TWI535723B - 螺－吲哚酮ｍｄｍ２拮抗劑 - Google Patents

螺－吲哚酮ｍｄｍ２拮抗劑 Download PDF

Info

Publication number
TWI535723B
TWI535723B TW100141225A TW100141225A TWI535723B TW I535723 B TWI535723 B TW I535723B TW 100141225 A TW100141225 A TW 100141225A TW 100141225 A TW100141225 A TW 100141225A TW I535723 B TWI535723 B TW I535723B
Authority
TW
Taiwan
Prior art keywords
group
compound
optionally substituted
hydrogen
formula
Prior art date
Application number
TW100141225A
Other languages
English (en)
Chinese (zh)
Other versions
TW201305177A (zh
Inventor
王少萌
趙玉軍
孫威
桑傑夫 庫馬
蘭斯 利奧波德
羅倫特 德布斯切
德里克 博勒爾
珍克里斯多福 凱瑞
奎米 阿曼尼
郭民
Original Assignee
密西根大學董事會
亞森塔授權公司
賽諾菲公司
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 密西根大學董事會, 亞森塔授權公司, 賽諾菲公司 filed Critical 密西根大學董事會
Publication of TW201305177A publication Critical patent/TW201305177A/zh
Application granted granted Critical
Publication of TWI535723B publication Critical patent/TWI535723B/zh

Links

Classifications

    • 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
    • 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
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • 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
    • 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

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)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
TW100141225A 2010-11-12 2011-11-11 螺－吲哚酮ｍｄｍ２拮抗劑 TWI535723B (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US41309410P 2010-11-12 2010-11-12
US201161451968P 2011-03-11 2011-03-11
US201161451958P 2011-03-11 2011-03-11
US201161470992P 2011-04-01 2011-04-01

Publications (2)

Publication Number Publication Date
TW201305177A TW201305177A (zh) 2013-02-01
TWI535723B true TWI535723B (zh) 2016-06-01

Family

ID=46048358

Family Applications (1)

Application Number Title Priority Date Filing Date
TW100141225A TWI535723B (zh) 2010-11-12 2011-11-11 螺－吲哚酮ｍｄｍ２拮抗劑

Country Status (27)

Country Link
US (2) US8680132B2 (enExample)
EP (1) EP2638046A4 (enExample)
JP (1) JP2014500870A (enExample)
KR (1) KR101929188B1 (enExample)
CN (1) CN103298818B (enExample)
AR (1) AR083849A1 (enExample)
AU (1) AU2011326395B2 (enExample)
CA (1) CA2817585A1 (enExample)
CO (1) CO6721010A2 (enExample)
CR (1) CR20130271A (enExample)
DO (1) DOP2013000104A (enExample)
EA (1) EA201390682A1 (enExample)
EC (1) ECSP13012678A (enExample)
GT (1) GT201300118A (enExample)
IL (1) IL226275A0 (enExample)
MA (1) MA34732B1 (enExample)
MX (1) MX2013005238A (enExample)
NI (1) NI201300041A (enExample)
NZ (1) NZ611866A (enExample)
PE (1) PE20140408A1 (enExample)
PH (1) PH12013500955A1 (enExample)
SG (1) SG190230A1 (enExample)
TW (1) TWI535723B (enExample)
UA (1) UA109464C2 (enExample)
UY (1) UY33725A (enExample)
WO (1) WO2012065022A2 (enExample)
ZA (1) ZA201304042B (enExample)

