JP7443057B2 - (S)-N-(5-((R)-2-(2,5-ジフルオロフェニル)ピロリジン-1-イル)-ピラゾロ[1,5-a]ピリミジン-3-イル)-3-ヒドロキシピロリジン-1-カルボキサミドの調製 - Google Patents

(S)-N-(5-((R)-2-(2,5-ジフルオロフェニル)ピロリジン-1-イル)-ピラゾロ[1,5-a]ピリミジン-3-イル)-3-ヒドロキシピロリジン-1-カルボキサミドの調製 Download PDF

Info

Publication number
JP7443057B2
JP7443057B2 JP2019512951A JP2019512951A JP7443057B2 JP 7443057 B2 JP7443057 B2 JP 7443057B2 JP 2019512951 A JP2019512951 A JP 2019512951A JP 2019512951 A JP2019512951 A JP 2019512951A JP 7443057 B2 JP7443057 B2 JP 7443057B2
Authority
JP
Japan
Prior art keywords
formula
compound
salt
mixture
nitro
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
JP2019512951A
Other languages
English (en)
Japanese (ja)
Other versions
JP2019516795A5 (enExample
JP2019516795A (ja
Inventor
マーク レイノルズ
チャールズ トッド アーリー
ステイシー スペンサー
デリク ジュエングスト
ブルーノ アッシュ
ユートン チアン
ジュリア ハース
スティーヴン ダブリュ. アンドリュース
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Loxo Oncology Inc
Original Assignee
Loxo Oncology Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=58794189&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=JP7443057(B2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Loxo Oncology Inc filed Critical Loxo Oncology Inc
Publication of JP2019516795A publication Critical patent/JP2019516795A/ja
Publication of JP2019516795A5 publication Critical patent/JP2019516795A5/ja
Application granted granted Critical
Publication of JP7443057B2 publication Critical patent/JP7443057B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs 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)
JP2019512951A 2016-05-18 2017-05-18 (S)-N-(5-((R)-2-(2,5-ジフルオロフェニル)ピロリジン-1-イル)-ピラゾロ[1,5-a]ピリミジン-3-イル)-3-ヒドロキシピロリジン-1-カルボキサミドの調製 Active JP7443057B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662338359P 2016-05-18 2016-05-18
US62/338,359 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

Publications (3)

Publication Number Publication Date
JP2019516795A JP2019516795A (ja) 2019-06-20
JP2019516795A5 JP2019516795A5 (enExample) 2020-07-02
JP7443057B2 true JP7443057B2 (ja) 2024-03-05

Family

ID=58794189

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2019512951A Active JP7443057B2 (ja) 2016-05-18 2017-05-18 (S)-N-(5-((R)-2-(2,5-ジフルオロフェニル)ピロリジン-1-イル)-ピラゾロ[1,5-a]ピリミジン-3-イル)-3-ヒドロキシピロリジン-1-カルボキサミドの調製

Country Status (27)

Country Link
US (1) US11214571B2 (enExample)
EP (2) EP3458456B1 (enExample)
JP (1) JP7443057B2 (enExample)
KR (1) KR102566858B1 (enExample)
CN (1) CN110049987B (enExample)
AU (1) AU2017268371B2 (enExample)
CA (1) CA3024603A1 (enExample)
CL (1) CL2018003264A1 (enExample)
CO (1) CO2018013015A2 (enExample)
DK (2) DK3458456T3 (enExample)
ES (2) ES2952056T3 (enExample)
FI (1) FI3800189T3 (enExample)
HR (2) HRP20201984T1 (enExample)
HU (2) HUE063877T2 (enExample)
IL (1) IL262964B (enExample)
LT (2) LT3458456T (enExample)
MX (1) MX392604B (enExample)
PE (1) PE20190437A1 (enExample)
PL (2) PL3800189T3 (enExample)
PT (2) PT3800189T (enExample)
RS (2) RS64698B1 (enExample)
RU (1) RU2745953C2 (enExample)
SG (1) SG11201810245WA (enExample)
SI (2) SI3458456T1 (enExample)
UA (1) UA127826C2 (enExample)
WO (1) WO2017201241A1 (enExample)
ZA (1) ZA201808534B (enExample)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT2350075E (pt) 2008-09-22 2014-06-09 Array Biopharma Inc Compostos imidazo[1,2b]piridazina substituídos como inibidores da trk cinase
ME03010B (me) 2008-10-22 2018-10-20 Array Biopharma Inc Jedinjenja supstituisanog pirazol0[1,5-]pirimidina као inhibitori trk kinaze
AR077468A1 (es) 2009-07-09 2011-08-31 Array Biopharma Inc Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa
PL2918588T3 (pl) 2010-05-20 2017-10-31 Array Biopharma Inc Związki makrocykliczne jako inhibitory kinazy TRK
TWI767858B (zh) 2014-11-16 2022-06-11 美商亞雷生物製藥股份有限公司 (S)-N-(5-((R)-2-(2,5-二氟苯基)-吡咯啶-1-基)-吡唑并[1,5-a]嘧啶-3-基)-3-羥基吡咯啶-1-甲醯胺硫酸氫鹽結晶型
CA3003153A1 (en) 2015-10-26 2017-05-04 Loxo Oncology, Inc. 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
DK3439662T3 (da) 2016-04-04 2024-09-02 Loxo Oncology Inc Væskeformige formuleringer af (s)-n-(5-((r)-2-(2,5-difluorphenyl)-pyrrolidin-1-yl)-pyrazol[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidin-1-carboxamid
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
WO2019029629A1 (en) * 2017-08-11 2019-02-14 Teligene Ltd SUBSTITUTED PYRAZOLOPYRIMIDINES FOR USE AS KINASE INHIBITORS
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

