HUE028882T2 - (S) -2-Amino-3- {4- [4- (2,4-dioxothiazolidin-5-ylmethyl) -phenoxy] -phenyl} -propionic acid and its methyl ester salts as interleukin inhibitors overweight or diabetes treatment - Google Patents
(S) -2-Amino-3- {4- [4- (2,4-dioxothiazolidin-5-ylmethyl) -phenoxy] -phenyl} -propionic acid and its methyl ester salts as interleukin inhibitors overweight or diabetes treatment Download PDFInfo
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- HUE028882T2 HUE028882T2 HUE06735487A HUE06735487A HUE028882T2 HU E028882 T2 HUE028882 T2 HU E028882T2 HU E06735487 A HUE06735487 A HU E06735487A HU E06735487 A HUE06735487 A HU E06735487A HU E028882 T2 HUE028882 T2 HU E028882T2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
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- C07D277/32—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 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
- C07D277/34—Oxygen atoms
-
- 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
- C07D277/32—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 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
- C07D277/36—Sulfur atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
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- Ophthalmology & Optometry (AREA)
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- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN347DE2005 | 2005-02-17 | ||
| US11/096,718 US7521465B2 (en) | 2003-01-17 | 2005-03-31 | Diphenyl ether derivatives |
Publications (1)
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|---|---|
| HUE028882T2 true HUE028882T2 (en) | 2017-01-30 |
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Country Status (9)
| Country | Link |
|---|---|
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| EP (1) | EP1848700B1 (enExample) |
| JP (1) | JP5134974B2 (enExample) |
| KR (1) | KR20070105364A (enExample) |
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| ES (1) | ES2566337T3 (enExample) |
| HU (1) | HUE028882T2 (enExample) |
| PL (1) | PL1848700T3 (enExample) |
| WO (1) | WO2006089225A1 (enExample) |
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| US9969980B2 (en) * | 2001-09-21 | 2018-05-15 | Garnet Biotherapeutics | Cell populations which co-express CD49c and CD90 |
| US9969977B2 (en) * | 2002-09-20 | 2018-05-15 | Garnet Biotherapeutics | Cell populations which co-express CD49c and CD90 |
| US7521465B2 (en) | 2003-01-17 | 2009-04-21 | Bexel Pharmaceuticals, Inc. | Diphenyl ether derivatives |
| US7781464B2 (en) * | 2003-01-17 | 2010-08-24 | Bexel Pharmaceuticals, Inc. | Heterocyclic diphenyl ethers |
| US7087576B2 (en) * | 2003-10-07 | 2006-08-08 | Bexel Pharmaceuticals, Inc. | Dipeptide phenyl ethers |
| KR100814109B1 (ko) | 2006-01-09 | 2008-03-14 | 한국생명공학연구원 | 로다닌 유도체, 이의 제조방법 및 이를 유효성분으로함유하는 약학적 조성물 |
| US7989480B2 (en) * | 2006-08-04 | 2011-08-02 | Decode Genetics Ehf | Aryl amino acid derivatives as inhibitors for treating inflammation |
| US20090069313A1 (en) * | 2007-09-06 | 2009-03-12 | Orchid Research Laboratories Ltd. | Novel MAO-A inhibitors |
| ATE536347T1 (de) | 2008-05-20 | 2011-12-15 | Merck Sharp & Dohme | Effiziente herstellung heterologer proteine unter verwendung von mannosyltransferaseinhibitoren |
| US20140187594A1 (en) | 2010-07-28 | 2014-07-03 | Orchid Chemicals And Pharmaceuticals Ltd | Diphenyl ether compounds for the treatment of liver, lung disorders, diabetic complications and cardiovascular diseases |
| WO2012153775A1 (ja) | 2011-05-10 | 2012-11-15 | 国立大学法人神戸大学 | Ras機能阻害作用を有するチオキソチアゾリジン誘導体 |
| EP4029859A1 (en) | 2014-11-21 | 2022-07-20 | Bsim Therapeutics, S.A. | 2-oxothiazolidin-4-one derivatives active as transthyretin ligands and uses thereof |
| TW202019923A (zh) * | 2018-07-16 | 2020-06-01 | 義大利商吉斯藥品公司 | 作為Ｒｈｏ－激酶抑制劑之酪胺酸醯胺衍生物 |
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| JPH0228168A (ja) * | 1988-04-14 | 1990-01-30 | Sankyo Co Ltd | チアゾール誘導体 |
| US20020049240A1 (en) | 1994-12-19 | 2002-04-25 | Beecham Group P.1.C. | Novel compounds |
| US5166137A (en) | 1991-03-27 | 1992-11-24 | Nobipols Forskningsstiftelse | Guluronic acid polymers and use of same for inhibition of cytokine production |
| US5441971A (en) | 1991-04-11 | 1995-08-15 | The Upjohn Company | Thiazolidinedione derivatives, production and use thereof |
| TW268952B (enExample) | 1993-02-26 | 1996-01-21 | Takeda Pharm Industry Co Ltd | |
