CN112041301A - 具有铁死亡诱导活性的化合物及其使用方法 - Google Patents

具有铁死亡诱导活性的化合物及其使用方法 Download PDF

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Publication number
CN112041301A
CN112041301A CN201980028824.0A CN201980028824A CN112041301A CN 112041301 A CN112041301 A CN 112041301A CN 201980028824 A CN201980028824 A CN 201980028824A CN 112041301 A CN112041301 A CN 112041301A
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alkyl
alkenyl
heterocyclyl
aryl
heteroaryl
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CN201980028824.0A
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English (en)
Chinese (zh)
Inventor
蒋春
陈瑞红
A·潘迪
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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Publication of CN112041301A publication Critical patent/CN112041301A/zh
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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
    • C07D471/02—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
    • A61K31/4353—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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof
    • 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
    • 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
    • C07D217/04—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 hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • 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
    • C07D217/12—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
    • 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
    • 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)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CN201980028824.0A 2018-02-28 2019-02-27 具有铁死亡诱导活性的化合物及其使用方法 Pending CN112041301A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862636614P 2018-02-28 2018-02-28
US62/636,614 2018-02-28
PCT/US2019/019854 WO2019168999A1 (en) 2018-02-28 2019-02-27 Compounds with ferroptosis inducing activity and methods of their use

Publications (1)

Publication Number Publication Date
CN112041301A true CN112041301A (zh) 2020-12-04

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CN201980028824.0A Pending CN112041301A (zh) 2018-02-28 2019-02-27 具有铁死亡诱导活性的化合物及其使用方法

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Country Link
US (2) US11098040B2 (https=)
EP (1) EP3759075B1 (https=)
JP (1) JP7348906B2 (https=)
KR (1) KR20200135961A (https=)
CN (1) CN112041301A (https=)
AR (2) AR114417A1 (https=)
AU (1) AU2019229256A1 (https=)
BR (1) BR112020017561A2 (https=)
CA (1) CA3092143A1 (https=)
EA (1) EA202091846A1 (https=)
ES (1) ES3038012T3 (https=)
IL (1) IL276788A (https=)
MX (2) MX2020008906A (https=)
SG (1) SG11202008230PA (https=)
TW (1) TW202000663A (https=)
WO (1) WO2019168999A1 (https=)

Cited By (4)

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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
CN114008024A (zh) * 2019-02-27 2022-02-01 费罗治疗公司 具有铁死亡诱导活性的化合物以及使用其的方法
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
CN120923499A (zh) * 2025-08-08 2025-11-11 兰州大学 一种铁死亡激动剂、缺氧响应型纳米共递送系统及其应用

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US11040964B2 (en) 2019-02-27 2021-06-22 Ferro Therapeutics, Inc. Compounds and methods of use
US20220227765A1 (en) * 2019-08-28 2022-07-21 Ferro Therapeutics, Inc. Pyrido-indole analogues as gpx4 inhibitors
CN110511253B (zh) * 2019-09-04 2023-10-13 上海药明康德新药开发有限公司 DNA编码化合物库构建中On-DNA四氢-β-咔啉类化合物的合成方法
CN110627786B (zh) * 2019-10-29 2020-11-24 株洲千金药业股份有限公司 一种他达拉非中间体的制备方法
JP2023509359A (ja) 2019-12-17 2023-03-08 フラグシップ パイオニアリング イノベーションズ ブイ，インコーポレーテッド 鉄依存性細胞分解の誘導物質との併用抗癌療法
US11998534B2 (en) * 2020-02-12 2024-06-04 Eubulus Biotherapeutics Inc. GPX4 inhibitor in combination with anticancer agent for treating proliferative disease
CN115243719B (zh) * 2020-03-06 2024-09-13 北京先通生物医药技术有限公司 CTB006与Ponatinib联合应用
TW202227399A (zh) * 2020-08-26 2022-07-16 美商費洛醫療公司 化合物及使用方法
AU2021391453A1 (en) * 2020-12-04 2023-07-13 Eubulus Biotherapeutics Inc. Heteroaryl-acetylenes, pharmaceutical compositions thereof, and their therapeutic applications
KR20220139813A (ko) * 2021-04-08 2022-10-17 서울대학교산학협력단 암 환자의 예후 예측용 바이오마커 및 이의 용도
US11541116B1 (en) 2022-01-07 2023-01-03 Kojin Therapeutics, Inc. Methods and compositions for inducing ferroptosis in vivo
WO2024015637A1 (en) * 2022-07-15 2024-01-18 Ferro Therapeutics, Inc. Glutathione peroxidase 4 (gpx4) inhibitors for the treatment of cancer
WO2024039860A1 (en) * 2022-08-19 2024-02-22 Olema Pharmaceuticals, Inc. 2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole derivatives as estrogen receptor modulators for the treatment of cancer
WO2024123412A1 (en) * 2022-12-09 2024-06-13 The University Of Toledo Ferroptosis inducers to treat cancer

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US20030225092A1 (en) * 2000-06-07 2003-12-04 Orme Mark W. Chemical compounds
WO2001094347A1 (en) * 2000-06-08 2001-12-13 Lilly Icos Llc Tetracyclic diketopiperazine compounds as pdev inhibitors
WO2002028858A2 (en) * 2000-10-02 2002-04-11 Lilly Icos Llc Hexahydropyrazino `1'2' : 1, 6!- pyrido `3, 4-b! indole-1, 4-dione derivatives for the treatment of cardiovascular disorders and erectile disfunction
WO2007016361A2 (en) * 2005-07-29 2007-02-08 Concert Pharmaceuticals Inc. Novel pharmaceutical compounds
FR2916200A1 (fr) * 2007-05-18 2008-11-21 Fourtillan Snc Nouveaux derives des 1,2,3,4,6,7,12,12a-octahydro pyrazino[1',2':1,6]pyrido[3,4-b]indoles, leur preparation et leur utilisation en therapeutique
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Publication number Priority date Publication date Assignee Title
CN114008024A (zh) * 2019-02-27 2022-02-01 费罗治疗公司 具有铁死亡诱导活性的化合物以及使用其的方法
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
CN113336748B (zh) * 2021-04-12 2022-03-25 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
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
CN120923499A (zh) * 2025-08-08 2025-11-11 兰州大学 一种铁死亡激动剂、缺氧响应型纳米共递送系统及其应用

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EP3759075B1 (en) 2025-07-23
TW202000663A (zh) 2020-01-01
US20230039846A1 (en) 2023-02-09
AR118205A1 (es) 2021-09-22
AR114417A1 (es) 2020-09-02
MX2023001527A (es) 2023-03-06
WO2019168999A1 (en) 2019-09-06
CA3092143A1 (en) 2019-09-06
AU2019229256A1 (en) 2020-09-17
SG11202008230PA (en) 2020-09-29
ES3038012T3 (en) 2025-10-08
BR112020017561A2 (pt) 2020-12-22
EA202091846A1 (ru) 2021-06-01
KR20200135961A (ko) 2020-12-04
JP7348906B2 (ja) 2023-09-21
US11098040B2 (en) 2021-08-24
JP2021515010A (ja) 2021-06-17
EP3759075A1 (en) 2021-01-06
MX2020008906A (es) 2021-02-26
US20190263802A1 (en) 2019-08-29
IL276788A (en) 2020-10-29

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