CN111699181A - Fap抑制剂 - Google Patents

Fap抑制剂 Download PDF

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Publication number
CN111699181A
CN111699181A CN201980010828.6A CN201980010828A CN111699181A CN 111699181 A CN111699181 A CN 111699181A CN 201980010828 A CN201980010828 A CN 201980010828A CN 111699181 A CN111699181 A CN 111699181A
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fapi
alkyl
cancer
compound
fap
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乌维·哈伯肯
阿纳斯塔西娅·洛克捷夫
托马斯·林德纳
沃尔特·米尔
弗雷德里克·吉塞尔
克莱门斯·克劳托奇维尔
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Fraunhofer Gesellschaft zur Foerderung der Angewandten Forschung eV
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Fraunhofer Gesellschaft zur Foerderung der Angewandten Forschung eV
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Priority to CN202410243596.1A priority Critical patent/CN118146196A/zh
Publication of CN111699181A publication Critical patent/CN111699181A/zh
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/06Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10Organic compounds
    • A61K49/101Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
    • A61K49/106Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
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    • A61K51/041Heterocyclic compounds
    • A61K51/044Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K51/0455Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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    • A61K51/04Organic compounds
    • A61K51/041Heterocyclic compounds
    • A61K51/044Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K51/0459Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04Organic compounds
    • A61K51/0497Organic compounds conjugates with a carrier being an organic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P35/00Antineoplastic agents
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
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    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06008Dipeptides with the first amino acid being neutral
    • C07K5/06017Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06026Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
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    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
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    • C07K5/10Tetrapeptides
    • C07K5/1002Tetrapeptides with the first amino acid being neutral
    • C07K5/1005Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/1008Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
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    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
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    • C07K7/06Linear peptides containing only normal peptide links having 5 to 11 amino acids
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  • Biophysics (AREA)
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  • Radiology & Medical Imaging (AREA)
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  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Dermatology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
CN201980010828.6A 2018-02-06 2019-02-06 Fap抑制剂 Pending CN111699181A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202410243596.1A CN118146196A (zh) 2018-02-06 2019-02-06 Fap抑制剂

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
EP18155420.5 2018-02-06
EP18155419.7 2018-02-06
EP18155420 2018-02-06
EP18155419 2018-02-06
EP18199641.4 2018-10-10
EP18199641 2018-10-10
PCT/EP2019/052952 WO2019154886A1 (en) 2018-02-06 2019-02-06 Fap inhibitor

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US (3) US20210038749A1 (https=)
EP (1) EP3749663A1 (https=)
JP (2) JP2021512949A (https=)
KR (3) KR102794330B1 (https=)
CN (2) CN111699181A (https=)
AU (5) AU2019219057B2 (https=)
CA (1) CA3088326A1 (https=)
CL (1) CL2020002026A1 (https=)
CO (1) CO2020009625A2 (https=)
IL (1) IL276594B2 (https=)
MX (1) MX2020008271A (https=)
PH (1) PH12020551205A1 (https=)
SG (1) SG11202007180QA (https=)
WO (1) WO2019154886A1 (https=)

