NO321696B1 - Kinolinderivater som inhibitorer av MEK-enzymer, fremgangsmate for fremstilling og anvendelse derav, samt farmasoytisk preparat. - Google Patents
Kinolinderivater som inhibitorer av MEK-enzymer, fremgangsmate for fremstilling og anvendelse derav, samt farmasoytisk preparat. Download PDFInfo
- Publication number
- NO321696B1 NO321696B1 NO20015448A NO20015448A NO321696B1 NO 321696 B1 NO321696 B1 NO 321696B1 NO 20015448 A NO20015448 A NO 20015448A NO 20015448 A NO20015448 A NO 20015448A NO 321696 B1 NO321696 B1 NO 321696B1
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- Prior art keywords
- carbon atoms
- alkyl
- formula
- optionally substituted
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- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
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- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- PSACHCMMPFMFAJ-UHFFFAOYSA-N nmm n-methylmorpholine Chemical compound CN1CCOCC1.CN1CCOCC1 PSACHCMMPFMFAJ-UHFFFAOYSA-N 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000009701 normal cell proliferation Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
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- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- QZZYYBQGTSGDPP-UHFFFAOYSA-N quinoline-3-carbonitrile Chemical class C1=CC=CC2=CC(C#N)=CN=C21 QZZYYBQGTSGDPP-UHFFFAOYSA-N 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- 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
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Quinoline Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Luminescent Compositions (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9910577.7A GB9910577D0 (en) | 1999-05-08 | 1999-05-08 | Chemical compounds |
| PCT/GB2000/001697 WO2000068201A1 (en) | 1999-05-08 | 2000-05-03 | Quinoline derivatives as inhibitors of mek enzymes |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20015448D0 NO20015448D0 (no) | 2001-11-07 |
| NO20015448L NO20015448L (no) | 2002-01-07 |
| NO321696B1 true NO321696B1 (no) | 2006-06-26 |
Family
ID=10852987
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20015448A NO321696B1 (no) | 1999-05-08 | 2001-11-07 | Kinolinderivater som inhibitorer av MEK-enzymer, fremgangsmate for fremstilling og anvendelse derav, samt farmasoytisk preparat. |
Country Status (26)
| Country | Link |
|---|---|
| EP (2) | EP1584619A1 (is) |
| JP (1) | JP2002544196A (is) |
| KR (1) | KR100667719B1 (is) |
| CN (1) | CN1219768C (is) |
| AT (1) | ATE319688T1 (is) |
| AU (1) | AU772846B2 (is) |
| BG (1) | BG106073A (is) |
| BR (1) | BR0010391A (is) |
| CA (1) | CA2372663A1 (is) |
| CZ (1) | CZ20013997A3 (is) |
| DE (1) | DE60026509T2 (is) |
| DK (1) | DK1178967T3 (is) |
| EE (1) | EE200100589A (is) |
| ES (1) | ES2258455T3 (is) |
| GB (2) | GB9910577D0 (is) |
| HU (1) | HUP0201219A3 (is) |
| IL (1) | IL146317A0 (is) |
| IS (1) | IS6138A (is) |
| NO (1) | NO321696B1 (is) |
| NZ (1) | NZ514980A (is) |
| PL (1) | PL352413A1 (is) |
| PT (1) | PT1178967E (is) |
| SK (1) | SK16102001A3 (is) |
| TR (1) | TR200103186T2 (is) |
| WO (1) | WO2000068201A1 (is) |
| ZA (1) | ZA200108971B (is) |
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| 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 |
| EP1337524A1 (en) * | 2000-11-02 | 2003-08-27 | AstraZeneca AB | Substituted quinolines as antitumor agents |
| EP1337513A1 (en) * | 2000-11-02 | 2003-08-27 | AstraZeneca AB | 4-substituted quinolines as antitumor agents |
| WO2002053528A1 (en) | 2000-12-29 | 2002-07-11 | Wyeth | Method for the regioselective preparation of substituted benzo[g]quinoline-3-carbonitriles and benzo[g]quinazolines |
