JP2005533073A - 酸性基によって置換されたジフェニルアゼチジノン、その製造方法、該化合物を含む医薬およびそれらの使用 - Google Patents
酸性基によって置換されたジフェニルアゼチジノン、その製造方法、該化合物を含む医薬およびそれらの使用 Download PDFInfo
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- JP2005533073A JP2005533073A JP2004514661A JP2004514661A JP2005533073A JP 2005533073 A JP2005533073 A JP 2005533073A JP 2004514661 A JP2004514661 A JP 2004514661A JP 2004514661 A JP2004514661 A JP 2004514661A JP 2005533073 A JP2005533073 A JP 2005533073A
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- Prior art keywords
- alkyl
- phenyl
- cooh
- compound
- conh
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/568—Four-membered rings
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Obesity (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10227508A DE10227508A1 (de) | 2002-06-19 | 2002-06-19 | Säuregruppen-substituierte Diphenylazetidinone, Verfahren zu deren Herstellung, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
| PCT/EP2003/005816 WO2004000805A1 (de) | 2002-06-19 | 2003-06-04 | Säuregruppen-substituierte diphenylazetidinone, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005533073A true JP2005533073A (ja) | 2005-11-04 |
| JP2005533073A5 JP2005533073A5 (https=) | 2006-07-13 |
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| JP2004514661A Abandoned JP2005533073A (ja) | 2002-06-19 | 2003-06-04 | 酸性基によって置換されたジフェニルアゼチジノン、その製造方法、該化合物を含む医薬およびそれらの使用 |
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|---|---|
| EP (1) | EP1517891B1 (https=) |
| JP (1) | JP2005533073A (https=) |
| KR (1) | KR20050008835A (https=) |
| CN (1) | CN100467448C (https=) |
| AR (1) | AR039690A1 (https=) |
| AU (1) | AU2003238210B2 (https=) |
| BR (1) | BR0311896A (https=) |
| CA (1) | CA2490112A1 (https=) |
| DE (1) | DE10227508A1 (https=) |
| EC (1) | ECSP045497A (https=) |
| HN (1) | HN2003000185A (https=) |
| HR (1) | HRPK20041201B3 (https=) |
| IL (1) | IL165789A0 (https=) |
| MA (1) | MA27206A1 (https=) |
| MX (1) | MXPA04012093A (https=) |
| NO (1) | NO20050134L (https=) |
| OA (1) | OA12869A (https=) |
| PA (1) | PA8576101A1 (https=) |
| PE (1) | PE20040564A1 (https=) |
| PL (1) | PL372700A1 (https=) |
| RS (1) | RS108404A (https=) |
| RU (1) | RU2287522C2 (https=) |
| SV (1) | SV2004001548A (https=) |
| TN (1) | TNSN04250A1 (https=) |
| TW (1) | TW200413311A (https=) |
| UA (1) | UA78577C2 (https=) |
| UY (1) | UY27853A1 (https=) |
| WO (1) | WO2004000805A1 (https=) |
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| GB0215579D0 (en) | 2002-07-05 | 2002-08-14 | Astrazeneca Ab | Chemical compounds |
| EP1699759B1 (en) | 2003-12-23 | 2010-10-20 | AstraZeneca AB | Diphenylazetidinone derivates possessing cholesterol absorption inhibitory activity |
| CN101115726A (zh) | 2004-12-03 | 2008-01-30 | 先灵公司 | 作为cb1拮抗剂的取代哌嗪 |
| US8361999B2 (en) | 2005-04-04 | 2013-01-29 | Pontificia Universidad Catolica De Chile | Methods of treating cholesterol gallstone disease with ezetimibe |
| DE602006010870D1 (de) | 2005-06-20 | 2010-01-14 | Schering Corp | Als antagonisten von histamin h3 geeignete piperidinderivate |
| SA06270191B1 (ar) | 2005-06-22 | 2010-03-29 | استرازينيكا ايه بي | مشتقات من 2- أزيتيدينون جديدة باعتبارها مثبطات لامتصاص الكوليسترول لعلاج حالات فرط نسبة الدهون في الدم |
| TW200811098A (en) | 2006-04-27 | 2008-03-01 | Astrazeneca Ab | Chemical compounds |
| CN103382174A (zh) * | 2006-06-23 | 2013-11-06 | 雅培制药有限公司 | 作为组胺h3受体调节物的环丙胺衍生物 |
| JP2010500300A (ja) | 2006-08-08 | 2010-01-07 | サノフィ−アベンティス | アリールアミノアリール−アルキル−置換イミダゾリジン−２，４−ジオン、それらの製造法、それらの化合物を含有する薬剤、およびそれらの使用 |
| DE102007002260A1 (de) | 2007-01-16 | 2008-07-31 | Sanofi-Aventis | Verwendung von substituierten Pyranonsäurederivaten zur Herstellung von Medikamenten zur Behandlung des Metabolischen Syndroms |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| CN101200443B (zh) * | 2007-10-17 | 2011-06-29 | 中国药科大学 | 氮杂环丁酮衍生物、其制备方法及含有它们的药物组合 |
