CN114008024A - 具有铁死亡诱导活性的化合物以及使用其的方法 - Google Patents

具有铁死亡诱导活性的化合物以及使用其的方法 Download PDF

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Publication number
CN114008024A
CN114008024A CN202080028989.0A CN202080028989A CN114008024A CN 114008024 A CN114008024 A CN 114008024A CN 202080028989 A CN202080028989 A CN 202080028989A CN 114008024 A CN114008024 A CN 114008024A
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alkyl
cycloalkyl
heterocyclyl
alkenyl
alkynyl
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Chinese (zh)
Inventor
蒋春
A·潘迪
陈瑞红
B·卡里塔
A·J·杜赖斯瓦米
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Ferro Therapeutics Inc
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Ferro Therapeutics Inc
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Priority claimed from US16/287,805 external-priority patent/US11098040B2/en
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Publication of CN114008024A publication Critical patent/CN114008024A/zh
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
    • C07D217/16—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals substituted by oxygen atoms
    • 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
    • A61K31/4365—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 having sulfur as a ring hetero atom, e.g. ticlopidine
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine 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
    • A61K31/5377—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
    • 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
    • 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
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
    • C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
    • C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/04—Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/12—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • 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
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
CN202080028989.0A 2019-02-27 2020-02-27 具有铁死亡诱导活性的化合物以及使用其的方法 Pending CN114008024A (zh)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
USPCT/US2019/019854 2019-02-27
US16/287,805 US11098040B2 (en) 2018-02-28 2019-02-27 Compounds and methods of use
PCT/US2019/019854 WO2019168999A1 (en) 2018-02-28 2019-02-27 Compounds with ferroptosis inducing activity and methods of their use
US16/287,805 2019-02-27
US201962893092P 2019-08-28 2019-08-28
US62/893,092 2019-08-28
PCT/US2020/020150 WO2020176757A1 (en) 2019-02-27 2020-02-27 Compounds with ferroptosis inducing activity and methods of their use

Publications (1)

Publication Number Publication Date
CN114008024A true CN114008024A (zh) 2022-02-01

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EP (1) EP3931183B1 (https=)
JP (1) JP7704680B2 (https=)
KR (1) KR20220012221A (https=)
CN (1) CN114008024A (https=)
AU (1) AU2020228056A1 (https=)
BR (1) BR112021016833A2 (https=)
CA (1) CA3131385A1 (https=)
EA (1) EA202192122A1 (https=)
ES (1) ES3013815T3 (https=)
IL (1) IL285730A (https=)
MX (1) MX2021010173A (https=)
SG (1) SG11202109035QA (https=)
TW (1) TW202045480A (https=)
WO (1) WO2020176757A1 (https=)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114984019A (zh) * 2022-07-15 2022-09-02 山东中医药大学 一种铁死亡抑制剂化合物及在肝损伤修复领域的应用
CN116983310A (zh) * 2023-08-29 2023-11-03 南方医科大学南方医院 一种治疗肝癌的药物组合物及其应用
CN117209521A (zh) * 2022-11-04 2023-12-12 台州道致科技股份有限公司 丙炔酰氯制备方法
CN118994147A (zh) * 2024-07-18 2024-11-22 中国海洋大学 一种基于疏水标签的gpx4蛋白降解剂及其制备方法和应用

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10118890B2 (en) 2014-10-10 2018-11-06 The Research Foundation For The State University Of New York Trifluoromethoxylation of arenes via intramolecular trifluoromethoxy group migration
TW202000663A (zh) 2018-02-28 2020-01-01 美商費洛醫療公司 化合物及使用方法
US11040964B2 (en) 2019-02-27 2021-06-22 Ferro Therapeutics, Inc. Compounds and methods of use
TW202227399A (zh) * 2020-08-26 2022-07-16 美商費洛醫療公司 化合物及使用方法
KR102759930B1 (ko) * 2022-01-17 2025-01-23 포항공과대학교 산학협력단 Marh6(marchf6) 조절제를 포함하는, 페로토시스 조절용 조성물 및 방법
WO2024015637A1 (en) * 2022-07-15 2024-01-18 Ferro Therapeutics, Inc. Glutathione peroxidase 4 (gpx4) inhibitors for the treatment of cancer
CN118047698A (zh) * 2024-01-30 2024-05-17 山东科巢生物制药有限公司 一种n-[(1r)-2-[1,1'-联苯]-4-基-1-(羟基甲基)乙基]氨基甲酸叔丁酯的制备方法

