AU2015247646B2 - MDM2 inhibitors and therapeutic methods using the same - Google Patents

MDM2 inhibitors and therapeutic methods using the same Download PDF

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Publication number
AU2015247646B2
AU2015247646B2 AU2015247646A AU2015247646A AU2015247646B2 AU 2015247646 B2 AU2015247646 B2 AU 2015247646B2 AU 2015247646 A AU2015247646 A AU 2015247646A AU 2015247646 A AU2015247646 A AU 2015247646A AU 2015247646 B2 AU2015247646 B2 AU 2015247646B2
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compound
mdm2
compounds
cancer
structural formula
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AU2015247646A1 (en
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Angelo AGUILAR
Liu Liu
Jianfeng Lu
Donna Mceachern
Shaomeng Wang
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University of Michigan (System)
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    • 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
    • C07D487/10—Spiro-condensed systems
    • 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
    • A61K31/435—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
    • 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
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N2005/1092—Details
    • A61N2005/1098—Enhancing the effect of the particle by an injected agent or implanted device

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Pathology (AREA)
  • Radiology & Medical Imaging (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
AU2015247646A 2014-04-17 2015-04-16 MDM2 inhibitors and therapeutic methods using the same Active AU2015247646B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201461980747P 2014-04-17 2014-04-17
US61/980,747 2014-04-17
PCT/US2015/026098 WO2015161032A1 (en) 2014-04-17 2015-04-16 Mdm2 inhibitors and therapeutic methods using the same

Publications (2)

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AU2015247646A1 AU2015247646A1 (en) 2016-10-27
AU2015247646B2 true AU2015247646B2 (en) 2019-06-06

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US (1) US9745314B2 (enExample)
EP (1) EP3131544B1 (enExample)
JP (2) JP6694827B2 (enExample)
KR (2) KR102599945B1 (enExample)
CN (2) CN106794171B (enExample)
AU (1) AU2015247646B2 (enExample)
CA (1) CA2945527C (enExample)
ES (1) ES2712973T3 (enExample)
IL (2) IL248211B (enExample)
MX (2) MX373045B (enExample)
SG (2) SG11201608667SA (enExample)
WO (1) WO2015161032A1 (enExample)

