UA127826C2 - СПОСІБ ОДЕРЖАННЯ (S)-N-(5-((R)-2-(2,5-ДИФТОРФЕНІЛ)ПІРОЛІДИН-1-ІЛ)-ПІРАЗОЛО[1,5-а]ПІРИМІДИН-3-ІЛ)-3-ГІДРОКСИПІРОЛІДИН-1-КАРБОКСАМІДУ - Google Patents
СПОСІБ ОДЕРЖАННЯ (S)-N-(5-((R)-2-(2,5-ДИФТОРФЕНІЛ)ПІРОЛІДИН-1-ІЛ)-ПІРАЗОЛО[1,5-а]ПІРИМІДИН-3-ІЛ)-3-ГІДРОКСИПІРОЛІДИН-1-КАРБОКСАМІДУ Download PDFInfo
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- UA127826C2 UA127826C2 UAA201812601A UAA201812601A UA127826C2 UA 127826 C2 UA127826 C2 UA 127826C2 UA A201812601 A UAA201812601 A UA A201812601A UA A201812601 A UAA201812601 A UA A201812601A UA 127826 C2 UA127826 C2 UA 127826C2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
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| US201662338359P | 2016-05-18 | 2016-05-18 | |
| PCT/US2017/033257 WO2017201241A1 (en) | 2016-05-18 | 2017-05-18 | Preparation of (s)-n-(5-((r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-y l)-3-hydroxypyrrolidine-1-carboxamide |
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| UA127826C2 true UA127826C2 (uk) | 2024-01-17 |
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| WO2010033941A1 (en) | 2008-09-22 | 2010-03-25 | Array Biopharma Inc. | Substituted imidazo[1,2b]pyridazine compounds as trk kinase inhibitors |
| MY169791A (en) | 2008-10-22 | 2019-05-15 | Array Biopharma Inc | Substituted pyrazolo [1,5-a] pyrimidine compounds as trk kinase inhibitors |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| ME03376B (me) | 2010-05-20 | 2020-01-20 | Array Biopharma Inc | Makrociklička jedinjenja kао inhibiтori trk kinaze |
| CN113354649B (zh) | 2014-11-16 | 2024-12-10 | 阵列生物制药公司 | 一种新的晶型 |
| EP3368039A1 (en) | 2015-10-26 | 2018-09-05 | The Regents of The University of Colorado, A Body Corporate | Point mutations in trk inhibitor-resistant cancer and methods relating to the same |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| FI3439662T3 (fi) | 2016-04-04 | 2024-09-04 | Loxo Oncology Inc | (s)-n-(5-((r)-2-(2,5-difluorifenyyli)pyrrolidin-1-yyli)pyratsolo[1,5-a]pyrimidin-3-yyli)-3-hydroksipyrrolidiini-1-karboksamidin nesteformulaatioita |
| EP3458456B1 (en) | 2016-05-18 | 2020-11-25 | Loxo Oncology Inc. | Preparation of (s)-n-(5-((r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| FI3661935T3 (fi) * | 2017-08-11 | 2023-01-13 | Kinaasin estäjinä käyttökelpoiset pyratsolipyrimidiinit | |
| CN109232582B (zh) * | 2018-11-28 | 2021-02-05 | 安礼特（上海）医药科技有限公司 | 拉洛替尼硫酸氢盐晶型及其制备和应用 |
| CN112457231A (zh) * | 2019-09-09 | 2021-03-09 | 上海医药工业研究院 | 一种拉罗替尼（Larotrectinib）中间体的消旋化方法 |
| CN110804059B (zh) * | 2019-09-30 | 2024-03-12 | 郑州泰基鸿诺医药股份有限公司 | 氨基甲酸酯类化合物、药物组合物及其应用 |
| CN111138437B (zh) * | 2019-12-04 | 2021-03-05 | 杭州华东医药集团新药研究院有限公司 | 取代的吡唑并[1,5-a]嘧啶氨基酸衍生物及其用途 |
| CN112624950A (zh) * | 2020-12-10 | 2021-04-09 | 北京蓝博特科技有限公司 | 一种(r)-2-(2,5-二氟苯基)吡咯烷的合成方法 |
| WO2022168115A1 (en) | 2021-02-05 | 2022-08-11 | Mylan Laboratories Limited | A process for the preparation of larotrectinib or its salts |
| CN113444070A (zh) * | 2021-07-28 | 2021-09-28 | 深圳市真味生物科技有限公司 | 一种由手性叔丁基亚磺酰胺合成手性尼古丁的制备方法 |
| CN115872905B (zh) * | 2021-09-29 | 2024-08-09 | 凯特立斯（深圳）科技有限公司 | 一种拉罗替尼中间体的制备方法 |
| WO2024023836A1 (en) | 2022-07-27 | 2024-02-01 | Mylan Laboratories Limited | Polymorphic form of larotrectinib sulfate |
| EP4382529A1 (en) | 2022-12-07 | 2024-06-12 | Bayer Consumer Care AG | A process for preparing pure (3s)-pyrrolidin-3-ol and pure (3s)-pyrrolidin-3-ol hydrochloride |
Family Cites Families (272)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ234143A (en) | 1989-06-28 | 1991-10-25 | Mcneil Ppc Inc | Aqueous pharmaceutical suspension formulation for administering substantially insoluble pharmaceutical agents |
| GB9212308D0 (en) * | 1992-06-10 | 1992-07-22 | Ici Plc | Therapeutic compositions |
| DE69422306T4 (de) | 1993-11-30 | 2000-09-07 | G.D. Searle & Co., Chicago | Substituierte pyrazolyl-benzolsulfonamide zur behandlung von entzündungen |
| US5430021A (en) | 1994-03-18 | 1995-07-04 | Pharmavene, Inc. | Hydrophobic drug delivery systems |
| US5877016A (en) | 1994-03-18 | 1999-03-02 | Genentech, Inc. | Human trk receptors and neurotrophic factor inhibitors |
| US5844092A (en) | 1994-03-18 | 1998-12-01 | Genentech, Inc. | Human TRK receptors and neurotrophic factor inhibitors |
| US6458811B1 (en) | 1996-03-26 | 2002-10-01 | Eli Lilly And Company | Benzothiophenes formulations containing same and methods |
| CA2206201A1 (en) | 1996-05-29 | 1997-11-29 | Yoshiaki Isobe | Pyrazole derivatives and their pharmaceutical use |
| JP3898296B2 (ja) | 1996-08-28 | 2007-03-28 | ポーラ化成工業株式会社 | ピロロピラゾロピリミジン化合物及びこれを有効成分とする医薬 |
| CA2285264A1 (en) | 1997-04-25 | 1998-11-05 | Michiyo Gyoten | Condensed pyridazine derivatives, their production and use |
| KR100708360B1 (ko) | 1999-01-21 | 2007-04-17 | 브리스톨-마이어스스퀴브컴파니 | 라스-파르네실트란스퍼라제 억제제와술포부틸에테르-7-β-시클로덱스트린 또는2-히드록시프로필-β-시클로덱스트린과의 착물 및 방법 |
