JP2007516206A - トリアゾロトリアジン化合物およびそれらの使用 - Google Patents
トリアゾロトリアジン化合物およびそれらの使用 Download PDFInfo
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- JP2007516206A JP2007516206A JP2006518669A JP2006518669A JP2007516206A JP 2007516206 A JP2007516206 A JP 2007516206A JP 2006518669 A JP2006518669 A JP 2006518669A JP 2006518669 A JP2006518669 A JP 2006518669A JP 2007516206 A JP2007516206 A JP 2007516206A
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- 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
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US48422103P | 2003-07-02 | 2003-07-02 | |
| US10/874,743 US7122548B2 (en) | 2003-07-02 | 2004-06-24 | Triazolotriazine compounds and uses thereof |
| PCT/US2004/020054 WO2005010005A1 (en) | 2003-07-02 | 2004-06-25 | Triazolotriazine compounds and uses thereof |
Publications (2)
| Publication Number | Publication Date |
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| JP2007516206A true JP2007516206A (ja) | 2007-06-21 |
| JP2007516206A5 JP2007516206A5 (https=) | 2007-08-09 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| JP2006518669A Withdrawn JP2007516206A (ja) | 2003-07-02 | 2004-06-25 | トリアゾロトリアジン化合物およびそれらの使用 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US7122548B2 (https=) |
| EP (1) | EP1644377A4 (https=) |
| JP (1) | JP2007516206A (https=) |
| CA (1) | CA2529238A1 (https=) |
| WO (1) | WO2005010005A1 (https=) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US7550470B2 (en) * | 2002-12-11 | 2009-06-23 | Merck & Co. Inc. | Substituted pyrazolo[1,5-A]pyrimidines as tyrosine kinase inhibitors |
| CN101198590B (zh) | 2005-08-24 | 2012-05-09 | 卫材R&D管理有限公司 | 吡啶衍生物及嘧啶衍生物（3） |
| CN101360748B (zh) * | 2005-11-30 | 2012-05-30 | 沃泰克斯药物股份有限公司 | c-MET抑制剂及其应用 |
| RU2419620C2 (ru) * | 2005-11-30 | 2011-05-27 | Вертекс Фармасьютикалз Инкорпорейтед | Ингибиторы с-мет и их применение |
| KR20080080584A (ko) * | 2005-11-30 | 2008-09-04 | 버텍스 파마슈티칼스 인코포레이티드 | ｃ-Ｍｅｔ의 억제제 및 이의 용도 |
| HRP20170103T1 (hr) | 2005-12-21 | 2017-03-24 | Janssen Pharmaceutica N.V. | Triazolopiridazini kao modulatori tirozin kinaze |
| WO2007103308A2 (en) | 2006-03-07 | 2007-09-13 | Array Biopharma Inc. | Heterobicyclic pyrazole compounds and methods of use |
| JP2009539878A (ja) * | 2006-06-08 | 2009-11-19 | アレイ バイオファーマ、インコーポレイテッド | キノリン化合物および使用方法 |
| US8198448B2 (en) | 2006-07-14 | 2012-06-12 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| PE20080403A1 (es) | 2006-07-14 | 2008-04-25 | Amgen Inc | Derivados heterociclicos fusionados y metodos de uso |
| US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| EP2057164A1 (en) * | 2006-08-07 | 2009-05-13 | Incyte Corporation | Triazolotriazines as kinase inhibitors |
| CA2661333C (en) | 2006-08-23 | 2014-08-05 | Eisai R&D Management Co., Ltd. | Salt of phenoxypyridine derivative or crystal thereof and process for producing the same |
| US7790885B2 (en) | 2006-08-31 | 2010-09-07 | Eisai R&D Management Co., Ltd. | Process for preparing phenoxypyridine derivatives |
| WO2008030744A2 (en) * | 2006-09-05 | 2008-03-13 | Board Of Regents, The University Of Texas System | Inhibitors of c-met and uses thereof |
| JP2010519174A (ja) * | 2006-09-18 | 2010-06-03 | バーテックス ファーマシューティカルズ インコーポレイテッド | ｃ−Ｍｅｔの複素環阻害薬およびその使用方法 |
| ES2555803T3 (es) | 2006-10-23 | 2016-01-08 | Cephalon, Inc. | Fusión de derivados bicíclicos 2,4-diaminopirimidina como utilizar inhibidores ALK y c-Met |
| BRPI0717320A2 (pt) * | 2006-10-23 | 2013-10-22 | Sgx Pharmaceuticals Inc | Triazóis bicíclicos como moduladores de proteína cinase |
| RS54510B1 (sr) * | 2006-11-22 | 2016-06-30 | Incyte Holdings Corporation | Imidazotriazini i imidazopirimidini kao inhibitori kinaze |
| WO2008079294A1 (en) * | 2006-12-20 | 2008-07-03 | Amgen Inc. | Substituted heterocycles and methods of use |
| AU2007338792B2 (en) | 2006-12-20 | 2012-05-31 | Amgen Inc. | Substituted heterocycles and methods of use |
