EA016959B1 - Замещенные пирролидиноны в качестве ингибиторов 11-бета-гидроксистероиддегидрогеназы 1 типа - Google Patents
Замещенные пирролидиноны в качестве ингибиторов 11-бета-гидроксистероиддегидрогеназы 1 типа Download PDFInfo
- Publication number
- EA016959B1 EA016959B1 EA200870471A EA200870471A EA016959B1 EA 016959 B1 EA016959 B1 EA 016959B1 EA 200870471 A EA200870471 A EA 200870471A EA 200870471 A EA200870471 A EA 200870471A EA 016959 B1 EA016959 B1 EA 016959B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- halogen
- dichloro
- ylmethyl
- compounds
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title description 14
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- 101710186107 11-beta-hydroxysteroid dehydrogenase 1 Proteins 0.000 title 1
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229960002277 tolazamide Drugs 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
Classifications
-
- 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
- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—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 one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Biomedical Technology (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74546706P | 2006-04-24 | 2006-04-24 | |
| PCT/US2007/067200 WO2007127693A1 (en) | 2006-04-24 | 2007-04-23 | Substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200870471A1 EA200870471A1 (ru) | 2009-06-30 |
| EA016959B1 true EA016959B1 (ru) | 2012-08-30 |
Family
ID=38512591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200870471A EA016959B1 (ru) | 2006-04-24 | 2007-04-23 | Замещенные пирролидиноны в качестве ингибиторов 11-бета-гидроксистероиддегидрогеназы 1 типа |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US7816349B2 (enExample) |
| EP (1) | EP2029529B1 (enExample) |
| JP (1) | JP5189078B2 (enExample) |
| CN (1) | CN101432263B (enExample) |
| AT (1) | ATE473210T1 (enExample) |
| AU (1) | AU2007244960B2 (enExample) |
| BR (1) | BRPI0710262A2 (enExample) |
| CA (1) | CA2649650C (enExample) |
| DE (1) | DE602007007614D1 (enExample) |
| DK (1) | DK2029529T3 (enExample) |
| EA (1) | EA016959B1 (enExample) |
| ES (1) | ES2346925T3 (enExample) |
| MX (1) | MX2008013644A (enExample) |
| PL (1) | PL2029529T3 (enExample) |
| PT (1) | PT2029529E (enExample) |
| WO (1) | WO2007127693A1 (enExample) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2008013484A (es) | 2006-04-21 | 2008-10-30 | Lilly Co Eli | Derivados de lactamas de ciclohexilpirazol como inhibidores de 11-beta-hidroxiesteroide deshidrogenasa 1. |
| WO2007124337A1 (en) * | 2006-04-21 | 2007-11-01 | Eli Lilly And Company | Biphenyl amide lactam derivatives as inhibitors of 11- beta-hydroxysteroid dehydrogenase 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 |
| 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 |
| MX2008013656A (es) * | 2006-04-25 | 2008-11-10 | Lilly Co Eli | Inhibidores de 11-beta-hidroxiesteroide deshidrogenasa. |
| ES2336849T3 (es) | 2006-04-25 | 2010-04-16 | Eli Lilly And Company | Inhibidores de 11-beta-hidroxiesteroide dehidrogenasa 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 |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| 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 |
| JP5734666B2 (ja) * | 2008-02-11 | 2015-06-17 | 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1,3−オキサアゼパン−2−オン及び1,3−ジアゼパン−2−オン阻害剤 |
| EP2291371B1 (en) * | 2008-05-01 | 2015-06-10 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| 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 |
| EP2291373B1 (en) * | 2008-05-01 | 2013-09-11 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| CA2723034A1 (en) * | 2008-05-01 | 2009-11-05 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| 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 |
| 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 |
| US8871208B2 (en) * | 2009-12-04 | 2014-10-28 | Abbvie Inc. | 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors and uses thereof |
