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CN111247150A - Fgfr抑制剂及其医药用途 - Google Patents

Fgfr抑制剂及其医药用途 Download PDF

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Publication number
CN111247150A
CN111247150A CN201880052899.8A CN201880052899A CN111247150A CN 111247150 A CN111247150 A CN 111247150A CN 201880052899 A CN201880052899 A CN 201880052899A CN 111247150 A CN111247150 A CN 111247150A
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compound
synthesis
acid
nmr
400mhz
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CN201880052899.8A
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CN111247150B (zh
Inventor
王一恺
张杨
陈正霞
陈琳琳
冯韬
黄荣新
李秋
李德尧
孙继奎
徐洋洋
李婕
黎健
陈曙辉
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Shanghai Runshi Pharmaceutical Technology Co ltd
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CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

本发明公开了一类FGFR抑制剂，及其在制备治疗与FGFR相关疾病的药物中的应用。具体公开了式（Ⅰ）所示化合物及其药学上可接受的盐。

Description

PCT国内申请，说明书已公开。

Claims (19)

  1. PCT国内申请，权利要求书已公开。
CN201880052899.8A 2017-08-15 2018-08-15 Fgfr抑制剂及其医药用途 Active CN111247150B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN201710698086 2017-08-15
CN2017106980863 2017-08-15
PCT/CN2018/100638 WO2019034076A1 (zh) 2017-08-15 2018-08-15 Fgfr抑制剂及其医药用途

Publications (2)

Publication Number Publication Date
CN111247150A true CN111247150A (zh) 2020-06-05
CN111247150B CN111247150B (zh) 2022-11-08

Family

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CN201880052899.8A Active CN111247150B (zh) 2017-08-15 2018-08-15 Fgfr抑制剂及其医药用途

Country Status (8)

Country Link
US (1) US11236094B2 (zh)
EP (1) EP3670513B1 (zh)
JP (1) JP7341122B2 (zh)
KR (1) KR102707041B1 (zh)
CN (1) CN111247150B (zh)
AU (1) AU2018317153B2 (zh)
RU (1) RU2771311C2 (zh)
WO (1) WO2019034076A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114712365A (zh) * 2022-06-07 2022-07-08 山东绿叶制药有限公司 Trk抑制剂在制备治疗迟发性运动障碍药物中的应用

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113454087B (zh) * 2019-02-15 2023-01-03 石药集团中奇制药技术（石家庄）有限公司 固体形式的fgfr抑制剂化合物及其制备方法
JP2022526713A (ja) 2019-03-21 2022-05-26 オンクセオ がんの処置のための、キナーゼ阻害剤と組み合わせたＤｂａｉｔ分子
JP2023500906A (ja) 2019-11-08 2023-01-11 インサーム（インスティテュ ナシオナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシェ メディカル） キナーゼ阻害剤に対する獲得抵抗性を有するがんの処置方法
CN114641293B (zh) * 2019-11-08 2024-05-31 石药集团中奇制药技术（石家庄）有限公司 一种fgfr抑制剂的用途
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
KR20230035031A (ko) 2020-06-05 2023-03-10 킨네이트 바이오파마 인크. 섬유아세포 성장 인자 수용체 키나아제의 억제제
TWI797711B (zh) * 2020-08-13 2023-04-01 大陸商上海和譽生物醫藥科技有限公司 一種fgfr及其突變抑制劑，其製備方法和應用
CN114057749B (zh) * 2021-11-19 2023-12-22 药雅科技(上海)有限公司 不可逆炔类杂环化合物fgfr抑制剂的制备方法和用途
CN114853740B (zh) * 2021-02-03 2023-08-01 药雅科技(上海)有限公司 炔类嘧啶化合物作为fgfr抑制剂的制备方法和用途
CN115433190B (zh) * 2021-06-02 2024-09-20 药雅科技(上海)有限公司 不可逆杂环化合物fgfr抑制剂的制备方法和用途
US20240109896A1 (en) * 2021-02-03 2024-04-04 Ya Therapeutics Inc Fgfr kinase inhibitor and use thereof
CN115141176B (zh) * 2021-03-31 2023-08-22 药雅科技(上海)有限公司 炔代吲哚类fgfr抑制剂及其制备方法和用途
CN115215868A (zh) * 2021-04-14 2022-10-21 药雅科技(上海)有限公司 杂环化合物fgfr抑制剂的制备方法和用途
KR20250164828A (ko) 2023-03-30 2025-11-25 레볼루션 메디슨즈, 인크. Ras gtp 가수분해 유도를 위한 조성물 및 이의 용도
TW202508595A (zh) 2023-05-04 2025-03-01 美商銳新醫藥公司 用於ｒａｓ相關疾病或病症之組合療法
US20250049810A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025080946A2 (en) 2023-10-12 2025-04-17 Revolution Medicines, Inc. Ras inhibitors
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
WO2025240847A1 (en) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Ras inhibitors
WO2025255438A1 (en) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025265060A1 (en) 2024-06-21 2025-12-26 Revolution Medicines, Inc. Therapeutic compositions and methods for managing treatment-related effects
WO2026006747A1 (en) 2024-06-28 2026-01-02 Revolution Medicines, Inc. Ras inhibitors
WO2026015801A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015796A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015790A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015825A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Use of ras inhibitor for treating pancreatic cancer