| UA74546C2 (en) | 1999-04-06 | 2006-01-16 | Boehringer Ingelheim Ca Ltd | Macrocyclic peptides having activity relative to hepatitis c virus, a pharmaceutical composition and use of the pharmaceutical composition |
| US6534085B1 (en) | 1999-09-23 | 2003-03-18 | Bioresponse L.L.C. | Phytochemicals for promoting weight loss |
| CA2412494C (en) | 2000-06-22 | 2012-10-23 | Genentech, Inc. | Agonist anti-trk-c monoclonal antibodies |
| GB0028575D0 (en) | 2000-11-23 | 2001-01-10 | Elan Corp Plc | Oral pharmaceutical compositions containing cyclodextrins |
| GB0121919D0 (en) * | 2001-09-11 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| BR0116388A (pt) | 2000-12-22 | 2003-09-30 | Astrazeneca Ab | Composto, processo para preparar um composto, composição farmacêutica e método para tratar, em um animal de sangue quente, distúrbios de alimentação e uso de um composto |
| TWI312347B (en) | 2001-02-08 | 2009-07-21 | Eisai R&D Man Co Ltd | Bicyclic nitrogen-containing condensed ring compounds |
| CA2975521A1 (en) | 2001-05-30 | 2002-12-05 | Genentech, Inc. | Anti-ngf antibodies for the treatment of various disorders |
| US7101572B2 (en) | 2001-12-07 | 2006-09-05 | Unilab Pharmatech, Ltd. | Taste masked aqueous liquid pharmaceutical composition |
| US20030199525A1 (en) | 2002-03-21 | 2003-10-23 | Hirst Gavin C. | Kinase inhibitors |
| US7662826B2 (en) | 2002-04-23 | 2010-02-16 | Shionogi & Co., Ltd. | Pyrazolo [1,5-a] pyrimidine derivative and nad (p) h oxidase inhibitor containing the same |
| US7449488B2 (en) | 2002-06-04 | 2008-11-11 | Schering Corporation | Pyrazolopyrimidines as protein kinase inhibitors |
| US6982253B2 (en) | 2002-06-05 | 2006-01-03 | Supergen, Inc. | Liquid formulation of decitabine and use of the same |
| ITMI20021620A1 (it) | 2002-07-23 | 2004-01-23 | Novuspharma Spa | Composto ad ativita' antitumorale |
| JP4024624B2 (ja) | 2002-08-26 | 2007-12-19 | 富士通株式会社 | 半導体装置の製造方法及び製造装置 |
| MXPA05002571A (es) | 2002-09-04 | 2005-09-08 | Schering Corp | Pirazolopirimidinas como inhibidores de cinasa dependientes de ciclina. |
| US7196078B2 (en) | 2002-09-04 | 2007-03-27 | Schering Corpoartion | Trisubstituted and tetrasubstituted pyrazolopyrimidines as cyclin dependent kinase inhibitors |
| US8580782B2 (en) | 2002-09-04 | 2013-11-12 | Merck Sharp & Dohme Corp. | Substituted pyrazolo[1,5-a]pyrimidines as cyclin dependent kinase inhibitors |
| US7119200B2 (en) | 2002-09-04 | 2006-10-10 | Schering Corporation | Pyrazolopyrimidines as cyclin dependent kinase inhibitors |
| US7550470B2 (en) | 2002-12-11 | 2009-06-23 | Merck & Co. Inc. | Substituted pyrazolo[1,5-A]pyrimidines as tyrosine kinase inhibitors |
| AU2003298942A1 (en) | 2002-12-11 | 2004-06-30 | Merck And Co., Inc. | Tyrosine kinase inhibitors |
| GB0303910D0 (en) | 2003-02-20 | 2003-03-26 | Merck Sharp & Dohme | Therapeutic agents |
| ES2325440T3 (es) | 2003-02-20 | 2009-09-04 | Smithkline Beecham Corporation | Compuestos de pirimidina. |
| WO2004082458A2 (en) | 2003-02-21 | 2004-09-30 | The Johns Hopkins University | Tyrosine kinome |
| JP2004277337A (ja) | 2003-03-14 | 2004-10-07 | Sumitomo Pharmaceut Co Ltd | ピラゾロ［１，５−ａ］ピリミジン誘導体 |
| US20070179161A1 (en) | 2003-03-31 | 2007-08-02 | Vernalis (Cambridge) Limited. | Pyrazolopyrimidine compounds and their use in medicine |
| JP2006522744A (ja) | 2003-04-11 | 2006-10-05 | ノボ ノルディスク アクティーゼルスカブ | グルココルチコイド受容体アゴニスト療法に伴う副作用を最小化するための、１１β−ヒドロキシステロイドデヒドロゲナーゼ１型阻害剤およびグルココルチコイド受容体アゴニストを使用する併用療法 |
| WO2004089471A2 (en) | 2003-04-11 | 2004-10-21 | Novo Nordisk A/S | NEW PYRAZOLO[1,5-a] PYRIMIDINES DERIVATIVES AND PHARMACEUTICAL USE THEREOF |
| US20060094699A1 (en) | 2003-04-11 | 2006-05-04 | Kampen Gita Camilla T | Combination therapy using an 11beta-hydroxysteroid dehydrogenase type 1 inhibitor and a glucocorticoid receptor agonist to minimize the side effects associated with glucocorticoid receptor agonist therapy |
| US20070042941A1 (en) | 2003-04-28 | 2007-02-22 | Mitsuomi Hirashima | Galectin 9-inducing factors |
| JO2785B1 (en) | 2003-05-27 | 2014-03-15 | شركة جانسين فارماسوتيكا ان. في | Quinazoline derivatives |
| JP2005008581A (ja) | 2003-06-20 | 2005-01-13 | Kissei Pharmaceut Co Ltd | 新規なピラゾロ［１，５−ａ］ピリミジン誘導体、それを含有する医薬組成物およびそれらの用途 |
| EA009517B1 (ru) | 2003-06-27 | 2008-02-28 | Байер Кропсайенс Аг | Пиразолопиримидины |
| AR045056A1 (es) | 2003-07-15 | 2005-10-12 | Amgen Inc | Anticuerpos anti-ngf humanos neutralizantes como inhibidores selectivos de la via de ngf |
| US7491794B2 (en) | 2003-10-14 | 2009-02-17 | Intermune, Inc. | Macrocyclic compounds as inhibitors of viral replication |
| CA2543116A1 (en) | 2003-10-27 | 2005-05-19 | Genelabs Technologies, Inc. | Methods for preparing 7-(2'-substituted-.szlig.-d-ribofuranosyl)-4-(nr2r3)-5-(substituted ethyn-1-yl)-pyrrolo[2,3-d]pyrimidine derivatives |