Cited By (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111511408A (zh) * 2017-10-23 2020-08-07 约翰霍普金斯大学 靶向成纤维细胞活化蛋白-α(FAP-α)的成像剂及放射治疗剂
CN112023064A (zh) * 2020-11-03 2020-12-04 南京大为科创服务有限责任公司 用于标记核素211At的成纤维细胞活化蛋白抑制剂的锡基衍生物及其制备方法和应用
CN112194651A (zh) * 2020-10-12 2021-01-08 南方医科大学南方医院 一种pet示踪剂的前体化合物及其应用
CN112409414A (zh) * 2020-12-01 2021-02-26 北京师范大学 锝-99m标记含异腈的FAPI衍生物及制备方法和应用
CN112522388A (zh) * 2020-12-18 2021-03-19 上海市东方医院(同济大学附属东方医院) 成纤维细胞激活蛋白作为药物靶点在治疗骨关节炎中的用途
CN112933253A (zh) * 2020-11-13 2021-06-11 上海市质子重离子临床技术研发中心 一种放射性核素标记fapi的化合物及其合成工艺方法
CN113292538A (zh) * 2021-05-10 2021-08-24 北京肿瘤医院(北京大学肿瘤医院) 靶向肿瘤相关成纤维细胞激活蛋白的化合物及其制备方法和应用与靶向fap的肿瘤显影剂
CN113444146A (zh) * 2021-06-01 2021-09-28 南方医科大学南方医院 靶向成纤维细胞活化蛋白探针、制备方法及其在制备pet显像剂中的应用
CN113582975A (zh) * 2021-07-03 2021-11-02 上海蓝纳成生物技术有限公司 一种截短型伊文思蓝修饰的成纤维细胞活化蛋白抑制剂及其制备方法和应用
CN113603678A (zh) * 2021-08-10 2021-11-05 上海蓝纳成生物技术有限公司 一种靶向成纤维细胞活化蛋白的诊断药物及其制备方法
CN113621021A (zh) * 2021-08-10 2021-11-09 上海蓝纳成生物技术有限公司 一种靶向成纤维细胞活化蛋白的治疗药物及其制备方法
CN113880811A (zh) * 2021-09-29 2022-01-04 厦门大学附属第一医院 Fapi二聚体化合物、基于fapi二聚体的肿瘤诊断pet显像剂及其制备方法和应用
CN113880810A (zh) * 2021-09-24 2022-01-04 厦门大学 一种核素标记的配合物及其制备方法和应用
CN114315795A (zh) * 2021-11-30 2022-04-12 北京师范大学 68Ga标记的靶向成纤维细胞激活蛋白的抑制剂类放射性探针及其制备方法
CN114369084A (zh) * 2021-02-10 2022-04-19 上海蓝纳成生物技术有限公司 一种截短型伊文思蓝修饰的成纤维细胞活化蛋白抑制剂及其制备方法和应用
CN114380795A (zh) * 2020-10-22 2022-04-22 四川大学华西医院 氘代fap抑制剂及其应用
WO2022135325A1 (zh) * 2020-12-21 2022-06-30 苏州药明博锐生物科技有限公司 成纤维细胞活化蛋白抑制剂
WO2022135326A1 (zh) * 2020-12-21 2022-06-30 苏州药明博锐生物科技有限公司 成纤维细胞活化蛋白抑制剂
WO2022135327A1 (zh) * 2020-12-21 2022-06-30 苏州药明博锐生物科技有限公司 成纤维细胞活化蛋白抑制剂
WO2022160338A1 (zh) * 2021-02-01 2022-08-04 五一一制药股份有限公司 成纤维细胞活化蛋白-α显像剂的放射性标记配体及其制备方法
WO2022170732A1 (zh) * 2021-02-10 2022-08-18 上海蓝纳成生物技术有限公司 一种截短型伊文思蓝修饰的成纤维细胞活化蛋白抑制剂及其制备方法和应用
CN115505032A (zh) * 2022-09-29 2022-12-23 烟台蓝纳成生物技术有限公司 一种成纤维细胞活化蛋白FAP和整合素αvβ3双重靶向化合物及其制备方法和应用
CN115651009A (zh) * 2022-11-14 2023-01-31 中山大学附属第一医院 一种[18F]F-LuFL的自动化合成方法
CN115746043A (zh) * 2022-11-14 2023-03-07 中山大学附属第一医院 一种靶向成纤维细胞激活蛋白的抑制剂类放射性探针及其制备方法和应用
WO2023040828A1 (zh) * 2021-09-14 2023-03-23 菲柏生物医学技术(广州)有限公司 靶向FAP阳性细胞的siRNA缀合物及其药物组合物和应用
