydrogen atom, a lower alkoxy group having 1 to 4 carbon atoms
  • R 4 represents a hydrogen atom
  • trifluoromethyl represents a lower alkoxy group having 1 to 4 carbon atoms, a nitrogen atom, an unsubstituted or optionally substituted phenoxy group or a benzyloxy group
  • the compound can be produced by hydrolyzing the C00R 6 site of the compound (second step).
  • the reaction in the first step can be carried out in a solvent such as methylene chloride, chloroform, tetrahydrofuran, ethyl acetate, and ⁇ -dimethylformamide.
  • the reaction can be carried out at a reaction temperature of -50 ° C to 150 ° C, preferably at room temperature to the reflux temperature of the solvent.
  • the reaction in the second step can be performed under alkaline conditions.
  • the alkaline conditions lithium hydroxide, sodium hydroxide, lithium hydroxide or a mixture of these alkali metal hydroxides with methanol, ethanol, tetrahydrofuran and the like are used.
  • the reaction can be carried out at a reaction temperature of ⁇ 20 ° C. to 100 ° C., preferably 0 ° C. to 50 ° C.
  • ⁇ 3 is an alkyl group having 1 to 10 carbon atoms, ⁇ is 1, and the carboxylic acid moiety is in the para position of H 2 (lb. And lb) can be produced, for example, by the following method (Scheme 2).
  • R 1 represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms
  • R 2 represents a hydrogen atom, a lower alkoxy group having 1 to 4 carbon atoms
  • R 3 represents a 1 to 10 carbon atoms.
  • R 4 represents a hydrogen atom, a trifluoromethyl group, a lower alkoxy group having 1 to 4 carbon atoms, a nitrogen atom, an unsubstituted or optionally substituted benzyloxy group or a benzyloxy group.
  • ⁇ ⁇ fi 4 and are as described above] can be prepared by the C 00R 6 sites of the compound represented by hydrolyzing (second step).
  • the reaction in the third step is performed in the presence of a metal catalyst such as activated carbon supported on palladium, activated carbon supported on platinum, platinum oxide, or alumina supported on rhodium, in a solvent such as ethanol, methanol, tetrahydrofuran, ethyl acetate, or -dimethylformamide.
  • Hydrogen pressure can be reduced from 98.1kPa to 491kPa.
  • the reaction can be carried out at a temperature of 0 ° C to 100 ° C, preferably at room temperature to 80 ° C.
  • the reaction of the fourth step was carried out in a solvent such as methylene chloride, chloroform, tetrahydrofuran, ethyl acetate, ⁇ dimethylformamide, etc. You can do it.
  • the reaction can be carried out at a reaction temperature of -50 ° C to 150 ° C, preferably at room temperature to the reflux temperature of the solvent.
  • the reaction in the fifth step can be carried out under alkaline conditions.
  • the alkaline conditions lithium hydroxide, sodium hydroxide, lithium hydroxide or a mixture of these alkali metal hydroxides with methanol, ethanol, tetrahydrofuran and the like are used.
  • the reaction can be carried out at a reaction temperature of ⁇ 20 ° C. to 100 ° C., preferably 0 ° C. to 50 ° 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, syrups and the like.
  • Other compositions for oral administration include sprays.
  • Injections for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions.
  • 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.
  • FCS / DMEM Dulbecco's modified Eagle's medium
  • STRATAGENE Receptor plasmid that expresses a protein and its repo overnight plasmid
  • ⁇ Michitake luciferase for internal standard
  • Plasmid (PR0MEGA) was serum-free with ribofectamine and cotransfected. Thereafter, the test compound was added in 10 SFCS / DMEM, and 24 hours later, both luciferase activities were measured and corrected by the internal standard. Industrial applicability ''
  • the substituted carboxylic acid derivative represented by the general formula (1) which is a compound of the present invention, a pharmaceutically acceptable salt thereof and a hydrate thereof have a transcription activating effect on human PPAR isoform and have hyperlipidemia. It is useful as a prophylactic / therapeutic agent for metabolic diseases such as arteriosclerosis, glucoseuria and obesity.

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Abstract

L'invention concerne des dérivés d'acide carboxylique substitués, qui se lient au récepteur α activé par un proliférateur de peroxisome (PPARα) en tant que ligand de celui-ci et qui activent ce dernier, de sorte qu'ils exercent, entre autres, un effet abaisseur du taux de lipides, un effet de prévention de l'artériosclérose, un effet anti-obésité, un effet hypoglycémique ; et leur procédé de production. L'invention porte notamment sur des dérivés d'acide carboxylique substitués représentés par la formule générale (I) et sur des sels et des hydrates de ceux-ci, acceptables au plan pharmaceutique, ainsi que sur le procédé de production desdits composés. Dans ladite formule, R?1, R3 et R5¿ représentent chacun hydrogène ou alkyle inférieur ; R2 représente hydrogène ou alcoxy inférieur ; R4 représente hydrogène, trifluorométhyle, alcoxy inférieur, halogéno, phénoxy ou benzyloxy éventuellement substitué ; n vaut un entier de 0 à 3 ; et le substituant carboxylate est situé en position p pour ce qui concerne R2 ou en position p pour ce qui concerne (CH¿2?)n.
PCT/JP2001/010563 2000-12-05 2001-12-04 Derives d'acide carboxylique substitues Ceased WO2002046146A1 (fr)