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004520324A (ja) 2000-12-22 2004-07-08 アストラゼネカ アクチボラグ カルバゾール誘導体およびニューロペプチドy5受容体リガンドとしてのそれらの使用
JP2012506446A (ja) 2008-10-22 2012-03-15 アレイ バイオファーマ、インコーポレイテッド TRKキナーゼ阻害剤としての置換ピラゾロ[1,5−a]ピリミジン化合物
JP2017535550A (ja) 2014-11-16 2017-11-30 アレイ バイオファーマ、インコーポレイテッド (S)−N−(5−((R)−2−(2,5−ジフルオロフェニル)−ピロリジン−1−イル)−ピラゾロ[1,5−a]ピリミジン−3−イル)−3−ヒドロキシピロリジン−1−カルボキサミド硫酸水素塩の結晶形

Family Cites Families (269)

* Cited by examiner, † Cited by third party
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
ATE212985T1 (de) 1993-11-30 2002-02-15 Searle & Co Tricyclische,substituierte pyrazolyl- benzolsulfonamide und ihre verwendung als cyclooxygenase ii inhibitoren
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
ATE283270T1 (de) 1997-04-25 2004-12-15 Takeda Chemical Industries Ltd Condensierte pyridazine derivate,deren herstellung und verwendung
PL195280B1 (pl) 1999-01-21 2007-08-31 Bristol Myers Squibb Co Kompleks inhibitora RAS-farnezylotransferazy o ulepszonej rozpuszczalności w wodzie i trwałości oraz kompozycja inhibitora RAS-farnezylotransferazy
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
DK1292680T3 (da) 2000-06-22 2010-03-08 Genentech Inc Agonist-anti-TrkC monoklonale antistoffer
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
TWI312347B (en) 2001-02-08 2009-07-21 Eisai R&D Man Co Ltd Bicyclic nitrogen-containing condensed ring compounds
AU2002308722B2 (en) 2001-05-30 2007-05-17 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
US7119200B2 (en) 2002-09-04 2006-10-10 Schering Corporation 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
ATE469903T1 (de) 2002-09-04 2010-06-15 Schering Corp Zur behandlung von krebserkrankungen geeignete pyrazolopyrimidine
US7196078B2 (en) 2002-09-04 2007-03-27 Schering Corpoartion Trisubstituted and tetrasubstituted pyrazolopyrimidines as cyclin dependent kinase inhibitors
WO2004052315A2 (en) 2002-12-11 2004-06-24 Merck & Co., Inc. 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
EP1597251B1 (en) 2003-02-20 2009-06-10 SmithKline Beecham Corporation Pyrimidine compounds
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
WO2004087707A1 (en) 2003-03-31 2004-10-14 Vernalis (Cambridge) Limited Pyrazolopyrimidine compounds and their use in medicine
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
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
AU2004234286A1 (en) 2003-04-28 2004-11-11 Galpharma Co., Ltd Galectin 9-inducing factor
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
NZ588527A (en) 2003-07-15 2012-06-29 Amgen Inc Human anti-NGF neutralizing antibodies as selective NGF pathway inhibitors
US7491794B2 (en) 2003-10-14 2009-02-17 Intermune, Inc. Macrocyclic compounds as inhibitors of viral replication
WO2005044835A1 (en) 2003-10-27 2005-05-19 Genelabs Technologies, Inc. METHODS FOR PREPARING 7-(2'-SUBSTITUTED-ß-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
AR047496A1 (es) 2003-11-28 2006-01-25 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.
ES2527118T3 (es) 2003-12-19 2015-01-20 Plexxikon Inc. Compuestos y procedimientos de desarrollo de moduladores de Ret
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
UA91677C2 (ru) 2004-03-30 2010-08-25 Интермюн, Инк. Макроциклические соединения как ингибиторы вирусной репликации
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
US7528138B2 (en) 2004-11-04 2009-05-05 Vertex Pharmaceuticals Incorporated Pyrazolo[1,5-a]pyrimidines useful as inhibitors of protein kinases
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
WO2006087538A1 (en) 2005-02-16 2006-08-24 Astrazeneca Ab Chemical compounds
CN101119996A (zh) 2005-02-16 2008-02-06 阿斯利康(瑞典)有限公司 化学化合物
AU2006227300B2 (en) 2005-03-21 2012-02-02 Eli Lilly And Company Imidazopyridazine compounds
EP1877057A1 (en) 2005-04-27 2008-01-16 AstraZeneca AB Use of pyrazolyl-pyrimidine derivatives in the treatment of pain
WO2006123113A2 (en) 2005-05-16 2006-11-23 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.
PT1893612E (pt) 2005-06-22 2011-11-21 Plexxikon Inc Derivados de pirrolo [2,3-b]piridina como inibidores de proteína quinase
US20070025540A1 (en) 2005-07-07 2007-02-01 Roger Travis Call center routing based on talkativeness
EP1924594A2 (en) 2005-07-25 2008-05-28 Intermune, Inc. Novel macrocyclic inhibitors of hepatitis c virus replication
US20100216798A1 (en) 2005-07-29 2010-08-26 Astellas Pharma Inc Fused heterocycles as lck inhibitors
US20070184117A1 (en) 2005-08-03 2007-08-09 Stephen Gregory Tocopheryl polyethylene glycol succinate powder and process for preparing same
