JP6503386B2 - ＭＤＭ２−ｐ５３阻害剤としての新しいスピロ［３Ｈ−インドール−３，２’−ピロリジン］−２（１Ｈ）−オン化合物および誘導体 - Google Patents

ＭＤＭ２−ｐ５３阻害剤としての新しいスピロ［３Ｈ−インドール−３，２’−ピロリジン］−２（１Ｈ）−オン化合物および誘導体 Download PDF

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JP6503386B2
JP6503386B2 JP2016575738A JP2016575738A JP6503386B2 JP 6503386 B2 JP6503386 B2 JP 6503386B2 JP 2016575738 A JP2016575738 A JP 2016575738A JP 2016575738 A JP2016575738 A JP 2016575738A JP 6503386 B2 JP6503386 B2 JP 6503386B2
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JP2017527532A (ja
JP2017527532A5 (Direct
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ハーラルト ヴァインスタブル
ハーラルト ヴァインスタブル
アンドレアス ゴウルナー
アンドレアス ゴウルナー
ユルゲン ラムハーター
ユルゲン ラムハーター
トビアス ヴュンベルク
トビアス ヴュンベルク
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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
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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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/20—Spiro-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
    • C07D471/22—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 systems contains four or more hetero rings
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    • 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
    • C07D487/12—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 three hetero rings
    • C07D487/20—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
    • C07D491/20—Spiro-condensed systems

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  • Health & Medical Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
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  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Oncology (AREA)
  • Transplantation (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
JP2016575738A 2014-07-03 2015-07-02 ＭＤＭ２−ｐ５３阻害剤としての新しいスピロ［３Ｈ−インドール−３，２’−ピロリジン］−２（１Ｈ）−オン化合物および誘導体 Active JP6503386B2 (ja)

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EP14175620 2014-07-03
EP14175620.5 2014-07-03
PCT/EP2015/065134 WO2016001376A1 (en) 2014-07-03 2015-07-02 New spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors

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JP2017527532A JP2017527532A (ja) 2017-09-21
JP2017527532A5 JP2017527532A5 (Direct) 2018-08-16
JP6503386B2 true JP6503386B2 (ja) 2019-04-17

