ES2590905T3 - Inhibidores de la tirosina quinasa de Bruton - Google Patents
Inhibidores de la tirosina quinasa de Bruton Download PDFInfo
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- ES2590905T3 ES2590905T3 ES13166272.8T ES13166272T ES2590905T3 ES 2590905 T3 ES2590905 T3 ES 2590905T3 ES 13166272 T ES13166272 T ES 13166272T ES 2590905 T3 ES2590905 T3 ES 2590905T3
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25078709P | 2009-10-12 | 2009-10-12 | |
| US250787P | 2009-10-12 | ||
| US12/581,062 US7741330B1 (en) | 2009-10-12 | 2009-10-16 | Pyrazolo-pyrimidine inhibitors of Bruton's tyrosine kinase |
| US12/581,044 US7718662B1 (en) | 2009-10-12 | 2009-10-16 | Pyrazolo-pyrimidine inhibitors of bruton's tyrosine kinase |
| US581062 | 2009-10-16 | ||
| US581044 | 2009-10-16 |
Publications (2)
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| ES2590905T3 true ES2590905T3 (es) | 2016-11-24 |
| ES2590905T8 ES2590905T8 (es) | 2020-12-09 |
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| ES13166272.8T Active ES2590905T3 (es) | 2009-10-12 | 2010-10-12 | Inhibidores de la tirosina quinasa de Bruton |
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| Country | Link |
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| EP (2) | EP2650294B1 (OSRAM) |
| JP (2) | JP5717109B2 (OSRAM) |
| KR (1) | KR20120097376A (OSRAM) |
| CN (1) | CN102656173B (OSRAM) |
| AU (1) | AU2010306921C1 (OSRAM) |
| BR (1) | BR112012008624A2 (OSRAM) |
| CA (1) | CA2776543A1 (OSRAM) |
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| CR (1) | CR20120244A (OSRAM) |
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| NZ (1) | NZ599396A (OSRAM) |
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| ZA (1) | ZA201202552B (OSRAM) |
Families Citing this family (142)
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| PT2201840E (pt) | 2006-09-22 | 2012-02-14 | Pharmacyclics Inc | Inibidores da tirosina quinase de bruton |
| US8809273B2 (en) | 2007-03-28 | 2014-08-19 | Pharmacyclics, Inc. | Inhibitors of Bruton's tyrosine kinase |
| US20100101977A1 (en) * | 2008-06-05 | 2010-04-29 | United Comb & Novelty Corporation | Stackable Packaging For Lipped Containers |
| TWI458721B (zh) | 2008-06-27 | 2014-11-01 | Celgene Avilomics Res Inc | 雜芳基化合物及其用途 |
| US8338439B2 (en) | 2008-06-27 | 2012-12-25 | Celgene Avilomics Research, Inc. | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| US11351168B1 (en) | 2008-06-27 | 2022-06-07 | Celgene Car Llc | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| AU2009270856B2 (en) | 2008-07-16 | 2013-07-25 | Pharmacyclics Llc | Inhibitors of Bruton's tyrosine kinase for the treatment of solid tumors |
| KR101705158B1 (ko) | 2009-05-05 | 2017-02-09 | 다나-파버 캔서 인스티튜트 인크. | Ｅｇｆｒ 억제제 및 질환 치료방법 |
| US7741330B1 (en) * | 2009-10-12 | 2010-06-22 | Pharmacyclics, Inc. | Pyrazolo-pyrimidine inhibitors of Bruton's tyrosine kinase |
| EA201890869A3 (ru) | 2010-06-03 | 2019-03-29 | Фармасайкликс, Инк. | Применение ингибиторов тирозинкиназы брутона (btk) |
| WO2012003544A1 (en) * | 2010-07-09 | 2012-01-12 | The Walter And Eliza Hall Institute Of Medical Research | Protein kinase inhibitors and methods of treatment |
| RU2013109393A (ru) * | 2010-08-10 | 2014-09-20 | Сэлджин Авиаломикс Ресеарч, Инк. | Безилатная соль ингибитора втк |
| CA2815858C (en) | 2010-11-01 | 2018-10-16 | Celgene Avilomics Research, Inc. | Heterocyclic compounds and uses thereof |
| EP2635285B1 (en) | 2010-11-01 | 2017-05-03 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| EP2637502B1 (en) | 2010-11-10 | 2018-01-10 | Celgene CAR LLC | Mutant-selective egfr inhibitors and uses thereof |
| WO2012135801A1 (en) | 2011-04-01 | 2012-10-04 | University Of Utah Research Foundation | Substituted n-(3-(pyrimidin-4-yl)phenyl)acrylamide analogs as tyrosine receptor kinase btk inhibitors |
