CN119301111A - 作为protac中的降解决定子的2,4-二氧代四氢嘧啶基衍生物 - Google Patents

作为protac中的降解决定子的2,4-二氧代四氢嘧啶基衍生物 Download PDF

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Publication number
CN119301111A
CN119301111A CN202380029742.4A CN202380029742A CN119301111A CN 119301111 A CN119301111 A CN 119301111A CN 202380029742 A CN202380029742 A CN 202380029742A CN 119301111 A CN119301111 A CN 119301111A
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Prior art keywords
formula
compound
tautomer
salt
mmol
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Pending
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CN202380029742.4A
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English (en)
Chinese (zh)
Inventor
P·班伯勒
J·D·哈林
A·H·米娅
A·J·纳丁
C·M·罗伯逊
R·R·莎
I·E·D·史密斯
C·P·廷沃思
C·R·韦拉卫
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GlaxoSmithKline Intellectual Property Development Ltd
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GlaxoSmithKline Intellectual Property Development Ltd
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Priority claimed from GBGB2204142.0A external-priority patent/GB202204142D0/en
Priority claimed from GBGB2213816.8A external-priority patent/GB202213816D0/en
Priority claimed from GBGB2301448.3A external-priority patent/GB202301448D0/en
Application filed by GlaxoSmithKline Intellectual Property Development Ltd filed Critical GlaxoSmithKline Intellectual Property Development Ltd
Publication of CN119301111A publication Critical patent/CN119301111A/zh
Pending legal-status Critical Current

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    • 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
    • C07D401/14—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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—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
    • C07D403/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—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
    • C07D403/10—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 carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms 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
    • C07D471/04—Ortho-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
    • C07D471/02—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
    • 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
    • C07D487/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (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)
  • Medicinal Preparation (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN202380029742.4A 2022-03-24 2023-03-22 作为protac中的降解决定子的2,4-二氧代四氢嘧啶基衍生物 Pending CN119301111A (zh)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
GBGB2204142.0A GB202204142D0 (en) 2022-03-24 2022-03-24 Novel compounds
GB2204142.0 2022-03-24
GBGB2213816.8A GB202213816D0 (en) 2022-09-22 2022-09-22 Novel compounds
GB2213816.8 2022-09-22
GBGB2301448.3A GB202301448D0 (en) 2023-02-01 2023-02-01 Novel compounds
GB2301448.3 2023-02-01
GB202301757 2023-02-08
GB2301757.7 2023-02-08
PCT/EP2023/057338 WO2023180388A1 (en) 2022-03-24 2023-03-22 2,4-dioxotetrahydropyrimidinyl derivatives as degrons in protacs

Publications (1)

Publication Number Publication Date
CN119301111A true CN119301111A (zh) 2025-01-10

Family

ID=85937360

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202380029742.4A Pending CN119301111A (zh) 2022-03-24 2023-03-22 作为protac中的降解决定子的2,4-二氧代四氢嘧啶基衍生物

Country Status (6)

Country Link
US (1) US20250205344A1 (https=)
EP (1) EP4499628A1 (https=)
JP (1) JP2025510074A (https=)
CN (1) CN119301111A (https=)
CA (1) CA3246569A1 (https=)
WO (1) WO2023180388A1 (https=)

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EP4647431A1 (en) * 2023-01-04 2025-11-12 Gan & lee Pharm Co., Ltd. Compound and method for targeted degradation of androgen receptor
TW202508568A (zh) 2023-04-07 2025-03-01 瑞典商阿斯特捷利康公司 Ｉｒａｋ４蛋白水解靶向嵌合體
WO2025011623A1 (zh) * 2023-07-12 2025-01-16 上海壹迪生物技术有限公司 氰基喹啉类靶向蛋白降解分子、其制备方法和应用
TW202530192A (zh) 2023-09-22 2025-08-01 英商葛蘭素史密斯克藍智慧財產發展有限公司 新穎化合物
TW202532055A (zh) * 2023-11-22 2025-08-16 大陸商廣東東陽光藥業股份有限公司 靶向降解雄激素受體的雙功能嵌合體的雜環化合物及其用途
WO2025125575A1 (en) 2023-12-14 2025-06-19 Astrazeneca Ab Irak4 protacs
TW202543650A (zh) 2024-03-08 2025-11-16 美商海爾達醫療運營公司 異雙官能化合物及其在治療疾病中之用途
WO2025261436A1 (zh) * 2024-06-19 2025-12-26 上海翰森生物医药科技有限公司 含氮杂环类衍生物抑制剂、其制备方法和应用

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US7737149B2 (en) 2006-12-21 2010-06-15 Astrazeneca Ab N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-4-(3,5-dimethylpiperazin-1-yl)benzamide and salts thereof
RU2738833C9 (ru) 2014-04-14 2022-02-28 Арвинас, Оперэйшнз, Инк. Имидные модуляторы протеолиза и способы их применения
GB201506872D0 (en) 2015-04-22 2015-06-03 Ge Oil & Gas Uk Ltd Novel compounds
WO2017007612A1 (en) 2015-07-07 2017-01-12 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
EP3454856B1 (en) 2016-05-10 2024-09-11 C4 Therapeutics, Inc. Heterocyclic degronimers for target protein degradation
CN110506039A (zh) 2016-10-11 2019-11-26 阿尔维纳斯股份有限公司 用于雄激素受体靶向降解的化合物和方法
IL312367A (en) * 2017-01-31 2024-06-01 Arvinas Operations Inc Cereblon ligands and bifunctional compounds comprising the same
IL315310A (en) 2017-12-26 2024-10-01 Kymera Therapeutics Inc Irak degraders and uses thereof
WO2020118098A1 (en) * 2018-12-05 2020-06-11 Vividion Therapeutics, Inc. Substituted isoindolinones as modulators of cereblon-mediated neo-substrate recruitment
EP3917916A4 (en) 2019-01-30 2022-12-14 Montelino Therapeutics, Inc. Bi-functional compounds and methods for targeted ubiquitination of androgen receptor
CN114269331A (zh) 2019-03-28 2022-04-01 埃萨制药股份有限公司 雄激素受体调节剂和用作蛋白水解靶向嵌合体配体的方法
WO2020211822A1 (zh) 2019-04-18 2020-10-22 成都海创药业有限公司 一类靶向降解雄激素受体的双功能嵌合体杂环化合物及其用途
US12331061B2 (en) 2019-04-18 2025-06-17 Accutar Biotechnology Inc. Compounds having BET, estrogen receptor, and androgen receptor degradation activity and uses thereof
CA3154386A1 (en) 2019-10-17 2021-04-22 Michael Berlin Bifunctional molecules containing an e3 ubiquitine ligase binding moiety linked to a bcl6 targeting moiety
CA3195695A1 (en) 2020-09-30 2022-04-07 Astrazeneca Ab Compounds and their use in treating cancer

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EP4499628A1 (en) 2025-02-05
CA3246569A1 (en) 2023-09-28
JP2025510074A (ja) 2025-04-14
US20250205344A1 (en) 2025-06-26
WO2023180388A1 (en) 2023-09-28

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