JP4754487B2 - グルカゴン様ペプチド（ｇｌｐ）−１化合物またはメラノコルチン４受容体（ｍｃ４）アゴニストペプチドの経口デリバリーのための化合物、方法および製剤 - Google Patents
グルカゴン様ペプチド（ｇｌｐ）−１化合物またはメラノコルチン４受容体（ｍｃ４）アゴニストペプチドの経口デリバリーのための化合物、方法および製剤 Download PDFInfo
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49653703P | 2003-08-20 | 2003-08-20 | |
| US60/496,537 | 2003-08-20 | ||
| PCT/US2004/024387 WO2005019212A1 (en) | 2003-08-20 | 2004-08-18 | Compounds, methods and formulations for the oral delivery of a glucagon like peptide (glp)-1 compound or an melanocortin 4 receptor (mc4) agonist peptide |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2007502817A JP2007502817A (ja) | 2007-02-15 |
| JP2007502817A5 JP2007502817A5 (enExample) | 2007-05-31 |
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Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2380372C2 (ru) * | 2005-07-08 | 2010-01-27 | Сосьете Де Консей Де Решерш Э Д'Аппликасьон Сьентифик С.А.С. | Лиганды рецепторов меланокортинов |
| CA2614678A1 (en) | 2005-07-08 | 2007-01-18 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R | Ligands of melanocortin receptors |
| USRE48164E1 (en) * | 2006-08-31 | 2020-08-18 | Emisphere Technologies Inc. | Compounds and compositions for delivering active agents |
| ES2618315T3 (es) | 2007-05-25 | 2017-06-21 | Ipsen Pharma S.A.S. | Ligandos del receptor de melanocortina modificados con hidantoína |
| MX2010013436A (es) * | 2008-06-09 | 2011-06-21 | Palatin Technologies Inc | Peptidos especificos del receptor de melanocortina para el tratamiento de disfuncion sexual. |
| NZ596617A (en) | 2009-06-08 | 2014-04-30 | Palatin Technologies Inc | Melanocortin receptor-specific peptides |
| UY32690A (es) * | 2009-06-08 | 2011-01-31 | Astrazeneca Ab | Péptidos específicos para receptores de melanocortina |
| EP2440572B1 (en) | 2009-06-08 | 2017-04-05 | Palatin Technologies, Inc. | Lactam-bridged melanocortin receptor-specific peptides |
| WO2011063366A1 (en) | 2009-11-23 | 2011-05-26 | Palatin Technologies, Inc. | Melanocortin-1 receptor-specific cyclic peptides |
| KR20120102716A (ko) | 2009-11-23 | 2012-09-18 | 팔라틴 테크놀로지스 인코포레이티드 | 멜라노코르틴-1 수용체 특이적 선형 펩티드 |
| US10357348B2 (en) * | 2013-08-19 | 2019-07-23 | Warren Matthew Leevy | Fluid manifold |
| US20160244860A1 (en) * | 2015-02-20 | 2016-08-25 | Cytec Industries Inc. | Aliphatic-aromatic heterocyclic compounds and uses thereof in metal extractant compositions |
| WO2016168388A2 (en) | 2015-04-14 | 2016-10-20 | Palatin Technologies, Inc. | Therapies for obesity, diabetes and related indications |
| CN105017136A (zh) * | 2015-07-24 | 2015-11-04 | 陈吉美 | 一种2-溴-3-甲氧基吡啶的制备方法 |
| JP2020506950A (ja) | 2017-02-08 | 2020-03-05 | バイエル アクチェンゲゼルシャフトＢａｙｅｒ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | トリアゾールチオン誘導体 |
| EP3580218A1 (en) | 2017-02-08 | 2019-12-18 | Bayer CropScience Aktiengesellschaft | Novel triazole derivatives |
| WO2018145932A1 (en) | 2017-02-08 | 2018-08-16 | Bayer Cropscience Aktiengesellschaft | Triazole derivatives and their use as fungicides |
| JP2020507579A (ja) | 2017-02-10 | 2020-03-12 | バイエル アクチェンゲゼルシャフトＢａｙｅｒ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | １−（フェノキシ−ピリジニル）−２−（１，２，４−トリアゾール−１−イル）−エタノール誘導体を含む有害微生物を制御するための組成物 |
| WO2020020816A1 (en) | 2018-07-26 | 2020-01-30 | Bayer Aktiengesellschaft | Novel triazole derivatives |