Families Citing this family (64)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7759383B2 (en) 2005-02-22 2010-07-20 The Regents Of The University Of Michigan Small molecule inhibitors of MDM2 and the uses thereof
CA2677045C (en) 2007-01-31 2016-10-18 Dana-Farber Cancer Institute, Inc. Stabilized p53 peptides and uses thereof
KR101623985B1 (ko) 2007-03-28 2016-05-25 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 스티칭된 폴리펩티드
AU2010319595B2 (en) 2009-11-12 2015-09-17 The Regents Of The University Of Michigan Spiro-oxindole MDM2 antagonists
US8440693B2 (en) 2009-12-22 2013-05-14 Novartis Ag Substituted isoquinolinones and quinazolinones
KR102104762B1 (ko) 2010-08-13 2020-04-24 에일러론 테라퓨틱스 인코포레이티드 펩티도미메틱 거대고리
HUE038714T2 (hu) 2011-03-10 2018-11-28 Daiichi Sankyo Co Ltd Dispiropirrolidin származék
CA2835422C (en) 2011-05-11 2016-10-11 The Regents Of The University Of Michigan Spiro-oxindole mdm2 antagonists
CN108929375A (zh) 2011-10-18 2018-12-04 爱勒让治疗公司 拟肽大环化合物
KR102112373B1 (ko) 2012-02-15 2020-05-18 에일러론 테라퓨틱스 인코포레이티드 펩티드모방체 마크로사이클
EP2819688A4 (en) 2012-02-15 2015-10-28 Aileron Therapeutics Inc PEPTIDOMIMETIC MACROCYCLES CROSS-LINKED WITH TRIAZOLE AND THIOETHER
US8993614B2 (en) 2012-03-15 2015-03-31 F. Hoffmann-La Roche Ag Substituted pyrrolidine-2-carboxamides
CN104321325B (zh) 2012-05-24 2016-11-16 诺华股份有限公司 吡咯并吡咯烷酮化合物
KR20150082307A (ko) 2012-11-01 2015-07-15 에일러론 테라퓨틱스 인코포레이티드 이치환 아미노산 및 이의 제조 및 사용 방법
TW201429969A (zh) 2012-12-20 2014-08-01 Merck Sharp & Dohme 作爲ｈｄｍ２抑制劑之經取代咪唑吡啶
EP2752191A1 (en) 2013-01-07 2014-07-09 Sanofi Compositions and methods using hdm2 antagonist and mek inhibitor
US9556180B2 (en) 2013-01-22 2017-01-31 Novartis Ag Pyrazolo[3,4-d]pyrimidinone compounds as inhibitors of the P53/MDM2 interaction
US9403827B2 (en) 2013-01-22 2016-08-02 Novartis Ag Substituted purinone compounds
EA029312B1 (ru) 2013-05-27 2018-03-30 Новартис Аг Производные имидазопирролидинона и их применение при лечении заболеваний
KR20160012197A (ko) 2013-05-28 2016-02-02 노파르티스 아게 피라졸로-피롤리딘-4-온 유도체 및 질환의 치료에서의 그의 용도
MX2015016421A (es) 2013-05-28 2016-03-03 Novartis Ag Derivados de pirazolo-pirrolidin-4-ona como inhibidores de bet y su uso en el tratamiento de enfermedades.
AU2014351413B2 (en) 2013-11-21 2017-06-01 Novartis Ag Pyrrolopyrrolone derivatives and their use as BET inhibitors
CA2939121C (en) 2014-01-28 2020-11-24 Mayo Foundation For Medical Education And Research Effective treatment of osteoarthritis, pulmonary disease, ophthalmic disease, and atherosclerosis by removing senescent cells at the site of the disease
MX373045B (es) 2014-04-17 2020-05-26 Univ Michigan Regents Inhibidores de mdm2 y metodos terapeuticos que utilizan el mismo.
TW201613576A (en) * 2014-06-26 2016-04-16 Novartis Ag Intermittent dosing of MDM2 inhibitor
WO2016001376A1 (en) 2014-07-03 2016-01-07 Boehringer Ingelheim International Gmbh New spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors
EP3183255B1 (en) 2014-08-18 2023-07-05 Hudson Biopharma Inc. Spiropyrrolidines as mdm2 inhibitors
SI3183254T1 (sl) 2014-08-21 2019-08-30 Boehringer Ingelheim International Gmbh Nove spiro(3H-indol-3,2'pirolidin)-2(1H)-onske spojine in derivati kot inhibitorji MDM2-P53
SG10201902598VA (en) 2014-09-24 2019-04-29 Aileron Therapeutics Inc Peptidomimetic macrocycles and formulations thereof
CN106999541A (zh) 2014-09-24 2017-08-01 艾瑞朗医疗公司 拟肽大环化合物及其用途
MX2017011834A (es) 2015-03-20 2018-04-11 Aileron Therapeutics Inc Macrociclos peptidomimeticos y usos de los mismos.