| PL2693881T3 (pl) | 2011-04-01 | 2020-03-31 | University Of Utah Research Foundation | Podstawione analogi N-fenylopirymidyno-2-aminy jako inhibitory kinazy AXL |
| PL2710005T3 (pl) * | 2011-05-17 | 2017-07-31 | Principia Biopharma Inc. | Inhibitory kinazy tyrozynowej |
| ES2770550T3 (es) | 2011-05-17 | 2020-07-02 | Univ California | Inhibidores de quinasa |
| US9376438B2 (en) | 2011-05-17 | 2016-06-28 | Principia Biopharma, Inc. | Pyrazolopyrimidine derivatives as tyrosine kinase inhibitors |
| AU2012275275A1 (en) * | 2011-06-28 | 2014-01-23 | Pharmacyclics Llc | Methods and compositions for inhibition of bone resorption |
| AU2012283775A1 (en) * | 2011-07-13 | 2014-01-23 | Pharmacyclics Llc | Inhibitors of Bruton's tyrosine kinase |
| EP3409278B8 (en) | 2011-07-21 | 2020-11-04 | Sumitomo Dainippon Pharma Oncology, Inc. | Heterocyclic protein kinase inhibitors |
| CA2853498A1 (en) | 2011-10-28 | 2013-05-02 | Celgene Avilomics Research, Inc. | Methods of treating a bruton's tyrosine kinase disease or disorder |
| 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 |
| TW201336847A (zh) * | 2012-02-07 | 2013-09-16 | Taiho Pharmaceutical Co Ltd | 喹啉基吡咯并嘧啶化合物或其鹽 |
| MX351863B (es) * | 2012-02-23 | 2017-10-30 | Taiho Pharmaceutical Co Ltd | Compuesto de anillo fusionado quinolilpirrolopirimidilo o sal del mismo. |
| BR112014022789B1 (pt) | 2012-03-15 | 2022-04-19 | Celgene Car Llc | Formas sólidas de um inibidor de quinase de receptor do fator de crescimento epidérmico, composição farmacêutica e usos do mesmo |
| RU2711077C9 (ru) | 2012-03-15 | 2020-08-11 | Селджен Кар Ллс | Соли ингибитора киназы рецептора эпидермального фактора роста |
| US9522917B2 (en) | 2012-04-11 | 2016-12-20 | Acerta Pharma B.V. | Bruton's tyrosine kinase inhibitors for hematopoietic mobilization |
| JP6182593B2 (ja) | 2012-04-20 | 2017-08-16 | アドヴィーナス セラピューティクス リミテッド | 置換ヘテロ二環化合物、組成物及び医薬並びにそれらの用途 |
| WO2013157021A1 (en) | 2012-04-20 | 2013-10-24 | Advinus Therapeutics Limited | Bicyclic compounds, compositions and medicinal applications thereof |
| JP6175495B2 (ja) * | 2012-05-31 | 2017-08-02 | ファーマサイエンス・インコーポレイテッドＰｈａｒｍａｓｃｉｅｎｃｅ Ｉｎｃ． | プロテインキナーゼ阻害薬 |
| CA3218491A1 (en) * | 2012-06-04 | 2013-12-12 | Pharmacyclics Llc | Crystalline forms of a bruton's tyrosine kinase inhibitor |
| WO2014018567A1 (en) | 2012-07-24 | 2014-01-30 | Pharmacyclics, Inc. | Mutations associated with resistance to inhibitors of bruton's tyrosine kinase (btk) |
| SMT201900344T1 (it) | 2012-09-10 | 2019-07-11 | Principia Biopharma Inc | Composti di pirazolopirimidina come inibitori di chinasi |
| CN104822663B (zh) | 2012-10-04 | 2017-03-08 | 犹他大学研究基金会 | 作为酪氨酸受体激酶btk抑制剂的取代的n‑(3‑(嘧啶‑4‑基)苯基)丙烯酰胺类似物 |
| JP6401169B2 (ja) | 2012-10-04 | 2018-10-03 | ユニヴァーシティー オブ ユタ リサーチ ファウンデーション | チロシン受容体キナーゼｂｔｋ阻害剤としての置換ｎ−（３−（ピリミジン−４−イル）フェニル）アクリルアミド類似体 |
| JP2015537033A (ja) | 2012-11-15 | 2015-12-24 | ファーマサイクリックス，インク． | キナーゼ阻害剤としてのピロロピリミジン化合物 |
| CN103848810A (zh) | 2012-11-30 | 2014-06-11 | 北京赛林泰医药技术有限公司 | 鲁顿酪氨酸激酶抑制剂 |
| WO2014100748A1 (en) | 2012-12-21 | 2014-06-26 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| EP2953457B1 (en) | 2013-02-08 | 2020-04-08 | Celgene CAR LLC | Erk inhibitors and uses thereof |
| TWI558706B (zh) * | 2013-02-22 | 2016-11-21 | Taiho Pharmaceutical Co Ltd | A tricyclic compound and a tricyclic compound which can be produced by the production method |
| US10202356B2 (en) | 2013-03-14 | 2019-02-12 | Tolero Pharmaceuticals, Inc. | JAK2 and ALK2 inhibitors and methods for their use |
| EP2970300B1 (en) * | 2013-03-15 | 2018-05-16 | Boehringer Ingelheim International GmbH | Heteroaromatic compounds as btk inhibitors |
| MX380171B (es) * | 2013-03-15 | 2025-03-12 | Janssen Pharmaceutica Nv | Procesos e intermedios para preparar un medicamento. |
