CN109071532A - Fgfr4抑制剂、其制备方法和应用 - Google Patents

Fgfr4抑制剂、其制备方法和应用 Download PDF

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Publication number
CN109071532A
CN109071532A CN201780013978.3A CN201780013978A CN109071532A CN 109071532 A CN109071532 A CN 109071532A CN 201780013978 A CN201780013978 A CN 201780013978A CN 109071532 A CN109071532 A CN 109071532A
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base
alkyl
heterocyclic ring
circle heterocyclic
compound
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CN109071532B (zh
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高鹏
修文华
王少宝
刘磊
包如迪
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Jiangsu Hansoh Pharmaceutical Group Co Ltd
Shanghai Hansoh Biomedical Co Ltd
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Jiangsu Hansoh Pharmaceutical Group Co Ltd
Shanghai Hansoh Biomedical Co Ltd
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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
    • C07D471/02—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
    • 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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • A61K31/5355—Non-condensed oxazines and containing further 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
    • A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (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)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pyridine Compounds (AREA)

Abstract

本发明涉及一种具有式(I)结构的FGFR4抑制剂、其制备方法和应用。本发明所开发的式(I)系列化合物对FGFR4激酶活性具有很强的抑制作用，并具有非常高的选择性，可广泛应用于制备治疗癌症特别是肝癌、胃癌、前列腺癌、皮肤癌、卵巢癌、肺癌、乳腺癌或结肠癌的药物，有望开发成新一代FGFR4抑制剂药物。

Description

PCT国内申请，说明书已公开。

Claims (26)

  1. PCT国内申请，权利要求书已公开。
CN201780013978.3A 2016-05-20 2017-05-16 Fgfr4抑制剂、其制备方法和应用 Active CN109071532B (zh)

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CN202110435282.8A CN113105454B (zh) 2016-05-20 2017-05-16 Fgfr4抑制剂、其制备方法和应用
CN202110442076.XA CN113234072B (zh) 2016-05-20 2017-05-16 Fgfr4抑制剂、其制备方法和应用

Applications Claiming Priority (5)

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CN201610339009 2016-05-20
CN2016103390094 2016-05-20
CN2016111665987 2016-12-16
CN201611166598 2016-12-16
PCT/CN2017/084564 WO2017198149A1 (zh) 2016-05-20 2017-05-16 Fgfr4抑制剂、其制备方法和应用

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US (1) US11667631B2 (zh)
EP (1) EP3444250A4 (zh)
JP (1) JP7103952B2 (zh)
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HK (1) HK1258018A1 (zh)
TW (1) TWI751163B (zh)
WO (1) WO2017198149A1 (zh)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108948004A (zh) * 2016-05-27 2018-12-07 杭州英创医药科技有限公司 作为fgfr4抑制剂的杂环化合物
CN109563091A (zh) * 2016-08-12 2019-04-02 江苏豪森药业集团有限公司 Fgfr4抑制剂及其制备方法和应用
CN109745321A (zh) * 2017-11-08 2019-05-14 上海翰森生物医药科技有限公司 包含fgfr4抑制剂的药物组合物
WO2023207944A1 (zh) * 2022-04-26 2023-11-02 石药集团中奇制药技术（石家庄）有限公司 Fgfr4抑制剂的晶型及应用

Families Citing this family (11)

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EP3057943B1 (en) 2013-10-18 2018-04-25 Eisai R&D Management Co., Ltd. Pyrimidine fgfr4 inhibitors
KR102548229B1 (ko) 2015-04-14 2023-06-27 에자이 알앤드디 매니지먼트 가부시키가이샤 결정질 fgfr4 억제제 화합물 및 그의 용도
US11357769B2 (en) 2016-05-10 2022-06-14 Eisai R&D Management Co., Ltd. Drug combinations for reducing cell viability and/or cell proliferation
WO2019085927A1 (zh) * 2017-10-31 2019-05-09 江苏豪森药业集团有限公司 Fgfr4抑制剂的盐、晶体、制备方法及其用途
CN110225913B (zh) * 2017-10-31 2021-10-15 江苏豪森药业集团有限公司 Fgfr4抑制剂晶型及其制备方法
CN110240598B (zh) * 2018-03-09 2023-07-25 上海翰森生物医药科技有限公司 甲酰胺衍生物的制备方法及其中间体化合物
TWI723480B (zh) * 2018-07-27 2021-04-01 大陸商北京加科思新藥研發有限公司 用作fgfr4抑制劑的稠環衍生物
CN111662285B (zh) * 2019-03-07 2023-05-16 江苏豪森药业集团有限公司 2-氧代-1,3-氧杂氮杂环庚衍生物的制备方法
AU2020298246A1 (en) * 2019-06-21 2022-01-27 Terns Pharmaceuticals Inc. Compounds for inhibiting FGFR4
CN113072550B (zh) * 2020-01-06 2023-08-08 周龙兴 一种高选择性成纤维细胞生长因子受体抑制剂和应用
WO2022089648A1 (en) * 2020-11-02 2022-05-05 Jacobio Pharmaceuticals Co., Ltd. Crystalline forms of salts of fgfr4 inhibitor

