WO2004046170A3 - Tubulysine, herstellungsverfahren und tubulysin-mittel - Google Patents

Tubulysine, herstellungsverfahren und tubulysin-mittel Download PDF

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Publication number
WO2004046170A3
WO2004046170A3 PCT/EP2003/011603 EP0311603W WO2004046170A3 WO 2004046170 A3 WO2004046170 A3 WO 2004046170A3 EP 0311603 W EP0311603 W EP 0311603W WO 2004046170 A3 WO2004046170 A3 WO 2004046170A3
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
aryl
alkenyl
tubulysin
tubulysins
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/EP2003/011603
Other languages
English (en)
French (fr)
Other versions
WO2004046170A2 (de
Inventor
Gerhard Hoefle
Nicole Glaser
Heinrich Steinmetz
Thomas Leibold
Florenz Sasse
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.)
Helmholtz Zentrum fuer Infektionsforschung HZI GmbH
Original Assignee
Helmholtz Zentrum fuer Infektionsforschung HZI GmbH
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 Helmholtz Zentrum fuer Infektionsforschung HZI GmbH filed Critical Helmholtz Zentrum fuer Infektionsforschung HZI GmbH
Priority to EP03775204A priority Critical patent/EP1562979B1/de
Priority to AU2003283282A priority patent/AU2003283282A1/en
Priority to DE50310721T priority patent/DE50310721D1/de
Priority to JP2004552485A priority patent/JP4620467B2/ja
Priority to US10/535,630 priority patent/US7754885B2/en
Publication of WO2004046170A2 publication Critical patent/WO2004046170A2/de
Publication of WO2004046170A3 publication Critical patent/WO2004046170A3/de
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • C07D417/12—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 chain containing hetero atoms as chain links
    • 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
    • C07D417/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/021—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)n-C(=0)-, n being 5 or 6; for n > 6, classification in C07K5/06 - C07K5/10, according to the moiety having normal peptide bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Die Erfindung betrifft eine Verbindung der folgenden allgemeinen Formel (Tubulysin) mit den folgenden Bedeutungen für R, R1, R2, R3, R4, R5, R6, R7,R8 R9, R10, R11, S, T, U, V, W, X, Y und Z: R = H, C1-4-Alkyl, Aryl, OR1, NR1R2 oder NH- (CH2) 2-R1 = H, C1-6-Alkyl oder Aryl R2 = H, C1-6-Alkyl oder Aryl S = H, Hal, NO2 oder NHR3 U = H, Hal, NO2 oder NHR3 R3 = H, HCO oder C1-4-Alkyl-CO T = H oder OR4 R4 = H, C1-4-Alkyl, Aryl, COR5, P (O) (OR6) 2 oder SO3R6 R5 = C1-6-Alkyl, Alkenyl, Aryl oder Heteroaryl R6 = H, C1-4-Alkyl oder Metallion V = H oder R7 oder (für W = O) O R7 = H, C1-4-Alkyl oder COR8 R8 = C-1-4-Alkyl, Alkenyl oder Aryl W = H oder C1-4-Alkyl oder (für V = O) O X = H, C1-4-Alkyl, Alkenyl oder CH20R9 R9 = H, C1-4-Alkyl, Alkenyl, Aryl oder COR10 R10 = C1-6-Alkyl, Alkenyl, Aryl oder Heteroaryl Y = (für Z = CH3 oder COR11)freies Elektronenpaar oder (für Z =CH3) O R11 = C1-4-Alkyl, CF3 oder Aryl und/oder Z = (für Y = O oder freies Elektronenpaar) CH3 oder (für Y = freies Elektronenpaar) COR11.
PCT/EP2003/011603 2002-11-21 2003-10-20 Tubulysine, herstellungsverfahren und tubulysin-mittel Ceased WO2004046170A2 (de)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP03775204A EP1562979B1 (de) 2002-11-21 2003-10-20 Tubulysine, herstellungsverfahren und tubulysin-mittel
AU2003283282A AU2003283282A1 (en) 2002-11-21 2003-10-20 Tubulysins, method for producing the same and tubulysin preparations
DE50310721T DE50310721D1 (de) 2002-11-21 2003-10-20 Tubulysine, herstellungsverfahren und tubulysin-mittel
JP2004552485A JP4620467B2 (ja) 2002-11-21 2003-10-20 チューブライシン、その製造方法、及び、チューブライシン製剤
US10/535,630 US7754885B2 (en) 2002-11-21 2003-10-20 Tubulysins, method for producing the same and tubulysin preparations

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10254439.5 2002-11-21
DE10254439A DE10254439A1 (de) 2002-11-21 2002-11-21 Tubulysine, Herstellungsverfahren und Tubulysin-Mittel

Publications (2)

Publication Number Publication Date
WO2004046170A2 WO2004046170A2 (de) 2004-06-03
WO2004046170A3 true WO2004046170A3 (de) 2004-07-01

Family

ID=32240267

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2003/011603 Ceased WO2004046170A2 (de) 2002-11-21 2003-10-20 Tubulysine, herstellungsverfahren und tubulysin-mittel

Country Status (7)