US20070191306A1 (en) 2005-08-17 2007-08-16 Bristol-Myers Squibb Company FACTOR Xa INHIBITOR FORMULATION AND METHOD
AU2006283592A1 (en) 2005-08-22 2007-03-01 Amgen Inc. Pyrazolopyridine and pyrazolopyrimidine compounds useful as kinase enzymes modulators
US20070049591A1 (en) 2005-08-25 2007-03-01 Kalypsys, Inc. Inhibitors of MAPK/Erk Kinase
MX2008002524A (es) 2005-08-25 2008-03-14 Creabilis Therapeutics Spa Conjugados polimericos de k-252a y sus derivados.
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
US7645762B2 (en) 2005-10-06 2010-01-12 Schering Corporation Substituted pyrazolo[1,5-a] pyrimidines as protein kinase inhibitors
EP1948633B1 (en) 2005-10-11 2011-08-10 Centre National De La Recherche Scientifique (Cnrs) 3 -hydroxyflavone derivatives for the detection and the quantification of cell apoptosis
KR20080056295A (ko) 2005-10-11 2008-06-20 인터뮨, 인크. C형 간염 바이러스 복제를 억제하기 위한 화합물 및 방법
US8101625B2 (en) 2005-10-21 2012-01-24 Exelixis, Inc. Pyrimidinones 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
EP1968579A1 (en) 2005-12-30 2008-09-17 Astex Therapeutics Limited Pharmaceutical compounds
WO2007084815A2 (en) 2006-01-19 2007-07-26 Janssen Pharmaceutica, N.V. Substituted thienopyrimidine kinase inhibitors
EP1978958A4 (en) 2006-01-24 2009-12-02 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
US7723330B2 (en) 2006-03-07 2010-05-25 Array Biopharma Inc. Heterobicyclic pyrazole compounds and methods of use
ZA200808966B (en) 2006-03-27 2010-03-31 Nerviano Medical Sciences Srl Pyridyl- and pyrimidinyl-substituted pyrrole-, thiophene- and furane-derivatives as kinase inhibitors
GB0606805D0 (en) 2006-04-04 2006-05-17 Novartis Ag Organic compounds
BRPI0710874A2 (pt) 2006-04-26 2012-02-14 Hoffmann La Roche compostos de tienopirimidina, processos de produção dos referidos compostos, composições farmacêuticas contendo os mesmos, kit, produto, e usos dos compostos
CA2652442C (en) 2006-05-18 2014-12-09 Eisai R & D Management Co., Ltd. Antitumor agent for thyroid cancer
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
WO2008016131A1 (en) 2006-08-04 2008-02-07 Takeda Pharmaceutical Company Limited Fused heterocyclic compound
TW200817409A (en) 2006-08-04 2008-04-16 Takeda Pharmaceutical Fused heterocyclic derivative and use thereof
US7531539B2 (en) 2006-08-09 2009-05-12 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
EP2063962A2 (en) 2006-09-07 2009-06-03 Biogen Idec MA Inc. Irak modulators for treating an inflammatory condition, cell proliferative disorder, immune disorder
WO2008031551A2 (en) 2006-09-12 2008-03-20 Novartis Forschungsstiftung, Zweigniederlassung 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
NZ576234A (en) 2006-11-06 2011-06-30 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
PE20121126A1 (es) 2006-12-21 2012-08-24 Plexxikon Inc Compuestos pirrolo [2,3-b] piridinas como moduladores de quinasa
CA2673736A1 (en) 2006-12-21 2008-07-03 Plexxikon, Inc. Compounds and methods for kinase modulation, and indications therefor
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
CN101720322A (zh) 2007-05-04 2010-06-02 Irm责任有限公司 作为c-kit和pdgfr激酶抑制剂的化合物和组合物
WO2008155421A2 (en) 2007-06-21 2008-12-24 Janssen Pharmaceutica Nv Indolin-2-ones and aza-indolin-2-ones
AR067478A1 (es) 2007-07-09 2009-10-14 Astrazeneca Ab Compuestos derivados de morfolina pirimidina
AU2008276063B2 (en) 2007-07-17 2013-11-28 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
EP2178861B1 (en) 2007-07-19 2014-08-20 Merck Sharp & Dohme Corp. Heterocyclic amide compounds as protein kinase inhibitors
JP5506674B2 (ja) 2007-07-20 2014-05-28 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置換インダゾール誘導体
WO2009017838A2 (en) 2007-08-01 2009-02-05 Exelixis, Inc. Combinations of jak-2 inhibitors and other agents
BRPI0815370B8 (pt) 2007-08-10 2021-05-25 Regeneron Pharma anticorpos humanos de alta afinidade contra o fator de crescimento neural humano e seu uso, molécula de ácido nucleico, vetor de expressão, método para produção de um anticorpo anti-ngf humano e composiçao farmacêutica
BRPI0817681A2 (pt) 2007-10-16 2015-04-14 Wyeth Llc Compostos de tienopirimidina e pirazolopirimidina e seu uso como inibidores de mtor quinase e pi3 quinase
MX2010004494A (es) 2007-10-23 2010-08-30 Novartis Ag Uso de anticuerpos de trkb para el tratamiento de trastornos respiratorios.
EP2217601A1 (en) 2007-11-08 2010-08-18 Centro Nacional de Investigaciones Oncológicas (CNIO) Imidazopyridazines for use as protein kinase inhibitors
