MXPA05001367A - Composiciones de pirazol utiles como inhibidores de gsk-3. - Google Patents
Composiciones de pirazol utiles como inhibidores de gsk-3.Info
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- MXPA05001367A MXPA05001367A MXPA05001367A MXPA05001367A MXPA05001367A MX PA05001367 A MXPA05001367 A MX PA05001367A MX PA05001367 A MXPA05001367 A MX PA05001367A MX PA05001367 A MXPA05001367 A MX PA05001367A MX PA05001367 A MXPA05001367 A MX PA05001367A
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- C—CHEMISTRY; METALLURGY
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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Families Citing this family (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7473691B2 (en) | 2000-09-15 | 2009-01-06 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| ATE346064T1 (de) | 2000-09-15 | 2006-12-15 | Vertex Pharma | Pyrazolverbindungen als protein-kinasehemmer |
| US6660731B2 (en) | 2000-09-15 | 2003-12-09 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| WO2002068415A1 (en) | 2000-12-21 | 2002-09-06 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| US20040009981A1 (en) | 2002-03-15 | 2004-01-15 | David Bebbington | Compositions useful as inhibitors of protein kinases |
| MY141867A (en) | 2002-06-20 | 2010-07-16 | Vertex Pharma | Substituted pyrimidines useful as protein kinase inhibitors |
| JP4733388B2 (ja) | 2002-08-02 | 2011-07-27 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ｇｓｋ−３のインヒビターとして有用なピラゾール組成物 |
| US7601718B2 (en) | 2003-02-06 | 2009-10-13 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of protein kinases |
| WO2006007864A1 (en) * | 2004-07-17 | 2006-01-26 | Max Planck Geselllschaft Zur Förderung Der Wissenschaft | Treating neurodegenerative conditions |
| CA2579143A1 (en) | 2004-09-13 | 2006-03-23 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| US8771754B2 (en) * | 2004-09-17 | 2014-07-08 | Vanderbilt University | Use of GSK3 inhibitors in combination with radiation therapies |
| EP1917259B1 (en) | 2005-08-18 | 2012-01-25 | Vertex Pharmaceuticals Incorporated | Pyrazine kinase inhibitors |
| EP2275095A3 (en) | 2005-08-26 | 2011-08-17 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| EP2258359A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
| CA2625153A1 (en) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
| CA2625210A1 (en) | 2005-10-31 | 2007-05-10 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| WO2007056163A2 (en) | 2005-11-03 | 2007-05-18 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as kinase inhibitors |
| EP2537849A3 (en) | 2006-01-17 | 2013-04-03 | Vertex Pharmaceuticals, Inc. | Azaindoles useful as inhibitors of janus kinases |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| JP2009536669A (ja) | 2006-05-09 | 2009-10-15 | ブレインセルス，インコーポレイティド | アンジオテンシン調節による神経新生 |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| ATE537151T1 (de) | 2006-10-31 | 2011-12-15 | Pfizer Prod Inc | Pyrazolinverbindungen als mineralocorticoidrezeptorantagonisten |
| NZ576750A (en) * | 2006-11-02 | 2012-01-12 | Vertex Pharma | Aminopyridines and aminopyrimidines useful as inhibitors of protein kinases |
| AU2007333650A1 (en) | 2006-12-19 | 2008-06-26 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as inhibitors of protein kinases |