Country Link
US (1) US7754885B2 (de)
EP (2) EP1562979B1 (de)
JP (1) JP4620467B2 (de)
AT (1) ATE412659T1 (de)
AU (1) AU2003283282A1 (de)
DE (2) DE10254439A1 (de)
WO (1) WO2004046170A2 (de)

Cited By (7)

* Cited by examiner, † Cited by third party
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US9138484B2 (en) 2007-06-25 2015-09-22 Endocyte, Inc. Conjugates containing hydrophilic spacer linkers
US9187521B2 (en) 2007-10-25 2015-11-17 Endocyte, Inc. Tubulysins and processes for preparing
US9505747B2 (en) 2012-03-29 2016-11-29 Endocyte, Inc. Processes for preparing tubulysin derivatives and conjugates thereof
US9550734B2 (en) 2004-07-23 2017-01-24 Endocyte, Inc. Bivalent linkers and conjugates thereof
US9555139B2 (en) 2007-03-14 2017-01-31 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins
US11229708B2 (en) 2015-12-04 2022-01-25 Seagen Inc. Conjugates of quaternized tubulysin compounds
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds

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WO2003097647A1 (en) * 2002-05-15 2003-11-27 Endocyte, Inc. Vitamin-mitomycin conjugates
AU2003266233A1 (en) * 2002-07-09 2004-01-23 Morphochem Aktiengesellschaft Fur Kombinatorische Chemie Novel tubulysin analogues
DK1592457T3 (da) 2003-01-27 2012-10-22 Endocyte Inc Folat-vinblastin-konjugat som lægemiddel
EP1863816B1 (de) * 2005-03-16 2014-06-25 Endocyte, Inc. Synthese und aufreinigung von pteroinsäure und konjugaten davon
EP2382995A3 (de) * 2005-08-19 2013-09-25 Endocyte, Inc. Ligandenkonjugate von Vincaalkaloiden, Analoga und Derivaten
AU2006279304A1 (en) * 2005-08-19 2007-02-22 Endocyte, Inc. Multi-drug ligand conjugates
WO2008101231A2 (en) 2007-02-16 2008-08-21 Endocyte, Inc. Methods and compositions for treating and diagnosing kidney disease
US8980833B2 (en) * 2007-05-10 2015-03-17 R&D-Biopharmaceuticals Gmbh Tubulysine derivatives
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
US8476451B2 (en) * 2007-07-20 2013-07-02 The Regents Of The University Of California Tubulysin D analogues
EP2181101A2 (de) * 2007-07-20 2010-05-05 Helmholtz-Zentrum für Infektionsforschung GmbH Tubulysin-d-analoga
EP2174947A1 (de) * 2008-09-25 2010-04-14 Universität des Saarlandes Bioaktive Prätubulysine und Verwendung davon
IT1394860B1 (it) 2009-07-22 2012-07-20 Kemotech S R L Composti farmaceutici
US8394922B2 (en) 2009-08-03 2013-03-12 Medarex, Inc. Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
EP2409983A1 (de) 2010-07-19 2012-01-25 Leibniz-Institut für Pflanzenbiochemie (IPB) Tubulysinanaloga
AU2011285532B2 (en) 2010-08-06 2015-09-10 Endocyte, Inc. Processes for preparing tubulysins
WO2012171020A1 (en) 2011-06-10 2012-12-13 Mersana Therapeutics, Inc. Protein-polymer-drug conjugates
CN104244718A (zh) * 2011-12-05 2014-12-24 伊格尼卡生物治疗公司 抗体-药物缀合物以及相关化合物、组合物和方法
US10080805B2 (en) 2012-02-24 2018-09-25 Purdue Research Foundation Cholecystokinin B receptor targeting for imaging and therapy
US9981046B2 (en) 2012-05-15 2018-05-29 Concortis Biosystems, Corp., a wholly owned Subsidiary of Sorrento Therapeutics, Inc. Drug-conjugates, conjugation methods, and uses thereof
US11873281B2 (en) 2012-07-12 2024-01-16 Hangzhou Dac Biotech Co., Ltd. Conjugates of cell binding molecules with cytotoxic agents
PL2872157T3 (pl) 2012-07-12 2020-07-13 Hangzhou Dac Biotech Co., Ltd Koniugaty wiążących komórkę cząsteczek ze środkami cytotoksycznymi
EP2708243A1 (de) 2012-09-17 2014-03-19 OntoChem GmbH Rezeptor-Ligand-verbundene zytotoxische Moleküle
EP2908818A4 (de) 2012-10-16 2016-07-13 Endocyte Inc Wirkstofffreisetzungskonjugate mit unnatürlichen aminosäuren und verfahren zur verwendung
BR112015011118B1 (pt) 2012-11-15 2022-12-13 Endocyte, Inc Conjugado; composição farmacêutica; e uso de um conjugado
US10131682B2 (en) 2012-11-24 2018-11-20 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to a cell binding molecules
CA2892863C (en) 2012-12-10 2022-03-15 Mersana Therapeutics, Inc. Polymeric scaffold based on phf for targeted drug delivery
WO2014093640A1 (en) 2012-12-12 2014-06-19 Mersana Therapeutics,Inc. Hydroxy-polmer-drug-protein conjugates
RS56169B1 (sr) 2013-02-14 2017-11-30 Bristol Myers Squibb Co Jedinjenja tubulisina, metode pripreme i primena
US20140249315A1 (en) 2013-03-01 2014-09-04 Endocyte, Inc. Processes for preparing tubulysins
US10781259B2 (en) 2013-06-06 2020-09-22 Magenta Therapeutics, Inc. Modified antibodies and related compounds, compositions, and methods of use
WO2015057876A1 (en) 2013-10-15 2015-04-23 Sorrento Therapeutics Inc. Drug-conjugates with a targeting molecule and two different drugs
ES2826398T3 (es) 2013-10-15 2021-05-18 Seagen Inc Enlazadores-fármacos pegilados para una mejor farmacocinética de los conjugados ligando-fármaco
WO2015113760A1 (en) * 2014-01-28 2015-08-06 Tube Pharmaceuticals Gmbh Cytotoxic tubulysin compounds for conjugation
CA2938919C (en) 2014-02-28 2020-12-29 Hangzhou Dac Biotech Co., Ltd Charged linkers and their uses for conjugation
MX2016012830A (es) 2014-04-11 2017-01-05 Medimmune Llc Anticuerpos contra el receptor 2 del factor de crecimiento epidermico humano (her2) biespecificos.
US10077287B2 (en) 2014-11-10 2018-09-18 Bristol-Myers Squibb Company Tubulysin analogs and methods of making and use
CN105641707B (zh) * 2014-11-11 2020-11-24 杭州多禧生物科技有限公司 细胞毒素分子同细胞结合受体分子的共轭体
EP3250238B1 (de) 2015-01-28 2022-06-01 Sorrento Therapeutics, Inc. Antikörper-wirkstoff-konjugate
FI3319936T3 (fi) 2015-07-12 2026-03-12 Hangzhou Dac Biotech Co Ltd Silloituslinkkereitä soluun sitoutuvien molekyylien konjugoimiseksi
US9839687B2 (en) 2015-07-15 2017-12-12 Suzhou M-Conj Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
SMT202000285T1 (it) 2015-11-10 2020-07-08 Medimmune Llc Molecole di legame specifiche per asct2 e loro usi
KR20180134351A (ko) 2016-03-25 2018-12-18 시애틀 지네틱스, 인크. 페길화된 약물-링커 및 그의 중간체의 제조를 위한 공정
CA3042442C (en) 2016-11-14 2024-01-02 Hangzhou Dac Biotech Co., Ltd Conjugation linkers, cell binding molecule-drug conjugates containing the linkers, methods of making and uses of such conjugates with the linkers
AU2018237683A1 (en) 2017-03-24 2019-10-31 Seagen Inc. Process for the preparation of glucuronide drug-linkers and intermediates thereof
US10988546B2 (en) 2017-08-01 2021-04-27 Medimmune, Llc BCMA monoclonal antibody-drug conjugate
JP2022540395A (ja) 2019-06-29 2022-09-15 ハンジョウ ディーエーシー バイオテック シーオー．，エルティディ． 細胞結合性分子－チューブリシン誘導体共役体及びその調製方法
US20220241377A1 (en) 2019-07-24 2022-08-04 Molgenie GmbH Receptor-targeting peptide-drug conjugates
CR20230146A (es) 2020-09-11 2023-06-07 Medimmune Ltd Moléculas de unión a b7-h4 terapéuticas
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TW202448517A (zh) 2023-02-16 2024-12-16 瑞典商阿斯特捷利康公司 用治療性結合分子治療癌症的組合療法

