JO2998B1 - مشتقات بيبيريدينون كمثبطات mdm2 لعلاج السرطان - Google Patents

مشتقات بيبيريدينون كمثبطات mdm2 لعلاج السرطان

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Publication number
JO2998B1
JO2998B1 JOP/2011/0182A JOP20110182A JO2998B1 JO 2998 B1 JO2998 B1 JO 2998B1 JO P20110182 A JOP20110182 A JO P20110182A JO 2998 B1 JO2998 B1 JO 2998B1
Authority
JO
Jordan
Prior art keywords
treatment
cancer
mdm2 inhibitors
piperidinone derivatives
mdm2
Prior art date
Application number
JOP/2011/0182A
Other languages
English (en)
Inventor
Jiao Xianyun
Huang Xin
Yan Xuelei
Wang Xiaodong
Buenrostro Gonzalez Ana
M Fox Brian
S Lucas Brian
Fisher Benjamin
A Heath Julie
C Medina Julio
Eksterowicz John
D Low Jonathan
mcintosh Joel
Liu Jiwen
Fu Jiasheng
Zhu Jiang
Duquette Jason
T Mihalic Jeffrey
Deignan Jeffrey
Michael W Gribble Jr
J Gustin Darin
Sun Daqing
J Kopecky David
Mcminn Dustin
V Connors Richard
Chen Xiaoqi
Fu Zice
Ma Zhihua
Li Zhihong
H Olson Steven
Lai Sujen
Kayser Frank
M Roveto Philip
Gonzalez Lopez De Turiso Felix
R Mcgee Lawrence
Johnson Michael
D Bartberger Michael
Yu Ming
P Beck Hilary
Wang Yingcai
Li Yihong
Rew Yosup
Original Assignee
Amgen Inc
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=44504412&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=JO2998(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Amgen Inc filed Critical Amgen Inc
Application granted granted Critical
Publication of JO2998B1 publication Critical patent/JO2998B1/ar

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/40—Oxygen atoms
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    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/45—Non condensed piperidines, e.g. piperocaine having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
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    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
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    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4535—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
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    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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Abstract

يتعلق الاختراع الحالي بتوفير مركبات تثبيط MDM2 وفقًا للصيغة I، حيث تم تحديد المتغيرات أعلاه، وحيث المركبات المذكورة مفيدة كعوامل علاجية، وبصفة خاصة لمعالجة أمراض السرطان. يتعلق الاختراع الحالي أيضاً بتركيبات صيدلانية تحتوي على مثبط MDM2
JOP/2011/0182A 2010-06-04 2011-06-02 مشتقات بيبيريدينون كمثبطات mdm2 لعلاج السرطان JO2998B1 (ar)

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Families Citing this family (53)

* 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
JO2998B1 (ar) * 2010-06-04 2016-09-05 Amgen Inc مشتقات بيبيريدينون كمثبطات mdm2 لعلاج السرطان
US20130267699A1 (en) 2011-06-24 2013-10-10 California Institute Of Technology Quaternary heteroatom containing compounds
US8822679B2 (en) * 2011-06-24 2014-09-02 California Institute Of Technology Quaternary heteroatom containing compounds
CA2850166C (en) * 2011-09-27 2019-12-03 Amgen Inc. Heterocyclic compounds as mdm2 inhibitors for the treatment of cancer
JP6495654B2 (ja) 2011-10-24 2019-04-03 アサナ バイオサイエンシズ，リミティド ライアビリティ カンパニー シクロヘキシルアミン類
EP2847177B1 (en) 2012-05-09 2017-10-11 Boehringer Ingelheim International GmbH Methods for making oxetan-3-ylmethanamines
US8846657B2 (en) 2012-12-20 2014-09-30 Merck Sharp & Dohme Corp. Substituted imidazopyridines as HDM2 inhibitors
US11407721B2 (en) 2013-02-19 2022-08-09 Amgen Inc. CIS-morpholinone and other compounds as MDM2 inhibitors for the treatment of cancer
WO2014130470A1 (en) * 2013-02-19 2014-08-28 Amgen Inc. Cis-morpholinone and other compounds as mdm2 inhibitors for the treatment of cancer
WO2014134201A1 (en) * 2013-02-28 2014-09-04 Amgen Inc. A benzoic acid derivative mdm2 inhibitor for the treatment of cancer
EP2970237B1 (en) * 2013-03-14 2017-09-27 Amgen Inc. Heteroaryl acid morpholinone compounds as mdm2 inhibitors for the treatment of cancer
CN105358530A (zh) * 2013-06-10 2016-02-24 美国安进公司 制备mdm2抑制剂的方法及其结晶形式
MX391859B (es) * 2013-11-11 2025-03-12 Amgen Inc Terapia de combinacion que incluye un inhibidor mdm2 y uno o mas agentes farmaceuticamente activos adicionales para el tratamiento de canceres
WO2015082384A1 (en) * 2013-12-05 2015-06-11 F. Hoffmann-La Roche Ag Novel combination treatment for acute myeloid leukemia (aml)
MX373045B (es) 2014-04-17 2020-05-26 Univ Michigan Regents Inhibidores de mdm2 y metodos terapeuticos que utilizan el mismo.