| US8066118B1 (en) | 2006-12-25 | 2011-11-29 | Marty Van Tassell | Device for using nonwoven towels in the dairy industry |
| EP2170894A1 (en) * | 2007-06-21 | 2010-04-07 | Janssen Pharmaceutica N.V. | Polymorphic and hydrate forms, salts and process for preparing 6-{difluoro[6-(1-methyl-1h-pyrazol-4-yl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}quinoline |
| JP2009132660A (ja) | 2007-11-30 | 2009-06-18 | Eisai R & D Management Co Ltd | 食道癌治療用組成物 |
| UY31676A1 (es) | 2008-02-28 | 2009-09-30 | "derivados de 3-metil-imidiazo-[1,2-b]-piridazina" | |
| TWI472529B (zh) | 2008-05-21 | 2015-02-11 | Incyte Corp | ２－氟－Ｎ－甲基－４－〔７－（喹啉－６－基－甲基）－咪唑并〔１，２－ｂ〕〔１，２，４〕三－２－基〕苯甲醯胺之鹽類及其相關製備方法 |
| CA2724715A1 (en) | 2008-05-22 | 2009-11-26 | Amgen Inc. | Heterocycles as protein kinase inhibitors |
| CN102137939A (zh) * | 2008-08-29 | 2011-07-27 | 霍夫曼-拉罗奇有限公司 | 不依赖vegf的肿瘤的诊断和治疗 |
| JP2012504606A (ja) * | 2008-10-01 | 2012-02-23 | ラディック インスティテュート フォー キャンサー リサーチ | 癌の治療方法 |
| US8592448B2 (en) | 2008-11-20 | 2013-11-26 | OSI Pharmaceuticals, LLC | Substituted pyrrolo[2,3-b]-pyridines and -pyrazines |
| NZ596616A (en) * | 2009-05-28 | 2013-05-31 | Vertex Pharma | Aminopyrazole triazolothiadiazole inhibitors of c-met protien kinase |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| EA201200260A1 (ru) | 2009-08-12 | 2012-09-28 | Новартис Аг | Гетероциклические гидразоны и их применение для лечения рака и воспаления |
| CA2771432A1 (en) | 2009-08-20 | 2011-02-24 | Novartis Ag | Heterocyclic oxime compounds |
| EA030141B1 (ru) | 2009-12-31 | 2018-06-29 | Хатчисон Медифарма Лимитед | Определенные триазолопиридины и триазолопиразины, их композиции и способы их применения |
| MX2012008898A (es) | 2010-02-03 | 2012-11-06 | Incyte Corp | Imidazo - [1, 2 - b] [1, 2, 4] triazinas como inhibidores de c - met. |
| AR081039A1 (es) | 2010-05-14 | 2012-05-30 | Osi Pharmaceuticals Llc | Inhibidores biciclicos fusionados de quinasa |
| EP2569315A1 (en) | 2010-05-14 | 2013-03-20 | OSI Pharmaceuticals, LLC | Fused bicyclic kinase inhibitors |
| CN102532141A (zh) | 2010-12-08 | 2012-07-04 | 中国科学院上海药物研究所 | [1，2，4]三唑并[4，3-b][1，2，4]三嗪类化合物、其制备方法和用途 |
| JP2014513724A (ja) | 2011-05-16 | 2014-06-05 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 融合二環キナーゼ阻害剤 |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| RU2016141385A (ru) | 2014-03-24 | 2018-04-28 | Дженентек, Инк. | Лечение рака антагонистами с-мет и их корреляция с экспрессией hgf |
| WO2020103939A1 (zh) * | 2018-11-22 | 2020-05-28 | 上海科技大学 | 三唑并环类化合物、其制备方法、中间体和应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1042471A (en) | 1963-01-16 | 1966-09-14 | Ilford Ltd | Penta-azaindenes, their production and use in photographic emulsions |
| FR1379480A (fr) | 1963-01-16 | 1964-11-20 | Ilford Ltd | Nouveaux penta-aza-indènes, préparation et utilisation de ces composés |
| GB1028809A (en) | 1964-01-21 | 1966-05-11 | Ferrania Spa | Process for stabilizing photographic emulsions |
| US4405619A (en) | 1981-09-02 | 1983-09-20 | Diamond Shamrock Corporation | Antiinflammatory substituted-1,2,4-triazolo[4,3-b]-1,2,4-triazines |
| IT1269176B (it) | 1994-01-11 | 1997-03-21 | Isagro Srl | Eterobicicli ad attivita' fungicida |
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2004
- 2004-06-24 US US10/874,743 patent/US7122548B2/en not_active Expired - Fee Related
- 2004-06-25 EP EP04776943A patent/EP1644377A4/en not_active Withdrawn
- 2004-06-25 JP JP2006518669A patent/JP2007516206A/ja not_active Withdrawn
- 2004-06-25 WO PCT/US2004/020054 patent/WO2005010005A1/en not_active Ceased
- 2004-06-25 CA CA002529238A patent/CA2529238A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA2529238A1 (en) | 2005-02-03 |
| EP1644377A4 (en) | 2007-09-05 |
| EP1644377A1 (en) | 2006-04-12 |
| WO2005010005A1 (en) | 2005-02-03 |
| US20050075340A1 (en) | 2005-04-07 |
| US7122548B2 (en) | 2006-10-17 |
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