CN114728936A - 用于治疗癌症的双功能化合物 - Google Patents

用于治疗癌症的双功能化合物 Download PDF

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Publication number
CN114728936A
CN114728936A CN202080076232.9A CN202080076232A CN114728936A CN 114728936 A CN114728936 A CN 114728936A CN 202080076232 A CN202080076232 A CN 202080076232A CN 114728936 A CN114728936 A CN 114728936A
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China
Prior art keywords
group
absent
formula
alkyl
cancer
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Pending
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CN202080076232.9A
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English (en)
Chinese (zh)
Inventor
M·杜普莱西斯
D·高福赫托
R·赫特
E·乔夫切瓦
B·库恩
K·拉扎斯基
梁焱科
T·利贝斯
L·J·马丁
R·E·马丁
B·J·穆勒
R·诺克罗斯
P·施密德
J-y·瓦克
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
F Hoffmann La Roche AG
C4 Therapeutics Inc
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F Hoffmann La Roche AG
C4 Therapeutics Inc
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Application filed by F Hoffmann La Roche AG, C4 Therapeutics Inc filed Critical F Hoffmann La Roche AG
Publication of CN114728936A publication Critical patent/CN114728936A/zh
Pending legal-status Critical Current

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    • 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
    • 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
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • C07D401/14—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
    • 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
    • C07D487/02—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 two hetero rings
    • C07D487/08—Bridged 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
    • C07D487/02—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 two hetero rings
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN202080076232.9A 2019-10-29 2020-10-28 用于治疗癌症的双功能化合物 Pending CN114728936A (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201962927340P 2019-10-29 2019-10-29
US62/927,340 2019-10-29
EP19209344.1 2019-11-15
EP19209344 2019-11-15
PCT/EP2020/080265 WO2021083949A1 (en) 2019-10-29 2020-10-28 Bifunctional compounds for the treatment of cancer

Publications (1)

Publication Number Publication Date
CN114728936A true CN114728936A (zh) 2022-07-08

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CN202080076232.9A Pending CN114728936A (zh) 2019-10-29 2020-10-28 用于治疗癌症的双功能化合物

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Country Link
US (1) US20230024096A1 (https=)
EP (1) EP4051674A1 (https=)
JP (1) JP2023511472A (https=)
CN (1) CN114728936A (https=)
WO (1) WO2021083949A1 (https=)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116284202A (zh) * 2023-03-28 2023-06-23 华侨大学 白桦脂酸的PROTACs化合物及其制备方法和应用
WO2024213125A1 (zh) * 2023-04-14 2024-10-17 南京再明医药有限公司 Brm选择性降解剂及其应用
WO2025061035A1 (zh) * 2023-09-19 2025-03-27 南京再明医药有限公司 Brm选择性降解剂化合物及其应用
CN119798218A (zh) * 2024-12-31 2025-04-11 南京优氟医药科技有限公司 一种e3酶配体-连接链复合物及其制备方法
WO2026061475A1 (zh) * 2024-09-19 2026-03-26 标新生物医药科技(上海)有限公司 含有芳基取代杂芳基的双功能蛋白降解剂及其应用

