CONTRAST AGENTS FOR MAGNETIC RESONANCE IMAGING

• US 20200129645A1
• Filed: 06/18/2018
• Published: 04/30/2020
• Est. Priority Date: 06/19/2017
• Status: Abandoned Application

• Current Assignee: Georg-August-Universitat Gottingen Stiftung Offenlichen Rechts (Georg-August-Universität Göttingen)
• Original Assignee: Georg-August-Universitat Gottingen Stiftung Offenlichen Rechts (Georg-August-Universität Göttingen)
• Inventors: MEYER, Franc, SCEPANIAK, Jeremiah
• Application Number:
  US16/624,125
• Publication Number:
  US 20200129645A1
• Time in Patent Office: Days
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/103 the complex-forming compound being acyclic, e.g. DTPA
• CPC Class Codes: C07D 213/04 having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 231/10 having two or three double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 233/04 having one double bond between ring members or between a ring member and a non-ring member
• CPC Class Codes: C07D 233/54 having two double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 239/06 having one double bond between ring members or between a ring member and a non-ring member
• CPC Class Codes: C07D 241/06 having one or two double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: G01R 33/5605 by transferring coherence or polarization from a spin species to another, e.g. creating magnetization transfer contrast [MTC], polarization transfer using nuclear Overhauser enhancement [NOE]

Abstract

The present invention provides contrast agents of the formula [N(A₁,A₂,A₃) M](counter ion(s)) for use in a diagnostic method practiced on the human or animal body. It also refers to the contrast agents, as well as pharmaceutical compositions containing same. Further, it relates to a method of in vitro medical imaging, especially of diagnostic imaging, comprising administering said compound to a sample.

Claims

1-18. -18. (canceled)

34. A contrast agent of the formula [N(A₁,A₂,A₃) M](counter ion(s)) for use in a diagnostic method practiced on the human or animal body, wherein

N is a nitrogen atom;

M is a divalent metal ion selected from transition metals of the group;

V^II, Cr^II, Fe^II, Co^II, Ni^II, and Cu^II;

the counter ion(s) being pharmaceutically acceptable; and

wherein

A₁, A₂, and A₃ are independently selected from the group of ligands consisting of;

19. A method of diagnostic imaging which comprises administering a patient a contrast agent according claim 34.

20. The method according to claim 19, wherein the contrast agent is a magnetic resonance imaging contrast agent.

21. The method according to claim 19, wherein the transition metal is Fe^II, Co^II, Ni^II, and Cu^II.

22. The method according to claim 19, wherein the contrast agent is water-soluble.

23. The method according to claim 19, wherein A₁, A₂, and A₃ are the same.

24. The method according to claim 19, wherein the diagnostic method is medical imaging.

25. The method according to claim 19, wherein A1, A2, and A3 are independently selected from the group consisting of:

26. The method according to claim 19, wherein the counter ion(s) is/are selected from the group consisting of acetate (OAc⁻

), chloride (Cl⁻

), iodide (I⁻

), bromide (Br⁻

), nitrate (NO₃⁻

), triflate (OTf⁻

) and sulfate (SO₄²⁻

).

27. The method according to claim 19, wherein

R₁, R₄, R₅, and R₆ are independently selected from the group consisting of:

H, F, Cl, Br, I methyl, OMe, OH, and CF₃, wherein R₂ is H, or OH; and

R₃═

H or CH₃.

28. The method according to claim 19, wherein

R₁, R₂, R₃, R₄, R₅, and R₆ are independently selected from the group consisting of:

H, OH, SH, CF₃, CN, halogen, optionally substituted C_1-4 alkyl, C_1-4 heteroalkyl, C_3-7 cycloalkyl, C_3-7 heterocycloalkyl, C_4-12 aryl C(O)NH₂ or C(O)OH and C_4-12 heteroaryl groups.

wherein R₆ is H, OH, or an C_1-4 alkyl; and

wherein if R² does not equal H, OH, SH, C(O)NH₂, or C(O)OH, at least one of R₁, R₃, R₄, and R₅ must equal OH, SH, NH₂, C(O)NH₂, C(O)OH.

29. The method according to claim 19, wherein

R₁═

H, F, Cl, Br, I, CH₃, OCH₃, OH or CF₃;

R₂, R₄, R₅, and R₆═

H; and

R₃═

H or CH₃.

30. The method according to claim 19, wherein

at least one of R₁═

OH;

R₂, R₄, R₅, and R₆═

H; and

R₃═

H or CH₃.

31. The method according to claim 19, wherein one or more of R₂, R₃, R₄, R₅, R₆ and each of R₁ is coupled to a probe, or label, wherein the probe or label can be an antibody, peptide, or a dye, or ¹⁹F-based probe.

32. The method according to claim 19, wherein A₁, A₂, and A₃ are selected from

33. The method according to claim 32, wherein the counter ion is trifluoromethanesulfonate or chloride and the metal is Fe or Co or Ni.

35. A pharmaceutical composition comprising a contrast agent as defined in claim 34 and at least one pharmaceutically acceptable excipient.

36. A method of in vitro medical imaging, especially of diagnostic imaging, comprising administering a compound as defined in claim 34 to a sample.

37. A contrast agent as defined in claim 34, wherein the pharmaceutically acceptable counterion(s) is/are selected from the group consisting of acetate (OAc⁻

), chloride (Cl⁻

), iodide (I⁻

), bromide (Br⁻

), nitrate (NO₃⁻

), triflate (OTf) and sulfate (SO₄²⁻

).