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JP2002547885A JPWO2002046146A1 (ja) 2000-12-05 2001-12-04 置換カルボン酸誘導体
AU2002222573A AU2002222573A1 (en) 2000-12-05 2001-12-04 Substituted carboxylic acid derivatives

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004076402A1 (fr) * 2003-02-27 2004-09-10 Aventis Pharma Deutschland Gmbh Derives d'arylcycloalkyle a chaines laterales ramifiees en tant que modulateurs de recepteur ppar, procede de preparation associe et utilisation de ces derives comme medicaments
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
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
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
WO2006101108A1 (fr) * 2005-03-23 2006-09-28 Kyorin Pharmaceutical Co., Ltd. Nouveau derive acide aminophenylalcanoique cyclique
US7148246B2 (en) 2003-02-27 2006-12-12 Sanofi-Aventis Deutschland Gmbh Cycloalkyl derivatives having bioisosteric carboxylic acid groups, processes for their preparation and their use as pharmaceuticals
US7335671B2 (en) 2003-02-27 2008-02-26 Sanofi-Aventis Deutschland Gmbh Arylcycloalkyl-substituted alkanoic acid derivatives, processes for their preparation and their use as pharmaceuticals
US7902367B2 (en) 2004-08-11 2011-03-08 Kyorin Pharmaceutical Co., Ltd. Cyclic amino benzoic acid derivative
WO2014150646A1 (fr) * 2013-03-15 2014-09-25 Bristol-Myers Squibb Company Inhibiteurs de l'ido
CN105209443A (zh) * 2013-03-15 2015-12-30 百时美施贵宝公司 吲哚胺2,3-双加氧酶(ido)抑制剂

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999054321A1 (fr) * 1998-04-21 1999-10-28 Aventis Pharma Limited Diamines substituees et leur utilisation en tant qu'inhibiteurs d'adhesion cellulaire
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)

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999054321A1 (fr) * 1998-04-21 1999-10-28 Aventis Pharma Limited Diamines substituees et leur utilisation en tant qu'inhibiteurs d'adhesion cellulaire
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)

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
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
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
JP2006519196A (ja) * 2003-02-27 2006-08-24 サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング Ｐｐａｒ受容体モジュレーターとしての分枝側鎖を有するアリールシクロアルキル誘導体、その製造方法および医薬としてのその使用
WO2004076402A1 (fr) * 2003-02-27 2004-09-10 Aventis Pharma Deutschland Gmbh Derives d'arylcycloalkyle a chaines laterales ramifiees en tant que modulateurs de recepteur ppar, procede de preparation associe et utilisation de ces derives comme medicaments
US7148246B2 (en) 2003-02-27 2006-12-12 Sanofi-Aventis Deutschland Gmbh Cycloalkyl derivatives having bioisosteric carboxylic acid groups, processes for their preparation and their use as pharmaceuticals
US7220876B2 (en) 2003-02-27 2007-05-22 Sanofi-Aventis Deutschland Gmbh Arylcycloalkyl derivatives having branched side chains, processes for their preparation and their use as pharmaceuticals
US7335671B2 (en) 2003-02-27 2008-02-26 Sanofi-Aventis Deutschland Gmbh Arylcycloalkyl-substituted alkanoic acid derivatives, processes for their preparation and their use as pharmaceuticals
CN100417641C (zh) * 2003-02-27 2008-09-10 塞诺菲-安万特德国有限公司 作为ppar受体调节剂的具有支侧链的芳基环烷基衍生物,它们的制备方法和它们作为药物的用途
US7872034B2 (en) 2003-02-27 2011-01-18 Sanofi-Aventis Deutschland Gmbh Arylcycloalkyl-substituted alkanoic acid derivatives, processes for their preparation and their use as pharmaceuticals
US7902367B2 (en) 2004-08-11 2011-03-08 Kyorin Pharmaceutical Co., Ltd. Cyclic amino benzoic acid derivative
WO2006101108A1 (fr) * 2005-03-23 2006-09-28 Kyorin Pharmaceutical Co., Ltd. Nouveau derive acide aminophenylalcanoique cyclique
WO2014150646A1 (fr) * 2013-03-15 2014-09-25 Bristol-Myers Squibb Company Inhibiteurs de l'ido
CN105209443A (zh) * 2013-03-15 2015-12-30 百时美施贵宝公司 吲哚胺2,3-双加氧酶(ido)抑制剂
CN105324362A (zh) * 2013-03-15 2016-02-10 百时美施贵宝公司 Ido抑制剂
JP2016518324A (ja) * 2013-03-15 2016-06-23 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Ｉｄｏ阻害剤
US9624188B2 (en) 2013-03-15 2017-04-18 Bristol-Myers Squibb Company IDO inhibitors
US9675571B2 (en) 2013-03-15 2017-06-13 Bristol-Myers Squibb Company Inhibitors of indoleamine 2,3-dioxygenase (IDO)
EA028424B1 (ru) * 2013-03-15 2017-11-30 Бристол-Майерс Сквибб Компани Ингибиторы ido
AU2014235816B2 (en) * 2013-03-15 2018-05-17 Bristol-Myers Squibb Company IDO inhibitors

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