Compounds for use as iron (III) MRI contrast agents containing anionic pendents and ancillary groups

Patent metadata

Field	Value
Publication number	US-11344635-B2
Application number	US-201916973349-A
Country	US
Kind code	B2
Filing date	Nov 18, 2019
Priority date	Nov 16, 2018
Publication date	May 31, 2022
Grant date	May 31, 2022

Abstract

Macrocyclic complexes and macrocyclic compounds. The macrocyclic complexes or macrocyclic compounds have a TACN moiety with one or more amine group(s) or a O- or S-substituted TACN moiety. The macrocyclic complexes have a high-spin Fe(III) atom coordinated to the TACN moiety. The macrocyclic complexes can be used in imaging methods.

First claim

The invention claimed is:

1. A macrocyclic complex comprising:
a 1,4,7-triazacyclononane (TACN) moiety or an O-substituted TACN moiety having a structure:

wherein R 1 , Z 1 , Z 2 , and Z 3 are anionic pendent groups independently chosen from:

deprotonated analogs thereof, and combinations thereof,
wherein R 3 is a substituted or unsubstituted alkyl or a substituted or unsubstituted aryl group and R 4 is a substituted alkyl or unsubstituted alkyl or a substituted or unsubstituted aryl group; and
a high-spin Fe(III) cation complexed to the TACN moiety and at least one anionic pendent group substituent of the TACN moiety, or a high-spin Fe(III) cation complexed to the O-substituted TACN moiety and at least one anionic pendent group substituent of the O-substituted TACN moiety,

wherein:
when the macrocyclic complex is:

Z 1 and Z 2 are

and Z 3 is not

and
when the macrocyclic complex is:

Z 1 and Z 2 are

wherein R 4 is an unsubstituted aryl, and Z 3 is not

wherein R 4 is an unsubstituted aryl.

2. The macrocyclic complex of claim 1 , wherein at least one or all of the one or more pendent groups is covalently bound to a nitrogen atom on the TACN moiety or an O-substituted TACN moiety.

3. The macrocyclic complex of claim 1 , wherein the macrocyclic complex has at least one open coordination site.

4. The macrocyclic complex of claim 1 , wherein the macrocyclic complex has at least one water complexed to the high-spin Fe(III) cation.

5. A macrocyclic complex comprising:
a 1,4,7-triazacyclononane (TACN) moiety having a structure:

wherein Z 1 and Z 2 are anionic pendent groups independently chosen from:

deprotonated analogs thereof, and combinations thereof,
R 1 is an anionic pendent groups independently chosen from:

deprotonated analogs thereof, and combinations thereof,
wherein R 2 is a substituted or unsubstituted alkyl group, a substituted or unsubstituted aromatic group or a substituted ether; R 3 is a substituted or unsubstituted alkyl or a substituted or unsubstituted aryl group; R 4 is a substituted alkyl or unsubstituted alkyl or a substituted or unsubstituted aryl group; and Q 1 is aryl substituted with an anionic group, an alkyl group substituted with an anionic group or an aralkyl group substituted with an anionic group; and
a high-spin Fe(III) cation complexed to the TACN moiety and at least one anionic pendent group substituent of the TACN moiety.

6. The macrocyclic complex of claim 5 , wherein at least one or all of the one or more pendent groups is covalently bound to a nitrogen atom on the TACN moiety.

7. The macrocyclic complex of claim 5 , wherein the macrocyclic complex has at least one open coordination site.

8. The macrocyclic complex of claim 5 , wherein the macrocyclic complex has at least one water and/or at least one hydroxide complexed to the high-spin Fe(III) cation.

Assignees

• Univ New York State Res Found

Inventors

• Morrow Janet R
• Lin Zuiru
• Asik Didar
• Snyder Eric M
• Kras Elizabeth A

Classifications

• C07F19/00 Primary

  Metal compounds according to more than one of main groups C07F1/00 - C07F17/00 · CPC title

• C07F9/6515

  having three nitrogen atoms as the only ring hetero atoms · CPC title

• C07F15/025

  without a metal-carbon linkage · CPC title

• C07F9/65583

  each of the hetero rings containing nitrogen as ring hetero atom · CPC title

• A61K49/106 Primary

  the complex-forming compound being cyclic, e.g. DOTA · CPC title