JP4116437B2 - β−アミロイドペプチドの放出および／または合成を阻害するラクタム化合物 - Google Patents

β−アミロイドペプチドの放出および／または合成を阻害するラクタム化合物 Download PDF

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Publication number
JP4116437B2
JP4116437B2 JP2002549245A JP2002549245A JP4116437B2 JP 4116437 B2 JP4116437 B2 JP 4116437B2 JP 2002549245 A JP2002549245 A JP 2002549245A JP 2002549245 A JP2002549245 A JP 2002549245A JP 4116437 B2 JP4116437 B2 JP 4116437B2
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methyl
tetrahydro
amino
reaction
formula
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Expired - Fee Related
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Japanese (ja)
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JP2004517090A (ja
JP2004517090A5 (cg-RX-API-DMAC10.html
Inventor
ジェイムズ・エドモンド・オーディア
バーゲス・ジョン
リー・エイチ・ラティマー
ステイシー・リー・マクダニエル
ジェフリー・スコット・ニッセン
ユージーン・ディ・ソーセット
ジェイ・エス・トゥン
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イーライ リリー アンド カンパニー
エラン ファーマシューティカルズ，インコーポレイテッド
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    • 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
    • C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D223/16—Benzazepines; Hydrogenated benzazepines
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Hydrogenated Pyridines (AREA)
  • Medicinal Preparation (AREA)
JP2002549245A 2000-11-17 2001-11-05 β−アミロイドペプチドの放出および／または合成を阻害するラクタム化合物 Expired - Fee Related JP4116437B2 (ja)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US24955200P 2000-11-17 2000-11-17
PCT/US2001/027799 WO2002047671A2 (en) 2000-11-17 2001-11-05 Lactam compound to inhibit beta-amyloid peptide release or synthesis

Publications (3)

Publication Number Publication Date
JP2004517090A JP2004517090A (ja) 2004-06-10
JP2004517090A5 JP2004517090A5 (cg-RX-API-DMAC10.html) 2006-08-17
JP4116437B2 true JP4116437B2 (ja) 2008-07-09

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JP2002549245A Expired - Fee Related JP4116437B2 (ja) 2000-11-17 2001-11-05 β−アミロイドペプチドの放出および／または合成を阻害するラクタム化合物

