CA2694209C - Azepine derivatives as gamma-secretase inhibitors - Google Patents
Azepine derivatives as gamma-secretase inhibitors Download PDFInfo
- Publication number
- CA2694209C CA2694209C CA2694209A CA2694209A CA2694209C CA 2694209 C CA2694209 C CA 2694209C CA 2694209 A CA2694209 A CA 2694209A CA 2694209 A CA2694209 A CA 2694209A CA 2694209 C CA2694209 C CA 2694209C
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- compound
- phenyl
- compounds
- azepin
- 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.)
- Expired - Fee Related
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- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 150000005181 nitrobenzenes Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
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- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 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
- 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
- 239000000523 sample Substances 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
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
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- 239000011343 solid material Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
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- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
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- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 238000002560 therapeutic procedure Methods 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
- 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
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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 |
|---|---|---|---|
| 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 (2)
| Publication Number | Publication Date |
|---|---|
| CA2694209A1 CA2694209A1 (en) | 2009-02-19 |
| CA2694209C true CA2694209C (en) | 2013-09-17 |
Family
ID=39811736
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2694209A Expired - Fee Related CA2694209C (en) | 2007-08-14 | 2008-08-04 | Azepine derivatives as gamma-secretase inhibitors |
Country Status (11)
| Country | Link |
|---|---|
| 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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| CA2669693C (en) | 2006-11-15 | 2018-06-12 | Massachusetts Eye & Ear Infirmary | Generation of inner ear cells |
| 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 |
| WO2013036679A1 (en) * | 2011-09-07 | 2013-03-14 | Satori Pharmaceuticals, Inc. | Compounds useful for treating neurodegenerative disorders |
| CA2884309A1 (en) | 2012-09-07 | 2014-03-13 | Massachusetts Eye And Ear Infirmary | Methods and compositions for regenerating hair cells and/or supporting cells from differentiated cochlear cells or differentiated utricular cells by modulation of notch and cmyc activity |
| HK1211875A1 (en) | 2012-09-07 | 2016-06-03 | Massachusetts Eye & Ear Infirmary | Treating hearing loss |
| CN104822677A (zh) | 2012-09-21 | 2015-08-05 | 百时美施贵宝公司 | 氟烷基-1,4-苯并二氮杂*酮化合物 |
| 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 |
| 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 |
| US9249157B2 (en) | 2012-09-21 | 2016-02-02 | Bristol-Myers Squibb Company | Tricyclic heterocycle compounds |
| WO2014047397A1 (en) | 2012-09-21 | 2014-03-27 | Bristol-Myers Squibb Company | Fluoroalkyl and fluorocycloalkyl 1,4-benzodiazepinone compounds as notch|inhibitors |
| US9242940B2 (en) | 2012-09-21 | 2016-01-26 | Bristol-Myers Squibb Company | N-substituted bis(fluoroalkyl)-1,4-benzodiazepinone compounds |
| US9273075B2 (en) | 2012-09-21 | 2016-03-01 | Bristol-Myers Squibb Company | Prodrugs of 1,4-benzodiazepinone 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 |