CN103992334A (zh) * 2014-05-29 2014-08-20 中国人民解放军第二军医大学 吲哚酮螺四氢硫代吡喃类抗肿瘤衍生物及其制备方法
JP6503386B2 (ja) 2014-07-03 2019-04-17 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
MX373033B (es) 2014-08-21 2020-05-27 Boehringer Ingelheim Int Nuevos compuestos de espiro[3h-indol-3,2´-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53.
TW201702218A (zh) 2014-12-12 2017-01-16 美國杰克森實驗室 關於治療癌症、自體免疫疾病及神經退化性疾病之組合物及方法
US10421696B2 (en) 2014-12-18 2019-09-24 California Institute Of Technology Enantioselective synthesis of α-quaternary mannich adducts by palladium-catalyzed allylic alkylation
CA2981041C (en) 2015-03-27 2023-09-05 California Institute Of Technology Asymmetric catalytic decarboxylative alkyl alkylation using low catalyst concentrations and a robust precatalyst
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
EP3359542B1 (en) * 2015-10-09 2021-03-17 Boehringer Ingelheim International GmbH Spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors
US10040784B2 (en) 2016-03-11 2018-08-07 California Institute Of Technology Compositions and methods for acylating lactams
CN113788818A (zh) * 2016-04-06 2021-12-14 密执安大学评议会 Mdm2蛋白质降解剂
BR112018070859A2 (pt) * 2016-04-12 2019-02-05 Univ Michigan Regents degradantes da proteína de bet
TWI794171B (zh) 2016-05-11 2023-03-01 美商滬亞生物國際有限公司 Ｈｄａｃ抑制劑與ｐｄ-ｌ１抑制劑之組合治療
TWI808055B (zh) 2016-05-11 2023-07-11 美商滬亞生物國際有限公司 Hdac 抑制劑與 pd-1 抑制劑之組合治療
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
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
US10358422B2 (en) 2017-11-01 2019-07-23 California Institute Of Technology Methods for enantioselective allylic alkylation of esters, lactones, and lactams with unactivated allylic alcohols
EP3759090A1 (en) 2018-03-02 2021-01-06 Inflazome Limited Novel compounds
IL319432A (en) 2018-04-30 2025-05-01 Kartos Therapeutics Inc Methods of treating cancer
BR112021003839A2 (pt) 2018-08-31 2021-07-27 Amgen Inc. processos para preparar um inibidor mdm2
CN110963958B (zh) * 2018-09-30 2025-10-10 上海长森药业有限公司 一种mdm2抑制剂，及其制备方法、药物组合物和应用
EP3699173A1 (en) 2018-10-18 2020-08-26 California Institute of Technology Gem-disubstituted pyrrolidines, piperazines, and diazepanes, and compositions and methods of making the same
AR116904A1 (es) * 2018-12-11 2021-06-23 Kartos Therapeutics Inc Métodos y composiciones para el tratamiento de un trastorno oftálmico
GB201919219D0 (en) 2019-12-23 2020-02-05 Otsuka Pharma Co Ltd Cancer biomarkers
CN113149998B (zh) * 2020-01-23 2024-05-31 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
BR112022017093A2 (pt) 2020-02-27 2023-02-14 Syngenta Crop Protection Ag Compostos de diazina-bisamida ativos em termos pesticidas
MX2022011602A (es) 2020-03-19 2023-01-04 Kymera Therapeutics Inc Degradadores de la proteína de homólogo de ratón de minuto 2 (mdm2) y usos de los mismos.
