WO2026044975A1 - Inhibiteur bivalent à base de protéine de choc thermique 90, son procédé de préparation et son utilisation - Google Patents

Inhibiteur bivalent à base de protéine de choc thermique 90, son procédé de préparation et son utilisation

Info

Publication number
WO2026044975A1
WO2026044975A1 PCT/CN2024/136610 CN2024136610W WO2026044975A1 WO 2026044975 A1 WO2026044975 A1 WO 2026044975A1 CN 2024136610 W CN2024136610 W CN 2024136610W WO 2026044975 A1 WO2026044975 A1 WO 2026044975A1
Authority
WO
WIPO (PCT)
Prior art keywords
heat shock
acid
protein
shock protein
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
PCT/CN2024/136610
Other languages
English (en)
Chinese (zh)
Inventor
王磊
尤启冬
吴秋宇
唐美伦
张秋月
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.)
China Pharmaceutical University
Original Assignee
China Pharmaceutical University
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
Application filed by China Pharmaceutical University filed Critical China Pharmaceutical University
Publication of WO2026044975A1 publication Critical patent/WO2026044975A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Indole Compounds (AREA)

Abstract

La présente invention concerne un inhibiteur de la protéine de choc thermique 90. L'invention concerne un inhibiteur bivalent à base de protéine de choc thermique 90, son procédé de préparation et son utilisation. L'inhibiteur bivalent est un composé ayant une formule développée telle que représentée dans la formule I : A-L-B Formule I, ou un sel, un solvate ou un isomère optique pharmaceutiquement acceptable de celui-ci, A et B étant des inhibiteurs d'ATP de la protéine de choc thermique 90, et la structure de motif de L étant un groupe de liaison flexible de PEG ou d'alcanes, ou un groupe de liaison rigide comprenant un aryle, un hétéroalkyle ou un hétéroaryle. L'inhibiteur bivalent peut inhiber efficacement l'activité de chaperon moléculaire HSP90, empêcher le repliement et la modification d'une protéine de substrat, dégrader la protéine de substrat par l'intermédiaire d'une voie de dégradation de l'ubiquitine-protéasome, induire une dimérisation non native de HSP90, et interférer avec des interactions protéine-protéine associées à HSP90. De plus, l'inhibiteur bivalent réduit la réponse de choc thermique induite par l'inhibition de HSP90, et présente une activité puissante dans la dégradation de la protéine de substrat.
PCT/CN2024/136610 2024-08-30 2024-12-04 Inhibiteur bivalent à base de protéine de choc thermique 90, son procédé de préparation et son utilisation Pending WO2026044975A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202411205387.4A CN119100970B (zh) 2024-08-30 2024-08-30 基于热休克蛋白90的二价抑制剂及其制备方法和应用
CN202411205387.4 2024-08-30

Publications (1)

Publication Number Publication Date
WO2026044975A1 true WO2026044975A1 (fr) 2026-03-05

Family

ID=93714892

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2024/136610 Pending WO2026044975A1 (fr) 2024-08-30 2024-12-04 Inhibiteur bivalent à base de protéine de choc thermique 90, son procédé de préparation et son utilisation

Country Status (2)

Country Link
CN (1) CN119100970B (fr)
WO (1) WO2026044975A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0995757A2 (fr) * 1998-08-26 2000-04-26 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Inhibiteurs bivalemtes de la proteasome
CN101193862A (zh) * 2005-04-13 2008-06-04 阿斯特克斯治疗有限公司 羟基苯甲酰胺衍生物和其作为hsp90抑制剂的用途
CN104718209A (zh) * 2012-08-23 2015-06-17 密执安大学评议会 Iap蛋白的二价抑制剂和使用其的治疗方法
CN107056771A (zh) * 2017-01-23 2017-08-18 中国药科大学 Bromodomain蛋白二价抑制剂及其制备方法和应用
CN114957291A (zh) * 2015-11-25 2022-08-30 达纳-法伯癌症研究所股份有限公司 二价溴结构域抑制剂及其用途

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120022070A1 (en) * 2008-10-06 2012-01-26 Emory University Heat Shock Protein 90 Inhibitors, Methods Of Preparing Same, And Methods For Their Use
KR20120108181A (ko) * 2011-03-23 2012-10-05 주식회사 레고켐 바이오사이언스 열충격 단백질(ｈｓｐ９０)의 저해능을 갖는 미토콘드리아 특이적 항암제
AU2018386218A1 (en) * 2017-12-14 2020-07-02 Tva (Abc), Llc HSP90-targeting conjugates and formulations thereof
CN116836179A (zh) * 2023-04-27 2023-10-03 华东师范大学 具有肿瘤靶向的溴结构域蛋白brd4抑制剂

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0995757A2 (fr) * 1998-08-26 2000-04-26 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Inhibiteurs bivalemtes de la proteasome
CN101193862A (zh) * 2005-04-13 2008-06-04 阿斯特克斯治疗有限公司 羟基苯甲酰胺衍生物和其作为hsp90抑制剂的用途
CN104718209A (zh) * 2012-08-23 2015-06-17 密执安大学评议会 Iap蛋白的二价抑制剂和使用其的治疗方法
CN114957291A (zh) * 2015-11-25 2022-08-30 达纳-法伯癌症研究所股份有限公司 二价溴结构域抑制剂及其用途
CN107056771A (zh) * 2017-01-23 2017-08-18 中国药科大学 Bromodomain蛋白二价抑制剂及其制备方法和应用

Also Published As

Publication number Publication date
CN119100970B (zh) 2025-09-30
CN119100970A (zh) 2024-12-10

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