JP5385904B2 - γ−セクレターゼ阻害剤 - Google Patents
γ−セクレターゼ阻害剤 Download PDFInfo
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- JP5385904B2 JP5385904B2 JP2010521080A JP2010521080A JP5385904B2 JP 5385904 B2 JP5385904 B2 JP 5385904B2 JP 2010521080 A JP2010521080 A JP 2010521080A JP 2010521080 A JP2010521080 A JP 2010521080A JP 5385904 B2 JP5385904 B2 JP 5385904B2
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- Prior art keywords
- compound
- amyloid
- methyl
- added
- solution
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- 229940069328 povidone Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- PAQZWJGSJMLPMG-UHFFFAOYSA-N propylphosphonic anhydride Substances CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 231100000212 subchronic toxicity study Toxicity 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CRJXCNMGTGXBEP-MBIQTGHCSA-N tert-butyl n-[(2s)-1-[(1-methyl-2-oxo-5-phenyl-3h-azepin-3-yl)amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CN(C)C(=O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)C)C=C1C1=CC=CC=C1 CRJXCNMGTGXBEP-MBIQTGHCSA-N 0.000 description 1
- 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
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 239000003656 tris buffered saline Substances 0.000 description 1
- 229960001005 tuberculin Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000004246 zinc acetate Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/12—Nitrogen atoms not forming part of a nitro radical
-
- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US95572007P | 2007-08-14 | 2007-08-14 | |
| US60/955,720 | 2007-08-14 | ||
| PCT/US2008/072049 WO2009023453A1 (en) | 2007-08-14 | 2008-08-04 | Azepine derivatives as gamma-secretase inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010536766A JP2010536766A (ja) | 2010-12-02 |
| JP2010536766A5 JP2010536766A5 (OSRAM) | 2011-09-22 |
| JP5385904B2 true JP5385904B2 (ja) | 2014-01-08 |
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| JP2010521080A Expired - Fee Related JP5385904B2 (ja) | 2007-08-14 | 2008-08-04 | γ−セクレターゼ阻害剤 |
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| US (1) | US8188069B2 (OSRAM) |
| EP (1) | EP2178844A1 (OSRAM) |
| JP (1) | JP5385904B2 (OSRAM) |
| KR (1) | KR101136260B1 (OSRAM) |
| CN (1) | CN101778826B (OSRAM) |
| AU (1) | AU2008287124B2 (OSRAM) |
| BR (1) | BRPI0815135A2 (OSRAM) |
| CA (1) | CA2694209C (OSRAM) |
| EA (1) | EA017286B1 (OSRAM) |
| MX (1) | MX2010001754A (OSRAM) |
| WO (1) | WO2009023453A1 (OSRAM) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2010509919A (ja) | 2006-11-15 | 2010-04-02 | マサチューセッツ・アイ・アンド・イア・インファーマリー | 内耳細胞の生成 |
| CA2743436C (en) | 2008-11-24 | 2017-10-31 | Massachusetts Eye & Ear Infirmary | Pathways to generate hair cells |
| TWI530489B (zh) | 2011-03-22 | 2016-04-21 | 必治妥美雅史谷比公司 | 雙（氟烷基）－１，４－苯二氮呯酮化合物 |
| US20130060023A1 (en) * | 2011-09-07 | 2013-03-07 | Satori Pharmaceuticals, Inc. | Compounds useful for treating neurodegenerative disorders |
