CN109952290B - Fgfr4抑制剂及其制备方法和应用 - Google Patents

Fgfr4抑制剂及其制备方法和应用 Download PDF

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Publication number
CN109952290B
CN109952290B CN201780070537.7A CN201780070537A CN109952290B CN 109952290 B CN109952290 B CN 109952290B CN 201780070537 A CN201780070537 A CN 201780070537A CN 109952290 B CN109952290 B CN 109952290B
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mmol
reaction
ethyl acetate
compound
added
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CN109952290A (zh
Inventor
陈正霞
龙超峰
张杨
陈小新
王一恺
戴美碧
刘卓伟
赵海霞
刘星
胡国平
黎健
陈曙辉
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Guangdong Zhongsheng Pharmaceutical Co Ltd
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Guangdong Zhongsheng Pharmaceutical Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • 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
    • 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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
    • C07D213/53—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • 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)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN201780070537.7A 2016-11-17 2017-11-17 Fgfr4抑制剂及其制备方法和应用 Active CN109952290B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN2016110124315 2016-11-17
CN201611012431 2016-11-17
PCT/CN2017/111634 WO2018090973A1 (zh) 2016-11-17 2017-11-17 Fgfr4抑制剂及其制备方法和应用

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CN109952290A CN109952290A (zh) 2019-06-28
CN109952290B true CN109952290B (zh) 2022-05-03

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US (1) US11008292B2 (cg-RX-API-DMAC7.html)
EP (1) EP3543227B1 (cg-RX-API-DMAC7.html)
JP (1) JP7063899B2 (cg-RX-API-DMAC7.html)
KR (1) KR102249632B1 (cg-RX-API-DMAC7.html)
CN (1) CN109952290B (cg-RX-API-DMAC7.html)
AU (1) AU2017359819B2 (cg-RX-API-DMAC7.html)
CA (1) CA3043948C (cg-RX-API-DMAC7.html)
IL (1) IL266659B (cg-RX-API-DMAC7.html)
MX (1) MX389403B (cg-RX-API-DMAC7.html)
NZ (1) NZ754218A (cg-RX-API-DMAC7.html)
WO (1) WO2018090973A1 (cg-RX-API-DMAC7.html)
ZA (1) ZA201903845B (cg-RX-API-DMAC7.html)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL274274B2 (en) * 2017-11-01 2023-11-01 Guangdong Zhongsheng Pharmaceutical Co Ltd Salt form and crystal form of compound as fgfr4 inhibitor and preparation method thereof

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007082434A1 (en) * 2006-01-20 2007-07-26 Shanghai Allist Pharmaceutical., Inc. Quinazoline derivatives,preparation methods and uses thereof
WO2012136099A1 (zh) * 2011-04-02 2012-10-11 齐鲁制药有限公司 4-(取代苯氨基)喹唑啉衍生物及其制备方法、药物组合物和用途
WO2014139465A1 (en) * 2013-03-15 2014-09-18 Hutchison Medipharma Limited Novel pyrimidine and pyridine compounds and their usage
WO2016115412A1 (en) * 2015-01-18 2016-07-21 Newave Pharmaceutical Llc Dual-warhead covalent inhibitors of fgfr-4
CN105899490A (zh) * 2013-10-18 2016-08-24 卫材R&D管理有限公司 嘧啶fgfr4抑制剂
WO2016164703A1 (en) * 2015-04-09 2016-10-13 Eisai R & D Management Co., Ltd. Fgfr4 inhibitors

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109627239B (zh) 2012-07-11 2021-10-12 缆图药品公司 成纤维细胞生长因子受体的抑制剂
AU2016248056B2 (en) 2015-04-14 2020-07-23 Eisai R&D Management Co., Ltd. Crystalline FGFR4 inhibitor compound and uses thereof
IL274274B2 (en) * 2017-11-01 2023-11-01 Guangdong Zhongsheng Pharmaceutical Co Ltd Salt form and crystal form of compound as fgfr4 inhibitor and preparation method thereof

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007082434A1 (en) * 2006-01-20 2007-07-26 Shanghai Allist Pharmaceutical., Inc. Quinazoline derivatives,preparation methods and uses thereof
WO2012136099A1 (zh) * 2011-04-02 2012-10-11 齐鲁制药有限公司 4-(取代苯氨基)喹唑啉衍生物及其制备方法、药物组合物和用途
WO2014139465A1 (en) * 2013-03-15 2014-09-18 Hutchison Medipharma Limited Novel pyrimidine and pyridine compounds and their usage
CN105899490A (zh) * 2013-10-18 2016-08-24 卫材R&D管理有限公司 嘧啶fgfr4抑制剂
WO2016115412A1 (en) * 2015-01-18 2016-07-21 Newave Pharmaceutical Llc Dual-warhead covalent inhibitors of fgfr-4
WO2016164703A1 (en) * 2015-04-09 2016-10-13 Eisai R & D Management Co., Ltd. Fgfr4 inhibitors

Also Published As

Publication number Publication date
US20200062716A1 (en) 2020-02-27
WO2018090973A1 (zh) 2018-05-24
IL266659B (en) 2022-01-01
JP2019537613A (ja) 2019-12-26
JP7063899B2 (ja) 2022-05-09
CN109952290A (zh) 2019-06-28
CA3043948C (en) 2021-08-31
MX389403B (es) 2025-03-20
EP3543227B1 (en) 2020-12-30
NZ754218A (en) 2021-07-30
EP3543227A1 (en) 2019-09-25
CA3043948A1 (en) 2018-05-24
AU2017359819A1 (en) 2019-06-20
IL266659A (en) 2019-07-31
US11008292B2 (en) 2021-05-18
EP3543227A4 (en) 2019-10-30
KR20190077085A (ko) 2019-07-02
AU2017359819B2 (en) 2020-05-28
MX2019005723A (es) 2019-10-21
KR102249632B1 (ko) 2021-05-10
ZA201903845B (en) 2020-12-23

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