| MY141220A (en) | 2003-11-17 | 2010-03-31 | Astrazeneca Ab | Pyrazole derivatives as inhibitors of receptor tyrosine kinases |
| PE20051046A1 (es) | 2003-11-28 | 2006-01-11 | Novartis Ag | Derivados de diaril-urea en el tratamiento de enfermedades dependientes de la quinasa de proteina |
| MXPA06007017A (es) | 2003-12-18 | 2006-08-31 | Janssen Pharmaceutica Nv | Derivados de pirido y pirimidopirimidina como agentes antiproliferativos. |
| CN1925855B (zh) | 2003-12-19 | 2010-06-16 | 普莱希科公司 | 开发Ret调节剂的化合物和方法 |
| WO2005068424A1 (en) | 2004-01-20 | 2005-07-28 | Cell Therapeutics Europe S.R.L. | Indolinone derivatives as receptor tyrosine kinase ihibitors |
| US20050222171A1 (en) | 2004-01-22 | 2005-10-06 | Guido Bold | Organic compounds |
| WO2005099363A2 (en) | 2004-03-26 | 2005-10-27 | Whitehead Institute For Biomedical Research | Methods of diagnosing, preventing and treating cancer metastasis |
| CN1938311A (zh) | 2004-03-30 | 2007-03-28 | 因特蒙公司 | 作为病毒复制抑制剂的大环化合物 |
| GB0512324D0 (en) | 2005-06-16 | 2005-07-27 | Novartis Ag | Organic compounds |
| PE20060664A1 (es) | 2004-09-15 | 2006-08-04 | Novartis Ag | Amidas biciclicas como inhibidores de cinasa |
| PT1812440E (pt) | 2004-11-04 | 2011-01-25 | Vertex Pharma | Pirazolo[1,5-a]pirimidinas úteis enquanto inibidores de proteínas cinases |
| JO3088B1 (ar) | 2004-12-08 | 2017-03-15 | Janssen Pharmaceutica Nv | مشتقات كوينازولين كبيرة الحلقات و استعمالها بصفتها موانع كينيز متعددة الاهداف |
| DE102005003687A1 (de) | 2005-01-26 | 2006-07-27 | Sphingo Tec Gmbh | Immunoassay zur Bestimmung der Freisetzung von Neurotensin in die Zirkulation |
| CN101119996A (zh) | 2005-02-16 | 2008-02-06 | 阿斯利康(瑞典)有限公司 | 化学化合物 |
| ES2347172T3 (es) | 2005-02-16 | 2010-10-26 | Astrazeneca Ab | Compuestos quimicos. |
| EP1869049B1 (en) | 2005-03-21 | 2009-03-04 | Eli Lilly And Company | Imidazopyridazine compounds |
| CN101208093A (zh) | 2005-04-27 | 2008-06-25 | 阿斯利康(瑞典)有限公司 | 吡唑-嘧啶衍生物在治疗疼痛中的用途 |
| US20080287437A1 (en) | 2005-05-16 | 2008-11-20 | Astrazeneca Ab | Pyrazolylaminopyrimidine Derivatives Useful as Tyrosine Kinase Inhibitors |
| CN100406650C (zh) | 2005-06-05 | 2008-07-30 | 徐斌 | 一种抗特大变位的模块式梳型桥梁伸缩缝装置 |
| ITRM20050290A1 (it) | 2005-06-07 | 2006-12-08 | Lay Line Genomics Spa | Uso di molecole in grado di inibire il legame tra ngf e il suo recettore trka come analgesici ad effetto prolungato. |
| UA95244C2 (ru) | 2005-06-22 | 2011-07-25 | Плексикон, Инк. | Соединения и способ модулирования активности киназ, и показания для их применения |
| US20070025540A1 (en) | 2005-07-07 | 2007-02-01 | Roger Travis | Call center routing based on talkativeness |
| MX2008001166A (es) | 2005-07-25 | 2008-03-18 | Intermune Inc | Nuevos inhibidores macrociclicos de la replicacion del virus de hepatitis c. |
| EP1910369A1 (en) | 2005-07-29 | 2008-04-16 | Astellas Pharma Inc. | Fused heterocycles as lck inhibitors |
| CN101232871A (zh) | 2005-08-03 | 2008-07-30 | 伊士曼化工公司 | 生育酚聚乙二醇琥珀酸酯粉末及其制备方法 |
| US20070191306A1 (en) | 2005-08-17 | 2007-08-16 | Bristol-Myers Squibb Company | FACTOR Xa INHIBITOR FORMULATION AND METHOD |
| EP1926734A1 (en) | 2005-08-22 | 2008-06-04 | Amgen Inc. | Pyrazolopyridine and pyrazolopyrimidine compounds useful as kinase enzymes modulators |
| WO2007022999A1 (en) | 2005-08-25 | 2007-03-01 | Creabilis Therapeutics S.P.A. | Polymer conjugates of k-252a and derivatives thereof |
| US20070049591A1 (en) | 2005-08-25 | 2007-03-01 | Kalypsys, Inc. | Inhibitors of MAPK/Erk Kinase |
| DE102005042742A1 (de) | 2005-09-02 | 2007-03-08 | Schering Ag | Substituierte Imidazo[1,2b]pyridazine als Kinase-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel |
| US20070078136A1 (en) | 2005-09-22 | 2007-04-05 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
| BRPI0616985B1 (pt) | 2005-10-06 | 2021-10-26 | Merck Sharp & Dohme Corp. | Composto de pirazolo[1,5-a]pirimidina, e, uso de um composto |
| AR057979A1 (es) | 2005-10-06 | 2008-01-09 | Schering Corp | PIRAZOLPIRIMIDINAS COMO INHIBIDORAS DE PROTEíNA QUINASA. COMPOSICIONES FARMACEUTICAS. |
| ATE519757T1 (de) | 2005-10-11 | 2011-08-15 | Centre Nat Rech Scient | 3 hydroxyflavon-derivate zur erkennung und quantifizierung von zell-apoptosen |
| AU2006301966A1 (en) | 2005-10-11 | 2007-04-19 | Array Biopharma, Inc. | Compounds and methods for inhibiting hepatitis C viral replication |
| US8372851B2 (en) | 2005-10-21 | 2013-02-12 | Exelixis, Inc. | Pyrazolo pyrimidines as casein kinase II (CK2) modulators |
| WO2007057399A2 (en) | 2005-11-15 | 2007-05-24 | Boehringer Ingelheim International Gmbh | Treatment of cancer with indole derivatives |
| GB0524436D0 (en) | 2005-11-30 | 2006-01-11 | Novartis Ag | Organic compounds |
