ES2712973T3 - Inhibidores de MDM2 y métodos terapéuticos que usan los mismos - Google Patents

Inhibidores de MDM2 y métodos terapéuticos que usan los mismos Download PDF

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Publication number
ES2712973T3
ES2712973T3 ES15779988T ES15779988T ES2712973T3 ES 2712973 T3 ES2712973 T3 ES 2712973T3 ES 15779988 T ES15779988 T ES 15779988T ES 15779988 T ES15779988 T ES 15779988T ES 2712973 T3 ES2712973 T3 ES 2712973T3
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compounds
mdm2
compound according
cancer
structural formula
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Spanish (es)
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Shaomeng Wang
Angelo Aguilar
Liu Liu
Jianfeng Lu
Donna Mceachern
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University of Michigan System
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University of Michigan System
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/10Spiro-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic 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
    • A61K31/407Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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
    • A61K31/437Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/12Heterocyclic 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
    • C07D471/20Spiro-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N2005/1092Details
    • A61N2005/1098Enhancing 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)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical 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)
  • 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)
ES15779988T 2014-04-17 2015-04-16 Inhibidores de MDM2 y métodos terapéuticos que usan los mismos Active ES2712973T3 (es)

Applications Claiming Priority (2)

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

Publications (1)

Publication Number Publication Date
ES2712973T3 true ES2712973T3 (es) 2019-05-17

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ES15779988T Active ES2712973T3 (es) 2014-04-17 2015-04-16 Inhibidores de MDM2 y métodos terapéuticos que usan los mismos

Country Status (12)

Country Link
US (1) US9745314B2 (enExample)
EP (1) EP3131544B1 (enExample)
JP (2) JP6694827B2 (enExample)
KR (2) KR102599945B1 (enExample)
CN (2) CN111718354A (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 (43)

* 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
EP3131544B1 (en) * 2014-04-17 2018-12-12 The Regents of the University of Michigan Mdm2 inhibitors and therapeutic methods using the same
ES2739697T3 (es) 2014-08-21 2020-02-03 Boehringer Ingelheim Int Nuevos compuestos y derivados de espiro[3H-indol-3,2-pirrolidin]-2(1H)-ona como inhibidores de MDM2-p53
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
HRP20210960T1 (hr) 2015-10-09 2021-09-03 Boehringer Ingelheim International Gmbh Spojevi i derivati spiro[3h-indol-3,2’-pirolidin]-2(1h)-ona kao inhibitori mdm2-p53
JP7037500B2 (ja) * 2016-04-06 2022-03-16 ザ リージェンツ オブ ザ ユニヴァシティ オブ ミシガン Mdm2タンパク質分解剤
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
BR112020013069A2 (pt) * 2017-12-29 2020-12-01 Gan & Lee Pharmaceuticals compostos capazes de serem usados como inibidor de tumor, método de preparação dos mesmos e aplicação dos mesmos
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
CN114522167A (zh) 2018-07-31 2022-05-24 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
TWI725488B (zh) 2018-07-31 2021-04-21 大陸商蘇州亞盛藥業有限公司 Bcl-2抑制劑與化療藥的組合產品及其在預防及/或治療疾病中的用途
TWI752335B (zh) * 2018-07-31 2022-01-11 大陸商蘇州亞盛藥業有限公司 Bcl-2抑制劑與MDM2抑制劑的組合產品及其在預防及/或治療疾病中的用途
EA202091963A1 (ru) 2018-07-31 2021-05-13 Эсентейдж Фарма (Сучжоу) Ко., Лтд. СИНЕРГИЧЕСКИЙ ПРОТИВООПУХОЛЕВЫЙ ЭФФЕКТ ИНГИБИТОРА Bcl-2 В СОЧЕТАНИИ С РИТУКСИМАБОМ И/ИЛИ БЕНДАМУСТИНОМ ИЛИ ИНГИБИТОРА Bcl-2 В СОЧЕТАНИИ С CHOP
WO2020030016A1 (en) * 2018-08-08 2020-02-13 Ascentage Pharma (Suzhou) Co., Ltd. Combination of immunotherapies with mdm2 inhibitors
EP3697411A4 (en) * 2018-11-23 2021-08-18 Ascentage Pharma Group Corp Limited NEW PHARMACEUTICAL COMPOSITION AND ITS USE
AU2019399772B2 (en) * 2018-12-14 2021-11-04 Ascentage Pharma (Suzhou) Co., Ltd. A compound for treating osteoarthritis
CN111607647A (zh) * 2019-02-24 2020-09-01 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
EP3814358B1 (en) * 2019-07-11 2025-09-03 Ascentage Pharma (Suzhou) Co., Ltd. Method for preparing 2-indolinospirone compounds and intermediates thereof
US12233047B2 (en) * 2019-07-19 2025-02-25 Ascentage Pharma (Suzhou) Co., Ltd. Pharmaceutical combination and use thereof
CN112294965B (zh) * 2019-07-26 2023-03-14 苏州亚盛药业有限公司 Mdm2抑制剂的药物组合物及其在预防和/或治疗疾病中的用途
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
CN118812542A (zh) * 2020-01-23 2024-10-22 苏州亚盛药业有限公司 2-吲哚啉螺环酮类化合物或其盐、溶剂合物的无定形形式或结晶形式
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
IL296451B2 (en) 2020-03-19 2026-05-01 Kymera Therapeutics Inc MDM2 joints and their uses
US20230149356A1 (en) * 2020-04-14 2023-05-18 Ascentage Pharma (Suzhou) Co., Ltd. Novel medical use of mdm2 inhibitors
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
KR20230058124A (ko) 2020-08-27 2023-05-02 오츠카 세이야쿠 가부시키가이샤 Mdm2 길항제를 사용하는 암 치료를 위한 생체표지자
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
GB202103080D0 (en) 2021-03-04 2021-04-21 Otsuka Pharma Co Ltd Cancer biomarkers
WO2023011488A1 (zh) 2021-08-02 2023-02-09 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

