EA200001021A1 - Замещенные индолиноны с ингибирующим действием по отношению к киназам и циклин/cdk-комплексам - Google Patents

Замещенные индолиноны с ингибирующим действием по отношению к киназам и циклин/cdk-комплексам

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Publication number
EA200001021A1
EA200001021A1 EA200001021A EA200001021A EA200001021A1 EA 200001021 A1 EA200001021 A1 EA 200001021A1 EA 200001021 A EA200001021 A EA 200001021A EA 200001021 A EA200001021 A EA 200001021A EA 200001021 A1 EA200001021 A1 EA 200001021A1
Authority
EA
Eurasian Patent Office
Prior art keywords
cyclin
compounds
indolinons
kinas
substituted
Prior art date
Application number
EA200001021A
Other languages
English (en)
Other versions
EA003532B1 (ru
Inventor
Армин Хеккель
Райнер Вальтер
Вольфганг Грелл
Якобус К.А. Ван-Мэл
Норберт Редеманн
Original Assignee
Бёрингер Ингельхайм Фарма Кг
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 Бёрингер Ингельхайм Фарма Кг filed Critical Бёрингер Ингельхайм Фарма Кг
Publication of EA200001021A1 publication Critical patent/EA200001021A1/ru
Publication of EA003532B1 publication Critical patent/EA003532B1/ru

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • A61P31/10—Antimycotics
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • 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
    • 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
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/32—Oxygen atoms
    • C07D209/34—Oxygen atoms in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Communicable Diseases (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Virology (AREA)
  • Neurosurgery (AREA)
  • AIDS & HIV (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Molecular Biology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Indole Compounds (AREA)

Abstract

В заявке описываются замещенные индолиноны общей формулы (I)в которой R-Rи X имеют значения, указанные в п.1 формулы изобретения, их изомеры и их соли, прежде всего их физиологически приемлемые соли. Предлагаемые соединения обладают ценными фармакологическими свойствами, прежде всего ингибирующим действием по отношению к различным киназам и комплексам циклин/CDK, а также к пролиферации различных опухолевых клеток. В заявке описываются также лекарственные средства, содержащие эти соединения, применение указанных соединений и способ их получения.Международная заявка была опубликована вместе с отчетом о международном поиске.
EA200001021A 1998-04-15 1999-04-10 Замещенные индолиноны с ингибирующим действием по отношению к киназам и циклин/cdk-комплексам EA003532B1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19816624A DE19816624A1 (de) 1998-04-15 1998-04-15 Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel
PCT/EP1999/002436 WO1999052869A1 (de) 1998-04-15 1999-04-10 Substituierte indolinone mit inhibierender wirkung auf kinasen und cyclin/cdk-komplexe

Publications (2)

Publication Number Publication Date
EA200001021A1 true EA200001021A1 (ru) 2001-06-25
EA003532B1 EA003532B1 (ru) 2003-06-26

Family

ID=7864562

Family Applications (1)

Application Number Title Priority Date Filing Date
EA200001021A EA003532B1 (ru) 1998-04-15 1999-04-10 Замещенные индолиноны с ингибирующим действием по отношению к киназам и циклин/cdk-комплексам

Country Status (31)

Country Link
EP (1) EP1071665B1 (ru)
JP (1) JP4015365B2 (ru)
KR (1) KR100588250B1 (ru)
CN (1) CN100338036C (ru)
AR (1) AR015763A1 (ru)
AT (1) ATE251138T1 (ru)
AU (1) AU749829B2 (ru)
BG (1) BG64443B1 (ru)
BR (1) BR9909688A (ru)
CA (1) CA2323111C (ru)
CO (1) CO5011040A1 (ru)
DE (2) DE19816624A1 (ru)
DK (1) DK1071665T3 (ru)
EA (1) EA003532B1 (ru)
EE (1) EE04432B1 (ru)
ES (1) ES2207209T3 (ru)
HU (1) HUP0101568A3 (ru)
ID (1) ID26420A (ru)
IL (1) IL138036A0 (ru)
MY (1) MY122357A (ru)
NO (1) NO317298B1 (ru)
NZ (1) NZ507967A (ru)
PL (1) PL343314A1 (ru)
PT (1) PT1071665E (ru)
SK (1) SK283824B6 (ru)
TR (1) TR200002980T2 (ru)
TW (1) TW510897B (ru)
UA (1) UA63009C2 (ru)
WO (1) WO1999052869A1 (ru)
YU (1) YU59800A (ru)
ZA (1) ZA200004623B (ru)

