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

Info

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
Authority
CN
China
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
CN202380029742.4A
Other languages
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
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.)
GlaxoSmithKline Intellectual Property Development Ltd
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 CN119301111A publication Critical patent/CN119301111A/zh
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)
  • Plural Heterocyclic Compounds (AREA)
  • Medicinal Preparation (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
GB2204142.0 2022-03-24
GBGB2204142.0A GB202204142D0 (en) 2022-03-24 2022-03-24 Novel compounds
GBGB2213816.8A GB202213816D0 (en) 2022-09-22 2022-09-22 Novel compounds
GB2213816.8 2022-09-22
GB2301448.3 2023-02-01
GBGB2301448.3A GB202301448D0 (en) 2023-02-01 2023-02-01 Novel compounds
GB2301757.7 2023-02-08
GB202301757 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 (enExample)
EP (1) EP4499628A1 (enExample)
JP (1) JP2025510074A (enExample)
CN (1) CN119301111A (enExample)
CA (1) CA3246569A1 (enExample)
WO (1) WO2023180388A1 (enExample)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024146617A1 (zh) * 2023-01-04 2024-07-11 甘李药业股份有限公司 用于雄激素受体靶向降解的化合物和方法
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
IL326555A (en) * 2023-09-22 2026-04-01 Glaxosmithkline Ip Dev Ltd Androgen receptor protax
CN120025326A (zh) * 2023-11-22 2025-05-23 广东东阳光药业股份有限公司 一种靶向降解雄激素受体的双功能嵌合体的杂环化合物及其用途
US20250197411A1 (en) 2023-12-14 2025-06-19 Astrazeneca Ab Irak4 protacs
US12558428B2 (en) 2024-03-08 2026-02-24 Halda Therapeutics Opco, Inc. Heterobifunctional compounds and their use in treating disease
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
CN119591582A (zh) 2014-04-14 2025-03-11 阿尔维纳斯运营股份有限公司 基于酰亚胺的蛋白水解调节剂和相关使用方法
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
CN109562107A (zh) 2016-05-10 2019-04-02 C4医药公司 用于靶蛋白降解的杂环降解决定子体
LT3660004T (lt) 2016-10-11 2023-06-12 Arvinas Operations, Inc. Junginiai ir metodai, skirti tikslinei androgeno receptoriaus degradacijai
EP3577109A4 (en) * 2017-01-31 2020-11-18 Arvinas Operations, Inc. CEREMONY LIGANDS AND BIFUNCTIONAL COMPOUNDS CONTAINING THEM
IL315310A (en) 2017-12-26 2024-10-01 Kymera Therapeutics Inc Irak degraders and uses thereof
US20230045737A1 (en) * 2018-12-05 2023-02-09 Vividion Therapeutics, Inc. Substituted isoindolinones as modulators of cereblon-mediated neo-substrate recruitment
WO2020160295A1 (en) 2019-01-30 2020-08-06 Montelino Therapeutics, Llc Bi-functional compounds and methods for targeted ubiquitination of androgen receptor
KR20220004978A (ko) 2019-03-28 2022-01-12 에싸 파마 아이엔씨. 단백질 분해 표적 키메라 리간드로서 사용하기 위한 안드로겐 수용체 조절제 및 방법
US12331061B2 (en) 2019-04-18 2025-06-17 Accutar Biotechnology Inc. Compounds having BET, estrogen receptor, and androgen receptor degradation activity and uses thereof
KR20220004100A (ko) 2019-04-18 2022-01-11 하이노바 파마슈티컬스 인코포레이티드 안드로겐 수용체를 표적 분해하는 이중 기능성의 키메라 헤테로 고리 화합물 및 이의 용도
US12310975B2 (en) 2019-10-17 2025-05-27 Arvinas Operations, Inc. Modulators of BCL6 proteolysis and associated methods of use
EP4221756A1 (en) 2020-09-30 2023-08-09 Astrazeneca AB Compounds and their use in treating cancer

Also Published As

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

Similar Documents

Publication Publication Date Title
JP7603609B2 (ja) アンドロゲン受容体を標的に分解する二官能性キメラ複素環式化合物及びその使用
WO2023180388A1 (en) 2,4-dioxotetrahydropyrimidinyl derivatives as degrons in protacs
CN103153984B (zh) 酪氨酸蛋白激酶抑制剂
CN103582637B (zh) 酪氨酸激酶抑制剂
JP6128449B2 (ja) キナーゼ阻害剤
TWI770525B (zh) 作為泛素特異性蛋白酶７抑制劑之吡咯并及吡唑并嘧啶
CN102822170B (zh) 作为cFMS抑制剂的取代的N-(1H-吲唑-4-基)咪唑并[1,2-a]吡啶-3-羧酰胺化合物
JP6746679B2 (ja) 化合物
CN102264721B (zh) 用作atr激酶抑制剂的化合物
CN1407985A (zh) 用作钾通道抑制剂的杂环二氢嘧啶
CN1882347A (zh) Akt蛋白激酶抑制剂
CN1809576A (zh) 抗寄生物萜类生物碱
HK1049834A1 (zh) 用作磷酸二酯酶抑制剂的5-(2-取代的-5-杂环基磺酰基吡啶-3-基)-二氢吡唑并[4，3-d]嘧啶-7-酮类化合物
CN103476768A (zh) 6,5-杂环炔丙醇化合物及其用途
CN1878773A (zh) 作为crf1受体配位体的杂芳基稠合的吡啶,吡嗪及嘧啶
CN105793252B (zh) 布鲁顿氏酪氨酸激酶抑制剂
WO2025011623A1 (zh) 氰基喹啉类靶向蛋白降解分子、其制备方法和应用
CN101052629A (zh) 芳基－氨基取代的吡咯并嘧啶多激酶抑制化合物
CN103443107B (zh) 噻唑并嘧啶化合物
CN101039947A (zh) Hcv复制抑制剂
CN1968949A (zh) 脯氨酸衍生物和其作为二肽基肽酶iv抑制剂的用途
CN104024261B (zh) 咪唑并哒嗪化合物
HK1196359B (en) Imidazopyridazine compounds
CN104024261A (zh) 咪唑并哒嗪化合物
HK1196359A (en) Imidazopyridazine compounds

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination