WO1998027972A3 - Anti-amyloidogenic agents - Google Patents

Anti-amyloidogenic agents Download PDF

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Publication number
WO1998027972A3
WO1998027972A3 PCT/US1997/024181 US9724181W WO9827972A3 WO 1998027972 A3 WO1998027972 A3 WO 1998027972A3 US 9724181 W US9724181 W US 9724181W WO 9827972 A3 WO9827972 A3 WO 9827972A3
Authority
WO
WIPO (PCT)
Prior art keywords
acid
stabilizing
amyloidogenic protein
compound
amyloidogenic
Prior art date
Application number
PCT/US1997/024181
Other languages
French (fr)
Other versions
WO1998027972A9 (en
WO1998027972A8 (en
WO1998027972A2 (en
Inventor
Guzman Mirov Greta J De
Jeffery W Kelly
Zhihong Lai
Hilal A Lashuel
Scott A Peterson
Original Assignee
Texas A & M Univ Sys
Guzman Mirov Greta J De
Jeffery W Kelly
Zhihong Lai
Hilal A Lashuel
Scott A Peterson
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 Texas A & M Univ Sys, Guzman Mirov Greta J De, Jeffery W Kelly, Zhihong Lai, Hilal A Lashuel, Scott A Peterson filed Critical Texas A & M Univ Sys
Priority to AU57277/98A priority Critical patent/AU5727798A/en
Publication of WO1998027972A2 publication Critical patent/WO1998027972A2/en
Publication of WO1998027972A9 publication Critical patent/WO1998027972A9/en
Publication of WO1998027972A3 publication Critical patent/WO1998027972A3/en
Publication of WO1998027972A8 publication Critical patent/WO1998027972A8/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/603—Salicylic acid; Derivatives thereof having further aromatic rings, e.g. diflunisal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A61K31/055—Phenols the aromatic ring being substituted by halogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid

Abstract

A method for treating a human amyloid disease which includes administering a pharmaceutically effective amount of a composition to form an amyloidogenic protein-stabilizing aryl compound. These compounds include an amyloidogenic protein-stabilizing compound; said amyloidogenic protein-stabilizing compound is a nonsteroidal anti-inflammatory compound selected from 2,4,6-triiodophenol, mefenamic acid, diflunisal, meclofenamic acid, milrinone, ethacrynic acid, diclofenac, indomethacin, sulindac, fenclofenac, fenoprofen, flufenamic acid, and EMD 21388 (Merck), (i.e., 2-(3,5-dibromo-4-hydroxyphenyl)-4H-6-hydroxy-1-benzopyran-4-one see structure (I)).
PCT/US1997/024181 1996-12-23 1997-12-23 Anti-amyloidogenic agents WO1998027972A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU57277/98A AU5727798A (en) 1996-12-23 1997-12-23 Anti-amyloidogenic agents

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US77193896A 1996-12-23 1996-12-23
US08/771,938 1996-12-23

Publications (4)

Publication Number Publication Date
WO1998027972A2 WO1998027972A2 (en) 1998-07-02
WO1998027972A9 WO1998027972A9 (en) 1998-11-05
WO1998027972A3 true WO1998027972A3 (en) 1999-02-18
WO1998027972A8 WO1998027972A8 (en) 2001-05-31

Family

ID=25093393

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/024181 WO1998027972A2 (en) 1996-12-23 1997-12-23 Anti-amyloidogenic agents

Country Status (2)

