Compounds for use as iron(III) MRI contrast agents

Patent metadata

Field	Value
Publication number	US-12534487-B2
Application number	US-202217682695-A
Country	US
Kind code	B2
Filing date	Feb 28, 2022
Priority date	May 19, 2017
Publication date	Jan 27, 2026
Grant date	Jan 27, 2026

Abstract

Provided are macrocyclic compounds and compounds with two or more macrocyclic groups, iron coordinated macrocyclic compounds, and iron coordinated compounds with two or more macrocyclic groups. The iron is high-spin iron(III). The iron coordinated compounds may exhibit a negative redox potential (e.g., relative to a normal hydrogen electrode at a biologically relevant pH, for example, a pH of 6.5-7.5). The compounds can be used as MRI contrast agents.

First claim

The invention claimed is:

1 . A macrocyclic core having the following structure:

and Z 1 , Z 2 , and Z 3 are each independently H or one or more of the following pendant groups:

or a deprotonated analog thereof or a stereoisomer thereof, wherein R is methyl, and Ri is independently a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted alkyl group, and R 1 is not pendant donors;
Q 4 and Q 5 are each independently H, OCH 3 , CO 2 H, or substituted or unsubstituted alkyl groups of linear or branched structures, A is a substituted or unsubstituted alkyl group of linear or branched structure with C 1 to C 12 or is a substituted or unsubstituted aryl group or an amino acid, or a salt, a partial salt, a hydrate, a polymorph, or a stereoisomer thereof, wherein the macrocyclic core has structure II or III, Z 1 and Z 2 are each independently a pendant group;
wherein for all structures I, II, and III, each of Z 1 , Z 2 , and Z 3 , as applicable, are selected independently of each other, and at least one of R, Z 1 , Z 2 , and Z 3 is different than the remaining R, Z 1 , Z 2 , and Z 3 .

2 . The macrocyclic core of claim 1 , wherein the macrocyclic core has the following structure:

and at least one anionic pendant group.

3 . The macrocyclic core of claim 1 , wherein the macrocyclic core has the following structure:

4 . A macrocyclic core having the following structure:

Assignees

• Univ New York State Res Found

Inventors

• Morrow Janet R
• Snyder Eric M
• Asik Didar

Classifications

• A61K49/143

  the protein being an albumin, e.g. HSA, BSA, ovalbumin · CPC title

• A61K49/128

  comprising multiple complex or complex-forming groups, being either part of the linear polymeric backbone or being pending groups covalently linked to the linear polymeric backbone · CPC title

• A61K49/124

  dendrimers, dendrons, hyperbranched compounds · CPC title

• A61K49/106 Primary

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

• A61K49/085

  conjugated systems · CPC title