CA2474104C - N-oxides of n-phenyl-2-pyrimidine-amine derivatives - Google Patents
N-oxides of n-phenyl-2-pyrimidine-amine derivatives Download PDFInfo
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- CA2474104C CA2474104C CA2474104A CA2474104A CA2474104C CA 2474104 C CA2474104 C CA 2474104C CA 2474104 A CA2474104 A CA 2474104A CA 2474104 A CA2474104 A CA 2474104A CA 2474104 C CA2474104 C CA 2474104C
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07D401/14—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 three or more hetero rings
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (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)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Oncology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Communicable Diseases (AREA)
- Transplantation (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Liquid Crystal Substances (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0201508.9A GB0201508D0 (en) | 2002-01-23 | 2002-01-23 | Organic compounds |
| GB0201508.9 | 2002-01-23 | ||
| PCT/EP2003/000613 WO2003062220A1 (en) | 2002-01-23 | 2003-01-22 | N-oxyde of n-phenyl-2-pyrimidine-amine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2474104A1 CA2474104A1 (en) | 2003-07-31 |
| CA2474104C true CA2474104C (en) | 2012-04-17 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2474104A Expired - Fee Related CA2474104C (en) | 2002-01-23 | 2003-01-22 | N-oxides of n-phenyl-2-pyrimidine-amine derivatives |
Country Status (15)
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| EP (3) | EP1470120B1 (https=) |
| JP (2) | JP4213595B2 (https=) |
| KR (2) | KR20070058019A (https=) |
| CN (2) | CN100467461C (https=) |
| AT (1) | ATE380807T1 (https=) |
| BR (1) | BR0307058A (https=) |
| CA (1) | CA2474104C (https=) |
| DE (1) | DE60318013T2 (https=) |
| ES (2) | ES2294293T3 (https=) |
| GB (1) | GB0201508D0 (https=) |
| IL (2) | IL162979A (https=) |
| MX (1) | MXPA04007130A (https=) |
| PT (2) | PT2194049E (https=) |
| WO (1) | WO2003062220A1 (https=) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
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| DE60137273D1 (de) * | 2000-10-20 | 2009-02-12 | Eisai R&D Man Co Ltd | Verfahren zur Herstellung von 4-Phenoxy chinolin Derivaten |
| GB0201508D0 (en) * | 2002-01-23 | 2002-03-13 | Novartis Ag | Organic compounds |
| AU2004246800B2 (en) * | 2003-06-13 | 2008-12-04 | Novartis Ag | 2-aminopyrimidine derivatives as Raf kinase inhibitors |
| AU2005283422C1 (en) * | 2004-09-17 | 2017-02-02 | Eisai R & D Management Co., Ltd. | Medicinal composition |
| GB0512091D0 (en) * | 2005-06-14 | 2005-07-20 | Novartis Ag | Organic compounds |
| EP1925941B1 (en) * | 2005-08-01 | 2012-11-28 | Eisai R&D Management Co., Ltd. | Method for prediction of the efficacy of vascularization inhibitor |
| WO2007015578A1 (ja) | 2005-08-02 | 2007-02-08 | Eisai R & D Management Co., Ltd. | 血管新生阻害物質の効果を検定する方法 |
| CN101316590B (zh) * | 2005-11-07 | 2011-08-03 | 卫材R&D管理有限公司 | 血管生成抑制剂和c-kit激酶抑制剂的组合使用 |
| BRPI0620408B8 (pt) * | 2005-12-21 | 2021-05-25 | Novartis Ag | derivados de pirimidinil aril uréia sendo inibidores de fgf, seus usos, e preparação farmacêutica |
| RU2448708C3 (ru) * | 2006-05-18 | 2017-09-28 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Противоопухолевое средство против рака щитовидной железы |
| CA2662265A1 (en) * | 2006-09-01 | 2008-03-06 | Teva Pharmaceutical Industries Ltd. | Imatinib compositions |