| WO2007070504A2 (en) | 2005-12-13 | 2007-06-21 | Morton Grove Pharmaceuticals, Inc. | Stable and palatable oral liquid sumatriptan compositions |
| US8399442B2 (en) | 2005-12-30 | 2013-03-19 | Astex Therapeutics Limited | Pharmaceutical compounds |
| US20080108611A1 (en) | 2006-01-19 | 2008-05-08 | Battista Kathleen A | Substituted thienopyrimidine kinase inhibitors |
| WO2007087245A2 (en) | 2006-01-24 | 2007-08-02 | Merck & Co., Inc. | Ret tyrosine kinase inhibition |
| KR100846988B1 (ko) | 2006-03-06 | 2008-07-16 | 제일약품주식회사 | 신규한 티에노피리미딘 유도체 또는 이의 약학적으로허용가능한 염, 이의 제조방법 및 이를 함유하는 약학조성물 |
| WO2007103308A2 (en) * | 2006-03-07 | 2007-09-13 | Array Biopharma Inc. | Heterobicyclic pyrazole compounds and methods of use |
| BRPI0709680B8 (pt) | 2006-03-27 | 2021-05-25 | Nerviano Medical Sciences Srl | derivados de pirrol, tiofeno e furano substituídos por piridil e piridimil como inibidores de quinase |
| GB0606805D0 (en) | 2006-04-04 | 2006-05-17 | Novartis Ag | Organic compounds |
| WO2007129161A2 (en) | 2006-04-26 | 2007-11-15 | F. Hoffmann-La Roche Ag | Thieno [3, 2-d] pyrimidine derivative useful as pi3k inhibitor |
| CN104706637A (zh) | 2006-05-18 | 2015-06-17 | 卫材R&D管理有限公司 | 针对甲状腺癌的抗肿瘤剂 |
| EP1873157A1 (en) | 2006-06-21 | 2008-01-02 | Bayer Schering Pharma Aktiengesellschaft | Pyrazolopyrimidines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| TWI419889B (zh) | 2006-07-05 | 2013-12-21 | Mitsubishi Tanabe Pharma Corp | 吡唑并〔１，５-ａ〕嘧啶化合物 |
| EP2058309A4 (en) | 2006-08-04 | 2010-12-22 | Takeda Pharmaceutical | CONDENSED HETEROCYCLIC COMPOUND |
| AU2007279595A1 (en) | 2006-08-04 | 2008-02-07 | Takeda Pharmaceutical Company Limited | Fused heterocyclic derivative and use thereof |
| US7531539B2 (en) | 2006-08-09 | 2009-05-12 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
| CN101594909A (zh) | 2006-09-07 | 2009-12-02 | 比奥根艾迪克Ma公司 | 用于治疗炎性病症、细胞增殖性失调、免疫失调的irak调节剂 |
| EP2067039A2 (en) | 2006-09-12 | 2009-06-10 | Novartis Forschungsstiftung, Zweigniederlassung Friedrich Miescher Institute for Biomedical Research | Non-neuroendocrine cancer therapy |
| WO2008037477A1 (en) | 2006-09-29 | 2008-04-03 | Novartis Ag | Pyrazolopyrimidines as p13k lipid kinase inhibitors |
| JP2010508315A (ja) | 2006-10-30 | 2010-03-18 | ノバルティス アーゲー | 抗炎症剤としてのヘテロ環式化合物 |
| WO2008058126A2 (en) | 2006-11-06 | 2008-05-15 | Supergen, Inc. | Imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine derivatives and their use as protein kinase inhibitors |
| WO2008079909A1 (en) | 2006-12-21 | 2008-07-03 | Plexxikon, Inc. | Pyrrolo [2,3-b] pyridines as kinase modulators |
| JP2010514695A (ja) | 2006-12-21 | 2010-05-06 | プレキシコン，インコーポレーテッド | キナーゼ調節のための化合物および方法およびそのための適応症 |
| PE20121126A1 (es) | 2006-12-21 | 2012-08-24 | Plexxikon Inc | Compuestos pirrolo [2,3-b] piridinas como moduladores de quinasa |
| US7820684B2 (en) | 2007-03-01 | 2010-10-26 | Supergen, Inc. | Pharmaceutical formulations comprising salts of a protein kinase inhibitor and methods of using same |
| US20080234267A1 (en) | 2007-03-20 | 2008-09-25 | Karen Elizabeth Lackey | Compounds and Methods of Treatment |
| US20080234262A1 (en) | 2007-03-21 | 2008-09-25 | Wyeth | Pyrazolopyrimidine analogs and their use as mtor kinase and pi3 kinase inhibitors |
| CA2682016A1 (en) | 2007-03-28 | 2008-10-02 | Inovacia Ab | Pyrazolo [1,5-a]pyrimidines as inhibitors of stearoyl-coa desaturase |
| NZ580327A (en) | 2007-04-03 | 2012-02-24 | Array Biopharma Inc | IMIDAZO[1,2-a]PYRIDINE COMPOUNDS AS RECEPTOR TYROSINE KINASE INHIBITORS |
| EA019524B1 (ru) | 2007-05-04 | 2014-04-30 | Айрм Ллк | СОЕДИНЕНИЯ И КОМПОЗИЦИИ КАК ИНГИБИТОРЫ КИНАЗЫ с-kit И PDGFR |
| CA2687909C (en) | 2007-06-21 | 2015-09-15 | Janssen Pharmaceutica Nv | Indolin-2-ones and aza-indolin-2-ones |
| AU2008273889B2 (en) | 2007-07-09 | 2012-03-08 | Astrazeneca Ab | Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases |
| WO2009012283A1 (en) | 2007-07-17 | 2009-01-22 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| MY150032A (en) | 2007-07-19 | 2013-11-29 | Merck Sharp & Dohme | Heterocyclic amide compounds as protein kinase inhibitors |
| PT2176231T (pt) | 2007-07-20 | 2016-12-09 | Nerviano Medical Sciences Srl | Derivados de indazol substituídos activos como inibidores de quinases |
| WO2009017838A2 (en) | 2007-08-01 | 2009-02-05 | Exelixis, Inc. | Combinations of jak-2 inhibitors and other agents |
| MX2010001395A (es) | 2007-08-10 | 2010-03-10 | Regeneron Pharma | Anticuerpos humanos de alta afinidad de factor de crecimiento de nervio humano. |
| EA201000484A1 (ru) | 2007-10-16 | 2010-12-30 | ВАЙЕТ ЭлЭлСи | Тиенопиримидиновые и пиразолопиримидиновые соединения и их применение в качестве ингибиторов киназы mtor и киназы pi3 |
| EP2214706A1 (en) | 2007-10-23 | 2010-08-11 | Novartis AG | Use of trkb antibodies for the treatment of respiratory disorders |
