WO2022196734A1 - 含フッ素化合物および造影剤 - Google Patents

含フッ素化合物および造影剤 Download PDF

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Publication number
WO2022196734A1
WO2022196734A1 PCT/JP2022/011975 JP2022011975W WO2022196734A1 WO 2022196734 A1 WO2022196734 A1 WO 2022196734A1 JP 2022011975 W JP2022011975 W JP 2022011975W WO 2022196734 A1 WO2022196734 A1 WO 2022196734A1
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WO
WIPO (PCT)
Prior art keywords
fluorine
formula
general formula
unsubstituted
carbon atoms
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/JP2022/011975
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English (en)
French (fr)
Japanese (ja)
Inventor
直子 矢内
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.)
TDK Corp
Original Assignee
TDK Corp
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 TDK Corp filed Critical TDK Corp
Priority to JP2023507159A priority Critical patent/JPWO2022196734A1/ja
Priority to CN202280020932.5A priority patent/CN116981657A/zh
Priority to DE112022001543.8T priority patent/DE112022001543T5/de
Priority to US18/280,304 priority patent/US20240156994A1/en
Publication of WO2022196734A1 publication Critical patent/WO2022196734A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • 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
    • 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
    • A61K49/20—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations containing free radicals, e.g. trityl radical for overhauser

Definitions

  • R 1 , R 2 and R 3 are each independently an alkyl group having 1 to 10 carbon atoms substituted or unsubstituted with a substituent containing no fluorine atom.
  • X 1 is It is a substituent represented by any one of the following general formulas (3-1) to (3-4).
  • R 4 and R 5 are each independently an alkyl group having 1 to 10 carbon atoms and substituted or unsubstituted with a substituent containing no fluorine atom.
  • X 2 and X 3 are Each independently represents a substituent represented by any one of the following general formulas (3-1) to (3-4).
  • a fluorine-containing compound contained in the contrast agent having a short 19 F spin-lattice relaxation time T1
  • the shorter the T1 of the fluorine-containing compound the shorter the repetition time (TR) can be set. Therefore, the amount of signal obtained per unit time is increased, and a highly sensitive image can be obtained.
  • the 19 F spin-spin relaxation time (T2) of the fluorine-containing compound is too short, the signal intensity will decrease.
  • L 2 in formula (3-2), L 3 in formula (3-3), and L 4 in general formula (3-4) are fluorine in the same manner as L 1 in formula (3-1).
  • a chain hydrocarbon group having 1 to 10 carbon atoms substituted or unsubstituted by a substituent containing no atoms a chain hydrocarbon group having 1 to 5 carbon atoms substituted or unsubstituted by a substituent containing no fluorine atom is preferably a group, more preferably -(CH 2 ) 2 - or -(CH 2 ) 3 -.
  • L 2 in formula (3-2), L 3 in formula (3-3), and L 4 in general formula (3-4) are fluorine in the same manner as L 1 in formula (3-1).
  • Example 13 Synthesis of compound 23 ⁇ 2,2-diethyl-5-(2-((1,1,1,3,3,3-hexafluoro-2-(trifluoromethyl)propan-2-yl)oxy)ethyl)-5-methyl Synthesis of pyrrolidine-1-oxyl (23)> 2,2-diethyl-5-methyl-3 synthesized in the same manner as in Example 10 instead of 2,2,5-trimethyl-3,4-dihydro-2H-pyrrole-1-oxide (1-2) ,4-dihydro-2H-pyrrole-1-oxide (1-11) was used in the same manner as in Example 9 to obtain the desired product, 2,2-diethyl-5 represented by formula (23).
  • FIG. 1 is a 19 F-MRI T1-weighted image of Example 4 (compound 14).
  • FIG. 2 is a 19 F-MRI T1-weighted image of Example 6 (compound 16).
  • FIG. 3 is a T1-weighted 19 F-MRI image of Comparative Example 1 (compound A1).

