CA2945527C - Mdm2 inhibitors and therapeutic methods using the same - Google Patents

Mdm2 inhibitors and therapeutic methods using the same Download PDF

Info

Publication number
CA2945527C
CA2945527C CA2945527A CA2945527A CA2945527C CA 2945527 C CA2945527 C CA 2945527C CA 2945527 A CA2945527 A CA 2945527A CA 2945527 A CA2945527 A CA 2945527A CA 2945527 C CA2945527 C CA 2945527C
Authority
CA
Canada
Prior art keywords
compound
mdm2
compounds
pharmaceutically acceptable
cancer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CA2945527A
Other languages
English (en)
French (fr)
Other versions
CA2945527A1 (en
Inventor
Shaomeng Wang
Angelo AGUILAR
Liu Liu
Jianfeng Lu
Donna Mceachern
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Michigan System
Original Assignee
University of Michigan System
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of Michigan System filed Critical University of Michigan System
Publication of CA2945527A1 publication Critical patent/CA2945527A1/en
Application granted granted Critical
Publication of CA2945527C publication Critical patent/CA2945527C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (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)
CA2945527A 2014-04-17 2015-04-16 Mdm2 inhibitors and therapeutic methods using the same Active CA2945527C (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)

Publication Number Publication Date
CA2945527A1 CA2945527A1 (en) 2015-10-22
CA2945527C true CA2945527C (en) 2022-05-17

Family

ID=54321424

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2945527A Active CA2945527C (en) 2014-04-17 2015-04-16 Mdm2 inhibitors and therapeutic methods using the same

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 (42)

* 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
WO2015161032A1 (en) * 2014-04-17 2015-10-22 The Regents Of The University Of Michigan Mdm2 inhibitors and therapeutic methods using the same
EA038071B1 (ru) 2014-08-21 2021-07-01 Бёрингер Ингельхайм Интернациональ Гмбх СОЕДИНЕНИЕ СПИРО[3H-ИНДОЛ-3,2'-ПИРРОЛИДИН]-2(1H)-ОНА И ЕГО ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ 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
PT3359542T (pt) 2015-10-09 2021-05-25 Boehringer Ingelheim Int Compostos de espiro[3h-indole-3,2¿-pirrolidin]-2(1h)-ona e derivados como inibidores de mdm2-p53
CN113788818A (zh) * 2016-04-06 2021-12-14 密执安大学评议会 Mdm2蛋白质降解剂
ES2858151T3 (es) 2016-05-20 2021-09-29 Hoffmann La Roche Conjugados de PROTAC-anticuerpo y procedimientos de uso
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
US11339171B2 (en) * 2017-12-29 2022-05-24 Gan & Lee Pharmaceuticals MDM2 inhibitors
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
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
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
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
CN110772639B (zh) * 2018-07-31 2021-04-13 苏州亚盛药业有限公司 Bcl-2抑制剂与MDM2抑制剂的组合产品及其在预防和/或治疗疾病中的用途
JP2021534088A (ja) * 2018-08-08 2021-12-09 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 免疫療法とｍｄｍ２阻害剤の併用
TWI750539B (zh) * 2018-11-23 2021-12-21 大陸商蘇州亞盛藥業有限公司 新穎藥物組成物及其用途
CA3095702A1 (en) * 2018-12-14 2020-06-18 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
CN112209938B (zh) * 2019-07-11 2021-06-11 苏州亚盛药业有限公司 2-吲哚啉螺环酮类化合物的制备方法及其中间体
CN112237579B (zh) * 2019-07-19 2022-03-29 苏州亚盛药业有限公司 药物组合及其用途
AU2020323033A1 (en) * 2019-07-26 2021-04-22 Ascentage Pharma (Suzhou) Co., Ltd. Pharmaceutical composition of MDM2 inhibitor and use thereof for preventing and/or treating disease
CN112852959A (zh) 2019-11-27 2021-05-28 苏州亚盛药业有限公司 用于预测靶向细胞凋亡途径的化合物的抗癌功效的方法和组合物
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
EP4041736A4 (en) * 2020-01-23 2023-06-07 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
IL296451A (en) * 2020-03-19 2022-11-01 Kymera Therapeutics Inc Mdm2 degraders and uses thereof
WO2021208911A1 (en) * 2020-04-14 2021-10-21 Ascentage Pharma (Suzhou) Co., Ltd. Novel medical use of mdm2 inhibitors
US20230218575A1 (en) * 2020-06-15 2023-07-13 Ascentage Pharma (Suzhou) Co., Ltd. Microsuspension of an mdm2 inhibitor and therapeautic applications thereof
AU2021333983A1 (en) 2020-08-27 2023-01-05 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
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
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
CN116421598B (zh) * 2022-01-11 2024-08-30 苏州亚盛药业有限公司 用于治疗aml-mrc和mds的方法
WO2024240858A1 (en) 2023-05-23 2024-11-28 Valerio Therapeutics Protac molecules directed against dna damage repair system and uses thereof

