CA2947338C - Multi-fluoro-substituted compound as bruton's tyrosine kinase (btk) inhibitor - Google Patents

Multi-fluoro-substituted compound as bruton's tyrosine kinase (btk) inhibitor Download PDF

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CA2947338C
CA2947338C CA2947338A CA2947338A CA2947338C CA 2947338 C CA2947338 C CA 2947338C CA 2947338 A CA2947338 A CA 2947338A CA 2947338 A CA2947338 A CA 2947338A CA 2947338 C CA2947338 C CA 2947338C
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fluoro
pyrazolo
pyrimidin
pheny1
mmol
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CA2947338A1 (en
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Wei He
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ZHEJIANG DTRM BIOPHARMA Co Ltd
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ZHEJIANG DTRM BIOPHARMA Co Ltd
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    • 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
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    • 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
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CA2947338A 2014-04-29 2015-04-27 Multi-fluoro-substituted compound as bruton's tyrosine kinase (btk) inhibitor Active CA2947338C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN201410175783.7 2014-04-29
CN201410175783.7A CN105017256A (zh) 2014-04-29 2014-04-29 多氟化合物作为布鲁顿酪氨酸激酶抑制剂
PCT/CN2015/000290 WO2015165279A1 (zh) 2014-04-29 2015-04-27 多氟化合物作为布鲁顿酪氨酸激酶抑制剂

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CA2947338A1 CA2947338A1 (en) 2015-11-05
CA2947338C true CA2947338C (en) 2022-12-20

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CA2947338A Active CA2947338C (en) 2014-04-29 2015-04-27 Multi-fluoro-substituted compound as bruton's tyrosine kinase (btk) inhibitor

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US (3) US9532990B2 (enExample)
EP (1) EP3138842B1 (enExample)
JP (2) JP6670756B2 (enExample)
KR (2) KR20160144378A (enExample)
CN (3) CN105017256A (enExample)
AU (1) AU2015252654C1 (enExample)
BR (1) BR112016025132A2 (enExample)
CA (1) CA2947338C (enExample)
EA (2) EA037227B1 (enExample)
ES (1) ES2857251T3 (enExample)
IL (1) IL248546B (enExample)
MX (2) MX2021013118A (enExample)
WO (1) WO2015165279A1 (enExample)

Families Citing this family (51)