Family Cites Families (27)

* 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
NZ561215A (en) 2005-02-22 2010-12-24 Univ Michigan Small molecule inhibitors of MDM2 and uses thereof
KR20100129331A (ko) 2005-12-01 2010-12-08 에프. 호프만-라 로슈 아게 항암제로서 사용하기 위한 p53 및 mdm2 단백질 간 상호작용의 저해제로서의 2,4,5-트리페닐 이미다졸린 유도체
CA2644758A1 (en) * 2006-03-13 2007-09-20 F. Hoffmann-La Roche Ag Spiroindolinone derivatives
ES2350504T3 (es) * 2006-03-13 2011-01-24 F. Hoffmann-La Roche Ag Derivados de espiroindolinona.
SG174107A1 (en) * 2006-08-30 2011-09-29 Univ Michigan New 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
US8222288B2 (en) 2006-08-30 2012-07-17 The Regents Of The University Of Michigan 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
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
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
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
CA2800519A1 (en) * 2010-04-09 2011-10-13 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
CA2817585A1 (en) 2010-11-12 2012-05-18 The Regents Of The University Of Michigan Spiro-oxindole mdm2 antagonists
DK2684880T3 (en) * 2011-03-10 2018-05-22 Daiichi Sankyo Co Ltd DISPIROPYRROLIDINE DERIVATIVES
ES2624808T3 (es) * 2011-05-11 2017-07-17 The Regents Of The University Of Michigan Antagonistas de MDM2 espirooxindólicos
AU2012316055B2 (en) 2011-09-27 2016-05-12 Amgen Inc. Heterocyclic compounds as MDM2 inhibitors for the treatment of cancer
KR102447057B1 (ko) * 2013-09-04 2022-09-23 다이이찌 산쿄 가부시키가이샤 스피로옥시인돌 유도체의 제조 방법
EP3131544B1 (en) * 2014-04-17 2018-12-12 The Regents of the University of Michigan Mdm2 inhibitors and therapeutic methods using the same

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Publication number Publication date
SG10201913742TA (en) 2020-03-30
SG11201608667SA (en) 2016-11-29
MX373045B (es) 2020-05-26
IL269462B (en) 2021-05-31
AU2015247646A1 (en) 2016-10-27
IL248211B (en) 2019-10-31
KR20160136450A (ko) 2016-11-29
KR102599945B1 (ko) 2023-11-09
AU2015247646B2 (en) 2019-06-06
NZ724963A (en) 2021-10-29
CN106794171B (zh) 2020-03-24
WO2015161032A1 (en) 2015-10-22
KR20220054697A (ko) 2022-05-03
CA2945527C (en) 2022-05-17
US20150299211A1 (en) 2015-10-22
MX2020003939A (es) 2020-08-13
US9745314B2 (en) 2017-08-29
JP6909323B2 (ja) 2021-07-28
CN106794171A (zh) 2017-05-31
JP2020100662A (ja) 2020-07-02
MX2016013457A (es) 2017-05-04
JP2017511360A (ja) 2017-04-20
EP3131544A1 (en) 2017-02-22
EP3131544B1 (en) 2018-12-12
KR102389552B1 (ko) 2022-04-22
CN111718354A (zh) 2020-09-29
IL248211A0 (en) 2016-11-30
EP3131544A4 (en) 2017-08-30
JP6694827B2 (ja) 2020-05-20
CA2945527A1 (en) 2015-10-22
IL269462A (en) 2019-11-28

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