JP2009537559A - 代謝障害の処置のための化合物 - Google Patents
代謝障害の処置のための化合物 Download PDFInfo
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- JP2009537559A JP2009537559A JP2009511181A JP2009511181A JP2009537559A JP 2009537559 A JP2009537559 A JP 2009537559A JP 2009511181 A JP2009511181 A JP 2009511181A JP 2009511181 A JP2009511181 A JP 2009511181A JP 2009537559 A JP2009537559 A JP 2009537559A
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- carbon atoms
- compound
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- phenyl
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- 239000008117 stearic acid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- SFLXUZPXEWWQNH-UHFFFAOYSA-K tetrabutylazanium;tribromide Chemical compound [Br-].[Br-].[Br-].CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC SFLXUZPXEWWQNH-UHFFFAOYSA-K 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/32—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings 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
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- 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
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Emergency Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74763806P | 2006-05-18 | 2006-05-18 | |
| PCT/US2007/068745 WO2007137008A2 (en) | 2006-05-18 | 2007-05-11 | Compounds for the treatment of metabolic disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009537559A true JP2009537559A (ja) | 2009-10-29 |
| JP2009537559A5 JP2009537559A5 (enExample) | 2011-05-19 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009511181A Pending JP2009537559A (ja) | 2006-05-18 | 2007-05-11 | 代謝障害の処置のための化合物 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7935689B2 (enExample) |
| EP (1) | EP2019673A4 (enExample) |
| JP (1) | JP2009537559A (enExample) |
| KR (1) | KR20090010035A (enExample) |
| CN (1) | CN101437506A (enExample) |
| AU (1) | AU2007253929B2 (enExample) |
| CA (1) | CA2651598A1 (enExample) |
| IL (1) | IL195203A0 (enExample) |
| MX (1) | MX2008014560A (enExample) |
| NZ (1) | NZ572681A (enExample) |
| WO (1) | WO2007137008A2 (enExample) |
| ZA (1) | ZA200808963B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015508809A (ja) * | 2012-02-28 | 2015-03-23 | ピラマル エンタープライジーズ リミテッド | Ｇｐｒアゴニストとしてのフェニルアルカン酸誘導体 |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2530235T3 (es) * | 2003-02-13 | 2015-02-27 | Wellstat Therapeutics Corporation | Compuestos para el tratamiento de trastornos metabólicos |
| JP2009525982A (ja) * | 2006-02-02 | 2009-07-16 | ウェルスタット セラピューティクス コーポレイション | 代謝障害の治療のための化合物 |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| WO2009091732A1 (en) * | 2008-01-15 | 2009-07-23 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| DE102010015123A1 (de) | 2010-04-16 | 2011-10-20 | Sanofi-Aventis Deutschland Gmbh | Benzylamidische Diphenylazetidinone, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| WO2012120054A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120055A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2015028960A1 (en) * | 2013-08-28 | 2015-03-05 | Piramal Enterprises Limited | Substituted heterocyclic derivatives as gpr agonists and uses thereof |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0512352A2 (en) * | 1991-05-09 | 1992-11-11 | F. Hoffmann-La Roche Ag | Substituted carboxylic acid derivatives |
| US5243066A (en) * | 1991-07-05 | 1993-09-07 | Basf Aktiengesellschaft | Alkyl 2-aryl-2,2-dialkoxyacetates, the preparation thereof and a method of using them for preparing arylglyoxylic esters |
| JP2002520407A (ja) * | 1998-07-17 | 2002-07-09 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | 異脂肪血症、アテローム性動脈硬化および糖尿病の治療に有用な環状化合物、医薬組成物および製造方法 |
| JP2002371033A (ja) * | 2001-04-10 | 2002-12-26 | Sankyo Co Ltd | ω−アリール−α−置換脂肪酸誘導体 |
| WO2004073611A2 (en) * | 2003-02-13 | 2004-09-02 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| WO2004089927A1 (en) * | 2003-04-07 | 2004-10-21 | Cortical Pty Ltd | Novel methods for the treatment of inflammatory diseases |
