MX2007009405A - Compuestos inhibidores de raf y metodos. - Google Patents
Compuestos inhibidores de raf y metodos.Info
- Publication number
- MX2007009405A MX2007009405A MX2007009405A MX2007009405A MX2007009405A MX 2007009405 A MX2007009405 A MX 2007009405A MX 2007009405 A MX2007009405 A MX 2007009405A MX 2007009405 A MX2007009405 A MX 2007009405A MX 2007009405 A MX2007009405 A MX 2007009405A
- Authority
- MX
- Mexico
- Prior art keywords
- carbon atoms
- compound
- pyridin
- pyrazol
- disease
- Prior art date
Links
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Landscapes
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| MX2009004096A (es) | 2006-10-17 | 2009-06-16 | Stiefel Laboratories | Metabolitos de talarozol. |
| US20090082354A1 (en) * | 2007-09-20 | 2009-03-26 | Wyeth | Pyrazolo[5, 1-c] [1,2,4] triazines, methods for preparation and use thereof |
| WO2009111279A1 (en) * | 2008-02-29 | 2009-09-11 | Array Biopharma Inc. | Pyrazole [3, 4-b] pyridine raf inhibitors |
| KR20100122505A (ko) * | 2008-02-29 | 2010-11-22 | 어레이 바이오파마 인크. | Ｒａｆ 저해물질 화합물 및 이들의 이용 방법 |
| WO2009111260A1 (en) * | 2008-02-29 | 2009-09-11 | Wyeth | Phenylsulfonamide-substituted, pyrazolo[1, 5-a]pyrimidines, methods for preparation and uses thereof |
| WO2009108827A1 (en) * | 2008-02-29 | 2009-09-03 | Wyeth | Fused tricyclic pyrazolo[1, 5-a]pyrimidines, methods for preparation and uses thereof |
| JP2011513332A (ja) * | 2008-02-29 | 2011-04-28 | アレイ バイオファーマ、インコーポレイテッド | 癌の治療のためのｒａｆ阻害剤としてのｎ−（６−アミノピリジン−３−イル）−３−（スルホンアミド）ベンズアミド誘導体 |
| US20110003809A1 (en) * | 2008-02-29 | 2011-01-06 | Array Biopharma Inc. | Imidazo [4,5-b] pyridine derivatives used as raf inhibitors |
| JP2009286773A (ja) * | 2008-03-14 | 2009-12-10 | Bayer Cropscience Ag | 殺虫性縮環式アリール類 |
| PT2300013T (pt) | 2008-05-21 | 2017-10-31 | Ariad Pharma Inc | Derivados de fósforo como inibidores de cinases |
| US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
| CA2744563A1 (en) * | 2008-12-12 | 2010-06-17 | Ariad Pharmaceuticals, Inc. | Azaindole derivatives as kinase inhibitors |
| EP2440058A4 (en) | 2009-06-12 | 2012-11-21 | Dana Farber Cancer Inst Inc | MELTED HETEROCYCLIC COMPOUNDS AND APPLICATIONS THEREOF |
| JP2013503188A (ja) | 2009-08-28 | 2013-01-31 | アレイ バイオファーマ、インコーポレイテッド | Ｒａｆ阻害化合物およびその使用方法 |
| WO2011025938A2 (en) | 2009-08-28 | 2011-03-03 | Array Biopharma Inc. | Raf inhibitor compounds and methods of use thereof |
| US20120214811A1 (en) | 2009-08-28 | 2012-08-23 | Ignacio Aliagas | Raf inhibitor compounds and methods of use thereof |
| WO2011025947A1 (en) | 2009-08-28 | 2011-03-03 | Array Biopharma Inc. | Raf inhibitor compounds and methods of use thereof |
| US20120157451A1 (en) | 2009-08-28 | 2012-06-21 | Genentech, Inc | Raf inhibitor compounds and methods of use thereof |
| EP2470532A1 (en) | 2009-08-28 | 2012-07-04 | Array Biopharma, Inc. | 1h-pyrazolo [ 3, 4-b]pyridine compounds for inhibiting raf kinase |
| JP5806672B2 (ja) * | 2009-10-30 | 2015-11-10 | ドメイン・セラピューティクス | 新規オキシム誘導体及び代謝型グルタミン酸受容体のアロステリック調節因子としての利用 |
| CA2784807C (en) | 2009-12-29 | 2021-12-14 | Dana-Farber Cancer Institute, Inc. | Type ii raf kinase inhibitors |
