TWI820038B - 妥布賴森(tubulysins)及其中間產物之製備方法 - Google Patents

妥布賴森(tubulysins)及其中間產物之製備方法 Download PDF

Info

Publication number
TWI820038B
TWI820038B TW107131484A TW107131484A TWI820038B TW I820038 B TWI820038 B TW I820038B TW 107131484 A TW107131484 A TW 107131484A TW 107131484 A TW107131484 A TW 107131484A TW I820038 B TWI820038 B TW I820038B
Authority
TW
Taiwan
Prior art keywords
formula
composition
optionally substituted
compound
moiety
Prior art date
Application number
TW107131484A
Other languages
English (en)
Chinese (zh)
Other versions
TW201920128A (zh
Inventor
吳坤亮
金慶武
文戴爾 道博戴
Original Assignee
美商思進公司
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 美商思進公司 filed Critical 美商思進公司
Publication of TW201920128A publication Critical patent/TW201920128A/zh
Application granted granted Critical
Publication of TWI820038B publication Critical patent/TWI820038B/zh

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)
TW107131484A 2017-09-08 2018-09-07 妥布賴森(tubulysins)及其中間產物之製備方法 TWI820038B (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762556234P 2017-09-08 2017-09-08
US62/556,234 2017-09-08

Publications (2)

Publication Number Publication Date
TW201920128A TW201920128A (zh) 2019-06-01
TWI820038B true TWI820038B (zh) 2023-11-01

Family

ID=63963374

Family Applications (2)

Application Number Title Priority Date Filing Date
TW107131484A TWI820038B (zh) 2017-09-08 2018-09-07 妥布賴森(tubulysins)及其中間產物之製備方法
TW112136966A TW202428569A (zh) 2017-09-08 2018-09-07 妥布賴森(tubulysins)及其中間產物之製備方法

Family Applications After (1)

Application Number Title Priority Date Filing Date
TW112136966A TW202428569A (zh) 2017-09-08 2018-09-07 妥布賴森(tubulysins)及其中間產物之製備方法

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 (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10230872A1 (de) 2002-07-09 2004-01-22 Morphochem AG Aktiengesellschaft für kombinatorische Chemie Verfahren zur Herstellung von substituierten Thiazol-2-ylmethylestern
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
EP2708243A1 (en) * 2012-09-17 2014-03-19 OntoChem GmbH Receptor ligand linked cytotoxic molecules
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.
HRP20241124T1 (hr) * 2014-09-11 2024-11-22 Seagen Inc. Ciljana isporuka lijekovitih tvari koje sadrže tercijarni amin
CA2969689A1 (en) * 2014-12-03 2016-06-09 Genentech, Inc. Quaternary amine compounds and antibody-drug conjugates thereof
KR20170137725A (ko) * 2015-02-25 2017-12-13 윌리엄 마쉬 라이스 유니버시티 데스아세톡시투불리신 h 및 이의 유사체
MA50124A (fr) * 2017-09-08 2020-07-15 Seattle Genetics Inc Procédé de préparation de tubulysines et d'intermédiaires de celles-ci

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
期刊 Sani et al., "Total Synthesis of Tubulysins U and V", Angewandte Chemie, 119, 2007, pp 3596-3599. *

Also Published As

Publication number Publication date
IL272837B1 (en) 2024-02-01
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
IL272837B2 (en) 2024-06-01
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

Similar Documents

Publication Publication Date Title
CN114728073B (zh) 药物从生物活性化合物的内化缀合物的选择性释放
JP2023106627A (ja) Ｐｅｇ化薬物リンカー及びその中間体を調製するためのプロセス
CA3103151A1 (en) Compound having affinity substance to antibody and bioorthogonal functional group, or salt thereof
CN107108694B (zh) 含叔胺药物物质的靶向递送
KR20230133312A (ko) 캄프토테신 항체-약물 접합체 및 이의 사용 방법
TWI838358B (zh) 疏水性奧瑞他汀(auristatin)f化合物及其結合物
JP7605290B2 (ja) 化合物またはその塩、およびそれらにより得られる抗体
JP2023053386A (ja) チューブリシンおよびそれらの中間体の調製のためのプロセス
TWI825169B (zh) 妥布賴森(tubulysins)及其中間體之製備之替代方法
CA3208290A1 (en) Compound or salt thereof, and antibody obtained by using the same
HK40045709A (en) Alternative processes for the preparation of tubulysins and intermediates thereof
HK40036588A (en) Process for the preparation of tubulysins and intermediates thereof

Legal Events

Date Code Title Description
MM4A Annulment or lapse of patent due to non-payment of fees