RU2384331C2 - Способ лечения аномального роста клеток - Google Patents
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- RU2384331C2 RU2384331C2 RU2008122471/14A RU2008122471A RU2384331C2 RU 2384331 C2 RU2384331 C2 RU 2384331C2 RU 2008122471/14 A RU2008122471/14 A RU 2008122471/14A RU 2008122471 A RU2008122471 A RU 2008122471A RU 2384331 C2 RU2384331 C2 RU 2384331C2
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Cited By (4)
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|---|---|---|---|---|
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Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4242911B2 (ja) | 2004-08-26 | 2009-03-25 | ファイザー・インク | プロテインキナーゼ阻害薬としてのエナンチオピュアなアミノヘテロアリール化合物 |
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| US7790885B2 (en) | 2006-08-31 | 2010-09-07 | Eisai R&D Management Co., Ltd. | Process for preparing phenoxypyridine derivatives |
| JP2009132660A (ja) * | 2007-11-30 | 2009-06-18 | Eisai R & D Management Co Ltd | 食道癌治療用組成物 |
| DE102007061963A1 (de) | 2007-12-21 | 2009-06-25 | Merck Patent Gmbh | Pyridazinonderivate |
| US20090227556A1 (en) * | 2008-01-31 | 2009-09-10 | Eisai R&D Management Co., Ltd. | Receptor tyrosine kinase inhibitors comprising pyridine and pyrimidine derivatives |
| US20110206691A1 (en) | 2008-02-15 | 2011-08-25 | Mosse Yael P | Methods and Compositions for Treating Neuroblastoma |
| WO2009103061A2 (en) * | 2008-02-15 | 2009-08-20 | The Children's Hospital Of Philadelphia | Methods and compositions for identifying, diagnosing, and treating neuroblastoma |
| EP2248810A4 (en) * | 2008-02-18 | 2011-05-25 | Eisai R&D Man Co Ltd | METHOD FOR PRODUCING A PHENOXYPYRIDINE DERIVATIVE |
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| DE102009003954A1 (de) | 2009-01-07 | 2010-07-08 | Merck Patent Gmbh | Pyridazinonderivate |
| DE102009004061A1 (de) | 2009-01-08 | 2010-07-15 | Merck Patent Gmbh | Pyridazinonderivate |
| WO2011095196A1 (en) | 2010-02-05 | 2011-08-11 | Merck Patent Gmbh | Hetaryl-[1,8]naphthyridine derivatives |
| CA2780922A1 (en) * | 2010-02-11 | 2011-08-18 | OSI Pharmaceuticals, LLC | 7-aminofuropyridine derivatives |
| WO2011138751A2 (en) | 2010-05-04 | 2011-11-10 | Pfizer Inc. | Heterocyclic derivatives as alk inhibitors |
| CA2802644C (en) | 2010-06-25 | 2017-02-21 | Eisai R & D Management Co., Ltd. | Antitumor agent using compounds having kinase inhibitory effect in combination |
| EA201300080A1 (ru) | 2010-07-05 | 2013-06-28 | Мерк Патент Гмбх | Дипиридильные производные, пригодные для лечения заболеваний, индуцированных киназами |
| WO2012019132A2 (en) | 2010-08-06 | 2012-02-09 | Cell Signaling Technology, Inc. | Anaplastic lymphoma kinase in kidney cancer |
| WO2012119006A2 (en) * | 2011-03-03 | 2012-09-07 | Concert Pharmaceuticals, Inc. | Derivatives of pyrazole-substituted amino-heteroaryl compounds |
| US9145390B2 (en) | 2011-03-03 | 2015-09-29 | Concert Pharmaceuticals, Inc. | Derivatives of pyrazole-substituted amino-heteroaryl compounds |