| PH12012501361A1 (en) | 2009-12-31 | 2012-10-22 | Centro Nac De Investigaciones Oncologicas Cnio | Tricyclic compounds for use as kinase inhibitors |
| US20120122928A1 (en) | 2010-08-11 | 2012-05-17 | Bayer Cropscience Ag | Heteroarylpiperidine and -Piperazine Derivatives as Fungicides |
| EP2423210A1 (de) | 2010-08-25 | 2012-02-29 | Bayer CropScience AG | Heteroarylpiperidin- und -piperazinderivate als Fungizide |
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| EP2661434A4 (en) | 2011-01-06 | 2014-07-09 | Beta Pharma Canada Inc | NEW URGES FOR THE TREATMENT AND PREVENTION OF CANCER |
| WO2012098387A1 (en) | 2011-01-18 | 2012-07-26 | Centro Nacional De Investigaciones Oncológicas (Cnio) | 6, 7-ring-fused triazolo [4, 3 - b] pyridazine derivatives as pim inhibitors |
| WO2012104273A1 (de) | 2011-02-01 | 2012-08-09 | Bayer Cropscience Ag | Heteroarylpiperidin und -piperazinderivate als fungizide |
| WO2012145503A1 (en) | 2011-04-21 | 2012-10-26 | Novartis Ag | Pharmaceutical combinations |
| EP2704572B1 (en) | 2011-05-04 | 2015-12-30 | Ariad Pharmaceuticals, Inc. | Compounds for inhibiting cell proliferation in egfr-driven cancers |
| AR087405A1 (es) | 2011-08-01 | 2014-03-19 | Genentech Inc | Metodos para tratar el cancer por el uso de antagonistas de union al eje pd-1 e inhibidores de mek |
| KR20140064971A (ko) | 2011-09-19 | 2014-05-28 | 제넨테크, 인크. | c-met 길항제 및 B-raf 길항제를 포함하는 조합 치료 |
| WO2013074986A1 (en) | 2011-11-17 | 2013-05-23 | Dana-Farber Cancer Institute, Inc. | Inhibitors of c-jun-n-terminal kinase (jnk) |
| US9408885B2 (en) | 2011-12-01 | 2016-08-09 | Vib Vzw | Combinations of therapeutic agents for treating melanoma |
| EP2921481A1 (de) | 2011-12-27 | 2015-09-23 | Bayer Intellectual Property GmbH | 4-piperidine carboxylic acid derivatives |
| EP2797888B1 (en) * | 2011-12-31 | 2016-06-08 | BeiGene, Ltd. | Fused tricyclic compounds as raf kinase inhibitors |
| AU2013204563B2 (en) | 2012-05-05 | 2016-05-19 | Takeda Pharmaceutical Company Limited | Compounds for inhibiting cell proliferation in EGFR-driven cancers |
| KR20240146112A (ko) | 2012-08-17 | 2024-10-07 | 에프. 호프만-라 로슈 아게 | 코비메티닙 및 베무라피닙을 투여함을 포함하는 흑색종의 조합 치료법 |
| US10112927B2 (en) | 2012-10-18 | 2018-10-30 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (CDK7) |
| US10000483B2 (en) | 2012-10-19 | 2018-06-19 | Dana-Farber Cancer Institute, Inc. | Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof |
| US9758522B2 (en) | 2012-10-19 | 2017-09-12 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged small molecules as inducers of protein degradation |
| CN104994879A (zh) | 2013-02-22 | 2015-10-21 | 霍夫曼-拉罗奇有限公司 | 治疗癌症和预防药物抗性的方法 |
| JO3383B1 (ar) * | 2013-03-14 | 2019-03-13 | Lilly Co Eli | مثبطات cdc7 |
| MX2015011899A (es) | 2013-03-15 | 2016-05-05 | Genentech Inc | Metodos para el tratamiento de cáncer y prevención de resistencia a los fármacos para el cáncer. |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| WO2014206344A1 (en) | 2013-06-28 | 2014-12-31 | Beigene, Ltd. | Fused tricyclic amide compounds as multiple kinase inhibitors |
| ES2792183T3 (es) | 2013-09-13 | 2020-11-10 | Beigene Switzerland Gmbh | Anticuerpos anti-PD1 y su uso como productos terapéuticos y de diagnóstico |
