AU2019411556B2 - 2-Fluorinated bile acids for the treatment of neurodegenerative diseases - Google Patents

2-Fluorinated bile acids for the treatment of neurodegenerative diseases Download PDF

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Publication number
AU2019411556B2
AU2019411556B2 AU2019411556A AU2019411556A AU2019411556B2 AU 2019411556 B2 AU2019411556 B2 AU 2019411556B2 AU 2019411556 A AU2019411556 A AU 2019411556A AU 2019411556 A AU2019411556 A AU 2019411556A AU 2019411556 B2 AU2019411556 B2 AU 2019411556B2
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AU
Australia
Prior art keywords
compound
general formula
dihydroxy
difluoro
acid
Prior art date
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Application number
AU2019411556A
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English (en)
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AU2019411556A1 (en
Inventor
Oliver BANDMANN
Christopher Hastings
Bruno Jan Pol LINCLAU
Heather MORTIBOYS
Gemma PACKER
Joseph Watts
Alexander Charles Weymouth-Wilson
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.)
University of Southampton
Nzp Uk Ltd
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University of Southampton
Nzp Uk Ltd
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J9/00Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
    • C07J9/005Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • 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
    • C07JSTEROIDS
    • C07J11/00Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 3
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J31/00Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
    • C07J31/006Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J33/00Normal steroids having a sulfur-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J33/002Normal steroids having a sulfur-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J41/00Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0055Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J41/00Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0055Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
    • C07J41/0061Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives one of the carbon atoms being part of an amide group
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J43/00Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J43/003Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J51/00Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J71/00Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • C07J71/0005Oxygen-containing hetero ring
    • C07J71/001Oxiranes

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Epidemiology (AREA)
  • Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
AU2019411556A 2018-12-20 2019-12-20 2-Fluorinated bile acids for the treatment of neurodegenerative diseases Active AU2019411556B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB1820887.6 2018-12-20
GBGB1820887.6A GB201820887D0 (en) 2018-12-20 2018-12-20 Compounds
PCT/GB2019/053665 WO2020128514A1 (en) 2018-12-20 2019-12-20 2-fluorinated bile acids for the treatment of neurodegenerative diseases

Publications (2)

Publication Number Publication Date
AU2019411556A1 AU2019411556A1 (en) 2021-06-10
AU2019411556B2 true AU2019411556B2 (en) 2025-04-03

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
AU2019411556A Active AU2019411556B2 (en) 2018-12-20 2019-12-20 2-Fluorinated bile acids for the treatment of neurodegenerative diseases

Country Status (15)

Country Link
US (1) US20220073557A1 (https=)
EP (1) EP3898645B1 (https=)
JP (1) JP7503063B2 (https=)
KR (1) KR102856276B1 (https=)
CN (1) CN113330020B (https=)
AU (1) AU2019411556B2 (https=)
BR (1) BR112021011189A2 (https=)
CA (1) CA3123333A1 (https=)
EA (1) EA202191521A1 (https=)
ES (1) ES3036094T3 (https=)
GB (1) GB201820887D0 (https=)
IL (1) IL284093B2 (https=)
MX (1) MX2021007551A (https=)
SG (1) SG11202105465WA (https=)
WO (1) WO2020128514A1 (https=)

Families Citing this family (3)

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Publication number Priority date Publication date Assignee Title
EP4486318A4 (en) * 2022-03-02 2026-02-25 Boyce Thompson Institute For Plant Res Inc Cysteamides, related therapeutic compositions and associated processes
GB202208151D0 (en) 2022-06-01 2022-07-13 Nzp Uk Ltd Compounds
GB202314563D0 (en) 2023-09-22 2023-11-08 Nzp Uk Ltd Compounds

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014036379A2 (en) * 2012-08-31 2014-03-06 Metselex Bile acids prevent or abolish progression of parkinson's and related neurodegenerative diseases

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ298567A (en) * 1994-11-23 2000-01-28 Cocensys Inc Androstane and pregnane derivatives, pharmaceutical compositions and methods of treatment
WO1998005337A1 (en) * 1996-08-01 1998-02-12 Cocensys, Inc. Use of gaba and nmda receptor ligands for the treatment of migraine headache
FR2934596B1 (fr) * 2008-07-30 2015-04-10 Trophos Nouveaux derives de l'oxime de cholest-4-en-3-one, compositions pharmaceutiques les renfermant, et procede de preparation
ITMI20121344A1 (it) * 2012-07-31 2014-02-01 Erregierre Spa Processo di preparazione di acido ursodesossicolico ad elevata purezza
CN103333216A (zh) * 2013-06-04 2013-10-02 苏州大学 5α-6-酮-胆甾烷类似物及其应用
US20150112089A1 (en) 2013-10-22 2015-04-23 Metselex, Inc. Deuterated bile acids
US11072630B2 (en) * 2015-03-10 2021-07-27 Metselex, Inc. Fluorinated and alkylated bile acids
GB201812382D0 (en) * 2018-07-30 2018-09-12 Nzp Uk Ltd Compounds

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014036379A2 (en) * 2012-08-31 2014-03-06 Metselex Bile acids prevent or abolish progression of parkinson's and related neurodegenerative diseases

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HEATHER MORTIBOYS ET AL: "UDCA exerts beneficial effect on mitochondrial dysfunction in LRRK2-G2019S carriers and in vivo", NEUROLOGY, vol. 85, no. 10, 8 September 2015 (2015-09-08), pages 846 - 852 *
HEATHER MORTIBOYS ET AL: "Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson's disease", BRAIN, vol. 136, no. 10, 1 October 2013 (2013-10-01), pages 3038 - 3050 *
S. M. BELL ET AL: "Ursodeoxycholic Acid Improves Mitochondrial Function and Redistributes Drp1 in Fibroblasts from Patients with Either Sporadic or Familial Alzheimer's Disease", JOURNAL OF MOLECULAR BIOLOGY, vol. 430, no.21, 1 October 2018 *

Also Published As

Publication number Publication date
IL284093B1 (en) 2025-03-01
EP3898645C0 (en) 2025-06-25
AU2019411556A1 (en) 2021-06-10
WO2020128514A1 (en) 2020-06-25
IL284093A (en) 2021-08-31
EP3898645B1 (en) 2025-06-25
GB201820887D0 (en) 2019-02-06
KR20210125982A (ko) 2021-10-19
EP3898645A1 (en) 2021-10-27
CN113330020A (zh) 2021-08-31
ES3036094T3 (en) 2025-09-12
BR112021011189A2 (pt) 2021-08-31
JP2022514401A (ja) 2022-02-10
MX2021007551A (es) 2021-10-13
EA202191521A1 (ru) 2021-09-10
IL284093B2 (en) 2025-07-01
CN113330020B (zh) 2024-04-05
CA3123333A1 (en) 2020-06-25
US20220073557A1 (en) 2022-03-10
JP7503063B2 (ja) 2024-06-19
SG11202105465WA (en) 2021-06-29
KR102856276B1 (ko) 2025-09-05

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