CN115667242B - 作为nrf2活化剂的四氢异喹啉化合物 - Google Patents

作为nrf2活化剂的四氢异喹啉化合物 Download PDF

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CN115667242B
CN115667242B CN202180030434.4A CN202180030434A CN115667242B CN 115667242 B CN115667242 B CN 115667242B CN 202180030434 A CN202180030434 A CN 202180030434A CN 115667242 B CN115667242 B CN 115667242B
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methyl
carbonyl
carboxamide
tetrahydroisoquinoline
chloro
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CN115667242A (zh
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凯茜·路易丝·卢卡斯
艾玛·路易丝·布莱尼
巴里·菲利普·马丁
索斯藤·诺瓦克
尼古拉斯·查尔斯·雷
西蒙·罗丝·克伦普勒
艾琳·玛丽·苏华德
乔治·海德
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C4X Discovery Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/472Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/50Pyridazines; Hydrogenated pyridazines
    • A61K31/501Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic 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
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P13/12Drugs for disorders of the urinary system of the kidneys
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • 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
    • C07D401/06Heterocyclic 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 carbon chain containing only aliphatic carbon atoms
    • 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
    • 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
    • C07D405/14Heterocyclic 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 containing three or more hetero rings
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02Heterocyclic 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
    • C07D498/04Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Pulmonology (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Neurology (AREA)
  • Endocrinology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Obesity (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Emergency Medicine (AREA)
  • Neurosurgery (AREA)
  • Dermatology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CN202180030434.4A 2020-04-22 2021-04-22 作为nrf2活化剂的四氢异喹啉化合物 Active CN115667242B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB2005852.5A GB202005852D0 (en) 2020-04-22 2020-04-22 Therapeutic compounds
GB2005852.5 2020-04-22
PCT/GB2021/050975 WO2021214472A1 (en) 2020-04-22 2021-04-22 Tetrahydroisoquinoline compounds as nrf2 activators

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CN115667242A CN115667242A (zh) 2023-01-31
CN115667242B true CN115667242B (zh) 2025-02-28

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US (1) US20230159511A1 (enExample)
EP (1) EP4139295B1 (enExample)
JP (1) JP7751165B2 (enExample)
KR (1) KR20230004722A (enExample)
CN (1) CN115667242B (enExample)
AR (1) AR121913A1 (enExample)
AU (1) AU2021258539A1 (enExample)
BR (1) BR112022021370A2 (enExample)
CA (1) CA3174360A1 (enExample)
ES (1) ES3031970T3 (enExample)
GB (1) GB202005852D0 (enExample)
IL (1) IL297440A (enExample)
MX (1) MX2022013396A (enExample)
PH (1) PH12022552773A1 (enExample)
WO (1) WO2021214472A1 (enExample)
ZA (1) ZA202211464B (enExample)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RS64836B1 (sr) 2018-10-22 2023-12-29 C4X Discovery Ltd Terapijska jedinjenja
JP2024542974A (ja) 2021-10-25 2024-11-19 シーフォーエックス・ディスカバリー・リミテッド Keap1結合剤であるテトラヒドロイソキノリン化合物
AU2023204960A1 (en) * 2022-01-07 2024-05-16 Chugai Seiyaku Kabushiki Kaisha Nitrogen-containing heterocyclic compound having nrf2 activation effect
WO2024130411A1 (en) * 2022-12-21 2024-06-27 Variational Ai Inc. Protease inhibitors and methods of using same
EP4696692A1 (en) * 2023-06-19 2026-02-18 Chugai Seiyaku Kabushiki Kaisha Crystal of nitrogen-containing heterocyclic compound having nrf2 activation effect
EP4596534A1 (en) * 2024-01-31 2025-08-06 University of Copenhagen Noncovalent small-molecule inhibitors of the keap1-nrf2 interaction
TW202604491A (zh) 2024-05-13 2026-02-01 瑞典商阿斯特捷利康公司 用於療法中之keap1抑制劑

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013067036A1 (en) * 2011-10-31 2013-05-10 Rutgers, The State University Of New Jersey Direct inhibitors of keap1-nrf2 interaction as antioxidant inflammation modulators
WO2020084300A1 (en) * 2018-10-22 2020-04-30 C4X Discovery Limited Therapeutic compounds

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20180017038A (ko) * 2015-06-15 2018-02-20 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 Nrf2 조절제
JP2020097526A (ja) * 2017-03-28 2020-06-25 武田薬品工業株式会社 複素環化合物

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013067036A1 (en) * 2011-10-31 2013-05-10 Rutgers, The State University Of New Jersey Direct inhibitors of keap1-nrf2 interaction as antioxidant inflammation modulators
WO2020084300A1 (en) * 2018-10-22 2020-04-30 C4X Discovery Limited Therapeutic compounds

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Publication number Publication date
JP2023524207A (ja) 2023-06-09
AR121913A1 (es) 2022-07-20
WO2021214472A1 (en) 2021-10-28
EP4139295B1 (en) 2025-04-09
CA3174360A1 (en) 2021-10-28
JP7751165B2 (ja) 2025-10-08
ZA202211464B (en) 2025-05-28
KR20230004722A (ko) 2023-01-06
MX2022013396A (es) 2022-12-13
CN115667242A (zh) 2023-01-31
US20230159511A1 (en) 2023-05-25
PH12022552773A1 (en) 2024-03-25
IL297440A (en) 2022-12-01
GB202005852D0 (en) 2020-06-03
BR112022021370A2 (pt) 2022-12-06
EP4139295A1 (en) 2023-03-01
AU2021258539A1 (en) 2022-11-10
ES3031970T3 (en) 2025-07-14

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