| KR20140022829A (ko) | 2011-03-09 | 2014-02-25 | 메르크 파텐트 게엠베하 | 피리도 [2, 3 - ｂ] 피라진 유도체 및 그 치료적 용도 |
| US20140350050A1 (en) * | 2011-09-21 | 2014-11-27 | Teligene Ltd. | Pyridine compounds as inhibitors of kinase |
| PT2810937T (pt) | 2012-01-31 | 2017-03-03 | Daiichi Sankyo Co Ltd | Derivado de piridona |
| EP2822953B9 (en) | 2012-03-06 | 2017-06-21 | Pfizer Inc | Macrocyclic derivatives for the treatment of proliferative diseases |
| WO2013148537A1 (en) * | 2012-03-29 | 2013-10-03 | Ning Xi | Substituted spirobicyclic compounds and methods of use |
| DK2838998T3 (en) | 2012-04-18 | 2018-01-15 | Cell Signaling Technology Inc | EGFR AND ROS1 IN CANCER |
| CN103509008A (zh) * | 2012-06-22 | 2014-01-15 | 康瑟特制药公司 | 吡唑取代的氨基-杂芳基化合物的衍生物 |
| WO2014020467A2 (en) | 2012-07-30 | 2014-02-06 | Fresenius Kabi Oncology Ltd | Process for the preparation of pyrazole substituted aminoheteroaryl compounds |
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| CA3000386A1 (en) | 2015-09-30 | 2017-04-06 | Merck Patent Gmbh | Combination of a pd-1 axis binding antagonist and an alk inhibitor for treating alk-negative cancer |
| US12066428B2 (en) * | 2015-11-20 | 2024-08-20 | Agilent Technologies, Inc. | Cell-substrate impedance monitoring of cancer cells |
| HRP20240617T1 (hr) | 2016-05-20 | 2024-07-19 | Biohaven Therapeutics Ltd. | Primjena riluzola, prolijekova riluzola ili analoga riluzola sa imunoterapijama za liječenje raka |
| GB201616116D0 (en) * | 2016-09-22 | 2016-11-09 | Astrazeneca Ab | Use of c-Met inhibitors to treat cancers harbouring MET mutations |
| RU2750539C2 (ru) | 2017-02-08 | 2021-06-29 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Фармацевтическая композиция для лечения опухоли |
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| CN108047231B (zh) * | 2018-01-02 | 2020-02-11 | 江苏医药职业学院 | [1,2,4]三嗪并[6,1-a]异吲哚化合物的盐酸盐及其应用 |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2174977C2 (ru) * | 1995-03-30 | 2001-10-20 | Пфайзер Инк. | Производные 4-(замещенного фениламино)хиназолина или их фармацевтически приемлемые соли, способ ингибирования рецепторной тирозинкиназы и фармацевтическая композиция |
| US20050009840A1 (en) * | 2003-02-26 | 2005-01-13 | Sugen, Inc. | Aminoheteroaryl compounds as protein kinase inhibitors |
| WO2005026129A1 (en) * | 2003-09-15 | 2005-03-24 | Gpc Biotech Ag | Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases |
| RU2260592C2 (ru) * | 1999-04-15 | 2005-09-20 | Бристол-Маерс Сквибб Ко. | Циклические ингибиторы протеинтирозинкиназ |
| WO2005112918A1 (en) * | 2004-05-05 | 2005-12-01 | Celgene Corporation | Methods and compositions using selective cytokine inhibitory drugs for treatment and management of cancers and other diseases |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4725601A (en) | 1985-06-04 | 1988-02-16 | Fujisawa Pharmaceutical Co., Ltd. | Certain imidazo[1,2-a]pyridines useful in the treatment of ulcers |
| GB9201693D0 (en) | 1992-01-27 | 1992-03-11 | Smithkline Beecham Intercredit | Compounds |
