TW200944526A - Carbamate and urea inhibitors of 11β-hydroxysteroid dehydrogenase 1 - Google Patents
Carbamate and urea inhibitors of 11β-hydroxysteroid dehydrogenase 1 Download PDFInfo
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- TW200944526A TW200944526A TW098112970A TW98112970A TW200944526A TW 200944526 A TW200944526 A TW 200944526A TW 098112970 A TW098112970 A TW 098112970A TW 98112970 A TW98112970 A TW 98112970A TW 200944526 A TW200944526 A TW 200944526A
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- Prior art keywords
- alkyl
- group
- optionally substituted
- cvc3
- aryl
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- 239000003112 inhibitor Substances 0.000 title description 21
- 102100036506 11-beta-hydroxysteroid dehydrogenase 1 Human genes 0.000 title description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title description 3
- 239000004202 carbamide Substances 0.000 title description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 title description 2
- 101710186107 11-beta-hydroxysteroid dehydrogenase 1 Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 287
- 238000000034 method Methods 0.000 claims abstract description 271
- 150000003839 salts Chemical class 0.000 claims abstract description 87
- 238000011282 treatment Methods 0.000 claims abstract description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
- 201000010099 disease Diseases 0.000 claims abstract description 22
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- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 674
- 125000001072 heteroaryl group Chemical group 0.000 claims description 197
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- -1 alkyl Halogen Chemical class 0.000 claims description 178
- 125000000623 heterocyclic group Chemical group 0.000 claims description 163
- 229910052736 halogen Inorganic materials 0.000 claims description 136
- 150000002367 halogens Chemical group 0.000 claims description 133
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 96
- 125000003545 alkoxy group Chemical group 0.000 claims description 79
- 229910052739 hydrogen Inorganic materials 0.000 claims description 77
- 239000001257 hydrogen Substances 0.000 claims description 77
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 67
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 61
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 54
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 52
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 49
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 42
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 40
- 125000005843 halogen group Chemical group 0.000 claims description 40
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 38
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 36
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 34
- 125000003107 substituted aryl group Chemical group 0.000 claims description 34
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- 230000000694 effects Effects 0.000 claims description 23
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- 125000000304 alkynyl group Chemical group 0.000 claims description 20
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 18
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 15
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 14
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- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 claims description 8
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 7
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- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 6
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- 101100451537 Caenorhabditis elegans hsd-1 gene Proteins 0.000 claims description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
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- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims 1
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- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical group [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| US12507208P | 2008-04-22 | 2008-04-22 |
Publications (1)
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| TW200944526A true TW200944526A (en) | 2009-11-01 |
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Family Applications (1)
