TWI863657B - 巨環化合物及其用途 - Google Patents

巨環化合物及其用途 Download PDF

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Publication number
TWI863657B
TWI863657B TW112141425A TW112141425A TWI863657B TW I863657 B TWI863657 B TW I863657B TW 112141425 A TW112141425 A TW 112141425A TW 112141425 A TW112141425 A TW 112141425A TW I863657 B TWI863657 B TW I863657B
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compound
cancer
tumor
day
mice
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TW112141425A
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Chinese (zh)
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TW202426457A (zh
Inventor
義人 岸
吉良和信
伊藤憲
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哈佛大學校長及研究員協會
日商衛材R&D企管股份有限公司
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Priority claimed from US15/814,105 external-priority patent/US9938288B1/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39558Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D309/00Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/04Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D493/00Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/22Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/32Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Mycology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microbiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Biomedical Technology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Display Devices Of Pinball Game Machines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
TW112141425A 2017-04-05 2018-04-03 巨環化合物及其用途 TWI863657B (zh)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US201762482030P 2017-04-05 2017-04-05
US62/482,030 2017-04-05
US201762526677P 2017-06-29 2017-06-29
US62/526,677 2017-06-29
US201762586416P 2017-11-15 2017-11-15
US62/586,416 2017-11-15
US15/814,105 US9938288B1 (en) 2017-04-05 2017-11-15 Macrocyclic compound and uses thereof
US15/814,105 2017-11-15

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TW202426457A TW202426457A (zh) 2024-07-01
TWI863657B true TWI863657B (zh) 2024-11-21

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US (2) US11725015B2 (https=)
EP (2) EP4119563A3 (https=)
JP (4) JP7168580B2 (https=)
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Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10556910B2 (en) 2014-06-30 2020-02-11 President And Fellows Of Harvard College Synthesis of halichondrin analogs and uses thereof
US10344038B2 (en) 2015-04-30 2019-07-09 President And Fellows Of Harvard College Chromium-mediated coupling and application to the synthesis of halichondrins
JP6978758B2 (ja) 2016-11-11 2021-12-08 プレジデント アンド フェローズ オブ ハーバード カレッジ パラジウム媒介ケトール化
ES2931533T3 (es) * 2017-04-05 2022-12-30 Harvard College Compuesto macrocíclico y usos del mismo
US9938288B1 (en) 2017-04-05 2018-04-10 President And Fellows Of Harvard College Macrocyclic compound and uses thereof
HUE061306T2 (hu) * 2017-07-06 2023-06-28 Harvard College Halikondrinok szintézise
US11498892B2 (en) 2017-07-06 2022-11-15 President And Fellows Of Harvard College Fe/Cu-mediated ketone synthesis
CN111566113B (zh) * 2017-11-15 2024-01-09 哈佛大学的校长及成员们 大环化合物及其用途

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016003975A1 (en) * 2014-06-30 2016-01-07 President And Fellows Of Harvard College Synthesis of halichondrin analogs and uses thereof
WO2016176560A1 (en) * 2015-04-30 2016-11-03 President And Fellows Of Harvard College Chromium-mediated coupling and application to the synthesis of halichondrins
TWI781163B (zh) * 2017-04-05 2022-10-21 哈佛大學校長及研究員協會 巨環化合物及其用途

