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WO2000049019A3 - Neue epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung - Google Patents

Neue epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung Download PDF

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Publication number
WO2000049019A3
WO2000049019A3 PCT/EP2000/001331 EP0001331W WO0049019A3 WO 2000049019 A3 WO2000049019 A3 WO 2000049019A3 EP 0001331 W EP0001331 W EP 0001331W WO 0049019 A3 WO0049019 A3 WO 0049019A3
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WIPO (PCT)
Prior art keywords
compounds
novel
epothilone derivatives
tumours
order
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/EP2000/001331
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English (en)
French (fr)
Other versions
WO2000049019A2 (de
Inventor
Ulrich Klar
Wolfgang Schwede
Werner Skuballa
Bernd Buchmann
Michael Schirner
Andreas Menrad
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Bayer Pharma AG
Original Assignee
Schering AG
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Publication date
Application filed by Schering AG filed Critical Schering AG
Priority to AU38048/00A priority Critical patent/AU3804800A/en
Publication of WO2000049019A2 publication Critical patent/WO2000049019A2/de
Publication of WO2000049019A3 publication Critical patent/WO2000049019A3/de
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
    • C07D493/14—Ortho-condensed 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
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Die vorliegende Erfindung betrifft die neuen Epothilon-Derivate der allgemeinen Formel (I), worin die Substituenten Y, Z, R?1a, R1b, R2a, R2b¿, G'-G-E-E', R?5, R6, R7, R8, R14¿ und X die in der Beschreibung näher angegebenen Bedeutungen haben. Die neuen Verbindungen interagieren mit Tubulin, indem sie gebildete Mikrotubuli stabilisieren. Sie sind in der Lage, die Zellteilung phasenspezifisch zu beeinflussen und sind zur Behandlung maligner Tumoren geeignet, beispielsweise Ovarial-, Magen-, Colon-, Adeno-, Brust-, Lungen-, Kopf- und Nacken-Karzinome, malignes Melanom, akute lymphozytäre und myelocytäre Leukämie. Ausserdem sind sie zur Anti-Angiogenese-Therapie sowie zur Behandlung chronischer entzündlicher Erkrankungen (Psoriasis, Arthritis) geeignet. Zur Vermeidung unkontrollierter Zellwucherungen an sowie der besseren Verträglichkeit von medizinischen Implantaten lassen sie sich in polymere Materialien auf- bzw. einbringen. Die erfindungsgemässen Verbindungen können alleine oder zur Erzielung additiver oder synergistischer Wirkungen in Kombination mit weiteren in der Tumortherapie anwendbaren Prinzipien und Substanzklassen verwendet werden.
PCT/EP2000/001331 1999-02-18 2000-02-18 Neue epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung Ceased WO2000049019A2 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU38048/00A AU3804800A (en) 1999-02-18 2000-02-18 Novel epothilone derivatives, method for producing them and their pharmaceuticaluse

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19908760.1 1999-02-18
DE19908760A DE19908760A1 (de) 1999-02-18 1999-02-18 Neue Epothilon-Derivate, Verfahren zu deren Herstellung und ihre pharmazeutische Verwendung

Publications (2)

Publication Number Publication Date
WO2000049019A2 WO2000049019A2 (de) 2000-08-24
WO2000049019A3 true WO2000049019A3 (de) 2001-03-01

Family

ID=7899229

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/001331 Ceased WO2000049019A2 (de) 1999-02-18 2000-02-18 Neue epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung

Country Status (3)

