WO2006021441A1 - Acides biphenylcarboxyliques, derives de ceux-ci et leur utilisation en therapie - Google Patents

Acides biphenylcarboxyliques, derives de ceux-ci et leur utilisation en therapie Download PDF

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Publication number
WO2006021441A1
WO2006021441A1 PCT/EP2005/009188 EP2005009188W WO2006021441A1 WO 2006021441 A1 WO2006021441 A1 WO 2006021441A1 EP 2005009188 W EP2005009188 W EP 2005009188W WO 2006021441 A1 WO2006021441 A1 WO 2006021441A1
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WO
WIPO (PCT)
Prior art keywords
compound
compound according
formula
acid
biphenyl
Prior art date
Application number
PCT/EP2005/009188
Other languages
English (en)
Inventor
Nigel Ramsden
Francis Wilson
Alison Reid
Valerie Reader
Warren Miller
Richard John Harrison
Mihiro Sunose
Remedios Hernandez-Perni
Jeremy Major
Cyrille Boussard
Kathryn Smelt
Jess Taylor
Adeline Leformal
Andrew Cansfield
Svenja Burckhardt
Original Assignee
Cellzome Ag
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 Cellzome Ag filed Critical Cellzome Ag
Publication of WO2006021441A1 publication Critical patent/WO2006021441A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
    • C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
    • C07C57/62—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings and other rings

Definitions

  • pharmaceutically acceptable means approved by a regulatory agency such as the EMEA (Europe) and/or the FDA (US) and/or any other national regulatory agency for use in animals, preferably in humans.
  • either one or more interactors (either in their wild-type form or carrying certain mutations and/or modifications) of the ⁇ -secretase complex of an animal, preferably a mammal, more preferably humans, might be expressed in certain cell lines and the effect of the compounds according to the invention might be studied.
  • Mutated forms of the interactor(s) used can either be mutated forms which have been described in certain animals, preferably mammals, more preferably humans or mutated forms which have not previously been described in said animals.
  • modifications include, but are not limited to, glycosylation, phosphorylation, prenylation, myristylation and farnesylation.
  • the invention further relates to the use of the compounds according to the invention for the treatment of a disease associated with an elevated level of AB42-production.
  • the invention relates to a composition
  • a composition comprising a compound according to the invention in a mixture with an inert carrier, where said inert carrier is a pharmaceutical carrier.
  • Methods of introduction include, but are not limited to, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, and oral routes.
  • a controlled release system can be placed in proximity of the therapeutic target, i.e., the brain, thus requiring only a fraction of the systemic dose (e.g. Goodson, 1984, In: Medical Applications of Controlled Release, supra, Vol. 2, 115). Other controlled release systems are discussed in the review by Langer (1990, Science 249, 1527).
  • test material is formulated in 10% DMSO/90% hydroxypropyl ⁇ cyclodextrin (10% w/v in phosphate buffered saline)
  • Blood samples are taken from a lateral tail vein not used for dosing.
  • the cranium of the rat is then opened and the brain carefully removed and washed with saline and excess saline removed with adsorbent paper. The brain is then rapidly frozen and stored at approximately -20 C pending analysis of test compound concentrations.
  • Blood is collected at sacrifice.
  • the blood collection is performed via a heart puncture during anesthesia with a mixture of Ketalar (Ketamin), Rompun (Xylazin 2%) and Atropin (2; 1:1) and collected in heparinised Eppendorf tubes. Blood is centrifuged at 4000 g for 5 minutes at 4°C.

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Neurosurgery (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Hospice & Palliative Care (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Psychiatry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne des composés répondant à la formule générale (I) ayant les définitions de R1-R4 données ci-après, et/ou un sel ou un ester de ceux-ci. En outre, l’invention concerne l’utilisation desdits composés comme médicament, préférablement pour le traitement de la maladie d’Alzheimer et leur utilisation pour la modulation de l’activité de la Ϝ-sécrétase.
PCT/EP2005/009188 2004-08-25 2005-08-25 Acides biphenylcarboxyliques, derives de ceux-ci et leur utilisation en therapie WO2006021441A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP04020131.1 2004-08-25
EP04020131 2004-08-25
US64210805P 2005-01-10 2005-01-10
US60/642,108 2005-01-10