Family Cites Families (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK187280A (da) 1980-04-30 1981-10-31 Novo Industri As Ruhedsreducerende middel til et fuldvaskemiddel fuldvaskemiddel og fuldvaskemetode
US5436238A (en) 1992-03-12 1995-07-25 President And Fellows Of Harvard College Halichondrins and related compounds
US5338865A (en) 1992-03-12 1994-08-16 President And Fellows Of Harvard College Synthesis of halichondrin B and norhalichondrin B
GB9206244D0 (en) * 1992-03-23 1992-05-06 Pharma Mar Sa Cytotoxic compound from a marine sponge
DE4229425A1 (de) 1992-09-03 1994-03-10 Kodak Ag Vorrichtung zum stapelweisen Ablegen und Ausrichten von einzeln zugeführten Blättern
US5352804A (en) * 1993-01-19 1994-10-04 Arizona Board Of Regents, A Body Corporate, Acting On Behalf Of Arizona State University Isolation and structure of Halistatin 2
US5426194A (en) * 1993-01-19 1995-06-20 Arizona Board Of Regents, A Body Corporate Acting On Behalf Of Arizona State University Isolation and structure of Halistatin 1
JP2818381B2 (ja) 1994-01-18 1998-10-30 帝人株式会社 7−チアプロスタグランジン類およびその製造法
US6653341B1 (en) 1998-06-17 2003-11-25 Eisai Co., Ltd. Methods and compositions for use in treating cancer
US8097648B2 (en) * 1998-06-17 2012-01-17 Eisai R&D Management Co., Ltd. Methods and compositions for use in treating cancer
US6214865B1 (en) 1998-06-17 2001-04-10 Eisai Co., Ltd. Macrocyclic analogs and methods of their use and preparation
JP2001305734A (ja) 2000-04-20 2001-11-02 Fuji Photo Film Co Ltd 光重合性組成物
JP2003261447A (ja) 2002-03-07 2003-09-16 Kyosei Seiyaku Kk 抗腫瘍剤
EP2522663B1 (en) 2004-06-03 2015-04-01 Eisai R&D Management Co., Ltd. Intermediates for the preparation of halichondrin B
US7842815B2 (en) * 2004-06-17 2010-11-30 Infinity Pharmaceuticals, Inc. Compounds and methods for inhibiting the interaction of BCL proteins with binding partners
EP1831697A4 (en) 2004-12-09 2011-01-26 Eisai R&D Man Co Ltd SEARCH FOR TUBULINISOTYPES IN CANCER THERAPY USING HALICHONDRIN B ANALOG
JP2009184924A (ja) 2006-05-31 2009-08-20 Eisai R & D Management Co Ltd 生物学的試薬用化合物
MY153742A (en) 2007-03-07 2015-03-13 Interdigital Tech Corp Method and apparatus for generating and processing a mac-ehs protocol data unit
US20100254996A1 (en) 2007-06-18 2010-10-07 Medimmune, Llc Synergistic treatment of cells that express epha2 and erbb2
RU2489437C2 (ru) 2007-10-03 2013-08-10 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Промежуточные соединения и способы синтеза аналогов галихондрина в
RU2010118063A (ru) 2007-11-16 2011-12-27 ЭЙСАЙ Ар энд Ди МЕНЕДЖМЕНТ КО., ЛТД. (JP) Новое промежуточное соединение для синтеза аналога галихондрина в и новая реакция десульфонилирования, применяемая для получения промежуточного соединения
CN105801599A (zh) 2008-04-04 2016-07-27 卫材R&D管理有限公司 软海绵素b类似物
WO2011094339A1 (en) 2010-01-26 2011-08-04 Eisai R&D Management Co., Ltd. Furo [3, 2 -b] pyrane derivatives useful in the synthesis of halichondrin b analogs
WO2012096926A2 (en) 2011-01-10 2012-07-19 President And Fellows Of Harvard College Method for delivering agents into cells using bacterial toxins
WO2012147900A1 (en) * 2011-04-28 2012-11-01 Eisai R&D Management Co., Ltd. Microreactor process for halichondrin b analog synthesis
CN104024237B (zh) 2011-12-16 2016-02-24 阿方拉研究股份有限公司 用于制备3-((2s,5s)-4-亚甲基-5-(3-氧代丙基)四氢呋喃-2-基)丙醇衍生物的方法及其有用的中间体