Country Link
AU (1) AU3804800A (de)
DE (1) DE19908760A1 (de)
WO (1) WO2000049019A2 (de)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6849651B2 (en) 1996-12-03 2005-02-01 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US6965034B2 (en) 1996-12-03 2005-11-15 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1511036B (zh) * 2001-02-27 2010-05-05 诺瓦提斯公司 包含信号转导抑制剂和埃坡霉素衍生物的联合形式
EP1383490B1 (de) * 2001-03-14 2012-04-25 Bristol-Myers Squibb Company Kombination aus epothilon-analog und chemotherapeutika zur behandlung von proliferativen erkrankungen
AU2008203233B2 (en) * 2001-07-19 2010-04-29 Novartis Ag Combinations comprising epothilones and pharmaceutical uses thereof
TWI315982B (en) 2001-07-19 2009-10-21 Novartis Ag Combinations comprising epothilones and pharmaceutical uses thereof
US20030176368A1 (en) * 2001-09-06 2003-09-18 Danishefsky Samuel J. Synthesis of epothilones, intermediates thereto and analogues thereof
TWI287986B (en) * 2001-12-13 2007-10-11 Novartis Ag Use of Epothilones for the treatment of the carcinoid syndrome
ES2337134T3 (es) 2002-03-12 2010-04-21 Bristol-Myers Squibb Company Derivados de c3-ciano-epotilona.
ATE476995T1 (de) * 2002-06-10 2010-08-15 Novartis Pharma Gmbh Epothilone enthaltende kombinationen und deren pharmazeutische verwendungen
US7649006B2 (en) 2002-08-23 2010-01-19 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
US6921769B2 (en) 2002-08-23 2005-07-26 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
CN1759115A (zh) 2002-08-23 2006-04-12 索隆-基特林癌症研究协会 埃坡霉素(epothilone),合成埃坡霉素的中间体,其类似物及其用途
EP1674098A1 (de) 2004-12-23 2006-06-28 Schering Aktiengesellschaft Stabile, unbedenkliche parenterale Formulierungen von hochreaktiven organischen Arzneimitteln mit niedriger oder keiner wässrigen Löslichkeit
WO2007062288A2 (en) * 2005-11-22 2007-05-31 The Scripps Research Institute Chemical synthesis of a highly potent epothilone
EP2065054A1 (de) 2007-11-29 2009-06-03 Bayer Schering Pharma Aktiengesellschaft Kombinationen mit einem Prostaglandin und Verwendungen davon
DE102007059752A1 (de) 2007-12-10 2009-06-18 Bayer Schering Pharma Aktiengesellschaft Funktionalisierte, feste Polymernanopartikel enthaltend Epothilone
EP2070521A1 (de) 2007-12-10 2009-06-17 Bayer Schering Pharma Aktiengesellschaft Nanopartikel mit modifizierter Oberfläche
EP2210584A1 (de) 2009-01-27 2010-07-28 Bayer Schering Pharma Aktiengesellschaft Stabile Polymerzusammensetzung mit einem Epothilon und einem amphiphilischen Blockpolymer
US9764038B2 (en) 2011-12-23 2017-09-19 Innate Pharma Enzymatic conjugation of antibodies
EP2872894B1 (de) 2012-07-13 2019-04-17 Innate Pharma Screening von konjugierten antikörpern
WO2014072482A1 (en) 2012-11-09 2014-05-15 Innate Pharma Recognition tags for tgase-mediated conjugation
WO2014140300A1 (en) 2013-03-15 2014-09-18 Innate Pharma Solid phase tgase-mediated conjugation of antibodies
WO2014202773A1 (en) 2013-06-20 2014-12-24 Innate Pharma Enzymatic conjugation of polypeptides
AU2014283185B2 (en) 2013-06-21 2019-05-02 Araris Biotech Ltd. Enzymatic conjugation of polypeptides
WO2019092148A1 (en) 2017-11-10 2019-05-16 Innate Pharma Antibodies with functionalized glutamine residues

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997019086A1 (de) * 1995-11-17 1997-05-29 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilonderivate, herstellung und verwendung
WO1999007692A2 (de) * 1997-08-09 1999-02-18 Schering Aktiengesellschaft Neue epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung
WO1999065913A2 (de) * 1998-06-18 1999-12-23 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilon-nebenkomponenten

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997019086A1 (de) * 1995-11-17 1997-05-29 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilonderivate, herstellung und verwendung
WO1999007692A2 (de) * 1997-08-09 1999-02-18 Schering Aktiengesellschaft Neue epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung
WO1999065913A2 (de) * 1998-06-18 1999-12-23 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilon-nebenkomponenten

Non-Patent Citations (7)

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CHOU T C ET AL: "DESOXYEPOTHILONE B: AN EFFICACIOUS MICROTUBULE-TARGETED ANTITUMOR AGENT WITH A PROMISING IN VIVO PROFILE RELATIVE TO EPOTHILONE B", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA,US,NATIONAL ACADEMY OF SCIENCE. WASHINGTON, vol. 95, no. 16, 1998, pages 9642 - 9647, XP000910107, ISSN: 0027-8424 *
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K C NICOLAOU ET AL: "Probing the ring size of epothilones: total synthesis of [14]-, [15]-, [17]-, and [18]Epothilones A", ANGEWANDTE CHEMIE. INTERNATIONAL EDITION,DE,VERLAG CHEMIE. WEINHEIM, vol. 37, no. 1/02, 1998, pages 81 - 84, XP002131226, ISSN: 0570-0833 *
ZHEN YANG ET AL: "ANGEWANDTE CHEMIE,DE,VCH VERLAGSGESELLSCHAFT, WEINHEIM", ANGEWANDTE CHEMIE,DE,VCH VERLAGSGESELLSCHAFT, WEINHEIM, vol. 109, no. 1/02, 1997, pages 170 - 172, XP002095722, ISSN: 0044-8249 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6849651B2 (en) 1996-12-03 2005-02-01 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US6965034B2 (en) 1996-12-03 2005-11-15 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
US6972335B2 (en) 1996-12-03 2005-12-06 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
USRE41990E1 (en) 1996-12-03 2010-12-07 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof

Also Published As

Publication number Publication date
WO2000049019A2 (de) 2000-08-24
AU3804800A (en) 2000-09-04
DE19908760A1 (de) 2000-08-24

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