Families Citing this family (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0811643D0 (en) 2008-06-25 2008-07-30 Cancer Rec Tech Ltd New therapeutic agents
AU2015247646B2 (en) * 2014-04-17 2019-06-06 The Regents Of The University Of Michigan MDM2 inhibitors and therapeutic methods using the same
JP6591532B2 (ja) 2014-08-21 2019-10-16 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
US9962380B2 (en) * 2015-09-23 2018-05-08 Wisconsin Alumni Research Foundation Methods for treating cognitive deficits associated with fragile X syndrome
GB201517216D0 (en) 2015-09-29 2015-11-11 Cancer Res Technology Ltd And Astex Therapeutics Ltd Pharmaceutical compounds
GB201517217D0 (en) 2015-09-29 2015-11-11 Astex Therapeutics Ltd And Cancer Res Technology Ltd Pharmaceutical compounds
HUE054985T2 (hu) 2015-10-09 2021-11-29 Boehringer Ingelheim Int Spiro[3H-indol-3,2'-pirrolidin]-2(1H)-on vegyületek és számrazékok, mint MDM2-P53 inhibitorok
AU2017246452C1 (en) 2016-04-06 2021-06-03 The Regents Of The University Of Michigan MDM2 protein degraders
CN109152843A (zh) 2016-05-20 2019-01-04 豪夫迈·罗氏有限公司 Protac抗体缀合物及其使用方法
GB201704966D0 (en) 2017-03-28 2017-05-10 Astex Therapeutics Ltd Pharmaceutical compounds
GB201704965D0 (en) 2017-03-28 2017-05-10 Astex Therapeutics Ltd Pharmaceutical compounds
EA202091583A1 (ru) * 2017-12-29 2020-10-08 Ган Энд Ли Фармасьютикалз Соединения, которые могут применяться в качестве ингибитора опухоли, способ их получения и их применение
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
KR102039696B1 (ko) 2018-04-23 2019-11-04 충남대학교산학협력단 세포내 결핵균 제어를 위한 p53 발현 조절 가능한 조성물 (K279-1558) 또는 방법
US11478469B2 (en) 2018-07-31 2022-10-25 Ascentage Pharma (Suzhou) Co., Ltd. Combination product of BCL-2 inhibitor and MDM2 inhibitor and use thereof in the prevention and/or treatment of diseases
CA3095699A1 (en) 2018-07-31 2020-02-06 Ascentage Pharma (Suzhou) Co., Ltd. Combination product of bcl-2 inhibitor and chemotherapeutic agent and use thereof in the prevention and/or treatment of diseases
CN110772521A (zh) 2018-07-31 2020-02-11 苏州亚盛药业有限公司 Bcl-2抑制剂或Bcl-2/Bcl-xL抑制剂与BTK抑制剂的组合产品及其用途
AU2019315466B2 (en) 2018-07-31 2022-05-19 Ascentage Pharma (Suzhou) Co., Ltd. Synergistic antitumor effect of Bcl-2 inhibitor combined with rituximab and/or bendamustine or Bcl-2 inhibitor combined with CHOP
EP3833445A4 (en) * 2018-08-08 2022-04-27 Ascentage Pharma (Suzhou) Co., Ltd. COMBINATION OF IMMUNOTHERAPIES WITH MDM2 INHIBITORS
WO2020103922A1 (en) 2018-11-23 2020-05-28 Ascentage Pharma (Suzhou) Co., Ltd. Novel pharmaceutical composition and use thereof
EP3697412B1 (en) * 2018-12-14 2026-02-25 Ascentage Pharma (Suzhou) Co., Ltd. A compound for treating osteoarthritis
EP3814525A4 (en) * 2019-02-24 2022-04-13 Ascentage Pharma (Suzhou) Co., Ltd. TREATMENT METHODS AND BIOMARKERS FOR MDM2 INHIBITORS
WO2021004516A1 (en) * 2019-07-11 2021-01-14 Ascentage Pharma (Suzhou) Co., Ltd. Method for preparing 2-indolinospirone compound and intermediate thereof
US12233047B2 (en) * 2019-07-19 2025-02-25 Ascentage Pharma (Suzhou) Co., Ltd. Pharmaceutical combination and use thereof
TW202118488A (zh) * 2019-07-26 2021-05-16 大陸商蘇州亞盛藥業有限公司 Mdm2抑制劑的藥物組合物及其在預防和/或治療疾病中的用途
WO2021104442A1 (en) * 2019-11-27 2021-06-03 Ascentage Pharma (Suzhou) Co., Ltd. Method and compositions for predicting anti-cancer efficacy of compounds targeting apoptosis pathway
US11850239B2 (en) 2019-12-19 2023-12-26 Ascentage Pharma (Suzhou) Co., Ltd. MDM2 inhibitor and a platinum compound for cancer treatment
GB201919219D0 (en) 2019-12-23 2020-02-05 Otsuka Pharma Co Ltd Cancer biomarkers
US20230064976A1 (en) * 2020-01-23 2023-03-02 Ascentage Pharma (Suzhou) Co., Ltd. Amorphous form or crystalline form of 2-indolinolinololylspironone compounds or their salts, solvent complexes
WO2021175192A1 (en) * 2020-03-02 2021-09-10 Ascentage Pharma (Suzhou) Co., Ltd. Treatment methods and biomarkers for mdm2 inhibitors
WO2021188948A1 (en) 2020-03-19 2021-09-23 Kymera Therapeutics, Inc. Mdm2 degraders and uses thereof
CN113521064A (zh) * 2020-04-14 2021-10-22 苏州亚盛药业有限公司 Mdm2抑制剂的新用途
CN113801120B (zh) * 2020-06-15 2024-03-22 苏州亚盛药业有限公司 Mdm2抑制剂的微悬浮液以及治疗应用
JP2023539867A (ja) 2020-08-27 2023-09-20 大塚製薬株式会社 Mdm2アンタゴニストを用いた癌治療に関するバイオマーカー
CN112022812B (zh) * 2020-11-03 2021-01-29 上海亚盛医药科技有限公司 一种包含杂环类化合物的组合物、其制备方法和应用
WO2022170108A1 (en) * 2021-02-04 2022-08-11 Aileron Therapeutics, Inc. Peptidomimetic macrocycles and uses thereof in prevention of radiation injury
US12245355B2 (en) 2021-02-19 2025-03-04 Mevion Medical Systems, Inc. Gantry for a particle therapy system
WO2022183006A1 (en) 2021-02-25 2022-09-01 Mayo Foundation For Medical Education And Research Compounds for programmable protein degradation and methods of use for the disease treatment
GB202103080D0 (en) 2021-03-04 2021-04-21 Otsuka Pharma Co Ltd Cancer biomarkers
JP2024528174A (ja) 2021-08-02 2024-07-26 アセンテージ ファーマ(スーチョウ)カンパニー,リミティド 医薬組合せおよびその使用
WO2023056069A1 (en) 2021-09-30 2023-04-06 Angiex, Inc. Degrader-antibody conjugates and methods of using same
WO2023134707A1 (en) * 2022-01-11 2023-07-20 Ascentage Pharma (Suzhou) Co., Ltd. Methods for treating aml-mrc and mds
WO2024240858A1 (en) 2023-05-23 2024-11-28 Valerio Therapeutics Protac molecules directed against dna damage repair system and uses thereof
WO2025223392A1 (zh) * 2024-04-22 2025-10-30 苏州亚盛药业有限公司 Mdm2抑制剂的用途及使用方法
WO2026115509A1 (en) 2024-11-29 2026-06-04 Assia Chemical Industries Ltd. Solid state forms of alrizomadlin and process for preparation thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080188506A1 (en) * 2007-02-07 2008-08-07 Qingjie Ding Spiroindolinone derivatives
US20120264738A1 (en) * 2011-03-10 2012-10-18 Yuuichi Sugimoto Dispiropyrrolidine derivatives
US20120289494A1 (en) * 2011-05-11 2012-11-15 Sanofi Spiro-oxindole mdm2 antagonists