| EP1966186A1 (en) * | 2006-10-26 | 2008-09-10 | Sicor Inc. | Process for the preparation of imatinib |
| EP2009008A1 (en) * | 2006-10-26 | 2008-12-31 | Sicor, Inc. | Imatinib base, and imatinib mesylate and processes for preparation thereof |
| CN101225085B (zh) * | 2007-01-17 | 2011-09-21 | 天津天士力集团有限公司 | 苯基呋咱氮类一氧化氮供体型2-苯胺嘧啶衍生物、其制备方法、含有该化合物的组合物及其用途 |
| CN101600694A (zh) | 2007-01-29 | 2009-12-09 | 卫材R&D管理有限公司 | 未分化型胃癌治疗用组合物 |
| CN101245061B (zh) * | 2007-02-13 | 2012-09-19 | 天津天士力集团有限公司 | N-(5-氨基-2-甲基苯基)-4-(3-吡啶基)-2-嘧啶胺类一氧化氮供体型衍生物，制备方法及其用途 |
| US7550591B2 (en) | 2007-05-02 | 2009-06-23 | Chemagis Ltd. | Imatinib production process |
| US8242271B2 (en) | 2007-06-04 | 2012-08-14 | Avila Therapeutics, Inc. | Heterocyclic compounds and uses thereof |
| ES2607794T3 (es) | 2007-06-07 | 2017-04-04 | Intra-Cellular Therapies, Inc. | Compuestos heterocíclicos novedosos y usos de los mismos |
| WO2008153959A1 (en) | 2007-06-07 | 2008-12-18 | Intra-Cellular Therapies, Inc. | Novel heterocycle compounds and uses thereof |
| BRPI0817946A2 (pt) * | 2007-09-25 | 2015-05-05 | Teva Pharma | Composições de imatinibe estável |
| KR101513326B1 (ko) * | 2007-11-09 | 2015-04-17 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 혈관 신생 저해 물질과 항종양성 백금 착물의 병용 |
| AU2009210098B2 (en) * | 2008-01-29 | 2013-06-13 | Eisai R & D Management Co., Ltd. | Combined use of angiogenesis inhibitor and taxane |
| EP2255192A1 (en) * | 2008-03-26 | 2010-12-01 | Merck Patent GmbH | Method of long term storage of substrate-coupled beads |
| CN101417995B (zh) * | 2008-11-21 | 2012-06-06 | 陈依军 | 苯氧基嘧啶衍生物及其制备方法和用途 |
| DK2468281T3 (en) | 2009-08-19 | 2016-03-21 | Eisai R&D Man Co Ltd | Quinolinderivatholdig pharmaceutical composition |
| WO2011162343A1 (ja) | 2010-06-25 | 2011-12-29 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | キナーゼ阻害作用を有する化合物の併用による抗腫瘍剤 |
| CN103402519B (zh) | 2011-04-18 | 2015-11-25 | 卫材R&D管理有限公司 | 肿瘤治疗剂 |
| JP6038128B2 (ja) | 2011-06-03 | 2016-12-07 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | レンバチニブ化合物に対する甲状腺癌対象及び腎臓癌対象の反応性を予測及び評価するためのバイオマーカー |
| AU2013364953A1 (en) | 2012-12-21 | 2015-04-30 | Eisai R&D Management Co., Ltd. | Amorphous form of quinoline derivative, and method for producing same |
| EP2997377B1 (en) | 2013-05-14 | 2018-07-18 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
| CN103588754B (zh) * | 2013-11-04 | 2015-05-27 | 遵义医学院 | 伊马替尼的制备方法 |
| PT3524595T (pt) | 2014-08-28 | 2022-09-19 | Eisai R&D Man Co Ltd | Derivado de quinolina altamente puro e método para produção do mesmo |
| AU2016224583B2 (en) | 2015-02-25 | 2021-06-03 | Eisai R&D Management Co., Ltd. | Method for suppressing bitterness of quinoline derivative |
| KR102662228B1 (ko) | 2015-03-04 | 2024-05-02 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
| BR112017027227B1 (pt) | 2015-06-16 | 2023-12-12 | Eisai R&D Management Co., Ltd | Agente anti-câncer |
| JP6553726B2 (ja) | 2015-08-20 | 2019-07-31 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍治療剤 |
| JP6581320B2 (ja) | 2017-02-08 | 2019-09-25 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍治療用医薬組成物 |
| EP3624800A4 (en) | 2017-05-16 | 2021-02-17 | Eisai R&D Management Co., Ltd. | TREATMENT OF HEPATOCELLULAR CARCINOMA |
| CN107573322A (zh) * | 2017-09-06 | 2018-01-12 | 南京优科生物医药研究有限公司 | 伊马替尼双氮氧化物、其制备方法和用途 |
