WO2008145116A3 - Triphenylphosphonium-derivate zum gezielten transport und freisetzen von substanzen in mitochondrien sowie verfahren zu deren verwendung - Google Patents

Triphenylphosphonium-derivate zum gezielten transport und freisetzen von substanzen in mitochondrien sowie verfahren zu deren verwendung Download PDF

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Publication number
WO2008145116A3
WO2008145116A3 PCT/DE2008/000910 DE2008000910W WO2008145116A3 WO 2008145116 A3 WO2008145116 A3 WO 2008145116A3 DE 2008000910 W DE2008000910 W DE 2008000910W WO 2008145116 A3 WO2008145116 A3 WO 2008145116A3
Authority
WO
WIPO (PCT)
Prior art keywords
mitochondria
substances
derivatives
release
triphenylphosphonium
Prior art date
Application number
PCT/DE2008/000910
Other languages
English (en)
French (fr)
Other versions
WO2008145116A2 (de
Inventor
Michael Ristow
Marc Birringer
Original Assignee
Friedrich-Schiller-Universität Jena
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 Friedrich-Schiller-Universität Jena filed Critical Friedrich-Schiller-Universität Jena
Publication of WO2008145116A2 publication Critical patent/WO2008145116A2/de
Publication of WO2008145116A3 publication Critical patent/WO2008145116A3/de

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
    • C07F9/6552—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring
    • C07F9/65522—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring condensed with carbocyclic rings or carbocyclic ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/54—Quaternary phosphonium compounds
    • C07F9/5407—Acyclic saturated phosphonium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/54—Quaternary phosphonium compounds
    • C07F9/5442—Aromatic phosphonium compounds (P-C aromatic linkage)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
    • C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Die Erfindung betrifft Triphenylphosphonium-Derivate zur gezielten Anreicherung und Freisetzung von Substanzen in Mitochondrien sowie Verfahren zu deren Verwendung. Aufgabe war es, pharmakologische Wirkstoffe in weit größerer Vielfalt definiert in Mitochondrien zu akkumulieren und dort gezielt sowie mit hoher Spezifität und Effektivität, wie auch ohne störende Nebeneffekte dieser Wirkstoffe, freizusetzen. Erfindungsgemäß sind Triphenylphosphonium-Derivate der allgemeinen Verbindung I gemäß der allgemeinen Formel I des ersten Patentanspruches vorgesehen, welche mit der jeweils gebundenen biologisch aktiven Substanz in Mitochondrien transportiert werden. In diesen wird die biologisch aktive Substanz durch mitochondriale Enzyme freigesetzt. Die Derivate finden beispielsweise Anwendung bei der Induktion der Apoptose in Krebszellen (Chemotherapie), zur Steigerung der mitochondrialen Aktivität (z.B. oxidative Phosphorylierung) und damit zur Verzögerung altersassoziierter Erkrankungen, wie z.B. Diabetes mellitus Typ 2.
PCT/DE2008/000910 2007-05-30 2008-05-29 Triphenylphosphonium-derivate zum gezielten transport und freisetzen von substanzen in mitochondrien sowie verfahren zu deren verwendung WO2008145116A2 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102007025423.9 2007-05-30
DE200710025423 DE102007025423A1 (de) 2007-05-30 2007-05-30 Triphenylphosphonium-Derivate zum gezielten Transport und Freisetzen von Substanzen in Mitochondrien sowie Verfahren zu deren Verwendung

Publications (2)

Publication Number Publication Date
WO2008145116A2 WO2008145116A2 (de) 2008-12-04
WO2008145116A3 true WO2008145116A3 (de) 2009-09-03

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2008/000910 WO2008145116A2 (de) 2007-05-30 2008-05-29 Triphenylphosphonium-derivate zum gezielten transport und freisetzen von substanzen in mitochondrien sowie verfahren zu deren verwendung

Country Status (2)

Country Link
DE (1) DE102007025423A1 (de)
WO (1) WO2008145116A2 (de)