CA2706946A1 (en) 2007-11-28 2009-06-04 Schering Corporation 2-fluoropyrazolo[1,5-a]pyrimidines as protein kinase inhibitors
JP5400791B2 (ja) 2007-12-04 2014-01-29 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 置換ジヒドロプテリジン−6−オン誘導体、その製造方法及びキナーゼ阻害剤としてのその使用
EP2235062A1 (en) 2008-01-17 2010-10-06 Irm Llc Improved anti-trkb antibodies
US20090227556A1 (en) 2008-01-31 2009-09-10 Eisai R&D Management Co., Ltd. Receptor tyrosine kinase inhibitors comprising pyridine and pyrimidine derivatives
AU2009221177B2 (en) 2008-03-03 2013-05-30 Ucb Biopharma Sprl Pharmaceutical solutions, process of preparation and therapeutic uses
KR100963051B1 (ko) 2008-03-14 2010-06-09 광동제약 주식회사 입자크기가 조절된 술포데히드로아비에트산을 함유한쓴맛이 저감된 경구용 액상 조성물
US8207165B2 (en) 2008-03-28 2012-06-26 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
CN102056927B (zh) 2008-05-13 2014-06-25 Irm责任有限公司 作为激酶抑制剂的稠合含氮杂环及其组合物
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
GEP20125502B (en) 2008-05-23 2012-04-25 Novartis Ag Derivatives of quinolines and quinoxalines as protein tyrosine kinase inhibitors
CA2727389A1 (en) 2008-06-10 2009-12-17 Prabha N. Ibrahim 5h-pyrrolo [2,3-b] pyrazine derivatives for kinase modulation, and indications therefor
US8946226B2 (en) 2008-07-29 2015-02-03 Nerviano Medical Sciences S.R.L. Use of CDK inhibitor for the treatment of glioma
EP2376492B1 (en) 2008-09-19 2015-04-08 Nerviano Medical Sciences S.r.l. 3,4 DIHYDRO-2H-PYRROLO[1,2-a]PYRAZIN-1-ONE DERIVATIVES
PT2350075E (pt) 2008-09-22 2014-06-09 Array Biopharma Inc Compostos imidazo[1,2b]piridazina substituídos como inibidores da trk cinase
CN102271515B (zh) 2008-10-31 2014-07-02 健泰科生物技术公司 吡唑并嘧啶jak抑制剂化合物和方法
JP2012509859A (ja) 2008-11-24 2012-04-26 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 中皮腫の治療のためのcdk阻害物質
JO3265B1 (ar) 2008-12-09 2018-09-16 Novartis Ag مثبطات بيريديلوكسى اندولات vegf-r2 واستخدامها لعلاج المرض
AU2010213578B2 (en) 2009-02-12 2015-01-29 Cell Signaling Technology, Inc. Mutant ROS expression in human cancer
WO2010111527A1 (en) 2009-03-26 2010-09-30 Plexxikon, Inc. Pyrazolo [ 3, 4 -b] pyridines as kinase inhibitors and their medical use
EP3045457B1 (en) 2009-06-15 2018-05-09 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
ES2652287T3 (es) 2009-12-21 2018-02-01 Samumed, Llc 1H-pirazol [3,4-b] piridinas y usos terapéuticos de las mismas
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
BR112012025593A2 (pt) 2010-04-06 2019-06-25 Caris Life Sciences Luxembourg Holdings biomarcadores em circulação para doença
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
TWI619713B (zh) 2010-04-21 2018-04-01 普雷辛肯公司 用於激酶調節的化合物和方法及其適應症
PL2918588T3 (pl) 2010-05-20 2017-10-31 Array Biopharma Inc Związki makrocykliczne jako inhibitory kinazy TRK
JP5908466B2 (ja) 2010-06-09 2016-04-26 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 Raf及びmek阻害剤に対する耐性を与えるmek1変異
EP3333188B1 (en) 2010-08-19 2022-02-09 Zoetis Belgium S.A. Anti-ngf antibodies and their use
WO2012034095A1 (en) 2010-09-09 2012-03-15 Irm Llc Compounds and compositions as trk inhibitors
US8637516B2 (en) 2010-09-09 2014-01-28 Irm Llc Compounds and compositions as TRK inhibitors
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
CN103619879A (zh) 2010-12-01 2014-03-05 奥尔德生物控股有限责任公司 抗ngf组合物及其用途
CN103339134B (zh) 2011-01-26 2015-12-23 内尔维阿诺医学科学有限公司 三环吡咯并衍生物、它们的制备方法和它们作为激酶抑制剂的应用
ES2586588T3 (es) 2011-01-26 2016-10-17 Nerviano Medical Sciences S.R.L. Derivados tricíclicos, procedimiento para su preparación y su uso como inhibidores de quinasa
SI2672967T1 (sl) 2011-02-07 2018-12-31 Plexxikon Inc. Spojine in postopki za kinazno modulacijo in indikacije zanjo
EP2678336B1 (en) 2011-02-24 2016-04-20 Nerviano Medical Sciences S.r.l. Thiazolylphenyl-benzenesulfonamido derivatives as kinase inhibitors
MX2013009767A (es) 2011-02-25 2013-10-01 Irm Llc Compuestos y composiciones como inhibidores de trk.
US9284298B2 (en) 2011-04-11 2016-03-15 Nerviano Medical Sciences S.R.L. Pyrazolyl-pyrimidine derivatives as kinase inhibitors
EP2699564B1 (en) 2011-04-19 2016-12-14 Nerviano Medical Sciences S.r.l. Substituted pyrimidinyl-pyrroles active as kinase inhibitors
EP2707359B1 (en) 2011-05-12 2016-11-30 Nerviano Medical Sciences S.r.l. Substituted indazole derivatives active as kinase inhibitors
KR102001364B1 (ko) 2011-05-13 2019-07-22 어레이 바이오파마 인크. Trka 키나제 저해제로서의 피롤리디닐 유레아 및 피롤리디닐 티오유레아 화합물
WO2013014039A1 (en) 2011-07-28 2013-01-31 Nerviano Medical Sciences S.R.L. Alkynyl substituted pyrimidinyl-pyrroles active as kinases inhibitors