US20230313313A1 (en) 2020-08-27 2023-10-05 Otsuka Pharmaceutical Co., Ltd. Biomarkers for cancer therapy using mdm2 antagonists
CN112213428A (zh) * 2020-10-13 2021-01-12 辽宁科技大学 一种超临界co2中进行非催化乙酰基化反应及其在线检测方法
WO2022159644A1 (en) 2021-01-23 2022-07-28 Newave Pharmaceutical Inc. Spirocyclic mdm2 modulator and uses thereof
GB202103080D0 (en) 2021-03-04 2021-04-21 Otsuka Pharma Co Ltd Cancer biomarkers
WO2023056069A1 (en) 2021-09-30 2023-04-06 Angiex, Inc. Degrader-antibody conjugates and methods of using same
WO2023230059A1 (en) * 2022-05-24 2023-11-30 Newave Pharmaceutical Inc. Mdm2 degrader
US20250352535A1 (en) * 2022-06-06 2025-11-20 Kymera Therapeutics, Inc. Mdm2 degraders and uses thereof
CN115322126B (zh) * 2022-09-13 2023-04-28 九江学院 一种多芳烃类化合物及其制备方法和应用
WO2024240858A1 (en) 2023-05-23 2024-11-28 Valerio Therapeutics Protac molecules directed against dna damage repair system and uses thereof

Family Cites Families (84)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH436295A (de) 1961-11-13 1967-05-31 Mcneilab Inc Verfahren zur Herstellung neuer 3-Morpholinone
DE3246148A1 (de) 1982-12-14 1984-06-14 Troponwerke GmbH & Co KG, 5000 Köln Pyrazolo(4.3-b)(1.4)oxazine, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
WO1995023135A1 (en) 1991-03-07 1995-08-31 Fisons Corporation Diphenyl-2-piperidinone and -2-pyrrolidinone derivatives having anti-convulsant and neuroprotective activity
US5334720A (en) 1991-03-07 1994-08-02 Fisons Corporation Diphenyl-1-(aminoalkyl)-2-piperidinone and -2-pyrrolidinone derivatives having anticonvulsant properties
CA2517691A1 (en) 1994-08-19 1996-02-29 Abbott Laboratories Endothelin antagonists
DK0885215T3 (da) 1996-02-13 2006-08-14 Abbott Lab Nye benzo-1,3-dioxolyl- og benzofuranyl-substituerede pyrrolidinderivater som endthelinantagonister
US6159990A (en) 1997-06-18 2000-12-12 Synaptic Pharmaceutical Corporation Oxazolidinones as α1A receptor antagonists
TR200101233T2 (tr) 1997-08-04 2002-06-21 Abbott Laboratories Endotelin antagonistleri.
AU1910299A (en) 1997-12-18 1999-07-05 Eli Lilly And Company Peptidomimetic template-based combinatorial libraries
US6770658B2 (en) 1998-09-09 2004-08-03 Inflazyme Pharmaceuticals Ltd. Substituted γ-phenyl-Δ-lactams and uses related thereto
US7214540B2 (en) 1999-04-06 2007-05-08 Uab Research Foundation Method for screening crystallization conditions in solution crystal growth
US6630006B2 (en) 1999-06-18 2003-10-07 The Regents Of The University Of California Method for screening microcrystallizations for crystal formation
US7195670B2 (en) 2000-06-27 2007-03-27 California Institute Of Technology High throughput screening of crystallization of materials
US7052545B2 (en) 2001-04-06 2006-05-30 California Institute Of Technology High throughput screening of crystallization of materials
WO2002017912A1 (en) 2000-08-31 2002-03-07 Abbott Laboratories Endothelin antagonists
WO2002042731A2 (en) 2000-11-20 2002-05-30 Parallel Synthesis Technologies, Inc. Methods and devices for high throughput crystallization
CA2436774A1 (en) 2001-01-30 2002-08-08 R. Michael Lawrence Sulfonamide lactam inhibitors of factor xa
ATE409181T1 (de) 2001-05-08 2008-10-15 Univ Yale Proteomimetische verbindungen und verfahren
WO2002094787A1 (en) 2001-05-23 2002-11-28 Ucb, S.A. 2-oxo-piperidinyl- and 2-oxo-azepanyl alkanoic acid derivativ es for the treatment of epilepsy and other neurological disorders
DE60225719T2 (de) 2001-12-18 2009-04-23 F. Hoffmann-La Roche Ag Cis-2,4,5- triphenyl-imidazoline und ihre verwendung bei der behandlung von tumoren
US6860940B2 (en) 2002-02-11 2005-03-01 The Regents Of The University Of California Automated macromolecular crystallization screening
US6916833B2 (en) * 2003-03-13 2005-07-12 Hoffmann-La Roche Inc. Substituted piperidines
US7425638B2 (en) 2003-06-17 2008-09-16 Hoffmann-La Roche Inc. Cis-imidazolines
MXPA06013246A (es) 2004-05-18 2007-02-08 Hoffmann La Roche Nuevas imidazolinas cis.
