CL2017000381A1 - Nuevos compuestos de spiro[3h-indol-3,2'-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53 - Google Patents

Nuevos compuestos de spiro[3h-indol-3,2'-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53

Info

Publication number
CL2017000381A1
CL2017000381A1 CL2017000381A CL2017000381A CL2017000381A1 CL 2017000381 A1 CL2017000381 A1 CL 2017000381A1 CL 2017000381 A CL2017000381 A CL 2017000381A CL 2017000381 A CL2017000381 A CL 2017000381A CL 2017000381 A1 CL2017000381 A1 CL 2017000381A1
Authority
CL
Chile
Prior art keywords
mdm2
inhibitors
pyrrolidin
spiro
indole
Prior art date
Application number
CL2017000381A
Other languages
English (en)
Inventor
Juergen Ramharter
Joachim Broeker
Annika Gille
Andreas Gollner
Manuel Henry
Nina Toelle
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 CL2017000381A1 publication Critical patent/CL2017000381A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/20—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
    • A61K31/435—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
    • A61K31/535—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
    • A61K31/5365—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 ortho- or peri-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
    • A61K31/535—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
    • A61K31/537—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 spiro-condensed or forming part of bridged 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • 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
    • 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
    • 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
    • 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
    • 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
    • C07D487/12—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 three hetero rings
    • C07D487/20—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/18—Oxygen-containing compounds, e.g. metal carbonyls

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Pain & Pain Management (AREA)
  • Polymers & Plastics (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

<p>LA PRESENTE INVENCIÓN ABARCA COMPUESTOS DE LA FORMULA (I)</p> <p>* incluir figura de estructura hoja resumen (pagina 4) fecha 15-02-2017</p> <p>DONDE LOS GRUPOS R1 A R7 , A, V, W, X, Y, N, R Y Q SE DEFINEN EN LA REIVINDICACIÓN 1, SU USA COMO INHIBIDORES DE LA INTERACCIÓN MDM2- P53, COMPOSICIONES FARMACÉUTICAS QUE CONTIENEN COMPUESTOS DE ESTA CLASE, SU USO COMO MEDICAMENTOS, EN ESPECIAL COMO AGENTES PARA EL TRATAMIENTO Y/O PREVENCIÓN DE LAS ENFERMEDADES ONCOLÓGICAS, E INTERMEDIARIOS SINTÉTICOS.</p>
CL2017000381A 2014-08-21 2017-02-15 Nuevos compuestos de spiro[3h-indol-3,2'-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53 CL2017000381A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP14181746 2014-08-21

Publications (1)

Publication Number Publication Date
CL2017000381A1 true CL2017000381A1 (es) 2017-10-30

Family

ID=51359320

Family Applications (1)

Application Number Title Priority Date Filing Date
CL2017000381A CL2017000381A1 (es) 2014-08-21 2017-02-15 Nuevos compuestos de spiro[3h-indol-3,2'-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53

Country Status (26)