EP2788351B1 (en) 2011-10-07 2017-06-28 Nerviano Medical Sciences S.r.l. SUBSTITUTED 3,4-DIHYDROPYRROLO[1,2-a]PYRAZIN-1(2H)-ONE DERIVATIVES AS KINASE INHIBITORS
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
WO2013059740A1 (en) 2011-10-21 2013-04-25 Foundation Medicine, Inc. Novel alk and ntrk1 fusion molecules and uses thereof
BR112014011465A2 (pt) 2011-11-14 2017-05-09 Tesaro Inc modulação de determinadas quinases de tirosina
ES2686501T3 (es) 2011-12-12 2018-10-18 Dr. Reddy's Laboratories Ltd. Pirazolo[1,5-a]piridinas sustituidas como inhibidores de la quinasa del receptor de tropomiosina (Trk)
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
US9242977B2 (en) 2012-04-26 2016-01-26 Ono Pharmaceutical Co., Ltd. Trk-inhibiting compound
JP2013226108A (ja) 2012-04-27 2013-11-07 Astellas Pharma Inc 新規ntrk2活性化変異の検出法
PL3333166T3 (pl) 2012-05-23 2020-09-07 Nerviano Medical Sciences S.R.L. Proces otrzymywania n-[5-(3,5-difluorobenzylo)-1h-indazol-3-ilo]- 4-(4-metylopiperazyn-1-ylo)-2-(tetrahydropiran- 4-yloamino)benzamidu
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
NZ702930A (en) 2012-06-28 2017-05-26 Mcneil Ppc Inc Racecadotril liquid compositions
NZ703495A (en) 2012-07-11 2018-02-23 Blueprint Medicines Corp Inhibitors of the fibroblast growth factor receptor
US10954567B2 (en) 2012-07-24 2021-03-23 Pharmacyclics Llc Mutations associated with resistance to inhibitors of Bruton's Tyrosine Kinase (BTK)
EP2689778A1 (en) 2012-07-27 2014-01-29 Pierre Fabre Medicament Derivatives of azaindoles or diazaindoles for treating pain
WO2014019908A2 (en) 2012-08-02 2014-02-06 Nerviano Medical Sciences S.R.L. Substituted pyrroles active as kinases inhibitors
WO2014036387A2 (en) 2012-08-31 2014-03-06 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
EP4223770A3 (en) 2012-11-05 2023-10-18 Foundation Medicine, Inc. Novel 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
US9896435B2 (en) 2012-11-13 2018-02-20 Array Biopharma Inc. N-pyrrolidinyl,N′-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors
WO2014078322A1 (en) 2012-11-13 2014-05-22 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
US9828360B2 (en) 2012-11-13 2017-11-28 Array Biopharma Inc. Pyrrolidinyl 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
US9969694B2 (en) 2012-11-13 2018-05-15 Array Biopharma Inc. N-(arylalkyl)-N′-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors
ME02879B (me) 2012-11-13 2018-04-20 Array Biopharma Inc Jedinjenja biciklične uree, tiouree, guanidina i cijanoguanidina korisna za lečenje bola
WO2014078372A1 (en) 2012-11-13 2014-05-22 Array Biopharma Inc. Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
US9809578B2 (en) 2012-11-13 2017-11-07 Array Biopharma Inc. Pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trkA kinase inhibitors
US9822118B2 (en) 2012-11-13 2017-11-21 Array Biopharma Inc. Bicyclic heteroaryl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors
HK1213189A1 (zh) 2012-11-29 2016-06-30 耶达研究及发展有限公司 预防肿瘤转移、癌症治疗和预後及鉴定为推定转移抑制剂的试剂的方法
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
SG11201506514QA (en) 2013-02-19 2015-09-29 Ono Pharmaceutical Co 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
US8937071B2 (en) 2013-03-15 2015-01-20 Glaxosmithkline Intellectual Property Development Limited Compounds as rearranged during transfection (RET) inhibitors
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
AU2014236947A1 (en) 2013-03-15 2015-09-03 The Trustees Of Columbia University In The City Of New York Fusion proteins and methods thereof
ES2900301T3 (es) 2013-03-15 2022-03-16 Novartis Ag Biomarcadores asociados con la inhibición de BRM
EP2971152B1 (en) 2013-03-15 2018-08-01 The Board Of Trustees Of The Leland Stanford Junior University Identification and use of circulating nucleic acid tumor markers
EP2970231A1 (en) 2013-03-15 2016-01-20 Blueprint Medicines Corporation Piperazine derivatives and their use as kit modulators
US10072298B2 (en) 2013-04-17 2018-09-11 Life Technologies Corporation Gene fusions and gene variants associated with cancer
WO2014172046A2 (en) 2013-04-17 2014-10-23 Life Technologies Corporation Gene fusions and gene variants associated with cancer
JP6397897B2 (ja) 2013-05-14 2018-09-26 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 ピロロ[2,3−d]ピリミジン誘導体、その製造方法及びキナーゼ阻害剤としてのその使用
MX2015015966A (es) 2013-05-30 2016-04-13 Plexxikon Inc Compuestos para la modulacion de cinasas e indicaciones para los mismos.
TWI610923B (zh) 2013-07-11 2018-01-11 Betta Pharmaceuticals Co Ltd 酪氨酸蛋白激酶調節劑及其應用方法
