TWI855070B - Fgfr抑制劑及其使用方法 - Google Patents

Fgfr抑制劑及其使用方法 Download PDF

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Publication number
TWI855070B
TWI855070B TW109115853A TW109115853A TWI855070B TW I855070 B TWI855070 B TW I855070B TW 109115853 A TW109115853 A TW 109115853A TW 109115853 A TW109115853 A TW 109115853A TW I855070 B TWI855070 B TW I855070B
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Taiwan
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nitrogen
independently selected
compound
oxygen
sulfur
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TW109115853A
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Chinese (zh)
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TW202108141A (zh
Inventor
貝瑞 圖雷
海克 尚恩赫爾
亞歷山大 Ｍ 泰勒
法比奇 佐丹尼多
德米特里 Ｔ 莫斯塔卡斯
湯瑪士 Ｈ 麥林
布蘭蒂 Ｍ 禾森
瑪莉 Ｍ 麥德
培林 阿亞
迪納 Ａ 夏倫
拉維 克魯克拉斯里亞
亞歷山卓 波席歐
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美商傳達治療有限公司
美商Ｄ Ｅ 蕭爾研究有限公司
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    • 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
    • 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
    • A61K31/495—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
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • 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
    • C07D487/22—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 four or more hetero rings
    • 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
    • C07D491/02—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
    • 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
    • C07D491/02—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
    • 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
    • C07D491/02—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
    • 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
    • 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
    • C07D498/04—Ortho-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
    • C07D498/22—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
    • 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)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
TW109115853A 2019-05-13 2020-05-13 Fgfr抑制劑及其使用方法 TWI855070B (zh)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201962846991P 2019-05-13 2019-05-13
US62/846,991 2019-05-13
US202062993957P 2020-03-24 2020-03-24
US62/993,957 2020-03-24
US202063011469P 2020-04-17 2020-04-17
US63/011,469 2020-04-17

Publications (2)

Publication Number Publication Date
TW202108141A TW202108141A (zh) 2021-03-01
TWI855070B true TWI855070B (zh) 2024-09-11

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US (2) US12522605B2 (https=)
EP (2) EP3968999B1 (https=)
JP (2) JP7527309B2 (https=)
KR (2) KR20260030158A (https=)
CN (2) CN114126620B (https=)
AU (2) AU2020274083B9 (https=)
BR (1) BR112021022457A2 (https=)
CA (1) CA3137458A1 (https=)
CL (1) CL2021002882A1 (https=)
ES (1) ES2974985T3 (https=)
IL (2) IL287940B2 (https=)
MX (1) MX2021013146A (https=)
PE (1) PE20220573A1 (https=)
PH (1) PH12021552862A1 (https=)
SG (1) SG11202111327XA (https=)
TW (1) TWI855070B (https=)
WO (1) WO2020231990A1 (https=)

Cited By (2)

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US12522605B2 (en) 2019-05-13 2026-01-13 Relay Therapeutics, Inc. FGFR inhibitors and methods of use thereof
TWI921912B (zh) 2019-05-13 2026-04-11 美商傳達治療有限公司 Fgfr抑制劑及其使用方法