| EP2983674A4 (en) | 2013-04-08 | 2017-05-10 | Dennis M. Brown | Therapeutic benefit of suboptimally administered chemical compounds |
| US8957080B2 (en) | 2013-04-09 | 2015-02-17 | Principia Biopharma Inc. | Tyrosine kinase inhibitors |
| BR112015025260B1 (pt) | 2013-04-25 | 2021-11-03 | Beigene, Ltd | Compostos heterocíclicos fundidos como inibidores da proteína quinase, sua composição, combinação e uso |
| GB201309085D0 (en) | 2013-05-20 | 2013-07-03 | Redx Pharma Ltd | Compounds |
| KR20160099081A (ko) | 2013-07-26 | 2016-08-19 | 업데이트 파마 인코포레이트 | 비산트렌의 치료 효과 개선용 조합 방법 |
| AR097204A1 (es) | 2013-08-02 | 2016-02-24 | Pharmacyclics Inc | Métodos de tratamiento de tumores sólidos |
| EP3033079B1 (en) | 2013-08-12 | 2018-10-31 | Pharmacyclics LLC | Methods for the treatment of her2 amplified cancer |
| NO3037424T3 (OSRAM) | 2013-08-22 | 2018-04-07 | ||
| US20170050936A1 (en) | 2013-08-23 | 2017-02-23 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| US9492471B2 (en) | 2013-08-27 | 2016-11-15 | Celgene Avilomics Research, Inc. | Methods of treating a disease or disorder associated with Bruton'S Tyrosine Kinase |
| RS63571B9 (sr) | 2013-09-13 | 2023-02-28 | Beigene Switzerland Gmbh | Anti-pd1 antitela i njihova primena kao terapeutska i dijagnostička sredstva |
| US9624224B2 (en) | 2013-09-30 | 2017-04-18 | Pharmacyclics Llc | Inhibitors of Bruton's tyrosine kinase |
| WO2015057992A1 (en) | 2013-10-16 | 2015-04-23 | Izumi Raquel | Btk inhibitors for hematopoietic mobilization |
| CA2929747C (en) * | 2013-12-13 | 2018-01-23 | F. Hoffmann-La Roche Ag | Inhibitors of bruton's tyrosine kinase |
| US9415049B2 (en) | 2013-12-20 | 2016-08-16 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| AU2015225745B2 (en) * | 2014-02-03 | 2017-04-20 | Cadila Healthcare Limited | Heterocyclic compounds |
| KR20220027271A (ko) | 2014-02-21 | 2022-03-07 | 프린시피아 바이오파마, 인코퍼레이티드 | Btk 억제제의 염 및 고체 형태 |
| CA2942528A1 (en) | 2014-03-20 | 2015-09-24 | Pharmacyclics Inc. | Phospholipase c gamma 2 and resistance associated mutations |
| WO2015181633A2 (en) | 2014-04-11 | 2015-12-03 | Acerta Pharma B.V. | Methods of blocking the cxcr-4/sdf-1 signaling pathway with inhibitors of bruton's tyrosine kinase |
| WO2015164213A1 (en) | 2014-04-23 | 2015-10-29 | The Research Foundation For The State University Of New York | A rapid and efficient bioorthogonal ligation reaction and boron-containing heterocycles useful in conjuction therewith |
| CN105017256A (zh) | 2014-04-29 | 2015-11-04 | 浙江导明医药科技有限公司 | 多氟化合物作为布鲁顿酪氨酸激酶抑制剂 |
| WO2015172713A1 (zh) * | 2014-05-13 | 2015-11-19 | 广东东阳光药业有限公司 | 一种中间体的制备方法 |
| CN104086551B (zh) * | 2014-06-06 | 2016-09-21 | 人福医药集团股份公司 | 化合物及其制备方法和用途 |
| GB201410430D0 (en) | 2014-06-11 | 2014-07-23 | Redx Pharma Ltd | Compounds |
| US10544225B2 (en) | 2014-07-03 | 2020-01-28 | Beigene, Ltd. | Anti-PD-L1 antibodies and their use as therapeutics and diagnostics |
| WO2016019233A1 (en) | 2014-08-01 | 2016-02-04 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| MX2017001671A (es) | 2014-08-07 | 2017-07-04 | Pharmacyclics Llc | Formulaciones novedosas de un inhibidor de la tirosina cinasa de bruton. |
| EP3179858B1 (en) | 2014-08-13 | 2019-05-15 | Celgene Car Llc | Forms and compositions of an erk inhibitor |
| ES2727952T3 (es) * | 2014-10-01 | 2019-10-21 | Ratiopharm Gmbh | Sal de adición de ácido de ibrutinib |
| TW201702218A (zh) | 2014-12-12 | 2017-01-16 | 美國杰克森實驗室 | 關於治療癌症、自體免疫疾病及神經退化性疾病之組合物及方法 |
| CA2970723C (en) | 2014-12-18 | 2023-09-05 | Principia Biopharma Inc. | Treatment of pemphigus |
| EP3042903B1 (en) | 2015-01-06 | 2019-08-14 | Impetis Biosciences Ltd. | Substituted hetero-bicyclic compounds, compositions and medicinal applications thereof |
| MA41350A (fr) * | 2015-01-14 | 2017-11-21 | Janssen Pharmaceutica Nv | Synthèse d'un inhibiteur de la tyrosine kinase de bruton |