| CN111793038B (zh) * | 2019-04-08 | 2022-08-12 | 新发药业有限公司 | 一种取代噁唑化合物的环保制备方法 |
| WO2025158275A1 (en) | 2024-01-24 | 2025-07-31 | Pfizer Inc. | Combination therapy using glucose-dependent insulinotropic polypeptide receptor antagonist compounds and glp-1 receptor agonist compounds |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1129393A (en) * | 1965-12-13 | 1968-10-02 | Miles Lab | Tetrazolyl alkanoic acids |
| JPH04234857A (ja) * | 1990-04-12 | 1992-08-24 | Hoechst Ag | ３，５−ジ置換２−イソキサゾリンおよびイソキサゾール、それらの製法およびそれらを含有する薬学的組成物 |
| JPH1160571A (ja) * | 1996-07-19 | 1999-03-02 | Takeda Chem Ind Ltd | 複素環化合物、その製造法および用途 |
| WO2002050091A1 (en) * | 2000-12-21 | 2002-06-27 | Glaxo Group Limited | Macrolide antibiotics |
| JP2002212171A (ja) * | 2000-11-17 | 2002-07-31 | Takeda Chem Ind Ltd | イソオキサゾール誘導体 |
| WO2002064607A1 (fr) * | 2001-02-14 | 2002-08-22 | Meiji Seika Kaisha, Ltd. | Nouveaux derives de macrolides a 16 elements modifies en 12 et 13 |
| GB2373186A (en) * | 2001-02-23 | 2002-09-18 | Astrazeneca Ab | Pharmaceutical combinations of a CCR3 antagonist and a compound which is usefulreatment of asthma, allergic disease or inflammation |
| WO2002096359A2 (en) * | 2001-05-30 | 2002-12-05 | Merck & Co., Inc. | Piperazine pentanamide hiv protease inhibitors |
| JP2003507456A (ja) * | 1999-08-24 | 2003-02-25 | アストラゼネカ ユーケイ リミテッド | ケモカインレセプター活性のモジュレーターとして有用な置換ピペリジン化合物 |
| WO2003015785A1 (en) * | 2001-08-15 | 2003-02-27 | Icos Corporation | 2h-phthalazin-1-ones and methods for use thereof |
| WO2003057215A1 (en) * | 2001-12-28 | 2003-07-17 | Takeda Chemical Industries, Ltd. | Neurotrophic factor production/secretion accelerator |
| JP2004277397A (ja) * | 2002-05-24 | 2004-10-07 | Takeda Chem Ind Ltd | １，２−アゾール誘導体 |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US595503A (en) * | 1897-12-14 | Cross-clevis | ||
| US2423709A (en) * | 1947-07-08 | X-aryl thiazole | ||
| US3578671A (en) * | 1967-11-06 | 1971-05-11 | Wyeth John & Brother Ltd | Oxazoles |
| FR2374910A1 (fr) * | 1976-10-23 | 1978-07-21 | Choay Sa | Preparation a base d'heparine, comprenant des liposomes, procede pour l'obtenir et medicaments contenant de telles preparations |
| CH671155A5 (enExample) * | 1986-08-18 | 1989-08-15 | Clinical Technologies Ass | |
| US5693338A (en) * | 1994-09-29 | 1997-12-02 | Emisphere Technologies, Inc. | Diketopiperazine-based delivery systems |
| US5541155A (en) * | 1994-04-22 | 1996-07-30 | Emisphere Technologies, Inc. | Acids and acid salts and their use in delivery systems |
| US5643957A (en) * | 1993-04-22 | 1997-07-01 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5866536A (en) * | 1995-03-31 | 1999-02-02 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US6001347A (en) * | 1995-03-31 | 1999-12-14 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5650386A (en) * | 1995-03-31 | 1997-07-22 | Emisphere Technologies, Inc. | Compositions for oral delivery of active agents |
| US5989539A (en) * | 1995-03-31 | 1999-11-23 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| CN1151836C (zh) * | 1995-03-31 | 2004-06-02 | 艾米斯菲尔技术有限公司 | 用作传送活性剂的化合物和组合物 |
| US5965121A (en) * | 1995-03-31 | 1999-10-12 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5820881A (en) * | 1995-04-28 | 1998-10-13 | Emisphere Technologies, Inc. | Microspheres of diamide-dicarboxylic acids |