| NZ577798A (en) | 2006-12-21 | 2012-04-27 | Vertex Pharma | 5-cyano-4- (pyrrolo [2, 3b] pyridine-3-yl) -pyrimidine derivatives useful as protein kinase inhibitors |
| US8802638B1 (en) | 2007-01-25 | 2014-08-12 | University Of South Florida | Flavonoid treatment of glycogen synthase kinase-based disease |
| JP2010518014A (ja) * | 2007-01-31 | 2010-05-27 | バーテックス ファーマシューティカルズ インコーポレイテッド | キナーゼ阻害剤として有用な２−アミノピリジン誘導体 |
| WO2008112651A2 (en) | 2007-03-09 | 2008-09-18 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as inhibitors of protein kinases |
| MX2009009592A (es) | 2007-03-09 | 2009-11-10 | Vertex Pharma | Aminopiridinas utiles como inhibidores de proteinas cinasas. |
| WO2008112642A1 (en) | 2007-03-09 | 2008-09-18 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as inhibitors of protein kinases |
| AU2008240313A1 (en) | 2007-04-13 | 2008-10-23 | Aj Park | Aminopyrimidines useful as kinase inhibitors |
| CN101801959A (zh) | 2007-05-02 | 2010-08-11 | 沃泰克斯药物股份有限公司 | 可用作激酶抑制剂的氨基嘧啶类化合物 |
| CN101679378A (zh) | 2007-05-02 | 2010-03-24 | 沃泰克斯药物股份有限公司 | 用作激酶抑制剂的噻唑和吡唑 |
| US8648069B2 (en) | 2007-06-08 | 2014-02-11 | Abbvie Inc. | 5-substituted indazoles as kinase inhibitors |
| MX2009013213A (es) * | 2007-06-08 | 2010-03-30 | Abbott Lab | Indazoles 5-sustituidos 5-heteroarilo como inhibidores de cinasa. |
| JP5553751B2 (ja) * | 2007-07-31 | 2014-07-16 | バーテックス ファーマシューティカルズ インコーポレイテッド | ５−フルオロ−１Ｈ−ピラゾロ［３，４−ｂ］ピリジン−３−アミンおよびその誘導体を調製するためのプロセス |
| KR20090031122A (ko) * | 2007-09-21 | 2009-03-25 | 주식회사 중외제약 | 인다졸 골격을 함유하는 화합물, 이의 제조방법 및 상기화합물을 함유하는 약제학적 조성물 |
| NZ586662A (en) | 2007-12-19 | 2012-08-31 | Vertex Pharma | PYRAZOLO[1,5-a]PYRIMIDINES USEFUL AS JANUS KINASE 2 INHIBITORS |
| JP2011513483A (ja) * | 2008-03-10 | 2011-04-28 | バーテックス ファーマシューティカルズ インコーポレイテッド | タンパク質キナーゼの阻害剤として有用なピリミジンおよびピリジン |
| WO2009154697A2 (en) | 2008-05-28 | 2009-12-23 | Massachusetts Institute Of Technology | Disc-1 pathway activators in the control of neurogenesis |
| WO2010099217A1 (en) | 2009-02-25 | 2010-09-02 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| WO2010098888A1 (en) * | 2009-02-27 | 2010-09-02 | Massachusetts Institute Of Technology | Uses of chemicals to modulate gsk-3 signaling for treatment of bipolar disorder and other brain disorders |
| KR20100101054A (ko) * | 2009-03-07 | 2010-09-16 | 주식회사 메디젠텍 | 세포핵에서 세포질로의 ｇｓｋ３의 이동을 억제하는 화합물을 함유하는 세포핵에서 세포질로의 ｇｓｋ３ 이동에 의해 발생되는 질환의 치료 또는 예방용 약학적 조성물 |
| SG10201405826RA (en) | 2009-06-17 | 2014-12-30 | Vertex Pharma | Inhibitors of influenza viruses replication |
| WO2011059388A1 (en) * | 2009-11-13 | 2011-05-19 | Astrazeneca Ab | Oxazolo[4,5-c]pyridine substituted pyrazine |
| US8592485B2 (en) | 2010-06-17 | 2013-11-26 | Healthpartners Research Foundation | Methods and pharmaceutical compositions for treating the animal central nervous system for psychiatric disorders |
| KR20120063283A (ko) * | 2010-12-07 | 2012-06-15 | 제일약품주식회사 | 신규한 피라졸로 피리딘 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 포함하는 약학적 조성물 |
| RU2013132681A (ru) | 2010-12-16 | 2015-01-27 | Вертекс Фармасьютикалз Инкорпорейтед | Ингибиторы репликации вирусов гриппа |
| UA118010C2 (uk) | 2011-08-01 | 2018-11-12 | Вертекс Фармасьютікалз Інкорпорейтед | Інгібітори реплікації вірусів грипу |