| US10266535B2 (en) | 2015-01-21 | 2019-04-23 | Hefei Institutes Of Physical Science, Chinese Academy Of Sciences | Inhibitor of FLT3 kinase and use thereof |
| CN105481862B (zh) * | 2015-01-21 | 2018-08-21 | 中国科学院合肥物质科学研究院 | Flt3激酶的新型抑制剂及其用途 |
| CN105859721B (zh) * | 2015-01-22 | 2018-04-17 | 浙江京新药业股份有限公司 | 一种伊布鲁替尼的制备方法 |
| EP3257855B1 (en) * | 2015-02-12 | 2020-04-22 | Shanghai Dude Medical Science and Technology Co., Ltd. | Method for preparing ibrutinib |
| CN107613769A (zh) | 2015-02-17 | 2018-01-19 | 润新生物公司 | 某些化学实体、组合物和方法 |
| IL315294A (en) | 2015-03-03 | 2024-10-01 | Pharmacyclics Llc | Pharmaceutical formulations of bruton's tyrosine kinase inhibitor |
| US10045990B2 (en) | 2015-03-04 | 2018-08-14 | Arizona Board Of Regents On Behalf Of Arizona State University | ERBB4 inhibitors and methods of use thereof |
| US9717745B2 (en) | 2015-03-19 | 2017-08-01 | Zhejiang DTRM Biopharma Co. Ltd. | Pharmaceutical compositions and their use for treatment of cancer and autoimmune diseases |
| CN106146508A (zh) * | 2015-03-19 | 2016-11-23 | 浙江导明医药科技有限公司 | 优化的联合用药及其治疗癌症和自身免疫疾病的用途 |
| CN106146516B (zh) * | 2015-04-20 | 2019-02-15 | 北京睿创康泰医药研究院有限公司 | 依鲁替尼药物杂质的制备方法 |
| KR20240070721A (ko) * | 2015-06-03 | 2024-05-21 | 프린시피아 바이오파마, 인코퍼레이티드 | 티로신 키나제 억제제 |
| US9394312B1 (en) * | 2015-06-14 | 2016-07-19 | Mark Quang Nguyen | Ibrutinib prodrugs, pharmaceutical compositions thereof, and methods of use |
| MA42242A (fr) | 2015-06-24 | 2018-05-02 | Principia Biopharma Inc | Inhibiteurs de la tyrosine kinase |
| HK1258779A1 (zh) | 2015-09-16 | 2019-11-22 | Loxo Oncology Inc. | 用於治療癌症的作為btk抑制劑的吡唑並嘧啶衍生物 |
| MA55064A (fr) * | 2015-12-16 | 2021-09-29 | Loxo Oncology Inc | Composés utilisés comme inhibiteurs de kinase |
| UY37046A (es) | 2015-12-24 | 2017-07-31 | Takeda Pharmaceuticals Co | Cocristal, método de produccion del mismo,y medicamento que contiene dicho cocristal |
| CN107406453B (zh) * | 2016-01-05 | 2018-12-28 | 江苏恒瑞医药股份有限公司 | 一种btk激酶抑制剂的结晶形式及其制备方法 |
| CN108472259A (zh) * | 2016-01-19 | 2018-08-31 | 詹森药业有限公司 | 包含btk抑制剂的配制品/组合物 |
| US10793566B2 (en) | 2016-01-21 | 2020-10-06 | Zibo Biopolar Changsheng Pharmaceutical Co. Ltd. | Bruton's tyrosine kinase inhibitors |
| JP6950897B2 (ja) * | 2016-01-21 | 2021-10-13 | ジーボ・バイオポーラー・チャンシェン・ファーマシューティカル・カンパニー・リミテッドＺｉｂｏ Ｂｉｏｐｏｌａｒ Ｃｈａｎｇｓｈｅｎｇ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｃｏ． Ｌｔｄ． | ブルトン型チロシンキナーゼ阻害剤 |
| CN106995446B (zh) * | 2016-01-22 | 2021-07-02 | 山东新时代药业有限公司 | 布鲁顿酪氨酸激酶抑制剂制备方法 |
| EP3426637B1 (en) | 2016-03-11 | 2022-02-09 | Angel Pharmaceutical Co., Ltd. | Compounds and methods for modulating bruton's tyrosine kinase |
| WO2017198049A1 (zh) * | 2016-05-16 | 2017-11-23 | 浙江予川医药科技有限公司 | 作为btk抑制剂的吡唑并嘧啶衍生物及其制备方法和药物组合物 |
| WO2018005849A1 (en) | 2016-06-29 | 2018-01-04 | Principia Biopharma Inc. | Modified release formulations of 2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile |
| WO2018007885A1 (en) | 2016-07-05 | 2018-01-11 | Beigene, Ltd. | COMBINATION OF A PD-l ANTAGONIST AND A RAF INHIBITOR FOR TREATING CANCER |
| WO2018035061A1 (en) | 2016-08-15 | 2018-02-22 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| JP7402685B2 (ja) | 2016-08-16 | 2023-12-21 | ベイジーン スウィッツァーランド ゲーエムベーハー | （ｓ）－７－（１－アクリロイルピペリジン－４－イル）－２－（４－フェノキシフェニル）－４，５，６，７－テトラ－ヒドロピラゾロ［１，５－ａ］ピリミジン－３－カルボキサミドの結晶形、その調製、及びその使用 |
| AU2017313085B2 (en) | 2016-08-19 | 2024-06-20 | Beone Medicines I Gmbh | Use of a combination comprising a Btk inhibitor for treating cancers |
| BR112019005337A2 (pt) | 2016-09-19 | 2019-08-27 | Mei Pharma Inc | terapia combinada |
| JOP20190073A1 (ar) | 2016-10-31 | 2019-04-07 | Taiho Pharmaceutical Co Ltd | مثبط انتقائي لمستقبل عامل نمو بشروي (egfr) لطافر إدخال exon 20 |
| JOP20190113A1 (ar) * | 2016-11-18 | 2019-05-15 | Biocad Joint Stock Co | مثبطات بروتون تيروزين كيناز |