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JP2021017595A (ja) * 2019-07-18 2021-02-15 花王株式会社 アニオン変性セルロース
US12441707B2 (en) 2019-12-30 2025-10-14 Tyra Biosciences, Inc. Indazole compounds
EP4143196A4 (en) 2020-04-29 2024-04-17 Relay Therapeutics, Inc. PI3K-A INHIBITORS AND METHODS OF USE THEREOF
TW202233625A (zh) * 2020-11-18 2022-09-01 美商傳達治療有限公司 Ｆｇｆｒ抑制劑及其製造及使用方法
CN115160319B (zh) * 2021-04-01 2023-12-26 西安新通药物研究股份有限公司 含1,3-苯并二氧戊环结构的化合物及其制备方法与用途
WO2022206939A1 (zh) * 2021-04-03 2022-10-06 海南耀臻生物医药科技有限公司 作为fgfr抑制剂的杂环化合物及其应用
CN117677621A (zh) * 2021-08-04 2024-03-08 江苏恒瑞医药股份有限公司 含氮杂环化合物、其制备方法及其在医药上的应用
KR20240075952A (ko) * 2021-09-23 2024-05-30 3에이치 파머슈티컬즈 컴퍼니 리미티드 Fgfr 억제제 및 이의 사용 방법
WO2023104035A1 (zh) * 2021-12-06 2023-06-15 英矽智能科技(上海)有限公司 取代的单环或双环杂环化合物，其制法与医药上的用途
JP2025505230A (ja) * 2022-02-08 2025-02-21 上海奕拓醫藥科技有限責任公司 二環式ヘテロアリール化合物およびその使用
EP4499616A4 (en) * 2022-03-31 2025-10-29 Acerand Therapeutics Hong Kong Ltd SPIROBICYLICIOUS COMPOUNDS
WO2023202625A1 (zh) * 2022-04-20 2023-10-26 深圳福沃药业有限公司 Fgfr2抑制剂及使用方法
WO2023220131A2 (en) * 2022-05-10 2023-11-16 Relay Therapeutics, Inc. PI3Kα INHIBITORS AND METHODS OF USE THEREOF
CN117186103A (zh) * 2022-06-01 2023-12-08 安徽诺全药业有限公司 氘代杂环化合物及其制备方法和应用
CN119421872A (zh) * 2022-06-29 2025-02-11 上海翰森生物医药科技有限公司 杂环类衍生物抑制剂、其制备方法和应用
TW202412758A (zh) * 2022-06-29 2024-04-01 香港商英矽智能科技知識產權有限公司 Fgfr2與fgfr3抑制劑及其用途
CN117402161A (zh) * 2022-07-06 2024-01-16 上海科恩泰生物医药科技有限公司 一种具有fgfr抑制作用的亚砜亚胺类化合物、包含其的药物组合物及其用途
AU2023338193A1 (en) * 2022-09-07 2025-03-20 Eli Lilly And Company Pyrazolo[1,5-a]pyridine and imidazo[1,2-a]pyridine derivatives as fgfr3 inhibitors for the treatment of cancer
WO2024083111A1 (zh) * 2022-10-18 2024-04-25 首药控股(北京)股份有限公司 一种新型杂环化合物
CN115594682B (zh) * 2022-10-26 2024-03-15 苏州浦合医药科技有限公司 Fgfr2抑制剂
CN120344533A (zh) * 2022-11-22 2025-07-18 海思科医药集团股份有限公司 一种嘧啶衍生物及其在医药上的应用
CN120752227A (zh) * 2023-02-24 2025-10-03 希格生科（深圳）有限公司 α，β-不饱和酰胺类化合物及其应用
CN120712269A (zh) * 2023-03-20 2025-09-26 英矽智能科技知识产权有限公司 Fgfr2和fgfr3的抑制剂及其用途
WO2024208315A1 (zh) * 2023-04-07 2024-10-10 中国医药研究开发中心有限公司 芳香杂环类化合物及其制备方法和医药用途
CN121263414A (zh) * 2023-05-26 2026-01-02 上海艾力斯医药科技股份有限公司 杂芳环类化合物、其药物组合物及其应用
CN119894900A (zh) * 2023-06-05 2025-04-25 康百达（四川）生物医药科技有限公司 一种吡咯并嘧啶衍生物及其在医药上的应用
CN117343068B (zh) * 2023-09-28 2026-04-28 上海相辉医药科技有限公司 一种FGFR2抑制剂Lirafugratinib(RLY-4008)的制备方法
WO2025067484A1 (en) * 2023-09-28 2025-04-03 Acerand Therapeutics (Hong Kong) Limited Crystal forms and salts of spirobicyclic compound
CN121693505A (zh) * 2023-11-17 2026-03-17 上海齐鲁制药研究中心有限公司 含氮杂芳基衍生物、其制备方法及其在医药上的应用
WO2025140636A1 (zh) * 2023-12-29 2025-07-03 广州科恩泰生物医药科技有限公司 一种亚砜亚胺类化合物的酸式盐的晶型及其制备方法和用途
WO2025149021A1 (zh) * 2024-01-10 2025-07-17 海思科医药集团股份有限公司 一种吡啶并吡咯衍生物及其在医药上的应用
WO2025237312A1 (zh) * 2024-05-15 2025-11-20 深圳福沃药业有限公司 一类含苯并异噁唑结构的高选择性fgfr2抑制剂及其制备方法和应用
CN121270563A (zh) * 2024-07-01 2026-01-06 北京鞍石生物科技股份有限公司 稠环化合物及其制备方法和应用
CN120136834B (zh) * 2025-02-13 2026-02-03 浙江工业大学 一种手性吡喃环化合物及其合成方法和应用

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