US7893278B2 (en) 2004-06-17 2011-02-22 Hoffman-La Roche Inc. CIS-imidazolines
EP1809282B1 (en) 2004-10-18 2013-01-09 Amgen, Inc Thiadiazole compounds and methods of use
US7579368B2 (en) 2005-03-16 2009-08-25 Hoffman-La Roche Inc. Cis-imidazolines
CA2603258A1 (en) 2005-04-04 2006-10-12 Eisai Co., Ltd. Dihydropyridine compounds and compositions for headaches
EP2311814A1 (en) 2005-12-01 2011-04-20 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
EP1987000A2 (en) * 2006-01-13 2008-11-05 Schering Corporation Diaryl piperidines as cb1 modulators
EP1981884B1 (en) 2006-01-18 2012-06-13 Amgen, Inc Thiazole compounds as protein kinase b (pkb) inhibitors
US20070213341A1 (en) 2006-03-13 2007-09-13 Li Chen Spiroindolinone derivatives
GB0606283D0 (en) 2006-03-29 2006-05-10 Cyclacel Ltd Process
CN101595107A (zh) 2006-06-30 2009-12-02 先灵公司 能提高p53活性的有取代哌啶及其用途
WO2008010953A2 (en) 2006-07-19 2008-01-24 University Of Georgia Research Foundation, Inc. Pyridinone diketo acids: inhibitors of hiv replication in combination therapy
WO2008021338A2 (en) 2006-08-15 2008-02-21 Wyeth Tricyclic oxazolidone derivatives useful as pr modulators
US20080045560A1 (en) 2006-08-15 2008-02-21 Wyeth Pyrrolidine and related derivatives useful as PR modulators
US8820639B2 (en) 2006-11-03 2014-09-02 Assa Abloy Ab Security feature RFID card
TW200831080A (en) 2006-12-15 2008-08-01 Irm Llc Compounds and compositions as inhibitors of cannabinoid receptor 1 activity
GB0722769D0 (en) 2007-11-21 2008-01-02 Biolipox Ab New compounds
EP2137150A1 (en) * 2007-03-12 2009-12-30 Biolipox AB Piperidinones useful in the treatment of inflammation
US7705018B2 (en) 2007-03-23 2010-04-27 Amgen Inc. Substituted quinolines and their uses in treatment of inflammatory and related conditions
AU2008231304B2 (en) 2007-03-23 2011-05-12 Amgen Inc. Heterocyclic compounds and their uses
EP2132207A2 (en) 2007-03-23 2009-12-16 Amgen Inc. Heterocyclic compounds and their uses
AR065860A1 (es) * 2007-03-29 2009-07-08 Novartis Ag 3-imidazolil-indoles para el tratamiento de enfermedades proliferativas
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
US7834179B2 (en) * 2007-05-23 2010-11-16 Hoffmann-La Roche Inc. Spiroindolinone derivatives
WO2009004430A1 (en) 2007-06-29 2009-01-08 Pfizer Inc. N-benzyl oxazolidinones and related heterocycleic compounds as potentiators of glutamate receptors
EA018708B1 (ru) 2007-07-09 2013-10-30 Астразенека Аб ПРОИЗВОДНЫЕ МОРФОЛИНОПИРИМИДИНА, ИСПОЛЬЗУЕМЫЕ ПРИ ЗАБОЛЕВАНИЯХ, СВЯЗАННЫХ С mTOR КИНАЗОЙ И/ИЛИ PI3K
WO2009011871A2 (en) 2007-07-17 2009-01-22 Amgen Inc. Thiadiazole modulators of pkb
WO2009011880A2 (en) 2007-07-17 2009-01-22 Amgen Inc. Heterocyclic modulators of pkb
ES2401557T3 (es) 2007-08-02 2013-04-22 Amgen, Inc Moduladores de Pl3 cinasas y métodos de uso
MX2010003868A (es) 2007-10-09 2010-04-27 Hoffmann La Roche Cis-imidazolinas quirales.
US7776875B2 (en) 2007-12-19 2010-08-17 Hoffman-La Roche Inc. Spiroindolinone derivatives
WO2009085185A1 (en) 2007-12-19 2009-07-09 Amgen Inc. Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
CL2008003798A1 (es) 2007-12-19 2009-10-09 Amgen Inc Compuestos derivados de heterobiciclos aromaticos sustituidos, inhibidores de pi3 quinasa; composicion farmaceutica; utiles en el tratamiento de cancer, melanomas, glioblastomas, entre otras enfermedades.