| GB9604242D0 (en) * | 1996-02-28 | 1996-05-01 | Glaxo Wellcome Inc | Chemical compounds |
| ATE338754T1 (de) * | 1996-07-19 | 2006-09-15 | Takeda Pharmaceutical | Heterocyclische verbindungen, ihre herstellung und verwendung |
| US6313088B1 (en) * | 1997-02-07 | 2001-11-06 | Emisphere Technologies, Inc. | 8-[(2-hydroxy-4-methoxy benzoyl) amino]-octanoic acid compositions for delivering active agents |
| EP0993831B1 (en) * | 1997-02-07 | 2008-01-09 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| WO2000040203A2 (en) | 1999-01-08 | 2000-07-13 | Emisphere Technologies, Inc. | Polymeric delivery agents and delivery agent compounds |
| JP4854855B2 (ja) * | 1999-02-11 | 2012-01-18 | エミスフェアー・テクノロジーズ・インク | オキサジアゾール化合物及び活性剤をデリバリーするための組成物 |
| AU3378100A (en) | 1999-02-26 | 2000-09-14 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| IL145546A0 (en) | 1999-04-05 | 2002-06-30 | Emisphere Tech Inc | Disodium salts, monohydrates, and ethanol solvates for delivering active agents |
| AR035016A1 (es) * | 1999-08-25 | 2004-04-14 | Takeda Chemical Industries Ltd | Composicion de azol promotor de produccion/secrecion de neurotrofina, compuesto prodroga del mismo, composicion farmaceutica que lo comprende y uso del mismo para preparar esta ultima. |
| CA2388240C (en) | 1999-11-05 | 2010-04-20 | Emisphere Technologies, Inc. | Phenoxy carboxylic acid compounds and compositions for delivering active agents |
| WO2001044199A1 (en) | 1999-12-16 | 2001-06-21 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| JP4879433B2 (ja) | 2000-01-13 | 2012-02-22 | エミスフェアー・テクノロジーズ・インク | 活性剤を送達するための化合物および組成物 |
| JP2004521857A (ja) | 2000-06-29 | 2004-07-22 | エミスフェアー・テクノロジーズ・インク | 活性剤の送達のための化合物及び組成物 |
| CA2420178A1 (en) * | 2000-08-23 | 2002-03-07 | Eli Lilly And Company | Oxazolyl-aryloxyacetic acid derivatives and their use as ppar agonists |
| MXPA03001558A (es) * | 2000-08-23 | 2003-06-06 | Lilly Co Eli | Agonistas del receptor activado del proliferador de peroxisoma. |
| AU2002215218A1 (en) * | 2000-11-17 | 2002-05-27 | Takeda Chemical Industries Ltd. | Isoxazole derivatives |
| US6969057B2 (en) | 2001-10-30 | 2005-11-29 | Illinois Tool Works Inc. | Method and apparatus for adjusting and positioning air caps |
| BR0307727A (pt) | 2002-02-20 | 2005-01-25 | Lilly Co Eli | Fomulação |
| WO2003099793A1 (en) | 2002-05-24 | 2003-12-04 | Takeda Pharmaceutical Company Limited | 1,2-azole derivatives with hypoglycemic and hypolipidemic activity |
| MXPA05013951A (es) | 2003-06-19 | 2006-02-24 | Lilly Co Eli | Agonsita del receptor de la melanocortina 4 (mc4) y sus usos. |
| EP1658273B1 (en) * | 2003-08-20 | 2007-01-03 | Eli Lilly And Company | Compounds, methods and formulations for the oral delivery of a glucagon like peptide (glp)-1 compound or an melanocortin 4 receptor (mc4) agonist peptide |
-
2004
- 2004-08-18 MX MXPA06001916A patent/MXPA06001916A/es active IP Right Grant
- 2004-08-18 BR BRPI0413676A patent/BRPI0413676B8/pt not_active IP Right Cessation
- 2004-08-18 JP JP2006523866A patent/JP4754487B2/ja not_active Expired - Fee Related
- 2004-08-18 CN CNB2004800227912A patent/CN100398536C/zh not_active Expired - Fee Related
- 2004-08-18 DE DE602004006279T patent/DE602004006279T2/de not_active Expired - Lifetime
