WO2001081342A3 - 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
WO2001081342A3
WO2001081342A3 PCT/EP2001/004552 EP0104552W WO0181342A3 WO 2001081342 A3 WO2001081342 A3 WO 2001081342A3 EP 0104552 W EP0104552 W EP 0104552W WO 0181342 A3 WO0181342 A3 WO 0181342A3
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well
epothilone derivatives
suited
treatment
novel
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PCT/EP2001/004552
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English (en)
French (fr)
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WO2001081342A2 (de
Inventor
Bernd Buchmann
Ulrich Klar
Werner Skuballa
Wolfgang Schwede
Rosemarie Lichtner
Jens Hoffmann
Original Assignee
Schering Ag
Bernd Buchmann
Ulrich Klar
Werner Skuballa
Wolfgang Schwede
Rosemarie Lichtner
Jens Hoffmann
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.)
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Application filed by Schering Ag, Bernd Buchmann, Ulrich Klar, Werner Skuballa, Wolfgang Schwede, Rosemarie Lichtner, Jens Hoffmann filed Critical Schering Ag
Priority to EP01936262A priority Critical patent/EP1276740A2/de
Priority to US10/257,925 priority patent/US20040058969A1/en
Priority to JP2001578432A priority patent/JP2003531207A/ja
Priority to AU2001262221A priority patent/AU2001262221A1/en
Publication of WO2001081342A2 publication Critical patent/WO2001081342A2/de
Publication of WO2001081342A3 publication Critical patent/WO2001081342A3/de
Priority to NO20025029A priority patent/NO20025029L/no

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen 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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • 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
    • C07D417/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
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    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
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    • 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)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Rheumatology (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Die vorliegende Erfindung beschreibt die neuen Epothilon-Derivate der allgemeinen Formel (I) worin R5 für ein Halogenatom oder eine Cyanogruppe steht und die anderen Substituenten die in der Beschreibung 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/EP2001/004552 2000-04-19 2001-04-19 Neue epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung WO2001081342A2 (de)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP01936262A EP1276740A2 (de) 2000-04-19 2001-04-19 Neue epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung
US10/257,925 US20040058969A1 (en) 2000-04-19 2001-04-19 Novel epothilone derivatives, method for the preparation thereof and their pharmaceutical use
JP2001578432A JP2003531207A (ja) 2000-04-19 2001-04-19 新規エポチロン誘導体、その製造方法及びその医薬としての使用
AU2001262221A AU2001262221A1 (en) 2000-04-19 2001-04-19 Novel epothilone derivatives, method for the preparation thereof and their pharmaceutical use
NO20025029A NO20025029L (no) 2000-04-19 2002-10-18 Nye epotilonderivater, fremgangsmÕte for fremstilling derav og deres farmasöytiske anvendelse

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10020517A DE10020517A1 (de) 2000-04-19 2000-04-19 Neue Epothilon-Derivate, Verfahren zu deren Herstellung und ihre pharmazeutische Verwendung
DE10020517.8 2000-04-19

Publications (2)

Publication Number Publication Date
WO2001081342A2 WO2001081342A2 (de) 2001-11-01
WO2001081342A3 true WO2001081342A3 (de) 2002-05-10

Family

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Application Number Title Priority Date Filing Date
PCT/EP2001/004552 WO2001081342A2 (de) 2000-04-19 2001-04-19 Neue epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung

Country Status (7)

Country Link
US (1) US20040058969A1 (de)
EP (1) EP1276740A2 (de)
JP (1) JP2003531207A (de)
AU (1) AU2001262221A1 (de)
DE (1) DE10020517A1 (de)
NO (1) NO20025029L (de)
WO (1) WO2001081342A2 (de)

Cited By (1)