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
WO2007063013A1 (en) 2005-12-01 2007-06-07 F. Hoffmann-La Roche Ag 2,4,5-triphenyl imidazoline derivatives as inhibitors of the interaction between p53 and mdm2 proteins for use as anticancer agents
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
EP1996591B1 (en) * 2006-03-13 2011-01-12 F. Hoffmann-La Roche AG Spiroindolinone derivatives
EP2063887B1 (en) * 2006-08-30 2013-05-29 The Regents of the University of 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
BRPI0919325A2 (pt) 2008-09-18 2021-03-30 F.Hoffmann-La Roche Ag Pirrolidina-2-carboxamidas substituídas
US8354444B2 (en) 2008-09-18 2013-01-15 Hoffmann-La Roche Inc. Substituted pyrrolidine-2-carboxamides
US8076482B2 (en) * 2009-04-23 2011-12-13 Hoffmann-La Roche Inc. 3,3′-spiroindolinone derivatives
KR20120099462A (ko) * 2009-11-12 2012-09-10 더 리젠츠 오브 더 유니버시티 오브 미시건 스피로-옥신돌 ｍｄｍ2 길항제
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
US8680132B2 (en) 2010-11-12 2014-03-25 The Regents Of The University Of Michigan Spiro-oxindole MDM2 antagonists
PT2684880T (pt) * 2011-03-10 2018-04-27 Daiichi Sankyo Co Ltd Derivado de dispiropirrolidina
US8629141B2 (en) * 2011-05-11 2014-01-14 The Regents Of The University Of Michigan Spiro-oxindole MDM2 antagonists
MX352672B (es) 2011-09-27 2017-12-04 Amgen Inc Compuestos heterocíclicos como inhibidores de mdm2 para el tratamiento del cáncer.
EP3042906B1 (en) * 2013-09-04 2019-10-23 Daiichi Sankyo Company, Limited Method for producing a spirooxindole derivative
WO2015161032A1 (en) * 2014-04-17 2015-10-22 The Regents Of The University Of Michigan Mdm2 inhibitors and therapeutic methods using the same

Also Published As

Publication number Publication date
EP3131544B1 (en) 2018-12-12
KR20160136450A (ko) 2016-11-29
AU2015247646A1 (en) 2016-10-27
WO2015161032A1 (en) 2015-10-22
JP2020100662A (ja) 2020-07-02
CN106794171A (zh) 2017-05-31
MX2020003939A (es) 2020-08-13
IL248211B (en) 2019-10-31
CN106794171B (zh) 2020-03-24
JP6694827B2 (ja) 2020-05-20
KR20220054697A (ko) 2022-05-03
AU2015247646B2 (en) 2019-06-06
IL269462B (en) 2021-05-31
ES2712973T3 (es) 2019-05-17
MX2016013457A (es) 2017-05-04
US9745314B2 (en) 2017-08-29
KR102599945B1 (ko) 2023-11-09
CN111718354A (zh) 2020-09-29
US20150299211A1 (en) 2015-10-22
KR102389552B1 (ko) 2022-04-22
EP3131544A1 (en) 2017-02-22
IL248211A0 (en) 2016-11-30
JP2017511360A (ja) 2017-04-20
NZ724963A (en) 2021-10-29
SG11201608667SA (en) 2016-11-29
JP6909323B2 (ja) 2021-07-28
CA2945527A1 (en) 2015-10-22
IL269462A (en) 2019-11-28
MX373045B (es) 2020-05-26
SG10201913742TA (en) 2020-03-30
EP3131544A4 (en) 2017-08-30

Similar Documents

Publication Publication Date Title
CA2945527C (en) Mdm2 inhibitors and therapeutic methods using the same
US8629141B2 (en) Spiro-oxindole MDM2 antagonists
ES2425965T3 (es) Nuevos inhibidores de moléculas pequeñas de MDM2 y usos de los mismos
US9394303B2 (en) Small molecule inhibitors of MCL-1 and uses thereof
US8877796B2 (en) Spiro-oxindole MDM2 antagonists
US9302120B2 (en) Spiro-oxindole MDM2 antagonists
EP2831067B1 (en) Small molecule inhibitors of mcl-1 and uses thereof
EP3285583B1 (en) Small molecule inhibitors of mcl-1 and uses thereof
EP3934634B1 (en) Substituted bicyclic and tetracyclic quinones and related methods of use
HK40061093B (en) Substituted bicyclic and tetracyclic quinones and related methods of use
HK40061093A (en) Substituted bicyclic and tetracyclic quinones and related methods of use
NZ724963B2 (en) Mdm2 inhibitors and therapeutic methods using the same
NZ617580B2 (en) Spiro-oxindole mdm2 antagonists

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20200226