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9550734B2 (en) 2004-07-23 2017-01-24 Endocyte, Inc. Bivalent linkers and conjugates thereof
US9555139B2 (en) 2007-03-14 2017-01-31 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins
US9138484B2 (en) 2007-06-25 2015-09-22 Endocyte, Inc. Conjugates containing hydrophilic spacer linkers
US9187521B2 (en) 2007-10-25 2015-11-17 Endocyte, Inc. Tubulysins and processes for preparing
US9505747B2 (en) 2012-03-29 2016-11-29 Endocyte, Inc. Processes for preparing tubulysin derivatives and conjugates thereof
US11229708B2 (en) 2015-12-04 2022-01-25 Seagen Inc. Conjugates of quaternized tubulysin compounds
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds

Also Published As

Publication number Publication date
DE10254439A1 (de) 2004-06-03
JP4620467B2 (ja) 2011-01-26
DE50310721D1 (de) 2008-12-11
JP2006518704A (ja) 2006-08-17
EP1562979B1 (de) 2008-10-29
EP2028185A1 (de) 2009-02-25
US7754885B2 (en) 2010-07-13
US20060128754A1 (en) 2006-06-15
AU2003283282A1 (en) 2004-06-15
WO2004046170A2 (de) 2004-06-03
ATE412659T1 (de) 2008-11-15
AU2003283282A8 (en) 2004-06-15
EP1562979A2 (de) 2005-08-17

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