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US (1) US20050261495A1 (cg-RX-API-DMAC10.html)
EP (1) EP1341531B1 (cg-RX-API-DMAC10.html)
JP (1) JP4116437B2 (cg-RX-API-DMAC10.html)
KR (1) KR100819679B1 (cg-RX-API-DMAC10.html)
CN (1) CN1486184A (cg-RX-API-DMAC10.html)
AR (1) AR035927A1 (cg-RX-API-DMAC10.html)
AU (2) AU2002243192B2 (cg-RX-API-DMAC10.html)
BR (1) BR0115427A (cg-RX-API-DMAC10.html)
CA (1) CA2427227C (cg-RX-API-DMAC10.html)
CY (1) CY1106366T1 (cg-RX-API-DMAC10.html)
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DE (1) DE60126132T2 (cg-RX-API-DMAC10.html)
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EC (1) ECSP034600A (cg-RX-API-DMAC10.html)
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HR (1) HRP20030383B1 (cg-RX-API-DMAC10.html)
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SI (1) SI1341531T1 (cg-RX-API-DMAC10.html)
SK (1) SK288065B6 (cg-RX-API-DMAC10.html)
TW (1) TWI305204B (cg-RX-API-DMAC10.html)
UA (1) UA74849C2 (cg-RX-API-DMAC10.html)
WO (1) WO2002047671A2 (cg-RX-API-DMAC10.html)
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Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
CA2603320A1 (en) 2005-04-08 2006-10-19 Daiichi Sankyo Company, Limited Pyridylmethylsulfone derivative
ATE550019T1 (de) 2005-05-17 2012-04-15 Merck Sharp & Dohme Cis-4-ä(4-chlorophenyl)sulfonylü-4-(2,5- difluorophenyl)cyclohexanepropansäure zur behandlug von krebs
EP1985615A4 (en) 2006-01-31 2011-12-14 Api Corp PROCESS FOR THE PREPARATION OF BENZAZEPINONE
CA2676715A1 (en) 2007-02-12 2008-08-21 Merck & Co., Inc. Piperazine derivatives for treatment of ad and related conditions
CL2008002060A1 (es) * 2007-07-16 2008-11-21 Wyeth Corp Compuestos derivados de sulfonamida, inhibidores de la produccion de beta amiloide; metodo de preparacion; composicion farmaceutica; kit farmaceutico; y uso en el tratamiento de enfermedades tales como alzheimer, angiopatia amiloide, sindrome de down, entre otras.
KR101136260B1 (ko) 2007-08-14 2012-04-19 일라이 릴리 앤드 캄파니 감마-세크레타제 억제제로서의 아제핀 유도체
TW200920362A (en) 2007-09-11 2009-05-16 Daiichi Sankyo Co Ltd Alkylsulfone derivatives
CN101945853B (zh) 2007-12-21 2014-08-20 配体药物公司 选择性雄激素受体调节剂(sarm)及其应用
WO2009128057A2 (en) 2008-04-18 2009-10-22 UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN et al Psycho-pharmaceuticals
EP2413932A4 (en) 2009-04-01 2012-09-19 Merck Sharp & Dohme HAMMER OF ACT ACTIVITY
CA2777043C (en) 2009-10-14 2015-12-15 Schering Corporation Substituted piperidines that increase p53 activity and the uses thereof
EP2584903B1 (en) 2010-06-24 2018-10-24 Merck Sharp & Dohme Corp. Novel heterocyclic compounds as erk inhibitors
CN103068980B (zh) 2010-08-02 2017-04-05 瑟纳治疗公司 使用短干扰核酸（siNA）的RNA干扰介导的联蛋白（钙粘蛋白关联蛋白质），β1（CTNNB1）基因表达的抑制
RU2745848C2 (ru) 2010-08-17 2021-04-01 Сирна Терапьютикс, Инк. ОПОСРЕДУЕМОЕ РНК-ИНТЕРФЕРЕНЦИЕЙ ИНГИБИРОВАНИЕ ЭКСПРЕССИИ ГЕНОВ ВИРУСА ГЕПАТИТА B (HBV) С ПРИМЕНЕНИЕМ МАЛОЙ ИНТЕРФЕРИРУЮЩЕЙ НУКЛЕИНОВОЙ КИСЛОТЫ (миНК)
EP2613782B1 (en) 2010-09-01 2016-11-02 Merck Sharp & Dohme Corp. Indazole derivatives useful as erk inhibitors
US9242981B2 (en) 2010-09-16 2016-01-26 Merck Sharp & Dohme Corp. Fused pyrazole derivatives as novel ERK inhibitors
WO2012040444A2 (en) * 2010-09-24 2012-03-29 Bristol-Myers Squibb Company Treatment of patients with incipient alzheimer's disease
WO2012058210A1 (en) 2010-10-29 2012-05-03 Merck Sharp & Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACIDS (siNA)