| EP3046557A1 (en) | 2013-09-20 | 2016-07-27 | Stichting Het Nederlands Kanker Instituut | Rock in combination with mapk-pathway |
| WO2015041534A1 (en) | 2013-09-20 | 2015-03-26 | Stichting Het Nederlands Kanker Instituut | P90rsk in combination with raf/erk/mek |
| CA2927917C (en) | 2013-10-18 | 2022-08-09 | Syros Pharmaceuticals, Inc. | Heteroaromatic compounds useful for the treatment of proliferative diseases |
| JP6491202B2 (ja) | 2013-10-18 | 2019-03-27 | デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド | サイクリン依存性キナーゼ７（ｃｄｋ７）の多環阻害剤 |
| EP3122900A1 (en) | 2014-03-24 | 2017-02-01 | F. Hoffmann-La Roche AG | Cancer treatment with c-met antagonists and correlation of the latter with hgf expression |
| US20170027940A1 (en) | 2014-04-10 | 2017-02-02 | Stichting Het Nederlands Kanker Instituut | Method for treating cancer |
| US10017477B2 (en) | 2014-04-23 | 2018-07-10 | Dana-Farber Cancer Institute, Inc. | Janus kinase inhibitors and uses thereof |
| US9862688B2 (en) | 2014-04-23 | 2018-01-09 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged janus kinase inhibitors and uses thereof |
| WO2015178770A1 (en) | 2014-05-19 | 2015-11-26 | Stichting Het Nederlands Kanker Instituut | Compositions for cancer treatment |
| JP2017517552A (ja) | 2014-06-13 | 2017-06-29 | ジェネンテック， インコーポレイテッド | 抗癌剤耐性の治療及び防止方法 |
| US20170114323A1 (en) | 2014-06-19 | 2017-04-27 | Whitehead Institute For Biomedical Research | Uses of kinase inhibitors for inducing and maintaining pluripotency |
| CN106604742B (zh) | 2014-07-03 | 2019-01-11 | 百济神州有限公司 | 抗pd-l1抗体及其作为治疗剂及诊断剂的用途 |
| AR101210A1 (es) | 2014-07-15 | 2016-11-30 | Genentech Inc | Métodos de tratamiento de cáncer usando antagonistas de unión al eje pd-1 e inhibidores de mek |
| SG11201700496WA (en) | 2014-07-22 | 2017-02-27 | Cb Therapeutics Inc | Anti-pd-1 antibodies |
| SG10201901057UA (en) | 2014-08-05 | 2019-03-28 | Cb Therapeutics Inc | Anti-pd-l1 antibodies |
| EP3236959B1 (en) | 2014-12-23 | 2025-09-24 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
| CA2978518C (en) | 2015-03-27 | 2023-11-21 | Nathanael S. Gray | Inhibitors of cyclin-dependent kinases |
| JP7320741B2 (ja) | 2015-04-15 | 2023-08-04 | ベイジーン リミテッド | Ｂ－ｒａｆキナーゼのマレイン酸塩、結晶形、調整方法、及びその使用 |
| CA2986441A1 (en) | 2015-06-12 | 2016-12-15 | Dana-Farber Cancer Institute, Inc. | Combination therapy of transcription inhibitors and kinase inhibitors |
| JP7028766B2 (ja) | 2015-09-09 | 2022-03-02 | ダナ－ファーバー キャンサー インスティテュート， インコーポレイテッド | サイクリン依存性キナーゼの阻害剤 |
| JP6952691B2 (ja) | 2015-11-19 | 2021-10-20 | ジェネンテック， インコーポレイテッド | Ｂ−ｒａｆ阻害剤及び免疫チェックポイント阻害剤を使用してがんを治療する方法 |
| CN109475536B (zh) | 2016-07-05 | 2022-05-27 | 百济神州有限公司 | 用于治疗癌症的PD-l拮抗剂和RAF抑制剂的组合 |
| PT3500299T (pt) | 2016-08-19 | 2024-02-21 | Beigene Switzerland Gmbh | Combinação de zanubrutinib com um anticorpo anti-cd20 ou anti-pd-1 para utilização no tratamento do cancro |
| IL297717A (en) | 2016-12-01 | 2022-12-01 | Arvinas Operations Inc | History of tetrahydronaphthalene and tetrahydroisoquinoline as estrogen receptor antagonists |
| US11173211B2 (en) | 2016-12-23 | 2021-11-16 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides |
| MX2019007649A (es) * | 2016-12-23 | 2019-09-10 | Arvinas Operations Inc | Compuestos y metodos para la degradacion dirigida de polipeptidos de fibrosarcoma acelerado rapidamente. |
| CN110461847B (zh) | 2017-01-25 | 2022-06-07 | 百济神州有限公司 | (S)-7-(1-(丁-2-炔酰基)哌啶-4-基)-2-(4-苯氧基苯基)-4,5,6,7-四氢吡唑并[1,5-a]嘧啶-3-甲酰胺的结晶形式、其制备及用途 |
| US11471538B2 (en) | 2017-02-10 | 2022-10-18 | INSERM (Institut National de la Santéet de la Recherche Medicale) | Methods and pharmaceutical compositions for the treatment of cancers associated with activation of the MAPK pathway |
| TW202515616A (zh) | 2017-06-26 | 2025-04-16 | 英屬開曼群島商百濟神州有限公司 | 抗pd-1抗體或其抗原結合片段在製備治療用於患有肝細胞癌(hcc)之藥物的用途 |
| WO2019108795A1 (en) | 2017-11-29 | 2019-06-06 | Beigene Switzerland Gmbh | Treatment of indolent or aggressive b-cell lymphomas using a combination comprising btk inhibitors |
| EP3732285A1 (en) | 2017-12-28 | 2020-11-04 | Tract Pharmaceuticals, Inc. | Stem cell culture systems for columnar epithelial stem cells, and uses related thereto |
| WO2020005807A1 (en) | 2018-06-25 | 2020-01-02 | Dana-Farber Cancer Institute, Inc. | Taire family kinase inhibitors and uses thereof |
| EP3902542A4 (en) | 2018-12-28 | 2022-09-07 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 and uses thereof |
| EP4021450B1 (en) | 2019-08-26 | 2025-11-05 | Arvinas Operations, Inc. | Methods of treating breast cancer with tetrahydronaphthalene derivatives as estrogen receptor degraders |
| WO2021120890A1 (en) * | 2019-12-20 | 2021-06-24 | Novartis Ag | Pyrazolyl derivatives useful as anti-cancer agents |
| EP4204418A1 (en) | 2020-08-28 | 2023-07-05 | Arvinas Operations, Inc. | Rapidly accelerating fibrosarcoma protein degrading compounds and associated methods of use |
| EP4211128A1 (en) | 2020-09-14 | 2023-07-19 | Arvinas Operations, Inc. | Crystalline forms of a compound for the targeted degradation of estrogen receptor |
| BR112023007912A2 (pt) * | 2020-10-30 | 2024-01-02 | Novartis Ag | Formas cristalinas de um composto inibidor de kras g12c |
| US12371667B2 (en) | 2021-05-13 | 2025-07-29 | Washington University | Enhanced methods for inducing and maintaining naive human pluripotent stem cells |
| KR20240090781A (ko) * | 2021-11-30 | 2024-06-21 | 아비스코 테라퓨틱스 컴퍼니 리미티드 | 피라졸 유도체, 그 제조방법 및 약학에서의 응용 |
| CN119301101A (zh) * | 2022-07-29 | 2025-01-10 | 四川科伦博泰生物医药股份有限公司 | 甲基吡唑化合物、包含其的药物组合物及其制备方法和用途 |
| TW202432544A (zh) | 2022-09-07 | 2024-08-16 | 美商亞文納營運公司 | 快速加速纖維肉瘤降解化合物及相關使用方法 |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1245283A (en) | 1968-10-04 | 1971-09-08 | Labaz | Pyrazole derivatives |
| JP2753659B2 (ja) | 1990-09-03 | 1998-05-20 | 株式会社大塚製薬工場 | ピラゾール誘導体 |
| US5356897A (en) | 1991-09-09 | 1994-10-18 | Fujisawa Pharmaceutical Co., Ltd. | 3-(heteroaryl)-pyrazololi[1,5-a]pyrimidines |
| JPH05125079A (ja) | 1991-11-05 | 1993-05-21 | Otsuka Pharmaceut Factory Inc | ピラゾロ［１，５−ａピリミジン誘導体 |
| PT714898E (pt) | 1994-06-21 | 2002-04-29 | Otsuka Pharma Co Ltd | Derivado de pirazolo¬1,5-a|pirimidina |
| US5486534A (en) | 1994-07-21 | 1996-01-23 | G. D. Searle & Co. | 3,4-substituted pyrazoles for the treatment of inflammation |
| CN1169149A (zh) | 1995-09-28 | 1997-12-31 | 株式会社大制药工场 | 止痛组合物 |