CN115838393A (zh) * 2023-02-16 2023-03-24 烟台蓝纳成生物技术有限公司 用于fapi合成的中间体及其制备方法和应用
CN116120290A (zh) * 2023-03-01 2023-05-16 广东药科大学附属第一医院 一种靶向成纤维细胞激活蛋白的mr探针的制备方法
WO2023098920A1 (zh) * 2022-09-29 2023-06-08 烟台蓝纳成生物技术有限公司 一种双重靶向化合物及其制备方法和应用
WO2023130587A1 (zh) * 2022-01-05 2023-07-13 四川大学华西医院 一种水溶性甲基苄醚衍生物、正电子核素探针、核素标记物及制备方法和应用
CN116874545A (zh) * 2023-09-07 2023-10-13 山东第一医科大学(山东省医学科学院) 偶联药物及其制备方法与在制备治疗类风湿关节炎滑膜药物中的应用
CN116924982A (zh) * 2023-07-07 2023-10-24 北京脑重大疾病研究院 放射性(4-喹啉基)甘氨酰基-2-氰基吡咯烷衍生物及其制备方法和应用
CN117105912A (zh) * 2023-09-01 2023-11-24 广东药科大学附属第一医院 一种靶向成纤维细胞激活蛋白的二聚体mr探针的制备方法
CN117143080A (zh) * 2023-08-30 2023-12-01 北京师范大学 一种含肼基尼古酰胺基的fapi-46衍生物及其应用
CN117255685A (zh) * 2021-04-02 2023-12-19 约翰霍普金斯大学 靶向成纤维细胞活化蛋白α和/或前列腺特异性膜抗原的异二价剂和同二价剂
WO2024078592A1 (zh) * 2022-10-14 2024-04-18 无锡诺宇医药科技有限公司 靶向成纤维细胞活化蛋白的药物及其应用
CN118324791A (zh) * 2024-03-15 2024-07-12 东莞市人民医院 含硼化合物及其制备方法和应用
CN118754876A (zh) * 2024-09-06 2024-10-11 烟台蓝纳成生物技术有限公司 一种靶向fap的前体化合物的纯化方法及应用
CN118754877A (zh) * 2024-09-06 2024-10-11 烟台蓝纳成生物技术有限公司 一种靶向fap的示踪剂前体化合物、制备及其应用
CN118791466A (zh) * 2023-04-14 2024-10-18 南京医科大学 一种放射性探针前体的制备方法
WO2024222888A1 (zh) * 2023-04-27 2024-10-31 中国科学院上海药物研究所 一种fap抑制剂和靶向fap核素探针及其应用
WO2024230728A1 (zh) 2023-05-08 2024-11-14 江苏恒瑞医药股份有限公司 靶向成纤维细胞活化蛋白的配体
CN118955616A (zh) * 2024-05-01 2024-11-15 杭州景嘉航生物医药科技有限公司 一种靶向结合成纤维细胞活化蛋白化合物及应用
CN118978511A (zh) * 2024-08-02 2024-11-19 江苏华益科技有限公司 一种靶向fap化合物及其制备方法
WO2025118255A1 (zh) * 2023-12-08 2025-06-12 北京师范大学 一种放射性标记fapi配合物及其制备方法和应用
WO2025124439A1 (zh) * 2023-12-13 2025-06-19 无锡诺宇医药科技有限公司 Fap靶向放射性药物
WO2025153023A1 (en) * 2024-01-17 2025-07-24 C Ray Therapeutics (Shanghai) Co., Ltd. Fibroblast activation protein ligands and the use thereof
WO2025167951A1 (zh) * 2024-02-07 2025-08-14 苏州博锐创合医药有限公司 一种成纤维细胞活化蛋白抑制剂
CN120590399A (zh) * 2024-04-10 2025-09-05 无锡诺宇医药科技有限公司 靶向成纤维细胞活化蛋白的酸加成盐和晶型及其用途
CN121226360A (zh) * 2025-10-31 2025-12-30 西安交通大学医学院第一附属医院 一种含4-氰基噻唑烷修饰的fapi衍生物及其应用
WO2026007968A1 (zh) * 2024-07-01 2026-01-08 杭州景嘉航生物医药科技有限公司 一种靶向结合成纤维细胞活化蛋白的化合物及应用
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