| CN109761970B (zh) * | 2019-01-26 | 2020-06-09 | 中国药科大学 | 一种蛋白靶向降解嵌合分子、制备方法及应用 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4607041A (en) * | 1983-04-27 | 1986-08-19 | Fisons Plc | Antihypertensive 2-phenyl Hantzsch dihydropyridines |
| TW225528B (https=) | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| US5521184A (en) * | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| DE4444288A1 (de) * | 1994-12-13 | 1996-06-20 | Rainer Dr Med Etzel | Verwendung von Weihrauch zur Behandlung der Alzheimer-Krankheit |
| WO1996026726A1 (en) * | 1995-02-28 | 1996-09-06 | Hoechst Marion Roussel, Inc. | Pharmaceutical composition for piperidinoalkanol compounds |
| CO4940418A1 (es) | 1997-07-18 | 2000-07-24 | Novartis Ag | Modificacion de cristal de un derivado de n-fenil-2- pirimidinamina, procesos para su fabricacion y su uso |
| GB9914258D0 (en) | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
| ITMI992711A1 (it) | 1999-12-27 | 2001-06-27 | Novartis Ag | Composti organici |
| GB0022438D0 (en) * | 2000-09-13 | 2000-11-01 | Novartis Ag | Organic Compounds |
| GB0201508D0 (en) * | 2002-01-23 | 2002-03-13 | Novartis Ag | Organic compounds |
| US7279576B2 (en) * | 2002-12-31 | 2007-10-09 | Deciphera Pharmaceuticals, Llc | Anti-cancer medicaments |
-
2002
- 2002-01-23 GB GBGB0201508.9A patent/GB0201508D0/en not_active Ceased
-
2003
- 2003-01-22 KR KR1020077011065A patent/KR20070058019A/ko not_active Withdrawn
- 2003-01-22 PT PT101504421T patent/PT2194049E/pt unknown
- 2003-01-22 AT AT03731700T patent/ATE380807T1/de active
- 2003-01-22 MX MXPA04007130A patent/MXPA04007130A/es active IP Right Grant
- 2003-01-22 WO PCT/EP2003/000613 patent/WO2003062220A1/en not_active Ceased
- 2003-01-22 BR BR0307058-1A patent/BR0307058A/pt not_active IP Right Cessation
- 2003-01-22 JP JP2003562099A patent/JP4213595B2/ja not_active Expired - Fee Related
- 2003-01-22 PT PT03731700T patent/PT1470120E/pt unknown
- 2003-01-22 EP EP03731700A patent/EP1470120B1/en not_active Expired - Lifetime
- 2003-01-22 US US10/502,291 patent/US7557105B2/en not_active Expired - Fee Related
- 2003-01-22 KR KR1020047011382A patent/KR100778163B1/ko not_active Expired - Fee Related
- 2003-01-22 DE DE60318013T patent/DE60318013T2/de not_active Expired - Lifetime
- 2003-01-22 CN CNB038027089A patent/CN100467461C/zh not_active Expired - Fee Related
- 2003-01-22 ES ES03731700T patent/ES2294293T3/es not_active Expired - Lifetime
- 2003-01-22 EP EP10150442.1A patent/EP2194049B1/en not_active Expired - Lifetime
- 2003-01-22 CN CNA200910002666XA patent/CN101468984A/zh active Pending
- 2003-01-22 ES ES10150442.1T patent/ES2503734T3/es not_active Expired - Lifetime
- 2003-01-22 CA CA2474104A patent/CA2474104C/en not_active Expired - Fee Related
- 2003-01-22 EP EP07101787A patent/EP1783126A3/en not_active Withdrawn
-
2004
- 2004-07-12 IL IL162979A patent/IL162979A/en unknown
-
2008
- 2008-08-13 JP JP2008208640A patent/JP5027076B2/ja not_active Expired - Fee Related
-
2009
- 2009-06-04 US US12/478,082 patent/US20090239879A1/en not_active Abandoned
-
2010
- 2010-05-17 US US12/781,430 patent/US20100222362A1/en not_active Abandoned
- 2010-10-03 IL IL208399A patent/IL208399A/en unknown
-
2011
- 2011-07-05 US US13/176,289 patent/US20110294820A1/en not_active Abandoned
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2014
- 2014-07-14 US US14/330,404 patent/US20140323494A1/en not_active Abandoned
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