JP2018528217A (ja) 2015-09-10 2018-09-27 エルロン・セラピューティクス・インコーポレイテッドＡｉｌｅｒｏｎ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． Ｍｃｌ−１のモジュレーターとしてのペプチド模倣大環状分子
AR106314A1 (es) 2015-10-09 2018-01-03 Boehringer Ingelheim Int COMPUESTOS DE ESPIRO[3H-INDOL-3,2’-PIRROLIDIN]-2(1H)-ONA Y DERIVADOS COMO INHIBIDORES DE MDM2 - p53
CN105693738A (zh) * 2016-01-14 2016-06-22 绍兴文理学院 3’-苯基螺[吲哚啉-3,2’-吡咯烷]-2-酮类衍生物及其制备方法和应用
SG11201808728QA (en) * 2016-04-06 2018-11-29 Univ Michigan Regents Mdm2 protein degraders
CA3020281A1 (en) 2016-04-06 2017-10-12 The Regents Of The University Of Michigan Monofunctional intermediates for ligand-dependent target protein degradation
ES2858151T3 (es) 2016-05-20 2021-09-29 Hoffmann La Roche Conjugados de PROTAC-anticuerpo y procedimientos de uso
CN107652296B (zh) * 2016-07-26 2020-08-04 南开大学 螺环氧化吲哚酰腙衍生物及其制备方法和在防治植物病毒、杀菌、杀虫方面的应用
WO2018027477A1 (zh) 2016-08-08 2018-02-15 肖飞 螺环吲哚酮聚乙二醇碳酸酯类化合物和其组合物、制备方法及用途
AU2017362040C1 (en) 2016-11-15 2020-09-10 Novartis Ag Dose and regimen for HDM2-p53 interaction inhibitors
US9822128B1 (en) 2017-06-01 2017-11-21 King Saud University Substituted spirooxindoles
CN109988070B (zh) * 2017-12-29 2022-07-26 南京富润凯德生物医药有限公司 反式-1-羟基-1-(三氟甲基)-3-氨基环丁烷盐酸盐的中间体及制备方法和应用
WO2019128877A1 (zh) * 2017-12-29 2019-07-04 甘李药业股份有限公司 一种可用作肿瘤抑制剂的化合物及其制备方法与应用
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
MX2021003999A (es) 2018-10-08 2021-06-23 Univ Michigan Regents Moleculas de bajo peso molecular degradadoras de la proteina mdm2.
WO2021188948A1 (en) 2020-03-19 2021-09-23 Kymera Therapeutics, Inc. Mdm2 degraders and uses thereof
WO2022109360A1 (en) 2020-11-23 2022-05-27 Enanta Pharmaceuticals, Inc. Novel spiropyrrolidine derived antiviral agents
WO2022159644A1 (en) * 2021-01-23 2022-07-28 Newave Pharmaceutical Inc. Spirocyclic mdm2 modulator and uses thereof
CN112876488B (zh) * 2021-02-18 2021-12-21 苏州大学 螺环吲哚啉衍生物及其制备方法和应用
CN116917009A (zh) 2021-02-19 2023-10-20 美国迈胜医疗系统有限公司 用于粒子治疗系统的机架
CN115215872A (zh) * 2021-04-15 2022-10-21 中国科学院上海药物研究所 具有取代苯基螺[吲哚啉-3,3′-吡咯烷]结构的小分子化合物
WO2022235605A1 (en) 2021-05-04 2022-11-10 Enanta Pharmaceuticals, Inc. Novel macrocyclic antiviral agents
US12398147B2 (en) 2021-05-11 2025-08-26 Enanta Pharmaceuticals, Inc. Macrocyclic spiropyrrolidine derived antiviral agents
US12479854B2 (en) 2021-07-29 2025-11-25 Enanta Pharmaceuticals, Inc. Spiropyrrolidine derived antiviral agents
WO2023056069A1 (en) 2021-09-30 2023-04-06 Angiex, Inc. Degrader-antibody conjugates and methods of using same
WO2023086352A1 (en) 2021-11-12 2023-05-19 Enanta Pharmaceuticals, Inc. Novel spiropyrrolidine derived antiviral agents
US11858945B2 (en) 2021-11-12 2024-01-02 Enanta Pharmaceuticals, Inc. Alkyne-containing antiviral agents
US11919910B2 (en) 2021-11-12 2024-03-05 Enanta Pharmaceuticals, Inc. Spiropyrrolidine derived antiviral agents
US12145941B2 (en) 2021-12-08 2024-11-19 Enanta Pharmaceuticals, Inc. Heterocyclic antiviral agents
US11993600B2 (en) 2021-12-08 2024-05-28 Enanta Pharmaceuticals, Inc. Saturated spirocyclics as antiviral agents
CN116283701B (zh) * 2021-12-21 2025-04-22 中国科学院上海药物研究所 具有4-(取代氨甲基)-5-新戊基-n-取代基吡咯烷-2-甲酰胺结构的化合物
US12145942B2 (en) 2022-04-05 2024-11-19 Enanta Pharmaceuticals, Inc. Spiropyrrolidine derived antiviral agents
CN118047784B (zh) * 2022-10-13 2025-09-16 中国科学院上海药物研究所 具有取代苯基螺[吲哚啉-3,3′-吡咯烷]结构的小分子化合物
WO2024240858A1 (en) 2023-05-23 2024-11-28 Valerio Therapeutics Protac molecules directed against dna damage repair system and uses thereof

