CN100349856C - 丙酸衍生物及其作为hPPAR活化剂的用途 - Google Patents

丙酸衍生物及其作为hPPAR活化剂的用途 Download PDF

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Publication number
CN100349856C
CN100349856C CNB038193221A CN03819322A CN100349856C CN 100349856 C CN100349856 C CN 100349856C CN B038193221 A CNB038193221 A CN B038193221A CN 03819322 A CN03819322 A CN 03819322A CN 100349856 C CN100349856 C CN 100349856C
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methyl
amino
acetate
methylphenoxy
trifluoromethyl
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Expired - Fee Related
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CNB038193221A
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Chinese (zh)
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CN1675168A (zh
Inventor
P·J·贝斯维克
J·D·哈林
S·克利恩托斯
V·K·帕特尔
J·辛普森
M·H·拉姆伯特三世
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SmithKline Beecham Corp
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SmithKline Beecham Corp
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72Nitrogen atoms
    • C07D213/74Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/54Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/56Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
    • C07C217/58Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/78Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C07C217/80Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/34Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
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    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00Carboxylic acid amides
    • C07C233/01Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/16Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/17Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/18Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
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    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00Carboxylic acid nitriles
    • C07C255/49Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/58Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
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    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/01Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
    • C07C311/02Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C311/08Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/22Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
    • C07C311/29Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/24Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/25Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32One oxygen, sulfur or nitrogen atom
    • C07D239/42One nitrogen atom
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D241/00Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/20Nitrogen atoms
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    • C07C2601/00Systems containing only non-condensed rings
    • C07C2601/02Systems containing only non-condensed rings with a three-membered ring

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Cardiology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Emergency Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Child & Adolescent Psychology (AREA)
  • Endocrinology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
CNB038193221A 2002-06-20 2003-06-18 丙酸衍生物及其作为hPPAR活化剂的用途 Expired - Fee Related CN100349856C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0214254.5A GB0214254D0 (en) 2002-06-20 2002-06-20 Chemical compounds
GB0214254.5 2002-06-20

Publications (2)

Publication Number Publication Date
CN1675168A CN1675168A (zh) 2005-09-28
CN100349856C true CN100349856C (zh) 2007-11-21

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US (1) US7199239B2 (enExample)
EP (1) EP1513795A2 (enExample)
JP (1) JP2005534673A (enExample)
KR (1) KR20050013590A (enExample)
CN (1) CN100349856C (enExample)
AU (1) AU2003245963C1 (enExample)
BR (1) BR0311935A (enExample)
CA (1) CA2489359A1 (enExample)
GB (1) GB0214254D0 (enExample)
IL (1) IL165477A0 (enExample)
IS (1) IS7575A (enExample)
MX (1) MXPA04012858A (enExample)
NO (1) NO20045327L (enExample)
NZ (1) NZ537209A (enExample)
PL (1) PL375075A1 (enExample)
RU (1) RU2316539C2 (enExample)
WO (1) WO2004000762A2 (enExample)
ZA (1) ZA200410054B (enExample)