| EP2671885A1 (en) * | 2012-06-05 | 2013-12-11 | Ares Trading S.A. | Imidazo-oxadiazole and Imidazo-thiadiazole derivatives |
| US8992951B2 (en) | 2013-01-09 | 2015-03-31 | Sapna Life Sciences Corporation | Formulations, procedures, methods and combinations thereof for reducing or preventing the development, or the risk of development, of neuropathology as a result of trauma |
| DK3702443T3 (da) | 2013-03-14 | 2022-04-04 | Brigham & Womens Hospital Inc | Sammensætninger og fremgangsmåder til opformering og dyrkning af epiteliale stamceller |
| PT3068776T (pt) | 2013-11-13 | 2019-08-26 | Vertex Pharma | Inibidores da replicação de vírus da gripe |
| WO2015073481A1 (en) | 2013-11-13 | 2015-05-21 | Vertex Pharmaceuticals Incorporated | Methods of preparing inhibitors of influenza viruses replication |
| US20170165230A1 (en) | 2014-04-09 | 2017-06-15 | Christopher Rudd | Use of gsk-3 inhibitors or activators which modulate pd-1 or t-bet expression to modulate t cell immunity |
| KR101731624B1 (ko) * | 2014-07-01 | 2017-05-04 | 광주과학기술원 | 세포 리프로그래밍 유도용 조성물 |
| KR102493376B1 (ko) | 2014-09-03 | 2023-01-27 | 더 브리검 앤드 우먼즈 하스피털, 인크. | 청력 손실의 치료를 위해 내이 털세포를 생성하기 위한 조성물, 시스템, 및 방법 |
| EP3294735B8 (en) | 2015-05-13 | 2022-01-05 | Vertex Pharmaceuticals Incorporated | Inhibitors of influenza viruses replication |
| JP6704416B2 (ja) | 2015-05-13 | 2020-06-03 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | インフルエンザウイルスの複製の阻害剤を調製する方法 |
| JP2019506153A (ja) | 2016-01-08 | 2019-03-07 | マサチューセッツ インスティテュート オブ テクノロジー | 分化した腸内分泌細胞およびインスリン産生細胞の作製 |
| CN107151235B (zh) * | 2016-03-04 | 2019-12-13 | 上海市计划生育科学研究所 | 噻二唑烷二酮基gsk3抑制剂在调节精子运动能力中的用途 |
| WO2018217766A1 (en) | 2017-05-22 | 2018-11-29 | Whitehead Institute For Biomedical Research | Kcc2 expression enhancing compounds and uses thereof |
| WO2020052648A1 (zh) * | 2018-09-14 | 2020-03-19 | 江苏恒瑞医药股份有限公司 | 一种杂芳基并[4,3-c]嘧啶-5-胺类衍生物的晶型及制备方法 |
| WO2020163812A1 (en) | 2019-02-08 | 2020-08-13 | Frequency Therapeutics, Inc. | Valproic acid compounds and wnt agonists for treating ear disorders |
Family Cites Families (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3133081A (en) | 1964-05-12 | J-aminoindazole derivatives | ||
| US3935183A (en) | 1970-01-26 | 1976-01-27 | Imperial Chemical Industries Limited | Indazole-azo phenyl compounds |
| BE754242A (fr) | 1970-07-15 | 1971-02-01 | Geigy Ag J R | Diamino-s-triazines et dinitro-s-triazines |
| US3998951A (en) | 1974-03-13 | 1976-12-21 | Fmc Corporation | Substituted 2-arylquinazolines as fungicides |
| DE2458965C3 (de) | 1974-12-13 | 1979-10-11 | Bayer Ag, 5090 Leverkusen | 3-Amino-indazol-N-carbonsäure-Derivate, Verfahren zu ihrer Herstellung sowie sie enthaltende Arzneimittel |
| MA18829A1 (fr) | 1979-05-18 | 1980-12-31 | Ciba Geigy Ag | Derives de la pyrimidine,procedes pour leur preparation,compositions pharmaceutiques contenant ces composes et leur utilisation therapeutique |
| DOP1981004033A (es) | 1980-12-23 | 1990-12-29 | Ciba Geigy Ag | Procedimiento para proteger plantas de cultivo de la accion fitotoxica de herbicidas. |
| SE8102194L (sv) | 1981-04-06 | 1982-10-07 | Pharmacia Ab | Terapeutiskt aktiv organisk forening och farmaceutisk beredning innehallande denna |
