CN106794171B - Mdm2抑制剂和使用其的治疗方法 - Google Patents

Mdm2抑制剂和使用其的治疗方法 Download PDF

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Publication number
CN106794171B
CN106794171B CN201580032547.2A CN201580032547A CN106794171B CN 106794171 B CN106794171 B CN 106794171B CN 201580032547 A CN201580032547 A CN 201580032547A CN 106794171 B CN106794171 B CN 106794171B
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compound
cancer
mdm2
compounds
disease
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CN106794171A (zh
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S.王
A.阿圭拉
L.刘
J.卢
D.麦凯彻恩
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University of Michigan System
University of Michigan Ann Arbor
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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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  • Veterinary Medicine (AREA)
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  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • 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)
  • Hematology (AREA)
  • Oncology (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)
CN201580032547.2A 2014-04-17 2015-04-16 Mdm2抑制剂和使用其的治疗方法 Active CN106794171B (zh)

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CN (2) CN106794171B (https=)
AU (1) AU2015247646B2 (https=)
CA (1) CA2945527C (https=)
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111718354A (zh) * 2014-04-17 2020-09-29 密歇根大学董事会 Mdm2抑制剂和使用其的治疗方法
US11478470B2 (en) 2018-07-31 2022-10-25 Ascentage Pharma (Suzhou) Co., Ltd. Combination product of Bcl-2 inhibitor or Bcl-2/Bcl-xL dual inhibitor and BTK inhibitor and use thereof in the prevention and/or treatment of diseases
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
US11491167B2 (en) 2018-07-31 2022-11-08 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
US11554127B2 (en) 2018-07-31 2023-01-17 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

Families Citing this family (38)

* 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
RS59111B1 (sr) 2014-08-21 2019-09-30 Boehringer Ingelheim Int Nova jedinjenja spiro[3h-indol-3,2´-pirolidin]-2(1h)-ona i derivati kao mdm2-p53 inhibitori
US9962380B2 (en) * 2015-09-23 2018-05-08 Wisconsin Alumni Research Foundation Methods for treating cognitive deficits associated with fragile X syndrome
GB201517217D0 (en) 2015-09-29 2015-11-11 Astex Therapeutics Ltd And Cancer Res Technology Ltd Pharmaceutical compounds
GB201517216D0 (en) 2015-09-29 2015-11-11 Cancer Res Technology Ltd And Astex Therapeutics Ltd Pharmaceutical compounds
KR20240158360A (ko) 2015-10-09 2024-11-04 베링거 인겔하임 인터내셔날 게엠베하 Mdm2-p53 억제제로서의 스피로[3h-인돌-3,2'-피롤리딘]-2(1h)-온 화합물 및 유도체
SG11201808728QA (en) * 2016-04-06 2018-11-29 Univ Michigan Regents 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
GB201704965D0 (en) 2017-03-28 2017-05-10 Astex Therapeutics Ltd Pharmaceutical compounds
GB201704966D0 (en) 2017-03-28 2017-05-10 Astex Therapeutics Ltd Pharmaceutical compounds
MX2020006816A (es) * 2017-12-29 2020-09-03 Gan & Lee Pharmaceuticals Compuestos que pueden usarse como inhibidor tumoral, metodo de preparacion de los mismos y aplicacion de los mismos.
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
WO2020030016A1 (en) * 2018-08-08 2020-02-13 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
WO2020119614A1 (en) * 2018-12-14 2020-06-18 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
EP3814358B1 (en) * 2019-07-11 2025-09-03 Ascentage Pharma (Suzhou) Co., Ltd. Method for preparing 2-indolinospirone compounds and intermediates thereof
WO2021013028A1 (en) 2019-07-19 2021-01-28 Ascentage Pharma (Suzhou) Co., Ltd. Pharmaceutical combination and use thereof
US12194024B2 (en) * 2019-07-26 2025-01-14 Ascentage Pharma (Suzhou) Co., Ltd. Pharmaceutical composition of MDM2 inhibitor and use thereof for preventing and/or treating disease
US12287338B2 (en) 2019-11-27 2025-04-29 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
CN113337602A (zh) * 2020-03-02 2021-09-03 苏州亚盛药业有限公司 Mdm2抑制剂的治疗方法和生物标志物
KR20230005160A (ko) 2020-03-19 2023-01-09 카이메라 쎄라퓨틱스 인코포레이티드 Mdm2 분해제 및 이의 용도
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
WO2021254277A1 (en) * 2020-06-15 2021-12-23 Ascentage Pharma (Suzhou) Co., Ltd. Microsuspension of an mdm2 inhibitor and therapeutic applications thereof
EP4204812A2 (en) 2020-08-27 2023-07-05 Otsuka Pharmaceutical Co., Ltd. Biomarkers for cancer therapy using mdm2 antagonists
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
JP2024511277A (ja) 2021-02-19 2024-03-13 メビオン・メディカル・システムズ・インコーポレーテッド 粒子線治療システムのためのガントリー
GB202103080D0 (en) 2021-03-04 2021-04-21 Otsuka Pharma Co Ltd Cancer biomarkers
CN117957018A (zh) 2021-08-02 2024-04-30 苏州亚盛药业有限公司 一种药物组合及其用途
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