| EP2217601A1 (en) | 2007-11-08 | 2010-08-18 | Centro Nacional de Investigaciones Oncológicas (CNIO) | Imidazopyridazines for use as protein kinase inhibitors |
| CN101970440A (zh) | 2007-11-28 | 2011-02-09 | 先灵公司 | 作为蛋白激酶抑制剂的2-氟吡唑并[1，5-a]嘧啶类 |
| WO2009071480A2 (en) | 2007-12-04 | 2009-06-11 | Nerviano Medical Sciences S.R.L. | Substituted dihydropteridin-6-one derivatives, process for their preparation and their use as kinase inhibitors |
| PE20091326A1 (es) | 2008-01-17 | 2009-09-18 | Irm Llc | Anticuerpos anti-trkb mejorados |
| JP2009203226A (ja) | 2008-01-31 | 2009-09-10 | Eisai R & D Management Co Ltd | ピリジン誘導体およびピリミジン誘導体を含有するレセプターチロシンキナーゼ阻害剤 |
| PL2273975T3 (pl) | 2008-03-03 | 2014-09-30 | Ucb Pharma Sa | Roztwory farmaceutyczne, sposoby wytwarzania i zastosowania terapeutyczne |
| KR100963051B1 (ko) | 2008-03-14 | 2010-06-09 | 광동제약 주식회사 | 입자크기가 조절된 술포데히드로아비에트산을 함유한쓴맛이 저감된 경구용 액상 조성물 |
| EP2254886B1 (en) | 2008-03-28 | 2016-05-25 | Nerviano Medical Sciences S.r.l. | 3,4-dihydro-2h-pyrazino[1,2-a]indol-1-one derivatives active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them |
| US20090275622A1 (en) | 2008-04-30 | 2009-11-05 | Prasoona Linga | Nizatidine formulations |
| KR101324804B1 (ko) | 2008-05-13 | 2013-11-01 | 아이알엠 엘엘씨 | 키나제 억제제로서의 질소 함유 융합 헤테로사이클 및 그의 조성물 |
| WO2009143018A2 (en) | 2008-05-19 | 2009-11-26 | Plexxikon, Inc. | Compounds and methods for kinase modulation, and indications therefor |
| PE20091846A1 (es) | 2008-05-19 | 2009-12-16 | Plexxikon Inc | DERIVADOS DE PIRROLO[2,3-d]-PIRIMIDINA COMO MODULADORES DE CINASAS |
| ES2554513T3 (es) | 2008-05-23 | 2015-12-21 | Novartis Ag | Derivados de quinolinas y quinoxalinas como inhibidores de la proteína tirosina quinasa |
| JP5767965B2 (ja) | 2008-06-10 | 2015-08-26 | プレキシコン インコーポレーテッドＰｌｅｘｘｉｋｏｎ Ｉｎｃ． | キナーゼを調節する５ｈ−ピロロ［２，３−ｂ］ピラジン誘導体、およびその適応症 |
| EP2323664B1 (en) | 2008-07-29 | 2015-01-07 | Nerviano Medical Sciences S.r.l. | Use of a cdk inhibitor for the treatment of glioma |
| JP5746032B2 (ja) | 2008-09-19 | 2015-07-08 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | ３，４−ジヒドロ−２Ｈ−ピロロ［１，２−ａ］ピラジン−１−オン誘導体 |
| WO2010033941A1 (en) | 2008-09-22 | 2010-03-25 | Array Biopharma Inc. | Substituted imidazo[1,2b]pyridazine compounds as trk kinase inhibitors |
| MY169791A (en) | 2008-10-22 | 2019-05-15 | Array Biopharma Inc | Substituted pyrazolo [1,5-a] pyrimidine compounds as trk kinase inhibitors |
| EP2348860B1 (en) | 2008-10-31 | 2015-05-27 | Genentech, Inc. | Pyrazolopyrimidine jak inhibitor compounds and methods |
| WO2010058006A1 (en) | 2008-11-24 | 2010-05-27 | Nerviano Medical Sciences S.R.L. | Cdk inhibitor for the treatment of mesothelioma |
| JO3265B1 (ar) | 2008-12-09 | 2018-09-16 | Novartis Ag | مثبطات بيريديلوكسى اندولات vegf-r2 واستخدامها لعلاج المرض |
| EP3266795A1 (en) | 2009-02-12 | 2018-01-10 | Cell Signaling Technology, Inc. | Method for detecting a fig-ros fusion polynucleotide |
| WO2010111527A1 (en) | 2009-03-26 | 2010-09-30 | Plexxikon, Inc. | Pyrazolo [ 3, 4 -b] pyridines as kinase inhibitors and their medical use |
| US8546413B2 (en) | 2009-06-15 | 2013-10-01 | Nerviano Medical Sciences S.R.L. | Substituted pyrimidinylpyrrolopyridinone derivatives, process for their preparation and their use as kinase inhibitors |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| LT3001903T (lt) | 2009-12-21 | 2018-01-10 | Samumed, Llc | 1h-pirazolo[3,4-b]piridinai ir jų terapinis panaudojimas |
| WO2011092120A1 (en) | 2010-01-29 | 2011-08-04 | Nerviano Medical Sciences S.R.L. | 6,7- dihydroimidazo [1,5-a] pyrazin-8 (5h) - one derivatives as protein kinase modulators |
| ES2594927T3 (es) | 2010-02-18 | 2016-12-23 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Métodos para prevenir las metástasis cancerosas |
| JP2013526852A (ja) | 2010-04-06 | 2013-06-27 | カリス ライフ サイエンシズ ルクセンブルク ホールディングス | 疾患に対する循環バイオマーカー |
| US8383793B2 (en) | 2010-04-15 | 2013-02-26 | St. Jude Children's Research Hospital | Methods and compositions for the diagnosis and treatment of cancer resistant to anaplastic lymphoma kinase (ALK) kinase inhibitors |
| TWI510487B (zh) | 2010-04-21 | 2015-12-01 | Plexxikon Inc | 用於激酶調節的化合物和方法及其適應症 |
| ME03376B (me) | 2010-05-20 | 2020-01-20 | Array Biopharma Inc | Makrociklička jedinjenja kао inhibiтori trk kinaze |
| PT2580322T (pt) | 2010-06-09 | 2018-03-01 | Dana Farber Cancer Inst Inc | Uma mutação em mek1 que confere resistência aos inibidores de raf e mek |
| WO2012024650A2 (en) | 2010-08-19 | 2012-02-23 | Abbott Laboratories | Anti-ngf antibodies and their use |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| JP2014005206A (ja) | 2010-10-22 | 2014-01-16 | Astellas Pharma Inc | アリールアミノヘテロ環カルボキサミド化合物 |
| EP2646468B1 (en) | 2010-12-01 | 2018-07-25 | AlderBio Holdings LLC | Anti-ngf compositions and use thereof |