WO2012087772A1 (en) 2010-12-21 2012-06-28 Schering Corporation Indazole derivatives useful as erk inhibitors
EP2770987B1 (en) 2011-10-27 2018-04-04 Merck Sharp & Dohme Corp. Novel compounds that are erk inhibitors
CN102690231B (zh) * 2012-04-11 2014-07-09 南京友杰医药科技有限公司 治疗阿尔茨海默病潜在药物司马西特的合成方法
EP3919620A1 (en) 2012-05-02 2021-12-08 Sirna Therapeutics, Inc. Short interfering nucleic acid (sina) compositions
EP2892506B1 (en) 2012-09-07 2021-11-03 Massachusetts Eye & Ear Infirmary Treating hearing loss with the gamma-secretase inhibitor ly411575
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
CA2882950A1 (en) 2012-09-28 2014-04-03 Merck Sharp & Dohme Corp. Novel compounds that are erk inhibitors
SMT201700595T1 (it) 2012-11-28 2018-03-08 Merck Sharp & Dohme Composizioni e metodi per trattare il cancro
WO2014100065A1 (en) 2012-12-20 2014-06-26 Merck Sharp & Dohme Corp. Substituted imidazopyridines as hdm2 inhibitors
WO2014120748A1 (en) 2013-01-30 2014-08-07 Merck Sharp & Dohme Corp. 2,6,7,8 substituted purines as hdm2 inhibitors
EP2987496B1 (en) 2013-04-19 2018-08-08 National University Corporation Okayama University Treatment agent for cognitive disorders, induced by amyloid -protein, therapeutic agent for alzheimer's disease, and treatment method and pathological analysis method related to these
WO2015034925A1 (en) 2013-09-03 2015-03-12 Moderna Therapeutics, Inc. Circular polynucleotides
EP3613418A1 (en) 2014-01-17 2020-02-26 Ligand Pharmaceuticals, Inc. Methods and compositions for modulating hormone levels
EP3212773B1 (en) 2014-10-29 2021-09-15 Massachusetts Eye and Ear Infirmary Efficient delivery of therapeutic molecules to cells of the inner ear
KR102362222B1 (ko) 2016-05-16 2022-02-11 더 제너럴 하스피탈 코포레이션 폐 상피 공학에서 인간 기도 줄기 세포
US10975084B2 (en) 2016-10-12 2021-04-13 Merck Sharp & Dohme Corp. KDM5 inhibitors
EP3706742B1 (en) 2017-11-08 2023-03-15 Merck Sharp & Dohme LLC Prmt5 inhibitors
WO2019094312A1 (en) 2017-11-08 2019-05-16 Merck Sharp & Dohme Corp. Prmt5 inhibitors
US11590152B2 (en) 2018-01-26 2023-02-28 Massachusetts Eye And Ear Infirmary Treatment of hearing loss
CA3108388A1 (en) 2018-08-07 2020-02-13 Merck Sharp & Dohme Corp. Prmt5 inhibitors
WO2020033282A1 (en) 2018-08-07 2020-02-13 Merck Sharp & Dohme Corp. Prmt5 inhibitors
WO2020033285A1 (en) 2018-08-07 2020-02-13 Merck Sharp & Dohme Corp. Prmt5 inhibitors
EP3833667B1 (en) 2018-08-07 2024-03-13 Merck Sharp & Dohme LLC Prmt5 inhibitors
AU2020257397B2 (en) 2019-04-19 2026-02-26 Ligand Pharmaceuticals Inc. Crystalline forms and methods of producing crystalline forms of a compound
EP4076460B1 (en) 2019-12-17 2026-01-21 Merck Sharp & Dohme LLC 1,4-dihydro-2h-spiro[isoquinoline-3,4'-piperidine derivatives as prmt5 inhibitors for the treatment of cancer
EP4076459B1 (en) 2019-12-17 2026-04-29 Merck Sharp & Dohme LLC Prmt5 inhibitors
ES3022307T3 (en) 2019-12-17 2025-05-28 Merck Sharp & Dohme Llc Prmt5 inhibitors
ES3074517T3 (en) 2019-12-17 2026-07-21 Merck Sharp & Dohme Llc 4-(3,4-dihydroisoquinolin-2(1h)-yl)-3-hydroxypiperidine derivatives as prmt5 inhibitors for the treatment of cancer and sickle cell disease
CN120225528A (zh) 2022-09-02 2025-06-27 默沙东有限责任公司 依喜替康衍生的拓扑异构酶-1抑制剂药物组合物及其用途
KR20250079227A (ko) 2022-10-25 2025-06-04 머크 샤프 앤드 돔 엘엘씨 엑사테칸-유래 adc 링커-페이로드, 제약 조성물, 및 그의 용도
KR20250116773A (ko) 2022-12-14 2025-08-01 머크 샤프 앤드 돔 엘엘씨 아우리스타틴 링커-페이로드, 제약 조성물, 및 그의 용도

