JP2011518819A - アリール−キノリル化合物及びその使用 - Google Patents
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Classifications
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Landscapes
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Applications Claiming Priority (5)
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| US4790208P | 2008-04-25 | 2008-04-25 | |
| GBGB0807609.3A GB0807609D0 (en) | 2008-04-25 | 2008-04-25 | Therapeutic compounds and their use |
| US61/047,902 | 2008-04-25 | ||
| GB0807609.3 | 2008-04-25 | ||
| PCT/GB2009/001077 WO2009130487A1 (en) | 2008-04-25 | 2009-04-27 | Aryl-quinolyl compounds and their use |
Publications (2)
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| JP2011518819A true JP2011518819A (ja) | 2011-06-30 |
| JP2011518819A5 JP2011518819A5 (enExample) | 2012-04-26 |
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| JP2011505593A Withdrawn JP2011518819A (ja) | 2008-04-25 | 2009-04-27 | アリール−キノリル化合物及びその使用 |
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| US (1) | US8383816B2 (enExample) |
| EP (1) | EP2285805B1 (enExample) |
| JP (1) | JP2011518819A (enExample) |
| CN (1) | CN102066371A (enExample) |
| AU (1) | AU2009239785A1 (enExample) |
| BR (1) | BRPI0911525A2 (enExample) |
| CA (1) | CA2721575A1 (enExample) |
| GB (1) | GB0807609D0 (enExample) |
| WO (1) | WO2009130487A1 (enExample) |
| ZA (1) | ZA201007395B (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020143120A (ja) * | 2013-06-28 | 2020-09-10 | ベイジーン リミテッド | Ｒａｆキナーゼおよび／またはＲａｆキナーゼの二量体阻害剤としての縮合三環式ウレア系化合物 |
| JP2024526197A (ja) * | 2021-06-24 | 2024-07-17 | エルジー・ケム・リミテッド | Ｒｏｎ阻害剤としての新規なウレア誘導体化合物 |
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| EP2229391B1 (en) | 2007-12-19 | 2014-08-06 | Cancer Research Technology Limited | Pyrido[2,3-b]pyrazine-8-substituted compounds and their use |
| WO2009111277A1 (en) * | 2008-02-29 | 2009-09-11 | Array Biopharma Inc. | Imdizo [4. 5-b] pyridine derivatives used as raf inhibitors |
| EP2265574A1 (en) * | 2008-02-29 | 2010-12-29 | Array Biopharma, Inc. | N- (6-aminopyridin-3-yl) -3- (sulfonamido) benzamide derivatives as b-raf inhibitors for the treatment of cancer |
| AR070535A1 (es) * | 2008-02-29 | 2010-04-14 | Array Biopharma Inc | Compuestos inhibidores de raf y metodos para usarlos |
| AU2009222144A1 (en) * | 2008-02-29 | 2009-09-11 | Array Biopharma Inc. | Pyrazole [3, 4-b] pyridine Raf inhibitors |
| GB0807609D0 (en) | 2008-04-25 | 2008-06-04 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| CA2786834C (en) | 2010-02-01 | 2018-10-16 | Cancer Research Technology Limited | 1-(5-tert-butyl-2-phenyl-2h-pyrazol-3-yl)-3-[2-fluoro-4-(1-methyl-2-oxo-2,3-dihydro-1h-imidazo[4,5-b]pyridin-7-yloxy)-phenyl]-urea and related compounds and their use in therapy |
| US8933228B2 (en) | 2010-06-17 | 2015-01-13 | Respivert, Ltd. | Respiratory formulations and compounds for use therein |
| SG193301A1 (en) * | 2011-03-09 | 2013-10-30 | Merck Patent Gmbh | Pyrido [2, 3 - b] pyrazine derivatives and their therapeutical uses |
| GB201320732D0 (en) | 2013-11-25 | 2014-01-08 | Cancer Rec Tech Ltd | Methods of chemical synthesis |
| GB201320729D0 (en) * | 2013-11-25 | 2014-01-08 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| EP3575305A1 (fr) | 2018-05-31 | 2019-12-04 | Biocidal Alternative Solutions | Procédé de fabrication de composés comprenant un groupe fonctionnel oxazolopyridinones |