CN104080793B (zh) 2011-12-29 2017-09-19 阿方拉研究股份有限公司 2‑((2s,3s,4r,5r)‑5‑((s)‑3‑氨基‑2‑羟基丙‑1‑基)‑4‑甲氧基‑3‑(苯磺酰甲基)四氢呋喃‑2‑基)乙醛衍生物以及它们的制备方法
WO2013142999A1 (en) 2012-03-30 2013-10-03 Alphora Research Inc. Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein
CA2863243A1 (en) * 2012-11-30 2014-06-05 Hangzhou Zylox Pharma Co., Ltd. Rafamycin analogs and methods for making same
AR096238A1 (es) 2013-05-15 2015-12-16 Alphora Res Inc Proceso para preparar derivados de 3-((2s,5s)-4-metilen-5-(3-oxopropil)tetrahidrofuran-2-il)propanol e intermediarios útiles para el mismo
CA2916537C (en) 2013-07-03 2021-07-27 Alphora Research Inc. Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein including intermediates containing -so2-(p-tolyl) groups
EP3689881B1 (en) 2013-11-04 2022-01-12 Eisai R&D Management Co., Ltd. Macrocyclization reactions and intermediates useful in the synthesis of analogs of halichondrin b
MX384292B (es) 2013-12-06 2025-03-14 Eisai R&D Man Co Ltd Metodos utiles en la sintesis de analogos de halicondrina b.
WO2016038624A1 (en) 2014-09-09 2016-03-17 Cipla Limited "process for the preparation of macrocyclic ketone analogs of halichondrin b or pharmaceutically acceptable salts and intermediates thereof"
KR102743950B1 (ko) 2015-05-07 2024-12-18 에자이 알앤드디 매니지먼트 가부시키가이샤 할리콘드린 마크롤라이드의 합성에 유용한 마크로고리화 반응 및 중간체 및 기타 단편
KR102637759B1 (ko) * 2015-07-01 2024-02-19 시그널켐 라이프사이언시즈 코포레이션 탄산 무수화효소 억제제로서의 아릴 설폰아마이드 화합물 및 이의 치료상 용도
EP3423105B1 (en) 2016-03-02 2021-05-05 Eisai R&D Management Co., Ltd. Eribulin-based antibody-drug conjugates and methods of use
JP6978758B2 (ja) 2016-11-11 2021-12-08 プレジデント アンド フェローズ オブ ハーバード カレッジ パラジウム媒介ケトール化
JP2020508315A (ja) 2017-02-20 2020-03-19 ポリフォー・アクチェンゲゼルシャフトPolyphor Ag がんを治療するための薬剤組合せ
US9938288B1 (en) 2017-04-05 2018-04-10 President And Fellows Of Harvard College Macrocyclic compound and uses thereof
HUE061306T2 (hu) 2017-07-06 2023-06-28 Harvard College Halikondrinok szintézise
US11498892B2 (en) 2017-07-06 2022-11-15 President And Fellows Of Harvard College Fe/Cu-mediated ketone synthesis
US20230135188A1 (en) 2017-07-06 2023-05-04 President And Fellows Of Harvard College Fe/cu-mediated ketone synthesis
WO2019009956A1 (en) 2017-07-06 2019-01-10 President And Fellows Of Harvard College SUMMARY OF MEDIUM MEDIATED KETONE
CN111566113B (zh) 2017-11-15 2024-01-09 哈佛大学的校长及成员们 大环化合物及其用途
WO2022019921A1 (en) 2020-07-24 2022-01-27 President And Fellows Of Harvard College Ketone synthesis and applications

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016003975A1 (en) * 2014-06-30 2016-01-07 President And Fellows Of Harvard College Synthesis of halichondrin analogs and uses thereof
WO2016176560A1 (en) * 2015-04-30 2016-11-03 President And Fellows Of Harvard College Chromium-mediated coupling and application to the synthesis of halichondrins
TWI781163B (zh) * 2017-04-05 2022-10-21 哈佛大學校長及研究員協會 巨環化合物及其用途

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MD3606928T2 (ro) 2022-12-31
WO2018187331A8 (en) 2018-12-06
US12421248B2 (en) 2025-09-23
KR20240023674A (ko) 2024-02-22
HRP20221385T1 (hr) 2023-01-06
JOP20190234A1 (ar) 2019-10-03
WO2018187331A1 (en) 2018-10-11
CN110831946A (zh) 2020-02-21
AU2022291454B2 (en) 2024-03-28
US20210261566A1 (en) 2021-08-26
KR102634732B1 (ko) 2024-02-13
CA3056945A1 (en) 2018-10-11
RU2019135531A (ru) 2021-05-05
ES2931533T3 (es) 2022-12-30
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