MA50065A - Dérivés de composés de spiro[3h-indole-3,2´-pyrrolidine]-2(1h)-one et dérivés utilisés comme inhibiteurs de mdm2-p53 - Google Patents

Dérivés de composés de spiro[3h-indole-3,2´-pyrrolidine]-2(1h)-one et dérivés utilisés comme inhibiteurs de mdm2-p53

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Publication number
MA50065A
MA50065A MA050065A MA50065A MA50065A MA 50065 A MA50065 A MA 50065A MA 050065 A MA050065 A MA 050065A MA 50065 A MA50065 A MA 50065A MA 50065 A MA50065 A MA 50065A
Authority
MA
Morocco
Prior art keywords
mdm2
inhibitors
compounds
spiro
pyrrolidine
Prior art date
Application number
MA050065A
Other languages
English (en)
Other versions
MA50065B1 (fr
Inventor
Joachim Broeker
Annika Gille
Stefan Goepper
Andreas Gollner
Manuel Henry
Guenther Huchler
Nina Kerres
Christiane Kofink
Juergen Ramharter
Harald Weinstabl
Original Assignee
Boehringer Ingelheim Int
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 Boehringer Ingelheim Int filed Critical Boehringer Ingelheim Int
Publication of MA50065A publication Critical patent/MA50065A/fr
Publication of MA50065B1 publication Critical patent/MA50065B1/fr

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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
    • C07D487/22—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 four or more hetero rings
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4162—1,2-Diazoles condensed with heterocyclic ring 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
    • A61K31/435—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
    • 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
    • A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring 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
    • A61K31/435—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
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
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    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
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    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
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    • 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
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • 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
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • 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
    • C07D471/22—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 systems contains four or more hetero rings

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Pain & Pain Management (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Neurosurgery (AREA)
  • Dermatology (AREA)
  • Biomedical Technology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Neurology (AREA)
  • Hematology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Toxicology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Urology & Nephrology (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

La présente invention concerne des composés de formule (i) dans laquelle les groupes r1 à r4, r7, a, d, e, f, v, w, x, y, n, r et q sont définis dans la revendication 1, leur utilisation à titre d'inhibiteurs de l'interaction mdm2-p53, des compositions pharmaceutiques les contenant, leur utilisation à titre de médicaments, notamment à titre d'agents destinés à traiter et/ou à prévenir les maladies oncologiques, et les intermédiaires formés au cours de leur synthèse.
MA50065A 2015-10-09 2016-10-07 Dérivés de composés de spiro[3h-indole-3,2´-pyrrolidine]-2(1h)-one et dérivés utilisés comme inhibiteurs de mdm2-p53 MA50065B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP15189210 2015-10-09
PCT/EP2016/074008 WO2017060431A1 (fr) 2015-10-09 2016-10-07 Composés de spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one et leurs dérivés à titre d'inhibiteurs de mdm2-p53

Publications (2)

Publication Number Publication Date
MA50065A true MA50065A (fr) 2018-08-15
MA50065B1 MA50065B1 (fr) 2021-06-30

Family

ID=54292702

Family Applications (1)

Application Number Title Priority Date Filing Date
MA50065A MA50065B1 (fr) 2015-10-09 2016-10-07 Dérivés de composés de spiro[3h-indole-3,2´-pyrrolidine]-2(1h)-one et dérivés utilisés comme inhibiteurs de mdm2-p53

Country Status (31)

