CN110382499A - Fgfr抑制剂及其应用 - Google Patents

Fgfr抑制剂及其应用 Download PDF

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Publication number
CN110382499A
CN110382499A CN201880013847.XA CN201880013847A CN110382499A CN 110382499 A CN110382499 A CN 110382499A CN 201880013847 A CN201880013847 A CN 201880013847A CN 110382499 A CN110382499 A CN 110382499A
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base
pyrido
chloro
pyrimidine
dimethoxyphenyl
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CN110382499B (zh
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徐晓峰
王家炳
丁列明
刘湘永
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Betta Pharmaceuticals Co Ltd
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Betta Pharmaceuticals Co Ltd
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    • 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
    • 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
    • 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with 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
    • A61K31/495—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
    • 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
    • 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

Abstract

一种作为成纤维细胞生长因子受体(FGFR)抑制剂的氮杂三环类化合物(如式Ⅰ所示)，及其药物组合物、制备方法，以及其在治疗FGFR介导的疾病中的用途。氮杂三环类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。

Description

PCT国内申请，说明书已公开。

Claims (43)

  1. PCT国内申请，权利要求书已公开。
CN201880013847.XA 2017-02-27 2018-02-27 Fgfr抑制剂及其应用 Active CN110382499B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CNPCT/CN2017/074967 2017-02-27
CN2017074967 2017-02-27
PCT/CN2018/077314 WO2018153373A1 (zh) 2017-02-27 2018-02-27 Fgfr抑制剂及其应用

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CN110382499A true CN110382499A (zh) 2019-10-25
CN110382499B CN110382499B (zh) 2023-01-03

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US (1) US11365196B2 (zh)
EP (1) EP3587419A4 (zh)
JP (1) JP6876833B2 (zh)
KR (1) KR20190126344A (zh)
CN (1) CN110382499B (zh)
AU (1) AU2018226315B2 (zh)
CA (1) CA3054455C (zh)
RU (1) RU2745035C1 (zh)
SG (1) SG11201907909TA (zh)
TW (1) TWI741155B (zh)
WO (1) WO2018153373A1 (zh)

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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
CN110857300B (zh) * 2018-08-23 2021-11-05 上海凌达生物医药有限公司 一类稠环三氮唑类化合物、制备方法和用途
WO2020043078A1 (zh) * 2018-08-27 2020-03-05 贝达药业股份有限公司 新型氮杂三环类化合物的盐型、晶型及其用途
KR102328435B1 (ko) * 2018-09-11 2021-11-18 재단법인 대구경북첨단의료산업진흥재단 신규 피리도-피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 단백질 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물
US20220002307A1 (en) * 2018-09-27 2022-01-06 Betta Pharmaceuticals Co., Ltd Fgfr4 inhibitor and use thereof
KR20210131369A (ko) * 2019-03-08 2021-11-02 쇼우야오 홀딩스 (베이징) 코., 엘티디. Fgfr4 키나아제 억제제 및 이의 제조 방법과 용도
AU2020242287A1 (en) 2019-03-21 2021-09-02 INSERM (Institut National de la Santé et de la Recherche Médicale) A Dbait molecule in combination with kinase inhibitor for the treatment of cancer
WO2021018003A1 (zh) * 2019-07-26 2021-02-04 贝达药业股份有限公司 Egfr抑制剂、组合物及其制备方法
US20220259235A1 (en) * 2019-07-26 2022-08-18 Betta Pharmaceuticals Co., Ltd EGFR Inhibitor, Composition, and Preparation Method Therefor
TW202128173A (zh) * 2019-10-09 2021-08-01 美商G1治療公司 失調之纖維母細胞生長因子受體訊息傳遞的癌症之標靶性治療
US20220401436A1 (en) 2019-11-08 2022-12-22 INSERM (Institute National de la Santé et de la Recherche Médicale) Methods for the treatment of cancers that have acquired resistance to kinase inhibitors
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
EP4130004A4 (en) * 2020-03-27 2024-04-10 Betta Pharmaceuticals Co Ltd SALT AND CRYSTALLINE FORMS OF FGFR4 INHIBITOR AND THEIR USES
IL302807A (en) 2020-11-18 2023-07-01 Deciphera Pharmaceuticals Llc GCN2 and PERK kinase inhibitors and methods of using them

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US4666812A (en) * 1985-01-26 1987-05-19 Hoechst Aktiengesellschaft Electrophotographic material with pyrimido-pyridobenzimidazole compound
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EP2543372A1 (en) * 2011-07-08 2013-01-09 Helmholtz-Zentrum für Infektionsforschung GmbH Medicament for the treatment of liver cancer
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DE2929414A1 (de) * 1979-07-20 1981-02-05 Hoechst Ag Pyrimido- eckige klammer auf 5',4' zu 5,6 eckige klammer zu -pyrido- eckige klammer auf 1,2-a eckige klammer zu -benzimidazole, verfahren zu ihrer herstellung und deren verwendung
US4666812A (en) * 1985-01-26 1987-05-19 Hoechst Aktiengesellschaft Electrophotographic material with pyrimido-pyridobenzimidazole compound
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
EP2543372A1 (en) * 2011-07-08 2013-01-09 Helmholtz-Zentrum für Infektionsforschung GmbH Medicament for the treatment of liver cancer
WO2013007708A1 (en) * 2011-07-08 2013-01-17 Helmholtz-Zentrum für Infektionsforschung GmbH Medicament for treatment of liver cancer
CN105481858A (zh) * 2014-10-11 2016-04-13 上海医药集团股份有限公司 一种含氮稠杂环化合物、其制备方法、组合物及应用

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CA3054455C (en) 2021-10-26
KR20190126344A (ko) 2019-11-11
RU2745035C1 (ru) 2021-03-18
WO2018153373A1 (zh) 2018-08-30
CN110382499B (zh) 2023-01-03
TW201831483A (zh) 2018-09-01
EP3587419A4 (en) 2020-08-05
JP2020509089A (ja) 2020-03-26
AU2018226315B2 (en) 2021-01-28
TWI741155B (zh) 2021-10-01
US20210130353A1 (en) 2021-05-06
EP3587419A1 (en) 2020-01-01
US11365196B2 (en) 2022-06-21
JP6876833B2 (ja) 2021-05-26
SG11201907909TA (en) 2019-09-27
CA3054455A1 (en) 2018-08-30
AU2018226315A1 (en) 2019-10-03

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