IL272837B2 - Process for the preparation of tubulysins and intermediates thereof - Google Patents

Process for the preparation of tubulysins and intermediates thereof

Info

Publication number
IL272837B2
IL272837B2 IL272837A IL27283720A IL272837B2 IL 272837 B2 IL272837 B2 IL 272837B2 IL 272837 A IL272837 A IL 272837A IL 27283720 A IL27283720 A IL 27283720A IL 272837 B2 IL272837 B2 IL 272837B2
Authority
IL
Israel
Prior art keywords
formula
composition
salt
compound
optical
Prior art date
Application number
IL272837A
Other languages
English (en)
Hebrew (he)
Other versions
IL272837B1 (en
IL272837A (en
Original Assignee
Seagen Inc
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 Seagen Inc filed Critical Seagen Inc
Publication of IL272837A publication Critical patent/IL272837A/en
Publication of IL272837B1 publication Critical patent/IL272837B1/en
Publication of IL272837B2 publication Critical patent/IL272837B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817—Toxins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • 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
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Toxicology (AREA)
  • Cell Biology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
IL272837A 2017-09-08 2018-09-07 Process for the preparation of tubulysins and intermediates thereof IL272837B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762556234P 2017-09-08 2017-09-08
PCT/US2018/050095 WO2019051322A1 (en) 2017-09-08 2018-09-07 PROCESS FOR THE PREPARATION OF TUBULYSINS AND INTERMEDIATES THEREOF

Publications (3)

Publication Number Publication Date
IL272837A IL272837A (en) 2020-04-30
IL272837B1 IL272837B1 (en) 2024-02-01
IL272837B2 true IL272837B2 (en) 2024-06-01

Family

ID=63963374

Family Applications (1)

Application Number Title Priority Date Filing Date
IL272837A IL272837B2 (en) 2017-09-08 2018-09-07 Process for the preparation of tubulysins and intermediates thereof

Country Status (15)

Country Link
US (2) US11389543B2 (enExample)
EP (1) EP3679036A1 (enExample)
JP (2) JP2020533308A (enExample)
KR (1) KR20200051733A (enExample)
CN (1) CN111601803A (enExample)
AU (1) AU2018329951B2 (enExample)
BR (1) BR112020004495A2 (enExample)
CA (1) CA3073766A1 (enExample)
EA (1) EA202090670A1 (enExample)
IL (1) IL272837B2 (enExample)
MA (1) MA50124A (enExample)
MX (1) MX2020001928A (enExample)
SG (1) SG11202001543XA (enExample)
TW (2) TWI820038B (enExample)
WO (1) WO2019051322A1 (enExample)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MA50124A (fr) * 2017-09-08 2020-07-15 Seattle Genetics Inc Procédé de préparation de tubulysines et d'intermédiaires de celles-ci
KR20210073525A (ko) * 2018-09-07 2021-06-18 씨젠 인크. 튜불리신 및 이의 중간체의 제조를 위한 대체 방법들
JP2024510435A (ja) 2021-03-18 2024-03-07 シージェン インコーポレイテッド 生体活性化合物の内部移行複合体からの選択的薬物放出

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004005269A1 (de) * 2002-07-09 2004-01-15 Morphochem Ag Komb Chemie Verfahren zur herstellung von substituierten thiazol-2-ylmethylestern
WO2008106080A2 (en) * 2007-02-27 2008-09-04 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Synthesis of desacetoxytubulysin h and analogs thereof
EP2708243A1 (en) * 2012-09-17 2014-03-19 OntoChem GmbH Receptor ligand linked cytotoxic molecules
WO2016040684A1 (en) * 2014-09-11 2016-03-17 Seattle Genetics, Inc Targeted delivery of tertiary amine-containing drug substances
WO2016090050A1 (en) * 2014-12-03 2016-06-09 Genentech, Inc. Quaternary amine compounds and antibody-drug conjugates thereof
WO2016138288A1 (en) * 2015-02-25 2016-09-01 William Marsh Rice University Desacetoxytubulysin h and analogs thereof

Family Cites Families (9)

