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)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| 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 (enExample) | 2011-09-22 |
| JP5385904B2 true JP5385904B2 (ja) | 2014-01-08 |
Family
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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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| EP (1) | EP2178844A1 (enExample) |
| JP (1) | JP5385904B2 (enExample) |
| KR (1) | KR101136260B1 (enExample) |
| CN (1) | CN101778826B (enExample) |
| AU (1) | AU2008287124B2 (enExample) |
| BR (1) | BRPI0815135A2 (enExample) |
| CA (1) | CA2694209C (enExample) |
| EA (1) | EA017286B1 (enExample) |
| MX (1) | MX2010001754A (enExample) |
| WO (1) | WO2009023453A1 (enExample) |
Families Citing this family (34)
| 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 |
| EP2381936B2 (en) | 2008-11-24 | 2020-02-12 | Massachusetts Eye & Ear Infirmary | Pathways to generate auditory 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 |
| AU2013312305B2 (en) | 2012-09-07 | 2018-06-28 | Massachusetts Eye And Ear Infirmary | Methods and compositions for regenerating hair cells and/or supporting cells |
| HK1211875A1 (en) | 2012-09-07 | 2016-06-03 | Massachusetts Eye & Ear Infirmary | Treating hearing loss |
| 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 |
| WO2014047391A1 (en) | 2012-09-21 | 2014-03-27 | Bristol-Myers Squibb Company | Prodrugs of 1,4-benzodiazepinone compounds |
| EP2897954B1 (en) | 2012-09-21 | 2016-10-26 | Bristol-Myers Squibb Company | Fluoroalkyl-1,4-benzodiazepinone compounds |
| CN104797569A (zh) | 2012-09-21 | 2015-07-22 | 百时美施贵宝公司 | 取代的1,5-苯并二氮杂*酮化合物 |
| EP2897946B1 (en) | 2012-09-21 | 2016-11-16 | Bristol-Myers Squibb Company | N-substituted bis(fluoroalkkyl)-1,4-benzodiazepinone compounds as notch inhibitors |
| EP2897960B1 (en) | 2012-09-21 | 2016-08-03 | Bristol-Myers Squibb Company | Tricyclic heterocyclic compounds as notch inhibitors |
| CN104854094A (zh) | 2012-09-21 | 2015-08-19 | 百时美施贵宝公司 | 氟烷基二苯并二氮杂*酮化合物 |
| WO2014047374A1 (en) | 2012-09-21 | 2014-03-27 | Bristol-Myers Squibb Company | Alkyl, fluoroalkyl-1,4-benzodiazepinone compounds |
| US9427442B2 (en) | 2012-09-21 | 2016-08-30 | Bristol-Myers Squibb Company | Fluoroalkyl and fluorocycloalkyl 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 |
| US11370823B2 (en) | 2014-10-29 | 2022-06-28 | Massachusetts Eye And Ear Infirmary | Efficient delivery of therapeutic molecules to cells of the inner ear |
| US11185536B2 (en) | 2015-12-04 | 2021-11-30 | 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 |
| WO2017180385A1 (en) | 2016-04-12 | 2017-10-19 | Eli Lilly And Company | Combination therapy with notch and pi3k/mtor inhibitors for use in treating cancer |
| MX380779B (es) | 2016-04-12 | 2025-03-12 | Lilly Co Eli | Terapia combinatoria con inhibidores notch y cdk4/6 |
| AU2017268078B2 (en) | 2016-05-16 | 2023-03-02 | The General Hospital Corporation | Human airway stem cells in lung epithelial engineering |
| JP7194022B2 (ja) | 2016-05-20 | 2022-12-21 | イーライ リリー アンド カンパニー | Ｎｏｔｃｈ阻害剤とＰＤ－１またはＰＤ－Ｌ１阻害剤との併用療法 |
| EP3525796A1 (en) | 2016-10-12 | 2019-08-21 | Eli Lilly and Company | Targeted treatment of mature t-cell lymphoma |
| AU2017376109A1 (en) | 2016-12-16 | 2019-07-11 | Pipeline Therapeutics, Inc. | Methods of treating cochlear synaptopathy |
| AU2018222749B2 (en) | 2017-02-17 | 2024-04-18 | Fred Hutchinson Cancer Center | Combination therapies for treatment of BCMA-related cancers and autoimmune disorders |
| EP3615068A1 (en) | 2017-04-28 | 2020-03-04 | Novartis AG | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
| US20200055948A1 (en) | 2017-04-28 | 2020-02-20 | Novartis Ag | Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor |
| MA50564A (fr) | 2017-11-06 | 2020-09-16 | Hutchinson Fred Cancer Res | Association d'une thérapie cellulaire et d'un inhibiteur de gamma secrétase |
| WO2019148067A1 (en) | 2018-01-26 | 2019-08-01 | Massachusetts Eye And Ear Infirmary | Treatment of hearing loss |
| UY38251A (es) | 2018-06-01 | 2019-12-31 | Novartis Ag | Moléculas de unión contra bcma y usos de las mismas |
| WO2020261093A1 (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)
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| HUP0001232A3 (en) * | 1996-12-23 | 2001-02-28 | Elan Pharmaceuticals Inc San F | Cycloalkyl, lactam, lactone derivatives and their thio analogues inhibiting betha-amyloid peptide release and/or its synthesis and pharmaceutical compositions containing the compounds |
| 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 |
| EP1636196A1 (en) * | 2003-03-14 | 2006-03-22 | AstraZeneca AB | Novel lactams and uses thereof |
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2008
- 2008-08-04 EP EP08827545A patent/EP2178844A1/en not_active Withdrawn
- 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
- 2008-08-04 US US12/669,048 patent/US8188069B2/en not_active Expired - Fee Related
- 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 MX MX2010001754A patent/MX2010001754A/es active IP Right Grant
- 2008-08-04 CA CA2694209A patent/CA2694209C/en not_active Expired - Fee Related
- 2008-08-04 BR BRPI0815135-0A2A patent/BRPI0815135A2/pt not_active IP Right Cessation
- 2008-08-04 KR KR1020107002906A patent/KR101136260B1/ko not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20100197660A1 (en) | 2010-08-05 |
| BRPI0815135A2 (pt) | 2015-02-03 |
| US8188069B2 (en) | 2012-05-29 |
| EA201070278A1 (ru) | 2010-06-30 |
| WO2009023453A1 (en) | 2009-02-19 |
| KR101136260B1 (ko) | 2012-04-19 |
| CA2694209C (en) | 2013-09-17 |
| CN101778826A (zh) | 2010-07-14 |
| CA2694209A1 (en) | 2009-02-19 |
| AU2008287124B2 (en) | 2013-06-06 |
| KR20100032924A (ko) | 2010-03-26 |
| EA017286B1 (ru) | 2012-11-30 |
| JP2010536766A (ja) | 2010-12-02 |
| EP2178844A1 (en) | 2010-04-28 |
| MX2010001754A (es) | 2010-05-14 |
| AU2008287124A1 (en) | 2009-02-19 |
| CN101778826B (zh) | 2012-10-31 |
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