| MA46995A (fr) | 2016-12-03 | 2019-10-09 | Acerta Pharma Bv | Méthodes et compositions pour l'utilisation de lymphocytes t thérapeutiques en association avec des inhibiteurs de kinase |
| CN110461847B (zh) | 2017-01-25 | 2022-06-07 | 百济神州有限公司 | (S)-7-(1-(丁-2-炔酰基)哌啶-4-基)-2-(4-苯氧基苯基)-4,5,6,7-四氢吡唑并[1,5-a]嘧啶-3-甲酰胺的结晶形式、其制备及用途 |
| CN109311883B (zh) * | 2017-02-09 | 2021-03-19 | 合肥合源药业有限公司 | Flt3激酶抑制剂或其盐的晶型及其制备方法 |
| WO2019001417A1 (en) | 2017-06-26 | 2019-01-03 | Beigene, Ltd. | IMMUNOTHERAPY FOR HEPATOCELLULAR CARCINOMA |
| US11377449B2 (en) | 2017-08-12 | 2022-07-05 | Beigene, Ltd. | BTK inhibitors with improved dual selectivity |
| ES2972895T3 (es) | 2017-09-01 | 2024-06-17 | Taiho Pharmaceutical Co Ltd | Inhibidor selectivo del EGFR mutante en el exón 18 y/o en el exón 21 |
| TW201922256A (zh) | 2017-10-27 | 2019-06-16 | 中國大陸商浙江導明醫藥科技有限公司 | 治療淋巴樣惡性疾病之方法 |
| US11786529B2 (en) | 2017-11-29 | 2023-10-17 | Beigene Switzerland Gmbh | Treatment of indolent or aggressive B-cell lymphomas using a combination comprising BTK inhibitors |
| CN108191871B (zh) * | 2018-01-02 | 2020-02-18 | 成都倍特药业有限公司 | 新型布鲁顿酪氨酸激酶抑制剂及其制备方法和应用 |
| CA3096984A1 (en) | 2018-04-05 | 2019-10-10 | Sumitomo Dainippon Pharma Oncology, Inc. | Axl kinase inhibitors and use of the same |
| US20210113562A1 (en) | 2018-04-13 | 2021-04-22 | Sumitomo Dainippon Pharma Oncology, Inc. | Pim kinase inhibitors for treatment of myeloproliferative neoplasms and fibrosis associated with cancer |
| MX2021000977A (es) | 2018-07-26 | 2021-04-12 | Sumitomo Pharma Oncology Inc | Metodos para tratar enfermedades asociadas con expresion anormal de receptor de activina a tipo 1 (acvr1) e inhibidores de acvr1 para uso en los mismos. |
| CN109134472B (zh) * | 2018-09-20 | 2020-02-11 | 浙江理工大学 | 一种3-(4-苯氧基苯基)-1H-吡唑并[3,4-d]嘧啶-4-胺的合成工艺 |
| CN110964016B (zh) * | 2018-09-29 | 2021-05-28 | 南京药捷安康生物科技有限公司 | 氨基降茨烷衍生物及其制备方法与应用 |
| CN109369654A (zh) * | 2018-11-20 | 2019-02-22 | 山东大学 | 1，3-二取代-4-氨基吡唑并嘧啶类化合物及其制备方法和应用 |
| EP3898626A1 (en) | 2018-12-19 | 2021-10-27 | Array Biopharma, Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of fgfr tyrosine kinases |
| WO2020131674A1 (en) | 2018-12-19 | 2020-06-25 | Array Biopharma Inc. | 7-((3,5-dimethoxyphenyl)amino)quinoxaline derivatives as fgfr inhibitors for treating cancer |
| CN111454268B (zh) | 2019-01-18 | 2023-09-08 | 明慧医药（上海）有限公司 | 作为布鲁顿酪氨酸激酶抑制剂的环状分子 |
| CA3127502A1 (en) | 2019-02-12 | 2020-08-20 | Sumitomo Dainippon Pharma Oncology, Inc. | Formulations comprising heterocyclic protein kinase inhibitors |
| BR112021024131A2 (pt) | 2019-05-31 | 2022-01-11 | Haisco Pharmaceuticals Pte Ltd | Derivado de anel inibidor de btk, método de preparação para o mesmo e aplicação farmacêutica do mesmo |
| WO2020249001A1 (zh) | 2019-06-10 | 2020-12-17 | 百济神州瑞士有限责任公司 | 一种含有布鲁顿氏酪氨酸激酶抑制剂的口服固体片剂及其制备方法 |
| CN110606848A (zh) * | 2019-08-27 | 2019-12-24 | 药雅科技(上海)有限公司 | 一种5-氮杂吲哚衍生物Bruton′s酪氨酸激酶抑制剂及其制备方法与用途 |
| TWI877239B (zh) | 2019-10-14 | 2025-03-21 | 美商普林斯匹亞生物製藥公司 | 藉由投予(R)-2-[3-[4-胺基-3-(2-氟-4-苯氧基-苯基)吡唑并[3,4-d]嘧啶-1-基]哌啶-1-羰基]-4-甲基-4-[4-(氧呾-3-基)哌-1-基]戊-2-烯腈來治療免疫血小板減少症之方法 |
| WO2021089395A1 (en) | 2019-11-08 | 2021-05-14 | Nerviano Medical Sciences S.R.L. | Gem-disubstituted heterocyclic compounds and their use as idh inhibitors |
| US11969418B2 (en) | 2020-01-20 | 2024-04-30 | Genzyme Corporation | Therapeutic tyrosine kinase inhibitors for relapsing multiple sclerosis (RMS) |
| BR112022014149A2 (pt) | 2020-01-22 | 2022-09-27 | Principia Biopharma Inc | Formas cristalinas de 2-[3-[4-amino-3-(2-fluoro-4-fenóxi-fenil)-1h-pirazolo[3,4-d]pirimidina-1-il]piperidina-1-carbonil]-4-metil-4-[4-(oxetan-3-il)piperazin-1-il]pent-2-enenitrila |
| CN113943294A (zh) * | 2020-07-15 | 2022-01-18 | 成都海博为药业有限公司 | 一种作为btk抑制剂的化合物及其制备方法与用途 |