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WO2002038563A2 (en) * 2000-11-08 2002-05-16 Lilly Icos Llc Condensed pyrazindione derivatives as pde inhibitors
WO2015084749A1 (en) * 2013-12-02 2015-06-11 The Trustees Of Columbia University In The City Of New York Modulating ferroptosis and treating excitotoxic disorders
US20170066773A1 (en) * 2015-08-26 2017-03-09 Blueprint Medicines Corporation Compounds and compositions useful for treating disorders related to ntrk
WO2019168999A1 (en) * 2018-02-28 2019-09-06 Ferro Therapeutics, Inc. Compounds with ferroptosis inducing activity and methods of their use
CN113336748A (zh) * 2021-04-12 2021-09-03 北京大学 一种gpx4蛋白降解剂及其制备方法和应用、一种抗肿瘤细胞药物
US20230114107A1 (en) * 2019-12-17 2023-04-13 Flagship Pioneering Innovations V, Inc. Combination anti-cancer therapies with inducers of iron-dependent cellular disassembly

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US20190008961A1 (en) * 2016-01-07 2019-01-10 The Broad Institute, Inc. Compounds and methods for increasing tumor infiltration by immune cells
WO2018118711A1 (en) * 2016-12-19 2018-06-28 The Trustees Of Columbia University In The City Of New York Small molecule ferroptosis inducers

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002038563A2 (en) * 2000-11-08 2002-05-16 Lilly Icos Llc Condensed pyrazindione derivatives as pde inhibitors
WO2015084749A1 (en) * 2013-12-02 2015-06-11 The Trustees Of Columbia University In The City Of New York Modulating ferroptosis and treating excitotoxic disorders
US20160297748A1 (en) * 2013-12-02 2016-10-13 The Trustees Of Columbia University In The City Of New York Compounds, compositions, and methods for modulating ferroptosis and treating excitotoxic disorders
US20170066773A1 (en) * 2015-08-26 2017-03-09 Blueprint Medicines Corporation Compounds and compositions useful for treating disorders related to ntrk
WO2019168999A1 (en) * 2018-02-28 2019-09-06 Ferro Therapeutics, Inc. Compounds with ferroptosis inducing activity and methods of their use
CN112041301A (zh) * 2018-02-28 2020-12-04 费罗治疗公司 具有铁死亡诱导活性的化合物及其使用方法
US20230114107A1 (en) * 2019-12-17 2023-04-13 Flagship Pioneering Innovations V, Inc. Combination anti-cancer therapies with inducers of iron-dependent cellular disassembly
CN113336748A (zh) * 2021-04-12 2021-09-03 北京大学 一种gpx4蛋白降解剂及其制备方法和应用、一种抗肿瘤细胞药物

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114984019A (zh) * 2022-07-15 2022-09-02 山东中医药大学 一种铁死亡抑制剂化合物及在肝损伤修复领域的应用
CN114984019B (zh) * 2022-07-15 2023-08-22 山东中医药大学 一种铁死亡抑制剂化合物及在肝损伤修复领域的应用
CN117209521A (zh) * 2022-11-04 2023-12-12 台州道致科技股份有限公司 丙炔酰氯制备方法
CN116983310A (zh) * 2023-08-29 2023-11-03 南方医科大学南方医院 一种治疗肝癌的药物组合物及其应用
CN116983310B (zh) * 2023-08-29 2024-04-30 南方医科大学南方医院 一种治疗肝癌的药物组合物及其应用
CN118994147A (zh) * 2024-07-18 2024-11-22 中国海洋大学 一种基于疏水标签的gpx4蛋白降解剂及其制备方法和应用

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MX2021010173A (es) 2021-12-10
KR20220012221A (ko) 2022-02-03
JP7704680B2 (ja) 2025-07-08
AU2020228056A1 (en) 2021-09-16
BR112021016833A2 (pt) 2021-11-23
ES3013815T3 (en) 2025-04-15
CA3131385A1 (en) 2020-09-03
EA202192122A1 (ru) 2021-12-15
TW202045480A (zh) 2020-12-16
EP3931183B1 (en) 2025-02-12
EP3931183A1 (en) 2022-01-05
SG11202109035QA (en) 2021-09-29
IL285730A (en) 2021-10-31
WO2020176757A1 (en) 2020-09-03
JP2022522694A (ja) 2022-04-20

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