JP2009504611A5 - - Google Patents
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- Publication number
- JP2009504611A5 JP2009504611A5 JP2008525574A JP2008525574A JP2009504611A5 JP 2009504611 A5 JP2009504611 A5 JP 2009504611A5 JP 2008525574 A JP2008525574 A JP 2008525574A JP 2008525574 A JP2008525574 A JP 2008525574A JP 2009504611 A5 JP2009504611 A5 JP 2009504611A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- cycloalkyl
- aryl
- heteroaryl
- heterocyclyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 229910052731 fluorine Inorganic materials 0.000 claims 46
- 229910052799 carbon Inorganic materials 0.000 claims 44
- 125000000623 heterocyclic group Chemical group 0.000 claims 42
- 239000011737 fluorine Substances 0.000 claims 39
- -1 diastereomers Chemical class 0.000 claims 38
- 125000001072 heteroaryl group Chemical group 0.000 claims 36
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 35
- 125000003118 aryl group Chemical group 0.000 claims 32
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 30
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 30
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 30
- 229910052794 bromium Inorganic materials 0.000 claims 30
- 229910052801 chlorine Inorganic materials 0.000 claims 30
- 239000000460 chlorine Substances 0.000 claims 30
- 150000001875 compounds Chemical class 0.000 claims 26
- 125000004093 cyano group Chemical group *C#N 0.000 claims 26
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 25
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 24
- 229910052739 hydrogen Inorganic materials 0.000 claims 21
- 239000001257 hydrogen Substances 0.000 claims 21
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 19
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 19
- 150000002431 hydrogen Chemical class 0.000 claims 16
- 125000004043 oxo group Chemical group O=* 0.000 claims 16
- 229910052717 sulfur Inorganic materials 0.000 claims 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 9
- 125000005842 heteroatom Chemical group 0.000 claims 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 7
- 125000001153 fluoro group Chemical group F* 0.000 claims 6
- 229910052757 nitrogen Inorganic materials 0.000 claims 6
- 229910052760 oxygen Inorganic materials 0.000 claims 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 3
- 239000000556 agonist Substances 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 3
- 125000004434 sulfur atom Chemical group 0.000 claims 3
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 claims 2
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 claims 2
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 claims 2
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 claims 2
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 claims 2
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 claims 2
- 239000002439 beta secretase inhibitor Substances 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 239000003112 inhibitor Substances 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 230000003551 muscarinic effect Effects 0.000 claims 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 claims 1
- 229940124801 5-HT6 antagonist Drugs 0.000 claims 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 1
- 229940082496 Adrenoreceptor antagonist Drugs 0.000 claims 1
- 229940124638 COX inhibitor Drugs 0.000 claims 1
- 102000018997 Growth Hormone Human genes 0.000 claims 1
- 108010051696 Growth Hormone Proteins 0.000 claims 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims 1
- 229940127523 NMDA Receptor Antagonists Drugs 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 238000004220 aggregation Methods 0.000 claims 1
- 230000002776 aggregation Effects 0.000 claims 1
- 230000006933 amyloid-beta aggregation Effects 0.000 claims 1
- 239000003242 anti bacterial agent Substances 0.000 claims 1
- 229940088710 antibiotic agent Drugs 0.000 claims 1
- 239000003963 antioxidant agent Substances 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000000544 cholinesterase inhibitor Substances 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims 1
- 239000003540 gamma secretase inhibitor Substances 0.000 claims 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims 1
- 229930195712 glutamate Natural products 0.000 claims 1
- 239000000122 growth hormone Substances 0.000 claims 1
- 239000003395 histamine H3 receptor antagonist Substances 0.000 claims 1
- 150000004677 hydrates Chemical class 0.000 claims 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000001067 neuroprotector Effects 0.000 claims 1
- 239000002858 neurotransmitter agent Substances 0.000 claims 1
- 239000000181 nicotinic agonist Substances 0.000 claims 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims 1
- 239000004031 partial agonist Substances 0.000 claims 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 229940044551 receptor antagonist Drugs 0.000 claims 1
- 239000002464 receptor antagonist Substances 0.000 claims 1
- 239000002469 receptor inverse agonist Substances 0.000 claims 1
- 102000005962 receptors Human genes 0.000 claims 1
- 108020003175 receptors Proteins 0.000 claims 1
- 230000028327 secretion Effects 0.000 claims 1