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Publication number Priority date Publication date Assignee Title
PT3023100T (pt) 2013-07-18 2019-05-29 Taiho Pharmaceutical Co Ltd Fármaco antitumoral para administração intermitente de inibidor de fgfr
ES2819398T3 (es) 2013-07-18 2021-04-15 Taiho Pharmaceutical Co Ltd Agente terapéutico para el cáncer resistente al inhibidor de FGFR
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
WO2016079693A1 (en) * 2014-11-19 2016-05-26 Sun Pharmaceutical Industries Limited A process for the preparation of ibrutinib
EP3257855B1 (en) * 2015-02-12 2020-04-22 Shanghai Dude Medical Science and Technology Co., Ltd. Method for preparing ibrutinib
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
CN106146511A (zh) * 2015-04-03 2016-11-23 安润医药科技（苏州）有限公司 吡唑并嘧啶衍生物、制备方法、药物组合物及用途
CN106146512B (zh) * 2015-04-09 2018-07-17 北京睿创康泰医药研究院有限公司 依鲁替尼的制备方法
CA2981886A1 (en) 2015-04-16 2016-10-20 Icahn School Of Medicine At Mount Sinai Ksr antagonists
AU2017226389B2 (en) 2016-03-04 2023-02-02 Taiho Pharmaceutical Co., Ltd. Preparation and composition for treatment of malignant tumors
US11883404B2 (en) 2016-03-04 2024-01-30 Taiho Pharmaceuticals Co., Ltd. Preparation and composition for treatment of malignant tumors
JP6959252B2 (ja) * 2016-03-24 2021-11-02 ミッション セラピューティクス リミティド Ｄｕｂ阻害剤としての１−シアノピロリジン誘導体
WO2018002958A1 (en) 2016-06-30 2018-01-04 Sun Pharma Advanced Research Company Limited Novel hydrazide containing compounds as btk inhibitors
CN106146518A (zh) * 2016-06-30 2016-11-23 苏州爱玛特生物科技有限公司 一种布鲁顿酪氨酸激酶抑制剂中间体及其制备方法
GB201616511D0 (en) 2016-09-29 2016-11-16 Mission Therapeutics Limited Novel compounds
US10711006B2 (en) * 2016-11-15 2020-07-14 Hangzhou Hertz Pharmaceutical Co., Ltd. Selective Bruton's tyrosine kinase inhibitor and use thereof
CN110545826A (zh) 2016-12-03 2019-12-06 朱诺治疗学股份有限公司 用于与激酶抑制剂组合使用治疗性t细胞的方法和组合物
CN106831788B (zh) * 2017-01-22 2020-10-30 鲁南制药集团股份有限公司 伊布替尼精制方法
CN110494433B (zh) 2017-03-22 2023-03-17 廖细斌 布鲁顿酪氨酸激酶抑制剂
CN107501270B (zh) * 2017-09-01 2019-06-28 宏腾建设集团有限公司 一种含有磺酰吖丙啶结构的化合物、药物组合物以及其应用
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
CN109970740A (zh) * 2017-12-27 2019-07-05 广东众生药业股份有限公司 4-氨基-嘧啶并氮杂环衍生物及其制备方法和用途
PL3769765T3 (pl) 2018-03-19 2024-06-10 Taiho Pharmaceutical Co., Ltd. Kompozycja farmaceutyczna zawierająca alkilosiarczan sodu
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
US20210387990A1 (en) * 2018-11-09 2021-12-16 Taiho Pharmaceutical Co., Ltd. Method for producing dimethoxybenzene compound
CN111171035B (zh) * 2018-11-13 2021-03-30 山东大学 4-苯氧基苯基吡唑并嘧啶酰胺衍生物的制备方法和应用
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
WO2020187626A1 (de) 2019-03-15 2020-09-24 Bayer Aktiengesellschaft Speziell substituierte 3-phenyl-5-spirocyclopentyl-3-pyrrolin-2-one und deren verwendung als herbizide
AU2020242287A1 (en) 2019-03-21 2021-09-02 INSERM (Institut National de la Santé et de la Recherche Médicale) A Dbait molecule in combination with kinase inhibitor for the treatment of cancer
AU2020307631B9 (en) * 2019-06-27 2024-07-04 Hangzhou Healzen Therapeutics Co., Ltd. Casein kinase 1ε inhibitor, pharmaceutical composition and application thereof
WO2021038540A1 (en) 2019-08-31 2021-03-04 Sun Pharma Advanced Research Company Limited Cycloalkylidene carboxylic acids and derivatives as btk inhibitors
AU2020355845B2 (en) * 2019-09-26 2023-04-06 Jumbo Drug Bank Co., Ltd. Pyrazolopyridine compounds as selective BTK kinase inhibitors
KR20220098759A (ko) 2019-11-08 2022-07-12 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) 키나제 억제제에 대해 내성을 획득한 암의 치료 방법
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
EP3865535A1 (en) 2020-02-11 2021-08-18 Bosti Trading Ltd. New method of synthesis of chitosan derivatives and uses thereof
TW202144465A (zh) 2020-02-11 2021-12-01 瑞士商諾和席卓股份有限公司 合成聚葡萄胺糖衍生物之新方法及其用途
WO2021184154A1 (en) * 2020-03-16 2021-09-23 Flash Therapeutics, Llc Compounds for treating or inhibiting recurrence of acute myeloid leukemia
WO2021252488A1 (en) 2020-06-08 2021-12-16 Halia Therapeutics, Inc. Inhibitors of nek7 kinase
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
WO2022081512A1 (en) * 2020-10-12 2022-04-21 Synubi Pharmaceuticals Llc Compositions and methods of treatment of neuroinflammatory diseases with bruton's tyrosine kinase inhibitors
CN112574046A (zh) * 2020-12-17 2021-03-30 深圳市华先医药科技有限公司 一种制备(1r,3s)-3-氨基环戊醇盐酸盐的方法
US20240100172A1 (en) 2020-12-21 2024-03-28 Hangzhou Jijing Pharmaceutical Technology Limited Methods and compounds for targeted autophagy
CN116669770A (zh) * 2020-12-23 2023-08-29 耶达研究与发展有限公司 甲基丙烯酰胺蛋白质结合剂及其用途
JP2024505558A (ja) * 2021-02-03 2024-02-06 アキュター バイオテクノロジー インコーポレイテッド ブルトン型チロシンキナーゼ（ｂｔｋ）分解剤としての置換ピロロピリミジンおよびピラゾロピリミジン
AR126678A1 (es) 2021-08-06 2023-11-01 Novochizol Sa Composiciones para el cuidado de las plantas y usos de las mismas
CN117835822A (zh) 2021-08-06 2024-04-05 诺和席卓股份有限公司 包含可溶性交联壳聚糖的复合凝胶、聚合物支架、聚集体和薄膜的制备及其用途
CN114605418B (zh) * 2022-03-15 2023-09-05 广东医科大学附属医院 一类具有抗肿瘤活性的依鲁替尼丙烯酰胺类衍生物及其合成方法与应用
CN117430610A (zh) * 2023-10-11 2024-01-23 宁夏医科大学 一种氘代稠合杂环化合物及其制备方法和应用
CN117903141B (zh) * 2023-12-19 2024-11-05 江苏长泰药业股份有限公司 一种化合物及其盐、在制备治疗癌症药物和激酶抑制剂中的用途、治疗癌症的药物
WO2025202889A1 (en) * 2024-03-28 2025-10-02 Array Biopharma Inc. Her2 mutation inhibitors