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA9711537B (en) * 1996-12-23 1998-06-25 Athena Neurosciences Inc Eli L Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting ß-amyloid peptide release and/or its synthesis by use of such compounds.
AU4707999A (en) * 1998-06-22 2000-01-10 Elan Pharmaceuticals, Inc. Compounds for inhibiting beta-amyloid peptide release and/or its synthesis
AU1569501A (en) * 1999-11-09 2001-06-06 Eli Lilly And Company Beta-aminoacid compounds useful for inhibiting beta-amyloid peptide release and/or its synthesis
DE60135489D1 (de) * 2000-11-17 2008-10-02 Lilly Co Eli Lactam dipeptid und dessen verwendung zur inhibierung der beta-amyloid peptid frisetzung
UA74849C2 (en) * 2000-11-17 2006-02-15 Lilly Co Eli Lactam
UA77165C2 (en) * 2000-11-17 2006-11-15 Lilly Co Eli (n)-((s)-2-hydroxy-3-methyl-butyryl)-1-(l-alaninyl)-(s)-1-amino-3-methyl-4,5,6,7-tetrahydro-2h-3-benzazepin-2-one dihydrate, processes for manufacturing and pharmaceutical composition

Also Published As

Publication number Publication date
AR035927A1 (es) 2004-07-28
JP2004517090A (ja) 2004-06-10
AU2002243192B2 (en) 2006-07-20
NO20032236L (no) 2003-07-10
HUP0301842A3 (en) 2010-03-29
UA74849C2 (en) 2006-02-15
NZ525854A (en) 2004-06-25
EA200300580A1 (ru) 2003-10-30
HUP0301842A2 (hu) 2003-09-29
SI1341531T1 (sl) 2007-06-30
HK1059731A1 (en) 2004-07-16
EA005954B1 (ru) 2005-08-25
MY134559A (en) 2007-12-31
WO2002047671A2 (en) 2002-06-20
IL155960A (en) 2009-06-15
PL362688A1 (en) 2004-11-02
PE20020802A1 (es) 2002-09-10
US20050261495A1 (en) 2005-11-24
CN1486184A (zh) 2004-03-31
SK5592003A3 (en) 2003-12-02
KR20030051846A (ko) 2003-06-25
MXPA03004292A (es) 2004-02-12
DE60126132D1 (de) 2007-03-08
CA2427227C (en) 2010-08-17
ZA200303789B (en) 2004-08-16
ECSP034600A (es) 2003-06-25
WO2002047671A3 (en) 2003-03-06
BR0115427A (pt) 2003-10-07
CZ20031351A3 (cs) 2003-11-12
KR100819679B1 (ko) 2008-04-04
DK1341531T3 (da) 2007-05-14
ES2278804T3 (es) 2007-08-16
TWI305204B (en) 2009-01-11
EP1341531A2 (en) 2003-09-10
NO324324B1 (no) 2007-09-24
HRP20030383B1 (hr) 2007-12-31
CA2427227A1 (en) 2002-06-20
DZ3453A1 (fr) 2002-06-20
HRP20030383A2 (en) 2005-10-31
IL155960A0 (en) 2003-12-23
AU4319202A (en) 2002-06-24
EP1341531B1 (en) 2007-01-17
DE60126132T2 (de) 2007-10-18
HU228117B1 (en) 2012-11-28
PL212199B1 (pl) 2012-08-31
SK288065B6 (sk) 2013-04-03
CY1106366T1 (el) 2011-10-12
PT1341531E (pt) 2007-04-30
NO20032236D0 (no) 2003-05-16

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