Country Link
US (4) US10144739B2 (fr)
EP (1) EP3359542B1 (fr)
JP (1) JP6602470B2 (fr)
KR (2) KR102722493B1 (fr)
CN (5) CN119569739A (fr)
AR (1) AR106314A1 (fr)
AU (1) AU2016333721B2 (fr)
BR (1) BR112018007155B1 (fr)
CL (1) CL2018000666A1 (fr)
CO (1) CO2018003565A2 (fr)
CY (1) CY1124284T1 (fr)
DK (1) DK3359542T3 (fr)
EA (1) EA036013B1 (fr)
ES (1) ES2873895T3 (fr)
HR (1) HRP20210960T1 (fr)
HU (1) HUE054985T2 (fr)
IL (1) IL258073B (fr)
LT (1) LT3359542T (fr)
MA (1) MA50065B1 (fr)
MX (1) MX377009B (fr)
MY (1) MY199688A (fr)
PE (1) PE20181205A1 (fr)
PH (1) PH12018500763A1 (fr)
PL (1) PL3359542T3 (fr)
PT (1) PT3359542T (fr)
RS (1) RS61936B1 (fr)
SA (1) SA518391307B1 (fr)
SI (1) SI3359542T1 (fr)
TW (1) TWI737635B (fr)
UA (1) UA123905C2 (fr)
WO (1) WO2017060431A1 (fr)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10138251B2 (en) 2014-04-11 2018-11-27 Boehringer Ingelheim International Gmbh Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one compounds and derivatives as MDM2-P53 inhibitors
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.
EP3359542B1 (fr) 2015-10-09 2021-03-17 Boehringer Ingelheim International GmbH Dérivés de composés de spiro[3h-indole-3,2´-pyrrolidine]-2(1h)-one et dérivés utilisés comme inhibiteurs de mdm2-p53
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
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
BR112019021032A2 (pt) 2017-04-05 2020-05-05 Boehringer Ingelheim International Gmbh terapia combinada anticâncer
EA202091583A1 (ru) * 2017-12-29 2020-10-08 Ган Энд Ли Фармасьютикалз Соединения, которые могут применяться в качестве ингибитора опухоли, способ их получения и их применение
EP3511334A1 (fr) * 2018-01-16 2019-07-17 Adamed sp. z o.o. Composés de 1,2,3',5'-tetrahydro-2'h-spiro[indole-3,1'-pyrrolo[3,4-c]pyrrole] -2,3'-dione comme agents thérapeutiques activant le tp53
US12480163B2 (en) * 2018-07-18 2025-11-25 Dana-Farber Cancer Institute, Inc. Compositions and methods for identification assessment, prevention, and treatment of Ewing sarcoma using TP53 dependency biomarkers and modulators
US10590147B1 (en) 2019-09-10 2020-03-17 King Saud University Spirooxindole-pyrrolothiazole heterocyclic hybrids
US11285159B2 (en) * 2019-11-05 2022-03-29 Abbvie Inc. Dosing regimens for use in treating myelofibrosis and MPN-related disorders with navitoclax
BR112022023462A2 (pt) 2020-06-02 2022-12-20 Boehringer Ingelheim Int 2-amino-3-ciano tiofenos anulados e derivados para o tratamento de câncer
US12577240B2 (en) 2020-07-11 2026-03-17 Pfizer Inc. Antiviral heteroaryl ketone derivatives
US11351149B2 (en) 2020-09-03 2022-06-07 Pfizer Inc. Nitrile-containing antiviral compounds
CN112047951A (zh) * 2020-10-16 2020-12-08 吉林大学 手性螺[吡咯-2，2’-呋喃]化合物及其制备方法
US12037346B2 (en) 2021-04-13 2024-07-16 Nuvalent, Inc. Amino-substituted heteroaryls for treating cancers with EGFR mutations
EP4384166A1 (fr) 2021-08-09 2024-06-19 Boehringer Ingelheim International GmbH Composition orale comprenant un antagoniste de mdm2 pour la thérapie anticancéreuse
US20250129095A1 (en) 2021-12-01 2025-04-24 Boehringer Ingelheim Int'l GmbH Corp. Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer
CN118591540A (zh) 2021-12-01 2024-09-03 勃林格殷格翰国际有限公司 包含环状2-氨基-3-氰基噻吩的kras降解化合物
CN119841847A (zh) 2021-12-01 2025-04-18 勃林格殷格翰国际有限公司 用于治疗癌症的环状2-氨基-3-氰基噻吩及其衍生物
JP2024543976A (ja) 2021-12-01 2024-11-26 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 癌の処置のための環化２－アミノ－３－シアノチオフェン及び誘導体
US20250129096A1 (en) 2021-12-01 2025-04-24 Boehringer Ingelheim Int'l GmbH Corp. Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer
TW202440585A (zh) 2022-12-22 2024-10-16 德商百靈佳殷格翰國際股份有限公司 MDM2-p53抑制劑之晶型及醫藥組合物
JP2025540433A (ja) 2022-12-23 2025-12-11 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アンタゴニストの製造のための新規方法
WO2024238404A2 (fr) * 2023-05-12 2024-11-21 Pmv Pharmaceuticals, Inc. Polythérapie pour le traitement du cancer
AR132802A1 (es) 2023-05-30 2025-07-30 Boehringer Ingelheim Int 2-amino-3-cianotiofenos con anillos espirocíclicos y derivados para el tratamiento del cáncer
TW202510886A (zh) 2023-05-31 2025-03-16 德商百靈佳殷格翰國際股份有限公司 作為用於預測癌症治療反應性之生物標記之存活素