Country Link
US (5) US10246467B2 (es)
EP (1) EP3183254B1 (es)
JP (1) JP6591532B2 (es)
KR (2) KR20170042779A (es)
CN (1) CN107001385B (es)
AR (1) AR101600A1 (es)
AU (1) AU2015306128B2 (es)
BR (1) BR112017002942B1 (es)
CA (1) CA2956129C (es)
CL (1) CL2017000381A1 (es)
CY (1) CY1122127T1 (es)
DK (1) DK3183254T3 (es)
EA (1) EA038071B1 (es)
ES (1) ES2739697T3 (es)
HR (1) HRP20191414T1 (es)
HU (1) HUE046057T2 (es)
IL (1) IL250280B (es)
LT (1) LT3183254T (es)
MX (1) MX373033B (es)
PH (1) PH12017500252B1 (es)
PL (1) PL3183254T3 (es)
PT (1) PT3183254T (es)
RS (1) RS59111B1 (es)
SI (1) SI3183254T1 (es)
TW (1) TW201625617A (es)
WO (1) WO2016026937A1 (es)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6577958B2 (ja) 2014-04-11 2019-09-18 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 スピロ［３Ｈ−インドール−３，２’−ピロリジン］−２（１Ｈ）−オン誘導体およびＭＤＭ２−ｐ５３阻害剤としてのそれらの使用
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
NO2721710T3 (es) 2014-08-21 2018-03-31
JP6591532B2 (ja) 2014-08-21 2019-10-16 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
HUE054985T2 (hu) 2015-10-09 2021-11-29 Boehringer Ingelheim Int Spiro[3H-indol-3,2'-pirrolidin]-2(1H)-on vegyületek és számrazékok, mint MDM2-P53 inhibitorok
AU2017246452C1 (en) 2016-04-06 2021-06-03 The Regents Of The University Of Michigan MDM2 protein degraders
CN109152843A (zh) 2016-05-20 2019-01-04 豪夫迈·罗氏有限公司 Protac抗体缀合物及其使用方法
MX2019011945A (es) * 2017-04-05 2019-11-28 Boehringer Ingelheim Int Terapia de combinacion contra cancer.
CN107290543A (zh) * 2017-05-02 2017-10-24 南方医科大学 一种检测细胞内与p53转录激活域相互作用蛋白的方法
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
JP2020193181A (ja) * 2019-05-30 2020-12-03 東ソー株式会社 芳香族ニトリル化合物の製造方法
AU2020313090A1 (en) * 2019-07-17 2021-12-23 Noxopharm Limited Immuno-oncology therapy using isoflavone compounds
CN116034106B (zh) 2020-06-02 2025-11-04 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-氰基噻吩及衍生物
CN116583275A (zh) * 2020-09-21 2023-08-11 诺华股份有限公司 用于治疗或预防造血细胞移植后血液肿瘤复发的mdm2抑制剂
CN112375086A (zh) * 2020-12-11 2021-02-19 浙江工业大学 一种手性螺[呋喃-3,3′-假吲哚]-2-酮类化合物的制备方法
WO2022183006A1 (en) 2021-02-25 2022-09-01 Mayo Foundation For Medical Education And Research Compounds for programmable protein degradation and methods of use for the disease treatment
RU2770902C1 (ru) * 2021-05-24 2022-04-25 Федеральное государственное автономное образовательное учреждение высшего образования "Пермский государственный национальный исследовательский университет" (ПГНИУ) 3-Арил-6H-спиро[бензо[b]фуро[3',4':2,3]пирроло[1,2-d][1,4]оксазин 5,3'-индолин]-1,2,2',6-тетраоны, обладающие противовоспалительной активностью, и способ их получения
WO2023056069A1 (en) 2021-09-30 2023-04-06 Angiex, Inc. Degrader-antibody conjugates and methods of using same
CR20240233A (es) 2021-12-01 2024-07-17 Univ Vanderbilt Tiofenos 2-amino-3-ciano anulados y derivados para el tratamiento del cáncer
EP4441050A1 (en) 2021-12-01 2024-10-09 Boehringer Ingelheim International GmbH Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer
EP4441051A1 (en) 2021-12-01 2024-10-09 Boehringer Ingelheim International GmbH Kras degrading compounds comprising annulated 2-amino-3-cyano thiophenes
TW202337432A (zh) 2021-12-01 2023-10-01 德商百靈佳殷格翰國際股份有限公司 用於治療癌症之環狀2-胺基-3-氰基噻吩及衍生物
TW202340208A (zh) 2021-12-01 2023-10-16 德商百靈佳殷格翰國際股份有限公司 用於治療癌症之環狀2-胺基-3-氰基噻吩及衍生物
CN114831991B (zh) * 2022-06-10 2024-02-06 陕西科技大学 Gsk2334470用于制备抗真菌药物及其增效剂的应用
US11944604B1 (en) 2023-03-10 2024-04-02 King Saud University Nanoformulation of spriooxindole and methods for treating hepatocellular carcinoma
WO2024240858A1 (en) 2023-05-23 2024-11-28 Valerio Therapeutics Protac molecules directed against dna damage repair system and uses thereof
US20250019385A1 (en) 2023-05-30 2025-01-16 Boehringer Ingelheim International Gmbh Spirocyclic annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer
WO2026114918A1 (en) 2024-11-27 2026-06-04 Boehringer Ingelheim International Gmbh Spirocyclic annulated 2-amino-3-cyano thiophene derivatives as kras inhibitors for the treatment of cancer
US20260146049A1 (en) 2024-11-27 2026-05-28 Boehringer Ingelheim International Gmbh Spirocyclic annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer
US20260146050A1 (en) 2024-11-27 2026-05-28 Boehringer Ingelheim International Gmbh Kras degrading compounds comprising spirocyclic annulated 2 amino-3-cyano thiophenes
WO2026114957A1 (en) 2024-11-27 2026-06-04 Boehringer Ingelheim International Gmbh Spirocyclic annulated 2-amino-3-cyano thiophene derivatives as kras degraders for the treatment of cancer