| WO2012101029A1 (en) | 2011-01-26 | 2012-08-02 | Nerviano Medical Sciences S.R.L. | Tricyclic derivatives, process for their preparation and their use as kinase inhibitors |
| EP2668190B1 (en) | 2011-01-26 | 2016-08-17 | Nerviano Medical Sciences S.r.l. | Tricyclic pyrrolo derivatives, process for their preparation and their use as kinase inhibitors |
| US9624213B2 (en) | 2011-02-07 | 2017-04-18 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| CN103403002B (zh) | 2011-02-24 | 2016-06-22 | 内尔维阿诺医学科学有限公司 | 作为激酶抑制剂的噻唑基苯基-苯磺酰氨基衍生物 |
| MA34969B1 (fr) | 2011-02-25 | 2014-03-01 | Irm Llc | Composes et compositions en tant qu inibiteurs de trk |
| EP2702055A1 (en) | 2011-04-11 | 2014-03-05 | Nerviano Medical Sciences S.r.l. | Pyrazolyl-pyrimidine derivatives as kinase inhibitors |
| JP5970537B2 (ja) | 2011-04-19 | 2016-08-17 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | キナーゼ阻害薬として活性な置換ピリミジニル−ピロール |
| PT2707359T (pt) | 2011-05-12 | 2017-01-09 | Nerviano Medical Sciences Srl | Derivados de indazol substituídos ativos como inibidores de quinase |
| CA2835835C (en) | 2011-05-13 | 2019-04-02 | Array Biopharma Inc. | Pyrrolidinyl urea and pyrrolidinyl thiourea compounds as trka kinase inhibitors |
| JP6016915B2 (ja) | 2011-07-28 | 2016-10-26 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | キナーゼ阻害剤として活性なアルキニル置換ピリミジニルピロール |
| JP6063945B2 (ja) | 2011-10-07 | 2017-01-18 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | キナーゼ阻害剤としての４−アルキル置換３，４−ジヒドロピロロ［１，２−ａ］ピラジン−１（２Ｈ）−オン誘導体 |
| US9145418B2 (en) | 2011-10-07 | 2015-09-29 | Nerviano Medical Sciences S.R.L. | Substituted 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-ones as protein kinase inhibitors |
| WO2013059740A1 (en) | 2011-10-21 | 2013-04-25 | Foundation Medicine, Inc. | Novel alk and ntrk1 fusion molecules and uses thereof |
| EP2779833A4 (en) | 2011-11-14 | 2015-03-18 | Tesaro Inc | MODULATION OF SPECIFIC TYROSINE KINASES |
| AU2012351748B2 (en) | 2011-12-12 | 2016-04-14 | Dr. Reddy's Laboratories Ltd. | Substituted pyrazolo[1,5-a] pyridine as tropomyosin receptor kinase (Trk) inhibitors |
| US8377946B1 (en) | 2011-12-30 | 2013-02-19 | Pharmacyclics, Inc. | Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors |
| TW201350479A (zh) | 2012-04-26 | 2013-12-16 | Ono Pharmaceutical Co | Ｔｒｋ阻害化合物 |
| JP2013226108A (ja) | 2012-04-27 | 2013-11-07 | Astellas Pharma Inc | 新規ｎｔｒｋ２活性化変異の検出法 |
| ES2751944T3 (es) | 2012-05-23 | 2020-04-02 | Nerviano Medical Sciences Srl | Proceso para la preparación de N-[5-(3,5-difluoro-bencil)-1H-indazol-3-il]-4-(4-metil-piperazin-1-il)-2-(tetrahidro-piran-4-ilamino)-benzamida |
| TWI585088B (zh) | 2012-06-04 | 2017-06-01 | 第一三共股份有限公司 | 作爲激酶抑制劑之咪唑并［１，２－ｂ］嗒衍生物 |
| EP2866802B1 (en) | 2012-06-28 | 2016-07-27 | Johnson & Johnson Consumer Inc. | Racecadotril liquid compositions |
| SG11201500125QA (en) | 2012-07-11 | 2015-02-27 | Blueprint Medicines Corp | Inhibitors of the fibroblast growth factor receptor |
| CN104704129A (zh) | 2012-07-24 | 2015-06-10 | 药品循环公司 | 与对布鲁顿酪氨酸激酶(btk)抑制剂的抗性相关的突变 |
| EP2689778A1 (en) | 2012-07-27 | 2014-01-29 | Pierre Fabre Medicament | Derivatives of azaindoles or diazaindoles for treating pain |
| BR112015002152B1 (pt) | 2012-08-02 | 2021-04-27 | Nerviano Medical Sciences S.R.L. | Compostos de pirróis substituídos ativos como inibidores de quinases, processo para a preparação de tais compostos, composição farmacêutica, método in vitro para a inibição da atividade de proteínas quinases da família jak e produto compreendendo os referidos compostos |
| EP2890815B1 (en) | 2012-08-31 | 2019-03-20 | The Regents of the University of Colorado | Methods for diagnosis and treatment of cancer |
| JP6513567B2 (ja) | 2012-09-07 | 2019-05-15 | エクセリクシス， インク． | 肺腺癌の治療で使用するためのｍｅｔ、ｖｅｇｆｒ、およびｒｅｔの阻害剤 |
| US20140084039A1 (en) | 2012-09-24 | 2014-03-27 | Electro Scientific Industries, Inc. | Method and apparatus for separating workpieces |
| JP2014082984A (ja) | 2012-10-23 | 2014-05-12 | Astellas Pharma Inc | 新規ｎｔｒｋ２活性化変異の検出法 |
| EP2914621B1 (en) | 2012-11-05 | 2023-06-07 | Foundation Medicine, Inc. | Novel ntrk1 fusion molecules and uses thereof |
| US11230589B2 (en) | 2012-11-05 | 2022-01-25 | Foundation Medicine, Inc. | Fusion molecules and uses thereof |
| ES2755772T3 (es) | 2012-11-07 | 2020-04-23 | Nerviano Medical Sciences Srl | Pirimidinil y piridinilpirrolopiridinonas sustituidas, proceso para su preparación y su uso como inhibidores de cinasas |
| WO2014078372A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| RS55593B1 (sr) | 2012-11-13 | 2017-06-30 | Array Biopharma Inc | Jedinjenja biciklične uree, tiouree, guanidina i cijanoguanidina korisna za lečenje bola |
