WO2000049019A3 - Novel epothilone derivatives, method for producing them and their pharmaceutical use - Google Patents

Novel epothilone derivatives, method for producing them and their pharmaceutical use 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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WO
WIPO (PCT)
Prior art keywords
compounds
novel
epothilone derivatives
tumours
order
Prior art date
Application number
PCT/EP2000/001331
Other languages
German (de)
French (fr)
Other versions
WO2000049019A2 (en
Inventor
Ulrich Klar
Wolfgang Schwede
Werner Skuballa
Bernd Buchmann
Michael Schirner
Andreas Menrad
Original Assignee
Schering Ag
Ulrich Klar
Wolfgang Schwede
Werner Skuballa
Bernd Buchmann
Michael Schirner
Andreas Menrad
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 Schering Ag, Ulrich Klar, Wolfgang Schwede, Werner Skuballa, Bernd Buchmann, Michael Schirner, Andreas Menrad filed Critical Schering Ag
Priority to AU38048/00A priority Critical patent/AU3804800A/en
Publication of WO2000049019A2 publication Critical patent/WO2000049019A2/en
Publication of WO2000049019A3 publication Critical patent/WO2000049019A3/en

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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

The invention relates to novel epothilone derivatives of general formula (I), wherein the substituents Y, Z, R?1a, R1b, R2a, R2b¿, G'-G-E-E', R?5, R6, R7, R8, R14¿ and X have the meanings specified in the description. The novel compounds interact with tubulin by stabilising the microtubuli which are formed. They are able to influence the cell division phase-specifically and are suitable for treating malignant tumours such as cancers of the ovaries, stomach, colon, glands, breasts, lungs and head and neck, malignant melanoma and acute lymphocytic and myelocytic leukaemia. The compounds are also suitable for anti-angiogenesis therapy and for treating chronic inflammatory diseases (psoriasis, arthritis) and can be deposited on or in polymer materials in order to prevent uncontrolled cell proliferations on medical implants and to improve the compatibility thereof. The inventive compounds can be used alone or in combination with other principles and classes of substances that can be used in the therapy of tumours in order to achieve additive or synergistic effects.
PCT/EP2000/001331 1999-02-18 2000-02-18 Novel epothilone derivatives, method for producing them and their pharmaceutical use WO2000049019A2 (en)

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 (en) 1999-02-18 1999-02-18 New, chemically and metabolically stable epothilon derivatives having modified macrocyclic ring, useful e.g. for treating malignant tumors or chronic inflammatory disease, are cell division regulators

Publications (2)

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

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/001331 WO2000049019A2 (en) 1999-02-18 2000-02-18 Novel epothilone derivatives, method for producing them and their pharmaceutical use

Country Status (3)

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

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 (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL207197B1 (en) * 2001-02-27 2010-11-30 Novartis Ag Combination comprising a signal transduction inhibitor and an epothilone derivative
JP2004529904A (en) * 2001-03-14 2004-09-30 ブリストル−マイヤーズ　スクイブ　カンパニー Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases
TWI315982B (en) * 2001-07-19 2009-10-21 Novartis Ag Combinations comprising epothilones and pharmaceutical uses thereof
AU2008203233B2 (en) * 2001-07-19 2010-04-29 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 (en) 2002-03-12 2010-04-21 Bristol-Myers Squibb Company DERIVATIVES OF C3-CIANO-EPOTILONE.
MXPA04012444A (en) * 2002-06-10 2005-04-19 Novartis Ag Combinations comprising epothilones and pharmaceutical uses thereof.
US7649006B2 (en) 2002-08-23 2010-01-19 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
SI1767535T1 (en) 2002-08-23 2010-03-31 Sloan Kettering Inst Cancer Synthesis of epothilones, intermediates thereto, analogues and uses thereof
EP1674098A1 (en) 2004-12-23 2006-06-28 Schering Aktiengesellschaft Stable and tolerable parental formulations of highly reactive organic drug substances with low or no solubility in water
EP1959952A4 (en) * 2005-11-22 2011-02-23 Scripps Research Inst Chemical synthesis of a highly potent epothilone
EP2065054A1 (en) 2007-11-29 2009-06-03 Bayer Schering Pharma Aktiengesellschaft Combinations comprising a prostaglandin and uses thereof
DE102007059752A1 (en) 2007-12-10 2009-06-18 Bayer Schering Pharma Aktiengesellschaft Functionalized solid polymer nanoparticles containing epothilones
EP2070521A1 (en) 2007-12-10 2009-06-17 Bayer Schering Pharma Aktiengesellschaft Surface-modified nanoparticles
EP2210584A1 (en) 2009-01-27 2010-07-28 Bayer Schering Pharma Aktiengesellschaft Stable polymeric composition comprising an epothilone and an amphiphilic block copolymer
US9717803B2 (en) 2011-12-23 2017-08-01 Innate Pharma Enzymatic conjugation of polypeptides
US10132799B2 (en) 2012-07-13 2018-11-20 Innate Pharma Screening of conjugated antibodies
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
JP6744212B2 (en) 2013-06-21 2020-08-19 イナート・ファルマ・ソシエテ・アノニムＩｎｎａｔｅ Ｐｈａｒｍａ Ｐｈａｒｍａ Ｓ．Ａ． Enzymatic binding 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 (en) * 1995-11-17 1997-05-29 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilone derivatives, preparation and use
WO1999007692A2 (en) * 1997-08-09 1999-02-18 Schering Aktiengesellschaft New epothilone derivatives, method for producing same and their pharmaceutical use
WO1999065913A2 (en) * 1998-06-18 1999-12-23 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilone minor constituents

Patent Citations (3)

* Cited by examiner, † Cited by third party
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WO1997019086A1 (en) * 1995-11-17 1997-05-29 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilone derivatives, preparation and use
WO1999007692A2 (en) * 1997-08-09 1999-02-18 Schering Aktiengesellschaft New epothilone derivatives, method for producing same and their pharmaceutical use
WO1999065913A2 (en) * 1998-06-18 1999-12-23 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilone minor constituents

Non-Patent Citations (7)

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HANESSIAN, STEPHEN ET AL: "Total Synthesis and Absolute Configuration of (-)-Anthoplalone", J. ORG. CHEM. (1999), 64(13), 4893-4900, XP002152894 *
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K C NICOLAOU ET AL: "NATURE,MACMILLAN JOURNALS LTD. LONDON,GB", NATURE,MACMILLAN JOURNALS LTD. LONDON,GB, vol. 387, no. 6630, 15 May 1997 (1997-05-15), pages 268 - 272, XP002095721, ISSN: 0028-0836 *
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 *
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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
WO2000049019A2 (en) 2000-08-24
AU3804800A (en) 2000-09-04
DE19908760A1 (en) 2000-08-24

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