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PT1599468E (pt) 2003-01-14 2008-01-14 Arena Pharm Inc Derivados de arilo e heteroarilo 1,2,3.-trissubstituídos comomoduladores do metabolismo, e profilaxia e tratamento dedesordens relacionadas tais como diabetes e hiperglicemia
GB2423781B (en) 2003-03-19 2007-03-28 Varco Int Apparatus and method for moving drilled cuttings
US7244763B2 (en) 2003-04-17 2007-07-17 Warner Lambert Company Llc Compounds that modulate PPAR activity and methods of preparation
AR045047A1 (es) * 2003-07-11 2005-10-12 Arena Pharm Inc Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos
EP2287165A3 (en) 2003-07-14 2011-06-22 Arena Pharmaceuticals, Inc. Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto
WO2005007627A1 (ja) * 2003-07-18 2005-01-27 Nihon Nohyaku Co., Ltd. フェニルピリジン誘導体、その中間体及びこれを有効成分とする除草剤
EP1745014B1 (en) 2004-05-05 2011-07-06 High Point Pharmaceuticals, LLC Novel compounds, their preparation and use
WO2005105726A1 (en) 2004-05-05 2005-11-10 Novo Nordisk A/S Novel compounds, their preparation and use
BR122017014864B1 (pt) 2004-06-22 2018-06-05 Varco I/P, Inc. Método e sistema para processamento de material de detritos de perfuração
DE102004046623A1 (de) * 2004-09-25 2006-03-30 Bayer Healthcare Ag Neue Pyrimidin-Derivate und ihre Verwendung
MY148521A (en) 2005-01-10 2013-04-30 Arena Pharm Inc Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto
US7301033B2 (en) 2005-01-27 2007-11-27 Kowa Co., Ltd. PPAR-activating compound
EP2298742B1 (en) 2005-06-30 2014-01-08 High Point Pharmaceuticals, LLC phenoxy acetic acids as PPAR delta activators
EP2386540A1 (en) 2005-12-22 2011-11-16 High Point Pharmaceuticals, LLC Novel compounds, their preparation and use
CA2645719A1 (en) 2006-03-09 2007-09-13 High Point Pharmaceuticals, Llc Compounds that modulate ppar activity, their preparation and use
RU2538276C2 (ru) * 2009-04-23 2015-01-10 Пирамал Имэджинг СА Новые прекурсорные молекулы для меченных f-18 пэт радиоактивных индикаторов
WO2011002814A2 (en) * 2009-06-30 2011-01-06 Ligand Pharmaceuticals Inc. Biaryl oxyacetic acid compounds
JP2012041325A (ja) 2010-08-23 2012-03-01 Bayer Cropscience Ag オキサジアゾリノン誘導体およびその有害生物の防除用途
JP5941916B2 (ja) 2010-09-22 2016-06-29 アリーナ ファーマシューティカルズ, インコーポレイテッド Gpr119レセプターのモジュレーターおよびそれに関連する障害の処置
WO2015035171A1 (en) 2013-09-09 2015-03-12 High Point Pharmaceuticals, Llc Use of a ppar-delta agonist for treating muscle atrophy
PL3242666T3 (pl) 2015-01-06 2025-02-17 Arena Pharmaceuticals, Inc. Związek do zastosowania w leczeniu dolegliwości związanych z receptorem s1p1
DK3310760T3 (da) 2015-06-22 2022-10-24 Arena Pharm Inc Krystallinsk L-argininsalt af (R)-2-(7-(4-cyclopentyl-3-(trifluormethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3- yl)eddikesyre til anvendelse ved S1P1-receptor-associerede lidelser
CN110520124A (zh) 2017-02-16 2019-11-29 艾尼纳制药公司 用于治疗原发性胆汁性胆管炎的化合物和方法
BR112020024762A2 (pt) 2018-06-06 2021-03-23 Arena Pharmaceuticals, Inc. métodos de tratamento de condições relacionadas ao receptor s1p1
WO2023147309A1 (en) 2022-01-25 2023-08-03 Reneo Pharmaceuticals, Inc. Use of ppar-delta agonists in the treatment of disease

Citations (3)

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GB1503953A (en) * 1974-06-04 1978-03-15 Fujisawa Pharmaceutical Co Substituted-phenyl substituted-alkyl ethers and the preparation thereof
EP1067109A1 (en) * 1998-03-10 2001-01-10 Ono Pharmaceutical Co., Ltd. Carboxylic acid derivatives and drugs containing the same as the active ingredient
WO2002028821A2 (de) * 2000-10-05 2002-04-11 Bayer Aktiengesellschaft Propionsäurederivate mit ppar-alpha aktivierenden eigenschaften.

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DE2320387A1 (de) * 1973-04-21 1974-10-31 Boehringer Mannheim Gmbh Phenoxyalkylcarbonsaeurederivate und verfahren zur herstellung derselben
US4214094A (en) * 1977-03-30 1980-07-22 Fujisawa Pharmaceutical Co., Ltd. Substituted-phenyl substituted-alkyl ethers and the preparation thereof
GB9306453D0 (en) * 1993-03-29 1993-05-19 Zeneca Ltd Heterocyclic derivatives
GB9822473D0 (en) 1998-10-16 1998-12-09 Glaxo Group Ltd Chemical compounds

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
GB1503953A (en) * 1974-06-04 1978-03-15 Fujisawa Pharmaceutical Co Substituted-phenyl substituted-alkyl ethers and the preparation thereof
EP1067109A1 (en) * 1998-03-10 2001-01-10 Ono Pharmaceutical Co., Ltd. Carboxylic acid derivatives and drugs containing the same as the active ingredient
WO2002028821A2 (de) * 2000-10-05 2002-04-11 Bayer Aktiengesellschaft Propionsäurederivate mit ppar-alpha aktivierenden eigenschaften.

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BR0311935A (pt) 2005-03-22
NZ537209A (en) 2006-10-27
MXPA04012858A (es) 2005-06-08
PL375075A1 (en) 2005-11-14
RU2004137092A (ru) 2005-09-10
CA2489359A1 (en) 2003-12-31
US20060074111A1 (en) 2006-04-06
IL165477A0 (en) 2006-01-15
WO2004000762A3 (en) 2004-10-14
RU2316539C2 (ru) 2008-02-10
IS7575A (is) 2004-11-30
US7199239B2 (en) 2007-04-03
EP1513795A2 (en) 2005-03-16
AU2003245963B2 (en) 2008-06-26
AU2003245963C1 (en) 2008-12-11
NO20045327L (no) 2005-03-10
ZA200410054B (en) 2006-02-22
WO2004000762A2 (en) 2003-12-31
JP2005534673A (ja) 2005-11-17
AU2003245963A1 (en) 2004-01-06
GB0214254D0 (en) 2002-07-31
KR20050013590A (ko) 2005-02-04
CN1675168A (zh) 2005-09-28

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