US10705087B2 (en) 2013-07-26 2020-07-07 Japanese Foundation For Cancer Research Detection method for NTRK3 fusion
WO2015017533A1 (en) 2013-07-30 2015-02-05 Blueprint Medicines Corporation Ntrk2 fusions
WO2015017528A1 (en) 2013-07-30 2015-02-05 Blueprint Medicines Corporation Pik3c2g fusions
WO2015039006A1 (en) 2013-09-16 2015-03-19 The General Hospital Corporation Methods of treating cancer
US9200002B2 (en) 2013-10-17 2015-12-01 Blueprint Medicines Corporation Compositions useful for treating disorders related to KIT
US9334263B2 (en) 2013-10-17 2016-05-10 Blueprint Medicines Corporation Compositions useful for treating disorders related to kit
WO2015061229A1 (en) 2013-10-24 2015-04-30 Georgetown University Methods and compositions for treating cancer
HUE059037T2 (hu) 2013-10-25 2022-10-28 Blueprint Medicines Corp Fibroblaszt növekedési faktor receptor gátlók
WO2015064621A1 (ja) 2013-10-29 2015-05-07 公益財団法人がん研究会 新規融合体及びその検出法
WO2015108992A1 (en) 2014-01-15 2015-07-23 Blueprint Medicines Corporation Heterobicyclic compounds and their use as fgfr4 receptor inhibitors
DK3636649T3 (da) 2014-01-24 2024-05-21 Turning Point Therapeutics Inc Diarylmakrocykler som modulatorer af proteinkinaser
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
US20170044622A1 (en) 2014-04-18 2017-02-16 Blueprint Medicines Corporation Pik3ca fusions
WO2015161277A1 (en) 2014-04-18 2015-10-22 Blueprint Medicines Corporation Met fusions
HRP20191593T1 (hr) 2014-05-15 2019-11-29 Array Biopharma Inc 1-((3s,4r)-4-(3-fluorfenil)-1-(2-metoksietil)pirolidin-3-il)-3-(4-metil-3-(2-metilpirimidin-5-il)-1-fenil-1h-pirazol-5-il)urea kao inhibitor trka kinaze
WO2015183837A1 (en) 2014-05-27 2015-12-03 Brian Haynes Compositions, methods, and uses related to ntrk2-tert fusions
WO2015183836A1 (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
EP3155131B1 (en) 2014-06-10 2020-02-12 Blueprint Medicines Corporation Raf1 fusions
EP3155118A1 (en) 2014-06-10 2017-04-19 Blueprint Medicines Corporation Pkn1 fusions
EP3169809B1 (en) 2014-07-17 2020-04-29 Blueprint Medicines Corporation Prkc fusions
WO2016011141A1 (en) 2014-07-17 2016-01-21 Blueprint Medicines Corporation Fgr fusions
EP3169808B1 (en) 2014-07-17 2019-05-22 Blueprint Medicines Corporation Trio:tert fusion in cancer
JP2017523188A (ja) 2014-08-01 2017-08-17 ファーマサイクリックス エルエルシー Btk阻害剤を伴う治療に対するdlbclの応答を予測するためのバイオマーカー
US9688680B2 (en) 2014-08-04 2017-06-27 Blueprint Medicines Corporation Compositions useful for treating disorders related to kit
AU2015304438B2 (en) 2014-08-18 2019-06-20 Ono Pharmaceutical Co., Ltd. Acid-addition salt of Trk-inhibiting compound
US9988452B2 (en) 2014-10-14 2018-06-05 Novartis Ag Antibody molecules to PD-L1 and uses thereof
PL3218378T3 (pl) 2014-11-14 2020-10-19 Nerviano Medical Sciences S.R.L. Pochodne 6-amino-7-bicyklo-7-deazapuryny jako inhibitory kinaz białkowych
US20170356052A1 (en) 2014-11-18 2017-12-14 Blueprint Medicines Corporation Prkacb fusions
AU2015365587B2 (en) 2014-12-15 2020-07-23 Cmg Pharmaceutical Co., Ltd. Fused ring heteroaryl compounds and their use as TRK inhibitors
WO2016187508A2 (en) 2015-05-20 2016-11-24 The Broad Institute Inc. Shared neoantigens
AU2016270321B2 (en) 2015-05-29 2020-09-10 Ignyta, Inc. Compositions and methods for treating patients with RTK mutant cells
PE20180329A1 (es) 2015-06-01 2018-02-13 Loxo Oncology Inc Metodos para diagnosticar y tratar el cancer
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
EP3317285B1 (en) 2015-07-02 2021-01-27 Turning Point Therapeutics, Inc. Chiral diaryl macrocycles as modulators of protein kinases
CA3003153A1 (en) 2015-10-26 2017-05-04 Loxo Oncology, Inc. 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
WO2017155018A1 (ja) 2016-03-11 2017-09-14 小野薬品工業株式会社 Trk阻害剤抵抗性の癌治療剤
MA44612B1 (fr) 2016-04-04 2024-09-30 Loxo Oncology, Inc. Méthodes de traitement de cancers pédiatriques
US10045991B2 (en) 2016-04-04 2018-08-14 Loxo Oncology, Inc. Methods of treating pediatric cancers
DK3439662T3 (da) 2016-04-04 2024-09-02 Loxo Oncology Inc Væskeformige formuleringer af (s)-n-(5-((r)-2-(2,5-difluorphenyl)-pyrrolidin-1-yl)-pyrazol[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidin-1-carboxamid
WO2017184597A1 (en) 2016-04-19 2017-10-26 Exelixis, Inc. Triple negative breast cancer treatment method
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
EP3700576A1 (en) 2017-10-26 2020-09-02 Array Biopharma Inc. Formulations of a macrocyclic trk kinase inhibitor
EP3773725A1 (en) 2018-03-29 2021-02-17 Loxo Oncology Inc. Treatment of trk-associated cancers