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

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1209360C (zh) * 1999-02-18 2005-07-06 舍林股份公司 16－卤－依泊昔酮衍生物、其制备方法及其医药用途
US20020058286A1 (en) * 1999-02-24 2002-05-16 Danishefsky Samuel J. Synthesis of epothilones, intermediates thereto and analogues thereof
EP1340498A1 (de) * 2002-03-01 2003-09-03 Schering Aktiengesellschaft Verwendung von Epothilonen zur Behandlung von mit proliferativen Prozessen assoziierten Gehirnerkrankungen
US7211593B2 (en) * 2002-03-12 2007-05-01 Bristol-Myers Squibb Co. C12-cyano epothilone derivatives
MXPA04012444A (es) * 2002-06-10 2005-04-19 Novartis Ag Combinaciones que comprenden epotilonas y sus usos farmaceuticos.
US7649006B2 (en) 2002-08-23 2010-01-19 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
WO2004018478A2 (en) 2002-08-23 2004-03-04 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
MXPA05003513A (es) * 2002-10-04 2005-06-03 Pharmacia Corp Composiciones farmaceuticas para tratamiento de enfermedad de parkinson.
WO2006017761A2 (en) * 2004-08-05 2006-02-16 Emory University Epothilone analogues as therapeutic agents
US20060121511A1 (en) 2004-11-30 2006-06-08 Hyerim Lee Biomarkers and methods for determining sensitivity to microtubule-stabilizing agents
EP1674098A1 (de) * 2004-12-23 2006-06-28 Schering Aktiengesellschaft Stabile, unbedenkliche parenterale Formulierungen von hochreaktiven organischen Arzneimitteln mit niedriger oder keiner wässrigen Löslichkeit
JP2008536479A (ja) 2005-02-11 2008-09-11 ユニバーシティ オブ サザン カリフォルニア ジスルフィド架橋を有するタンパク質の発現法
US8008256B2 (en) * 2006-05-01 2011-08-30 University Of Southern California Combination therapy for treatment of cancer
EP2065054A1 (de) 2007-11-29 2009-06-03 Bayer Schering Pharma Aktiengesellschaft Kombinationen mit einem Prostaglandin und Verwendungen davon
EP2070521A1 (de) 2007-12-10 2009-06-17 Bayer Schering Pharma Aktiengesellschaft Nanopartikel mit modifizierter Oberfläche
DE102007059752A1 (de) 2007-12-10 2009-06-18 Bayer Schering Pharma Aktiengesellschaft Funktionalisierte, feste Polymernanopartikel enthaltend Epothilone
WO2010056901A2 (en) 2008-11-13 2010-05-20 University Of Southern California Method of expressing proteins with disulfide bridges with enhanced yields and activity
EP2210584A1 (de) 2009-01-27 2010-07-28 Bayer Schering Pharma Aktiengesellschaft Stabile Polymerzusammensetzung mit einem Epothilon und einem amphiphilischen Blockpolymer
US9717803B2 (en) 2011-12-23 2017-08-01 Innate Pharma Enzymatic conjugation of polypeptides
WO2014009426A2 (en) 2012-07-13 2014-01-16 Innate Pharma Screening of conjugated antibodies
WO2014072482A1 (en) 2012-11-09 2014-05-15 Innate Pharma Recognition tags for tgase-mediated conjugation
US10611824B2 (en) 2013-03-15 2020-04-07 Innate Pharma Solid phase TGase-mediated conjugation of antibodies
WO2014202773A1 (en) 2013-06-20 2014-12-24 Innate Pharma Enzymatic conjugation of polypeptides
WO2014202775A1 (en) 2013-06-21 2014-12-24 Innate Pharma Enzymatic conjugation of polypeptides
WO2019092148A1 (en) 2017-11-10 2019-05-16 Innate Pharma Antibodies with functionalized glutamine residues

Citations (1)

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WO1997019086A1 (de) * 1995-11-17 1997-05-29 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilonderivate, herstellung und verwendung

Patent Citations (1)

* 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

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
M. SEFKOW ET AL.: "Derivatization of the C12-C13 functional groups of epothilones A, B and C", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 8, 1998, pages 3031 - 3036, XP004141869 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
AU2001262221A1 (en) 2001-11-07
JP2003531207A (ja) 2003-10-21
US20040058969A1 (en) 2004-03-25
NO20025029D0 (no) 2002-10-18
WO2001081342A2 (de) 2001-11-01
DE10020517A1 (de) 2001-10-25
NO20025029L (no) 2002-10-18
EP1276740A2 (de) 2003-01-22

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