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
PCT/JP2022/011975 2021-03-17 2022-03-16 含フッ素化合物および造影剤 Ceased WO2022196734A1 (ja)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2023507159A JPWO2022196734A1 (https=) 2021-03-17 2022-03-16
CN202280020932.5A CN116981657A (zh) 2021-03-17 2022-03-16 含氟化合物及造影剂
DE112022001543.8T DE112022001543T5 (de) 2021-03-17 2022-03-16 Fluorhaltige verbindung und kontrastmittel
US18/280,304 US20240156994A1 (en) 2021-03-17 2022-03-16 Fluorine-containing compound and contrast medium

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2021043724 2021-03-17
JP2021-043724 2021-03-17

Publications (1)

Publication Number Publication Date
WO2022196734A1 true WO2022196734A1 (ja) 2022-09-22

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PCT/JP2022/011975 Ceased WO2022196734A1 (ja) 2021-03-17 2022-03-16 含フッ素化合物および造影剤

Country Status (5)

Country Link
US (1) US20240156994A1 (https=)
JP (1) JPWO2022196734A1 (https=)
CN (1) CN116981657A (https=)
DE (1) DE112022001543T5 (https=)
WO (1) WO2022196734A1 (https=)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5362477A (en) * 1991-10-25 1994-11-08 Mallinckrodt Medical, Inc. 19F magnetic resonance imaging agents which include a nitroxide moiety
JP2008515793A (ja) * 2004-10-05 2008-05-15 ジーイー・ヘルスケア・リミテッド 脱保護の方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5318770A (en) * 1991-10-25 1994-06-07 Mallinckrodt Medical, Inc. Trifluoromethyl analogs of X-ray contrast media for magnetic resonance imaging

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5362477A (en) * 1991-10-25 1994-11-08 Mallinckrodt Medical, Inc. 19F magnetic resonance imaging agents which include a nitroxide moiety
JP2008515793A (ja) * 2004-10-05 2008-05-15 ジーイー・ヘルスケア・リミテッド 脱保護の方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
"Chemistry, Process Design, and Safety for the Nitration Industry /ACS /Symposium Series", vol. 854, 26 June 2003, AMERICAN CHEMICAL SOCIETY/OXFORD UNIVERSITY PRESS , US , ISSN: 0097-6156, article CAMERON NEIL R., BACON CATHERINE A., REID ALISTAIR J.: "The Use of PROXYL Nitroxides in Nitroxide-Mediated Polymerization", pages: 452 - 465, XP055967400, DOI: 10.1021/bk-2003-0854.ch032 *
CAMERON NEIL R., ALISTAIR J. REID,PIET SPAN,STEFAN A. F. BON,J. J. G. STEVEN VAN ES,ANTON L. GERMAN: "Studies on controlled radical polymerization using 5-membered cyclic PROXYL nitroxides and corresponding alkoxyamines", MACROMOLECULAR CHEMISTRY AND PHYSICS, WILEY-VCH VERLAG, WEINHEIM., DE, vol. 201, no. 17, 12 December 2000 (2000-12-12), DE , pages 2510 - 2518, XP055967402, ISSN: 1022-1352, DOI: 10.1002/1521-3935(20001101)201:17<2510::AID-MACP2510>3.0.CO;2-S *
ROUILLON JEAN, ARNOUX CAROLINE, MONNEREAU CYRILLE: "Determination of Photoinduced Radical Generation Quantum Efficiencies by Combining Chemical Actinometry and 19 F NMR Spectroscopy", ANALYTICAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 93, no. 5, 1 January 2021 (2021-01-01), US , pages 2926 - 2932, XP055967399, ISSN: 0003-2700, DOI: 10.1021/acs.analchem.0c04540ï¿¿ *

Also Published As

Publication number Publication date
CN116981657A (zh) 2023-10-31
US20240156994A1 (en) 2024-05-16
JPWO2022196734A1 (https=) 2022-09-22
DE112022001543T5 (de) 2023-12-28

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