| US5527546A (en) | 1994-08-10 | 1996-06-18 | Bayer Corporation | Human interleukin 6 inhibitor |
| ATE271128T1 (de) | 1995-05-11 | 2004-07-15 | Applied Research Systems | Inhibitoren der il-6 aktivitaet |
| TW577875B (en) | 1997-01-31 | 2004-03-01 | Shionogi & Co | Pyrrolidine derivatives with inhibitory activity for phospholipase A2 |
| US6331633B1 (en) | 1998-05-08 | 2001-12-18 | Calyx Therapeutics Inc. | Heterocyclic analogs of diphenylethylene compounds |
| US6699896B1 (en) | 1998-05-12 | 2004-03-02 | Wyeth | Oxazole-aryl-carboxylic acids useful in the treatment of insulin resistance and hyperglycemia |
| EP1082323A2 (en) | 1998-06-05 | 2001-03-14 | AstraZeneca UK Limited | Oxazolidinone derivatives, process for their preparation and pharmaceutical compositions containing them |
| WO2000000194A1 (en) | 1998-06-27 | 2000-01-06 | Photogenesis, Inc. | Ophthalmic uses of ppargamma agonists and ppargamma antagonists |
| EP1108713A4 (en) | 1998-08-27 | 2006-04-05 | Ono Pharmaceutical Co | CARBOXYLENE DERIVATIVES AND MEDICAMENTS CONTAINING THEM AS AN ACTIVE COMPONENT |
| HUP0200996A3 (en) | 1999-04-07 | 2003-01-28 | Sankyo Company Ltd Chuo Ku | Amine derivatives, pharmaceutical compositions containing them and their use |
| HRP20010795A2 (en) | 1999-04-28 | 2003-02-28 | Aventis Pharma Gmbh | Di-aryl acid derivatives as ppar receptor ligands |
| TWI284533B (en) | 1999-05-24 | 2007-08-01 | Sankyo Co | Pharmaceutical composition for treating hyperglycemia, impaired glucose tolerance, diabetes complications and for improving insulin resistant |
| ID29875A (id) | 1999-07-01 | 2001-10-18 | Geron Corp Cs | Penghambat-penghambat telomerase dan metode penggunaannya |
| US6730687B1 (en) | 1999-08-23 | 2004-05-04 | Kyorin Pharmaceutical Co., Ltd. | Substituted benzylthiazolidine-2, 4-dione derivatives |
| CN1384825A (zh) * | 1999-08-31 | 2002-12-11 | 马克西亚药品公司 | 亚苄基－噻唑烷二酮及其类似物以及它们在治疗糖尿病中的应用 |
| JP2001199888A (ja) | 2000-01-24 | 2001-07-24 | Fujimoto Brothers:Kk | 糖尿病治療剤 |
| JP2001308814A (ja) | 2000-04-19 | 2001-11-02 | Hitachi Ltd | フレーム構成自動識別通信装置 |
| DE60115132T2 (de) | 2000-04-21 | 2006-07-06 | Pfizer Products Inc., Groton | Thyroid-Rezeptorliganden |
| US6620830B2 (en) | 2000-04-21 | 2003-09-16 | Pfizer, Inc. | Thyroid receptor ligands |
| US6680387B2 (en) | 2000-04-24 | 2004-01-20 | Aryx Therapeutics | Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis |
| US6525202B2 (en) * | 2000-07-17 | 2003-02-25 | Wyeth | Cyclic amine phenyl beta-3 adrenergic receptor agonists |
| ATE363278T1 (de) | 2001-09-14 | 2007-06-15 | Novo Nordisk As | Neue liganden für die hisb10 zn2+ stellen des insulin-hexamers in der r-konformation |
| JP2005513026A (ja) * | 2001-11-15 | 2005-05-12 | インサイト サン ディエゴ インコーポレイテッド | 高コレステロール血症、異脂肪血症および他の代謝障害；癌、および他の疾患を治療するｎ−置換複素環 |
| US7521465B2 (en) | 2003-01-17 | 2009-04-21 | Bexel Pharmaceuticals, Inc. | Diphenyl ether derivatives |
| US6794401B2 (en) | 2003-01-17 | 2004-09-21 | Bexel Pharmaceuticals, Inc. | Amino acid phenoxy ethers |
| JP2007523842A (ja) | 2003-03-11 | 2007-08-23 | ノボ ノルディスク アクティーゼルスカブ | 酸安定化されたインスリンを含有する薬学的製剤 |
| US7087576B2 (en) | 2003-10-07 | 2006-08-08 | Bexel Pharmaceuticals, Inc. | Dipeptide phenyl ethers |
-
2005
- 2005-03-31 US US11/096,718 patent/US7521465B2/en not_active Expired - Fee Related
-
2006
- 2006-02-17 HU HUE06735487A patent/HUE028882T2/en unknown
- 2006-02-17 KR KR1020077021343A patent/KR20070105364A/ko not_active Ceased
- 2006-02-17 JP JP2007556366A patent/JP5134974B2/ja not_active Expired - Fee Related
- 2006-02-17 PL PL06735487T patent/PL1848700T3/pl unknown
- 2006-02-17 ES ES06735487.8T patent/ES2566337T3/es not_active Expired - Lifetime
- 2006-02-17 EP EP06735487.8A patent/EP1848700B1/en not_active Expired - Lifetime
- 2006-02-17 WO PCT/US2006/005846 patent/WO2006089225A1/en not_active Ceased
- 2006-02-17 CA CA2598087A patent/CA2598087C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP1848700B1 (en) | 2015-12-30 |
| US7521465B2 (en) | 2009-04-21 |
| CA2598087A1 (en) | 2006-08-24 |
| US20050288341A1 (en) | 2005-12-29 |
| WO2006089225A1 (en) | 2006-08-24 |
| CA2598087C (en) | 2014-05-27 |
| JP5134974B2 (ja) | 2013-01-30 |
| PL1848700T3 (pl) | 2016-08-31 |
| JP2008530242A (ja) | 2008-08-07 |
| ES2566337T3 (es) | 2016-04-12 |
| EP1848700A1 (en) | 2007-10-31 |
| KR20070105364A (ko) | 2007-10-30 |
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