CA2642662A1 - Compounds for the treatment of metabolic disorders - Google Patents
Compounds for the treatment of metabolic disorders Download PDFInfo
- Publication number
- CA2642662A1 CA2642662A1 CA002642662A CA2642662A CA2642662A1 CA 2642662 A1 CA2642662 A1 CA 2642662A1 CA 002642662 A CA002642662 A CA 002642662A CA 2642662 A CA2642662 A CA 2642662A CA 2642662 A1 CA2642662 A1 CA 2642662A1
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- Prior art keywords
- compound
- carbon atoms
- hydrogen
- formula
- alkyl
- Prior art date
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- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D263/14—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with radicals substituted by oxygen atoms
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
- A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
- A01N31/14—Ethers
-
- 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
- A61K31/075—Ethers or acetals
-
- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- 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
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- 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
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- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
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- Obesity (AREA)
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- Pregnancy & Childbirth (AREA)
- Vascular Medicine (AREA)
- Gynecology & Obstetrics (AREA)
- Gastroenterology & Hepatology (AREA)
- Emergency Medicine (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
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- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US77767806P | 2006-02-28 | 2006-02-28 | |
| US60/777,678 | 2006-02-28 | ||
| PCT/US2007/062574 WO2007101060A2 (en) | 2006-02-28 | 2007-02-22 | Compounds for the treatment of metabolic disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2642662A1 true CA2642662A1 (en) | 2007-09-07 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002642662A Abandoned CA2642662A1 (en) | 2006-02-28 | 2007-02-22 | Compounds for the treatment of metabolic disorders |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US20100227901A1 (enExample) |
| EP (1) | EP1988772B1 (enExample) |
| JP (1) | JP2009528375A (enExample) |
| KR (1) | KR20080098615A (enExample) |
| CN (1) | CN101394738A (enExample) |
| AT (1) | ATE530066T1 (enExample) |
| AU (1) | AU2007220868B2 (enExample) |
| CA (1) | CA2642662A1 (enExample) |
| IL (1) | IL193321A0 (enExample) |
| MX (1) | MX2008011022A (enExample) |
| NZ (1) | NZ570100A (enExample) |
| WO (1) | WO2007101060A2 (enExample) |
| ZA (1) | ZA200806444B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8500260B2 (en) | 2011-04-27 | 2013-08-06 | Xerox Corporation | Ink compositions incorporating substituted oxazoline compounds or substituted oxazoline derivatives |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008507288A (ja) | 2004-07-23 | 2008-03-13 | アクセルロン ファーマ インコーポレーテッド | ＡｃｔＲＩＩ受容体ポリペプチド、方法、および組成物 |
| BRPI0618947B1 (pt) | 2005-11-23 | 2022-07-19 | Acceleron Pharma Inc | Polipeptídeo actriia que se liga à ativina, polinucleotídeo isolado, polinucleotídeo recombinante, métodopara preparar um polipeptídeo actriia que se liga à ativina, preparação farmacêutica e uso de uma proteína de fusão actriia-fc para promover o crescimento ósseo e inibir a ressorção óssea |
| US8128933B2 (en) | 2005-11-23 | 2012-03-06 | Acceleron Pharma, Inc. | Method of promoting bone growth by an anti-activin B antibody |
| 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 |
| US8895016B2 (en) | 2006-12-18 | 2014-11-25 | Acceleron Pharma, Inc. | Antagonists of activin-actriia and uses for increasing red blood cell levels |
| TWI584815B (zh) | 2007-02-01 | 2017-06-01 | 艾瑟勒朗法瑪公司 | 活化素-ＡｃｔＲＩＩａ拮抗劑及其治療或預防乳癌之用途 |
| TW201627320A (zh) | 2007-02-02 | 2016-08-01 | 艾瑟勒朗法瑪公司 | 衍生自ＡｃｔＲＩＩＢ的變體與其用途 |
| MX2009008510A (es) | 2007-02-09 | 2010-01-15 | Acceleron Pharma Inc | Antagonistas de activina-actriia y usos para promover el crecimiento de huesos en pacientes con cancer. |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| CA2699936A1 (en) | 2007-09-18 | 2009-03-26 | Acceleron Pharma Inc. | Activin-actriia antagonists and uses for decreasing or inhibiting fsh secretion |
| WO2009091732A1 (en) * | 2008-01-15 | 2009-07-23 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| DK3750552T5 (da) | 2008-08-14 | 2024-08-26 | Acceleron Pharma Inc | Gdf-fælder |