| US20240002387A1 (en) * | 2020-11-25 | 2024-01-04 | Haisco Pharmaceuticals Pte. Ltd. | Method for preparing btk degrading agent |
| MX2023006854A (es) | 2020-12-10 | 2023-07-20 | Genzyme Corp | Forma cristalina de tolebrutinib, metodo de preparacion y uso de la misma. |
| CN113004246B (zh) * | 2021-02-22 | 2022-02-01 | 广西医科大学 | 1，3，5-三嗪-2-胺-4，6取代衍生物或其药学上可接受的盐和用途 |
| US11786531B1 (en) | 2022-06-08 | 2023-10-17 | Beigene Switzerland Gmbh | Methods of treating B-cell proliferative disorder |
| EP4611753A1 (en) | 2022-10-31 | 2025-09-10 | Sumitomo Pharma America, Inc. | Pim1 inhibitor for treating myeloproliferative neoplasms |
Family Cites Families (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2008A (en) * | 1841-03-18 | Gas-lamp eok conducting gas pkom ah elevated buhner to one below it | ||
| US3598122A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
| US3598123A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
| US3993073A (en) | 1969-04-01 | 1976-11-23 | Alza Corporation | Novel drug delivery device |
| US3710795A (en) | 1970-09-29 | 1973-01-16 | Alza Corp | Drug-delivery device with stretched, rate-controlling membrane |
| US4069307A (en) | 1970-10-01 | 1978-01-17 | Alza Corporation | Drug-delivery device comprising certain polymeric materials for controlled release of drug |
| US3731683A (en) | 1971-06-04 | 1973-05-08 | Alza Corp | Bandage for the controlled metering of topical drugs to the skin |
| US3742951A (en) | 1971-08-09 | 1973-07-03 | Alza Corp | Bandage for controlled release of vasodilators |
| US3996934A (en) | 1971-08-09 | 1976-12-14 | Alza Corporation | Medical bandage |
| BE795384A (fr) | 1972-02-14 | 1973-08-13 | Ici Ltd | Pansements |
| US3921636A (en) | 1973-01-15 | 1975-11-25 | Alza Corp | Novel drug delivery device |
| US3993072A (en) | 1974-08-28 | 1976-11-23 | Alza Corporation | Microporous drug delivery device |
| US4151273A (en) | 1974-10-31 | 1979-04-24 | The Regents Of The University Of California | Increasing the absorption rate of insoluble drugs |
| US3972995A (en) | 1975-04-14 | 1976-08-03 | American Home Products Corporation | Dosage form |
| US4077407A (en) | 1975-11-24 | 1978-03-07 | Alza Corporation | Osmotic devices having composite walls |
| US4031894A (en) | 1975-12-08 | 1977-06-28 | Alza Corporation | Bandage for transdermally administering scopolamine to prevent nausea |
| US4060084A (en) | 1976-09-07 | 1977-11-29 | Alza Corporation | Method and therapeutic system for providing chemotherapy transdermally |
| US4201211A (en) | 1977-07-12 | 1980-05-06 | Alza Corporation | Therapeutic system for administering clonidine transdermally |
| JPS5562012A (en) | 1978-11-06 | 1980-05-10 | Teijin Ltd | Slow-releasing preparation |
| US4230105A (en) | 1978-11-13 | 1980-10-28 | Merck & Co., Inc. | Transdermal delivery of drugs |
| US4229447A (en) | 1979-06-04 | 1980-10-21 | American Home Products Corporation | Intraoral methods of using benzodiazepines |
| CA1146866A (en) | 1979-07-05 | 1983-05-24 | Yamanouchi Pharmaceutical Co. Ltd. | Process for the production of sustained release pharmaceutical composition of solid medical material |
| US4291015A (en) | 1979-08-14 | 1981-09-22 | Key Pharmaceuticals, Inc. | Polymeric diffusion matrix containing a vasodilator |
| US4327725A (en) | 1980-11-25 | 1982-05-04 | Alza Corporation | Osmotic device with hydrogel driving member |
| US5116817A (en) | 1982-12-10 | 1992-05-26 | Syntex (U.S.A.) Inc. | LHRH preparations for intranasal administration |
| US4476116A (en) | 1982-12-10 | 1984-10-09 | Syntex (U.S.A.) Inc. | Polypeptides/chelating agent nasal compositions having enhanced peptide absorption |
| US4596795A (en) | 1984-04-25 | 1986-06-24 | The United States Of America As Represented By The Secretary, Dept. Of Health & Human Services | Administration of sex hormones in the form of hydrophilic cyclodextrin derivatives |
