WO2020063788A8 - Fgfr4抑制剂及其应用 - Google Patents

Fgfr4抑制剂及其应用 Download PDF

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Publication number
WO2020063788A8
WO2020063788A8 PCT/CN2019/108298 CN2019108298W WO2020063788A8 WO 2020063788 A8 WO2020063788 A8 WO 2020063788A8 CN 2019108298 W CN2019108298 W CN 2019108298W WO 2020063788 A8 WO2020063788 A8 WO 2020063788A8
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WO
WIPO (PCT)
Prior art keywords
fgfr4
inhibitor
fgfr4 inhibitor
neovascularization
apoptosis
Prior art date
Application number
PCT/CN2019/108298
Other languages
English (en)
French (fr)
Other versions
WO2020063788A1 (zh
Inventor
高金恒
孙中心
张贇
徐晓峰
刘湘永
王家炳
丁列明
Original Assignee
贝达药业股份有限公司
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
Priority to US17/280,309 priority Critical patent/US20220002307A1/en
Priority to CA3114147A priority patent/CA3114147A1/en
Priority to JP2021517318A priority patent/JP7446287B2/ja
Priority to KR1020217011210A priority patent/KR20210066839A/ko
Application filed by 贝达药业股份有限公司 filed Critical 贝达药业股份有限公司
Priority to EA202190885A priority patent/EA202190885A1/ru
Priority to MX2021003531A priority patent/MX2021003531A/es
Priority to BR112021005750-1A priority patent/BR112021005750A2/pt
Priority to SG11202103092VA priority patent/SG11202103092VA/en
Priority to EP19867204.0A priority patent/EP3848377A4/en
Priority to CN201980061921.XA priority patent/CN112771049B/zh
Priority to AU2019348120A priority patent/AU2019348120A1/en
Publication of WO2020063788A1 publication Critical patent/WO2020063788A1/zh
Priority to IL281798A priority patent/IL281798A/en
Priority to ZA2021/02192A priority patent/ZA202102192B/en
Publication of WO2020063788A8 publication Critical patent/WO2020063788A8/zh

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    • 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
    • C07D498/22—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 four or more hetero rings
    • 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
    • A61K31/437—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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • C07D487/12—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 three hetero rings
    • C07D487/14—Ortho-condensed 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
    • A61K31/435—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
    • A61K31/495—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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • 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
    • C07D471/02—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 two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • C07D471/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—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
    • C07D491/12—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 three hetero rings
    • C07D491/14—Ortho-condensed systems
    • C07D491/147—Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—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
    • C07D491/22—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 four or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/12—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 three hetero rings
    • C07D495/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
    • C07D513/14—Ortho-condensed 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)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

一种作为成纤维细胞生长因子受体4（FGFR4）抑制剂的化合物（如式I所示），及其药物组合物、制备方法，以及其在治疗FGFR4介导的疾病中的用途。上述化合物通过参与调节细胞增殖、凋亡、迁移、新生血管生成等多个过程而发挥作用。
PCT/CN2019/108298 2018-09-27 2019-09-26 Fgfr4抑制剂及其应用 WO2020063788A1 (zh)

Priority Applications (13)

Application Number Priority Date Filing Date Title
MX2021003531A MX2021003531A (es) 2018-09-27 2019-09-26 Inhibidor de fgfr4 y su uso.
JP2021517318A JP7446287B2 (ja) 2018-09-27 2019-09-26 Ｆｇｆｒ４阻害剤及びその使用
KR1020217011210A KR20210066839A (ko) 2018-09-27 2019-09-26 Fgfr4 저해제 및 그것의 용도
SG11202103092VA SG11202103092VA (en) 2018-09-27 2019-09-26 Fgfr4 inhibitor and use thereof
EA202190885A EA202190885A1 (ru) 2018-09-27 2019-09-26 Ингибитор fgfr4 и его применение
CA3114147A CA3114147A1 (en) 2018-09-27 2019-09-26 Fgfr4 inhibitor and use thereof
BR112021005750-1A BR112021005750A2 (pt) 2018-09-27 2019-09-26 inibidor de fgfr4 e uso do mesmo
US17/280,309 US20220002307A1 (en) 2018-09-27 2019-09-26 Fgfr4 inhibitor and use thereof
EP19867204.0A EP3848377A4 (en) 2018-09-27 2019-09-26 FGFR4 INHIBITOR AND USE THEREOF
CN201980061921.XA CN112771049B (zh) 2018-09-27 2019-09-26 Fgfr4抑制剂及其应用
AU2019348120A AU2019348120A1 (en) 2018-09-27 2019-09-26 FGFR4 inhibitor and use thereof
IL281798A IL281798A (en) 2018-09-27 2021-03-24 Prevents FGFR4 and its use
ZA2021/02192A ZA202102192B (en) 2018-09-27 2021-03-31 Fgfr4 inhibitor and use thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN2018107902 2018-09-27
CNPCT/CN2018/107902 2018-09-27