| DE102007054497B3 (de) | 2007-11-13 | 2009-07-23 | Sanofi-Aventis Deutschland Gmbh | Neue kristalline Diphenylazetidinonhydrate und Verfahren zu deren Herstellung |
| WO2010003624A2 (en) | 2008-07-09 | 2010-01-14 | Sanofi-Aventis | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
| WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
| CA2754384A1 (en) | 2009-03-06 | 2010-09-10 | Lipideon Biotechnology Ag | Pharmaceutical hypocholesterolemic compositions |
| CN101993403B (zh) | 2009-08-11 | 2012-07-11 | 浙江海正药业股份有限公司 | 氮杂环丁酮类化合物及医药应用 |
| MX2012001729A (es) | 2009-08-26 | 2012-06-13 | Sanofi Sa | Nuevos hidratos cristalinos de fluoroglicosido heteroaromatico, productos farmaceuticos que comprenden estos compuestos, y su empleo. |
| WO2011157827A1 (de) | 2010-06-18 | 2011-12-22 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| EP2683705B1 (de) | 2011-03-08 | 2015-04-22 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| US8871758B2 (en) | 2011-03-08 | 2014-10-28 | Sanofi | Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
| WO2012120052A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2683699B1 (de) | 2011-03-08 | 2015-06-24 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| US8828995B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
| 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 |
| KR102919209B1 (ko) | 2018-08-10 | 2026-01-28 | 다이아핀 테라퓨틱스, 엘엘씨 | 트리-펩타이드 그리고 대사, 심장혈관 및 염증성 장애의 치료 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LT3300B (en) * | 1992-12-23 | 1995-06-26 | Schering Corp | Combination of a cholesterol biosynhtesis inhibitor and a beta- lactam cholesterol absorbtion inhibitor |
| US5631365A (en) * | 1993-09-21 | 1997-05-20 | Schering Corporation | Hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents |
| US5756470A (en) * | 1996-10-29 | 1998-05-26 | Schering Corporation | Sugar-substituted 2-azetidinones useful as hypocholesterolemic agents |
| RU2181297C2 (ru) * | 2000-06-20 | 2002-04-20 | Эпштейн Олег Ильич | Способ лечения патологического синдрома и лекарственное средство |
| DE10042447A1 (de) * | 2000-08-29 | 2002-03-28 | Aventis Pharma Gmbh | Protein aus dem Darm von Wirbeltieren, welches Cholesterin absorbiert, sowie Verwendung dieses Proteins zur Identifizierung von Inhibitoren des intestinalen Cholesterintransports |
| AU2002231688A1 (en) * | 2000-12-21 | 2002-07-01 | Sanofi-Aventis Deutschland Gmbh | Diphenyl azetidinone derivatives, method for the production thereof, medicaments containing these compounds, and their use |
| IL156552A0 (en) * | 2000-12-21 | 2004-01-04 | Aventis Pharma Gmbh | Diphenyl azetidinone derivatives, method for the production thereof, medicaments containing these compounds, and their use |
| HRP20030498A2 (en) * | 2000-12-21 | 2005-04-30 | Aventis Pharma Deutschland Gmbh | Novel 1,2-diphenzylazetidinones, method for producing the same, medicaments containing said compounds, and the use thereof for treating disorders of the lipid metabolism |
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- 2003-06-04 EP EP03735535A patent/EP1517891B1/de not_active Expired - Lifetime
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- 2003-06-04 WO PCT/EP2003/005816 patent/WO2004000805A1/de not_active Ceased
- 2003-06-04 PL PL03372700A patent/PL372700A1/xx not_active Application Discontinuation
- 2003-06-04 RS YUP-1084/04A patent/RS108404A/sr unknown
- 2003-06-04 JP JP2004514661A patent/JP2005533073A/ja not_active Abandoned
- 2003-06-04 BR BR0311896-7A patent/BR0311896A/pt not_active IP Right Cessation
- 2003-06-04 KR KR10-2004-7020643A patent/KR20050008835A/ko not_active Ceased
- 2003-06-04 AU AU2003238210A patent/AU2003238210B2/en not_active Ceased
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