Country Link
AU (1) AU5727798A (en)
WO (1) WO1998027972A2 (en)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6306909B1 (en) 1997-03-12 2001-10-23 Queen's University At Kingston Anti-epileptogenic agents
BR0016652A (en) * 1999-12-23 2002-11-19 Neurochem Inc Methods to inhibit cerebral amyloid angiopathy, to treat a disease state characterized by cerebral amyloid angiopathy in an individual, and to diagnose cerebral amyloid angiopathy in an individual
EP1328261A2 (en) * 2000-04-12 2003-07-23 Minerva Biotechnologies Corporation Treatment of neurodegenerative disease
AU5702201A (en) * 2000-04-13 2001-10-30 Mayo Foundation Abeta<sub>42</sub> lowering agents
DE60223904T2 (en) 2001-01-26 2008-11-27 Btg International Ltd. BENZYLAMINANALOGEN
PT1988397E (en) 2002-12-19 2011-12-02 Scripps Research Inst Compositions and uses for stabilising transthyretin and inhibiting transthyretin misfolding
US6979750B1 (en) 2003-04-18 2005-12-27 The Regents Of The University Of California Thyronamine derivatives and analogs and methods of use thereof
US7321065B2 (en) 2003-04-18 2008-01-22 The Regents Of The University Of California Thyronamine derivatives and analogs and methods of use thereof
WO2004100998A2 (en) 2003-05-07 2004-11-25 General Electric Company Compositions and methods for non-invasive imaging of soluble beta-amyloid
WO2005113523A1 (en) 2004-05-20 2005-12-01 Foldrx Pharmaceuticals, Inc. 2-((hetero) aryl)-benzoxazole compounds and derivatives, compositions and methods for stabilizing transthyretin and inhibiting transthyretin misfolding
EP2277516A1 (en) 2004-06-23 2011-01-26 ReVision Therapeutics, Inc. Retinyl derivatives for treating ophtalmic conditions
US7678823B2 (en) 2004-10-04 2010-03-16 Myriad Pharmaceticals, Inc. Compounds for alzheimer's disease
JP4178281B2 (en) * 2004-12-08 2008-11-12 シリオン セラピューティクス， インコーポレイテッド Methods, assays and compositions for treating retinol-related diseases
WO2006110477A2 (en) * 2005-04-07 2006-10-19 Astrum Therapeutics Pty. Ltd. Compounds to treat amyloidosis and prevent death of beta-cells in type 2 diabetes mellitus
EP2007385A4 (en) * 2006-03-23 2010-08-18 Sinai School Medicine Cardiovascular composition and use the same for the treatment of alzheimers disease
WO2010042652A2 (en) 2008-10-08 2010-04-15 Amira Pharmaceuticals, Inc. Heteroalkyl biphenyl antagonists of prostaglandin d2 receptors
EP2266550A1 (en) * 2009-06-15 2010-12-29 Institut Curie Antagonists of ß-catenin for preventing and/or treating neurodegenerative disorders
JP5869677B2 (en) 2011-09-16 2016-02-24 ファイザー・インク Solid form of transthyretin dissociation inhibitor
AU2012327275B2 (en) 2011-10-24 2017-03-02 Som Innovation Biotech, S.L. New therapy for transthyretin-associated amyloidosis
US9169214B2 (en) 2012-12-21 2015-10-27 The Board Of Trustees Of The Leland Stanford Junior University Compounds and compositions that bind and stabilize transthyretin and their use for inhibiting transthyretin amyloidosis and protein-protein interactions
WO2016025129A1 (en) 2014-08-14 2016-02-18 Alhamadsheh Mamoun M Conjugation of pharmaceutically active agents with transthyretin ligands through adjustable linkers to increase serum half-life

Citations (3)

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US5192753A (en) * 1991-04-23 1993-03-09 Mcgeer Patrick L Anti-rheumatoid arthritic drugs in the treatment of dementia
WO1995022992A2 (en) * 1994-02-23 1995-08-31 Chiron Corp Method and compositions for increasing the serum half-life of pharmacologically active agents
EP0675103A2 (en) * 1994-03-01 1995-10-04 Scotia Holdings Plc Derivatives of essential fatty acids and nonsteroidal antiinflammatory drugs

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5192753A (en) * 1991-04-23 1993-03-09 Mcgeer Patrick L Anti-rheumatoid arthritic drugs in the treatment of dementia
WO1995022992A2 (en) * 1994-02-23 1995-08-31 Chiron Corp Method and compositions for increasing the serum half-life of pharmacologically active agents
EP0675103A2 (en) * 1994-03-01 1995-10-04 Scotia Holdings Plc Derivatives of essential fatty acids and nonsteroidal antiinflammatory drugs

Non-Patent Citations (13)

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Title
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BREITNER ET AL.: "Inverse association of anti-Inflammatory treatment and Alzheimer's disease", NEUROLOGY, vol. 44, 1994, pages 227 - 232, XP002070241 *
BREITNER J.C.S.: "The role of Anti-inflammatory Drgs in the revention and treatment of Alzheimer's disease", ANN. REV. MEDICINE, vol. 47, 1996, pages 401 - 411, XP002070240 *
FAGARASAN ET AL.: "IL-1 and anti-inflammatory drugs modulate A beta cytotoxicity in PC12 cells", BRAIN RESEARCH, vol. 723, no. 1,2, 1996, pages 231 - 234, XP002070244 *
GOTTSCHALK P.E.: "beta-amyloid induction of gelatinase B secretion in cultured microglia: inhibition by dexamethasone and indomethacin", NEUROREPORT, vol. 7, no. 18, 1996, pages 3077 - 3080, XP002070236 *
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MCKINNEY ET AL.: "Molecular Interaction of Toxic Chlorinated Dibenzo-p-dioxins and Dibenzofurans with Thyroxine Binding Prealbumin", J. MED. CHEM., vol. 28, no. 3, 1985, pages 375 - 381, XP002070246 *
MIROY ET AL.: "Inhibiting transthyretin amyloid fibril formation via protein stabilization", PROC. NATL. ACAD. SCI. USA, vol. 93, no. 26, 1996, pages 15051 - 15056, XP002070247 *
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Also Published As

Publication number Publication date
AU5727798A (en) 1998-07-17
WO1998027972A8 (en) 2001-05-31
WO1998027972A2 (en) 1998-07-02

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