CN101541747B - 作为11-β-羟基甾族化合物脱氢酶1的抑制剂的联苯基酰胺内酰胺衍生物 - Google Patents
作为11-β-羟基甾族化合物脱氢酶1的抑制剂的联苯基酰胺内酰胺衍生物 Download PDFInfo
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- CN101541747B CN101541747B CN2007800143164A CN200780014316A CN101541747B CN 101541747 B CN101541747 B CN 101541747B CN 2007800143164 A CN2007800143164 A CN 2007800143164A CN 200780014316 A CN200780014316 A CN 200780014316A CN 101541747 B CN101541747 B CN 101541747B
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- Prior art keywords
- ylmethyl
- xenyl
- cyclohexyl
- chloro
- carbonyl
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D207/12—Oxygen or sulfur atoms
-
- 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
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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
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- A—HUMAN NECESSITIES
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| PCT/US2007/066921 WO2007124337A1 (en) | 2006-04-21 | 2007-04-19 | Biphenyl amide lactam derivatives as inhibitors of 11- beta-hydroxysteroid dehydrogenase 1 |
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Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
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| MX2008013484A (es) * | 2006-04-21 | 2008-10-30 | Lilly Co Eli | Derivados de lactamas de ciclohexilpirazol como inhibidores de 11-beta-hidroxiesteroide deshidrogenasa 1. |
| JP5236628B2 (ja) | 2006-04-21 | 2013-07-17 | イーライ リリー アンド カンパニー | 11−β−ヒドロキシステロイドデヒドロゲナーゼ1阻害剤としての、シクロヘキシルイミダゾールラクタム誘導体 |
| AU2007244971B2 (en) | 2006-04-24 | 2012-01-19 | Eli Lilly And Company | Cyclohexyl substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| JP5189078B2 (ja) | 2006-04-24 | 2013-04-24 | イーライ リリー アンド カンパニー | 11−β−ヒドロキシステロイドデヒドロゲナーゼ1の阻害剤 |
| MY148079A (en) | 2006-04-24 | 2013-02-28 | Lilly Co Eli | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| US7968585B2 (en) | 2006-04-25 | 2011-06-28 | Eli Lilly And Company | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| ES2336849T3 (es) | 2006-04-25 | 2010-04-16 | Eli Lilly And Company | Inhibidores de 11-beta-hidroxiesteroide dehidrogenasa 1. |
| MX2008013656A (es) * | 2006-04-25 | 2008-11-10 | Lilly Co Eli | Inhibidores de 11-beta-hidroxiesteroide deshidrogenasa. |
| CN101448816B (zh) * | 2006-04-28 | 2013-08-07 | 伊莱利利公司 | 作为11-β-羟类固醇脱氢酶1的抑制剂的哌啶基取代的吡咯烷酮类 |
| CN101460470B (zh) | 2006-05-30 | 2011-05-18 | 阿斯利康(瑞典)有限公司 | 作为dgat1抑制剂的1,3,4-二唑衍生物 |
| EP2125750B1 (en) | 2007-02-26 | 2014-05-21 | Vitae Pharmaceuticals, Inc. | Cyclic urea and carbamate inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| WO2009017671A1 (en) | 2007-07-26 | 2009-02-05 | Vitae Pharmaceuticals, Inc. | Synthesis of inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| AR069207A1 (es) | 2007-11-07 | 2010-01-06 | Vitae Pharmaceuticals Inc | Ureas ciclicas como inhibidores de la 11 beta - hidroxi-esteroide deshidrogenasa 1 |
| EP2220048B1 (en) | 2007-11-16 | 2017-01-25 | Boehringer Ingelheim International GmbH | Aryl- and heteroarylcarbonyl derivatives of benzomorphanes and related scaffolds, medicaments containing such compounds and their use |
| US8440658B2 (en) | 2007-12-11 | 2013-05-14 | Vitae Pharmaceuticals, Inc. | Cyclic urea inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
| JP5662803B2 (ja) | 2007-12-20 | 2015-02-04 | アストラゼネカ アクチボラグ | Dgat1阻害剤としてのカルバモイル化合物190 |
| JP5301563B2 (ja) | 2008-05-01 | 2013-09-25 | ヴァイティー ファーマシューティカルズ,インコーポレイテッド | 11β−ヒドロキシステロイドデヒドロゲナーゼ1の環状インヒビター |
| EP2288596B1 (en) | 2008-05-13 | 2016-11-30 | Boehringer Ingelheim International GmbH | Alicyclic carboxylic acid derivatives of benzomorphans and related scaffolds, medicaments containing such compounds and their use |
