ZA200108971B - Quinoline derivatives as inhibitors of MEK enzymes. - Google Patents
Quinoline derivatives as inhibitors of MEK enzymes. Download PDFInfo
- Publication number
- ZA200108971B ZA200108971B ZA200108971A ZA200108971A ZA200108971B ZA 200108971 B ZA200108971 B ZA 200108971B ZA 200108971 A ZA200108971 A ZA 200108971A ZA 200108971 A ZA200108971 A ZA 200108971A ZA 200108971 B ZA200108971 B ZA 200108971B
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- ZA
- South Africa
- Prior art keywords
- carbon atoms
- group
- salkyl
- alkyl
- hydroxy
- Prior art date
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Classifications
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
- Luminescent Compositions (AREA)
- Quinoline Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9910577.7A GB9910577D0 (en) | 1999-05-08 | 1999-05-08 | Chemical compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200108971B true ZA200108971B (en) | 2003-01-30 |
Family
ID=10852987
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200108971A ZA200108971B (en) | 1999-05-08 | 2001-10-30 | Quinoline derivatives as inhibitors of MEK enzymes. |
Country Status (26)
| Country | Link |
|---|---|
| EP (2) | EP1584619A1 (fr) |
| JP (1) | JP2002544196A (fr) |
| KR (1) | KR100667719B1 (fr) |
| CN (1) | CN1219768C (fr) |
| AT (1) | ATE319688T1 (fr) |
| AU (1) | AU772846B2 (fr) |
| BG (1) | BG106073A (fr) |
| BR (1) | BR0010391A (fr) |
| CA (1) | CA2372663A1 (fr) |
| CZ (1) | CZ20013997A3 (fr) |
| DE (1) | DE60026509T2 (fr) |
| DK (1) | DK1178967T3 (fr) |
| EE (1) | EE200100589A (fr) |
| ES (1) | ES2258455T3 (fr) |
| GB (2) | GB9910577D0 (fr) |
| HU (1) | HUP0201219A3 (fr) |
| IL (1) | IL146317A0 (fr) |
| IS (1) | IS6138A (fr) |
| NO (1) | NO321696B1 (fr) |
| NZ (1) | NZ514980A (fr) |
| PL (1) | PL352413A1 (fr) |
| PT (1) | PT1178967E (fr) |
| SK (1) | SK16102001A3 (fr) |
| TR (1) | TR200103186T2 (fr) |
| WO (1) | WO2000068201A1 (fr) |
| ZA (1) | ZA200108971B (fr) |
Families Citing this family (81)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU8856201A (en) | 2000-09-01 | 2002-03-13 | Andel Inst Van | Inhibition of mitogen-activated protein kinase (mapk) pathway: a selective therapeutic strategy against melanoma |
| JP2004517059A (ja) | 2000-11-02 | 2004-06-10 | アストラゼネカ アクチボラグ | 抗腫瘍剤用の４−置換キノリン類 |
| EP1337524A1 (fr) * | 2000-11-02 | 2003-08-27 | AstraZeneca AB | Quinolines substituees comme agents antitumoraux |
| US7365197B2 (en) | 2000-12-29 | 2008-04-29 | Wyeth | Method for the regioselective preparation of substituted benzo[g]quinoline-3-carbonitriles and benzo[g]quinazolines |
| AU2002255852B2 (en) * | 2001-03-22 | 2006-11-09 | Van Andel Research Institute | Anthrax lethal factor inhibits tumor growth and angiogenesis |
| GB0112834D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| EP1412367A4 (fr) | 2001-06-21 | 2006-05-03 | Ariad Pharma Inc | Nouveaux quinolines et leurs utilisations |
| ES2272737T3 (es) | 2001-07-16 | 2007-05-01 | Astrazeneca Ab | Derivados de quinolina y su uso como inhibidores de tirosina quinasas. |