| JOP20180131B1 (ar) * | 2018-12-24 | 2023-03-28 | Univ Of Petra | مركبات الكوينولون المستبدلة واستخدامها في علاج السرطان وطريقة تحضيرها |
Family Cites Families (36)
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| JPS5665863A (en) | 1979-10-31 | 1981-06-03 | Tokyo Organ Chem Ind Ltd | Novel aniline derivative, its preparation and pesticide containing the same |
| JPS5738777A (en) | 1980-08-19 | 1982-03-03 | Sogo Yatsukou Kk | 2-sufanilamidopyrathyn derivative |
| US4666828A (en) | 1984-08-15 | 1987-05-19 | The General Hospital Corporation | Test for Huntington's disease |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4801531A (en) | 1985-04-17 | 1989-01-31 | Biotechnology Research Partners, Ltd. | Apo AI/CIII genomic polymorphisms predictive of atherosclerosis |
| US5272057A (en) | 1988-10-14 | 1993-12-21 | Georgetown University | Method of detecting a predisposition to cancer by the use of restriction fragment length polymorphism of the gene for human poly (ADP-ribose) polymerase |
| US5192659A (en) | 1989-08-25 | 1993-03-09 | Genetype Ag | Intron sequence analysis method for detection of adjacent and remote locus alleles as haplotypes |
| US5643755A (en) | 1994-10-07 | 1997-07-01 | Regeneron Pharmaceuticals Inc. | Nucleic acid encoding tie-2 ligand |
| US5879672A (en) | 1994-10-07 | 1999-03-09 | Regeneron Pharmaceuticals, Inc. | Tie-2 ligand 1 |
| WO1996009381A1 (en) | 1994-09-22 | 1996-03-28 | Helsinki University Licensing Ltd. Oy | Promoter for the receptor tyrosine kinase, tie |
| US6218529B1 (en) | 1995-07-31 | 2001-04-17 | Urocor, Inc. | Biomarkers and targets for diagnosis, prognosis and management of prostate, breast and bladder cancer |
| EP0951541B1 (en) | 1995-07-31 | 2005-11-30 | Urocor, Inc. | Biomarkers and targets for diagnosis, prognosis and management of prostate disease |
| ZA971896B (en) | 1996-03-26 | 1998-09-07 | Du Pont Merck Pharma | Aryloxy-and arythio-fused pyridines and pyrimidines and derivatives |
| CA2263479A1 (en) | 1996-09-25 | 1998-04-02 | Zeneca Limited | Quinoline derivatives inhibiting the effect of growth factors such as vegf |
| US6030831A (en) | 1997-09-19 | 2000-02-29 | Genetech, Inc. | Tie ligand homologues |
| CA2305370C (en) | 1997-09-26 | 2006-11-28 | Gerald Mcmahon | Azabenzimidazole-based compounds for modulating serine/threonine protein kinase function |
| GB9721437D0 (en) | 1997-10-10 | 1997-12-10 | Glaxo Group Ltd | Heteroaromatic compounds and their use in medicine |
| GB2356398A (en) | 1999-11-18 | 2001-05-23 | Lilly Dev Ct S A | Preparation of arylsulfamides |
| US6610688B2 (en) | 1999-12-21 | 2003-08-26 | Sugen, Inc. | 4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors |
| US6492529B1 (en) | 2000-01-18 | 2002-12-10 | Boehringer Ingelheim Pharmaceuticals, Inc. | Bis pyrazole-1H-pyrazole intermediates and their synthesis |
| JP2004517080A (ja) | 2000-11-29 | 2004-06-10 | グラクソ グループ リミテッド | Ｔｉｅ−２および／またはｖｅｇｆｒ−２の阻害剤として有用なベンゾイミダゾール誘導体 |
| JP4643909B2 (ja) | 2001-12-21 | 2011-03-02 | ザ ウェルカム トラスト リミテッド | 遺伝子 |
| EP1534268A4 (en) | 2002-08-09 | 2006-11-02 | Merck & Co Inc | TYROSINE KINASE INHIBITORS |
| TW200538120A (en) | 2004-02-20 | 2005-12-01 | Kirin Brewery | Compound having TGF-beta inhibitory activity and pharmaceutical composition containing same |
