CA3108773A1 - 2-arylbenzimidazoles as ppargc1a activators for treating neurodegenerative diseases - Google Patents

2-arylbenzimidazoles as ppargc1a activators for treating neurodegenerative diseases Download PDF

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Publication number
CA3108773A1
CA3108773A1 CA3108773A CA3108773A CA3108773A1 CA 3108773 A1 CA3108773 A1 CA 3108773A1 CA 3108773 A CA3108773 A CA 3108773A CA 3108773 A CA3108773 A CA 3108773A CA 3108773 A1 CA3108773 A1 CA 3108773A1
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Prior art keywords
alkyl
chosen
alkoxy
amino
halo
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CA3108773A
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English (en)
French (fr)
Inventor
Samuel D. BANISTER
Edgar Engleman
Khoa D. Nguyen
Mark Smith
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Leland Stanford Junior University
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Leland Stanford Junior University
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Publication of CA3108773A1 publication Critical patent/CA3108773A1/en
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    • 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
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/41841,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/18Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
    • 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
    • A61K31/4353Heterocyclic 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
    • A61K31/437Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/08Radicals containing only hydrogen and carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D263/00Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/56Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D263/57Aryl or substituted aryl radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D277/00Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62Benzothiazoles
    • C07D277/64Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
    • C07D277/66Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2 with aromatic rings or ring systems directly attached in position 2
    • 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
    • C07D401/04Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • 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
    • C07D417/02Heterocyclic 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 two hetero rings
    • C07D417/04Heterocyclic 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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6503Five-membered rings
    • C07F9/6506Five-membered rings having the nitrogen atoms in positions 1 and 3
    • C07F9/65068Five-membered rings having the nitrogen atoms in positions 1 and 3 condensed with carbocyclic rings or carbocyclic ring systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05Isotopically modified compounds, e.g. labelled

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Neurosurgery (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicinal Preparation (AREA)
CA3108773A 2018-08-06 2019-08-06 2-arylbenzimidazoles as ppargc1a activators for treating neurodegenerative diseases Pending CA3108773A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862714962P 2018-08-06 2018-08-06
US62/714,962 2018-08-06
PCT/US2019/045229 WO2020033359A1 (en) 2018-08-06 2019-08-06 2-arylbenzimidazoles as ppargc1a activators for treating neurodegenerative diseases

Publications (1)

Publication Number Publication Date
CA3108773A1 true CA3108773A1 (en) 2020-02-13

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CA3108773A Pending CA3108773A1 (en) 2018-08-06 2019-08-06 2-arylbenzimidazoles as ppargc1a activators for treating neurodegenerative diseases

Country Status (13)

Country Link
US (3) US12195432B2 (https=)
EP (1) EP3833344A4 (https=)
JP (2) JP7422737B2 (https=)
KR (1) KR20210068399A (https=)
CN (2) CN112805000A (https=)
AU (1) AU2019319745B2 (https=)
BR (1) BR112021002165A2 (https=)
CA (1) CA3108773A1 (https=)
IL (3) IL280664B2 (https=)
MX (2) MX2021001456A (https=)
SG (1) SG11202101285YA (https=)
TW (1) TWI904076B (https=)
WO (1) WO2020033359A1 (https=)

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US12195432B2 (en) 2018-08-06 2025-01-14 The Board Of Trustees Of The Leland Stanford Junior University 2-arylbenzimidazoles as Ppargc1a activators for treating neurodegenerative diseases
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CN112933232A (zh) * 2021-02-02 2021-06-11 袁玉佳 PGC-1α激活TFEB介导的自噬在制备治疗急性肾损伤的药物中的应用
EP4426295A1 (en) * 2021-11-02 2024-09-11 Tranquis Therapeutics, Inc. Selection and treatment of subjects having a circulating myeloid cell inflammatory phenotype
US20250262189A1 (en) * 2022-04-22 2025-08-21 Rdiscovery, LLC Treatment of diseases associated with reductive stress
EP4618982A1 (en) * 2022-11-18 2025-09-24 GOJO, Satoshi Uses of zln-005 and related compounds
WO2024118936A1 (en) * 2022-12-02 2024-06-06 Tranquis Therapeutics, Inc. 2-arylbenzimidazole compounds for the treatment of hemoglobinopathies

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US12195432B2 (en) 2018-08-06 2025-01-14 The Board Of Trustees Of The Leland Stanford Junior University 2-arylbenzimidazoles as Ppargc1a activators for treating neurodegenerative diseases

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BR112021002165A2 (pt) 2021-05-04
AU2019319745A1 (en) 2021-03-25
TW202019410A (zh) 2020-06-01
US12195432B2 (en) 2025-01-14
IL280664A (en) 2021-03-25
US20200299244A1 (en) 2020-09-24
AU2019319745B2 (en) 2025-06-26
MX2021001456A (es) 2021-05-27
IL280664B (en) 2022-12-01
US20210061769A1 (en) 2021-03-04
IL307972A (en) 2023-12-01
IL298535A (en) 2023-01-01
WO2020033359A1 (en) 2020-02-13
CN112805000A (zh) 2021-05-14
SG11202101285YA (en) 2021-03-30
US11111217B2 (en) 2021-09-07
TWI904076B (zh) 2025-11-11
US20210300877A1 (en) 2021-09-30
CN119033775A (zh) 2024-11-29
EP3833344A4 (en) 2022-07-06
IL280664B2 (en) 2023-04-01
US10851066B2 (en) 2020-12-01
MX2023012694A (es) 2023-11-21
JP2021534099A (ja) 2021-12-09
JP7422737B2 (ja) 2024-01-26
EP3833344A1 (en) 2021-06-16
IL298535B2 (en) 2024-03-01
JP2024056694A (ja) 2024-04-23
KR20210068399A (ko) 2021-06-09
IL298535B1 (en) 2023-11-01

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