| PL2324018T3 (pl) | 2008-07-25 | 2014-02-28 | Boehringer Ingelheim Int | Cykliczne inhibitory dehydrogenazy 11 beta-hydroksysteroidowej typu 1 |
| WO2010010150A1 (en) | 2008-07-25 | 2010-01-28 | Boehringer Ingelheim International Gmbh | Synthesis of inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 |
| CA2729998A1 (en) | 2008-07-25 | 2010-01-28 | Boehringer Ingelheim International Gmbh | Inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| JP5679997B2 (ja) * | 2009-02-04 | 2015-03-04 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 11β−ヒドロキシステロイドデヒドロゲナーゼ1の環状阻害剤 |
| EP2243479A3 (en) | 2009-04-20 | 2011-01-19 | Abbott Laboratories | Novel amide and amidine derivates and uses thereof |
| MA33216B1 (fr) | 2009-04-30 | 2012-04-02 | Boehringer Ingelheim Int | Inhibiteurs cycliques de la 11béta-hydroxysteroïde déshydrogénase 1 |
| WO2011011123A1 (en) | 2009-06-11 | 2011-01-27 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 based on the 1,3 -oxazinan- 2 -one structure |
| AU2010261499A1 (en) | 2009-06-19 | 2012-01-12 | Astrazeneca Ab | Pyrazine carboxamides as inhibitors of DGAT1 |
| EP2448928B1 (en) | 2009-07-01 | 2014-08-13 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| WO2011056737A1 (en) | 2009-11-05 | 2011-05-12 | Boehringer Ingelheim International Gmbh | Novel chiral phosphorus ligands |
| UY33001A (es) | 2009-11-06 | 2011-05-31 | Boehringer Ingelheim Int | Derivados arilo y heteroarilcarbonilo de hexahidroindenopiridina y octahidrobenzoquinolina |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| JP2013531636A (ja) | 2010-05-26 | 2013-08-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 2−オキソ−1,2−ジヒドロピリジン−4−イルボロン酸誘導体 |
| US8933072B2 (en) | 2010-06-16 | 2015-01-13 | Vitae Pharmaceuticals, Inc. | Substituted 5-,6- and 7-membered heterocycles, medicaments containing such compounds, and their use |
| 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 |
| EP2585444B1 (en) | 2010-06-25 | 2014-10-22 | Boehringer Ingelheim International GmbH | Azaspirohexanones as inhibitors of 11-beta-hsd1 for the treatment of metabolic disorders |
| 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 |
| 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 |
| WO2012059416A1 (en) | 2010-11-02 | 2012-05-10 | Boehringer Ingelheim International Gmbh | Pharmaceutical combinations for the treatment of metabolic disorders |
| TWI537258B (zh) | 2010-11-05 | 2016-06-11 | 百靈佳殷格翰國際股份有限公司 | 六氫茚并吡啶及八氫苯并喹啉之芳基-及雜環芳基羰基衍生物 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| EP2744783A1 (en) | 2011-08-17 | 2014-06-25 | Boehringer Ingelheim International GmbH | Indenopyridine derivatives |
| 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 |
| WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| CN110498774A (zh) * | 2018-05-18 | 2019-11-26 | 上海医药工业研究院 | 一种艾沙康唑中间体的制备方法 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004056744A1 (en) | 2002-12-23 | 2004-07-08 | Janssen Pharmaceutica N.V. | Adamantyl acetamides as hydroxysteroid dehydrogenase inhibitors |
| WO2005108361A1 (en) | 2004-05-07 | 2005-11-17 | Janssen Pharmaceutica N.V. | Adamantyl pyrrolidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors |
| MXPA06012932A (es) | 2004-05-07 | 2007-01-26 | Janssen Pharmaceutica Nv | Derivados de pirrolidin-2-ona y piperidin-2-ona como inhibidores de 11-beta hidroxiesteroide deshidrogenasa. |
| JP2008515956A (ja) | 2004-10-12 | 2008-05-15 | ノボ ノルディスク アクティーゼルスカブ | 11β−ヒドロキシステロイドデヒドロゲナーゼ1型活性スピロ化合物 |
| EP1807072B1 (en) | 2004-10-29 | 2009-01-07 | Eli Lilly And Company | Cycloalkyl lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| CN102731499B (zh) | 2004-11-10 | 2016-01-13 | 因塞特控股公司 | 内酰胺化合物及其作为药物的应用 |