| WO2014078331A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-(arylalkyl)-n'-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078378A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078417A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | Pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078325A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-(monocyclic aryl),n'-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| MX374242B (es) | 2012-11-13 | 2025-03-05 | Array Biopharma Inc | Compuestos de n-pirrolidinil, n' -pirazolil-urea, tiourea, guanidina y cianoguanidina como inhibidores de trka cinasa. |
| US9822118B2 (en) | 2012-11-13 | 2017-11-21 | Array Biopharma Inc. | Bicyclic heteroaryl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
| US9981959B2 (en) | 2012-11-13 | 2018-05-29 | Array Biopharma Inc. | Thiazolyl and oxazolyl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
| WO2014078328A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-bicyclic aryl,n'-pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| CA2877847A1 (en) | 2012-11-29 | 2014-06-05 | Yeda Research And Development Co. Ltd. | Methods of preventing tumor metastasis, treating and prognosing cancer and identifying agents which are putative metastasis inhibitors |
| US9447135B2 (en) | 2012-12-14 | 2016-09-20 | University Of Kentucky Research Foundation | Semi-synthetic mithramycin derivatives with anti-cancer activity |
| US9127055B2 (en) | 2013-02-08 | 2015-09-08 | Astellas Pharma Inc. | Method of treating pain with anti-human NGF antibody |
| AU2014219855B2 (en) | 2013-02-19 | 2017-09-28 | Ono Pharmaceutical Co., Ltd. | Trk-inhibiting compound |
| WO2014130975A1 (en) | 2013-02-22 | 2014-08-28 | Bastian Boris C | Fusion polynucleotides and fusion polypeptides associated with cancer and particularly melanoma and their uses as therapeutic and diagnostic targets |
| WO2014134096A1 (en) | 2013-02-27 | 2014-09-04 | Oregon Health & Science University | Methods of treating cancers characterized by aberrent ros1 activity |
| WO2014150751A2 (en) | 2013-03-15 | 2014-09-25 | Novartis Ag | Biomarkers associated with brm inhibition |
| WO2014160521A1 (en) | 2013-03-15 | 2014-10-02 | Blueprint Medicines Corporation | Piperazine derivatives and their use as kit modulators |
| WO2014151117A1 (en) | 2013-03-15 | 2014-09-25 | The Board Of Trustees Of The Leland Stanford Junior University | Identification and use of circulating nucleic acid tumor markers |
| AR095308A1 (es) | 2013-03-15 | 2015-10-07 | Glaxosmithkline Ip Dev Ltd | Compuesto de 2-piridona, composición farmacéutica que lo comprende y su uso para preparar un medicamento |
| WO2014152777A2 (en) | 2013-03-15 | 2014-09-25 | Insight Genetics, Inc. | Methods and compositions for the diagnosis and treatment of cancers resistant to ros1 inhibitors |
| EP2968551B1 (en) | 2013-03-15 | 2021-05-05 | The Trustees of Columbia University in the City of New York | Fusion proteins and methods thereof |
| AU2014254394B2 (en) | 2013-04-17 | 2020-06-18 | Life Technologies Corporation | Gene fusions and gene variants associated with cancer |
| US10072298B2 (en) | 2013-04-17 | 2018-09-11 | Life Technologies Corporation | Gene fusions and gene variants associated with cancer |
| EP2997030B1 (en) | 2013-05-14 | 2017-08-09 | Nerviano Medical Sciences S.R.L. | Pyrrolo[2,3-d]pyrimidine derivatives, process for their preparation and their use as kinase inhibitors |
| CN105228983A (zh) | 2013-05-30 | 2016-01-06 | 普莱希科公司 | 用于激酶调节的化合物及其适应症 |
| EP3019489A4 (en) | 2013-07-11 | 2016-12-28 | Betta Pharmaceuticals Co Ltd | MODULATORS OF TYROSINE KINASE PROTEIN AND METHODS OF USE |
| US10705087B2 (en) | 2013-07-26 | 2020-07-07 | Japanese Foundation For Cancer Research | Detection method for NTRK3 fusion |
| EP3628749A1 (en) | 2013-07-30 | 2020-04-01 | Blueprint Medicines Corporation | Ntrk2 fusions |
| EP3027654B1 (en) | 2013-07-30 | 2019-09-25 | Blueprint Medicines Corporation | Pik3c2g fusions |
| WO2015039006A1 (en) | 2013-09-16 | 2015-03-19 | The General Hospital Corporation | Methods of treating cancer |
| WO2015058129A1 (en) | 2013-10-17 | 2015-04-23 | Blueprint Medicines Corporation | Compositions useful for treating disorders related to kit |
| SI3057969T1 (sl) | 2013-10-17 | 2018-10-30 | Blueprint Medicines Corporation | Sestavki, uporabni za zdravljenje motenj, povezanih s KIT |
| CN105848654B (zh) | 2013-10-24 | 2018-10-02 | 乔治城大学 | 用于治疗癌症的方法和组合物 |
| RS63405B1 (sr) | 2013-10-25 | 2022-08-31 | Blueprint Medicines Corp | Inhibitori receptora faktora rasta fibroblasta |
| JPWO2015064621A1 (ja) | 2013-10-29 | 2017-03-09 | 公益財団法人がん研究会 | 新規融合体及びその検出法 |
| US9695165B2 (en) | 2014-01-15 | 2017-07-04 | Blueprint Medicines Corporation | Inhibitors of the fibroblast growth factor receptor |
| ES2933350T3 (es) | 2014-01-24 | 2023-02-06 | Turning Point Therapeutics Inc | Macrociclos de diarilo como moduladores de proteína quinasas |