| SE8102193L (sv) | 1981-04-06 | 1982-10-07 | Pharmacia Ab | Terapeutiskt aktiv organisk forening och dess anvendning |
| JPS58124773A (ja) * | 1982-01-20 | 1983-07-25 | Mitsui Toatsu Chem Inc | ５−メチルチオピリミジン誘導体とその製造法と農園芸用殺菌剤 |
| JPS59173249U (ja) | 1983-05-07 | 1984-11-19 | 日本碍子株式会社 | 避雷器素子を内蔵したオ−プンヒユ−ズカツトアウト |
| EP0136976A3 (de) | 1983-08-23 | 1985-05-15 | Ciba-Geigy Ag | Verwendung von Phenylpyrimidinen als Pflanzenregulatoren |
| DE3725638A1 (de) | 1987-08-03 | 1989-02-16 | Bayer Ag | Neue aryloxy (bzw. thio)aminopyrimidine |
| JPH0532662A (ja) | 1990-11-09 | 1993-02-09 | Nissan Chem Ind Ltd | 置換ピラゾール誘導体および農園芸用殺菌剤 |
| US5710158A (en) | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| US5597920A (en) | 1992-04-30 | 1997-01-28 | Neurogen Corporation | Gabaa receptor subtypes and methods for screening drug compounds using imidazoquinoxalines and pyrrolopyrimidines to bind to gabaa receptor subtypes |
| JPH0665237A (ja) | 1992-05-07 | 1994-03-08 | Nissan Chem Ind Ltd | 置換ピラゾール誘導体および農園芸用殺菌剤 |
| ATE325113T1 (de) | 1993-10-01 | 2006-06-15 | Novartis Pharma Gmbh | Pharmacologisch wirksame pyrimidinderivate und verfahren zu deren herstellung |
| JPH10509708A (ja) | 1994-11-10 | 1998-09-22 | コア セラピューティクス，インコーポレイティド | プロテイン・キナーゼのインヒビターとして有用な医薬ピラゾール組成物 |
| IL117659A (en) | 1995-04-13 | 2000-12-06 | Dainippon Pharmaceutical Co | Substituted 2-phenyl pyrimidino amino acetamide derivative process for preparing the same and a pharmaceutical composition containing same |
| WO1997009325A1 (en) | 1995-09-01 | 1997-03-13 | Signal Pharmaceuticals, Inc. | Pyrimidine carboxylates and related compounds and methods for treating inflammatory conditions |
| GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| US6716575B2 (en) | 1995-12-18 | 2004-04-06 | Sugen, Inc. | Diagnosis and treatment of AUR1 and/or AUR2 related disorders |
| AR007857A1 (es) | 1996-07-13 | 1999-11-24 | Glaxo Group Ltd | Compuestos heterociclicos fusionados como inhibidores de proteina tirosina quinasa, sus metodos de preparacion, intermediarios uso en medicina ycomposiciones farmaceuticas que los contienen. |
| JPH10130150A (ja) | 1996-09-05 | 1998-05-19 | Dainippon Pharmaceut Co Ltd | 酢酸アミド誘導体からなる医薬 |
| GB9619284D0 (en) | 1996-09-16 | 1996-10-30 | Celltech Therapeutics Ltd | Chemical compounds |
| WO1998014450A1 (en) | 1996-10-02 | 1998-04-09 | Novartis Ag | Pyrimidine derivatives and processes for the preparation thereof |
| AU738341B2 (en) | 1996-10-11 | 2001-09-13 | Abbott Gmbh & Co. Kg | Asparate ester inhibitors of interleukin-1beta converting enzyme |
| CA2306692C (en) | 1997-10-10 | 2010-09-21 | Cytovia, Inc. | Dipeptide apoptosis inhibitors and the use thereof |
| US6267952B1 (en) | 1998-01-09 | 2001-07-31 | Geltex Pharmaceuticals, Inc. | Lipase inhibiting polymers |
| JP2000026421A (ja) | 1998-01-29 | 2000-01-25 | Kumiai Chem Ind Co Ltd | ジアリ―ルスルフィド誘導体及び有害生物防除剤 |
| CA2321153A1 (en) | 1998-02-17 | 1999-08-19 | Timothy D. Cushing | Anti-viral pyrimidine derivatives |
| AU755273B2 (en) | 1998-03-16 | 2002-12-05 | Cytovia, Inc. | Dipeptide caspase inhibitors and the use thereof |
| YU76100A (sh) | 1998-06-02 | 2003-12-31 | Osi Pharmaceuticals Inc. | Pirolo(2,3-d) pirimidin preparati i njihova primena |
| CN1312807A (zh) * | 1998-06-19 | 2001-09-12 | 希龙公司 | 糖元合成酶激酶3的抑制剂 |