| JPH10101672A (ja) | 1996-08-06 | 1998-04-21 | Otsuka Pharmaceut Factory Inc | アデノシン増強剤 |
| JPH10101671A (ja) | 1996-08-08 | 1998-04-21 | Otsuka Pharmaceut Factory Inc | 一酸化窒素合成酵素阻害剤 |
| US6514977B1 (en) | 1997-05-22 | 2003-02-04 | G.D. Searle & Company | Substituted pyrazoles as p38 kinase inhibitors |
| RU2249591C2 (ru) | 1997-05-22 | 2005-04-10 | Дж.Д. Серл Энд Ко. | 3(5)-гетероарилзамещенные пиразолы в качестве ингибиторов киназы p38 |
| JP2000153671A (ja) | 1998-11-20 | 2000-06-06 | Fuji Photo Film Co Ltd | 感熱記録材料 |
| EP1173254A2 (en) | 1999-04-27 | 2002-01-23 | Smithkline Beecham Plc | Novel treatment of neurotraumatic conditions with a raf inhibitor |
| TWI271406B (en) | 1999-12-13 | 2007-01-21 | Eisai Co Ltd | Tricyclic condensed heterocyclic compounds, preparation method of the same and pharmaceuticals comprising the same |
| CA2369076A1 (en) | 2000-02-05 | 2001-08-09 | Vertex Pharmaceuticals Incorporated | Pyrazole compositions useful as inhibitors of erk |
| AU2001236720A1 (en) | 2000-02-05 | 2001-08-14 | Bemis, Guy | Compositions useful as inhibitors of erk |
| CZ20013540A3 (cs) | 2000-02-05 | 2002-03-13 | Vertex Pharmaceuticals Incorporated | Deriváty pyrazolu jako inhibitory ERK a farmaceutický prostředek, který je obsahuje |
| JP2003525936A (ja) | 2000-03-06 | 2003-09-02 | スミスクライン ビーチャム パブリック リミテッド カンパニー | Ｒａｆキナーゼ阻害物質としてのイミダゾール誘導体 |
| CA2423154A1 (en) | 2000-09-21 | 2002-03-28 | David Kenneth Dean | Imidazole derivatives as raf kinase inhibitors |
| KR100843281B1 (ko) | 2000-12-28 | 2008-07-09 | 오노 야꾸힝 고교 가부시키가이샤 | 삼환식 복소환 유도체 화합물 및 그 화합물을 유효성분으로 하는 의약 |
| ES2296910T3 (es) | 2001-01-22 | 2008-05-01 | Sankyo Company, Limited | Compuestos sustituidos con grupo amino biciclicos. |
| CA2440211A1 (en) * | 2001-03-09 | 2002-09-19 | Pfizer Products Inc. | Benzimidazole anti-inflammatory compounds |
| EP1382603B1 (en) | 2001-04-26 | 2008-07-23 | Eisai R&D Management Co., Ltd. | Nitrogenous fused-ring compound having pyrazolyl group as substituent and medicinal composition thereof |
| GB0112348D0 (en) | 2001-05-19 | 2001-07-11 | Smithkline Beecham Plc | Compounds |
| ES2289116T3 (es) * | 2001-05-24 | 2008-02-01 | Eli Lilly And Company | Nuevos derivados de pirrol como agentes farmaceuticos. |
| CA2456187A1 (en) | 2001-08-03 | 2003-02-13 | Qing Tang | Pyrazole-derived kinase inhibitors and uses thereof |
| WO2003011855A2 (en) | 2001-08-03 | 2003-02-13 | Vertex Pharmaceuticals Incorporated | Pyrazole-derived kinase inhibitors and uses thereof |
| GB0121490D0 (en) | 2001-09-05 | 2001-10-24 | Smithkline Beecham Plc | Ciompounds |
| GB0121494D0 (en) | 2001-09-05 | 2001-10-24 | Smithkline Beecham Plc | Compounds |
| US6897208B2 (en) | 2001-10-26 | 2005-05-24 | Aventis Pharmaceuticals Inc. | Benzimidazoles |
| US20040010027A1 (en) | 2001-12-17 | 2004-01-15 | Pharmacia & Upjohn Spa | Hydroxphenyl-pyrazole derivatives active as kinase inhibitors, process for their preparation and pharmaceutical comositions comprising them |
| JP4286146B2 (ja) * | 2001-12-18 | 2009-06-24 | メルク エンド カムパニー インコーポレーテッド | メタボトロピックグルタミン酸受容体−５のヘテロアリール置換ピラゾール系調節剤 |
| JP4399265B2 (ja) * | 2001-12-21 | 2010-01-13 | ヴァーナリス（ケンブリッジ）リミテッド | ３，４−ジアリールピラゾール、および癌の治療におけるそれらの使用 |