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| TW098112970A TW200944526A (en) | 2008-04-22 | 2009-04-20 | Carbamate and urea inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
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| EP (1) | EP2276730A2 (enExample) |
| JP (1) | JP5653907B2 (enExample) |
| AR (1) | AR071386A1 (enExample) |
| CA (1) | CA2721750A1 (enExample) |
| TW (1) | TW200944526A (enExample) |
| WO (1) | WO2009131669A2 (enExample) |
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| US8329897B2 (en) | 2007-07-26 | 2012-12-11 | Vitae Pharmaceuticals, Inc. | Synthesis of inhibitors of 11β-hydroxysteroid dehydrogenase type 1 |
| AR069207A1 (es) | 2007-11-07 | 2010-01-06 | Vitae Pharmaceuticals Inc | Ureas ciclicas como inhibidores de la 11 beta - hidroxi-esteroide deshidrogenasa 1 |
| CA2704628C (en) * | 2007-11-16 | 2016-11-29 | Boehringer Ingelheim International Gmbh | Aryl- and heteroarylcarbonyl derivatives of benzomorphanes and related scaffolds, medicaments containing such compounds and their use |
| CA2708303A1 (en) | 2007-12-11 | 2009-06-18 | Vitae Pharmaceuticals, Inc. | Cyclic urea inhibitors of 11.beta.-hydroxysteroid dehydrogenase 1 |
| TW200934490A (en) | 2008-01-07 | 2009-08-16 | Vitae Pharmaceuticals Inc | Lactam inhibitors of 11 &abgr;-hydroxysteroid dehydrogenase 1 |
| JP5490020B2 (ja) | 2008-01-24 | 2014-05-14 | 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の環状カルバゼート及びセミカルバジドインヒビター |
| US20110028445A1 (en) * | 2008-02-12 | 2011-02-03 | Boehringer Ingelheim International Gmbh | Urea derivatives of benzomorphanes and related scaffolds, medicaments containing such compounds and their use |
| US8598160B2 (en) | 2008-02-15 | 2013-12-03 | Vitae Pharmaceuticals, Inc. | Cycloalkyl lactame derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| TW200944526A (en) * | 2008-04-22 | 2009-11-01 | Vitae Pharmaceuticals Inc | Carbamate and urea inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
| US8569292B2 (en) | 2008-05-01 | 2013-10-29 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
| PL2300461T3 (pl) | 2008-05-01 | 2013-09-30 | Vitae Pharmaceuticals Inc | Cykliczne inhibitory dehydrogenazy 11beta-hydroksysteroidów 1 |
| CA2723034A1 (en) | 2008-05-01 | 2009-11-05 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| CL2009001151A1 (es) | 2008-05-13 | 2010-08-13 | Boehringer Ingelheim Int | Compuestos derivados de acidos carbociclicos aliciclicos de benzomorfanos, procedimiento de preparacion, composicion farmaceutica, utiles para tratar enfermedades influenciadas por la inhibicion de la enzima 11beta-hidroxiesteroide deshidrogenasa, como trastornos metabolicos. |
| JP5379160B2 (ja) | 2008-07-25 | 2013-12-25 | 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の環状インヒビター |
| TW201016691A (en) | 2008-07-25 | 2010-05-01 | Boehringer Ingelheim Int | Inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| WO2010010150A1 (en) | 2008-07-25 | 2010-01-28 | Boehringer Ingelheim International Gmbh | Synthesis of inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 |
| TW201022266A (en) | 2008-10-23 | 2010-06-16 | Boehringer Ingelheim Int | Urea derivatives of substituted nortropanes, medicaments containing such compounds and their use |
| EP2393807B1 (en) | 2009-02-04 | 2013-08-14 | Boehringer Ingelheim International GmbH | Cyclic inhibitors of 11 -hydroxysteroid dehydrogenase 1 |
| MA33216B1 (fr) | 2009-04-30 | 2012-04-02 | Boehringer Ingelheim Int | Inhibiteurs cycliques de la 11béta-hydroxysteroïde déshydrogénase 1 |
| EP2438049B1 (en) | 2009-06-02 | 2014-05-14 | Boehringer Ingelheim International GmbH | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| AR076936A1 (es) | 2009-06-02 | 2011-07-20 | Vitae Pharmaceuticals Inc | Inhibidores de carbamato y urea de la 11 beta hidroxiesteroide deshidrogenasa 1 |
| JP5656986B2 (ja) | 2009-06-11 | 2015-01-21 | 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 | 1,3−オキサジナン−2−オン構造に基づく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 |
| JP5749263B2 (ja) | 2009-07-01 | 2015-07-15 | 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 |
| US8552212B2 (en) | 2009-11-05 | 2013-10-08 | Boehringer Ingelheim International Gmbh | Chiral phosphorus ligands |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| CN102219759B (zh) * | 2010-04-16 | 2013-07-24 | 中国科学院上海药物研究所 | 芳基甲酰胺类化合物及其制备方法、药物组合物和用途 |
| US8648192B2 (en) | 2010-05-26 | 2014-02-11 | Boehringer Ingelheim International Gmbh | 2-oxo-1,2-dihydropyridin-4-ylboronic acid derivatives |