Publications (2)

Publication Number Publication Date
WO2020063788A1 WO2020063788A1 (zh) 2020-04-02
WO2020063788A8 true WO2020063788A8 (zh) 2023-03-30

Family

ID=69953396

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/108298 WO2020063788A1 (zh) 2018-09-27 2019-09-26 Fgfr4抑制剂及其应用

Country Status (15)

Country Link
US (1) US20220002307A1 (zh)
EP (1) EP3848377A4 (zh)
JP (1) JP7446287B2 (zh)
KR (1) KR20210066839A (zh)
CN (1) CN112771049B (zh)
AU (1) AU2019348120A1 (zh)
BR (1) BR112021005750A2 (zh)
CA (1) CA3114147A1 (zh)
EA (1) EA202190885A1 (zh)
IL (1) IL281798A (zh)
MX (1) MX2021003531A (zh)
SG (1) SG11202103092VA (zh)
TW (1) TWI822868B (zh)
WO (1) WO2020063788A1 (zh)
ZA (1) ZA202102192B (zh)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021190623A1 (zh) * 2020-03-27 2021-09-30 贝达药业股份有限公司 Fgfr4抑制剂的盐型、晶型及其用途
JP2022108517A (ja) * 2021-01-13 2022-07-26 地方独立行政法人東京都健康長寿医療センター 医薬組成物
EP4289852A1 (en) * 2021-02-08 2023-12-13 Medshine Discovery Inc. 5,6-dihydrothieno[3,4-h]quinazoline compound
CN114907350B (zh) * 2021-02-10 2023-12-29 上海凌达生物医药有限公司 一类含氮稠环类化合物、制备方法和用途

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050070554A1 (en) 2003-08-27 2005-03-31 Amgen Inc. Substituted heterocyclic compounds and methods of use
TWI461410B (zh) 2008-12-30 2014-11-21 Arqule Inc 經取代之５，６－二氫－６－苯基苯並〔f〕異喹啉－２－胺化合物類
TWI532742B (zh) * 2011-02-28 2016-05-11 艾伯維有限公司 激酶之三環抑制劑
MX2014010176A (es) 2012-02-23 2014-11-10 Abbvie Inc Inhibidores de cinasas de piridopirimidinona.
JP6458023B2 (ja) 2013-10-25 2019-01-23 ブループリント メディシンズ コーポレイション 繊維芽細胞成長因子受容体の阻害剤
GB201322602D0 (en) 2013-12-19 2014-02-05 Almac Discovery Ltd Pharmaceutical compounds
WO2018004258A1 (ko) * 2016-06-28 2018-01-04 한미약품 주식회사 신규한 헤테로시클릭 유도체 화합물 및 이의 용도
KR20180002053A (ko) * 2016-06-28 2018-01-05 한미약품 주식회사 신규한 헤테로시클릭 유도체 화합물 및 이의 용도
KR102534962B1 (ko) 2016-11-16 2023-05-22 임팩트 테라퓨틱스 (상하이), 인코포레이티드 8,9-디하이드로이미다졸[1,2-a]피리미도[5,4-e]피리미딘-5(6H)-케톤계 화합물
KR20190126344A (ko) * 2017-02-27 2019-11-11 베타 파머수티컬 컴퍼니 리미티드 Fgfr 억제제 및 이의 용도

Also Published As

Publication number Publication date
CN112771049A (zh) 2021-05-07
AU2019348120A1 (en) 2021-05-06
BR112021005750A2 (pt) 2021-06-29
EP3848377A4 (en) 2022-06-15
WO2020063788A1 (zh) 2020-04-02
TWI822868B (zh) 2023-11-21
US20220002307A1 (en) 2022-01-06
IL281798A (en) 2021-05-31
CN112771049B (zh) 2024-01-26
SG11202103092VA (en) 2021-04-29
CA3114147A1 (en) 2020-04-02
EA202190885A1 (ru) 2021-06-25
EP3848377A1 (en) 2021-07-14
JP2022502438A (ja) 2022-01-11
MX2021003531A (es) 2021-07-21
JP7446287B2 (ja) 2024-03-08
KR20210066839A (ko) 2021-06-07
ZA202102192B (en) 2022-06-29
TW202028211A (zh) 2020-08-01

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