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US6624171B1 (en) 1999-03-04 2003-09-23 Smithkline Beecham Corporation Substituted aza-oxindole derivatives
GB9904933D0 (en) * 1999-03-04 1999-04-28 Glaxo Group Ltd Compounds
GB9904995D0 (en) * 1999-03-04 1999-04-28 Glaxo Group Ltd Substituted aza-oxindole derivatives
DE19924401A1 (de) * 1999-05-27 2000-11-30 Boehringer Ingelheim Pharma Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel
ES2257313T3 (es) * 1999-08-27 2006-08-01 BOEHRINGER INGELHEIM PHARMA GMBH & CO.KG Indolinonas sustituidas en calidad de inhibidores de tirosina quinasa.
US6762180B1 (en) 1999-10-13 2004-07-13 Boehringer Ingelheim Pharma Kg Substituted indolines which inhibit receptor tyrosine kinases
UA75054C2 (ru) * 1999-10-13 2006-03-15 Бьорінгер Інгельхайм Фарма Гмбх & Ко. Кг Замещенные в положении 6 индолиноны, их получение и их применение как лекарственного средства
US6620818B1 (en) 2000-03-01 2003-09-16 Smithkline Beecham Corporation Method for reducing the severity of side effects of chemotherapy and/or radiation therapy
MY128449A (en) 2000-05-24 2007-02-28 Sugen Inc Prodrugs of 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives
WO2001094312A2 (en) 2000-06-02 2001-12-13 Sugen, Inc. Indolinone derivatives as protein kinase/phosphatase inhibitors
AU2002215053A1 (en) * 2000-11-27 2002-06-24 Pharmacia Italia S.P.A. Phenylacetamido- pyrazole derivatives and their use as antitumor agents
DE10117204A1 (de) 2001-04-06 2002-10-10 Boehringer Ingelheim Pharma In 6-Stellung substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel
PE20030062A1 (es) 2001-05-30 2003-02-08 Sugen Inc Derivados aralquilsulfonil-3-(pirrol-2-ilmetiliden)-2-indolinona como inhibidores de quinasas
DK1490062T3 (da) 2002-03-26 2008-04-28 Boehringer Ingelheim Pharma Glukokortikoidmimetika, fremgangsmåder til fremstilling deraf, farmaceutiske sammensætninger og anvendelser deraf
US7169936B2 (en) 2002-07-23 2007-01-30 Boehringer Ingelheim Pharma Gmbh & Co. Kg Indolinone derivatives substituted in the 6-position, their preparation and their use as medicaments
DE10233500A1 (de) * 2002-07-24 2004-02-19 Boehringer Ingelheim Pharma Gmbh & Co. Kg 3-Z-[1-(4-(N-((4-Methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylen]-6-methoxycarbonyl-2-indolinon-Monoethansulfonat und dessen Verwendung als Arzneimittel
DE10237423A1 (de) 2002-08-16 2004-02-19 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verwendung von LCK-Inhibitoren für die Behandlung von immunologischen Erkrankungen
JP4879492B2 (ja) * 2002-11-27 2012-02-22 アラーガン、インコーポレイテッド 疾患の治療のためのキナーゼ阻害剤
US20050043233A1 (en) 2003-04-29 2005-02-24 Boehringer Ingelheim International Gmbh Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis
UY28526A1 (es) 2003-09-24 2005-04-29 Boehringer Ingelheim Pharma Miméticos de glucocorticoides, métodos de preparación composiciones farmacéuticas y usos de los mismos
WO2005033330A2 (en) * 2003-10-03 2005-04-14 Boehringer Ingelheim Pharmaceuticals, Inc. Fluorescent probes for use in protein kinase inhibitor binding assay
DE102004012070A1 (de) * 2004-03-12 2005-09-29 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue cycloalkyl-haltige 5-Acylindolinone, deren Herstellung und deren Verwendung als Arzneimittel
US7795272B2 (en) 2004-03-13 2010-09-14 Boehringer Ingelheim Pharmaceutical, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
PE20060777A1 (es) 2004-12-24 2006-10-06 Boehringer Ingelheim Int Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas
JP2008525525A (ja) 2004-12-27 2008-07-17 ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド グルココルチコイドミメティクス、その製法、医薬組成物及び使用
CA2611401C (en) * 2005-06-10 2014-02-11 Merck Patent Gesellschaft Mit Beschraenkter Haftung Oxindoles as kinase inhibitors
WO2007057399A2 (en) * 2005-11-15 2007-05-24 Boehringer Ingelheim International Gmbh Treatment of cancer with indole derivatives
JP2010512331A (ja) 2006-12-06 2010-04-22 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 グルココルチコイド模倣薬、それらの製造方法、医薬組成物、及びこれらの使用
US8268859B2 (en) 2008-06-06 2012-09-18 Boehringer Ingelheim International Gmbh Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
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JP6072058B2 (ja) * 2011-11-14 2017-02-01 リガンド・ファーマシューティカルズ・インコーポレイテッド 顆粒球コロニー刺激因子受容体と結合する方法および組成物
WO2014150252A1 (en) * 2013-03-15 2014-09-25 Ligand Pharmaceuticals Incorporated Methods of treatment associated with the granulocyte colony-stimulating factor receptor
CN107033064B (zh) * 2017-04-28 2019-07-09 西安医学院 一种3-(吗啉取代芳亚胺基)吲哚类化合物及其制备方法和应用
CN111285872B (zh) * 2018-12-06 2022-05-17 北京志健金瑞生物医药科技有限公司 吲哚-2-酮衍生物及其制备方法与用途

