WO2001066564A3 - Gamma-secretase inhibitors - Google Patents

Gamma-secretase inhibitors Download PDF

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Publication number
WO2001066564A3
WO2001066564A3 PCT/GB2001/000855 GB0100855W WO0166564A3 WO 2001066564 A3 WO2001066564 A3 WO 2001066564A3 GB 0100855 W GB0100855 W GB 0100855W WO 0166564 A3 WO0166564 A3 WO 0166564A3
Authority
WO
WIPO (PCT)
Prior art keywords
gamma
secretase inhibitors
secretase
inhibitors
alzheimer
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.)
Ceased
Application number
PCT/GB2001/000855
Other languages
French (fr)
Other versions
WO2001066564A2 (en
Inventor
Pineiro Jose Luis Castro
Adrian Leonard Smith
Graeme Irvine Stevenson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Organon Pharma UK Ltd
Original Assignee
Merck Sharp and Dohme Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Merck Sharp and Dohme Ltd filed Critical Merck Sharp and Dohme Ltd
Priority to AU35799/01A priority Critical patent/AU782884B2/en
Priority to JP2001565729A priority patent/JP2003525947A/en
Priority to DE60112055T priority patent/DE60112055T2/en
Priority to AT01907933T priority patent/ATE299890T1/en
Priority to EP01907933A priority patent/EP1263774B1/en
Priority to CA002401525A priority patent/CA2401525A1/en
Priority to US10/204,962 priority patent/US7049296B2/en
Publication of WO2001066564A2 publication Critical patent/WO2001066564A2/en
Publication of WO2001066564A3 publication Critical patent/WO2001066564A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • 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
    • 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
    • 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
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • 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)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Novel urea derivatives of formula (I) are disclosed: The compounds are inhibitors of η-secretase, and hence useful in the treatment or prevention of Alzheimer's disease.
PCT/GB2001/000855 2000-03-03 2001-02-28 Gamma-secretase inhibitors Ceased WO2001066564A2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
AU35799/01A AU782884B2 (en) 2000-03-03 2001-02-28 Gamma-secretase inhibitors
JP2001565729A JP2003525947A (en) 2000-03-03 2001-02-28 Gamma-secretase inhibitor
DE60112055T DE60112055T2 (en) 2000-03-03 2001-02-28 INHIBITORS OF GAMMA SECRETASE
AT01907933T ATE299890T1 (en) 2000-03-03 2001-02-28 INHIBITORS OF GAMMA SECRETASE
EP01907933A EP1263774B1 (en) 2000-03-03 2001-02-28 Gamma-secretase inhibitors
CA002401525A CA2401525A1 (en) 2000-03-03 2001-02-28 Gamma-secretase inhibitors
US10/204,962 US7049296B2 (en) 2000-03-03 2001-02-28 Gamma-secretase inhibitors

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0005251.4 2000-03-03
GBGB0005251.4A GB0005251D0 (en) 2000-03-03 2000-03-03 Therapeutic compounds

Publications (2)

Publication Number Publication Date
WO2001066564A2 WO2001066564A2 (en) 2001-09-13
WO2001066564A3 true WO2001066564A3 (en) 2002-01-03

Family

ID=9886973

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2001/000855 Ceased WO2001066564A2 (en) 2000-03-03 2001-02-28 Gamma-secretase inhibitors

Country Status (10)

Country Link
US (1) US7049296B2 (en)
EP (1) EP1263774B1 (en)
JP (1) JP2003525947A (en)
AT (1) ATE299890T1 (en)
AU (1) AU782884B2 (en)
CA (1) CA2401525A1 (en)
DE (1) DE60112055T2 (en)
ES (1) ES2243452T3 (en)
GB (1) GB0005251D0 (en)
WO (1) WO2001066564A2 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8859628B2 (en) 2003-02-27 2014-10-14 JoAnne McLaurin Method for preventing, treating and diagnosing disorders of protein aggregation
US9139520B2 (en) 2007-12-21 2015-09-22 Ligand Pharmaceuticals Incorporated Selective androgen receptor modulators (SARMs) and uses thereof