| WO2002076496A1 (en) * | 2001-03-22 | 2002-10-03 | Van Andel Institute | Anthrax lethal factor inhibits tumor growth and angiogenesis |
| GB0112834D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| US6706699B2 (en) | 2001-06-21 | 2004-03-16 | Ariad Pharmaceuticals, Inc. | Quinolines and uses thereof |
| JP4326328B2 (ja) | 2001-07-16 | 2009-09-02 | アストラゼネカ アクチボラグ | キノリン誘導体及びそれらのチロシンキナーゼ阻害薬としての使用 |
| PL370137A1 (en) * | 2001-11-27 | 2005-05-16 | Wyeth Holdings Corporation | 3-cyanoquinolines as inhibitors of egf-r and her2 kinases |
| WO2003047582A1 (en) * | 2001-12-05 | 2003-06-12 | Astrazeneca Ab | Quinoline derivatives as antitumour agents |
| AU2002347359A1 (en) * | 2001-12-05 | 2003-06-17 | Astrazeneca Ab | Quinoline derivatives |
| WO2003048159A1 (en) * | 2001-12-05 | 2003-06-12 | Astrazeneca Ab | Quinoline derivatives |
| HUE025767T2 (en) | 2002-03-13 | 2016-05-30 | Array Biopharma Inc | N3-alkylated benzimidazole derivatives as MEK inhibitors |
| US7235537B2 (en) | 2002-03-13 | 2007-06-26 | Array Biopharma, Inc. | N3 alkylated benzimidazole derivatives as MEK inhibitors |
| AU2003226705B2 (en) * | 2002-03-30 | 2008-11-06 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 4-(N-phenylamino)-quinazolines / quinolines as tyrosine kinase 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 |
| GB0215823D0 (en) | 2002-07-09 | 2002-08-14 | Astrazeneca Ab | Quinazoline derivatives |
| ES2400339T3 (es) | 2002-07-15 | 2013-04-09 | Symphony Evolution, Inc. | Compuestos, composiciones farmacéuticas de los mismos y su uso en el tratamiento del cáncer |
| GB0225579D0 (en) * | 2002-11-02 | 2002-12-11 | Astrazeneca Ab | Chemical compounds |
| WO2004069250A1 (en) * | 2003-02-03 | 2004-08-19 | Astrazeneca Ab | 3-cyano-quinoline derivatives as non-receptor tyrosine kinase inhibitors |
| WO2004069249A1 (en) * | 2003-02-03 | 2004-08-19 | Astrazeneca Ab | 3-cyano-quinoline derivatives as non-receptor tyrosine kinase inhibitors |
| CA2527017A1 (en) * | 2003-05-27 | 2004-12-09 | Pfizer Products Inc. | Quinazolines and pyrido [3,4-d] pyrimidines as receptor tyrosine kinase inhibitors |
| US7538120B2 (en) | 2003-09-03 | 2009-05-26 | Array Biopharma Inc. | Method of treating inflammatory diseases |
| US7144907B2 (en) | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| JP4638436B2 (ja) | 2003-09-26 | 2011-02-23 | エグゼリクシス， インコーポレイテッド | ｃ−Ｍｅｔモジュレーターおよびその使用 |
| US7517994B2 (en) | 2003-11-19 | 2009-04-14 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| US7732616B2 (en) | 2003-11-19 | 2010-06-08 | Array Biopharma Inc. | Dihydropyridine and dihydropyridazine derivatives as inhibitors of MEK and methods of use thereof |
| AU2004293019B2 (en) | 2003-11-19 | 2010-10-28 | Array Biopharma Inc. | Bicyclic inhibitors of MEK and methods of use thereof |
| EP1684694A2 (en) | 2003-11-21 | 2006-08-02 | Array Biopharma, Inc. | Akt protein kinase inhibitors |
| US7432377B2 (en) * | 2004-01-16 | 2008-10-07 | Wyeth | Quinoline intermediates of receptor tyrosine kinase inhibitors and the synthesis thereof |
| TW200529846A (en) | 2004-02-20 | 2005-09-16 | Wyeth Corp | 3-quinolinecarbonitrile protein kinase inhibitors |
| EP1802579B1 (en) | 2004-10-20 | 2013-11-20 | Merck Serono SA | Derivatives of 3-arylaminopyridine |
| FR2884516B1 (fr) * | 2005-04-15 | 2007-06-22 | Cerep Sa | Antagonistes npy, preparation et utilisations |
| ES2405785T3 (es) | 2005-05-18 | 2013-06-03 | Array Biopharma Inc. | Inhibidores heterocíclicos de MEK y métodos de uso de los mismos |
| AR057455A1 (es) | 2005-07-22 | 2007-12-05 | Merck & Co Inc | Inhibidores de la transcriptasa reversa de vih y composicion farmaceutica |
