CN114521196A - 双官能团降解剂及其使用方法 - Google Patents

双官能团降解剂及其使用方法 Download PDF

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Publication number
CN114521196A
CN114521196A CN202080064750.9A CN202080064750A CN114521196A CN 114521196 A CN114521196 A CN 114521196A CN 202080064750 A CN202080064750 A CN 202080064750A CN 114521196 A CN114521196 A CN 114521196A
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group
tautomer
stereoisomer
prodrug
solvate
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Chinese (zh)
Inventor
L·阿里斯塔
V·布罗尼曼
P·L·达亚历山德罗
L·杜玛普姆-迈托尔
M-L·古德
C·黑巴赫
G·J·霍林沃思
I·K·J·热兰
L·C·克尔曼
J·洛伯
马缚鹏
A·武尔佩蒂
山田健
T·佐勒
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Novartis AG
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Novartis AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
    • 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
    • A61K47/55—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 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug
    • 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
    • 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
    • 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
    • C07D401/06—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 carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C07D401/14—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
    • C07D487/14—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN202080064750.9A 2019-09-16 2020-09-14 双官能团降解剂及其使用方法 Pending CN114521196A (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201962901161P 2019-09-16 2019-09-16
US62/901,161 2019-09-16
US201962905849P 2019-09-25 2019-09-25
US62/905,849 2019-09-25
PCT/IB2020/058535 WO2021053495A1 (en) 2019-09-16 2020-09-14 Bifunctional degraders and their methods of use

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CN114521196A true CN114521196A (zh) 2022-05-20

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US (1) US20220387602A1 (https=)
EP (1) EP4031247A1 (https=)
JP (1) JP7785663B2 (https=)
CN (1) CN114521196A (https=)
WO (1) WO2021053495A1 (https=)

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CN116981675A (zh) * 2020-12-31 2023-10-31 百济神州有限公司 通过布鲁顿氏酪氨酸激酶（btk）抑制剂与e3连接酶配体的缀合降解btk和使用方法
US20240216513A1 (en) * 2021-03-12 2024-07-04 Novartis Ag Fatty acid-bifunctional degrader conjugates and their methods of use
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WO2022266248A1 (en) * 2021-06-16 2022-12-22 Biotheryx, Inc. Sos1 protein degraders, pharmaceutical compositions thereof, and their therapeutic applications
WO2022272061A1 (en) * 2021-06-25 2022-12-29 Celgene Corporation Cereblon binding compounds, compositions thereof, and methods of treatment therewith
CN117561249A (zh) * 2021-06-25 2024-02-13 细胞基因公司 Cereblon结合化合物、其组合物及其用于治疗的方法
PE20240894A1 (es) * 2021-08-10 2024-04-24 Uppthera Inc Compuesto inductor de la degradacion de plk1 novedoso
US20240382600A1 (en) 2021-09-01 2024-11-21 Novartis Ag Bifunctional degraders comprising a tead binder
WO2023088406A1 (zh) * 2021-11-18 2023-05-25 正大天晴药业集团股份有限公司 稠合酰亚胺类衍生物
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KR20240128831A (ko) 2021-12-30 2024-08-27 베이진 스위찰랜드 게엠베하 브루톤 티로신 키나아제(btk) 억제제와 e3 리가아제 리간드의 접합에 의한 btk의 분해 및 사용 방법
JP7805983B2 (ja) * 2022-03-22 2026-01-26 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
WO2024020221A1 (en) * 2022-07-21 2024-01-25 Arvinas Operations, Inc. Modulators of tyk2 proteolysis and associated methods of use
JPWO2024043319A1 (https=) * 2022-08-26 2024-02-29
CN120530094A (zh) * 2023-01-12 2025-08-22 田边三菱制药株式会社 Cereblon E3连接酶结合化合物、包含其的药物组合物及其制造方法
KR20260029501A (ko) 2023-05-24 2026-03-04 베액티카 테라퓨틱스 아베 Tead에 대한 결합제로서의 방향족 아미드 및 이의 접합체
PE20260307A1 (es) 2023-06-14 2026-02-11 Astrazeneca Ab Degradadores de smarca2 y usos de estos
PE20260301A1 (es) 2023-06-14 2026-02-10 Astrazeneca Ab Derivados de 3-[3-amino-6-(2-hidroxifenil)piridazin-4-il]-3,8-diazabiciclo[3.2.1]octano como protacs degradantes de smarca2 para el tratamiento del cancer
CN117257796B (zh) * 2023-11-08 2025-09-16 复旦大学 奥巴克拉甲磺酸盐在制备抗bkv药物中的应用
CN120623148A (zh) * 2024-03-11 2025-09-12 北京深势科技有限公司 一种c-Myc降解剂及其制备方法和用途
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US20220387602A1 (en) 2022-12-08
JP7785663B2 (ja) 2025-12-15

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