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Publication number Priority date Publication date Assignee Title
ES2708763T3 (es) 2005-07-07 2019-04-11 Seattle Genetics Inc Compuestos de monometilvalina que tienen modificaciones de la cadena lateral de fenilalanina en el extremo C
PT2032606E (pt) 2006-05-30 2014-02-05 Genentech Inc Anticorpos e imunoconjugados e respetivas utilizações
CN109627287A (zh) 2007-02-23 2019-04-16 爱勒让治疗公司 三唑大环系统
CA2866612C (en) 2012-03-08 2018-01-16 Halozyme, Inc. Conditionally active ph-dependent cetuximab variant anti-epidermal growth factor receptor antibodies and method of use thereof
CN104640572B (zh) 2012-05-15 2018-04-27 索伦托医疗有限公司 药物偶联物，偶联方法，及其用途
CN104822656B (zh) 2012-05-15 2018-05-01 西雅图基因公司 自稳定接头偶联物
PE20160715A1 (es) 2013-05-31 2016-08-01 Genentech Inc Anticuerpos frente a acidos teicoicos de pared y conjugados
MX369758B (es) 2013-05-31 2019-11-20 Genentech Inc Anticuerpos anti-acido teicoico de pared y conjugados.
MA50124A (fr) * 2017-09-08 2020-07-15 Seattle Genetics Inc Procédé de préparation de tubulysines et d'intermédiaires de celles-ci

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004005269A1 (de) * 2002-07-09 2004-01-15 Morphochem Ag Komb Chemie Verfahren zur herstellung von substituierten thiazol-2-ylmethylestern
WO2008106080A2 (en) * 2007-02-27 2008-09-04 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Synthesis of desacetoxytubulysin h and analogs thereof
EP2708243A1 (en) * 2012-09-17 2014-03-19 OntoChem GmbH Receptor ligand linked cytotoxic molecules
WO2016040684A1 (en) * 2014-09-11 2016-03-17 Seattle Genetics, Inc Targeted delivery of tertiary amine-containing drug substances
WO2016090050A1 (en) * 2014-12-03 2016-06-09 Genentech, Inc. Quaternary amine compounds and antibody-drug conjugates thereof
WO2016138288A1 (en) * 2015-02-25 2016-09-01 William Marsh Rice University Desacetoxytubulysin h and analogs thereof

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
JEREMY S. PARKER ET AL,, THE DEVELOPMENT AND SCALE-UP OF AN ANTIBODY DRUG CONJUGATE TUBULYSIN PAYLOAD, 1 August 2017 (2017-08-01) *
MONICA SANI ET AL,, TOTAL SYNTHESIS OF TUBULYSINS?U AND V, 4 May 2007 (2007-05-04) *
P. SREEJITH SHANKAR ET AL,, SYNTHESIS AND CYTOTOXICITY EVALUATION OF DIASTEREOISOMERS AND N-TERMINAL ANALOGUES OF TUBULYSIN-U, 11 September 2013 (2013-09-11) *
PUBCHEM, 2-[(1S,3R)-1-ACETYLOXY-4-METHYL-3-[METHYL-[(2-METHYLPROPAN-2-YL)OXYCARBONYL]AMINO]PENTYL]- 1,3-THIAZOLE-4-CARBOXYLIC ACID, 21 March 2013 (2013-03-21) *
SREEJITH P. SHANKAR ET AL,, SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIP STUDIES OF NOVEL TUBULYSIN U ANALOGUES - EFFECT ON CYTOTOXICITY OF STRUCTURAL VARIATIONS IN THE TUBUVALINE FRAGMENT, 1 January 2013 (2013-01-01) *

Also Published As

Publication number Publication date
IL272837B1 (en) 2024-02-01
TWI820038B (zh) 2023-11-01
MA50124A (fr) 2020-07-15
JP2020533308A (ja) 2020-11-19
US20220323601A1 (en) 2022-10-13
AU2018329951A1 (en) 2020-04-16
MX2020001928A (es) 2020-03-24
WO2019051322A1 (en) 2019-03-14
CA3073766A1 (en) 2019-03-14
IL272837A (en) 2020-04-30
BR112020004495A2 (pt) 2020-09-08
US11389543B2 (en) 2022-07-19
US20200297864A1 (en) 2020-09-24
JP2023053386A (ja) 2023-04-12
KR20200051733A (ko) 2020-05-13
TW202428569A (zh) 2024-07-16
AU2018329951B2 (en) 2023-12-14
TW201920128A (zh) 2019-06-01
EP3679036A1 (en) 2020-07-15
EA202090670A1 (ru) 2020-07-28
SG11202001543XA (en) 2020-03-30
CN111601803A (zh) 2020-08-28

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