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004520324A (ja) 2000-12-22 2004-07-08 アストラゼネカ アクチボラグ カルバゾール誘導体およびニューロペプチドy5受容体リガンドとしてのそれらの使用
JP2012506446A (ja) 2008-10-22 2012-03-15 アレイ バイオファーマ、インコーポレイテッド TRKキナーゼ阻害剤としての置換ピラゾロ[1,5−a]ピリミジン化合物
JP2017535550A (ja) 2014-11-16 2017-11-30 アレイ バイオファーマ、インコーポレイテッド (S)−N−(5−((R)−2−(2,5−ジフルオロフェニル)−ピロリジン−1−イル)−ピラゾロ[1,5−a]ピリミジン−3−イル)−3−ヒドロキシピロリジン−1−カルボキサミド硫酸水素塩の結晶形

Also Published As

Publication number Publication date
KR102566858B1 (ko) 2023-08-11
ES2836222T3 (es) 2021-06-24
LT3458456T (lt) 2021-02-25
WO2017201241A1 (en) 2017-11-23
LT3800189T (lt) 2023-10-10
IL262964B (en) 2021-06-30
IL262964A (en) 2018-12-31
HUE053643T2 (hu) 2021-07-28
AU2017268371B2 (en) 2020-11-19
HUE063877T2 (hu) 2024-02-28
EP3458456B1 (en) 2020-11-25
CA3024603A1 (en) 2017-11-23
EP3458456A1 (en) 2019-03-27
RS64698B1 (sr) 2023-11-30
FI3800189T3 (fi) 2023-07-31
RU2018144557A (ru) 2020-06-18
EP3800189B1 (en) 2023-06-28
PT3458456T (pt) 2020-12-07
PT3800189T (pt) 2023-07-27
SI3458456T1 (sl) 2021-04-30
PL3800189T3 (pl) 2023-10-23
CO2018013015A2 (es) 2019-08-20
HRP20230704T1 (hr) 2023-10-27
AU2017268371A1 (en) 2018-12-06
KR20190039474A (ko) 2019-04-12
HRP20201984T1 (hr) 2021-04-16
RU2018144557A3 (enExample) 2020-06-18
NZ748520A (en) 2025-06-27
US11214571B2 (en) 2022-01-04
MX2018014116A (es) 2019-12-11
ZA201808534B (en) 2024-04-24
JP2019516795A (ja) 2019-06-20
ES2952056T3 (es) 2023-10-26
CN110049987A (zh) 2019-07-23
US20190218222A1 (en) 2019-07-18
SG11201810245WA (en) 2018-12-28
MX392604B (es) 2025-03-24
UA127826C2 (uk) 2024-01-17
EP3800189A1 (en) 2021-04-07
RU2745953C2 (ru) 2021-04-05
DK3458456T3 (da) 2020-12-14
BR112018073504A2 (pt) 2019-03-26
DK3800189T3 (da) 2023-07-31
CL2018003264A1 (es) 2019-06-21
PE20190437A1 (es) 2019-03-27
SI3800189T1 (sl) 2023-11-30
PL3458456T3 (pl) 2021-04-19
RS61463B1 (sr) 2021-03-31
CN110049987B (zh) 2022-02-18

