CN113646314A - Fgfr4激酶抑制剂及其制备方法和用途 - Google Patents

Fgfr4激酶抑制剂及其制备方法和用途 Download PDF

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CN113646314A
CN113646314A CN202080026854.0A CN202080026854A CN113646314A CN 113646314 A CN113646314 A CN 113646314A CN 202080026854 A CN202080026854 A CN 202080026854A CN 113646314 A CN113646314 A CN 113646314A
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alkyl
compound
pharmaceutically acceptable
polymorph
solvate
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CN113646314B (zh
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王静晗
姚金锁
段小伟
袁保昆
刘希杰
焦楠
闵汪洋
孙莹
路畅
孙颖慧
张久庆
季业龄
侯登
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Capital Pharmaceutical Holdings Beijing Co ltd
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Capital Pharmaceutical Holdings Beijing Co ltd
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Priority claimed from CN201910602669.0A external-priority patent/CN112174986A/zh
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    • 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
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
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    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
    • 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
    • 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
    • A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring 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
    • C07D487/04—Ortho-condensed systems
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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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    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • 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

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

Abstract

本发明涉及FGFR4激酶抑制剂及其制备方法和用途。本发明涉及式I的化合物、或其药学上可接受的盐、溶剂化物、多晶型物或异构体，及其在制备用来治疗FGFR4介导的疾病的药物中的用途。

Description

PCT国内申请，说明书已公开。

Claims (13)

  1. PCT国内申请，权利要求书已公开。
CN202080026854.0A 2019-03-08 2020-03-06 Fgfr4激酶抑制剂及其制备方法和用途 Active CN113646314B (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
CN201910178024.9A CN111662292A (zh) 2019-03-08 2019-03-08 Fgfr4激酶抑制剂及其制备方法和用途
CN2019101780249 2019-03-08
CN2019106026690 2019-07-05
CN201910602669.0A CN112174986A (zh) 2019-07-05 2019-07-05 Fgfr4激酶抑制剂及其制备方法和用途
PCT/CN2020/078098 WO2020182062A1 (zh) 2019-03-08 2020-03-06 Fgfr4激酶抑制剂及其制备方法和用途

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CN113646314B CN113646314B (zh) 2023-12-08

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US (1) US20220185811A1 (zh)
EP (1) EP3936509A4 (zh)
JP (1) JP7378488B2 (zh)
KR (1) KR20210131369A (zh)
CN (1) CN113646314B (zh)
WO (1) WO2020182062A1 (zh)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11591329B2 (en) 2019-07-09 2023-02-28 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
JP2023505258A (ja) 2019-12-04 2023-02-08 インサイト・コーポレイション Ｆｇｆｒ阻害剤としての三環式複素環
KR20220159457A (ko) * 2020-03-27 2022-12-02 베타 파머수티컬 컴퍼니 리미티드 Fgfr4 억제제의 염 형태, 결정 형태 및 그 용도
EP4352059A1 (en) 2021-06-09 2024-04-17 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
EP4352060A1 (en) * 2021-06-09 2024-04-17 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors

Citations (6)

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Publication number Priority date Publication date Assignee Title
CN1646529A (zh) * 2002-04-03 2005-07-27 霍夫曼-拉罗奇有限公司 咪唑并稠合化合物
WO2014011900A2 (en) * 2012-07-11 2014-01-16 Blueprint Medicines Inhibitors of the fibroblast growth factor receptor
WO2017050864A1 (en) * 2015-09-23 2017-03-30 Janssen Pharmaceutica Nv New compounds
WO2018004258A1 (ko) * 2016-06-28 2018-01-04 한미약품 주식회사 신규한 헤테로시클릭 유도체 화합물 및 이의 용도
WO2018113584A1 (zh) * 2016-12-19 2018-06-28 上海和誉生物医药科技有限公司 Fgfr4抑制剂、其制备方法与药学上的应用
WO2018153373A1 (zh) * 2017-02-27 2018-08-30 贝达药业股份有限公司 Fgfr抑制剂及其应用

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MX2015011514A (es) * 2013-03-15 2016-08-11 Celgene Avilomics Res Inc Compuestos de heteroarilo y sus usos.
US9695165B2 (en) 2014-01-15 2017-07-04 Blueprint Medicines Corporation Inhibitors of the fibroblast growth factor receptor
TW201900644A (zh) 2017-05-09 2019-01-01 大陸商南京聖和藥業股份有限公司 Fgfr4抑制劑及其制備與應用
EP3705480B1 (en) 2017-10-30 2024-02-28 Shanghai Ringene BioPharma Co., Ltd. Class of amino-substituted nitrogen-containing fused ring compounds, preparation method therefor, and use thereof

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1646529A (zh) * 2002-04-03 2005-07-27 霍夫曼-拉罗奇有限公司 咪唑并稠合化合物
WO2014011900A2 (en) * 2012-07-11 2014-01-16 Blueprint Medicines Inhibitors of the fibroblast growth factor receptor
WO2017050864A1 (en) * 2015-09-23 2017-03-30 Janssen Pharmaceutica Nv New compounds
WO2018004258A1 (ko) * 2016-06-28 2018-01-04 한미약품 주식회사 신규한 헤테로시클릭 유도체 화합물 및 이의 용도
WO2018113584A1 (zh) * 2016-12-19 2018-06-28 上海和誉生物医药科技有限公司 Fgfr4抑制剂、其制备方法与药学上的应用
WO2018153373A1 (zh) * 2017-02-27 2018-08-30 贝达药业股份有限公司 Fgfr抑制剂及其应用

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KR20210131369A (ko) 2021-11-02
JP7378488B2 (ja) 2023-11-13
US20220185811A1 (en) 2022-06-16
EP3936509A4 (en) 2022-03-30
EP3936509A1 (en) 2022-01-12
JP2022523448A (ja) 2022-04-22
CN113646314B (zh) 2023-12-08
WO2020182062A1 (zh) 2020-09-17

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