| DK1830841T3 (da) | 2004-12-20 | 2008-10-13 | Lilly Co Eli | Cycloalkyllactamderivater som inhibitorer af 11-beta-hydroxysteroid-dehydrogenase 1 |
| EP1830840B1 (en) | 2004-12-21 | 2008-07-16 | Eli Lilly And Company | Cycloalkyl lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| US20090264650A1 (en) | 2005-03-31 | 2009-10-22 | Nobuo Cho | Prophylactic/Therapeutic Agent for Diabetes |
| US7998959B2 (en) | 2006-01-12 | 2011-08-16 | Incyte Corporation | Modulators of 11-β hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| JP5236628B2 (ja) | 2006-04-21 | 2013-07-17 | イーライ リリー アンド カンパニー | 11−β−ヒドロキシステロイドデヒドロゲナーゼ1阻害剤としての、シクロヘキシルイミダゾールラクタム誘導体 |
| MX2008013484A (es) | 2006-04-21 | 2008-10-30 | Lilly Co Eli | Derivados de lactamas de ciclohexilpirazol como inhibidores de 11-beta-hidroxiesteroide deshidrogenasa 1. |
| AU2007244971B2 (en) | 2006-04-24 | 2012-01-19 | Eli Lilly And Company | Cyclohexyl substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| JP5189078B2 (ja) | 2006-04-24 | 2013-04-24 | イーライ リリー アンド カンパニー | 11−β−ヒドロキシステロイドデヒドロゲナーゼ1の阻害剤 |
| MY148079A (en) | 2006-04-24 | 2013-02-28 | Lilly Co Eli | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| ES2336849T3 (es) | 2006-04-25 | 2010-04-16 | Eli Lilly And Company | Inhibidores de 11-beta-hidroxiesteroide dehidrogenasa 1. |
| MX2008013656A (es) | 2006-04-25 | 2008-11-10 | Lilly Co Eli | Inhibidores de 11-beta-hidroxiesteroide deshidrogenasa. |
| US7968585B2 (en) | 2006-04-25 | 2011-06-28 | Eli Lilly And Company | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| CN101448816B (zh) | 2006-04-28 | 2013-08-07 | 伊莱利利公司 | 作为11-β-羟类固醇脱氢酶1的抑制剂的哌啶基取代的吡咯烷酮类 |
| CL2008001839A1 (es) | 2007-06-21 | 2009-01-16 | Incyte Holdings Corp | Compuestos derivados de 2,7-diazaespirociclos, inhibidores de 11-beta hidroxil esteroide deshidrogenasa tipo 1; composicion farmaceutica que comprende a dichos compuestos; utiles para tratar la obesidad, diabetes, intolerancia a la glucosa, diabetes tipo ii, entre otras enfermedades. |
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2007
- 2007-04-19 WO PCT/US2007/066921 patent/WO2007124337A1/en not_active Ceased
- 2007-04-19 AU AU2007240458A patent/AU2007240458B2/en not_active Ceased
- 2007-04-19 BR BRPI0710246-1A patent/BRPI0710246A2/pt not_active IP Right Cessation
- 2007-04-19 CN CN2007800143164A patent/CN101541747B/zh not_active Expired - Fee Related
- 2007-04-19 EP EP07760877.6A patent/EP2016047B1/en not_active Not-in-force
- 2007-04-19 MX MX2008013485A patent/MX2008013485A/es active IP Right Grant
- 2007-04-19 EA EA200870462A patent/EA014718B1/ru not_active IP Right Cessation
- 2007-04-19 US US12/297,349 patent/US8088776B2/en not_active Expired - Fee Related
- 2007-04-19 ES ES07760877T patent/ES2435115T3/es active Active
- 2007-04-19 JP JP2009506764A patent/JP5265521B2/ja not_active Expired - Fee Related
- 2007-04-19 CA CA2649741A patent/CA2649741C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP2016047A1 (en) | 2009-01-21 |
| WO2007124337A1 (en) | 2007-11-01 |
| ES2435115T3 (es) | 2013-12-18 |
| EA200870462A1 (ru) | 2009-04-28 |
| MX2008013485A (es) | 2008-10-30 |
| JP2009534414A (ja) | 2009-09-24 |
| CN101541747A (zh) | 2009-09-23 |
| WO2007124337A8 (en) | 2009-06-18 |
| CA2649741A1 (en) | 2007-11-01 |
| BRPI0710246A2 (pt) | 2011-08-09 |
| AU2007240458B2 (en) | 2012-03-15 |
| EA014718B1 (ru) | 2011-02-28 |
| CA2649741C (en) | 2013-08-27 |
| US20090156571A1 (en) | 2009-06-18 |
| US8088776B2 (en) | 2012-01-03 |
| EP2016047B1 (en) | 2013-08-28 |
| JP5265521B2 (ja) | 2013-08-14 |
| AU2007240458A1 (en) | 2007-11-01 |
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