| AU5777299A (en) | 1998-08-21 | 2000-03-14 | Du Pont Pharmaceuticals Company | Isoxazolo(4,5-d)pyrimidines as CRF antagonists |
| US6184226B1 (en) | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| WO2000021927A2 (en) * | 1998-10-08 | 2000-04-20 | Smithkline Beecham Plc | Pyrrole-2,5-diones as gsk-3 inhibitors |
| BR9914326A (pt) | 1998-10-08 | 2001-06-26 | Astrazeneca Ab | Uso de um composto, composto, processo para a preparação do mesmo, composição farmacêutica, e, método para produzir um efeito antiangiogênico e/ou de redução da permeabilidade vascular em animais de sangue quente em necessidade de um tal tratamento |
| GB9828640D0 (en) | 1998-12-23 | 1999-02-17 | Smithkline Beecham Plc | Novel method and compounds |
| GB9828511D0 (en) | 1998-12-24 | 1999-02-17 | Zeneca Ltd | Chemical compounds |
| WO2000042029A1 (en) | 1999-01-13 | 2000-07-20 | Warner-Lambert Company | 1-heterocycle substituted diarylamines |
| AU766081B2 (en) | 1999-03-30 | 2003-10-09 | Novartis Ag | Phthalazine derivatives for treating inflammatory diseases |
| JP2003502424A (ja) | 1999-06-17 | 2003-01-21 | シオノギ バイオリサーチ コーポレイション | Ｉｌ−１２産生の阻害物質 |
| GB9914258D0 (en) | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
| CA2381882C (en) | 1999-08-13 | 2011-01-25 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases |
| ATE396978T1 (de) | 1999-10-07 | 2008-06-15 | Amgen Inc | Triazin-kinase-hemmer |
| EA200200411A1 (ru) | 1999-11-30 | 2002-10-31 | Пфайзер Продактс Инк. | 2,4-диаминопиримидиновые соединения, полезные в качестве иммуносупрессоров |
| AU784878B2 (en) | 1999-12-02 | 2006-07-13 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 A2A and A3 receptors and uses thereof |
| US6376489B1 (en) | 1999-12-23 | 2002-04-23 | Icos Corporation | Cyclic AMP-specific phosphodiesterase inhibitors |
| MY125768A (en) | 1999-12-15 | 2006-08-30 | Bristol Myers Squibb Co | N-[5-[[[5-alkyl-2-oxazolyl]methyl]thio]-2-thiazolyl]-carboxamide inhibitors of cyclin dependent kinases |
| US20020065270A1 (en) | 1999-12-28 | 2002-05-30 | Moriarty Kevin Joseph | N-heterocyclic inhibitors of TNF-alpha expression |
| KR20010111298A (ko) | 2000-02-05 | 2001-12-17 | 버텍스 파마슈티칼스 인코포레이티드 | Ｅｒｋ의 억제제로서 유용한 피라졸 조성물 |
| JP2003532635A (ja) | 2000-02-17 | 2003-11-05 | アムジエン・インコーポレーテツド | キナーゼ阻害薬 |
| GB0004890D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| CA2398446A1 (en) * | 2000-04-18 | 2001-10-25 | Agouron Pharmaceuticals, Inc. | Pyrazoles for inhibiting protein kinases |
| WO2002000649A1 (en) | 2000-06-28 | 2002-01-03 | Astrazeneca Ab | Substituted quinazoline derivatives and their use as inhibitors |
| EP1313710A1 (en) | 2000-08-31 | 2003-05-28 | Pfizer Products Inc. | Pyrazole derivatives and their use as protein kinase inhibitors |
| ATE346064T1 (de) | 2000-09-15 | 2006-12-15 | Vertex Pharma | Pyrazolverbindungen als protein-kinasehemmer |
| US6660731B2 (en) | 2000-09-15 | 2003-12-09 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| US6610677B2 (en) | 2000-09-15 | 2003-08-26 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| US6613776B2 (en) | 2000-09-15 | 2003-09-02 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| US7473691B2 (en) | 2000-09-15 | 2009-01-06 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| EP1317453B1 (en) | 2000-09-15 | 2006-08-09 | Vertex Pharmaceuticals Incorporated | Isoxazoles and their use as inhibitors of erk |