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Publication number Priority date Publication date Assignee Title
US8044259B2 (en) 2000-08-03 2011-10-25 The Regents Of The University Of Michigan Determining the capability of a test compound to affect solid tumor stem cells
US6984522B2 (en) 2000-08-03 2006-01-10 Regents Of The University Of Michigan Isolation and use of solid tumor stem cells
US6696488B2 (en) 2000-08-11 2004-02-24 The Brigham And Women's Hospital, Inc. (Hydroxyethyl)ureas as inhibitors of alzheimer's β-amyloid production
ATE396174T1 (en) 2001-06-01 2008-06-15 Elan Pharm Inc HYDROXYALKYLAMINE DERIVATIVES AS BETA-SECRETASE INHIBITORS AND THE USE THEREOF FOR THE TREATMENT OF ALZHEIMER'S DISEASE OR SIMILAR DISEASES
WO2003050073A1 (en) * 2001-12-06 2003-06-19 Elan Pharmaceuticals, Inc. Substituted hydroxyethylamines
AU2004281142A1 (en) * 2003-10-20 2005-04-28 Locomogene, Inc. Method of inhibiting secretase activity
EP2369014A1 (en) 2004-02-03 2011-09-28 The Regents Of The University Of Michigan Office Of Technology Transfer Compositions and methods for characterizing, regulating, diagnosing and treating cancer
AU2005209909B8 (en) * 2004-02-03 2009-01-15 The Regents Of The University Of Michigan Compositions and methods for characterizing, regulating, diagnosing, and treating cancer
US20060252073A1 (en) * 2005-04-18 2006-11-09 Regents Of The University Of Michigan Compositions and methods for the treatment of cancer
JP2009503027A (en) * 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 Substituted ethane-1,2-diamine for the treatment of Alzheimer's disease II
EP1945754B1 (en) 2005-10-31 2014-07-23 The Regents Of The University Of Michigan Compositions and methods for treating and diagnosing cancer
WO2008121102A2 (en) * 2006-02-21 2008-10-09 The Regents Of The University Of Michigan Hedgehog signaling pathway antagonist cancer treatment
US8278345B2 (en) 2006-11-09 2012-10-02 Probiodrug Ag Inhibitors of glutaminyl cyclase
WO2008076556A2 (en) 2006-11-15 2008-06-26 Massachusetts Eye & Ear Infirmary Generation of inner ear cells
ATE554085T1 (en) 2006-11-30 2012-05-15 Probiodrug Ag NEW INHIBITORS OF GLUTAMINYL CYCLASE
EP2106439B1 (en) 2007-01-24 2014-11-12 The Regents of the University of Michigan Compositions and methods for treating and diagnosing pancreatic cancer
JP5930573B2 (en) 2007-03-01 2016-06-15 プロビオドルグ エージー New use of glutaminyl cyclase inhibitors
WO2008128985A1 (en) 2007-04-18 2008-10-30 Probiodrug Ag Thiourea derivatives as glutaminyl cyclase inhibitors
US8377886B2 (en) * 2007-09-14 2013-02-19 Albert Einstein College Of Medicine Of Yeshiva University Use of gamma secretase inhibitors and notch pathway inhibitors for treatment and prevention of renal disease
US20110200618A1 (en) * 2008-02-14 2011-08-18 Chang-Gyu Hahn Erbb4 inhibitors and uses thereof in treatment of neuropsychiatric disorders
WO2010060088A2 (en) 2008-11-24 2010-05-27 Massachusetts Eye & Ear Infirmary Pathways to generate hair cells
US20110177061A1 (en) 2009-07-10 2011-07-21 Martek Biosciences Corporation Methods of treating and preventing neurological disorders using docosahexaenoic acid
PL2475428T3 (en) 2009-09-11 2015-12-31 Probiodrug Ag Heterocylcic derivatives as inhibitors of glutaminyl cyclase
ES2586231T3 (en) 2010-03-03 2016-10-13 Probiodrug Ag Glutaminyl cyclase inhibitors
MX2012010470A (en) 2010-03-10 2012-10-09 Probiodrug Ag Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5).
US8541596B2 (en) 2010-04-21 2013-09-24 Probiodrug Ag Inhibitors
EP2686313B1 (en) 2011-03-16 2016-02-03 Probiodrug AG Benzimidazole derivatives as inhibitors of glutaminyl cyclase
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
EP2892506B1 (en) 2012-09-07 2021-11-03 Massachusetts Eye & Ear Infirmary Treating hearing loss with the gamma-secretase inhibitor ly411575
US8859286B2 (en) 2013-03-14 2014-10-14 Viacyte, Inc. In vitro differentiation of pluripotent stem cells to pancreatic endoderm cells (PEC) and endocrine cells
AU2014278178B2 (en) 2013-06-11 2021-01-21 President And Fellows Of Harvard College SC-beta cells and compositions and methods for generating the same
EP3613418A1 (en) 2014-01-17 2020-02-26 Ligand Pharmaceuticals, Inc. Methods and compositions for modulating hormone levels
EP3166627A1 (en) 2014-07-11 2017-05-17 Genentech, Inc. Notch pathway inhibition
WO2016022776A2 (en) 2014-08-06 2016-02-11 Massachusetts Eye And Ear Infirmary Increasing atoh1 life to drive sensorineural hair cell differentiantion
EP3324965A4 (en) 2015-07-24 2019-07-03 Oncotracker, Inc. GAMMA SECRETASE MODULATORS FOR THE TREATMENT OF IMMUNOSYSTEM DISORDER
WO2017096233A1 (en) 2015-12-04 2017-06-08 Massachusetts Eye And Ear Infirmary Treatment of hearing loss by inhibition of casein kinase 1
CN109219439B (en) 2016-01-29 2022-09-20 马萨诸塞眼科耳科诊所 Expansion and differentiation of inner ear support cells and methods of use thereof
KR102362222B1 (en) 2016-05-16 2022-02-11 더 제너럴 하스피탈 코포레이션 Human Airway Stem Cells in Lung Epithelial Engineering
EP3554502A4 (en) 2016-12-16 2021-01-06 Pipeline Therapeutics, Inc. Methods of treating cochlear synaptopathy
IL268349B2 (en) 2017-02-17 2024-08-01 Hutchinson Fred Cancer Res Combination therapies for the treatment of BCMA-associated cancer and autoimmune disorders
PL3461819T3 (en) 2017-09-29 2020-11-30 Probiodrug Ag Inhibitors of glutaminyl cyclase
WO2019099725A1 (en) 2017-11-15 2019-05-23 Semma Therapeutics, Inc. Islet cell manufacturing compositions and methods of use
WO2019169351A1 (en) 2018-03-02 2019-09-06 Semma Therapeutics, Inc. Methods of enhancing stem cell differentiation into beta cells
EP3833365A4 (en) 2018-08-10 2022-05-11 Vertex Pharmaceuticals Incorporated ISLET DIFFERENTIATION DERIVED FROM STEM CELLS
AU2020257397B2 (en) 2019-04-19 2026-02-26 Ligand Pharmaceuticals Inc. Crystalline forms and methods of producing crystalline forms of a compound
WO2021195362A1 (en) 2020-03-26 2021-09-30 Seagen Inc. Methods of treating multiple myeloma
JP7705448B2 (en) 2020-07-31 2025-07-09 バーテックス ファーマシューティカルズ インコーポレイテッド Pancreatic endocrine cell differentiation
JP2024542041A (en) 2021-11-01 2024-11-13 バーテックス ファーマシューティカルズ インコーポレイテッド Stem cell-derived pancreatic islet differentiation

