IL320628A - Cyclen based compounds and their gd(iii) complexes for use as multimodal pet/mri contrast agents - Google Patents

Cyclen based compounds and their gd(iii) complexes for use as multimodal pet/mri contrast agents

Info

Publication number
IL320628A
IL320628A IL320628A IL32062825A IL320628A IL 320628 A IL320628 A IL 320628A IL 320628 A IL320628 A IL 320628A IL 32062825 A IL32062825 A IL 32062825A IL 320628 A IL320628 A IL 320628A
Authority
IL
Israel
Prior art keywords
general formula
tetraazacyclododecane
methyl
triyl
iii
Prior art date
Application number
IL320628A
Other languages
Hebrew (he)
Inventor
Miloslav Polasek
Jan Kretschmer
Original Assignee
Ustav Organicke Chemie A Biochemie Av Cr V V I
Miloslav Polasek
Jan Kretschmer
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
Priority claimed from EP22212471.1A external-priority patent/EP4382136A1/en
Application filed by Ustav Organicke Chemie A Biochemie Av Cr V V I, Miloslav Polasek, Jan Kretschmer filed Critical Ustav Organicke Chemie A Biochemie Av Cr V V I
Publication of IL320628A publication Critical patent/IL320628A/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/041—Heterocyclic compounds
    • A61K51/0472—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/002—Heterocyclic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/004—Acyclic, carbocyclic or heterocyclic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur, selenium or tellurium
    • 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
    • C07D401/06—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 linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/003—Compounds containing elements of Groups 3 or 13 of the Periodic Table without C-Metal linkages
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6524—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having four or more nitrogen atoms as the only ring hetero atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Claims (12)

