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WO2024130166A3 - Compounds, compositions, and methods - Google Patents

Compounds, compositions, and methods Download PDF

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Publication number
WO2024130166A3
WO2024130166A3 PCT/US2023/084359 US2023084359W WO2024130166A3 WO 2024130166 A3 WO2024130166 A3 WO 2024130166A3 US 2023084359 W US2023084359 W US 2023084359W WO 2024130166 A3 WO2024130166 A3 WO 2024130166A3
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WO
WIPO (PCT)
Prior art keywords
methods
compositions
compounds
stereoisomer
stereoisomers
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2023/084359
Other languages
French (fr)
Other versions
WO2024130166A2 (en
Inventor
Lydia A. Auch
Alex L. BAGDASARIAN
Cyril Bucher
Javier De Vicente Fidalgo
Brian M. Fox
Benjamin J. HUFFMAN
John C. WIDEN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Denali Therapeutics Inc
Original Assignee
Denali Therapeutics Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Denali Therapeutics Inc filed Critical Denali Therapeutics Inc
Priority to EP23904700.4A priority Critical patent/EP4634161A2/en
Priority to CN202380093683.7A priority patent/CN121001995A/en
Priority to KR1020257023346A priority patent/KR20250134151A/en
Priority to AU2023395972A priority patent/AU2023395972A1/en
Publication of WO2024130166A2 publication Critical patent/WO2024130166A2/en
Publication of WO2024130166A3 publication Critical patent/WO2024130166A3/en
Priority to MX2025006999A priority patent/MX2025006999A/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • A61K31/41—Heterocyclic 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
    • A61K31/4196—1,2,4-Triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • 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
    • C07D401/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic 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
    • C07D405/02—Heterocyclic 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 two hetero rings
    • C07D405/04—Heterocyclic 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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic 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
    • C07D405/14—Heterocyclic 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
    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero 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
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic 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
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic 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
    • C07D498/04—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The present disclosure relates generally to small molecule inhibitors of axonal degeneration, or a pharmaceutically acceptable salt, isotopically enriched analog, stereoisomer, mixture of stereoisomers, or prodrug thereof, methods of making and intermediates thereof, and methods of using thereof.
PCT/US2023/084359 2022-12-16 2023-12-15 Compounds, compositions, and methods Ceased WO2024130166A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP23904700.4A EP4634161A2 (en) 2022-12-16 2023-12-15 Compounds, compositions, and methods
CN202380093683.7A CN121001995A (en) 2022-12-16 2023-12-15 Compounds, compositions, and methods
KR1020257023346A KR20250134151A (en) 2022-12-16 2023-12-15 Compounds, compositions and methods
AU2023395972A AU2023395972A1 (en) 2022-12-16 2023-12-15 Compounds, compositions, and methods
MX2025006999A MX2025006999A (en) 2022-12-16 2025-06-13 Compounds, compositions, and methods

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263433346P 2022-12-16 2022-12-16
US63/433,346 2022-12-16

Publications (2)

Publication Number Publication Date
WO2024130166A2 WO2024130166A2 (en) 2024-06-20
WO2024130166A3 true WO2024130166A3 (en) 2024-07-18

Family

ID=91486310

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2023/084359 Ceased WO2024130166A2 (en) 2022-12-16 2023-12-15 Compounds, compositions, and methods

Country Status (7)

Country Link
EP (1) EP4634161A2 (en)
KR (1) KR20250134151A (en)
CN (1) CN121001995A (en)
AU (1) AU2023395972A1 (en)
MX (1) MX2025006999A (en)
TW (1) TW202430153A (en)
WO (1) WO2024130166A2 (en)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4933338A (en) * 1986-04-21 1990-06-12 Laboratorios Del Dr. Esteve, S.A. Benzimidazolesulfonamides and their application as drugs
US5852195A (en) * 1994-05-06 1998-12-22 Pharmacia & Upjohn Company Pyranone compounds useful to treat retroviral infections
US20040023965A1 (en) * 1998-07-02 2004-02-05 Gilligan Paul Joseph Imidazo-triazines as corticotropin releasing factor antagonists
US20120309736A1 (en) * 2010-02-25 2012-12-06 Merck Sharp & Donme Corp Novel cyclic benzimidazole derivatives useful anti-diabetic agents
US20170240554A1 (en) * 2014-10-16 2017-08-24 Syngenta Participations Ag Pesticidally active tetracyclic heterocyclic derivatives with sulphur containing substituents
US20180327391A1 (en) * 2015-11-20 2018-11-15 Denali Therapeutice Inc. Compound, compositions, and methods

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4933338A (en) * 1986-04-21 1990-06-12 Laboratorios Del Dr. Esteve, S.A. Benzimidazolesulfonamides and their application as drugs
US5852195A (en) * 1994-05-06 1998-12-22 Pharmacia & Upjohn Company Pyranone compounds useful to treat retroviral infections
US20040023965A1 (en) * 1998-07-02 2004-02-05 Gilligan Paul Joseph Imidazo-triazines as corticotropin releasing factor antagonists
US20120309736A1 (en) * 2010-02-25 2012-12-06 Merck Sharp & Donme Corp Novel cyclic benzimidazole derivatives useful anti-diabetic agents
US20170240554A1 (en) * 2014-10-16 2017-08-24 Syngenta Participations Ag Pesticidally active tetracyclic heterocyclic derivatives with sulphur containing substituents
US20180327391A1 (en) * 2015-11-20 2018-11-15 Denali Therapeutice Inc. Compound, compositions, and methods

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEN DELIANG, OEZGUEN NUMAN, URVIL PETRI, FERGUSON COLIN, DANN SARA M, SAVIDGE TOR C: "Regulation of protein-ligand binding affinity by hydrogen bond pairing", SCIENCE ADVANCES, vol. 2, no. 3, 25 March 2016 (2016-03-25), pages e1501240, XP093197275, DOI: 10.1126/sciadv.1501240 *
LOCKETT, MR ET AL.: "The Binding of Benzoarylsulfonamide Ligands to Human Carbonic Anhydrase is Insensitive to Formal Fluorination of the Ligand", ANGEWANDTE CHEMIE, vol. 52, no. 30, 22 July 2013 (2013-07-22), pages 7714 - 7717, XP072083884, DOI: 10.1002/anie.201301813 *
SUPURAN, CT ET AL.: "Carbonic Anhydrase Inhibitors", MEDICINAL RESEARCH REVIEWS, vol. 23, no. 2, March 2003 (2003-03-01), pages 146 - 189, XP002542811, DOI: 10.1002/med.10025 *

Also Published As

Publication number Publication date
EP4634161A2 (en) 2025-10-22
TW202430153A (en) 2024-08-01
CN121001995A (en) 2025-11-21
MX2025006999A (en) 2025-09-02
WO2024130166A2 (en) 2024-06-20
AU2023395972A1 (en) 2025-07-03
KR20250134151A (en) 2025-09-09

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