| JPH07109260A (ja) | 1993-10-12 | 1995-04-25 | Fuji Photo Film Co Ltd | ５−アミノ−２−ニトロピリジン誘導体及び２，５−ジアミノ−３−ヒドロキシピリジン誘導体の製造方法 |
| SE9700661D0 (sv) | 1997-02-25 | 1997-02-25 | Astra Ab | New compounds |
| SE9801526D0 (sv) | 1998-04-29 | 1998-04-29 | Astra Ab | New compounds |
| GB9908410D0 (en) | 1999-04-13 | 1999-06-09 | Pfizer Ltd | Pyridines |
| EP1206265B1 (en) | 1999-06-30 | 2003-11-12 | Merck & Co., Inc. | Src kinase inhibitor compounds |
| NZ520484A (en) | 2000-02-16 | 2005-03-24 | Neurogen Corp | Substituted arylpyrazines that are modulators of CRF (corticotropin releasing factor) receptor and methods of treatment using them |
| GB0101577D0 (en) | 2001-01-22 | 2001-03-07 | Smithkline Beecham Plc | Compounds |
| US6825198B2 (en) | 2001-06-21 | 2004-11-30 | Pfizer Inc | 5-HT receptor ligands and uses thereof |
| US6992087B2 (en) | 2001-11-21 | 2006-01-31 | Pfizer Inc | Substituted aryl 1,4-pyrazine derivatives |
| JP4242911B2 (ja) * | 2004-08-26 | 2009-03-25 | ファイザー・インク | プロテインキナーゼ阻害薬としてのエナンチオピュアなアミノヘテロアリール化合物 |
| MX2007001986A (es) | 2004-08-26 | 2007-05-10 | Pfizer | Compuestos de aminoheteroarilo como inhibidores de proteina quinasa. |
| CA2577937C (en) * | 2004-08-26 | 2010-12-21 | Pfizer Inc. | Pyrazole-substituted aminoheteroaryl compounds as protein kinase inhibitors |
| DK1963302T3 (da) * | 2005-12-05 | 2013-04-02 | Pfizer Prod Inc | Polymorfer af en C-MET/HGFR-inhibitor |
-
2006
- 2006-11-23 US US12/095,114 patent/US7825137B2/en active Active
- 2006-11-23 DE DE602006018354T patent/DE602006018354D1/de active Active
- 2006-11-23 SI SI200630864T patent/SI1959955T1/sl unknown
- 2006-11-23 RU RU2008122471/14A patent/RU2384331C2/ru active
- 2006-11-23 BR BRPI0619424-9A patent/BRPI0619424B1/pt active IP Right Grant
- 2006-11-23 WO PCT/IB2006/003397 patent/WO2007066187A2/en not_active Ceased
- 2006-11-23 CA CA2632286A patent/CA2632286C/en active Active
- 2006-11-23 AU AU2006323027A patent/AU2006323027B2/en active Active
- 2006-11-23 PT PT06820997T patent/PT1959955E/pt unknown
- 2006-11-23 PL PL06820997T patent/PL1959955T3/pl unknown
- 2006-11-23 AT AT06820997T patent/ATE488237T1/de active
- 2006-11-23 EP EP06820997A patent/EP1959955B1/en active Active
- 2006-11-23 KR KR20087016376A patent/KR101026676B1/ko active Active
- 2006-11-23 NZ NZ568654A patent/NZ568654A/en unknown
- 2006-11-23 DK DK06820997.2T patent/DK1959955T3/da active
- 2006-12-04 TW TW095145034A patent/TWI321050B/zh active
- 2006-12-04 JP JP2006327355A patent/JP4619346B2/ja active Active
- 2006-12-05 AR ARP060105369A patent/AR056832A1/es not_active Application Discontinuation
-
2008
- 2008-05-15 IL IL191471A patent/IL191471A/en active IP Right Grant
-
2010
- 2010-11-24 CY CY20101101055T patent/CY1110931T1/el unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2174977C2 (ru) * | 1995-03-30 | 2001-10-20 | Пфайзер Инк. | Производные 4-(замещенного фениламино)хиназолина или их фармацевтически приемлемые соли, способ ингибирования рецепторной тирозинкиназы и фармацевтическая композиция |