| 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 |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA005274B1 (ru) * | 2000-05-22 | 2004-12-30 | Биовитрум Аб | Ингибиторы 11-бета-гидроксистероиддегидрогеназы типа 1 |
| RU2004110410A (ru) * | 2001-09-06 | 2005-10-20 | Шеринг Корпорейшн (US) | Ингибиторы 17-b гидроксистероид дегидрогеназы типа 3 для лечения андроген-зави симых заболеваний |
| WO2005108361A1 (en) * | 2004-05-07 | 2005-11-17 | Janssen Pharmaceutica N.V. | Adamantyl pyrrolidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors |
| EA200501045A1 (ru) * | 2002-12-23 | 2005-12-29 | Янссен Фармацевтика Н. В. | Адамантилацетамиды как ингибиторы 11-бета гидроксистероиддегидрогеназы |
| WO2006049952A1 (en) * | 2004-10-29 | 2006-05-11 | Eli Lilly And Company | Cycloalkyl lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
| 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 |
| WO2007124337A1 (en) | 2006-04-21 | 2007-11-01 | Eli Lilly And Company | Biphenyl amide lactam derivatives as inhibitors of 11- beta-hydroxysteroid dehydrogenase 1 |
| AU2007244971B2 (en) | 2006-04-24 | 2012-01-19 | Eli Lilly And Company | Cyclohexyl substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| 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. |
-
2007
- 2007-04-23 JP JP2009507916A patent/JP5189078B2/ja not_active Expired - Fee Related
- 2007-04-23 PL PL07761107T patent/PL2029529T3/pl unknown
- 2007-04-23 CA CA2649650A patent/CA2649650C/en not_active Expired - Fee Related
- 2007-04-23 PT PT07761107T patent/PT2029529E/pt unknown
- 2007-04-23 DK DK07761107.7T patent/DK2029529T3/da active
- 2007-04-23 WO PCT/US2007/067200 patent/WO2007127693A1/en not_active Ceased
- 2007-04-23 EA EA200870471A patent/EA016959B1/ru not_active IP Right Cessation
- 2007-04-23 BR BRPI0710262-3A patent/BRPI0710262A2/pt not_active IP Right Cessation
- 2007-04-23 CN CN2007800148702A patent/CN101432263B/zh not_active Expired - Fee Related
- 2007-04-23 US US12/297,969 patent/US7816349B2/en not_active Expired - Fee Related
- 2007-04-23 DE DE602007007614T patent/DE602007007614D1/de active Active
- 2007-04-23 EP EP07761107A patent/EP2029529B1/en not_active Not-in-force
- 2007-04-23 MX MX2008013644A patent/MX2008013644A/es active IP Right Grant
- 2007-04-23 AU AU2007244960A patent/AU2007244960B2/en not_active Ceased
- 2007-04-23 ES ES07761107T patent/ES2346925T3/es active Active
- 2007-04-23 AT AT07761107T patent/ATE473210T1/de active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA005274B1 (ru) * | 2000-05-22 | 2004-12-30 | Биовитрум Аб | Ингибиторы 11-бета-гидроксистероиддегидрогеназы типа 1 |
| RU2004110410A (ru) * | 2001-09-06 | 2005-10-20 | Шеринг Корпорейшн (US) | Ингибиторы 17-b гидроксистероид дегидрогеназы типа 3 для лечения андроген-зави симых заболеваний |
| EA200501045A1 (ru) * | 2002-12-23 | 2005-12-29 | Янссен Фармацевтика Н. В. | Адамантилацетамиды как ингибиторы 11-бета гидроксистероиддегидрогеназы |
| WO2005108361A1 (en) * | 2004-05-07 | 2005-11-17 | Janssen Pharmaceutica N.V. | Adamantyl pyrrolidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors |
| WO2006049952A1 (en) * | 2004-10-29 | 2006-05-11 | Eli Lilly And Company | Cycloalkyl lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
Also Published As
| Publication number | Publication date |
|---|---|
| PT2029529E (pt) | 2010-09-02 |
| CN101432263B (zh) | 2012-03-07 |
| JP5189078B2 (ja) | 2013-04-24 |
| DK2029529T3 (da) | 2010-09-20 |
| AU2007244960B2 (en) | 2012-03-01 |
| DE602007007614D1 (de) | 2010-08-19 |
| ES2346925T3 (es) | 2010-10-21 |
| AU2007244960A1 (en) | 2007-11-08 |
| JP2009534470A (ja) | 2009-09-24 |
| EP2029529B1 (en) | 2010-07-07 |
| US20090069326A1 (en) | 2009-03-12 |
| CA2649650A1 (en) | 2007-11-08 |
| WO2007127693A1 (en) | 2007-11-08 |
| US7816349B2 (en) | 2010-10-19 |
| MX2008013644A (es) | 2009-03-06 |
| BRPI0710262A2 (pt) | 2011-08-09 |
| EA200870471A1 (ru) | 2009-06-30 |
| ATE473210T1 (de) | 2010-07-15 |
| PL2029529T3 (pl) | 2010-11-30 |
| CN101432263A (zh) | 2009-05-13 |
| EP2029529A1 (en) | 2009-03-04 |
| CA2649650C (en) | 2014-01-14 |
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