| KR101723997B1 (ko) | 2014-02-05 | 2017-04-06 | 브이엠 온콜로지 엘엘씨 | 화합물의 조성물 및 이의 용도 |
| TWI672141B (zh) | 2014-02-20 | 2019-09-21 | 美商醫科泰生技 | 投予ｒｏｓ１突變癌細胞之分子 |
| US20170044621A1 (en) | 2014-04-18 | 2017-02-16 | Blueprint Medicines Corporation | Met fusions |
| WO2015161274A1 (en) | 2014-04-18 | 2015-10-22 | Blueprint Medicines Corporation | Pik3ca fusions |
| MA40434B1 (fr) | 2014-05-15 | 2019-09-30 | Array Biopharma Inc | 1-((3s,4r)-4-(3-fluorophényl)-1-(2-méthoxyéthyl)pyrrolidin-3-yl)-3-(4-méthyl-3-(2-méthylpyrimidin-5-yl)-1-phényl-1h-pyrazol-5-yl)urée comme inhibiteur de la kinase trka |
| WO2015183836A1 (en) | 2014-05-27 | 2015-12-03 | Brian Haynes | Compositions, methods, and uses related to ntrk2-tert fusions |
| WO2015183837A1 (en) | 2014-05-27 | 2015-12-03 | Brian Haynes | Compositions, methods, and uses related to ntrk2-tert fusions |
| WO2015184443A1 (en) | 2014-05-30 | 2015-12-03 | The Regents Of The University Of Colorado | Activating ntrk1 gene fusions predictive of kinase inhibitor therapy |
| EP3155118A1 (en) | 2014-06-10 | 2017-04-19 | Blueprint Medicines Corporation | Pkn1 fusions |
| WO2015191666A2 (en) | 2014-06-10 | 2015-12-17 | Blueprint Medicines Corporation | Raf1 fusions |
| US10370725B2 (en) | 2014-07-17 | 2019-08-06 | Blueprint Medicines Corporation | FGR fusions |
| WO2016011144A1 (en) | 2014-07-17 | 2016-01-21 | Blueprint Medicines Corporation | Tert fusions |
| US10370724B2 (en) | 2014-07-17 | 2019-08-06 | Blueprint Medicines Corporation | PRKC fusions |
| US20160032404A1 (en) | 2014-08-01 | 2016-02-04 | Pharmacyclics Llc | Biomarkers for predicting response of dlbcl to treatment with a btk inhibitor |
| US9688680B2 (en) | 2014-08-04 | 2017-06-27 | Blueprint Medicines Corporation | Compositions useful for treating disorders related to kit |
| US10399959B2 (en) | 2014-08-18 | 2019-09-03 | Ono Pharmaceutical Co., Ltd. | Acid-addition salt of Trk-inhibiting compound |
| EP4245376A3 (en) | 2014-10-14 | 2023-12-13 | Novartis AG | Antibody molecules to pd-l1 and uses thereof |
| KR102562866B1 (ko) | 2014-11-14 | 2023-08-04 | 네르비아노 메디칼 사이언시스 에스.알.엘. | 단백질 키나아제 억제제로서의 6-아미노-7-바이사이클로-7-데아자-퓨린 유도체 |
| CN113354649B (zh) * | 2014-11-16 | 2024-12-10 | 阵列生物制药公司 | 一种新的晶型 |
| EP3221700B1 (en) | 2014-11-18 | 2022-06-22 | Blueprint Medicines Corporation | Prkacb fusions |
| CA2971024C (en) | 2014-12-15 | 2023-09-26 | Handok Inc. | Fused ring heteroaryl compounds and their use as trk inhibitors |
| IL294183B2 (en) | 2015-05-20 | 2023-10-01 | Dana Farber Cancer Inst Inc | shared neoantigens |
| MA43943A (fr) | 2015-05-29 | 2018-12-12 | Ignyta Inc | Compositions et procédés pour traiter des patients avec des cellules mutantes rtk |
| HK1253093A1 (zh) | 2015-06-01 | 2019-06-06 | Loxo Oncology Inc. | 诊断和治疗癌症的方法 |
| US9782400B2 (en) | 2015-06-19 | 2017-10-10 | Macau University Of Science And Technology | Oncogenic ROS1 and ALK kinase inhibitor |
| AU2015101722A4 (en) | 2015-06-19 | 2016-05-19 | Macau University Of Science And Technology | Oncogenic ros1 and alk kinase inhibitor |
| GB201511546D0 (en) | 2015-07-01 | 2015-08-12 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers |
| AU2016287568B2 (en) | 2015-07-02 | 2020-08-20 | Turning Point Therapeutics, Inc. | Chiral diaryl macrocycles as modulators of protein kinases |
| EP3368039A1 (en) | 2015-10-26 | 2018-09-05 | The Regents of The University of Colorado, A Body Corporate | Point mutations in trk inhibitor-resistant cancer and methods relating to the same |
| US20170224662A1 (en) | 2016-01-22 | 2017-08-10 | The Medicines Company | Aqueous Formulations and Methods of Preparation and Use Thereof |
| JPWO2017155018A1 (ja) | 2016-03-11 | 2019-01-17 | 小野薬品工業株式会社 | Ｔｒｋ阻害剤抵抗性の癌治療剤 |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| AU2017246547B2 (en) | 2016-04-04 | 2023-02-23 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| FI3439662T3 (fi) | 2016-04-04 | 2024-09-04 | Loxo Oncology Inc | (s)-n-(5-((r)-2-(2,5-difluorifenyyli)pyrrolidin-1-yyli)pyratsolo[1,5-a]pyrimidin-3-yyli)-3-hydroksipyrrolidiini-1-karboksamidin nesteformulaatioita |
| CN109475545A (zh) | 2016-04-19 | 2019-03-15 | 埃克塞里艾克西斯公司 | 三阴性乳腺癌治疗方法 |
| WO2017201156A1 (en) | 2016-05-18 | 2017-11-23 | Duke University | Method of treating kras wild-type metastatic colorectal cell carcinoma using cabozantinib plus panitumumab |
| EP3458456B1 (en) | 2016-05-18 | 2020-11-25 | Loxo Oncology Inc. | Preparation of (s)-n-(5-((r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| WO2019084285A1 (en) | 2017-10-26 | 2019-05-02 | Qian Zhao | FORMULATIONS OF A MACROCYCLIC TRK KINASE INHIBITOR |
| WO2019191659A1 (en) | 2018-03-29 | 2019-10-03 | Loxo Oncology, Inc. | Treatment of trk-associated cancers |
-
2017
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