| PT2090575E (pt) | 2005-11-15 | 2011-06-06 | Array Biopharma Inc | Inibidores de erbb |
| CA2652328A1 (en) | 2006-05-15 | 2007-11-22 | Takeda Pharmaceutical Company Limited | Prophylactic and therapeutic agent for cancer |
| CA2656618C (en) | 2006-07-06 | 2014-08-26 | Array Biopharma Inc. | Cyclopenta [d] 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 |
| ATE493418T1 (de) | 2006-07-06 | 2011-01-15 | Array Biopharma Inc | Dihydrofuropyrimidine als akt- proteinkinaseinhibitoren |
| EP2054418B1 (en) | 2006-07-06 | 2011-11-09 | Array Biopharma Inc. | Dihydrothieno pyrimidines as akt protein kinase inhibitors |
| EP1921070A1 (de) | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung |
| MX2009007610A (es) | 2007-02-06 | 2009-07-24 | Boehringer Ingelheim Int | Heterociclicos biciclicos, medicamentos que contienen estos compuestos, su utilizacion y procedimientos para su preparacion. |
| EP1969932A1 (de) * | 2007-03-12 | 2008-09-17 | Bayer CropScience AG | Phenoxyphenylamidine und deren Verwendung als Fungizide |
| WO2008110280A2 (de) | 2007-03-12 | 2008-09-18 | Bayer Cropscience Ag | Phenoxy-substitutierte phenylamidin-derivativen und deren verwendung als fungiziden |
| JP5542282B2 (ja) | 2007-07-05 | 2014-07-09 | アレイ バイオファーマ、インコーポレイテッド | Ａｋｔプロテインキナーゼ阻害剤としてのピリミジルシクロペンタン |
| CN101801955B (zh) | 2007-07-05 | 2013-05-08 | 阵列生物制药公司 | 作为akt蛋白激酶抑制剂的嘧啶基环戊烷 |
| 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 |
| WO2009063070A2 (en) * | 2007-11-15 | 2009-05-22 | Clanotech Ab | Quinoline derivatives and their use as tyrosine kinase inhibitors |
| MX2010005483A (es) | 2007-11-20 | 2010-06-11 | Merck Sharp & Dohme | Inhibidores de transcriptasa inversa no nucleosidos. |
| AU2009204025B2 (en) | 2008-01-09 | 2014-02-20 | Array Biopharma Inc. | Hydroxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
| AU2009204019B2 (en) | 2008-01-09 | 2014-02-20 | Array Biopharma Inc. | Hydroxylated pyrimidyl cyclopentane as AKT protein kinase inhibitor |
| SI2245026T1 (sl) | 2008-02-07 | 2012-12-31 | Boehringer Ingelheim International Gmbh | Spirociklični heterocikli, zdravila, ki vsebujejo te spojine, njihova uporaba in postopek za njihovo pripravo |
| BRPI0916566B8 (pt) | 2008-08-04 | 2021-05-25 | Merck Patent Ges Mit Beschraenkter Haftung | isonicotinamida fenilamina, seu uso, composição farmacêutica, e kit |
| WO2010015522A1 (de) | 2008-08-08 | 2010-02-11 | Boehringer Ingelheim International Gmbh | Cyclohexyloxy-substituierte heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| ES2399384T3 (es) | 2008-11-10 | 2013-04-01 | Bayer Schering Pharma Ag | Sulfonamido fenoxibenzamidas sustituidas |
| TWI577664B (zh) | 2009-01-16 | 2017-04-11 | 艾克塞里克斯公司 | Ｎ-（４-｛〔６，７-雙（甲氧基）喹啉-４-基〕氧基｝苯基）-ｎ’-（４-氟苯基）環丙烷-１，１-二甲醯胺蘋果酸鹽、包含其之醫藥組合物及其用途 |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| EP2491014A1 (en) | 2009-10-21 | 2012-08-29 | Bayer Pharma Aktiengesellschaft | Substituted halophenoxybenzamide derivatives |
| EP2491016A1 (en) | 2009-10-21 | 2012-08-29 | Bayer Pharma Aktiengesellschaft | Substituted benzosulphonamides |
| WO2011047788A1 (en) | 2009-10-21 | 2011-04-28 | Bayer Schering Pharma Aktiengesellschaft | Substituted benzosulphonamides |
| BR112012015868A2 (pt) * | 2009-12-11 | 2017-06-20 | Autifony Therapeutics Ltd | derivados de imidazolidinadiona |
| US9187458B2 (en) | 2010-06-09 | 2015-11-17 | Tianjin Hemay Bio-Tech Co., Ltd. | Cyanoquinoline derivatives |
| EP2632899A1 (en) | 2010-10-29 | 2013-09-04 | Bayer Intellectual Property GmbH | Substituted phenoxypyridines |
| 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 |
| RU2631240C2 (ru) | 2011-04-01 | 2017-09-20 | Дженентек, Инк. | Комбинации соединений-ингибиторов акт и абиратерона, и способы применения |