Family Cites Families (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3989816A (en) 1975-06-19 1976-11-02 Nelson Research & Development Company Vehicle composition containing 1-substituted azacycloheptan-2-ones
US4444762A (en) 1980-04-04 1984-04-24 Nelson Research & Development Company Vehicle composition containing 1-substituted azacyclopentan-2-ones
US6605712B1 (en) 1990-12-20 2003-08-12 Arch Development Corporation Gene transcription and ionizing radiation: methods and compositions
US7759383B2 (en) 2005-02-22 2010-07-20 The Regents Of The University Of Michigan Small molecule inhibitors of MDM2 and the uses thereof
CN101316823B (zh) 2005-12-01 2013-05-22 霍夫曼-拉罗奇有限公司 用作抗癌剂的作为p53和MDM2蛋白之间相互作用的抑制剂的2,4,5-三苯基咪唑啉衍生物
CN101400680B (zh) * 2006-03-13 2012-04-25 霍夫曼-拉罗奇有限公司 螺吲哚满酮衍生物
DE602007011902D1 (de) * 2006-03-13 2011-02-24 Hoffmann La Roche Spiroindolinon-derivate
US8222288B2 (en) 2006-08-30 2012-07-17 The Regents Of The University Of Michigan Small molecule inhibitors of MDM2 and the uses thereof
US7737174B2 (en) 2006-08-30 2010-06-15 The Regents Of The University Of Michigan Indole inhibitors of MDM2 and the uses thereof
CA2661354C (en) * 2006-08-30 2012-12-18 The Regents Of The University Of Michigan New small molecule inhibitors of mdm2 and the uses thereof
US20080206794A1 (en) 2006-09-15 2008-08-28 Renovar Incorporated Systems And Methods For Characterizing Contrast Induced-Nephropathy
US8354444B2 (en) 2008-09-18 2013-01-15 Hoffmann-La Roche Inc. Substituted pyrrolidine-2-carboxamides
CA2734363C (en) 2008-09-18 2016-10-25 F. Hoffmann-La Roche Ag Substituted pyrrolidine-2-carboxamides
US8076482B2 (en) * 2009-04-23 2011-12-13 Hoffmann-La Roche Inc. 3,3′-spiroindolinone derivatives
CN104876938A (zh) * 2009-11-12 2015-09-02 密歇根大学董事会 螺-吲哚酮mdm2拮抗剂
US8088815B2 (en) 2009-12-02 2012-01-03 Hoffman-La Roche Inc. Spiroindolinone pyrrolidines
AU2011237782A1 (en) * 2010-04-09 2012-10-25 The Regents Of The University Of Michigan Biomarkers for MDM2 inhibitors for use in treating disease
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
PE20140408A1 (es) 2010-11-12 2014-04-10 Univ Michigan Derivados espiro-oxindol como antagonistas de mdm2
MX352672B (es) 2011-09-27 2017-12-04 Amgen Inc Compuestos heterocíclicos como inhibidores de mdm2 para el tratamiento del cáncer.
TWI635089B (zh) * 2013-09-04 2018-09-11 第一三共股份有限公司 螺氧基吲哚衍生物之製造方法
AU2015247646B2 (en) * 2014-04-17 2019-06-06 The Regents Of The University Of Michigan MDM2 inhibitors and therapeutic methods using the same