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WO2019140380A1 (en) 2018-01-12 2019-07-18 Kymera Therapeutics, Inc. Protein degraders and uses thereof
WO2020010227A1 (en) 2018-07-06 2020-01-09 Kymera Therapeutics, Inc. Protein degraders and uses thereof
WO2020251972A1 (en) 2019-06-10 2020-12-17 Kymera Therapeutics, Inc. Smarca degraders and uses thereof
WO2021126973A1 (en) * 2019-12-17 2021-06-24 Orionis Biosciences, Inc. Compounds modulating protein recruitment and/or degradation
WO2021133917A1 (en) 2019-12-23 2021-07-01 Kymera Therapeutics, Inc. Smarca inhibitors and uses thereof
EP4081308A4 (en) 2019-12-23 2024-01-24 Kymera Therapeutics, Inc. Smarca degraders and uses thereof
KR20230005160A (ko) 2020-03-19 2023-01-09 카이메라 쎄라퓨틱스 인코포레이티드 Mdm2 분해제 및 이의 용도
WO2021207291A1 (en) * 2020-04-06 2021-10-14 Foghorn Therapeutics Inc. Compounds and uses thereof
IL300397A (en) 2020-08-05 2023-04-01 C4 Therapeutics Inc Compounds for targeted knockdown of RET
EP4259144A4 (en) * 2020-12-09 2025-08-20 Kymera Therapeutics Inc SMARCA DEGRADING AGENTS AND THEIR USES
KR20240004983A (ko) * 2021-05-10 2024-01-11 포그혼 쎄라퓨틱스 인크. 화합물 및 이의 용도
CA3219183A1 (en) 2021-05-17 2022-11-24 Amedeo Caflisch N6-adenosine-methyltransferase inhibitors in cancer treatment
US20240358842A1 (en) * 2021-06-25 2024-10-31 Stablix, Inc. Protein stabilizing compounds containing usp7 ligands
US20250018046A1 (en) * 2021-07-07 2025-01-16 Biogen Ma Inc Compounds for targeting degradation of irak4 proteins
KR20240046498A (ko) 2021-08-09 2024-04-09 제넨테크, 인크. Brm의 조절에 사용하기 위한 페놀 유도체
WO2023039573A1 (en) * 2021-09-10 2023-03-16 H. Lee Moffitt Cancer Center And Research Institute, Inc. Compounds for targeted degradation of taf1
CN117384161A (zh) * 2022-07-04 2024-01-12 华东理工大学 靶向降解cdk蛋白的化合物及其应用
WO2024026083A1 (en) * 2022-07-29 2024-02-01 Ribon Therapeutics, Inc. Targeted protein degradation of parp14 for use in therapy
WO2024073507A1 (en) 2022-09-28 2024-04-04 Theseus Pharmaceuticals, Inc. Macrocyclic compounds and uses thereof
CN116120311B (zh) * 2022-11-28 2025-10-24 中国药科大学 一种靶向降解atr蛋白的双功能化合物及其制法与用途
TW202502750A (zh) 2023-06-08 2025-01-16 美商新銳思生物製藥股份有限公司 Smarca2之雙官能選擇性降解劑及其治療用途
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
WO2025006902A2 (en) * 2023-06-29 2025-01-02 Dana-Farber Cancer Institute, Inc. Synthesis and in vitro characterization of proteolysis targeting chimeras (protacs) for degradation of dna methyltransferase 1 (dnmt1)
WO2025094065A1 (en) 2023-11-01 2025-05-08 Aurigene Oncology Limited Amino-substituted pyridazine compounds as smarca2 and/or smarca4 degraders

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116284202A (zh) * 2023-03-28 2023-06-23 华侨大学 白桦脂酸的PROTACs化合物及其制备方法和应用
CN116284202B (zh) * 2023-03-28 2024-07-02 华侨大学 白桦脂酸的PROTACs化合物及其制备方法和应用
WO2024213125A1 (zh) * 2023-04-14 2024-10-17 南京再明医药有限公司 Brm选择性降解剂及其应用
WO2025061035A1 (zh) * 2023-09-19 2025-03-27 南京再明医药有限公司 Brm选择性降解剂化合物及其应用
WO2026061475A1 (zh) * 2024-09-19 2026-03-26 标新生物医药科技(上海)有限公司 含有芳基取代杂芳基的双功能蛋白降解剂及其应用
CN119798218A (zh) * 2024-12-31 2025-04-11 南京优氟医药科技有限公司 一种e3酶配体-连接链复合物及其制备方法

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WO2021083949A1 (en) 2021-05-06
EP4051674A1 (en) 2022-09-07
JP2023511472A (ja) 2023-03-20

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