| ATE365740T1 (de) | 2002-05-10 | 2007-07-15 | Smithkline Beecham Corp | Substituierte pyrazolopyrimidine |
| GB0217786D0 (en) | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Compounds |
| TW200417547A (en) | 2002-07-31 | 2004-09-16 | Smithkline Beecham Corp | Compounds |
| DE60309342T2 (de) * | 2002-08-09 | 2007-05-16 | Eli Lilly And Co., Indianapolis | Benzimidazole und benzothiazole als inhibitoren der map-kinase |
| US6967254B2 (en) | 2002-09-09 | 2005-11-22 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
| EP1543001B1 (en) | 2002-09-17 | 2007-08-15 | Eli Lilly And Company | Pyrazolopyridine derivatives as tgf beta signal transduction inhibitors for the treatment of cancer |
| BR0314302A (pt) | 2002-09-18 | 2005-07-05 | Pfizer Producs Inc | Compostos de pirazol como inibidores do fator de crescimento trnasformante (tgf) |
| WO2004026302A1 (en) | 2002-09-19 | 2004-04-01 | Eli Lilly And Company | Methods of inhibiting tgf beta with substituted pyrazoles |
| AU2003290734A1 (en) * | 2002-11-27 | 2004-06-23 | Eli Lilly And Company | Novel compounds as pharmaceutical agents |
| US7176210B2 (en) | 2003-02-10 | 2007-02-13 | Pfizer Inc. | Cannabinoid receptor ligands and uses thereof |
| CL2004000234A1 (es) | 2003-02-12 | 2005-04-15 | Biogen Idec Inc | Compuestos derivados 3-(piridin-2-il)-4-heteroaril-pirazol sustituidos, antagonistas de aik5 y/o aik4; composicion farmaceutica y uso del compuesto en el tratamiento de desordenes fibroticos como esclerodermia, lupus nefritico, cicatrizacion de herid |
| GB0313915D0 (en) * | 2003-06-16 | 2003-07-23 | Smithkline Beecham Corp | Compounds |
-
2006
- 2006-01-27 TW TW095103640A patent/TW200639163A/zh unknown
- 2006-02-02 BR BRPI0607346-8A patent/BRPI0607346A2/pt not_active IP Right Cessation
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- 2006-02-02 WO PCT/US2006/003654 patent/WO2006084015A2/en not_active Ceased
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- 2006-02-02 CA CA002596973A patent/CA2596973A1/en not_active Abandoned
- 2006-02-02 US US11/345,828 patent/US7491829B2/en not_active Expired - Fee Related
- 2006-02-02 EP EP06734199A patent/EP1846391A2/en not_active Withdrawn
- 2006-02-02 RU RU2007133111/04A patent/RU2007133111A/ru not_active Application Discontinuation
- 2006-02-02 AU AU2006210626A patent/AU2006210626A1/en not_active Abandoned
- 2006-02-02 KR KR1020077020119A patent/KR20070107104A/ko not_active Withdrawn
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| BRPI0607346A2 (pt) | 2009-09-01 |
| CA2596973A1 (en) | 2006-08-10 |
| CR9365A (es) | 2008-01-15 |
| EP1846391A2 (en) | 2007-10-24 |
| JP2008530011A (ja) | 2008-08-07 |
| US7491829B2 (en) | 2009-02-17 |
| TW200639163A (en) | 2006-11-16 |
| MA29310B1 (fr) | 2008-03-03 |
| IL185024A0 (en) | 2007-12-03 |
| US20060189627A1 (en) | 2006-08-24 |
| RU2007133111A (ru) | 2009-03-10 |
| NO20074473L (no) | 2007-10-31 |
| US20090176809A1 (en) | 2009-07-09 |
| AR053014A1 (es) | 2007-04-18 |
| KR20070107104A (ko) | 2007-11-06 |
| WO2006084015A3 (en) | 2006-11-23 |
| CN101282960A (zh) | 2008-10-08 |
| WO2006084015A2 (en) | 2006-08-10 |
| ZA200707289B (en) | 2009-09-30 |
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