CA3246569A1 - 2,4-DIOXOTETRAHYDROPYRIMIDINYL DERIVATIVES USED AS DEGRONS IN PROTACS - Google Patents

2,4-DIOXOTETRAHYDROPYRIMIDINYL DERIVATIVES USED AS DEGRONS IN PROTACS

Info

Publication number
CA3246569A1
CA3246569A1 CA3246569A CA3246569A CA3246569A1 CA 3246569 A1 CA3246569 A1 CA 3246569A1 CA 3246569 A CA3246569 A CA 3246569A CA 3246569 A CA3246569 A CA 3246569A CA 3246569 A1 CA3246569 A1 CA 3246569A1
Authority
CA
Canada
Prior art keywords
formula
compound
tautomer
salt
mmol
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CA3246569A
Other languages
English (en)
French (fr)
Inventor
Paul Bamborough
John David Harling
Afjal Hussain Miah
Alan John Nadin
Craig Michael ROBERTSON
Rishi Rajnikant SHAH
Ian Edward David Smith
Christopher Patrick TINWORTH
Christopher Roland Wellaway
Original Assignee
GlaxoSmithKline Intellectual Property Development Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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 CA3246569A1 publication Critical patent/CA3246569A1/en
Pending legal-status Critical Current

Links

Classifications

    • 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

Landscapes

  • 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)
CA3246569A 2022-03-24 2023-03-22 2,4-DIOXOTETRAHYDROPYRIMIDINYL DERIVATIVES USED AS DEGRONS IN PROTACS Pending CA3246569A1 (en)

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
CA3246569A1 true CA3246569A1 (en) 2023-09-28

Family

ID=85937360

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3246569A Pending CA3246569A1 (en) 2022-03-24 2023-03-22 2,4-DIOXOTETRAHYDROPYRIMIDINYL DERIVATIVES USED AS DEGRONS IN PROTACS

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=)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Also Published As

Publication number Publication date
EP4499628A1 (en) 2025-02-05
JP2025510074A (ja) 2025-04-14
US20250205344A1 (en) 2025-06-26
WO2023180388A1 (en) 2023-09-28
CN119301111A (zh) 2025-01-10

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