TWI399379B - 激酶抑制劑 - Google Patents
激酶抑制劑 Download PDFInfo
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- TWI399379B TWI399379B TW096133786A TW96133786A TWI399379B TW I399379 B TWI399379 B TW I399379B TW 096133786 A TW096133786 A TW 096133786A TW 96133786 A TW96133786 A TW 96133786A TW I399379 B TWI399379 B TW I399379B
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- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
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- Engineering & Computer Science (AREA)
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- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
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| US82516806P | 2006-09-11 | 2006-09-11 |
Publications (2)
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| TWI399379B true TWI399379B (zh) | 2013-06-21 |
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Country Status (32)
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE519763T1 (de) | 2008-02-25 | 2011-08-15 | Hoffmann La Roche | Pyrrolopyrazin-kinasehemmer |
| CN101952295B (zh) | 2008-02-25 | 2013-11-20 | 霍夫曼-拉罗奇有限公司 | 吡咯并吡嗪激酶抑制剂 |
| CN101945877B (zh) | 2008-02-25 | 2013-07-03 | 霍夫曼-拉罗奇有限公司 | 吡咯并吡嗪激酶抑制剂 |
| PT2250172E (pt) | 2008-02-25 | 2011-11-30 | Hoffmann La Roche | Inibidores de pirrolpirazina-cinase |
| CN101939324B (zh) | 2008-02-25 | 2014-10-15 | 霍夫曼-拉罗奇有限公司 | 吡咯并吡嗪激酶抑制剂 |
| CA2717991A1 (en) * | 2008-03-10 | 2009-09-17 | Sanofi-Aventis | Treatment for ocular-related disorders |
| FR2929851B1 (fr) | 2008-04-09 | 2012-11-30 | Centre Nat Rech Scient | Molecules inhibant une voie metabolique impliquant la proteine tyrosine kinase syk et procede d'identification de ces molecules |
| AR074437A1 (es) | 2008-12-03 | 2011-01-19 | Sanofi Aventis | Tratamiento para la glomerulonefritis |
| MX2011004793A (es) * | 2008-12-04 | 2011-05-30 | Sanofi Aventis | Formas cristalinas. |
| AR074776A1 (es) * | 2008-12-18 | 2011-02-09 | Sanofi Aventis | Metodo para tratar la degeneracion macular; modulando el sistema inmunitario del paciente |
| US20110112101A1 (en) * | 2009-03-05 | 2011-05-12 | Sanofi-Aventis | Treatment for ocular-related disorders |
| AR075869A1 (es) * | 2009-03-19 | 2011-05-04 | Sanofi Aventis | Sintesis de azaindoles |
| KR101790255B1 (ko) | 2009-12-23 | 2017-10-26 | 다케다 야쿠힌 고교 가부시키가이샤 | Ｓｙｋ 억제제로서의 융합된 헤테로방향족 피롤리디논 |
| US8518945B2 (en) | 2010-03-22 | 2013-08-27 | Hoffmann-La Roche Inc. | Pyrrolopyrazine kinase inhibitors |
| US8481541B2 (en) * | 2010-03-22 | 2013-07-09 | Hoffmann-La Roche Inc. | Pyrrolopyrazine kinase inhibitors |
| RU2012152352A (ru) * | 2010-05-20 | 2014-06-27 | Ф. Хоффманн-Ля Рош Аг | ПРОИЗВОДНЫЕ ПИРРОЛО[2,3-b]ПИРАЗИН-7-КАРБОКСАМИДА И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ИНГИБИТОРОВ JAK И SYK |
| EP2571881A1 (en) | 2010-05-20 | 2013-03-27 | F.Hoffmann-La Roche Ag | Pyrrolopyrazine derivatives as syk and jak inhibitors |
| EP2441755A1 (en) | 2010-09-30 | 2012-04-18 | Almirall, S.A. | Pyridine- and isoquinoline-derivatives as Syk and JAK kinase inhibitors |
| EP2489663A1 (en) | 2011-02-16 | 2012-08-22 | Almirall, S.A. | Compounds as syk kinase inhibitors |