Family Cites Families (44)

* 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
WO1999012904A1 (en) 1997-09-08 1999-03-18 Arqule, Inc. Spiro[pyrrolidine-2,3'-oxindole] compounds and methods of use
CA2371618A1 (en) 1999-04-28 2000-11-09 Yuji Ishihara Cyclic amide compounds, their production and use
AU2006216780B8 (en) 2005-02-22 2010-04-22 The Regents Of The University Of Michigan Small molecule inhibitors of MDM2 and uses thereof
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
DE602007011902D1 (de) 2006-03-13 2011-02-24 Hoffmann La Roche Spiroindolinon-derivate
US20070213341A1 (en) 2006-03-13 2007-09-13 Li Chen Spiroindolinone derivatives
WO2008005268A1 (en) 2006-06-30 2008-01-10 Schering Corporation Substituted piperidines that increase p53 activity and the uses thereof
CA2661354C (en) 2006-08-30 2012-12-18 The Regents Of The University Of Michigan New small molecule inhibitors of mdm2 and the uses thereof
BRPI0810082A2 (pt) 2007-03-29 2014-10-21 Novartis Ag 3-imidazolil-indóis para o tratamento de doenças 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
CN104876938A (zh) 2009-11-12 2015-09-02 密歇根大学董事会 螺-吲哚酮mdm2拮抗剂
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
PE20140408A1 (es) 2010-11-12 2014-04-10 Univ Michigan Derivados espiro-oxindol como antagonistas de mdm2
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
TR201807311T4 (tr) 2011-03-10 2018-06-21 Daiichi Sankyo Co Ltd Dispiropirolidin derivesi.
JO3363B1 (ar) 2011-04-13 2019-03-13 Epizyme Inc مركبات بنزين مستبدلة بأريل أو أريل غير متجانس
MX346375B (es) 2011-05-11 2017-03-16 Univ Michigan Regents Antagonistas de espiro-oxindol de mdm2.
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
JP6577958B2 (ja) 2014-04-11 2019-09-18 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 スピロ［３Ｈ−インドール−３，２’−ピロリジン］−２（１Ｈ）−オン誘導体およびＭＤＭ２−ｐ５３阻害剤としてのそれらの使用
AU2015247646B2 (en) 2014-04-17 2019-06-06 The Regents Of The University Of Michigan MDM2 inhibitors and therapeutic methods using the same
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
CN105829318B (zh) 2014-08-18 2018-10-02 哈德森生物医药有限公司 作为mdm2抑制剂的螺吡咯烷
JP6591532B2 (ja) * 2014-08-21 2019-10-16 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
NO2721710T3 (es) 2014-08-21 2018-03-31
HUE054985T2 (hu) 2015-10-09 2021-11-29 Boehringer Ingelheim Int Spiro[3H-indol-3,2'-pirrolidin]-2(1H)-on vegyületek és számrazékok, mint MDM2-P53 inhibitorok
PL3359541T3 (pl) 2015-10-09 2021-01-11 AbbVie Overseas S.à r.l. N-SULFONYLOWANE PIRAZOLO[3,4-b]PIRYDYNO-6-KARBOKSAMIDY I SPOSÓB ZASTOSOWANIA
CN108137484B (zh) 2015-10-09 2021-02-12 西北大学 作为用于治疗癫痫、成瘾和肝细胞癌的gaba氨基转移酶灭活剂的化合物