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992008698A1 (en) * 1990-11-19 1992-05-29 Monsanto Company Retroviral protease inhibitors

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU779875B2 (en) * 2000-01-24 2005-02-17 Merck Sharp & Dohme Limited Gamma-secretase inhibitors

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992008698A1 (en) * 1990-11-19 1992-05-29 Monsanto Company Retroviral protease inhibitors

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
H STEINER ET AL.: "Amyloidogenic function of Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis", BIOCHEMISTRY., vol. 38, no. 44, 1999, AMERICAN CHEMICAL SOCIETY. EASTON, PA., US, pages 14600 - 14605, XP002179219, ISSN: 0006-2960 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8859628B2 (en) 2003-02-27 2014-10-14 JoAnne McLaurin Method for preventing, treating and diagnosing disorders of protein aggregation
US9139520B2 (en) 2007-12-21 2015-09-22 Ligand Pharmaceuticals Incorporated Selective androgen receptor modulators (SARMs) and uses thereof

Also Published As

Publication number Publication date
EP1263774A2 (en) 2002-12-11
US20030055005A1 (en) 2003-03-20
AU3579901A (en) 2001-09-17
DE60112055T2 (en) 2006-04-27
JP2003525947A (en) 2003-09-02
DE60112055D1 (en) 2005-08-25
ES2243452T3 (en) 2005-12-01
CA2401525A1 (en) 2001-09-13
WO2001066564A2 (en) 2001-09-13
AU782884B2 (en) 2005-09-08
ATE299890T1 (en) 2005-08-15
US7049296B2 (en) 2006-05-23
EP1263774B1 (en) 2005-07-20
GB0005251D0 (en) 2000-04-26

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