| JP6486272B2 (ja) | 2012-09-07 | 2019-03-20 | マサチューセッツ・アイ・アンド・イア・インファーマリー | 有毛細胞および／または支持細胞再生のための方法および組成物 |
| EP3970725B1 (en) | 2012-09-07 | 2025-08-20 | Massachusetts Eye & Ear Infirmary | A gamma secretase inhibitor for treating hearing loss |
| US9242940B2 (en) | 2012-09-21 | 2016-01-26 | Bristol-Myers Squibb Company | N-substituted bis(fluoroalkyl)-1,4-benzodiazepinone compounds |
| EP2897954B1 (en) | 2012-09-21 | 2016-10-26 | Bristol-Myers Squibb Company | Fluoroalkyl-1,4-benzodiazepinone compounds |
| JP2015534553A (ja) | 2012-09-21 | 2015-12-03 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 置換１，５−ベンゾジアゼピノン化合物 |
| EP2897941B1 (en) | 2012-09-21 | 2016-09-07 | Bristol-Myers Squibb Company | Prodrugs of 1,4-benzodiazepinone compounds |
| EP2897938B1 (en) | 2012-09-21 | 2017-03-15 | Bristol-Myers Squibb Company | Fluoroalkyl dibenzodiazepinone compounds |
| TWI614238B (zh) | 2012-09-21 | 2018-02-11 | 必治妥美雅史谷比公司 | 雙（氟烷基）－１，４－苯并二氮呯酮化合物及其前藥 |
| CN104797584A (zh) | 2012-09-21 | 2015-07-22 | 百时美施贵宝公司 | 作为notch抑制剂的三环杂环化合物 |
| WO2014047397A1 (en) | 2012-09-21 | 2014-03-27 | Bristol-Myers Squibb Company | Fluoroalkyl and fluorocycloalkyl 1,4-benzodiazepinone compounds as notch|inhibitors |
| WO2014047374A1 (en) | 2012-09-21 | 2014-03-27 | Bristol-Myers Squibb Company | Alkyl, fluoroalkyl-1,4-benzodiazepinone compounds |
| CN105101968A (zh) | 2013-04-04 | 2015-11-25 | 百时美施贵宝公司 | 治疗增殖性疾病的组合疗法 |
| WO2015073524A1 (en) * | 2013-11-12 | 2015-05-21 | Drexel University | Novel methods of treating or preventing alzheimer's disease |
| WO2016022776A2 (en) | 2014-08-06 | 2016-02-11 | Massachusetts Eye And Ear Infirmary | Increasing atoh1 life to drive sensorineural hair cell differentiantion |
| EP3212773B1 (en) | 2014-10-29 | 2021-09-15 | Massachusetts Eye and Ear Infirmary | Efficient delivery of therapeutic molecules to cells of the inner ear |
| WO2017096233A1 (en) | 2015-12-04 | 2017-06-08 | Massachusetts Eye And Ear Infirmary | Treatment of hearing loss by inhibition of casein kinase 1 |
| AU2017212655B2 (en) | 2016-01-29 | 2024-01-18 | Decibel Therapeutics, Inc. | Expansion and differentiation of inner ear supporting cells and methods of use thereof |
| RU2754452C2 (ru) | 2016-04-12 | 2021-09-02 | Эли Лилли Энд Компани | Комбинированная терапия ингибиторами notch и pi3k/mtor для применения в лечении рака |
| ES2881801T3 (es) | 2016-04-12 | 2021-11-30 | Lilly Co Eli | Terapia de combinación con inhibidores de Notch y CDK4/6 para su uso en el tratamiento de cáncer de pulmón |
| EP3458076A4 (en) | 2016-05-16 | 2020-01-22 | The General Hospital Corporation | HUMAN RESPIRATORY STEM CELLS IN BREEDING LUNG EPITHEL |
| KR102463617B1 (ko) | 2016-05-20 | 2022-11-03 | 일라이 릴리 앤드 캄파니 | Notch 및 PD-1 또는 PD-L1 억제제를 이용한 조합 요법 |
| EP3525796A1 (en) | 2016-10-12 | 2019-08-21 | Eli Lilly and Company | Targeted treatment of mature t-cell lymphoma |
| JP6904612B2 (ja) | 2016-12-16 | 2021-07-21 | パイプライン セラピューティクス， インコーポレイテッド | 蝸牛シナプス障害を処置する方法 |