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080188506A1 (en) * 2007-02-07 2008-08-07 Qingjie Ding Spiroindolinone derivatives
US20120264738A1 (en) * 2011-03-10 2012-10-18 Yuuichi Sugimoto Dispiropyrrolidine derivatives
US20120289494A1 (en) * 2011-05-11 2012-11-15 Sanofi Spiro-oxindole mdm2 antagonists

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Shangary, S. et al, "Small-molecule inhibitors of the MDM2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapy." Annual review of pharmacology and toxicology 49 (2009): 223-241 *

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Publication number Publication date
US9745314B2 (en) 2017-08-29
JP6909323B2 (ja) 2021-07-28
EP3131544A4 (en) 2017-08-30
KR102599945B1 (ko) 2023-11-09
KR102389552B1 (ko) 2022-04-22
CA2945527C (en) 2022-05-17
KR20220054697A (ko) 2022-05-03
IL248211B (en) 2019-10-31
AU2015247646A1 (en) 2016-10-27
WO2015161032A1 (en) 2015-10-22
JP2020100662A (ja) 2020-07-02
NZ724963A (en) 2021-10-29
SG11201608667SA (en) 2016-11-29
MX2016013457A (es) 2017-05-04
MX2020003939A (es) 2020-08-13
JP2017511360A (ja) 2017-04-20
KR20160136450A (ko) 2016-11-29
EP3131544B1 (en) 2018-12-12
CN106794171A (zh) 2017-05-31
US20150299211A1 (en) 2015-10-22
MX373045B (es) 2020-05-26
CN111718354A (zh) 2020-09-29
CN106794171B (zh) 2020-03-24
ES2712973T3 (es) 2019-05-17
EP3131544A1 (en) 2017-02-22
SG10201913742TA (en) 2020-03-30
JP6694827B2 (ja) 2020-05-20
IL269462B (en) 2021-05-31
IL248211A0 (en) 2016-11-30
CA2945527A1 (en) 2015-10-22
IL269462A (en) 2019-11-28

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