| EP2582698B1 (en) | 2010-06-16 | 2016-09-14 | Vitae Pharmaceuticals, Inc. | Substituted 5-,6- and 7-membered heterocycles, medicaments containing such compounds, and their use |
| 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 |
| JP5813106B2 (ja) | 2010-06-25 | 2015-11-17 | 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 | 代謝障害の処置のための11−β−HSD1のインヒビターとしてのアザスピロヘキサノン |
| 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 |
| US8735585B2 (en) | 2011-08-17 | 2014-05-27 | 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 |
| 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 |
| EP3235813A1 (en) | 2016-04-19 | 2017-10-25 | Cidqo 2012, S.L. | Aza-tetra-cyclo derivatives |
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| WO1999037304A1 (en) | 1998-01-27 | 1999-07-29 | Aventis Pharmaceuticals Products Inc. | SUBSTITUTED OXOAZAHETEROCYCLYL FACTOR Xa INHIBITORS |
| US7410995B1 (en) * | 1998-08-14 | 2008-08-12 | Gpi Nil Holdings Inc. | N-linked sulfonamide of heterocyclic thioesters for vision and memory disorders |
| CZ2002323A3 (cs) | 1999-07-28 | 2002-05-15 | Aventis Pharmaceuticals Products Inc. | Substituované oxoazaheterocyklylové sloučeniny a farmaceutické prostředky, které je obsahují |
| CN1308324C (zh) * | 2000-08-31 | 2007-04-04 | 弗·哈夫曼-拉罗切有限公司 | 作为α-1肾上腺素能拮抗剂的喹唑啉衍生物 |
| DE60238709D1 (de) * | 2001-12-03 | 2011-02-03 | Hoffmann La Roche | 4-piperidinylalkylamin-derivate, antagonisten von muscarinrezeptoren |
| TW200403058A (en) | 2002-04-19 | 2004-03-01 | Bristol Myers Squibb Co | Heterocyclo inhibitors of potassium channel function |
| EP1537116B1 (en) * | 2002-09-04 | 2010-06-02 | Schering Corporation | Pyrazolopyrimidines suitable for the treatment of cancer diseases |
| CA2501611A1 (en) | 2002-10-11 | 2004-04-22 | Astrazeneca Ab | 1,4-disubstituted piperidine derivatives and their use as 11-betahsd1 inhibitors |
| WO2004056744A1 (en) | 2002-12-23 | 2004-07-08 | Janssen Pharmaceutica N.V. | Adamantyl acetamides as hydroxysteroid dehydrogenase inhibitors |
| JP2004315511A (ja) | 2003-03-31 | 2004-11-11 | Taisho Pharmaceut Co Ltd | Mch受容体アンタゴニスト |
| GB0325745D0 (en) | 2003-11-05 | 2003-12-10 | Astrazeneca Ab | Chemical compounds |
| GB0326029D0 (en) | 2003-11-07 | 2003-12-10 | Astrazeneca Ab | Chemical compounds |
| US7511159B2 (en) * | 2003-12-25 | 2009-03-31 | Ono Pharmaceutical Co., Ltd. | Azetidine ring compounds and drugs comprising the same |
| BRPI0512410A (pt) | 2004-06-24 | 2008-03-04 | Incyte Corp | compostos de amido e seu uso como produtos farmacêuticos |
| BRPI0512535A (pt) | 2004-06-24 | 2008-03-25 | Incyte Corp | compostos de piperidinas n-substituìdas, suas composições e métodos de modulações |
| JP2008518903A (ja) | 2004-11-02 | 2008-06-05 | ファイザー・インク | 置換および非置換アダマンチルアミドの新規化合物 |
| US20060148871A1 (en) | 2005-01-05 | 2006-07-06 | Rohde Jeffrey J | Metabolic stabilization of substituted adamantane |
| CA2621255A1 (en) | 2005-09-21 | 2007-04-05 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| EP1801098A1 (en) * | 2005-12-16 | 2007-06-27 | Merck Sante | 2-Adamantylurea derivatives as selective 11B-HSD1 inhibitors |
| JP2007204744A (ja) * | 2006-01-05 | 2007-08-16 | Toyobo Co Ltd | ポリエステル樹脂、ポリエステル樹脂組成物およびそれからなるポリエステル成形体並びにポリエステル成形体の製造方法 |
| US20070208001A1 (en) | 2006-03-03 | 2007-09-06 | Jincong Zhuo | Modulators of 11- beta hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| WO2009020140A1 (ja) | 2007-08-06 | 2009-02-12 | Dainippon Sumitomo Pharma Co., Ltd. | アダマンチルウレア誘導体 |
| TW200944526A (en) | 2008-04-22 | 2009-11-01 | Vitae Pharmaceuticals Inc | Carbamate and urea inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
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2009
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- 2009-04-21 EP EP09733956A patent/EP2276730A2/en not_active Withdrawn
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2013
- 2013-02-15 US US13/769,256 patent/US8828985B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20130244994A1 (en) | 2013-09-19 |
| WO2009131669A2 (en) | 2009-10-29 |
| US8399504B2 (en) | 2013-03-19 |
| WO2009131669A3 (en) | 2010-04-01 |
| US20110112062A1 (en) | 2011-05-12 |
| EP2276730A2 (en) | 2011-01-26 |
| AR071386A1 (es) | 2010-06-16 |
| CA2721750A1 (en) | 2009-10-29 |
| US8828985B2 (en) | 2014-09-09 |
| JP5653907B2 (ja) | 2015-01-14 |
| JP2011518218A (ja) | 2011-06-23 |
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