KR20190080956A - Ｅ3 리가아제 리간드와 브루톤 티로신 키나아제(ｂｔｋ) 억제제의 컨쥬게이션에 의한 ｂｔｋ의 분해 및 사용 방법 - Google Patents

Ｅ3 리가아제 리간드와 브루톤 티로신 키나아제(ｂｔｋ) 억제제의 컨쥬게이션에 의한 ｂｔｋ의 분해 및 사용 방법 Download PDF

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KR20190080956A
KR20190080956A KR1020197018106A KR20197018106A KR20190080956A KR 20190080956 A KR20190080956 A KR 20190080956A KR 1020197018106 A KR1020197018106 A KR 1020197018106A KR 20197018106 A KR20197018106 A KR 20197018106A KR 20190080956 A KR20190080956 A KR 20190080956A
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alkyl
independently
linker
bifunctional compound
formula
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나다나엘 에스 그레이
데니스 도브로볼스키
하이-창 후앙
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다나-파버 캔서 인스티튜트 인크.
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    • C07—ORGANIC CHEMISTRY
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    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D215/38—Nitrogen atoms
    • C07D215/40—Nitrogen atoms attached in position 8
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61K47/54—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 organic compound
    • A61K47/545—Heterocyclic compounds
    • A—HUMAN NECESSITIES
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    • 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
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
KR1020197018106A 2016-11-22 2017-11-22 Ｅ3 리가아제 리간드와 브루톤 티로신 키나아제(ｂｔｋ) 억제제의 컨쥬게이션에 의한 ｂｔｋ의 분해 및 사용 방법 Withdrawn KR20190080956A (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662425211P 2016-11-22 2016-11-22
US62/425,211 2016-11-22
PCT/US2017/063027 WO2018098288A1 (en) 2016-11-22 2017-11-22 Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use

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KR20190080956A true KR20190080956A (ko) 2019-07-08

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US (3) US10925967B2 (enExample)
EP (1) EP3544959A4 (enExample)
JP (1) JP2019535746A (enExample)
KR (1) KR20190080956A (enExample)
AU (1) AU2017363265B2 (enExample)
CA (1) CA3042294A1 (enExample)
WO (1) WO2018098288A1 (enExample)

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US10925967B2 (en) 2016-11-22 2021-02-23 Dana-Farber Cancer Institute, Inc. Degradation of Bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use
US11173211B2 (en) 2016-12-23 2021-11-16 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides
CN109422752B (zh) * 2017-09-03 2023-04-07 上海美志医药科技有限公司 一类具有抑制并降解布鲁顿酪氨酸蛋白激酶Btk活性的化合物
WO2019148150A1 (en) 2018-01-29 2019-08-01 Dana-Farber Cancer Institute, Inc. Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use
CN110240629B (zh) * 2018-03-09 2023-10-03 上海科技大学 蛋白降解靶向bcr-abl化合物及其抗肿瘤应用
CN111936498B (zh) 2018-03-26 2024-04-16 诺华股份有限公司 N-(3-(7H-吡咯并[2,3-d]嘧啶-4-基)苯基)苯甲酰胺衍生物
CN112912376A (zh) 2018-08-20 2021-06-04 阿尔维纳斯运营股份有限公司 用于治疗神经变性疾病的具有E3泛素连接酶结合活性并靶向α-突触核蛋白的蛋白水解靶向嵌合(PROTAC)化合物
JP2022525924A (ja) 2019-03-21 2022-05-20 コディアック バイオサイエンシーズ， インコーポレイテッド 細胞外小胞コンジュゲート及びその使用
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CN110204532B (zh) * 2019-05-15 2022-03-08 浙江工业大学 一种靶向egfr蛋白降解的化合物及其制备方法和应用
CN119954801A (zh) 2019-07-17 2025-05-09 阿尔维纳斯运营股份有限公司 Tau蛋白靶向化合物及相关使用方法
US20220281876A1 (en) * 2019-07-26 2022-09-08 Beigene, Ltd. Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use
US20220313829A1 (en) * 2019-08-05 2022-10-06 Shanghaitech University Egfr protein degradant and anti-tumor application thereof
WO2021053495A1 (en) * 2019-09-16 2021-03-25 Novartis Ag Bifunctional degraders and their methods of use
WO2021058017A1 (en) * 2019-09-29 2021-04-01 Beigene, Ltd. Degradation of androgen receptor (ar) by conjugation of ar antagonists with e3 ligase ligand and methods of use
CN119019369A (zh) 2019-10-17 2024-11-26 阿尔维纳斯运营股份有限公司 含有与bcl6靶向部分连接的e3泛素连接酶结合部分的双官能分子
WO2021237100A1 (en) 2020-05-21 2021-11-25 Codiak Biosciences, Inc. Methods of targeting extracellular vesicles to lung
JP2023539663A (ja) 2020-08-28 2023-09-15 アルビナス・オペレーションズ・インコーポレイテッド 急速進行性線維肉腫タンパク質分解化合物及び関連する使用方法
US20240241020A1 (en) 2020-09-23 2024-07-18 Lonza Sales Ag Process for preparing extracellular vesicles
CN114478532A (zh) * 2020-10-26 2022-05-13 上海美志医药科技有限公司 靶向降解Btk的化合物及其抗肿瘤用途
US20240246977A1 (en) * 2020-12-31 2024-07-25 Beigene Switzerland Gmbh Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and method of use
MX2023008296A (es) 2021-01-13 2023-09-29 Monte Rosa Therapeutics Inc Compuestos de isoindolinona.
WO2022221673A1 (en) 2021-04-16 2022-10-20 Arvinas Operations, Inc. Modulators of bcl6 proteolysis and associated methods of use
US20250136620A1 (en) * 2022-01-17 2025-05-01 Newave Pharmaceutical Inc. Btk degrader
JP2023140319A (ja) 2022-03-22 2023-10-04 アッヴィ・インコーポレイテッド ブルトン型チロシンキナーゼを分解するためのピリミジン
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US20160058872A1 (en) * 2014-04-14 2016-03-03 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
EP3288558B1 (en) 2015-04-30 2022-05-11 Bayer Pharma Aktiengesellschaft Combinations of inhibitors of irak4 with inhibitors of btk
WO2017079267A1 (en) * 2015-11-02 2017-05-11 Yale University Proteolysis targeting chimera compounds and methods of preparing and using same
WO2017117474A1 (en) * 2015-12-30 2017-07-06 Dana-Farber Cancer Institute, Inc. Bifunctional compounds for her3 degradation and methods of use
US10925967B2 (en) * 2016-11-22 2021-02-23 Dana-Farber Cancer Institute, Inc. Degradation of Bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use

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AU2017363265A1 (en) 2019-05-16
US20210100908A1 (en) 2021-04-08
WO2018098288A1 (en) 2018-05-31
JP2019535746A (ja) 2019-12-12
EP3544959A4 (en) 2020-11-11
US20230338551A1 (en) 2023-10-26
US20190262459A1 (en) 2019-08-29
US11730818B2 (en) 2023-08-22
AU2017363265B2 (en) 2021-11-04
US10925967B2 (en) 2021-02-23
CA3042294A1 (en) 2018-05-31
US12329821B2 (en) 2025-06-17

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