DE60317326T2 - Phenylalkansäure- und phenyloxyalkansäure-derivate als hppar aktivatore - Google Patents

Phenylalkansäure- und phenyloxyalkansäure-derivate als hppar aktivatore Download PDF

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Publication number
DE60317326T2
DE60317326T2 DE60317326T DE60317326T DE60317326T2 DE 60317326 T2 DE60317326 T2 DE 60317326T2 DE 60317326 T DE60317326 T DE 60317326T DE 60317326 T DE60317326 T DE 60317326T DE 60317326 T2 DE60317326 T2 DE 60317326T2
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DE
Germany
Prior art keywords
oxy
phenyl
pyridinyl
pentyl
acetic acid
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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.)
Expired - Fee Related
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DE60317326T
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German (de)
English (en)
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DE60317326D1 (de
Inventor
Richard Stevenage BELL
Paul John Stevenage BESWICK
Romain L. M. GOSMINI
Christopher Charles Stevenage HAMLETT
Nigel Paul Harlow KING
Vipulkumar Kantibhai Gl Stevenage PATEL
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SmithKline Beecham Corp
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SmithKline Beecham Corp
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Publication of DE60317326D1 publication Critical patent/DE60317326D1/de
Publication of DE60317326T2 publication Critical patent/DE60317326T2/de
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic 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
    • C07D213/02—Heterocyclic 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
    • C07D213/04—Heterocyclic 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
    • C07D213/24—Heterocyclic 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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/10—Thiols, 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 singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C323/18—Thiols, 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 singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
    • C07C323/20—Thiols, 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 singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton with singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
    • C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
    • C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic 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
    • C07D213/02—Heterocyclic 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
    • C07D213/04—Heterocyclic 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
    • C07D213/24—Heterocyclic 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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/32—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic 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
    • C07D213/02—Heterocyclic 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
    • C07D213/04—Heterocyclic 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
    • C07D213/24—Heterocyclic 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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/32—Sulfur atoms
    • C07D213/34—Sulfur atoms to which a second hetero atom is attached

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Child & Adolescent Psychology (AREA)
  • Hospice & Palliative Care (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Psychiatry (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Nutrition Science (AREA)
  • Epidemiology (AREA)
  • Pyridine Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
DE60317326T 2002-06-19 2003-06-18 Phenylalkansäure- und phenyloxyalkansäure-derivate als hppar aktivatore Expired - Fee Related DE60317326T2 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB0214149.7A GB0214149D0 (en) 2002-06-19 2002-06-19 Chemical compounds
GB0214149 2002-06-19
PCT/EP2003/006415 WO2004000315A1 (en) 2002-06-19 2003-06-18 Phenylalkanoic acid and phenyloxyalkanoic acid derivatives as hppar activators

Publications (2)

Publication Number Publication Date
DE60317326D1 DE60317326D1 (de) 2007-12-20
DE60317326T2 true DE60317326T2 (de) 2008-08-28

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DE60317326T Expired - Fee Related DE60317326T2 (de) 2002-06-19 2003-06-18 Phenylalkansäure- und phenyloxyalkansäure-derivate als hppar aktivatore

Country Status (25)

Country Link
US (1) US7338960B2 (enExample)
EP (1) EP1513526B1 (enExample)
JP (1) JP2005534672A (enExample)
KR (1) KR20050030624A (enExample)
CN (1) CN1674897A (enExample)
AT (1) ATE377420T1 (enExample)
AU (1) AU2003245962B2 (enExample)
BR (1) BR0311931A (enExample)
CA (1) CA2487909A1 (enExample)
CY (1) CY1107168T1 (enExample)
DE (1) DE60317326T2 (enExample)
DK (1) DK1513526T3 (enExample)
ES (1) ES2295601T3 (enExample)
GB (1) GB0214149D0 (enExample)
IL (1) IL165476A0 (enExample)
IS (1) IS7574A (enExample)
MX (1) MXPA04012857A (enExample)
NO (1) NO20045328L (enExample)
NZ (1) NZ537210A (enExample)
PL (1) PL375148A1 (enExample)
PT (1) PT1513526E (enExample)
RU (1) RU2323929C2 (enExample)
SI (1) SI1513526T1 (enExample)
WO (1) WO2004000315A1 (enExample)
ZA (1) ZA200410061B (enExample)