Also Published As

Publication number Publication date
CY1122127T1 (el) 2020-11-25
KR20230098695A (ko) 2023-07-04
CA2956129C (en) 2022-10-25
AR101600A1 (es) 2016-12-28
ES2739697T3 (es) 2020-02-03
PL3183254T3 (pl) 2019-10-31
AU2015306128B2 (en) 2020-03-26
DK3183254T3 (da) 2019-08-19
LT3183254T (lt) 2019-08-26
KR20170042779A (ko) 2017-04-19
EA201790425A1 (ru) 2017-07-31
US20160052938A1 (en) 2016-02-25
MX373033B (es) 2020-05-27
CA2956129A1 (en) 2016-02-25
CN107001385B (zh) 2020-03-13
US10919913B2 (en) 2021-02-16
EP3183254B1 (en) 2019-05-22
JP2017524025A (ja) 2017-08-24
US12312363B2 (en) 2025-05-27
US20190169209A1 (en) 2019-06-06
PT3183254T (pt) 2019-08-29
HRP20191414T1 (hr) 2019-11-01
BR112017002942A2 (pt) 2017-12-05
NZ728685A (en) 2024-01-26
US20210101912A1 (en) 2021-04-08
IL250280B (en) 2021-02-28
PH12017500252A1 (en) 2017-07-10
PH12017500252B1 (en) 2017-07-10
HUE046057T2 (hu) 2020-02-28
EP3183254A1 (en) 2017-06-28
JP6591532B2 (ja) 2019-10-16
TW201625617A (zh) 2016-07-16
IL250280A0 (en) 2017-03-30
US20240109913A1 (en) 2024-04-04
KR102627097B1 (ko) 2024-01-18
MX2017002260A (es) 2017-05-03
US20170247394A1 (en) 2017-08-31
WO2016026937A1 (en) 2016-02-25
EA038071B1 (ru) 2021-07-01
SI3183254T1 (sl) 2019-08-30
RS59111B1 (sr) 2019-09-30
AU2015306128A1 (en) 2017-02-23
BR112017002942B1 (pt) 2022-10-18
US10246467B2 (en) 2019-04-02
CN107001385A (zh) 2017-08-01

Similar Documents

Publication Publication Date Title
MX2017002260A (es) Nuevos compuestos de espiro[3h-indol-3,2´-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53.
CO2018003565A2 (es) Compuestos de espiro[3h-indol-3,2´-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53
ECSP20040257A (es) Nuevas piridopirimidinonas sustituidas con bencilamino y derivados como inhibidores de sos1
UY36112A (es) Compuestos de imidazo[4,5-c]quinolin-2-ona y su uso para tratar cáncer
CL2015000295A1 (es) Compuestos derivados de alquilpirimidina; composicion farmaceutica que los comprende; uso para el tratamiento de infecciones víricas y otras enfermedades.
ECSP17074645A (es) Azabenzimidazoles y su uso como moduladores del receptor ampa
CL2015003686A1 (es) Derivados de pirrolo[3,2-d]pirimidina para el tratamiento de infecciones víricas y otras enfermedades
CO2018013803A2 (es) 1h-pirazolo[4,3-b]piridinas como inhibidores de pde1
UY36265A (es) “derivados de pirrolo[2,3-d]pirimidina”.
ECSP16074478A (es) Compuestos novedosos
CL2015002222A1 (es) Compuestos de azabencimidazol como inhibidores de isoenzimas pde4 para el tratamiento del snc y otros trastornos.
NI201500096A (es) Compuesto químicos
CO2020004977A2 (es) Compuestos bicíclicos para su uso como inhibidores de la ripi quinasa
CL2020001062A1 (es) Sulfonas y sulfóxidos bicíclicos y métodos de uso de los mismos.
CL2017000223A1 (es) [1,2,4]triazolo[4,3-b]piridazinas para su uso en el tratamiento de enfermedades proliferativas
MX2016010524A (es) Derivados de piridazina para uso en la prevencion o tratamiento de trastorno ataxico.
CL2016000884A1 (es) Derivados de piperazina y su uso como medicamento.
CL2020001550A1 (es) Tratamientos combinados que comprenden la administración de 1h-pirazolo[4,3-b]piridinas.
CL2016000482A1 (es) Compuestos de tipo 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mglur2
CL2017003025A1 (es) Derivados(1,2-b)(1,2,4)de imidazotriazina como agentes antiparasitarios.
ECSP18056196A (es) Derivados de indano
CL2018001871A1 (es) Uso de inhibidores de la actividad o función de pi3k para el tratamiento del síndrome de sjögren primario