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WO2015059668A1 (en) * 2013-10-25 2015-04-30 Novartis Ag Ring-fused bicyclic pyridyl derivatives as fgfr4 inhibitors
WO2016151501A1 (en) * 2015-03-25 2016-09-29 Novartis Ag Pharmaceutical combinations
WO2016151500A1 (en) * 2015-03-25 2016-09-29 Novartis Ag Particles of n-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-((4-methyl-2- oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2h)-carboxamide

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WO2016054483A1 (en) 2014-10-03 2016-04-07 Novartis Ag Use of ring-fused bicyclic pyridyl derivatives as fgfr4 inhibitors
KR20190038485A (ko) * 2016-05-27 2019-04-08 항저우 인노게이트 파마 컴퍼니 리미티드 Fgfr4 저해제인 헤테로 고리 화합물

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
WO2015059668A1 (en) * 2013-10-25 2015-04-30 Novartis Ag Ring-fused bicyclic pyridyl derivatives as fgfr4 inhibitors
WO2016151501A1 (en) * 2015-03-25 2016-09-29 Novartis Ag Pharmaceutical combinations
WO2016151500A1 (en) * 2015-03-25 2016-09-29 Novartis Ag Particles of n-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-((4-methyl-2- oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2h)-carboxamide

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108948004A (zh) * 2016-05-27 2018-12-07 杭州英创医药科技有限公司 作为fgfr4抑制剂的杂环化合物
CN111689959A (zh) * 2016-05-27 2020-09-22 石药集团中奇制药技术（石家庄）有限公司 作为fgfr4抑制剂的杂环化合物
CN108948004B (zh) * 2016-05-27 2020-11-10 石药集团中奇制药技术（石家庄）有限公司 作为fgfr4抑制剂的杂环化合物
CN111689959B (zh) * 2016-05-27 2022-04-01 石药集团中奇制药技术（石家庄）有限公司 作为fgfr4抑制剂的杂环化合物
US11352353B2 (en) 2016-05-27 2022-06-07 Hangzhou Innogate Pharma Co., Ltd. Heterocyclic compound serving as FGFR4 inhibitor
CN109563091A (zh) * 2016-08-12 2019-04-02 江苏豪森药业集团有限公司 Fgfr4抑制剂及其制备方法和应用
CN109563091B (zh) * 2016-08-12 2022-04-29 江苏豪森药业集团有限公司 Fgfr4抑制剂及其制备方法和应用
CN109745321A (zh) * 2017-11-08 2019-05-14 上海翰森生物医药科技有限公司 包含fgfr4抑制剂的药物组合物
CN109745321B (zh) * 2017-11-08 2022-04-29 上海翰森生物医药科技有限公司 包含fgfr4抑制剂的药物组合物
WO2023207944A1 (zh) * 2022-04-26 2023-11-02 石药集团中奇制药技术（石家庄）有限公司 Fgfr4抑制剂的晶型及应用

Also Published As

Publication number Publication date
CN113234072B (zh) 2022-11-04
CN113105454A (zh) 2021-07-13
CN113105454B (zh) 2022-10-11
US11667631B2 (en) 2023-06-06
CN109071532B (zh) 2021-04-27
TW201741311A (zh) 2017-12-01
EP3444250A1 (en) 2019-02-20
CN113234072A (zh) 2021-08-10
US20190276451A1 (en) 2019-09-12
JP2019519513A (ja) 2019-07-11
HK1258018A1 (zh) 2019-11-01
WO2017198149A1 (zh) 2017-11-23
EP3444250A4 (en) 2019-09-25
JP7103952B2 (ja) 2022-07-20
TWI751163B (zh) 2022-01-01

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