| TW200616974A (en) | 2004-07-01 | 2006-06-01 | Astrazeneca Ab | Chemical compounds |
| AU2005278959A1 (en) | 2004-08-31 | 2006-03-09 | Astrazeneca Ab | Quinazolinone derivatives and their use as B-Raf inhibitors |
| GB0423554D0 (en) * | 2004-10-22 | 2004-11-24 | Cancer Rec Tech Ltd | Therapeutic compounds |
| GB0428082D0 (en) | 2004-12-22 | 2005-01-26 | Welcome Trust The Ltd | Therapeutic compounds |
| EP1957460A1 (en) | 2005-12-08 | 2008-08-20 | Millennium Pharmaceuticals, Inc. | Bicyclic compounds with kinase inhibitory activity |
| US7989461B2 (en) | 2005-12-23 | 2011-08-02 | Amgen Inc. | Substituted quinazolinamine compounds for the treatment of cancer |
| EP2013207B1 (en) | 2006-04-26 | 2012-04-25 | Cancer Research Technology Limited | Imidazo[4,5-b]pyridin-2-one compounds and analogs thereof as cancer therapeutic compounds |
| WO2008044688A1 (en) * | 2006-10-11 | 2008-04-17 | Daiichi Sankyo Company, Limited | Urea derivative |
| EP2229391B1 (en) | 2007-12-19 | 2014-08-06 | Cancer Research Technology Limited | Pyrido[2,3-b]pyrazine-8-substituted compounds and their use |
| GB0807609D0 (en) | 2008-04-25 | 2008-06-04 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| CA2786834C (en) | 2010-02-01 | 2018-10-16 | Cancer Research Technology Limited | 1-(5-tert-butyl-2-phenyl-2h-pyrazol-3-yl)-3-[2-fluoro-4-(1-methyl-2-oxo-2,3-dihydro-1h-imidazo[4,5-b]pyridin-7-yloxy)-phenyl]-urea and related compounds and their use in therapy |
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2008
- 2008-04-25 GB GBGB0807609.3A patent/GB0807609D0/en not_active Ceased
-
2009
- 2009-04-27 CA CA2721575A patent/CA2721575A1/en not_active Abandoned
- 2009-04-27 AU AU2009239785A patent/AU2009239785A1/en not_active Abandoned
- 2009-04-27 JP JP2011505593A patent/JP2011518819A/ja not_active Withdrawn
- 2009-04-27 US US12/988,619 patent/US8383816B2/en not_active Expired - Fee Related
- 2009-04-27 WO PCT/GB2009/001077 patent/WO2009130487A1/en not_active Ceased
- 2009-04-27 CN CN2009801234973A patent/CN102066371A/zh active Pending
- 2009-04-27 BR BRPI0911525-0A patent/BRPI0911525A2/pt not_active IP Right Cessation
- 2009-04-27 EP EP09734443.6A patent/EP2285805B1/en active Active
-
2010
- 2010-10-15 ZA ZA2010/07395A patent/ZA201007395B/en unknown
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020143120A (ja) * | 2013-06-28 | 2020-09-10 | ベイジーン リミテッド | Ｒａｆキナーゼおよび／またはＲａｆキナーゼの二量体阻害剤としての縮合三環式ウレア系化合物 |
| JP2021120411A (ja) * | 2013-06-28 | 2021-08-19 | ベイジーン リミテッド | Ｒａｆキナーゼおよび／またはＲａｆキナーゼの二量体阻害剤としての縮合三環式ウレア系化合物 |
| JP7207629B2 (ja) | 2013-06-28 | 2023-01-18 | ベイジーン リミテッド | Ｒａｆキナーゼおよび／またはＲａｆキナーゼの二量体阻害剤としての縮合三環式ウレア系化合物 |
| JP2024526197A (ja) * | 2021-06-24 | 2024-07-17 | エルジー・ケム・リミテッド | Ｒｏｎ阻害剤としての新規なウレア誘導体化合物 |
| JP2024526198A (ja) * | 2021-06-24 | 2024-07-17 | エルジー・ケム・リミテッド | Ｒｏｎ阻害剤としての新規なウレア誘導体化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2285805A1 (en) | 2011-02-23 |
| US8383816B2 (en) | 2013-02-26 |
| CA2721575A1 (en) | 2009-10-29 |
| EP2285805B1 (en) | 2014-07-23 |
| CN102066371A (zh) | 2011-05-18 |
| ZA201007395B (en) | 2011-12-28 |
| US20110053946A1 (en) | 2011-03-03 |
| AU2009239785A1 (en) | 2009-10-29 |
| WO2009130487A1 (en) | 2009-10-29 |
| BRPI0911525A2 (pt) | 2019-03-12 |
| GB0807609D0 (en) | 2008-06-04 |
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