| US8216997B2 (en) | 2008-08-14 | 2012-07-10 | Acceleron Pharma, Inc. | Methods for increasing red blood cell levels and treating anemia using a combination of GDF traps and erythropoietin receptor activators |
| MX355042B (es) | 2009-06-08 | 2018-04-02 | Acceleon Pharma Inc | Metodos para aumentar adipositos termogenicos. |
| CN107267520A (zh) | 2009-06-12 | 2017-10-20 | 阿塞勒隆制药公司 | 截短的actriib‑fc融合蛋白 |
| EP3260130B1 (en) * | 2009-11-03 | 2021-03-10 | Acceleron Pharma Inc. | Methods for treating fatty liver disease |
| ES2658292T3 (es) | 2009-11-17 | 2018-03-09 | Acceleron Pharma, Inc. | Proteínas ActRIIB y variantes y usos de las mismas con respecto a la inducción de la utrofina para el tratamiento de la distrofia muscular |
| 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 |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| 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 |
| CA2817008A1 (en) | 2010-11-08 | 2012-05-18 | Acceleron Pharma Inc. | Actriia binding agents and uses thereof |
| 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 |
| 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 |
| 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 |
| 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 |
| RU2678117C2 (ru) | 2012-11-02 | 2019-01-23 | Селджин Корпорейшн | Антагонисты активина-actrii и их применение для лечения нарушений костной ткани и других нарушений |
| CN114699529A (zh) | 2014-06-13 | 2022-07-05 | 阿塞勒隆制药公司 | 用于治疗溃疡的方法和组合物 |
| MA41052A (fr) | 2014-10-09 | 2017-08-15 | Celgene Corp | Traitement d'une maladie cardiovasculaire à l'aide de pièges de ligands d'actrii |
| EP3227675B1 (en) | 2014-12-03 | 2023-03-15 | Celgene Corporation | Activin-actrii antagonists and uses for treating myelodysplastic syndrome |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4824843A (en) * | 1987-06-25 | 1989-04-25 | Warner-Lambert Company | Substituted amide inhibitors of cholesterol absorption |
| JP3906935B2 (ja) * | 1995-12-18 | 2007-04-18 | 杏林製薬株式会社 | Ｎ−置換ジオキソチアゾリジルベンズアミド誘導体及びその製造法 |
| AU2001263083A1 (en) * | 2000-05-12 | 2001-11-26 | Ortho-Mcneil Pharmaceutical, Inc. | Biologically active 4h-benzo(1,4)oxazin-3-ones |
| RU2341513C2 (ru) * | 2001-06-12 | 2008-12-20 | Веллстат Терапьютикс Корпорейшн | Соединения для лечения метаболических заболеваний |
| CA2502297C (en) * | 2002-11-01 | 2011-12-13 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| ES2530235T3 (es) * | 2003-02-13 | 2015-02-27 | Wellstat Therapeutics Corporation | Compuestos para el tratamiento de trastornos metabólicos |
| ES2353601T3 (es) * | 2003-04-15 | 2011-03-03 | Wellstat Therapeutics Corporation | Compuestos para el tratamiento de trastornos metabólicos. |
| 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 |
| CA2522738C (en) * | 2003-04-30 | 2011-11-08 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| MXPA06001963A (es) * | 2003-08-20 | 2006-05-31 | Wellstat Therapeutics Corp | Compuestos para el tratamiento de trastornos metabolicos. |
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- 2007-02-22 CN CNA2007800071537A patent/CN101394738A/zh active Pending
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- 2007-02-22 EP EP07757326A patent/EP1988772B1/en not_active Not-in-force
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- 2007-02-22 AT AT07757326T patent/ATE530066T1/de not_active IP Right Cessation
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2008
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- 2008-08-07 IL IL193321A patent/IL193321A0/en unknown
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2011
- 2011-08-25 US US13/217,977 patent/US20120071526A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8500260B2 (en) | 2011-04-27 | 2013-08-06 | Xerox Corporation | Ink compositions incorporating substituted oxazoline compounds or substituted oxazoline derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| MX2008011022A (es) | 2008-09-10 |
| IL193321A0 (en) | 2009-08-03 |
| US20100227901A1 (en) | 2010-09-09 |
| EP1988772A4 (en) | 2010-10-27 |
| AU2007220868B2 (en) | 2011-06-09 |
| KR20080098615A (ko) | 2008-11-11 |
| ZA200806444B (en) | 2009-05-27 |
| CN101394738A (zh) | 2009-03-25 |
| WO2007101060A2 (en) | 2007-09-07 |
| JP2009528375A (ja) | 2009-08-06 |
| ATE530066T1 (de) | 2011-11-15 |
| WO2007101060A3 (en) | 2007-12-13 |
| US20120071526A1 (en) | 2012-03-22 |
| NZ570100A (en) | 2011-01-28 |
| EP1988772B1 (en) | 2011-10-26 |
| AU2007220868A1 (en) | 2007-09-07 |
| EP1988772A2 (en) | 2008-11-12 |
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