JP7426398B2 - Ｒａｓ阻害剤としての新規イソインドリノン置換インドールおよび誘導体 - Google Patents

Ｒａｓ阻害剤としての新規イソインドリノン置換インドールおよび誘導体 Download PDF

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JP7426398B2
JP7426398B2 JP2021549575A JP2021549575A JP7426398B2 JP 7426398 B2 JP7426398 B2 JP 7426398B2 JP 2021549575 A JP2021549575 A JP 2021549575A JP 2021549575 A JP2021549575 A JP 2021549575A JP 7426398 B2 JP7426398 B2 JP 7426398B2
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methyl
indol
dihydro
hydroxy
μmol
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JP2022523201A5 (enExample
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アンドレアス マントウリディス
アンドレアス ゴルナー
ディルク ケスラー
レティシア ジャニーヌ マルタン
ハーラルト ヴァインスタブル
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ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • 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
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
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    • 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
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    • 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
    • C07D403/06—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 only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
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    • 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
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    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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    • 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
    • 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)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
JP2021549575A 2019-02-26 2020-02-25 Ｒａｓ阻害剤としての新規イソインドリノン置換インドールおよび誘導体 Active JP7426398B2 (ja)

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EP19159299.7 2019-02-26
EP19159299 2019-02-26
PCT/EP2020/054897 WO2020173935A1 (en) 2019-02-26 2020-02-25 New isoindolinone substituted indoles and derivatives as ras inhibitors

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JP2022523201A JP2022523201A (ja) 2022-04-21
JP2022523201A5 JP2022523201A5 (enExample) 2023-03-03
JP7426398B2 true JP7426398B2 (ja) 2024-02-01

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US (1) US12281099B2 (enExample)
EP (1) EP3931188B1 (enExample)
JP (1) JP7426398B2 (enExample)
CN (1) CN113474340B (enExample)
WO (1) WO2020173935A1 (enExample)

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BR112020020307A2 (pt) 2018-04-04 2021-01-12 Arvinas Operations, Inc. Moduladores de proteólise e métodos de uso associados
AU2021263914B2 (en) 2020-04-29 2026-07-23 D.E. Shaw Research, Llc PI3K-α inhibitors and methods of use thereof
IL301298A (en) 2020-09-15 2023-05-01 Revolution Medicines Inc Indole derivatives as RAS inhibitors in cancer therapy
EP4313151A1 (en) 2021-03-31 2024-02-07 Sevenless Therapeutics Limited Sos1 inhibitors and ras inhibitors for use in the treatment of pain
GB202104609D0 (en) 2021-03-31 2021-05-12 Sevenless Therapeutics Ltd New Treatments for Pain
CN115232108B (zh) 2021-04-23 2025-04-18 领泰生物医药(绍兴)有限公司 Sos1降解剂及其制备方法和应用
AR127308A1 (es) 2021-10-08 2024-01-10 Revolution Medicines Inc Inhibidores ras
WO2023060362A1 (en) * 2021-10-15 2023-04-20 Genetolead Inc. Ras inhibitors, compositions and methods of use thereof
TW202334136A (zh) * 2021-11-03 2023-09-01 美商傳達治療有限公司 PI3Kα抑制劑及其製造與使用方法
WO2023114973A1 (en) 2021-12-17 2023-06-22 Shure Acquisition Holdings, Inc. Adaptive acoustic echo cancellation for a stereo audio signal
TW202340214A (zh) 2021-12-17 2023-10-16 美商健臻公司 做為shp2抑制劑之吡唑并吡𠯤化合物
EP4227307A1 (en) 2022-02-11 2023-08-16 Genzyme Corporation Pyrazolopyrazine compounds as shp2 inhibitors
CA3244999A1 (en) 2022-03-31 2025-06-13 Eisai R&D Management Co., Ltd. Pharmaceutical composition for treating tumors
EP4536364A1 (en) 2022-06-10 2025-04-16 Revolution Medicines, Inc. Macrocyclic ras inhibitors
EP4598538A1 (en) 2022-10-05 2025-08-13 Sevenless Therapeutics Limited New treatments for pain
PE20260006A1 (es) 2023-01-26 2026-01-06 Arvinas Operations Inc Protacs degradadores de kras basados en cereblon y usos relacionados con los mismos
KR20250166103A (ko) 2023-04-06 2025-11-27 에자이 알앤드디 매니지먼트 가부시키가이샤 종양 치료용 약제학적 조성물
CN121487951A (zh) 2023-04-07 2026-02-06 锐新医药公司 大环ras抑制剂
WO2024211712A1 (en) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Condensed macrocyclic compounds as ras inhibitors
AU2024251341A1 (en) 2023-04-14 2025-10-16 Revolution Medicines, Inc. Crystalline forms of a ras inhibitor
EP4695261A1 (en) 2023-04-14 2026-02-18 Revolution Medicines, Inc. Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof

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WO2018140513A1 (en) 2017-01-26 2018-08-02 Araxes Pharma Llc 1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1yl)prop-2-en-1-one derivatives and similar compounds as kras g12c modulators for treating cancer
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WO2018068017A1 (en) 2016-10-07 2018-04-12 Araxes Pharma Llc Heterocyclic compounds as inhibitors of ras and methods of use thereof
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CN113474340A (zh) 2021-10-01
WO2020173935A1 (en) 2020-09-03
EP3931188B1 (en) 2023-08-30
CN113474340B (zh) 2024-07-23
US20220144810A1 (en) 2022-05-12
US12281099B2 (en) 2025-04-22
EP3931188A1 (en) 2022-01-05
JP2022523201A (ja) 2022-04-21

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