Family Cites Families (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3361759A (en) 1963-10-07 1968-01-02 Upjohn Co 3-(2-pyrrolidinyl)-indoles and method of preparation
US4219560A (en) 1978-04-17 1980-08-26 Sandoz, Inc. Piperidine and pyrrolidine alcohols
US5574044A (en) 1994-10-27 1996-11-12 Merck & Co., Inc. Muscarine antagonists
EP1015430A4 (fr) 1997-09-08 2001-01-17 Arqule Inc Composes de spiro pyrrolidine-2,3'-oxindole] et procedes d'utilisation
CA2371618A1 (fr) 1999-04-28 2000-11-09 Yuji Ishihara Composes d'amides cycliques, leurs procedes de preparation et d'utilisation
EA019566B1 (ru) * 2005-02-22 2014-04-30 Дзе Риджентс Оф Дзе Юниверсити Оф Мичиган Низкомолекулярные ингибиторы mdm2
JP2006234861A (ja) 2005-02-22 2006-09-07 Fujinon Sano Kk 光学ガラスの製造方法，偏光変換素子の製造方法及び偏光変換素子
US20090111805A1 (en) 2005-02-24 2009-04-30 Pfizer Inc. Bicyclic heteroaromatic derivatives useful as anticancer agents
AU2007224452A1 (en) 2006-03-13 2007-09-20 F. Hoffmann-La Roche Ag Spiroindolinone derivatives
US20070213341A1 (en) 2006-03-13 2007-09-13 Li Chen Spiroindolinone derivatives
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
EA016145B1 (ru) 2006-08-30 2012-02-28 Дзе Риджентс Оф Дзе Юниверсити Оф Мичиган Новые низкомолекулярные ингибиторы mdm2 и их применение
AR065860A1 (es) 2007-03-29 2009-07-08 Novartis Ag 3-imidazolil-indoles para el tratamiento de enfermedades proliferativas
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
US7977358B2 (en) 2007-07-26 2011-07-12 Hoffmann-La Roche Inc. Pyrazol derivatives
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
AR073578A1 (es) 2008-09-15 2010-11-17 Priaxon Ag Pirrolidin-2-onas
US20100190814A1 (en) 2009-01-26 2010-07-29 Li Chen Spiroindolinone derivative prodrugs
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
US8288431B2 (en) 2010-02-17 2012-10-16 Hoffmann-La Roche Inc. Substituted spiroindolinones
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
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
MX2013005238A (es) 2010-11-12 2013-09-02 Univ Michigan Antagonistas de mdm2 de espiro-oxindol.
US20130053410A1 (en) 2011-03-03 2013-02-28 David Joseph Bartkovitz Substituted heteroaryl 2',3',7',7a'-tetrahydrospiro[pyrrole-3,6'-pyrrolo[1,2-c]imidazole]-1',2(1h,5'h)-dione
DK2684880T3 (en) 2011-03-10 2018-05-22 Daiichi Sankyo Co Ltd DISPIROPYRROLIDINE DERIVATIVES
JO3438B1 (ar) 2011-04-13 2019-10-20 Epizyme Inc مركبات بنزين مستبدلة بأريل أو أريل غير متجانس
BR112013028983A2 (pt) 2011-05-11 2017-02-07 Sanofi Sa antagonistas mdm2 espiro-oxindol
CN102443004A (zh) 2011-11-01 2012-05-09 南京工业大学 有机发光材料6,7,14,15-四氢-5,13-二取代苯并[1,2-c:4,5-c’]二吖啶类化合物、合成方法及应用
CN103910746B (zh) 2014-02-28 2016-08-03 中山大学 一类海洋真菌来源的Berkeleyones化合物及其制备方法和应用
US10138251B2 (en) 2014-04-11 2018-11-27 Boehringer Ingelheim International Gmbh Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one compounds and derivatives as MDM2-P53 inhibitors
MX373045B (es) 2014-04-17 2020-05-26 Univ Michigan Regents Inhibidores de mdm2 y metodos terapeuticos que utilizan el mismo.
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
ES2959097T3 (es) 2014-08-18 2024-02-20 Hudson Biopharma Inc Espiropirrolidinas como inhibidores de MDM2
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.
NO2721710T3 (fr) 2014-08-21 2018-03-31
EP3359542B1 (fr) 2015-10-09 2021-03-17 Boehringer Ingelheim International GmbH Dérivés de composés de spiro[3h-indole-3,2´-pyrrolidine]-2(1h)-one et dérivés utilisés comme inhibiteurs de mdm2-p53
JP6841821B2 (ja) 2015-10-09 2021-03-10 ノースウェスタン ユニバーシティ てんかん、嗜癖および肝細胞癌の処置のためのｇａｂａアミノトランスフェラーゼ不活性化剤としての（ｓ）−３−アミノ−４−（ジフルオロメチレニル）シクロペント−１−エン−１−カルボン酸および関連化合物
KR20180083323A (ko) 2015-10-09 2018-07-20 애브비 에스.에이.알.엘. N-설포닐화 피라졸로[3,4-b]피리딘-6-카복스아미드 및 사용 방법
JP2018017594A (ja) * 2016-07-27 2018-02-01 セイコーエプソン株式会社 動力伝達装置、ロボットおよびプリンター
CN106967049B (zh) 2017-03-22 2018-06-26 杭州师范大学 一种白藜芦醇系列荧光标记分子及其合成方法

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