EP4735113A1 - Dérivés de pyrazole en tant qu'inhibiteurs d'interaction pd-1/pd-l1 - Google Patents

Dérivés de pyrazole en tant qu'inhibiteurs d'interaction pd-1/pd-l1

Info

Publication number
EP4735113A1
EP4735113A1 EP24737945.6A EP24737945A EP4735113A1 EP 4735113 A1 EP4735113 A1 EP 4735113A1 EP 24737945 A EP24737945 A EP 24737945A EP 4735113 A1 EP4735113 A1 EP 4735113A1
Authority
EP
European Patent Office
Prior art keywords
alkyl
compound
represent
carcinoma
halogen
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
EP24737945.6A
Other languages
German (de)
English (en)
Inventor
Xavier THURU
Christian Bailly
Bruno QUESNEL
Frédérique Klupsch
Raphaël LE BIANNIC
Régis MILLET
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.)
Centre National de la Recherche Scientifique CNRS
Institut National de la Sante et de la Recherche Medicale INSERM
Centre Hospitalier Universitaire de Lille
Universite de Lille
Original Assignee
Centre National de la Recherche Scientifique CNRS
Institut National de la Sante et de la Recherche Medicale INSERM
Centre Hospitalier Universitaire de Lille
Universite de Lille
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 Centre National de la Recherche Scientifique CNRS, Institut National de la Sante et de la Recherche Medicale INSERM, Centre Hospitalier Universitaire de Lille, Universite de Lille filed Critical Centre National de la Recherche Scientifique CNRS
Publication of EP4735113A1 publication Critical patent/EP4735113A1/fr
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/38—Nitrogen atoms
    • C07D231/40—Acylated on said nitrogen atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • C07D401/02—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 two hetero rings
    • C07D401/04—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 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
    • 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
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Epidemiology (AREA)

Abstract

La présente demande concerne des dérivés de pyrazole en tant qu'inhibiteurs d'interaction PD-1/PD-L1. Les demandeurs ont conçu des composés de formule générale (I), dans laquelle R', R2, y3, R3, R4, R5, R6 et R7 sont tels que définis dans la description, qui sont capables de bloquer efficacement des interactions PD-1/PD-L1 afin de restaurer des réponses immunitaires antitumorales de sujets et d'éradiquer des cellules tumorales dormantes et toutes tumeurs dans lesquelles PD-L1 est impliqué dans l'évasion immunitaire. Les demandeurs ont confirmé que ces composés bloquaient les interactions PD-1/PD-L1 en effectuant des tests physico-chimiques (MST, NanoDSF) et des tests biologiques in vitro (essai FRET, essai de blocage Promega, dosage des lymphocytes T). Ces composés ont une affinité (Kd) de l'ordre du pM qui était supérieure à celle de l'anticorps atézolizumab utilisé en utilisation clinique, et ont une CI50 comparable ou meilleure par rapport à celle observée avec l'atézolizumab. Ainsi, la présente invention concerne également une composition pharmaceutique comprenant ledit ou lesdits composés et leurs utilisations dans le traitement de maladies associées à des interactions PD-1/PD-L1 (cancer, maladies inflammatoires chroniques, maladies neurologiques et infections chroniques).
EP24737945.6A 2023-06-30 2024-06-28 Dérivés de pyrazole en tant qu'inhibiteurs d'interaction pd-1/pd-l1 Pending EP4735113A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP23306103 2023-06-30
PCT/EP2024/068292 WO2025003429A1 (fr) 2023-06-30 2024-06-28 Dérivés de pyrazole en tant qu'inhibiteurs d'interaction pd-1/pd-l1

Publications (1)

Publication Number Publication Date
EP4735113A1 true EP4735113A1 (fr) 2026-05-06

Family

ID=87863588

Family Applications (1)

Application Number Title Priority Date Filing Date
EP24737945.6A Pending EP4735113A1 (fr) 2023-06-30 2024-06-28 Dérivés de pyrazole en tant qu'inhibiteurs d'interaction pd-1/pd-l1

Country Status (5)

Country Link
EP (1) EP4735113A1 (fr)
KR (1) KR20260035902A (fr)
CN (1) CN121752548A (fr)
AU (1) AU2024310722A1 (fr)
WO (1) WO2025003429A1 (fr)

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2284817T3 (es) * 2001-01-26 2007-11-16 Chugai Seiyaku Kabushiki Kaisha Procedimientos para el tratamiento de enfermedades con inhibidores de la malonil coa descarboxilasa.
EP3766544A1 (fr) 2019-07-18 2021-01-20 Centre Hospitalier Regional Universitaire de Lille Nouveaux dérivés de pyrazolone en tant qu'inhibiteurs de l'interaction pd-1/pd-l1
CN111333629B (zh) * 2020-04-10 2021-03-05 颜建发 苯基-1h-吡唑类衍生物及其在抗肿瘤药物中的应用
CN111320606B (zh) * 2020-04-10 2021-07-27 安徽实特医药科技有限公司 苯联吡唑并环类衍生物及其在抗肿瘤药物中的应用
WO2022115207A1 (fr) * 2020-11-25 2022-06-02 Trustees Of Dartmouth College Méthode permettant d'atténuer la neuroinflammation

Also Published As

Publication number Publication date
WO2025003429A1 (fr) 2025-01-02
KR20260035902A (ko) 2026-03-13
CN121752548A (zh) 2026-03-27
AU2024310722A1 (en) 2026-01-15

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