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NZ602579A (en) 2008-03-14 2013-12-20 Stephen John Ralph Mitochondrially delivered anti-cancer compounds
GB2540234B (en) 2015-02-19 2020-12-02 Council Scient Ind Res An antioxidant compound having anti atherosclerotic effect and preparation thereof
CZ307146B6 (cs) * 2015-03-31 2018-02-07 Kkcg Se Trifenylfosfoniové analogy biguanidu, způsob jejich přípravy a jejich použití jako léčiva
US11197872B2 (en) 2017-04-21 2021-12-14 Lunella Biotech, Inc. Vitamin C and doxycycline: a synthetic lethal combination therapy for eradicating cancer stem cells (CSCs)
WO2018195446A1 (en) 2017-04-21 2018-10-25 Lisanti Michael P Targeting hypoxic cancer stem cells (cscs) with doxycycline: implications for improving anti-angiogenic therapy
CR20190524A (es) 2017-05-19 2020-01-10 Lunella Biotech Inc Antimitoscinas: inhibidores específicos de la biogénesis mitocondrial para erradicar células madre cancerosas
US11497749B2 (en) 2017-10-24 2022-11-15 Lunella Biotech, Inc. Mitoflavoscins: targeting flavin-containing enzymes eliminates cancer stem cells (CSCS) by inhibiting mitochondrial respiration
CN111971040B (zh) 2017-11-24 2022-05-27 卢内拉生物技术有限公司 用于根除癌症干细胞的三苯基鏻衍生物化合物
CA3083487A1 (en) 2017-12-01 2019-06-06 Lunella Biotech, Inc. Repurposcins: targeted inhibitors of mitochondrial biogenesis for eradicating cancer stem cells
EP3728300A4 (de) 2017-12-20 2021-08-11 Lunella Biotech, Inc. Targeting von mitochondrialen fission durch mdivi-1-derivaten
WO2019136154A1 (en) 2018-01-03 2019-07-11 The Medical College Of Wisconsin, Inc. Mito-lonidamine, compositions and methods of use
CN112341493B (zh) * 2020-10-21 2023-08-15 重庆医药高等专科学校附属第一医院(重庆市职业病防治院重庆市第六人民医院重庆市中毒控制中心) 一种基于三苯基膦修饰的线粒体靶向褪黑素及其制备方法和应用
CN114716475A (zh) * 2022-03-04 2022-07-08 厦门大学 一种三苯基膦修饰舍曲林衍生物及其制备方法和应用
CN114748420B (zh) * 2022-04-12 2024-03-08 武汉科技大学 一种电荷自翻转激活线粒体靶向功效的两亲性聚合物胶束的制备方法
CN115417898B (zh) * 2022-08-02 2024-03-26 浙江工业大学 一种三苯基鏻单体化合物及其制备方法与在制备核酸递送纳米载体中的应用

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Publication number Priority date Publication date Assignee Title
JP2002338587A (ja) 2001-05-21 2002-11-27 Hokko Chem Ind Co Ltd カルボキシル基を含むホスホニウム塩の製造方法

Non-Patent Citations (3)

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Title
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; KUNZ, HORST: "Modification of 2-bromoethoxycarbonyl protective groups to 2-phosphonioethoxycarbonyl protective functions of amino acids", XP002495399, retrieved from STN Database accession no. 1977:30049 *
JUSTUS LIEBIGS ANNALEN DER CHEMIE , (9), 1674-9 CODEN: JLACBF; ISSN: 0075-4617, 1976 *
ROSS, GUENTHER F. ET AL: "Synthesis of Trifunctional PNA-Benzophenone Derivatives for Mitochondrial Targeting , Selective DNA Binding, and Photo-Cross-Linking", BIOCONJUGATE CHEMISTRY , 14(5), 962-966 CODEN: BCCHES; ISSN: 1043-1802, 2003, XP002495398 *

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Publication number Publication date
WO2008145116A2 (de) 2008-12-04
DE102007025423A1 (de) 2008-12-04

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