Similar Documents

Publication Publication Date Title
JP7443057B2 (ja) (S)-N-(5-((R)-2-(2,5-ジフルオロフェニル)ピロリジン-1-イル)-ピラゾロ[1,5-a]ピリミジン-3-イル)-3-ヒドロキシピロリジン-1-カルボキサミドの調製
CN100430397C (zh) 二肽基肽酶-iv抑制剂的磷酸盐
TWI549953B (zh) 7-環戊基-2-(5-哌-1-基-吡啶-2-基胺基)-7h-吡咯并[2,3-d]嘧啶-6-羧酸二甲醯胺之鹽類及其製備方法
JP2007531780A (ja) 新規な2−アミノ−イミダゾ[4,5−d]ピリダジン−4−オン及び2−アミノ−イミダゾ[4,5−c]ピリダジン−4−オン、その製法及び医薬としての使用
US10604502B2 (en) Substituted 5-cyanoindole compounds and uses thereof
RU2007147427A (ru) Кристаллические и другие формы солей, образованных из молочной кислоты и 4-амино-5-фтор-3-[6-(4-метилпиперазин-1-ил)-1н-бензимидазол-2-ил]-1н-хинолин-2-она
TW201803879A (zh) Mcl-1抑制劑及其使用方法
CA2990145A1 (en) Brk inhibitory compound
KR20140054068A (ko) 테노포비어 알라펜아미드 헤미푸마레이트
HUP0103466A2 (hu) Foszfo-diészteráz-4 gátló hatású helyettesített 1,8-naftiridin-4(1H)-on származékok és ezeket tartalmazó gyógyszerkészítmények
EP2906566B1 (en) Process for making thienopyrimidine compounds
KR102791742B1 (ko) (s)-3-아미노-4-(디플루오로메틸레닐)사이클로펜트-1-엔-1-카르복실산의 합성을 위한 공정
JP2017522301A (ja) テノホビルプロドラッグの新規な多結晶形並びにその製造方法及び用途
US11865095B2 (en) Combination drug substance of polyamine transport inhibitor and DFMO
JPWO2014034626A1 (ja) N−[2−({2−[(2S)−2−シアノピロリジン−1−イル]−2−オキソエチル}アミノ)−2−メチルプロピル]−2−メチルピラゾロ[1,5−a]ピリミジン−6−カルボキサミドの結晶
HK40011277B (en) Process for the preparation of a compound and salts thereof
HK40011277A (en) Process for the preparation of a compound and salts thereof
EP4400493A1 (en) Hydroxamic acid compound having enpp1 inhibitory activity and use thereof
JP7186874B2 (ja) ピラゾリル化合物およびその使用方法
BR112018073504B1 (pt) Processo para preparar (s)-n-(5-((r)-2-(2,5-difluorofenil)pirrolidin-1-il)- pirazol[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida e sais da mesma
CN121368478A (en) Preparation method of crystal soluble guanylate cyclase stimulant
US20250312335A1 (en) Flt combination therapy for cancer and compositions therefor
CN120698929A (zh) 一种联苯烯烃类化合物及其药物组合物和应用
HK1095144B (en) Phosphoric acid salt of a dipeptidyl peptidase-iv inhibitor
HK1211026B (en) Process for making thienopyrimidine compounds

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20181128

A711 Notification of change in applicant

Free format text: JAPANESE INTERMEDIATE CODE: A711

Effective date: 20190909

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A821

Effective date: 20190909

RD03 Notification of appointment of power of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7423

Effective date: 20191122

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20191122

RD04 Notification of resignation of power of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7424

Effective date: 20191125

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20200128

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20200518

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20200518

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20210409

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20210420

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20210706

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20220105

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20220425

C60 Trial request (containing other claim documents, opposition documents)

Free format text: JAPANESE INTERMEDIATE CODE: C60

Effective date: 20220425

A911 Transfer to examiner for re-examination before appeal (zenchi)

Free format text: JAPANESE INTERMEDIATE CODE: A911

Effective date: 20220506

C21 Notice of transfer of a case for reconsideration by examiners before appeal proceedings

Free format text: JAPANESE INTERMEDIATE CODE: C21

Effective date: 20220510

A912 Re-examination (zenchi) completed and case transferred to appeal board

Free format text: JAPANESE INTERMEDIATE CODE: A912

Effective date: 20220708

C211 Notice of termination of reconsideration by examiners before appeal proceedings

Free format text: JAPANESE INTERMEDIATE CODE: C211

Effective date: 20220712

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20231205

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20240221

R150 Certificate of patent or registration of utility model

Ref document number: 7443057

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150