| EP2723739B1 (en) | 2011-06-22 | 2016-08-24 | Takeda Pharmaceutical Company Limited | Substituted 6-aza-isoindolin-1-one derivatives |
| BR112015002262A2 (pt) * | 2012-08-21 | 2019-12-10 | Hoffmann La Roche | compostos, métodos para os tratamentos de uma condição inflamatória, artrite reumatóide, asma e distúrbio imunológico; composição farmacêutica, utilização do composto e invenção |
| SG11201600373YA (en) * | 2013-07-31 | 2016-02-26 | Gilead Sciences Inc | Syk inhibitors |
| AU2020242287A1 (en) | 2019-03-21 | 2021-09-02 | INSERM (Institut National de la Santé et de la Recherche Médicale) | 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 |
| CN116969927B (zh) * | 2023-06-07 | 2024-03-19 | 中南民族大学 | 一种从荜茇中提取分离的化合物及该化合物在制备抗炎药物中的应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040009983A1 (en) * | 1999-12-24 | 2004-01-15 | Cox Paul J. | Azaindoles |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1141949A (en) | 1966-02-23 | 1969-02-05 | Sterling Drug Inc | 7-azaindole derivatives |
| US3992392A (en) | 1973-04-27 | 1976-11-16 | The Ohio State University Research Foundation | Synthesis of indoles from anilines and intermediates therein |
| SE9100920D0 (sv) | 1991-03-27 | 1991-03-27 | Astra Ab | New active compounds |
| GB9226855D0 (en) * | 1992-12-23 | 1993-02-17 | Erba Carlo Spa | Vinylene-azaindole derivatives and process for their preparation |
| WO1995033748A1 (en) | 1994-06-09 | 1995-12-14 | Smithkline Beecham Corporation | Endothelin receptor antagonists |
| FR2732969B1 (fr) | 1995-04-14 | 1997-05-16 | Adir | Nouveaux composes pyridiniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| DK0948495T3 (da) | 1996-11-19 | 2004-06-01 | Amgen Inc | Aryl- og heteroarylsubstitueret, kondenseret pyrrol som antiinflammatoriske midler |
| US6312835B1 (en) | 1997-02-13 | 2001-11-06 | Queen's University At Kingston | Luminescent compounds and methods of making and using same |
| CA2283961A1 (en) | 1997-03-19 | 1998-09-24 | Basf Aktiengesellschaft | Pyrrolo[2,3d]pyrimidines and their use as tyrosine kinase inhibitors |
| WO1998047899A1 (en) | 1997-04-24 | 1998-10-29 | Ortho-Mcneil Corporation, Inc. | Substituted pyrrolopyridines useful in the treatment of inflammatory diseases |
| ES2241146T3 (es) | 1997-08-05 | 2005-10-16 | Pfizer Products Inc. | 4-aminopirrol(3,2-d)pirimidinas como antagonistas del receptor del neuropeptido y. |
| PL340412A1 (en) | 1997-10-20 | 2001-01-29 | Hoffmann La Roche | Bicyclic kinase inhibitors |
| ES2401070T3 (es) | 1998-03-06 | 2013-04-16 | Metabasis Therapeutics, Inc. | Nuevos profármacos para compuestos que contienen fósforo |
| WO1999051596A1 (en) | 1998-04-02 | 1999-10-14 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| EP1067931A1 (en) | 1998-04-02 | 2001-01-17 | Merck & Co., Inc. (a New Jersey corp.) | Antagonists of gonadotropin releasing hormone |
| ATE482945T1 (de) | 1998-05-26 | 2010-10-15 | Chugai Pharmaceutical Co Ltd | Heterozyklische indolderivate und mono- oder diazaindol-derivate |
| SK3852001A3 (en) | 1998-09-18 | 2003-03-04 | Basf Ag | 4-Aminopyrrolopyrimidines as kinase inhibitors |
| PE20010306A1 (es) | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