| MX2013011333A (es) | 2011-04-01 | 2014-04-16 | Genentech Inc | Combinaciones de compuestos inhibidores de akt y mek, y metodos de uso. |
| WO2012160130A1 (en) | 2011-05-25 | 2012-11-29 | Universite Paris Descartes | Erk inhibitors for use in treating spinal muscular atrophy |
| CN103204827B (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噻二唑化合物及其制备方法和用途 |
| WO2015038704A1 (en) | 2013-09-11 | 2015-03-19 | The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone | Compositions for preparing cardiomyocytes |
| AU2015328411C1 (en) | 2014-10-06 | 2022-03-03 | Dana-Farber Cancer Institute, Inc. | Angiopoietin-2 biomarkers predictive of anti-immune checkpoint response |
| MA41866A (fr) | 2015-03-31 | 2018-02-06 | Massachusetts Gen Hospital | Molécules à auto-assemblage pour l'administration ciblée de médicaments |
| WO2017040982A1 (en) * | 2015-09-02 | 2017-03-09 | The Regents Of The University Of California | Her3 ligands and uses thereof |
| MX2018004109A (es) | 2015-10-05 | 2018-09-27 | Univ Columbia | Activadores de flujo autofágico y fosfolipasa d y depuración de acumulaciones de proteína que incluyen tau y tratamiento de proteinopatías. |
| US11578074B2 (en) | 2017-09-01 | 2023-02-14 | Shanghai Pharmaceuticals Holding Cd., Ltd. | Nitrogenous heterocyclic compound, preparation method, intermediate, composition, and application |
| KR20210034587A (ko) * | 2018-06-21 | 2021-03-30 | 셀레스티아 바이오테크 아게 | 아미노 디아릴 에테르 및 아미노 디아릴 에테르 하이드로클로라이드염의 제조 방법 |
| CA3129665A1 (en) | 2019-03-21 | 2020-09-24 | Onxeo | A dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| KR20220098759A (ko) | 2019-11-08 | 2022-07-12 | 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) | 키나제 억제제에 대해 내성을 획득한 암의 치료 방법 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| 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 |
|---|---|---|---|---|
| AU733551B2 (en) * | 1996-09-25 | 2001-05-17 | Astrazeneca Ab | Qinoline derivatives inhibiting the effect of growth factors such as VEGF |
| UA73073C2 (uk) * | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
| PT993439E (pt) * | 1997-07-01 | 2004-12-31 | Warner Lambert Co | Derivados de acido 4-bromo ou 4-iodofenilaminobenzidroxamico e sua utilizacao como inibidores de mek |
| SI2253620T1 (sl) * | 1998-09-29 | 2014-06-30 | Wyeth Holdings Llc | Substituirani 3-cianokinolini kot inhibitorji protein tirozin-kinaz |
| PT1117659E (pt) * | 1998-09-29 | 2004-04-30 | Wyeth Corp | Cianoquinolinas substituidas como inibidores de tirosina-quinases de proteinas |
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1999
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2000
- 2000-04-19 GB GBGB0009532.3A patent/GB0009532D0/en not_active Ceased
- 2000-05-03 TR TR2001/03186T patent/TR200103186T2/xx unknown
- 2000-05-03 EP EP05013587A patent/EP1584619A1/en not_active Withdrawn
- 2000-05-03 BR BR0010391-8A patent/BR0010391A/pt not_active Application Discontinuation
- 2000-05-03 DK DK00927491T patent/DK1178967T3/da active
- 2000-05-03 NZ NZ514980A patent/NZ514980A/en unknown
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- 2000-05-03 AU AU45891/00A patent/AU772846B2/en not_active Ceased
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- 2000-05-03 EE EEP200100589A patent/EE200100589A/xx unknown
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- 2000-05-03 JP JP2000617181A patent/JP2002544196A/ja active Pending
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- 2000-05-03 KR KR1020017014244A patent/KR100667719B1/ko not_active IP Right Cessation
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