| SG11201907580SA (en) | 2017-02-17 | 2019-09-27 | Hutchinson Fred Cancer Res | Combination therapies for treatment of bcma-related cancers and autoimmune disorders |
| WO2018201051A1 (en) | 2017-04-28 | 2018-11-01 | Novartis Ag | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
| EP3615055A1 (en) | 2017-04-28 | 2020-03-04 | Novartis AG | Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor |
| AU2018359907A1 (en) | 2017-11-06 | 2020-05-07 | Fred Hutchinson Cancer Center | Combination of a cell therapy and a gamma secretase inhibitor |
| US11590152B2 (en) | 2018-01-26 | 2023-02-28 | Massachusetts Eye And Ear Infirmary | Treatment of hearing loss |
| TWI848951B (zh) | 2018-06-01 | 2024-07-21 | 瑞士商諾華公司 | 針對ｂｃｍａ之結合分子及其用途 |
| CA3144324A1 (en) | 2019-06-24 | 2020-12-30 | Novartis Ag | Dosing regimen and combination therapies for multispecific antibodies targeting b-cell maturation antigen |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2272305A1 (en) * | 1996-12-23 | 1998-07-02 | Elan Pharmaceuticals, Inc. | Cycloalkyl, lactam, lactone and related compounds as .beta.-amyloid peptide release inhibitors |
| UA74849C2 (en) | 2000-11-17 | 2006-02-15 | Lilly Co Eli | Lactam |
| US7468365B2 (en) * | 2000-11-17 | 2008-12-23 | Eli Lilly And Company | Lactam compound |
| TW200502221A (en) * | 2002-10-03 | 2005-01-16 | Astrazeneca Ab | Novel lactams and uses thereof |
| US7342007B2 (en) * | 2003-03-14 | 2008-03-11 | Astrazeneca Ab | Lactams and uses thereof |
-
2008
- 2008-08-04 CA CA2694209A patent/CA2694209C/en not_active Expired - Fee Related
- 2008-08-04 MX MX2010001754A patent/MX2010001754A/es active IP Right Grant
- 2008-08-04 KR KR1020107002906A patent/KR101136260B1/ko not_active Expired - Fee Related
- 2008-08-04 US US12/669,048 patent/US8188069B2/en not_active Expired - Fee Related
- 2008-08-04 EP EP08827545A patent/EP2178844A1/en not_active Withdrawn
- 2008-08-04 JP JP2010521080A patent/JP5385904B2/ja not_active Expired - Fee Related
- 2008-08-04 WO PCT/US2008/072049 patent/WO2009023453A1/en not_active Ceased
- 2008-08-04 BR BRPI0815135-0A2A patent/BRPI0815135A2/pt not_active IP Right Cessation
- 2008-08-04 CN CN2008801030083A patent/CN101778826B/zh not_active Expired - Fee Related
- 2008-08-04 AU AU2008287124A patent/AU2008287124B2/en not_active Ceased
- 2008-08-04 EA EA201070278A patent/EA017286B1/ru not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| US8188069B2 (en) | 2012-05-29 |
| CN101778826B (zh) | 2012-10-31 |
| KR101136260B1 (ko) | 2012-04-19 |
| EP2178844A1 (en) | 2010-04-28 |
| AU2008287124B2 (en) | 2013-06-06 |
| EA017286B1 (ru) | 2012-11-30 |
| US20100197660A1 (en) | 2010-08-05 |
| CN101778826A (zh) | 2010-07-14 |
| JP2010536766A (ja) | 2010-12-02 |
| KR20100032924A (ko) | 2010-03-26 |
| EA201070278A1 (ru) | 2010-06-30 |
| AU2008287124A1 (en) | 2009-02-19 |
| CA2694209A1 (en) | 2009-02-19 |
| CA2694209C (en) | 2013-09-17 |
| WO2009023453A1 (en) | 2009-02-19 |
| MX2010001754A (es) | 2010-05-14 |
| BRPI0815135A2 (pt) | 2015-02-03 |
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