| US4624848A (en) | 1984-05-10 | 1986-11-25 | Ciba-Geigy Corporation | Active agent containing hydrogel devices wherein the active agent concentration profile contains a sigmoidal concentration gradient for improved constant release, their manufacture and use |
| GB8518301D0 (en) | 1985-07-19 | 1985-08-29 | Fujisawa Pharmaceutical Co | Hydrodynamically explosive systems |
| US5011692A (en) | 1985-12-28 | 1991-04-30 | Sumitomo Pharmaceuticals Company, Limited | Sustained pulsewise release pharmaceutical preparation |
| US4755386A (en) | 1986-01-22 | 1988-07-05 | Schering Corporation | Buccal formulation |
| US5312325A (en) | 1987-05-28 | 1994-05-17 | Drug Delivery Systems Inc | Pulsating transdermal drug delivery system |
| US4968509A (en) | 1987-07-27 | 1990-11-06 | Mcneilab, Inc. | Oral sustained release acetaminophen formulation and process |
| US5052558A (en) | 1987-12-23 | 1991-10-01 | Entravision, Inc. | Packaged pharmaceutical product |
| US5033252A (en) | 1987-12-23 | 1991-07-23 | Entravision, Inc. | Method of packaging and sterilizing a pharmaceutical product |
| IL92966A (en) | 1989-01-12 | 1995-07-31 | Pfizer | Dispensing devices powered by hydrogel |
| US5739136A (en) | 1989-10-17 | 1998-04-14 | Ellinwood, Jr.; Everett H. | Intraoral dosing method of administering medicaments |
| US5017381A (en) | 1990-05-02 | 1991-05-21 | Alza Corporation | Multi-unit pulsatile delivery system |
| US5633009A (en) | 1990-11-28 | 1997-05-27 | Sano Corporation | Transdermal administration of azapirones |
| EP0580860B2 (en) | 1991-04-16 | 2004-12-15 | Nippon Shinyaku Company, Limited | Method of manufacturing solid dispersion |
| US5229135A (en) | 1991-11-22 | 1993-07-20 | Prographarm Laboratories | Sustained release diltiazem formulation |
| DE69231313T2 (de) | 1991-11-22 | 2001-03-15 | Procter & Gamble Pharmaceuticals, Inc. | Risedronat enthaltende Arzneimittel mit verzögerter Wirkstoffabgabe |
| US5340591A (en) | 1992-01-24 | 1994-08-23 | Fujisawa Pharmaceutical Co., Ltd. | Method of producing a solid dispersion of the sparingly water-soluble drug, nilvadipine |
| US5461140A (en) | 1992-04-30 | 1995-10-24 | Pharmaceutical Delivery Systems | Bioerodible polymers for solid controlled release pharmaceutical compositions |
| US5260068A (en) | 1992-05-04 | 1993-11-09 | Anda Sr Pharmaceuticals Inc. | Multiparticulate pulsatile drug delivery system |
| US5281420A (en) | 1992-05-19 | 1994-01-25 | The Procter & Gamble Company | Solid dispersion compositions of tebufelone |
| US5323907A (en) | 1992-06-23 | 1994-06-28 | Multi-Comp, Inc. | Child resistant package assembly for dispensing pharmaceutical medications |
| AU4198793A (en) | 1992-07-24 | 1994-01-27 | Takeda Chemical Industries Ltd. | Microparticle preparation and production thereof |
| US5700485A (en) | 1992-09-10 | 1997-12-23 | Children's Medical Center Corporation | Prolonged nerve blockade by the combination of local anesthetic and glucocorticoid |
| WO1994008568A1 (fr) | 1992-10-16 | 1994-04-28 | Nippon Shinyaku Co., Ltd. | Procede pour fabriquer des matrices de cire |
| US5260069A (en) | 1992-11-27 | 1993-11-09 | Anda Sr Pharmaceuticals Inc. | Pulsatile particles drug delivery system |
| US5686105A (en) | 1993-10-19 | 1997-11-11 | The Procter & Gamble Company | Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery |
| US6326469B1 (en) | 1994-04-22 | 2001-12-04 | Sugen, Inc. | Megakaryocytic protein tyrosine kinases |
| US5665378A (en) | 1994-09-30 | 1997-09-09 | Davis; Roosevelt | Transdermal therapeutic formulation |
| US5567441A (en) | 1995-03-24 | 1996-10-22 | Andrx Pharmaceuticals Inc. | Diltiazem controlled release formulation |
| JPH11505258A (ja) | 1995-05-17 | 1999-05-18 | セダーシナイ メディカル センター | 小腸における消化および吸収を改善させる脂肪酸を含む組成物 |