1. CLAIMS 1. Use of cyclen based compound of general formula (I)
2. N N
3. N N
4. A
5. ZA
6. NR
7. (I), wherein R is NO or F; A is independently selected from –CHCOOH; –CH(CH)COOH; ; –CH((CH)nCH)COOH, wherein n is an integer in the range of from 1 to 3; and –CHP(=O)(OH)Ph; Z is H or A; for preparation of a multimodal PET/MRI contrast agent by forming a Gd(III) chelate of the compound of general formula (I), and radiolabelling said Gd(III) chelate with F. 2. Use according to claim 1, wherein A and Z of the cyclen based compound of general formula (I) are the same, preferably selected from –CHP(=O)(OH)Ph; and –CH(CH)COOH. 3. Use according to claim 1, wherein all A of the cyclen based compound of general formula (I) are the same, preferably selected from –CHP(=O)(OH)Ph; and –CH(CH)COOH; and Z is hydrogen. 4. Use according to claim 1, wherein R of the cyclen based compound of general formula (I) is located in para-position in relation to the nitrogen atom of the pyridyl pendant arm. 5. Use according to claim 1, wherein the cyclen based compound of general formula (I) is selected from the group comprising: 2,2',2''-(10-((4-nitropyridin-2-yl)methyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid ( L ) 2,2',2''-(10-((6-nitropyridin-2-yl)methyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid ( L ) 2,2',2''-(10-((3-fluoropyridin-2-yl)methyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid ( L ) 2,2',2''-(10-((4-fluoropyridin-2-yl)methyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid ( L ) 2,2',2''-(10-((5-fluoropyridin-2-yl)methyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid ( L ) 2,2',2''-(10-((6-fluoropyridin-2-yl)methyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid ( L ) 2,2'-(4-((4-fluoropyridin-2-yl)methyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetic acid ( L ) 38 (2S,2'S,2''S)-2,2',2''-(10-((3-fluoropyridin-2-yl)methyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)tripropionic acid ( L ) ((4-((3-fluoropyridin-2-yl)methyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)bis(methylene))bis(phenylphosphinic acid) ( L ) 2,2'-(4-((4-nitropyridin-2-yl)methyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetic acid ( L ) (2S,2'S,2''S)-2,2',2''-(10-((4-fluoropyridin-2-yl)methyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)tripropionic acid ( L ) (2S,2'S,2''S)-2,2',2''-(10-((4-nitropyridin-2-yl)methyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)tripropionic acid ( L ) 6. Use of a coordination compound of Gd(III) ion with the cyclen based compound of general formula (I) as defined in any one of the preceding claims 1 to 5, for preparation of a multimodal PET/MRI contrast agent by radiolabelling said coordination compound with F. 7. A multimodal PET/MRI contrast agent of general formula (VI)
8. (VI), wherein A is independently selected from –CHCOOH; –CH(CH)COOH; –CH((CH)nCH)COOH, wherein n is an integer in the range of from 1 to 3; and –CHP(=O)(OH)Ph; Z is H or A; preferably F is in para-position in relation to the nitrogen atom of the pyridyl pendant arm. 8. A method of synthesis of the multimodal PET/MRI contrast agent of general formula (VI) as defined in claim 7, comprising the following steps: a) providing the cyclen based compound of general formula (I) as defined in claims 1 to 5; b) reacting the cyclen based compound of general formula (I) with Gd3+ ion, thereby forming a Gd(III) chelate of the compound of general formula (I); c) radiolabelling the Gd(III) chelate from step b) with F.
9. The method according to claim 8, wherein step c) is performed using F to F isotopic exchange on the pyridine moiety of the Gd(III) chelate, wherein R is F. 39
10. The method according to claim 8, wherein step c) is performed using nucleophilic aromatic substitution of nitro group with F on the pyridine moiety of the Gd(III) chelate, wherein R is nitro group.
11. A pharmaceutical formulation comprising the multimodal PET/MRI contrast agent of general formula (VI) according to claim 7, which further contains at least one conventionally used pharmaceutically acceptable auxiliary substance, preferably selected from the group containing solvents, buffers, ionization additives, antioxidants, antimicrobial additives.
12. The multimodal PET/MRI contrast agent of general formula (VI) according to claim 7 and/or the pharmaceutical formulation according to claim 11, for use in medicine, preferably in multimodal PET/MRI diagnostic methods. 40
IL320628A 2022-12-09 2023-12-08 Cyclen based compounds and their gd(iii) complexes for use as multimodal pet/mri contrast agents IL320628A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP22212471.1A EP4382136A1 (en) 2022-12-09 2022-12-09 Cyclen based compounds and their gd(iii) complexes for use as multimodal pet/mri contrast agents
EP23175898 2023-05-29
PCT/CZ2023/050087 WO2024120557A1 (en) 2022-12-09 2023-12-08 Cyclen based compounds and their gd(iii) complexes for use as multimodal pet/mri contrast agents

Publications (1)

Publication Number Publication Date
IL320628A true IL320628A (en) 2025-07-01

Family

ID=89507424

Family Applications (1)

Application Number Title Priority Date Filing Date
IL320628A IL320628A (en) 2022-12-09 2023-12-08 Cyclen based compounds and their gd(iii) complexes for use as multimodal pet/mri contrast agents

Country Status (6)

Country Link
EP (1) EP4619048A1 (en)
JP (1) JP2025540211A (en)
CN (1) CN120344272A (en)
AU (1) AU2023390519A1 (en)
IL (1) IL320628A (en)
WO (1) WO2024120557A1 (en)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3492460A1 (en) * 2017-12-01 2019-06-05 Ustav Organicke Chemie A Biochemie Av Cr, V.v.i. Compounds for separation of rare earth elements, method of separation, and use thereof
EP4127255A1 (en) * 2020-04-02 2023-02-08 SHINE Technologies, LLC Separation of rare earth elements

Also Published As

Publication number Publication date
WO2024120557A1 (en) 2024-06-13
AU2023390519A1 (en) 2025-05-22
CN120344272A (en) 2025-07-18
EP4619048A1 (en) 2025-09-24
JP2025540211A (en) 2025-12-11

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