Family Cites Families (69)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3219661A (en) 1962-12-14 1965-11-23 Warner Lambert Pharmaceutical Spirooxindole and spirodehydroindole alkaloids and process therefor
GB1056537A (en) 1963-07-16 1967-01-25 Smith Kline French Lab Improvements in or relating to crystalline alkaloids of mitragyna citiata and compositions thereof
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
RU2084449C1 (ru) 1994-03-02 1997-07-20 Всероссийский научный центр по безопасности биологически активных веществ 1-бензил-2-оксотриптамин гидрохлорид и его производные, обладающие гепатозащитной активностью
US5773455A (en) 1996-06-28 1998-06-30 Biomeasure, Incorporated Inhibitors of prenyl transferases
US7083983B2 (en) 1996-07-05 2006-08-01 Cancer Research Campaign Technology Limited Inhibitors of the interaction between P53 and MDM2
ATE467418T1 (de) 1997-01-20 2010-05-15 Immodal Pharmaka Gmbh Verfahren und stoffe zur freisetzung eines wachstumsfaktors aus endothelzellen, und nach dem verfahren freigesetzter wachstumsfaktor sowie seine verwendung
WO1999012904A1 (en) 1997-09-08 1999-03-18 Arqule, Inc. Spiro[pyrrolidine-2,3'-oxindole] compounds and methods of use
AU5301499A (en) 1998-08-20 2000-03-14 Chugai Seiyaku Kabushiki Kaisha Method for screening candidate compounds for drug against tumor
US7205404B1 (en) 1999-03-05 2007-04-17 Metabasis Therapeutics, Inc. Phosphorus-containing prodrugs
US6831155B2 (en) 1999-12-08 2004-12-14 President And Fellows Of Harvard College Inhibition of p53 degradation
CN1182083C (zh) 2001-10-08 2004-12-29 廖宜芳 一种杀虫灭菌的配位肥及其制造方法
CA2468783A1 (en) 2001-12-18 2003-06-26 F. Hoffmann-La Roche Ag Cis-imidazolines as mdm2 inhibitors
WO2003051359A1 (en) 2001-12-18 2003-06-26 F.Hoffmann-La Roche Ag Cis-2,4,5- triphenyl-imidazolines and their use in the treatment of tumors
JP4023184B2 (ja) 2002-03-11 2007-12-19 昭和電工株式会社 発光体粒子及びその製造方法並びにその用途
WO2003106384A2 (en) 2002-06-01 2003-12-24 Johns Hopkins University Novel boronic chalcone derivatives and uses thereof
AU2003291269A1 (en) 2002-11-08 2004-06-03 Irm Llc Methods and compositions for modulating p53 transcription factor
US20050227932A1 (en) 2002-11-13 2005-10-13 Tianbao Lu Combinational therapy involving a small molecule inhibitor of the MDM2: p53 interaction
AU2004212928A1 (en) 2003-02-13 2004-09-02 Bioveris Corporation Deazaflavin compounds and methods of use thereof
US6916833B2 (en) 2003-03-13 2005-07-12 Hoffmann-La Roche Inc. Substituted piperidines
US7132421B2 (en) 2003-06-17 2006-11-07 Hoffmann-La Roche Inc. CIS-imidazoles
US7425638B2 (en) 2003-06-17 2008-09-16 Hoffmann-La Roche Inc. Cis-imidazolines
US8173840B2 (en) 2003-07-29 2012-05-08 Signature R&D Holdings, Llc Compounds with high therapeutic index
US7589233B2 (en) 2003-07-29 2009-09-15 Signature R&D Holdings, Llc L-Threonine derivatives of high therapeutic index
KR20120116991A (ko) 2003-07-29 2012-10-23 시그너쳐 알 앤드 디 홀딩스, 엘엘씨 아미노산 프로드럭
WO2005063774A1 (en) 2003-12-22 2005-07-14 Johns Hopkins University Boronic acid aryl analogs
US8598127B2 (en) 2004-04-06 2013-12-03 Korea Research Institute Of Bioscience & Biotechnology Peptides for inhibiting MDM2 function
TWI350168B (en) 2004-05-07 2011-10-11 Incyte Corp Amido compounds and their use as pharmaceuticals
JP4814228B2 (ja) 2004-05-18 2011-11-16 エフ．ホフマン−ラ ロシュ アーゲー 新規ｃｉｓ−イミダゾリン