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JP4745244B2 (ja) 2003-11-05 2011-08-10 エフ．ホフマン−ラ ロシュ アーゲー Ｐｐａｒアゴニストとしてのフェニル誘導体
WO2005063729A1 (en) * 2003-12-25 2005-07-14 Takeda Pharmaceutical Company Limited 3-(4-benzyloxyphenyl)propanoic acid derivatives
BRPI0508098A (pt) 2004-02-27 2007-07-17 Amgen Inc compostos, composições farmacêuticas e métodos para uso no tratamento de distúrbios metabólicos
AR048523A1 (es) * 2004-04-07 2006-05-03 Kalypsys Inc Compuestos con estructura de aril sulfonamida y sulfonilo como moduladores de ppar y metodos para tratar trastornos metabolicos
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
MY147518A (en) * 2004-09-15 2012-12-31 Janssen Pharmaceutica Nv 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
US7465804B2 (en) 2005-05-20 2008-12-16 Amgen Inc. Compounds, pharmaceutical compositions and methods for their use in treating metabolic disorders
EP2298742B1 (en) 2005-06-30 2014-01-08 High Point Pharmaceuticals, LLC phenoxy acetic acids as PPAR delta activators
CA2621949A1 (en) * 2005-09-14 2007-03-22 Amgen Inc. Conformationally constrained 3- (4-hydroxy-phenyl) - substituted-propanoic acids useful for treating metabolic disorders
JO3006B1 (ar) 2005-09-14 2016-09-05 Janssen Pharmaceutica Nv املاح ليسين مبتكرة من مشتقات حامض 4-((فينوكسي الكيل)ثيو) فينوكسي الخليك
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
WO2007106469A2 (en) * 2006-03-14 2007-09-20 Amgen Inc. Bicyclic carboxylic acid derivatives useful for treating metabolic disorders
UY30288A1 (es) 2006-04-18 2007-08-31 Janssen Pharmaceutica Nv Derivados del ácido benzoazepin-oxi-acético como agonistas de ppar-delta usados para aumentar hdl-c. reducir ldl-c y reducir colesterol
CN101591227B (zh) * 2006-06-23 2012-09-05 赵昱 一类肉桂醇类衍生物及其制备方法和药物用途
US7687526B2 (en) * 2006-09-07 2010-03-30 Amgen Inc. Benzo-fused compounds for use in treating metabolic disorders
US7714008B2 (en) 2006-09-07 2010-05-11 Amgen Inc. Heterocyclic GPR40 modulators
WO2008066356A1 (en) 2006-12-02 2008-06-05 Seoul National University Industry Foundation Aryl compounds as ppar ligands and their use
EP2139843B1 (en) 2007-04-16 2013-12-25 Amgen, Inc Substituted biphenyl phenoxy-, thiophenyl- and aminophenylpropanoic acid gpr40 modulators
EP2184277B1 (en) * 2007-07-25 2015-07-01 Institute Of Pharmacology And Toxicology Academy Of Military Medical Sciences P.L.A. China Aryl pyrimidine derivatives, preparation methods and pharmaceutical uses thereof
EP2205548A1 (en) 2007-10-10 2010-07-14 Amgen, Inc Substituted biphenyl gpr40 modulators
CA2716352C (en) 2008-03-06 2013-05-28 Amgen Inc. Conformationally constrained carboxylic acid derivatives useful for treating metabolic disorders
EP2358656B1 (en) * 2008-10-15 2014-01-01 Amgen, Inc Spirocyclic gpr40 modulators
AU2012245344B2 (en) * 2011-04-22 2017-11-09 Jasco Pharmaceuticals, LLC Aminopyrimidine kinase inhibitors
NZ631569A (en) 2012-02-28 2016-10-28 Piramal Entpr Ltd Phenyl alkanoic acid derivatives as gpr agonists
KR101569522B1 (ko) 2013-04-18 2015-11-17 현대약품 주식회사 신규한 3-(4-(벤질옥시)페닐)헥스-4-이노익 산 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 대사성 질환의 예방 또는 치료용 약학적 조성물
WO2015035171A1 (en) 2013-09-09 2015-03-12 High Point Pharmaceuticals, Llc Use of a ppar-delta agonist for treating muscle atrophy
CN108503581A (zh) * 2018-04-12 2018-09-07 苏州康润医药有限公司 一种3-溴-6-氟-2-吡啶乙酮的合成方法
WO2023147309A1 (en) 2022-01-25 2023-08-03 Reneo Pharmaceuticals, Inc. Use of ppar-delta agonists in the treatment of disease

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HK1076712A1 (en) 2006-01-27
SI1513526T1 (sl) 2008-04-30
KR20050030624A (ko) 2005-03-30
BR0311931A (pt) 2005-04-05
NZ537210A (en) 2006-09-29
RU2004135539A (ru) 2005-08-10
AU2003245962A1 (en) 2004-01-06
EP1513526A1 (en) 2005-03-16
CY1107168T1 (el) 2012-10-24
ATE377420T1 (de) 2007-11-15
NO20045328L (no) 2005-03-09
RU2323929C2 (ru) 2008-05-10
DK1513526T3 (da) 2008-03-17
ZA200410061B (en) 2006-07-26
MXPA04012857A (es) 2005-02-24
CN1674897A (zh) 2005-09-28
CA2487909A1 (en) 2003-12-31
ES2295601T3 (es) 2008-04-16
US20060089394A1 (en) 2006-04-27
JP2005534672A (ja) 2005-11-17
GB0214149D0 (en) 2002-07-31
PT1513526E (pt) 2008-02-12
US7338960B2 (en) 2008-03-04
EP1513526B1 (en) 2007-11-07
IS7574A (is) 2004-11-30
WO2004000315A1 (en) 2003-12-31
IL165476A0 (en) 2006-01-15
DE60317326D1 (de) 2007-12-20
PL375148A1 (en) 2005-11-28
AU2003245962B2 (en) 2008-07-03

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