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101400679A (zh) * 2006-03-13 2009-04-01 霍夫曼-拉罗奇有限公司 螺吲哚满酮衍生物
CN101528223A (zh) * 2006-08-30 2009-09-09 密执安州立大学董事会 Mdm2的新型小分子抑制剂和其用途
CN102712650A (zh) * 2009-11-12 2012-10-03 密歇根大学董事会 螺-吲哚酮mdm2拮抗剂
CN103635473A (zh) * 2011-03-10 2014-03-12 第一三共株式会社 二螺吡咯烷衍生物
CN103717605A (zh) * 2011-05-11 2014-04-09 密执安州立大学董事会 螺-羟吲哚mdm2拮抗剂

Family Cites Families (22)

* 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
JP4870778B2 (ja) 2005-12-01 2012-02-08 エフ．ホフマン−ラ ロシュ アーゲー 抗ガン剤として使用されるｐ５３およびｍｄｍ２タンパク質間の相互作用の阻害剤としての２，４，５−トリフェニルイミダゾリン誘導体
JP2009530236A (ja) * 2006-03-13 2009-08-27 エフ．ホフマン−ラ ロシュ アーゲー スピロインドリノン誘導体
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
US20080206794A1 (en) 2006-09-15 2008-08-28 Renovar Incorporated Systems And Methods For Characterizing Contrast Induced-Nephropathy
US20080188506A1 (en) * 2007-02-07 2008-08-07 Qingjie Ding Spiroindolinone derivatives
US8354444B2 (en) 2008-09-18 2013-01-15 Hoffmann-La Roche Inc. Substituted pyrrolidine-2-carboxamides
MY160424A (en) 2008-09-18 2017-03-15 Hoffmann La Roche Substituted pyrrolidine-2-carboxyamides.
US8076482B2 (en) * 2009-04-23 2011-12-13 Hoffmann-La Roche Inc. 3,3′-spiroindolinone derivatives
US8088815B2 (en) 2009-12-02 2012-01-03 Hoffman-La Roche Inc. Spiroindolinone pyrrolidines
SG184288A1 (en) * 2010-04-09 2012-11-29 Univ 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
JP2014500870A (ja) 2010-11-12 2014-01-16 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
US9376425B2 (en) 2011-09-27 2016-06-28 Amgen, Inc. Heterocyclic compounds as MDM2 inhibitors for the treatment of cancer
KR20220136454A (ko) * 2013-09-04 2022-10-07 다이이찌 산쿄 가부시키가이샤 스피로옥시인돌 유도체의 제조 방법
CA2945527C (en) * 2014-04-17 2022-05-17 The Regents Of The University Of Michigan Mdm2 inhibitors and therapeutic methods using the same

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101400679A (zh) * 2006-03-13 2009-04-01 霍夫曼-拉罗奇有限公司 螺吲哚满酮衍生物
CN101528223A (zh) * 2006-08-30 2009-09-09 密执安州立大学董事会 Mdm2的新型小分子抑制剂和其用途
CN102712650A (zh) * 2009-11-12 2012-10-03 密歇根大学董事会 螺-吲哚酮mdm2拮抗剂
CN103635473A (zh) * 2011-03-10 2014-03-12 第一三共株式会社 二螺吡咯烷衍生物
CN103717605A (zh) * 2011-05-11 2014-04-09 密执安州立大学董事会 螺-羟吲哚mdm2拮抗剂

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Antonia F. Stepan等.Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor.《Journal of Medicinal Chemistry》.2012,第55卷第3414-3424页. *
Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor;Antonia F. Stepan等;《Journal of Medicinal Chemistry》;20120315;第55卷;第3414-3424页 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111718354A (zh) * 2014-04-17 2020-09-29 密歇根大学董事会 Mdm2抑制剂和使用其的治疗方法
US11478470B2 (en) 2018-07-31 2022-10-25 Ascentage Pharma (Suzhou) Co., Ltd. Combination product of Bcl-2 inhibitor or Bcl-2/Bcl-xL dual inhibitor and BTK inhibitor and use thereof in the prevention and/or treatment of diseases
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
US11491167B2 (en) 2018-07-31 2022-11-08 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
US11554127B2 (en) 2018-07-31 2023-01-17 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

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CN106794171A (zh) 2017-05-31
SG10201913742TA (en) 2020-03-30
EP3131544A4 (en) 2017-08-30
CA2945527A1 (en) 2015-10-22
AU2015247646B2 (en) 2019-06-06
JP6909323B2 (ja) 2021-07-28
EP3131544A1 (en) 2017-02-22
KR20220054697A (ko) 2022-05-03
ES2712973T3 (es) 2019-05-17
MX373045B (es) 2020-05-26
CN111718354A (zh) 2020-09-29
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