GB0419481D0 (en) 2004-09-02 2004-10-06 Cancer Rec Tech Ltd Isoindolin-1-one derivatives
KR101331786B1 (ko) 2004-09-22 2013-11-21 얀센 파마슈티카 엔.브이. Ｍｄｍ2 및 ｐ53간의 상호작용 저해제
WO2006091646A2 (en) * 2005-02-22 2006-08-31 The Regents Of The University Of Michigan Small molecule inhibitors of mdm2 and uses thereof
US7759383B2 (en) 2005-02-22 2010-07-20 The Regents Of The University Of Michigan Small molecule inhibitors of MDM2 and the uses thereof
PT1891075E (pt) 2005-05-24 2011-11-10 Merck Serono Sa Derivados espiro tricíclicos como moduladores do crth2
US7576082B2 (en) 2005-06-24 2009-08-18 Hoffman-La Roche Inc. Oxindole derivatives
US7495007B2 (en) 2006-03-13 2009-02-24 Hoffmann-La Roche Inc. Spiroindolinone derivatives
CA2644643C (en) 2006-03-22 2015-05-19 Janssen Pharmaceutica N.V. Inhibitors of the interaction between mdm2 and p53
US8222288B2 (en) 2006-08-30 2012-07-17 The Regents Of The University Of Michigan Small molecule inhibitors of MDM2 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
US7737174B2 (en) 2006-08-30 2010-06-15 The Regents Of The University Of Michigan Indole inhibitors of MDM2 and the uses thereof
ATE467413T1 (de) 2006-09-21 2010-05-15 Hoffmann La Roche Oxindolderivate als antikrebsmittel
US7638548B2 (en) 2006-11-09 2009-12-29 Hoffmann-La Roche Inc. Spiroindolinone derivatives
CN101605798A (zh) 2006-12-14 2009-12-16 第一三共株式会社 咪唑并噻唑衍生物
WO2008106507A2 (en) 2007-02-27 2008-09-04 University Of South Florida Mdm2/mdmx inhibitor peptide
EA200901212A1 (ru) 2007-03-29 2010-04-30 Новартис Аг 3-имидазолилиндолы, предназначенные для лечения пролиферативных заболеваний
US7625895B2 (en) 2007-04-12 2009-12-01 Hoffmann-Le Roche Inc. Diphenyl-dihydro-imidazopyridinones
WO2008130614A2 (en) 2007-04-20 2008-10-30 University Of Pittsburg-Of The Commonwealth System Of Higher Education Selective and dual-action p53/mdm2/mdm4 antagonists
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
JP5438008B2 (ja) 2007-09-21 2014-03-12 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ ＭＤＭ２とｐ５３の間の相互作用の阻害剤
CZ301561B6 (cs) 2007-12-04 2010-04-14 Výzkumný ústav živocišné výroby, v. v. i. Prostredek pro prevenci a potlacování kokcidióz
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
US7723372B2 (en) 2008-03-19 2010-05-25 Hoffman-La Roche Inc. Spiroindolinone derivatives
WO2009151069A1 (ja) 2008-06-12 2009-12-17 第一三共株式会社 ４，７－ジアザスピロ［２．５］オクタン環構造を有するイミダゾチアゾール誘導体
GB0811643D0 (en) 2008-06-25 2008-07-30 Cancer Rec Tech Ltd New therapeutic agents
US7928233B2 (en) 2009-02-10 2011-04-19 Hoffmann-La Roche Inc. Spiroindolinone pyridine derivatives
US8076482B2 (en) 2009-04-23 2011-12-13 Hoffmann-La Roche Inc. 3,3′-spiroindolinone derivatives
AU2010319595B2 (en) 2009-11-12 2015-09-17 The Regents Of The University Of Michigan Spiro-oxindole MDM2 antagonists
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
WO2011106650A2 (en) 2010-02-27 2011-09-01 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Novel p53-mdm2/p53-mdm4 antagonists to treat proliferative disease
CN103153302A (zh) 2010-04-09 2013-06-12 密歇根大学董事会 针对用于治疗疾病的mdm2抑制剂的生物标记
US8217044B2 (en) 2010-04-28 2012-07-10 Hoffmann-La Roche Inc. Spiroindolinone pyrrolidines
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
CA2835422C (en) 2011-05-11 2016-10-11 The Regents Of The University Of Michigan Spiro-oxindole mdm2 antagonists