| SE9502244D0 (sv) | 1995-06-20 | 1995-06-20 | Bioglan Ab | A composition and a process for the preparation thereof |
| US5837284A (en) | 1995-12-04 | 1998-11-17 | Mehta; Atul M. | Delivery of multiple doses of medications |
| US5858401A (en) | 1996-01-22 | 1999-01-12 | Sidmak Laboratories, Inc. | Pharmaceutical composition for cyclosporines |
| US6923983B2 (en) | 1996-02-19 | 2005-08-02 | Acrux Dds Pty Ltd | Transdermal delivery of hormones |
| US6929801B2 (en) | 1996-02-19 | 2005-08-16 | Acrux Dds Pty Ltd | Transdermal delivery of antiparkinson agents |
| US6458373B1 (en) | 1997-01-07 | 2002-10-01 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
| JP2001516353A (ja) * | 1997-03-19 | 2001-09-25 | ビーエーエスエフ アクチェンゲゼルシャフト | ピロロ［２，３ｄ］ピリミジンおよびチロシンキナーゼ阻害剤としてのこれらの使用 |
| US5840329A (en) | 1997-05-15 | 1998-11-24 | Bioadvances Llc | Pulsatile drug delivery system |
| US6391452B1 (en) | 1997-07-18 | 2002-05-21 | Bayer Corporation | Compositions for nasal drug delivery, methods of making same, and methods of removing residual solvent from pharmaceutical preparations |
| US5869090A (en) | 1998-01-20 | 1999-02-09 | Rosenbaum; Jerry | Transdermal delivery of dehydroepiandrosterone |
| US6946144B1 (en) | 1998-07-08 | 2005-09-20 | Oryxe | Transdermal delivery system |
| PL346700A1 (en) * | 1998-09-18 | 2002-02-25 | Basf Ag | Pyrrolopyrimidines as protein kinase inhibitors |
| EP1027886B1 (en) | 1999-02-10 | 2008-07-09 | Pfizer Products Inc. | Pharmaceutical solid dispersions |
| US6395300B1 (en) | 1999-05-27 | 2002-05-28 | Acusphere, Inc. | Porous drug matrices and methods of manufacture thereof |
| US6921763B2 (en) | 1999-09-17 | 2005-07-26 | Abbott Laboratories | Pyrazolopyrimidines as therapeutic agents |
| DE60004685T2 (de) * | 1999-09-17 | 2004-07-29 | Abbott Gmbh & Co. Kg | Pyrazolopyrimidine als arzneimittel |
| WO2001082901A1 (en) | 2000-04-28 | 2001-11-08 | Zengen, Inc. | New antibodies to biological membranes |
| US6465014B1 (en) | 2001-03-21 | 2002-10-15 | Isp Investments Inc. | pH-dependent sustained release, drug-delivery composition |
| MXPA03008560A (es) | 2001-03-22 | 2004-06-30 | Abbot Gmbh & Co Kg | Pirazolopirimidinas como agentes terapeuticos. |
| US6960563B2 (en) | 2001-08-31 | 2005-11-01 | Morton Grove Pharmaceuticals, Inc. | Spontaneous emulsions containing cyclosporine |
| CA2548951A1 (en) * | 2003-12-22 | 2005-07-14 | Gilead Sciences, Inc. | Kinase inhibitor phosphonate conjugates |
| BRPI0418031A (pt) * | 2003-12-22 | 2007-04-17 | Gilead Sciences Inc | inibidores de quinase fosfonato-substituìdos |
| EP1730148A4 (en) * | 2004-02-03 | 2009-08-19 | Abbott Lab | USE OF AMINOBENZOXAZOLES AS THERAPEUTIC AGENTS |
| JP2008520744A (ja) * | 2004-11-19 | 2008-06-19 | ザ・レジェンツ・オブ・ザ・ユニバーシティ・オブ・カリフォルニア | 抗炎症性ピラゾロピリミジン |
| AU2007347115A1 (en) * | 2006-04-04 | 2008-10-23 | The Regents Of The University Of California | PI3 kinase antagonists |
| PT2201840E (pt) | 2006-09-22 | 2012-02-14 | Pharmacyclics Inc | Inibidores da tirosina quinase de bruton |
| EA017865B1 (ru) * | 2007-03-28 | 2013-03-29 | Фармасайкликс, Инк. | Ингибиторы тирозинкиназы брутона |
| US7741330B1 (en) | 2009-10-12 | 2010-06-22 | Pharmacyclics, Inc. | Pyrazolo-pyrimidine inhibitors of Bruton's tyrosine kinase |
| UA109417C2 (uk) | 2009-10-14 | 2015-08-25 | Мерк Шарп Енд Доме Корп. | ЗАМІЩЕНІ ПІПЕРИДИНИ, ЯКІ ПІДВИЩУЮТЬ АКТИВНІСТЬ p53, І ЇХ ЗАСТОСУВАННЯ |
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2009
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- 2010-10-12 EP EP13166272.8A patent/EP2650294B1/en not_active Not-in-force
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- 2010-10-12 EP EP10823966A patent/EP2393816A2/en not_active Withdrawn
- 2010-10-12 WO PCT/US2010/052377 patent/WO2011046964A2/en not_active Ceased
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