| EP1318984A1 (en) | 2000-09-20 | 2003-06-18 | MERCK PATENT GmbH | 4-amino-quinazolines |
| US6716851B2 (en) | 2000-12-12 | 2004-04-06 | Cytovia, Inc. | Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators or caspases and inducers of apoptosis and the use thereof |
| DE10061863A1 (de) | 2000-12-12 | 2002-06-13 | Basf Ag | Verfahren zur Herstellung von Triethylendiamin (TEDA) |
| AU2002228922A1 (en) | 2000-12-12 | 2002-06-24 | Cytovia, Inc. | Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators of caspases and inducers of apoptosis and the use thereof |
| JP2004518662A (ja) * | 2000-12-19 | 2004-06-24 | 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 | Ｇｓｋ−３阻害剤としてのピラゾロ［３，４−ｃ］ピリジン |
| WO2002068415A1 (en) | 2000-12-21 | 2002-09-06 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| MY130778A (en) | 2001-02-09 | 2007-07-31 | Vertex Pharma | Heterocyclic inhibitiors of erk2 and uses thereof |
| US6949544B2 (en) | 2001-03-29 | 2005-09-27 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-Jun N-terminal kinases (JNK) and other protein kinases |
| DE60214701T2 (de) | 2001-04-13 | 2007-09-13 | Vertex Pharmaceuticals Inc., Cambridge | Inhibitoren von c-jun-n-terminalen-kinasen (jnk) und anderen proteinkinasen |
| WO2002085909A1 (en) | 2001-04-20 | 2002-10-31 | Vertex Pharmaceuticals Incorporated | 9-deazaguanine derivatives as inhibitors of gsk-3 |
| EP1404669A2 (en) | 2001-05-16 | 2004-04-07 | Vertex Pharmaceuticals Incorporated | Heterocyclic substituted pyrazoles as inhibitors of src and other protein kinases |
| ATE432929T1 (de) | 2001-06-15 | 2009-06-15 | Vertex Pharma | 5-(2-aminopyrimidin-4-yl)benzisoxazole als proteinkinasehemmer |
| ATE337312T1 (de) | 2001-07-03 | 2006-09-15 | Vertex Pharma | Isoxazolyl-pyrimidines als inhibitoren von src- und lck-protein-kinasen |
| EP2198867A1 (en) | 2001-12-07 | 2010-06-23 | Vertex Pharmaceuticals, Inc. | Pyrimidine-based compounds useful as GSK-3 inhibitors |
| ATE365733T1 (de) | 2002-03-15 | 2007-07-15 | Vertex Pharma | Zusammensetzungen brauchbar als protein-kinase- inhibitoren |
| US20040009981A1 (en) | 2002-03-15 | 2004-01-15 | David Bebbington | Compositions useful as inhibitors of protein kinases |
| AU2003225800A1 (en) | 2002-03-15 | 2003-09-29 | Hayley Binch | Azolylaminoazine as inhibitors of protein kinases |
| US7091343B2 (en) | 2002-03-15 | 2006-08-15 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of protein kinases |
| US20030207873A1 (en) | 2002-04-10 | 2003-11-06 | Edmund Harrington | Inhibitors of Src and other protein kinases |
| WO2003091246A1 (en) | 2002-04-26 | 2003-11-06 | Vertex Pharmaceuticals Incorporated | Pyrrole derivatives as inhibitors of erk2 and uses thereof |
| MY141867A (en) | 2002-06-20 | 2010-07-16 | Vertex Pharma | Substituted pyrimidines useful as protein kinase inhibitors |
| JP4570955B2 (ja) | 2002-07-09 | 2010-10-27 | バーテクス ファーマスーティカルズ インコーポレイテッド | プロテインキナーゼ阻害活性を持つイミダゾール類 |
| JP4733388B2 (ja) * | 2002-08-02 | 2011-07-27 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ｇｓｋ−３のインヒビターとして有用なピラゾール組成物 |
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