| CN105308030A (zh) | 2012-09-21 | 2016-02-03 | 百时美施贵宝公司 | 烷基、氟烷基-1,4-苯并二氮杂*酮化合物 |
| JP2016515625A (ja) | 2013-04-04 | 2016-05-30 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 増殖性疾患を治療するための併用療法 |
| WO2015073524A1 (en) * | 2013-11-12 | 2015-05-21 | Drexel University | Novel methods of treating or preventing alzheimer's disease |
| US20170314027A1 (en) | 2014-08-06 | 2017-11-02 | Massachusetts Eye And Ear Infirmary | Increasing atoh1 life to drive sensorineural hair cell differentiantion |
| WO2016069906A1 (en) | 2014-10-29 | 2016-05-06 | 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 |
| KR20180117628A (ko) | 2016-01-29 | 2018-10-29 | 매사추세츠 아이 앤드 이어 인퍼머리 | 내이 지지 세포의 확장 및 분화 및 그의 사용 방법 |
| 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 |
| WO2017180389A1 (en) | 2016-04-12 | 2017-10-19 | Eli Lilly And Company | Combination therapy with notch and cdk4/6 inhibitors for the treatment of cancer |
| KR102362222B1 (ko) | 2016-05-16 | 2022-02-11 | 더 제너럴 하스피탈 코포레이션 | 폐 상피 공학에서 인간 기도 줄기 세포 |
| 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 |
| BR112019017120A8 (pt) | 2017-02-17 | 2023-05-02 | Hutchinson Fred Cancer Res | Terapias de combinação para tratamento de cânceres e distúrbios autoimunes relacionados a bcma |
| 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 |
| EP3615068A1 (en) | 2017-04-28 | 2020-03-04 | Novartis AG | Bcma-targeting agent, 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 |
| US11492409B2 (en) | 2018-06-01 | 2022-11-08 | Novartis Ag | Binding molecules against BCMA and uses thereof |
| WO2020261093A1 (en) | 2019-06-24 | 2020-12-30 | Novartis Ag | Dosing regimen and combination therapies for multispecific antibodies targeting b-cell maturation antigen |
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| DE69739236D1 (de) * | 1996-12-23 | 2009-03-12 | Lilly Co Eli | Cycloalkyl-, lactam-, lacton- und verwandte verbindungen als hemmer der beta-amyloidpeptidfreisetzung |
| US7468365B2 (en) * | 2000-11-17 | 2008-12-23 | Eli Lilly And Company | Lactam compound |
| UA74849C2 (en) | 2000-11-17 | 2006-02-15 | Lilly Co Eli | Lactam |
| 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 |
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2008
- 2008-08-04 US US12/669,048 patent/US8188069B2/en not_active Expired - Fee Related
- 2008-08-04 CN CN2008801030083A patent/CN101778826B/zh not_active Expired - Fee Related
- 2008-08-04 MX MX2010001754A patent/MX2010001754A/es active IP Right Grant
- 2008-08-04 BR BRPI0815135-0A2A patent/BRPI0815135A2/pt not_active IP Right Cessation
- 2008-08-04 JP JP2010521080A patent/JP5385904B2/ja not_active Expired - Fee Related
- 2008-08-04 EA EA201070278A patent/EA017286B1/ru not_active IP Right Cessation
- 2008-08-04 EP EP08827545A patent/EP2178844A1/en not_active Withdrawn
- 2008-08-04 CA CA2694209A patent/CA2694209C/en not_active Expired - Fee Related
- 2008-08-04 AU AU2008287124A patent/AU2008287124B2/en not_active Ceased
- 2008-08-04 WO PCT/US2008/072049 patent/WO2009023453A1/en not_active Ceased
- 2008-08-04 KR KR1020107002906A patent/KR101136260B1/ko not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP2178844A1 (en) | 2010-04-28 |
| JP5385904B2 (ja) | 2014-01-08 |
| AU2008287124B2 (en) | 2013-06-06 |
| US8188069B2 (en) | 2012-05-29 |
| JP2010536766A (ja) | 2010-12-02 |
| EA017286B1 (ru) | 2012-11-30 |
| CN101778826B (zh) | 2012-10-31 |
| CN101778826A (zh) | 2010-07-14 |
| EA201070278A1 (ru) | 2010-06-30 |
| US20100197660A1 (en) | 2010-08-05 |
| WO2009023453A1 (en) | 2009-02-19 |
| MX2010001754A (es) | 2010-05-14 |
| KR101136260B1 (ko) | 2012-04-19 |
| BRPI0815135A2 (pt) | 2015-02-03 |
| CA2694209A1 (en) | 2009-02-19 |
| AU2008287124A1 (en) | 2009-02-19 |
| KR20100032924A (ko) | 2010-03-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20150804 |