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007056170A2 (en) * 2005-11-02 2007-05-18 Bayer Healthcare Ag Pyrrolo[2,1-f] [1,2,4] triazin-4-ylamines igf-1r kinase inhibitors for the treatment of cancer and other hyperproliferative diseases
WO2013087578A1 (en) * 2011-12-15 2013-06-20 Bayer Pharma Aktiengesellschaft Disubstituted benzothienyl-pyrrolotriazines and their use as fgfr kinase inhibitors
WO2013124316A1 (en) * 2012-02-23 2013-08-29 Bayer Intellectual Property Gmbh Substituted benzothienyl-pyrrolotriazines and uses thereof
CN104159900A (zh) * 2011-12-15 2014-11-19 拜耳知识产权有限责任公司 取代的苯并噻吩基-吡咯并三嗪及其在癌症治疗中的用途
WO2016091849A2 (en) * 2014-12-11 2016-06-16 Bayer Pharma Aktiengesellschaft Use of pan fgfr inhibitors and method of identifying patients with cancer eligible for treatment with a pan fgfr inhibitor
WO2016142312A1 (en) * 2015-03-09 2016-09-15 Bayer Pharma Aktiengesellschaft Substituted 2,3-dihydroimidazo[1,2-c]quinazoline-containing combinations

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0512324D0 (en) 2005-06-16 2005-07-27 Novartis Ag Organic compounds
RS51843B (sr) * 2005-11-17 2012-02-29 Osi Pharmaceuticals Llc. KONDENZOVANI BICIKLIČNI m TOR INHIBITORI
BRPI0914233A2 (pt) 2008-06-19 2015-11-03 Astrazeneca Ab composto, uso de um composto, métodos para produzir um efeito inibidor de fgfr e para produzir um efeito anticâncer em um animal de sangue quente, composição farmacêutica, e, método para tratar uma doença
BR112014018868B1 (pt) 2012-02-28 2021-02-09 Astellas Pharma Inc. composto heterocíclico aromático contendo nitrogênio, composição farmacêutica compreendendo dito composto e uso do mesmo
CN103450204B (zh) * 2012-05-31 2016-08-17 中国科学院上海药物研究所 吡咯[2，1-f][1，2，4]并三嗪类化合物，其制备方法及用途
US10124003B2 (en) 2013-07-18 2018-11-13 Taiho Pharmaceutical Co., Ltd. Therapeutic agent for FGFR inhibitor-resistant cancer

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007056170A2 (en) * 2005-11-02 2007-05-18 Bayer Healthcare Ag Pyrrolo[2,1-f] [1,2,4] triazin-4-ylamines igf-1r kinase inhibitors for the treatment of cancer and other hyperproliferative diseases
WO2013087578A1 (en) * 2011-12-15 2013-06-20 Bayer Pharma Aktiengesellschaft Disubstituted benzothienyl-pyrrolotriazines and their use as fgfr kinase inhibitors
CN104159900A (zh) * 2011-12-15 2014-11-19 拜耳知识产权有限责任公司 取代的苯并噻吩基-吡咯并三嗪及其在癌症治疗中的用途
WO2013124316A1 (en) * 2012-02-23 2013-08-29 Bayer Intellectual Property Gmbh Substituted benzothienyl-pyrrolotriazines and uses thereof
WO2016091849A2 (en) * 2014-12-11 2016-06-16 Bayer Pharma Aktiengesellschaft Use of pan fgfr inhibitors and method of identifying patients with cancer eligible for treatment with a pan fgfr inhibitor
WO2016142312A1 (en) * 2015-03-09 2016-09-15 Bayer Pharma Aktiengesellschaft Substituted 2,3-dihydroimidazo[1,2-c]quinazoline-containing combinations

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
何丹丹 等: "具有EGFR/HER2双重抑制作用的小分子抑制剂的研究进展", 《中南药学》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114712365A (zh) * 2022-06-07 2022-07-08 山东绿叶制药有限公司 Trk抑制剂在制备治疗迟发性运动障碍药物中的应用

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EP3670513B1 (en) 2023-09-20
US11236094B2 (en) 2022-02-01
JP7341122B2 (ja) 2023-09-08
RU2020110780A3 (zh) 2021-09-16
AU2018317153B2 (en) 2021-12-23
US20200207773A1 (en) 2020-07-02
RU2771311C2 (ru) 2022-04-29
KR20200041361A (ko) 2020-04-21
WO2019034076A1 (zh) 2019-02-21
KR102707041B1 (ko) 2024-09-19
RU2020110780A (ru) 2021-09-16
CN111247150B (zh) 2022-11-08
CA3072979A1 (en) 2019-02-21
EP3670513A1 (en) 2020-06-24
JP2020532500A (ja) 2020-11-12
EP3670513A4 (en) 2021-04-14
AU2018317153A1 (en) 2020-03-05

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