- 239000000387 serotonin 5-HT4 receptor agonist Substances 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
- 0 *C1C=CCC1 Chemical compound *C1C=CCC1 0.000 description 2
- RKIWYNBHJZIEJD-UHFFFAOYSA-N NN(CCCC1)S1(=O)=O Chemical compound NN(CCCC1)S1(=O)=O RKIWYNBHJZIEJD-UHFFFAOYSA-N 0.000 description 1
- MRBTUVJGLDSLEC-UHFFFAOYSA-N NN(CCCN1)S1(=O)=O Chemical compound NN(CCCN1)S1(=O)=O MRBTUVJGLDSLEC-UHFFFAOYSA-N 0.000 description 1
- PISNODKEJUFUNQ-UHFFFAOYSA-N NN(CCCO1)C1=O Chemical compound NN(CCCO1)C1=O PISNODKEJUFUNQ-UHFFFAOYSA-N 0.000 description 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05017477 | 2005-08-11 | ||
| PCT/EP2006/065151 WO2007017507A1 (de) | 2005-08-11 | 2006-08-08 | Inhibitoren der beta-sekretase zur behandlung der alzheimer- erkrankung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009504611A JP2009504611A (ja) | 2009-02-05 |
| JP2009504611A5 true JP2009504611A5 (enExample) | 2009-09-24 |
Family
ID=37102603
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008525574A Pending JP2009504611A (ja) | 2005-08-11 | 2006-08-08 | アルツハイマー病の治療用β−セクレターゼインヒビター |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20100298278A1 (enExample) |
| EP (1) | EP1915339A1 (enExample) |
| JP (1) | JP2009504611A (enExample) |
| CA (1) | CA2618013A1 (enExample) |
| WO (1) | WO2007017507A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7763609B2 (en) | 2003-12-15 | 2010-07-27 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| EP1919861A2 (de) * | 2005-08-11 | 2008-05-14 | Boehringer Ingelheim International GmbH | Verbindungen zur behandlung der alzheimer erkrankung |
| CA2618474A1 (en) * | 2005-08-11 | 2007-02-15 | Boehringer Ingelheim International Gmbh | Compounds for treating alzheimer's disease |
| RU2012129168A (ru) * | 2009-12-11 | 2014-01-20 | Сионоги Энд Ко. Лтд. | Производные оксазина |
| EP2578212B1 (en) | 2010-05-24 | 2016-07-06 | Farmalider, S.A. | Compound inhibiting activation of the enzyme erk1/2 for use in the treatment of neurogenerative illnesses |
| US20120053200A1 (en) * | 2010-09-01 | 2012-03-01 | Harald Mauser | Bace 2 inhibitors |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06507782A (ja) * | 1990-06-15 | 1994-09-08 | サイオス ノバ インコーポレイテッド | アルツハイマー病のアミロイド形成開症状を示すヒト以外の組換え哺乳動物 |
| AU652997B2 (en) * | 1991-01-21 | 1994-09-15 | Elan Pharmaceuticals, Inc. | Test and model for alzheimer's disease |
| DE69233109T2 (de) * | 1992-01-07 | 2004-05-19 | Elan Pharmaceuticals, Inc., San Francisco | Transgene tiermodelle fur alzheimer-krankheit |
| US5604102A (en) * | 1992-04-15 | 1997-02-18 | Athena Neurosciences, Inc. | Methods of screening for β-amyloid peptide production inhibitors |
| AU702293B2 (en) * | 1993-10-27 | 1999-02-18 | Athena Neurosciences, Inc. | Transgenic animals harboring APP allele having Swedish mutation |
| US5877399A (en) * | 1994-01-27 | 1999-03-02 | Johns Hopkins University | Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease |
| US5744346A (en) * | 1995-06-07 | 1998-04-28 | Athena Neurosciences, Inc. | β-secretase |
| JPH11507538A (ja) * | 1995-06-07 | 1999-07-06 | アテナ ニューロサイエンシズ インコーポレイティド | β−セクレターゼ、β−セクレターゼに対する抗体、及びβ−セクレターゼ阻害を検出するためのアッセイ |
| EP1453516A2 (de) * | 2001-10-17 | 2004-09-08 | Boehringer Ingelheim Pharma GmbH & Co.KG | 5-substituierte 4-amino-2-phenylamino-pyrimdinderivate und ihre verwendung als beta-amyloid modulatoren |
| AU2003206413A1 (en) * | 2002-01-04 | 2003-07-24 | Elan Pharmaceuticals, Inc. | Substituted amino carboxamides for the treatment of alzheimer's disease |
| US20050090449A1 (en) * | 2003-05-13 | 2005-04-28 | Boehringer Ingelheim International Gmbh | Novel statine derivatives for the treatment of Alzheimer's disease |
| JP2007516207A (ja) * | 2003-06-30 | 2007-06-21 | メルク エンド カムパニー インコーポレーテッド | アルツハイマー病の治療のためのＮ−アルキルフェニルカルボキサミドβ−セクレターゼ阻害剤 |
| EP1750719A2 (en) * | 2004-05-19 | 2007-02-14 | Boehringer Ingelheim International GmbH | Treatment of diseases associated with altered level of amyloid beta peptides |
| WO2005113582A1 (en) * | 2004-05-22 | 2005-12-01 | Boehringer Ingelheim International Gmbh | Substituted ethane-1,2-diamines for the treatment of alzheimer's disease |
| WO2006050861A2 (en) * | 2004-11-10 | 2006-05-18 | Boehringer Ingelheim International Gmbh | Statine derivatives for the treatment of alzheimer's disease |
| WO2006050862A1 (en) * | 2004-11-10 | 2006-05-18 | Boehringer Ingelheim International Gmbh | Statine derivatives for the treatment of alzheimer's disease |
| CA2603404A1 (en) * | 2005-03-30 | 2006-10-05 | Boehringer Ingelheim International Gmbh | Substituted 1,2-ethylendiamines, medicaments comprising said compound; their use and their method of manufacture |
| JP2009503027A (ja) * | 2005-08-03 | 2009-01-29 | 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 | アルツハイマー病ｉｉの治療のための置換エタン−１，２−ジアミン |
| US20090042867A1 (en) * | 2005-08-11 | 2009-02-12 | Klaus Fuchs | Compounds for the treatment of alzheimer's disease |
-
2006
- 2006-08-08 EP EP06792734A patent/EP1915339A1/de not_active Withdrawn
- 2006-08-08 CA CA002618013A patent/CA2618013A1/en not_active Abandoned
- 2006-08-08 WO PCT/EP2006/065151 patent/WO2007017507A1/de not_active Ceased
- 2006-08-08 US US12/063,270 patent/US20100298278A1/en not_active Abandoned
- 2006-08-08 JP JP2008525574A patent/JP2009504611A/ja active Pending