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GB9501567D0 (en) * 1995-01-26 1995-03-15 Pharmacia Spa Hydrosoluble 3-arylidene-2-oxindole derivatives as tyrosine kinase inhibitors
US5880141A (en) * 1995-06-07 1999-03-09 Sugen, Inc. Benzylidene-Z-indoline compounds for the treatment of disease
GB9718913D0 (en) * 1997-09-05 1997-11-12 Glaxo Group Ltd Substituted oxindole derivatives
DE19824922A1 (de) * 1998-06-04 1999-12-09 Boehringer Ingelheim Pharma Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel
UA75054C2 (ru) * 1999-10-13 2006-03-15 Бьорінгер Інгельхайм Фарма Гмбх & Ко. Кг Замещенные в положении 6 индолиноны, их получение и их применение как лекарственного средства

Also Published As

Publication number Publication date
IL138036A0 (en) 2001-10-31
HUP0101568A3 (en) 2002-12-28
ZA200004623B (en) 2001-05-30
MY122357A (en) 2006-04-29
EP1071665B1 (de) 2003-10-01
AR015763A1 (es) 2001-05-16
ID26420A (id) 2000-12-21
UA63009C2 (en) 2004-01-15
JP2002511449A (ja) 2002-04-16
CO5011040A1 (es) 2001-02-28
NO317298B1 (no) 2004-10-04
TR200002980T2 (tr) 2001-02-21
EE04432B1 (et) 2005-02-15
KR100588250B1 (ko) 2006-06-13
CN100338036C (zh) 2007-09-19
HUP0101568A2 (hu) 2001-09-28
BR9909688A (pt) 2000-12-19
BG64443B1 (en) 2005-02-28
DK1071665T3 (da) 2004-01-05
DE59907199D1 (de) 2003-11-06
EE200000598A (et) 2002-04-15
KR20010042731A (ko) 2001-05-25
CA2323111A1 (en) 1999-10-21
CN1297438A (zh) 2001-05-30
EP1071665A1 (de) 2001-01-31
TW510897B (en) 2002-11-21
NO20005151D0 (no) 2000-10-13
PL343314A1 (en) 2001-08-13
ATE251138T1 (de) 2003-10-15
NO20005151L (no) 2000-10-13
SK283824B6 (sk) 2004-02-03
WO1999052869A1 (de) 1999-10-21
AU749829B2 (en) 2002-07-04
EA003532B1 (ru) 2003-06-26
JP4015365B2 (ja) 2007-11-28
ES2207209T3 (es) 2004-05-16
AU3814999A (en) 1999-11-01
SK15132000A3 (sk) 2001-03-12
PT1071665E (pt) 2004-02-27
YU59800A (sh) 2003-04-30
BG104813A (en) 2001-08-31
NZ507967A (en) 2003-04-29
DE19816624A1 (de) 1999-10-21
CA2323111C (en) 2009-09-15

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MM4A Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s)

Designated state(s): AM AZ BY KZ KG MD TJ TM

MM4A Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s)

Designated state(s): RU