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US (1) US10576064B2 (Direct)
EP (1) EP3164401B1 (Direct)
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WO (1) WO2016001376A1 (Direct)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3129380B1 (en) 2014-04-11 2018-11-28 Boehringer Ingelheim International Gmbh Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one derivatives and their use as mdm2-p53 inhibitors
JP6503386B2 (ja) 2014-07-03 2019-04-17 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 ＭＤＭ２−ｐ５３阻害剤としての新しいスピロ［３Ｈ−インドール−３，２’−ピロリジン］−２（１Ｈ）−オン化合物および誘導体
CN107001385B (zh) 2014-08-21 2020-03-13 勃林格殷格翰国际有限公司 作为mdm2-p53抑制剂的螺-[3h-吲哚-3，2’-吡咯烷]-2(1h)-酮化合物及其衍生物
CN119569740A (zh) 2015-10-09 2025-03-07 勃林格殷格翰国际有限公司 作为mdm2-p53抑制剂的化合物及其衍生物
EP3440066B1 (en) 2016-04-06 2022-11-30 The Regents of The University of Michigan Mdm2 protein degraders
CN118436801A (zh) 2016-05-20 2024-08-06 豪夫迈·罗氏有限公司 Protac抗体缀合物及其使用方法
JP2020516604A (ja) 2017-04-05 2020-06-11 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 抗がん併用療法
SG11202006262TA (en) * 2017-12-29 2020-07-29 Gan & Lee Pharmaceuticals Compound capable of being used as tumor inhibitor, preparation method therefor, and application thereof
EP3511334A1 (en) * 2018-01-16 2019-07-17 Adamed sp. z o.o. 1,2,3',5'-tetrahydro-2'h-spiro[indole-3,1'-pyrrolo[3,4-c]pyrrole]-2,3'-dione compounds as therapeutic agents activating tp53
US12480163B2 (en) * 2018-07-18 2025-11-25 Dana-Farber Cancer Institute, Inc. Compositions and methods for identification assessment, prevention, and treatment of Ewing sarcoma using TP53 dependency biomarkers and modulators
SE542672C2 (en) 2018-09-14 2020-06-23 Ausferritic Ab Method for producing an ausferritic steel austempered during continuous cooling followed by annealing
US10590147B1 (en) 2019-09-10 2020-03-17 King Saud University Spirooxindole-pyrrolothiazole heterocyclic hybrids
WO2021245055A1 (en) 2020-06-02 2021-12-09 Boehringer Ingelheim International Gmbh Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer
WO2023056069A1 (en) 2021-09-30 2023-04-06 Angiex, Inc. Degrader-antibody conjugates and methods of using same
US20250145608A1 (en) 2021-12-01 2025-05-08 Boehringer Ingelheim Int'l GmbH Corp. Kras degrading compounds comprising annulated 2-amino-3-cyano thiophenes
PE20241356A1 (es) 2021-12-01 2024-07-03 Boehringer Ingelheim Int Tiofenos 2-amino-3-ciano anulados y derivados para el tratamiento del cancer
CN118574836A (zh) 2021-12-01 2024-08-30 勃林格殷格翰国际有限公司 用于治疗癌症的环状2-胺基-3-氰基噻吩及衍生物
CN119013272A (zh) 2021-12-01 2024-11-22 勃林格殷格翰国际有限公司 用于治疗癌症的环状2-氨基-3-氰基噻吩及其衍生物
JP2024543982A (ja) 2021-12-01 2024-11-26 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 がんの処置のための縮環２－アミノ－３－シアノチオフェン及び誘導体
WO2023239697A1 (en) * 2022-06-06 2023-12-14 Kymera Therapeutics, Inc. Mdm2 degraders and uses thereof
US11944604B1 (en) 2023-03-10 2024-04-02 King Saud University Nanoformulation of spriooxindole and methods for treating hepatocellular carcinoma
WO2024240858A1 (en) 2023-05-23 2024-11-28 Valerio Therapeutics Protac molecules directed against dna damage repair system and uses thereof
WO2024246099A1 (en) 2023-05-30 2024-12-05 Boehringer Ingelheim International Gmbh Spirocyclic annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer

Family Cites Families (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1015430A4 (en) 1997-09-08 2001-01-17 Arqule Inc SPIRO (PRROLIDIN-2,3'-OXOINDOL) COMPOUNDS AND METHOD FOR USE THEREOF
JP2006234861A (ja) 2005-02-22 2006-09-07 Fujinon Sano Kk 光学ガラスの製造方法，偏光変換素子の製造方法及び偏光変換素子
WO2006091646A2 (en) 2005-02-22 2006-08-31 The Regents Of The University Of Michigan Small molecule inhibitors of mdm2 and uses thereof
WO2006090261A1 (en) 2005-02-24 2006-08-31 Pfizer Products Inc. Bicyclic heteroaromatic derivatives useful as anticancer agents
KR101052706B1 (ko) 2006-03-13 2011-08-01 에프. 호프만-라 로슈 아게 스피로인돌리논 유도체
US20070213341A1 (en) 2006-03-13 2007-09-13 Li Chen Spiroindolinone derivatives
CA2656398A1 (en) 2006-06-30 2008-01-10 Schering Corporation Substituted piperidines that increase p53 activity and the uses thereof
CN101528223B (zh) 2006-08-30 2013-05-01 密执安州立大学董事会 Mdm2的新型小分子抑制剂和其用途
KR20090122403A (ko) 2007-03-29 2009-11-27 노파르티스 아게 증식성 질환의 치료를 위한 3-이미다졸릴-인돌
US7553833B2 (en) 2007-05-17 2009-06-30 Hoffmann-La Roche Inc. 3,3-spiroindolinone derivatives
US7834179B2 (en) 2007-05-23 2010-11-16 Hoffmann-La Roche Inc. Spiroindolinone derivatives
US8134001B2 (en) 2007-12-14 2012-03-13 Hoffmann-La Roche Inc. Spiroindolinone derivatives
US7776875B2 (en) 2007-12-19 2010-08-17 Hoffman-La Roche Inc. Spiroindolinone derivatives
TW201011009A (en) * 2008-09-15 2010-03-16 Priaxon Ag Novel pyrrolidin-2-ones
US20100190814A1 (en) 2009-01-26 2010-07-29 Li Chen Spiroindolinone derivative prodrugs
US8076482B2 (en) 2009-04-23 2011-12-13 Hoffmann-La Roche Inc. 3,3′-spiroindolinone derivatives
JP2013510860A (ja) 2009-11-12 2013-03-28 ザ、リージェンツ、オブ、ザ、ユニバーシティ、オブ、ミシガン スピロ−オキシインドールｍｄｍ２アンタゴニスト
US8088815B2 (en) 2009-12-02 2012-01-03 Hoffman-La Roche Inc. Spiroindolinone pyrrolidines
US8288431B2 (en) 2010-02-17 2012-10-16 Hoffmann-La Roche Inc. Substituted spiroindolinones
US8217044B2 (en) 2010-04-28 2012-07-10 Hoffmann-La Roche Inc. Spiroindolinone pyrrolidines
JO2998B1 (ar) 2010-06-04 2016-09-05 Amgen Inc مشتقات بيبيريدينون كمثبطات mdm2 لعلاج السرطان
US20120046306A1 (en) 2010-08-18 2012-02-23 David Joseph Bartkovitz Substituted Heteroaryl Spiropyrrolidine MDM2 Antagonists
US20120071499A1 (en) 2010-09-20 2012-03-22 Xin-Jie Chu Substituted Spiro[3H-Indole-3,6'(5'H)-[1H]Pyrrolo[1,2c]Imidazole-1',2(1H,2'H)-diones
UY33725A (es) 2010-11-12 2012-06-29 Sanofi Sa Antagonistas de mdm2 de espiro-oxindol
US20130053410A1 (en) 2011-03-03 2013-02-28 David Joseph Bartkovitz Substituted heteroaryl 2',3',7',7a'-tetrahydrospiro[pyrrole-3,6'-pyrrolo[1,2-c]imidazole]-1',2(1h,5'h)-dione
RU2612534C2 (ru) 2011-03-10 2017-03-09 Дайити Санкио Компани, Лимитед Диспиропирролидиновые производные
MX346375B (es) 2011-05-11 2017-03-16 Univ Michigan Regents Antagonistas de espiro-oxindol de mdm2.
CN102443004A (zh) 2011-11-01 2012-05-09 南京工业大学 有机发光材料6,7,14,15-四氢-5,13-二取代苯并[1,2-c:4,5-c’]二吖啶类化合物、合成方法及应用
CN103910746B (zh) 2014-02-28 2016-08-03 中山大学 一类海洋真菌来源的Berkeleyones化合物及其制备方法和应用
EP3129380B1 (en) 2014-04-11 2018-11-28 Boehringer Ingelheim International Gmbh Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one derivatives and their use as mdm2-p53 inhibitors
JP6503386B2 (ja) 2014-07-03 2019-04-17 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 ＭＤＭ２−ｐ５３阻害剤としての新しいスピロ［３Ｈ−インドール−３，２’−ピロリジン］−２（１Ｈ）−オン化合物および誘導体
NO2721710T3 (Direct) 2014-08-21 2018-03-31
CN107001385B (zh) 2014-08-21 2020-03-13 勃林格殷格翰国际有限公司 作为mdm2-p53抑制剂的螺-[3h-吲哚-3，2’-吡咯烷]-2(1h)-酮化合物及其衍生物
CN119569740A (zh) 2015-10-09 2025-03-07 勃林格殷格翰国际有限公司 作为mdm2-p53抑制剂的化合物及其衍生物

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JP2017527532A (ja) 2017-09-21
EP3164401B1 (en) 2018-12-26
US20160000764A1 (en) 2016-01-07
US10576064B2 (en) 2020-03-03
WO2016001376A1 (en) 2016-01-07

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