| GB9930698D0 (en) * | 1999-12-24 | 2000-02-16 | Rhone Poulenc Rorer Ltd | Chemical compounds |
| US6770666B2 (en) | 1999-12-27 | 2004-08-03 | Japan Tobacco Inc. | Fused-ring compounds and use thereof as drugs |
| YU54202A (sh) | 2000-01-18 | 2006-01-16 | Agouron Pharmaceuticals Inc. | Jedinjenja indazola, farmaceutske smeše i postupci za stimulisanje i inhibiranje ćelijske proliferacije |
| DE10009000A1 (de) | 2000-02-25 | 2001-08-30 | Basf Ag | Verfahren zur Herstellung substituierter Indole |
| CA2402516A1 (en) | 2000-03-20 | 2001-09-27 | Roopa Rai | Non-amidine containing protease inhibitors |
| JP2001302667A (ja) * | 2000-04-28 | 2001-10-31 | Bayer Ag | イミダゾピリミジン誘導体およびトリアゾロピリミジン誘導体 |
| US6673923B2 (en) | 2000-05-03 | 2004-01-06 | Tularik Inc. | Pyrazole antimicrobial agents |
| MXPA02010763A (es) | 2000-06-14 | 2003-03-10 | Warner Lambert Co | Heterociclicos biciclos-6,5 fusionados. |
| CA2424222A1 (en) | 2000-10-02 | 2002-04-11 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| GB0115109D0 (en) * | 2001-06-21 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
| WO2003000690A1 (en) | 2001-06-25 | 2003-01-03 | Aventis Pharmaceuticals Inc. | Synthesis of heterocyclic compounds employing microwave technology |
| AR035543A1 (es) | 2001-06-26 | 2004-06-16 | Japan Tobacco Inc | Agente terapeutico para la hepatitis c que comprende un compuesto de anillo condensado, compuesto de anillo condensado, composicion farmaceutica que lo comprende, compuestos de benzimidazol, tiazol y bifenilo utiles como intermediarios para producir dichos compuestos, uso del compuesto de anillo con |
| IL161576A0 (en) | 2001-10-26 | 2004-09-27 | Aventis Pharma Inc | Benzimidazoles and analogues and their use as protein kinases inhibitors |
| US20040082365A1 (en) * | 2002-07-18 | 2004-04-29 | Celerica Ltd | Digitization and transmitting cellular RF signals by several light wavelengths |
| EP1388541A1 (en) | 2002-08-09 | 2004-02-11 | Centre National De La Recherche Scientifique (Cnrs) | Pyrrolopyrazines as kinase inhibitors |
| WO2005014543A1 (ja) | 2003-08-06 | 2005-02-17 | Japan Tobacco Inc. | 縮合環化合物及びそのｈｃｖポリメラーゼ阻害剤としての利用 |
| EP1778687A2 (en) * | 2004-07-27 | 2007-05-02 | SGX Pharmaceuticals, Inc. | Fused ring heterocycle kinase modulators |
| GB0420719D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| FR2876582B1 (fr) | 2004-10-15 | 2007-01-05 | Centre Nat Rech Scient Cnrse | Utilisation de derives de pyrrolo-pyrazines pour la fabrication de medicaments pour le traitement de la mucoviscidose et de maladies liees a un defaut d'adressage des proteines dans les cellules |
| WO2006052712A1 (en) | 2004-11-08 | 2006-05-18 | Baxter International Inc. | Nanoparticulate compositions of tubulin inhibitor |
| NZ555566A (en) * | 2004-11-22 | 2009-12-24 | Vertex Pharma | Pyrrolopyrazines and pyrazolopyrazines useful as inhibitors of protein kinases |
| US20110112101A1 (en) | 2009-03-05 | 2011-05-12 | Sanofi-Aventis | Treatment for ocular-related disorders |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040009983A1 (en) * | 1999-12-24 | 2004-01-15 | Cox Paul J. | Azaindoles |
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