- 2004-08-18 CA CA2530983A patent/CA2530983C/en not_active Expired - Fee Related
- 2004-08-18 AU AU2004267044A patent/AU2004267044B8/en not_active Ceased
- 2004-08-18 AT AT04779447T patent/ATE361294T1/de not_active IP Right Cessation
- 2004-08-18 WO PCT/US2004/024387 patent/WO2005019212A1/en not_active Ceased
- 2004-08-18 ES ES04779447T patent/ES2286679T3/es not_active Expired - Lifetime
- 2004-08-18 US US10/566,012 patent/US20070293423A1/en not_active Abandoned
- 2004-08-18 EP EP04779447A patent/EP1658285B1/en not_active Expired - Lifetime
-
2008
- 2008-11-03 US US12/263,722 patent/US7947841B2/en not_active Expired - Fee Related
-
2011
- 2011-04-14 US US13/087,255 patent/US8546581B2/en not_active Expired - Fee Related
- 2011-05-09 JP JP2011104435A patent/JP2011207886A/ja active Pending
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1129393A (en) * | 1965-12-13 | 1968-10-02 | Miles Lab | Tetrazolyl alkanoic acids |
| JPH04234857A (ja) * | 1990-04-12 | 1992-08-24 | Hoechst Ag | ３，５−ジ置換２−イソキサゾリンおよびイソキサゾール、それらの製法およびそれらを含有する薬学的組成物 |
| JPH1160571A (ja) * | 1996-07-19 | 1999-03-02 | Takeda Chem Ind Ltd | 複素環化合物、その製造法および用途 |
| JP2003507456A (ja) * | 1999-08-24 | 2003-02-25 | アストラゼネカ ユーケイ リミテッド | ケモカインレセプター活性のモジュレーターとして有用な置換ピペリジン化合物 |
| JP2002212171A (ja) * | 2000-11-17 | 2002-07-31 | Takeda Chem Ind Ltd | イソオキサゾール誘導体 |
| WO2002050091A1 (en) * | 2000-12-21 | 2002-06-27 | Glaxo Group Limited | Macrolide antibiotics |
| WO2002064607A1 (fr) * | 2001-02-14 | 2002-08-22 | Meiji Seika Kaisha, Ltd. | Nouveaux derives de macrolides a 16 elements modifies en 12 et 13 |
| GB2373186A (en) * | 2001-02-23 | 2002-09-18 | Astrazeneca Ab | Pharmaceutical combinations of a CCR3 antagonist and a compound which is usefulreatment of asthma, allergic disease or inflammation |
| WO2002096359A2 (en) * | 2001-05-30 | 2002-12-05 | Merck & Co., Inc. | Piperazine pentanamide hiv protease inhibitors |
| WO2003015785A1 (en) * | 2001-08-15 | 2003-02-27 | Icos Corporation | 2h-phthalazin-1-ones and methods for use thereof |
| WO2003057215A1 (en) * | 2001-12-28 | 2003-07-17 | Takeda Chemical Industries, Ltd. | Neurotrophic factor production/secretion accelerator |
| JP2004277397A (ja) * | 2002-05-24 | 2004-10-07 | Takeda Chem Ind Ltd | １，２−アゾール誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| US7947841B2 (en) | 2011-05-24 |
| US20090239798A1 (en) | 2009-09-24 |
| CA2530983C (en) | 2012-09-25 |
| CA2530983A1 (en) | 2005-03-03 |
| ES2286679T3 (es) | 2007-12-01 |
| MXPA06001916A (es) | 2006-05-17 |
| US8546581B2 (en) | 2013-10-01 |
| BRPI0413676B8 (pt) | 2021-05-25 |
| DE602004006279T2 (de) | 2007-12-27 |
| US20070293423A1 (en) | 2007-12-20 |
| US20110190205A1 (en) | 2011-08-04 |
| DE602004006279D1 (de) | 2007-06-14 |
| BRPI0413676B1 (pt) | 2018-07-24 |
| ATE361294T1 (de) | 2007-05-15 |
| AU2004267044B8 (en) | 2009-12-17 |
| JP2011207886A (ja) | 2011-10-20 |
| CN100398536C (zh) | 2008-07-02 |
| AU2004267044A1 (en) | 2005-03-03 |
| BRPI0413676A (pt) | 2006-10-24 |
| EP1658285B1 (en) | 2007-05-02 |
| AU2004267044B2 (en) | 2009-12-03 |
| JP2007502817A (ja) | 2007-02-15 |
| CN1832944A (zh) | 2006-09-13 |
| WO2005019212A1 (en) | 2005-03-03 |
| EP1658285A1 (en) | 2006-05-24 |
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