| AR037438A1 (es) * | 2001-11-27 | 2004-11-10 | Wyeth Corp | 3-cianoquinolinas como inhibidores de egf-r y her2 quinasas, un proceso para su preparacion, composiciones farmaceuticas y el uso de dichos compuestos para la fabricacion de medicamentos |
| WO2003048159A1 (fr) * | 2001-12-05 | 2003-06-12 | Astrazeneca Ab | Derives de la quinoleine |
| AU2002347359A1 (en) * | 2001-12-05 | 2003-06-17 | Astrazeneca Ab | Quinoline derivatives |
| WO2003047582A1 (fr) * | 2001-12-05 | 2003-06-12 | Astrazeneca Ab | Derives de la quinoleine, utilises en tant qu'agents antitumoraux |
| CN101486682B (zh) | 2002-03-13 | 2013-08-14 | 阵列生物制药公司 | 作为mek抑制剂的n3烷基化苯并咪唑衍生物 |
| US7235537B2 (en) | 2002-03-13 | 2007-06-26 | Array Biopharma, Inc. | N3 alkylated benzimidazole derivatives as MEK inhibitors |
| US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
| CN1642552B (zh) * | 2002-03-30 | 2010-05-12 | 贝林格尔英格海姆法玛两合公司 | 作为酪氨酸激酶抑制剂的4-(n-苯氨基)-喹唑啉/喹啉 |
| GB0215823D0 (en) | 2002-07-09 | 2002-08-14 | Astrazeneca Ab | Quinazoline derivatives |
| CA2491191C (fr) | 2002-07-15 | 2014-02-04 | Exelixis, Inc. | Modulateurs de kinase de type recepteur et procedes d'utilisation |
| GB0225579D0 (en) * | 2002-11-02 | 2002-12-11 | Astrazeneca Ab | Chemical compounds |
| WO2004069250A1 (fr) * | 2003-02-03 | 2004-08-19 | Astrazeneca Ab | Derives de 3-cyano-quinoline utilises comme inhibiteurs de la tyrosine kinase non associee a un recepteur |
| WO2004069249A1 (fr) * | 2003-02-03 | 2004-08-19 | Astrazeneca Ab | Derives de la 3-cyano-quinoleine, en tant qu'inhibiteurs de tyrosine kinase non recepteurs |
| WO2004106308A1 (fr) * | 2003-05-27 | 2004-12-09 | Pfizer Products Inc. | Quinazolines et pyrido[3,4-d] pyrimidines utilises comme inhibiteurs de recepteurs tyrosine kinase |
| US7144907B2 (en) | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| US7538120B2 (en) | 2003-09-03 | 2009-05-26 | Array Biopharma Inc. | Method of treating inflammatory diseases |
| ES2925655T3 (es) | 2003-09-26 | 2022-10-19 | Exelixis Inc | Moduladores c-Met y métodos de uso |
| US7517994B2 (en) | 2003-11-19 | 2009-04-14 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| SI1682138T1 (sl) | 2003-11-19 | 2011-04-29 | Array Biopharma Inc | HETEROCIKLIÄŚNI INHIBITORJI MEK-a |
| US7732616B2 (en) | 2003-11-19 | 2010-06-08 | Array Biopharma Inc. | Dihydropyridine and dihydropyridazine derivatives as inhibitors of MEK and methods of use thereof |
| NZ547327A (en) | 2003-11-21 | 2009-08-28 | Array Biopharma Inc | AKT protein kinase inhibitors |
| RU2006127414A (ru) * | 2004-01-16 | 2008-02-27 | Вайет (Us) | Хинолиновые промежуточные соединения ингибиторов рецептора тирозинкиназы и их синтез |
| TW200529846A (en) | 2004-02-20 | 2005-09-16 | Wyeth Corp | 3-quinolinecarbonitrile protein kinase inhibitors |
| EP1802579B1 (fr) | 2004-10-20 | 2013-11-20 | Merck Serono SA | Dérivés de 3-arylaminopyridine |
| FR2884516B1 (fr) * | 2005-04-15 | 2007-06-22 | Cerep Sa | Antagonistes npy, preparation et utilisations |