Publications (1)

Publication Number Publication Date
WO2006021441A1 true WO2006021441A1 (fr) 2006-03-02

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2005/009188 WO2006021441A1 (fr) 2004-08-25 2005-08-25 Acides biphenylcarboxyliques, derives de ceux-ci et leur utilisation en therapie

Country Status (1)

Country Link
WO (1) WO2006021441A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8367863B2 (en) 2007-12-20 2013-02-05 Envivo Pharmaceuticals, Inc. Tetrasubstituted benzenes
US9802927B2 (en) 2015-06-10 2017-10-31 Denali Therapeutics, Inc. Oxadiazine compounds and methods of use thereof
CN108191966A (zh) * 2018-01-11 2018-06-22 台州学院 一种含导肽可穿越血脑屏障螯合脑内铁降自由基的多肽

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1098878A (en) * 1964-05-07 1968-01-10 Merck & Co Inc d-4-phenyl-ª‡-methylphenylacetic acid and its derivatives and anti-inflammatory compositions containing such compounds and their racemic forms
US3706782A (en) * 1969-07-09 1972-12-19 Bdh Pharmaceuticals Ltd Esters of p-biphenylylacetic acid with polyhydric alcohols
US3755427A (en) * 1964-01-24 1973-08-28 Boots Co Ltd 2-(mono-and difluoro-4-biphenyl)propionic acids
US3932499A (en) * 1970-10-12 1976-01-13 The Boots Company Limited 2-(Substituted biphenylyl) propionic acids

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3755427A (en) * 1964-01-24 1973-08-28 Boots Co Ltd 2-(mono-and difluoro-4-biphenyl)propionic acids
GB1098878A (en) * 1964-05-07 1968-01-10 Merck & Co Inc d-4-phenyl-ª‡-methylphenylacetic acid and its derivatives and anti-inflammatory compositions containing such compounds and their racemic forms
US3706782A (en) * 1969-07-09 1972-12-19 Bdh Pharmaceuticals Ltd Esters of p-biphenylylacetic acid with polyhydric alcohols
US3932499A (en) * 1970-10-12 1976-01-13 The Boots Company Limited 2-(Substituted biphenylyl) propionic acids

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
DATABASE MEDLINE US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; XP002355161, Database accession no. NLM14040576 *
F. BLICKE AND N. GRIER: "Antispasmodics. V", JOURNAL OF THE AMERICAN SOCIETY, vol. 65, 1943, pages 1725 - 1728, XP002353901 *
J. SAM, K. APARAJITHAN AND R. SHAFIK: "2-(4-biphenylyl)ethylamines: potential cardiovascular and CNS agents", JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 57, no. 4, 1968, pages 564 - 568, XP008055544 *
M. CARISSIMI, A. CATTANEO, R. D'AMBROSIO, E. GRUMELLI, E. MILLA AND F. RAVENNA: "Sintesi e proprieta' farmacologiche di nuovi derivati dell'acido fenilacetico", IL FARMACO, vol. 18, no. 5, 1963, pages 315 - 345, XP008055475 *
P. BAURES, S. PETERSON AND J. KELLY: "Discovering Transthyretin Amyloid Fibril Inhibitors by Limited Screening", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 6, 1998, pages 1389 - 1401, XP002353902 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8367863B2 (en) 2007-12-20 2013-02-05 Envivo Pharmaceuticals, Inc. Tetrasubstituted benzenes
US8664249B2 (en) 2007-12-20 2014-03-04 Envivo Pharmaceuticals, Inc. Tetrasubstituted benzenes
US9802927B2 (en) 2015-06-10 2017-10-31 Denali Therapeutics, Inc. Oxadiazine compounds and methods of use thereof
CN108191966A (zh) * 2018-01-11 2018-06-22 台州学院 一种含导肽可穿越血脑屏障螯合脑内铁降自由基的多肽
CN108191966B (zh) * 2018-01-11 2020-10-27 桂林医学院 一种含导肽可穿越血脑屏障螯合脑内铁降自由基的多肽

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