US20100256191A1 (en) 2007-12-26 2010-10-07 Eisai R&D Management Co., Ltd. Ampa receptor antagonists and zonisamide for epilepsy
WO2009114950A1 (en) 2008-03-21 2009-09-24 Chlorion Pharma, Inc. Substituted pyrrolidine and piperidine compounds, derivatives thereof, and methods for treating pain
MX2010010975A (es) 2008-04-07 2010-11-01 Amgen Inc Amino piridinas/pirimidinas gem-disustituidas y espirociclicas como inhibidores de ciclo celular.
EP2307400B1 (en) 2008-05-30 2014-04-23 Amgen, Inc Inhibitors of pi3 kinase
GB0811643D0 (en) 2008-06-25 2008-07-30 Cancer Rec Tech Ltd New therapeutic agents
AR073578A1 (es) * 2008-09-15 2010-11-17 Priaxon Ag Pirrolidin-2-onas
PE20110367A1 (es) 2008-09-18 2011-06-13 Hoffmann La Roche DERIVADOS DE 4-CIANO-4-FENIL-PIRROLIDIN-2-CARBOXAMIDAS SUSTITUIDAS COMO INHIBIDORES DE LA INTERACCION p53-MDM2
US20110263647A1 (en) 2009-01-15 2011-10-27 Amgen Inc. Fluoroisoquinoline substituted thiazole compounds and methods of use
WO2010096314A1 (en) 2009-02-18 2010-08-26 Amgen Inc. INDOLE/BENZIMIDAZOLE COMPOUNDS AS mTOR KINASE INHIBITORS
JP2012521354A (ja) 2009-03-20 2012-09-13 アムジエン・インコーポレーテツド Ｐｉ３キナーゼの阻害薬
US8076482B2 (en) 2009-04-23 2011-12-13 Hoffmann-La Roche Inc. 3,3′-spiroindolinone derivatives
UY32582A (es) 2009-04-28 2010-11-30 Amgen Inc Inhibidores de fosfoinositida 3 cinasa y/u objetivo mamífero
WO2010132598A1 (en) 2009-05-13 2010-11-18 Amgen Inc. Heteroaryl compounds as pikk inhibitors
UY32743A (es) 2009-06-25 2010-12-31 Amgen Inc Compuestos heterocíclicos y sus usos
JP2012531436A (ja) 2009-06-25 2012-12-10 アムジエン・インコーポレーテツド 複素環式化合物およびそれらのｐｉ３ｋ活性阻害剤としての使用
US8754089B2 (en) 2009-06-25 2014-06-17 Amgen Inc. Heterocyclic compounds and their uses
MX2011013666A (es) 2009-06-25 2012-03-06 Amgen Inc Compuestos heterociclicos y sus usos.
IN2012DN01693A (ar) 2009-08-26 2015-06-05 Novartis Ag
US8088815B2 (en) 2009-12-02 2012-01-03 Hoffman-La Roche Inc. Spiroindolinone pyrrolidines
US8440693B2 (en) 2009-12-22 2013-05-14 Novartis Ag Substituted isoquinolinones and quinazolinones
JO2998B1 (ar) 2010-06-04 2016-09-05 Amgen Inc مشتقات بيبيريدينون كمثبطات mdm2 لعلاج السرطان
CN102153557B (zh) 2011-01-21 2013-03-20 中国科学院上海有机化学研究所 具有乙二胺骨架的多手性中心氮杂环卡宾前体盐、合成方法及用途
CA2850166C (en) 2011-09-27 2019-12-03 Amgen Inc. Heterocyclic compounds as mdm2 inhibitors for the treatment of cancer
WO2014130470A1 (en) 2013-02-19 2014-08-28 Amgen Inc. Cis-morpholinone and other compounds as mdm2 inhibitors for the treatment of cancer
WO2014134201A1 (en) 2013-02-28 2014-09-04 Amgen Inc. A benzoic acid derivative mdm2 inhibitor for the treatment of cancer
EP2970237B1 (en) 2013-03-14 2017-09-27 Amgen Inc. Heteroaryl acid morpholinone compounds as mdm2 inhibitors for the treatment of cancer
CN105358530A (zh) 2013-06-10 2016-02-24 美国安进公司 制备mdm2抑制剂的方法及其结晶形式

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