| US8299076B2 (en) | 2005-05-18 | 2012-10-30 | Array Biopharma Inc. | Crystalline forms of 2-(2-flouro-4-iodophenylamino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide |
| AR057455A1 (es) * | 2005-07-22 | 2007-12-05 | Merck & Co Inc | Inhibidores de la transcriptasa reversa de vih y composicion farmaceutica |
| CA2632194C (fr) * | 2005-11-15 | 2012-01-03 | Array Biopharma Inc. | Inhibiteurs erbb |
| CA2652328A1 (fr) | 2006-05-15 | 2007-11-22 | Takeda Pharmaceutical Company Limited | Agent prophylactique et therapeutique contre le cancer |
| US8329701B2 (en) | 2006-07-06 | 2012-12-11 | Array Biopharma Inc. | Dihydrofuro pyrimidines as AKT protein kinase inhibitors |
| US8063050B2 (en) | 2006-07-06 | 2011-11-22 | Array Biopharma Inc. | Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
| ATE532789T1 (de) | 2006-07-06 | 2011-11-15 | Array Biopharma Inc | Dihydrothienopyrimidine als akt-proteinkinase- inhibitoren |
| WO2008006032A1 (fr) | 2006-07-06 | 2008-01-10 | Array Biopharma Inc. | Cyclopenta [d] pyrimidines utiles en tant qu'inhibiteurs de la protéine kinase akt |
| EP1921070A1 (fr) | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | heterocycles bicycliques, medicaments á base de ces composes, leur usage et procédé pour leur preparation |
| JP5377332B2 (ja) | 2007-02-06 | 2013-12-25 | 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 | 二環式へテロ環、それらの化合物を含む薬剤、その使用及びその製法 |
| BRPI0808846A2 (pt) | 2007-03-12 | 2019-09-24 | Bayer Cropscience Ag | fenoxifenilamidinas 3-substituídas e seu uso como fungicidas |
| EP1969932A1 (fr) * | 2007-03-12 | 2008-09-17 | Bayer CropScience AG | Phenoxyphenylamidine substituée et son utilisation en tant que fongicide |
| RU2486181C2 (ru) | 2007-07-05 | 2013-06-27 | Эррэй Биофарма Инк. | Пиримидилциклопентаны как ингибиторы акт-протеинкиназ |
| US8846683B2 (en) | 2007-07-05 | 2014-09-30 | Array Biopharma, Inc. | Pyrimidyl cyclopentanes as Akt protein kinase inhibitors |
| US9409886B2 (en) | 2007-07-05 | 2016-08-09 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
| EP2173723B3 (fr) | 2007-07-05 | 2014-11-19 | Array Biopharma Inc. | Pyrimidyl cyclopentanes utilsés comme inhibiteurs de la protéine kinase akt |
| CA2705820C (fr) | 2007-11-15 | 2016-06-07 | Clanotech Ab | Derives de quinoleine et leur utilisation en tant qu'inhibiteurs de la tyrosine kinase |
| CA2705834A1 (fr) | 2007-11-20 | 2009-05-28 | Merck Sharp & Dohme Corp. | Inhibiteurs non-nucleosidiques de la transcriptase inverse |
| ES2422733T3 (es) | 2008-01-09 | 2013-09-13 | Array Biopharma Inc | Pirimidilciclopentanos hidroxilados como inhibidores de proteínas cinasas AKT |
| AU2009204019B2 (en) | 2008-01-09 | 2014-02-20 | Array Biopharma Inc. | Hydroxylated pyrimidyl cyclopentane as AKT protein kinase inhibitor |
| EA019709B1 (ru) | 2008-02-07 | 2014-05-30 | Бёрингер Ингельхайм Интернациональ Гмбх | Спирогетероциклы и их применение в качестве лекарственных средств |
| PT2307376E (pt) | 2008-08-04 | 2016-02-26 | Merck Patent Gmbh | Novos compostos de fenilamino-isonicotinamida |