| WO2004091486A2 (en) * | 2003-04-15 | 2004-10-28 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| WO2004098496A2 (en) * | 2003-04-30 | 2004-11-18 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| JP2005501012A (ja) * | 2001-06-12 | 2005-01-13 | ウェルスタット セラピューティクス コーポレイション | 代謝障害治療用化合物 |
| JP2009528275A (ja) * | 2006-01-25 | 2009-08-06 | ウェルスタット セラピューティクス コーポレイション | 代謝障害を処置するための化合物 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2502297C (en) | 2002-11-01 | 2011-12-13 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| CN1777576A (zh) | 2003-04-22 | 2006-05-24 | 维尔斯达医疗公司 | 用于治疗代谢紊乱的化合物 |
| MXPA06001963A (es) | 2003-08-20 | 2006-05-31 | Wellstat Therapeutics Corp | Compuestos para el tratamiento de trastornos metabolicos. |
| WO2006127133A2 (en) | 2005-04-01 | 2006-11-30 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| US7820721B2 (en) | 2006-01-25 | 2010-10-26 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
-
2007
- 2007-05-11 CA CA002651598A patent/CA2651598A1/en not_active Abandoned
- 2007-05-11 KR KR1020087026318A patent/KR20090010035A/ko not_active Withdrawn
- 2007-05-11 NZ NZ572681A patent/NZ572681A/en not_active IP Right Cessation
- 2007-05-11 JP JP2009511181A patent/JP2009537559A/ja active Pending
- 2007-05-11 CN CNA2007800165233A patent/CN101437506A/zh active Pending
- 2007-05-11 EP EP07783635A patent/EP2019673A4/en not_active Withdrawn
- 2007-05-11 WO PCT/US2007/068745 patent/WO2007137008A2/en not_active Ceased
- 2007-05-11 MX MX2008014560A patent/MX2008014560A/es active IP Right Grant
- 2007-05-11 US US12/300,239 patent/US7935689B2/en active Active - Reinstated
- 2007-05-11 AU AU2007253929A patent/AU2007253929B2/en not_active Ceased
-
2008
- 2008-10-20 ZA ZA200808963A patent/ZA200808963B/xx unknown
- 2008-11-10 IL IL195203A patent/IL195203A0/en unknown
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0512352A2 (en) * | 1991-05-09 | 1992-11-11 | F. Hoffmann-La Roche Ag | Substituted carboxylic acid derivatives |
| US5243066A (en) * | 1991-07-05 | 1993-09-07 | Basf Aktiengesellschaft | Alkyl 2-aryl-2,2-dialkoxyacetates, the preparation thereof and a method of using them for preparing arylglyoxylic esters |
| JP2002520407A (ja) * | 1998-07-17 | 2002-07-09 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | 異脂肪血症、アテローム性動脈硬化および糖尿病の治療に有用な環状化合物、医薬組成物および製造方法 |
| JP2002371033A (ja) * | 2001-04-10 | 2002-12-26 | Sankyo Co Ltd | ω−アリール−α−置換脂肪酸誘導体 |
| JP2005501012A (ja) * | 2001-06-12 | 2005-01-13 | ウェルスタット セラピューティクス コーポレイション | 代謝障害治療用化合物 |
| WO2004073611A2 (en) * | 2003-02-13 | 2004-09-02 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| WO2004089927A1 (en) * | 2003-04-07 | 2004-10-21 | Cortical Pty Ltd | Novel methods for the treatment of inflammatory diseases |
| WO2004091486A2 (en) * | 2003-04-15 | 2004-10-28 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| WO2004098496A2 (en) * | 2003-04-30 | 2004-11-18 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| JP2009528275A (ja) * | 2006-01-25 | 2009-08-06 | ウェルスタット セラピューティクス コーポレイション | 代謝障害を処置するための化合物 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015508809A (ja) * | 2012-02-28 | 2015-03-23 | ピラマル エンタープライジーズ リミテッド | Ｇｐｒアゴニストとしてのフェニルアルカン酸誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101437506A (zh) | 2009-05-20 |
| MX2008014560A (es) | 2008-11-28 |
| AU2007253929A1 (en) | 2007-11-29 |
| AU2007253929B2 (en) | 2011-07-21 |
| EP2019673A2 (en) | 2009-02-04 |
| WO2007137008A3 (en) | 2008-08-28 |
| CA2651598A1 (en) | 2007-11-29 |
| EP2019673A4 (en) | 2010-06-16 |
| NZ572681A (en) | 2012-01-12 |
| WO2007137008A2 (en) | 2007-11-29 |
| ZA200808963B (en) | 2009-11-25 |
| KR20090010035A (ko) | 2009-01-28 |
| US20090163576A1 (en) | 2009-06-25 |
| US7935689B2 (en) | 2011-05-03 |
| IL195203A0 (en) | 2009-08-03 |
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