| RU2260592C2 (ru) * | 1999-04-15 | 2005-09-20 | Бристол-Маерс Сквибб Ко. | Циклические ингибиторы протеинтирозинкиназ |
| US20050009840A1 (en) * | 2003-02-26 | 2005-01-13 | Sugen, Inc. | Aminoheteroaryl compounds as protein kinase inhibitors |
| WO2005026129A1 (en) * | 2003-09-15 | 2005-03-24 | Gpc Biotech Ag | Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases |
| WO2005112918A1 (en) * | 2004-05-05 | 2005-12-01 | Celgene Corporation | Methods and compositions using selective cytokine inhibitory drugs for treatment and management of cancers and other diseases |
Non-Patent Citations (1)
| Title |
|---|
| BACKLUND M et al. Regulation of aryl hydrocarbon receptor signal transduction by protein tyrosine kinases // Cell Signal. 2005 Jan; 17(1): 39-48 - реферат, он-лайн [Найдено в Интернет на www.pubmed.com 08.05.2009], PMID: 15451023 [PubMed - indexed for MEDLINE. MA PC et al. A selective small molecule c-MET Inhibitor, PHA665752, cooperates with rapamycin // Clin Cancer Res. 2005 Mar 15;11(6):2312-9. реферат, он-лайн [Найдено в Интернет на www.pubmed.com 08.05.2009], PMID: 15788682 [PubMed - indexed for MEDLINE. * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2675850C2 (ru) * | 2012-11-06 | 2018-12-25 | Шанхай Фокон Фармасьютикал Ко Лтд | Ингибиторы alk-киназы |
| WO2014104924A1 (ru) * | 2012-12-28 | 2014-07-03 | Lobko Vladimir Pavlovich | Противоопухолевое средство (варианты) |
| RU2788606C2 (ru) * | 2018-03-22 | 2023-01-23 | Вертикаль Био АГ | Комбинация антитела против hgfr и hegfr для лечения опухоли и/или метастаза |
| US11814433B2 (en) | 2018-03-22 | 2023-11-14 | Vertical Bio Ag | Combination of anti-HGFR antibody and HEGFR for the treatment of a tumor and/or metastasis |
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| BRPI0619424B1 (pt) | 2022-02-08 |
| KR101026676B1 (ko) | 2011-04-04 |
| US20080300273A1 (en) | 2008-12-04 |
| WO2007066187A2 (en) | 2007-06-14 |
| EP1959955A2 (en) | 2008-08-27 |
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| DK1959955T3 (da) | 2011-02-07 |
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| JP4619346B2 (ja) | 2011-01-26 |
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| WO2007066187A3 (en) | 2008-01-17 |
| US7825137B2 (en) | 2010-11-02 |
| AU2006323027B2 (en) | 2012-08-02 |
| EP1959955B1 (en) | 2010-11-17 |
| BRPI0619424A2 (pt) | 2011-10-04 |
| CA2632286C (en) | 2011-11-15 |
| IL191471A (en) | 2013-03-24 |
| ATE488237T1 (de) | 2010-12-15 |
| PL1959955T3 (pl) | 2011-04-29 |
| TW200727899A (en) | 2007-08-01 |
| PT1959955E (pt) | 2011-01-04 |
| SI1959955T1 (sl) | 2011-02-28 |
| CY1110931T1 (el) | 2015-06-10 |
| KR20080072965A (ko) | 2008-08-07 |
| DE602006018354D1 (de) | 2010-12-30 |
| IL191471A0 (en) | 2009-08-03 |
| AU2006323027A1 (en) | 2007-06-14 |
| NZ568654A (en) | 2012-02-24 |
| CA2632286A1 (en) | 2007-06-14 |
| TWI321050B (en) | 2010-03-01 |
| AR056832A1 (es) | 2007-10-24 |
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