| CA2733153C (fr) | 2008-08-08 | 2016-11-08 | Boehringer Ingelheim International Gmbh | Heterocycles a substitution cyclohexyloxy, medicaments contenant ces composes, leur utilisation et procedes pour les preparer |
| ES2399384T3 (es) | 2008-11-10 | 2013-04-01 | Bayer Schering Pharma Ag | Sulfonamido fenoxibenzamidas sustituidas |
| TWI447108B (zh) | 2009-01-16 | 2014-08-01 | Exelixis Inc | Ｎ－（４－｛〔６，７雙（甲氧基）喹啉－４－基〕氧基｝苯基）－ｎ’－（４－氟苯基）環丙烷－１，１－二甲醯胺之蘋果酸鹽及其結晶型 |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| EP2491014A1 (fr) | 2009-10-21 | 2012-08-29 | Bayer Pharma Aktiengesellschaft | Dérivés d'halogénophénoxybenzamide substitués |
| WO2011047788A1 (fr) | 2009-10-21 | 2011-04-28 | Bayer Schering Pharma Aktiengesellschaft | Benzosulfonamides substitués |
| EP2491016A1 (fr) | 2009-10-21 | 2012-08-29 | Bayer Pharma Aktiengesellschaft | Benzosulfonamides substitués |
| CA2781685C (fr) * | 2009-12-11 | 2018-09-04 | Autifony Therapeutics Limited | Derives d'imidazolidinedione |
| AU2011264209B2 (en) | 2010-06-09 | 2014-08-07 | Tianjin Hemay Oncology Pharmaceutical Co., Ltd | Cyanoquinoline derivatives |
| JP2013542214A (ja) | 2010-10-29 | 2013-11-21 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 置換フェノキシピリジン類 |
| CN102020651B (zh) | 2010-11-02 | 2012-07-18 | 北京赛林泰医药技术有限公司 | 6-芳基氨基吡啶酮甲酰胺mek抑制剂 |
| CN103857395A (zh) | 2011-04-01 | 2014-06-11 | 基因泰克公司 | Akt抑制剂化合物和阿比特龙的组合及使用方法 |
| JP6147246B2 (ja) | 2011-04-01 | 2017-06-14 | ジェネンテック， インコーポレイテッド | Ａｋｔ及びｍｅｋ阻害剤化合物の組み合わせ、及び使用方法 |
| WO2012160130A1 (fr) | 2011-05-25 | 2012-11-29 | Universite Paris Descartes | Inhibiteurs de la voie erk pour le traitement de l'amyotrophie spinale |
| CN103204822B (zh) | 2012-01-17 | 2014-12-03 | 上海科州药物研发有限公司 | 作为蛋白激酶抑制剂的苯并噁唑化合物及其制备方法和用途 |
| WO2015038704A1 (fr) | 2013-09-11 | 2015-03-19 | The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone | Compositions pour prépaprer des cardiomyocytes |
| CA2963091A1 (fr) | 2014-10-06 | 2016-04-14 | Dana-Farber Cancer Institute, Inc. | Biomarqueurs a base d'angiopoietine -2 utilises pour la prediction de la reponse de point de controle anti-immunitaire |
| MA41866A (fr) | 2015-03-31 | 2018-02-06 | Massachusetts Gen Hospital | Molécules à auto-assemblage pour l'administration ciblée de médicaments |
| WO2017040982A1 (fr) * | 2015-09-02 | 2017-03-09 | The Regents Of The University Of California | Ligands her3 et utilisations de ceux-ci |
| BR112018006873A2 (pt) | 2015-10-05 | 2018-11-06 | The Trustees Of Columbia University In The City Of New York | ativadores do fluxo autofágico e fosfolipase d e depuração de agregados de proteína incluindo tau e tratamento de proteinopatias |
| WO2019042409A1 (fr) * | 2017-09-01 | 2019-03-07 | 上海医药集团股份有限公司 | Composé hétérocyclique azoté, procédé de préparation, intermédiaire, composition et application |
| AU2019289917A1 (en) * | 2018-06-21 | 2021-01-07 | Cellestia Biotech Ag | Process for making amino diaryl ethers and amino diaryl ethers hydrochloride salts |
