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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
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/DE2008/000910
Other languages
English (en)
French (fr)
Other versions
WO2008145116A2 (de
Inventor
Michael Ristow
Marc Birringer
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.)
Friedrich Schiller Universtaet Jena FSU
Original Assignee
Friedrich Schiller Universtaet Jena FSU
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 Universtaet Jena FSU filed Critical Friedrich Schiller Universtaet Jena FSU
Publication of WO2008145116A2 publication Critical patent/WO2008145116A2/de
Publication of WO2008145116A3 publication Critical patent/WO2008145116A3/de
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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

Landscapes

  • 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 Ceased WO2008145116A2 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
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
DE102007025423.9 2007-05-30

Publications (2)

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

Family

ID=39731640

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2008/000910 Ceased 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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* Cited by examiner, † Cited by third party
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CA2734208C (en) * 2008-03-14 2018-01-09 Jiri Neuzil Mitochondrially delivered anti-cancer compounds
US9580452B2 (en) 2015-02-19 2017-02-28 Council Of Scientific And Industrial Research 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
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
EP3612187B1 (de) 2017-04-21 2022-04-13 Lunella Biotech, Inc. Vitamin c und doxycyclin: eine synthetische letale kombinationstherapie zur eradikation von krebsstammzellen (cscs)
AU2018270129B2 (en) 2017-05-19 2021-01-07 Lunella Biotech, Inc. Antimitoscins: targeted inhibitors of mitochondrial biogenesis for eradicating cancer stem cells
RU2020116649A (ru) 2017-10-24 2021-11-30 Лунелла Байотек, Инк. Митофлавосцины: нацеливание на флавин-содержащие ферменты устраняет злокачественные стволовые клетки (cscs) посредством ингибирования митохондриального дыхания
US10980821B2 (en) 2017-11-24 2021-04-20 Lunella Biotech, Inc. Triphenylphosphonium-derivative compounds for eradicating cancer stem cells
EP3717015A4 (de) 2017-12-01 2021-07-28 Lunella Biotech, Inc. Repurposcine: gezielte inhibitoren der mitochondrialen biogenese zur vernichtung von krebsstammzellen
WO2019126179A1 (en) 2017-12-20 2019-06-27 Lunella Biotech, Inc. Targeting mitochondrial fission through mdivi-1 derivatives
CN111836622A (zh) 2018-01-03 2020-10-27 威斯康星州医药大学股份有限公司 线粒体-氯尼达明、组合物和使用方法
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
CN115850334A (zh) * 2022-12-21 2023-03-28 西安交通大学 三苯基鏻-羟基酪醇及其合成方法以及在制备抑制癌细胞增殖药物中的应用

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* Cited by examiner, † Cited by third party
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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 *

Also Published As

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

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