Also Published As

Publication number Publication date
AU2011326395A1 (en) 2013-05-09
AR083849A1 (es) 2013-03-27
EA201390682A1 (ru) 2014-01-30
JP2014500870A (ja) 2014-01-16
SG190230A1 (en) 2013-06-28
KR20140027913A (ko) 2014-03-07
US9302120B2 (en) 2016-04-05
ECSP13012678A (es) 2013-08-30
CN103298818A (zh) 2013-09-11
US8680132B2 (en) 2014-03-25
ZA201304042B (en) 2014-02-26
IL226275A0 (en) 2013-07-31
KR101929188B1 (ko) 2018-12-17
AU2011326395B2 (en) 2016-01-07
UA109464C2 (uk) 2015-08-25
US20140148494A1 (en) 2014-05-29
DOP2013000104A (es) 2013-10-15
UY33725A (es) 2012-06-29
US20120122947A1 (en) 2012-05-17
GT201300118A (es) 2014-08-05
MA34732B1 (fr) 2013-12-03
WO2012065022A3 (en) 2012-10-04
NI201300041A (es) 2013-12-17
WO2012065022A2 (en) 2012-05-18
CN103298818B (zh) 2016-06-29
PH12013500955A1 (en) 2015-11-06
NZ611866A (en) 2015-04-24
CR20130271A (es) 2013-10-03
TW201305177A (zh) 2013-02-01
MX2013005238A (es) 2013-09-02
PE20140408A1 (es) 2014-04-10
EP2638046A4 (en) 2014-06-25
CA2817585A1 (en) 2012-05-18
CO6721010A2 (es) 2013-07-31
EP2638046A2 (en) 2013-09-18

Similar Documents

Publication Publication Date Title
TWI535723B (zh) 螺－吲哚酮ｍｄｍ２拮抗劑
CN102712650B (zh) 螺-吲哚酮mdm2拮抗剂
CN103717605B (zh) 螺-羟吲哚mdm2拮抗剂
OA16409A (en) Spiro-oxindole MDM2 antagonists.

Legal Events

Date Code Title Description
MM4A Annulment or lapse of patent due to non-payment of fees