| US20220143049A1 (en) | 2019-03-21 | 2022-05-12 | Onxeo | A dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| EP4054579A1 (fr) | 2019-11-08 | 2022-09-14 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Méthodes pour le traitement de cancers qui ont acquis une résistance aux inhibiteurs de kinase |
| WO2021148581A1 (fr) | 2020-01-22 | 2021-07-29 | Onxeo | Nouvelle molécule dbait et son utilisation |
| TW202342018A (zh) | 2022-03-04 | 2023-11-01 | 美商奇奈特生物製藥公司 | Mek激酶抑制劑 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE300521T1 (de) * | 1996-09-25 | 2005-08-15 | Astrazeneca Ab | Chinolin-derivate die den effekt von wachstumsfaktoren wie vegf vezögern |
| UA73073C2 (uk) * | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
| HUP0003731A3 (en) * | 1997-07-01 | 2002-11-28 | Warner Lambert Co | 4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives and their use as mek inhibitors |
| DK1117659T3 (da) * | 1998-09-29 | 2004-03-22 | Wyeth Corp | Substituerede 3-cyanoquinoliner som hæmmere af proteintyrosinkinaser |
| AU6159499A (en) * | 1998-09-29 | 2000-04-17 | Wyeth Holdings Corporation | Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors |
-
1999
- 1999-05-08 GB GBGB9910577.7A patent/GB9910577D0/en not_active Ceased
-
2000
- 2000-04-19 GB GBGB0009532.3A patent/GB0009532D0/en not_active Ceased
- 2000-05-03 EP EP05013587A patent/EP1584619A1/fr not_active Withdrawn
- 2000-05-03 SK SK1610-2001A patent/SK16102001A3/sk unknown
- 2000-05-03 AT AT00927491T patent/ATE319688T1/de not_active IP Right Cessation
- 2000-05-03 DK DK00927491T patent/DK1178967T3/da active
- 2000-05-03 DE DE60026509T patent/DE60026509T2/de not_active Expired - Fee Related
- 2000-05-03 JP JP2000617181A patent/JP2002544196A/ja active Pending
- 2000-05-03 AU AU45891/00A patent/AU772846B2/en not_active Ceased
- 2000-05-03 KR KR1020017014244A patent/KR100667719B1/ko not_active IP Right Cessation
- 2000-05-03 PL PL00352413A patent/PL352413A1/xx not_active Application Discontinuation
- 2000-05-03 EP EP00927491A patent/EP1178967B1/fr not_active Expired - Lifetime
- 2000-05-03 CA CA002372663A patent/CA2372663A1/fr not_active Abandoned
- 2000-05-03 CN CNB008099596A patent/CN1219768C/zh not_active Expired - Fee Related
- 2000-05-03 BR BR0010391-8A patent/BR0010391A/pt not_active Application Discontinuation
- 2000-05-03 EE EEP200100589A patent/EE200100589A/xx unknown
- 2000-05-03 ES ES00927491T patent/ES2258455T3/es not_active Expired - Lifetime
- 2000-05-03 TR TR2001/03186T patent/TR200103186T2/xx unknown
- 2000-05-03 NZ NZ514980A patent/NZ514980A/en unknown
- 2000-05-03 WO PCT/GB2000/001697 patent/WO2000068201A1/fr active IP Right Grant
- 2000-05-03 IL IL14631700A patent/IL146317A0/xx unknown
- 2000-05-03 PT PT00927491T patent/PT1178967E/pt unknown
- 2000-05-03 CZ CZ20013997A patent/CZ20013997A3/cs unknown
- 2000-05-03 HU HU0201219A patent/HUP0201219A3/hu unknown
-
2001
- 2001-10-30 IS IS6138A patent/IS6138A/is unknown
- 2001-10-30 ZA ZA200108971A patent/ZA200108971B/en unknown
- 2001-11-01 BG BG106073A patent/BG106073A/xx unknown
- 2001-11-07 NO NO20015448A patent/NO321696B1/no unknown
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