Family Cites Families (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040127470A1 (en) * 1998-12-23 2004-07-01 Pharmacia Corporation Methods and compositions for the prevention or treatment of neoplasia comprising a Cox-2 inhibitor in combination with an epidermal growth factor receptor antagonist
GB0402143D0 (en) * 2004-01-30 2004-03-03 Smithkline Beecham Corp Novel compounds
SG166093A1 (en) * 2006-09-22 2010-11-29 Pharmacyclics Inc Inhibitors of brutonæs tyrosine kinase
EP1921149A1 (en) 2006-11-13 2008-05-14 AEterna Zentaris GmbH Microorganisms as carriers of nucleotide sequences coding for antigens and protein toxins, process of manufacturing and uses thereof
CN101674834B (zh) 2007-03-28 2013-06-12 环状药物公司 布鲁顿氏酪氨酸激酶(Bruton's tyrosine kinase)抑制剂
CA2730930C (en) * 2008-07-16 2015-01-13 Pharmacyclics, Inc. Inhibitors of bruton's tyrosine kinase for the treatment of solid tumors
US7741330B1 (en) 2009-10-12 2010-06-22 Pharmacyclics, Inc. Pyrazolo-pyrimidine inhibitors of Bruton's tyrosine kinase
CN102115476A (zh) * 2011-03-23 2011-07-06 常州大学 一种2H-吡唑并[3,4-d]嘧啶衍生物及合成方法
KR102027598B1 (ko) * 2011-05-17 2019-10-01 프린시피아 바이오파마, 인코퍼레이티드 타이로신 키나아제 저해제
WO2012158795A1 (en) * 2011-05-17 2012-11-22 Principia Biopharma Inc. Pyrazolopyrimidine derivatives as tyrosine kinase inhibitors
MX2014000518A (es) * 2011-07-13 2014-05-30 Pharmacyclics Inc Inhibidores de la tirosina quinasa de bruton.
EP2861599B1 (en) * 2012-06-18 2019-12-18 Principia Biopharma Inc. Reversible covalent pyrrolo- or pyrazolopyrimidines useful for the treatment of cancer and autoimmune diseases
CA2879400A1 (en) * 2012-07-30 2014-02-06 Concert Pharmaceuticals, Inc. Deuterated ibrutinib
CN104540455A (zh) * 2012-07-31 2015-04-22 安全电线控股有限责任公司 深度可控的贾姆什迪针
WO2014022569A1 (en) * 2012-08-03 2014-02-06 Principia Biopharma Inc. Treatment of dry eye
KR102203990B1 (ko) 2012-09-10 2021-01-18 프린시피아 바이오파마, 인코퍼레이티드 키나제 저해제로서의 피라졸로피리미딘 화합물
US9479134B2 (en) * 2013-03-04 2016-10-25 Texas Instruments Incorporated Position detecting system
WO2014143807A2 (en) 2013-03-15 2014-09-18 Stromatt Scott Anti-cd37 antibody and bcr pathway antagonist combination therapy for treatment of b-cell malignancies and disorders
EP2983670A4 (en) 2013-04-08 2017-03-08 Pharmacyclics LLC Ibrutinib combination therapy
MX2015014171A (es) 2013-04-08 2015-12-16 Bayer Pharma AG Uso de 2,3-dihidroimidazo[1,2-c]quinazolinas sustituidas.
US8957080B2 (en) * 2013-04-09 2015-02-17 Principia Biopharma Inc. Tyrosine kinase inhibitors
EP2999702A4 (en) * 2013-05-21 2017-01-11 Jiangsu Medolution Ltd. Substituted pyrazolopyrimidines as kinases inhibitors
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
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

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