IP Library › Granted Patent US 12,478,696
Granted Patent B2
US 12,478,696 · App. 18/983,625 · Granted Nov 25, 2025

Gadolinium chelate compounds for use in magnetic resonance imaging

Inventors: Markus Berger (Berlin, DE); Jessica Lohrke (Berlin, DE); Christoph-Stephan Hilger (Berlin, DE); Gregor Jost (Berlin, DE); Thomas Frenzel (Berlin, DE); Detlev Suelzle (Berlin, DE); Johannes Platzek (Berlin, DE); Olaf Panknin (Berlin, DE); Hubertus Pietsch (Kleinmachnow, DE)
Assignee: BAYER PHARMA AKTIENGESELLSCHAFT
A61K49/106C07D257/02
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Quick Facts
Patent No.
US 12,478,696
App. No.
18/983,625
Granted
Nov 25, 2025
Kind
B2
Abstract

An aqueous pharmaceutical composition including compound having the formula of tetragadolinium [4,10-bis(carboxylatomethyl)-7-{-3,6,12,15-tetraoxo-16-[4,7,10-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis({[({2-[4,7,10-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino)acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate wherein the stereochemistry at the chiral carbon of the four alanine substituents is selected from the group consisting of RRRR, SSSS, RSSS, RRSS, and RRRS stereoisomers, and racemic and diastereomeric mixtures of any thereof, or a tautomer, a hydrate, a solvate, or a salt thereof, or a mixture of same is described. The compounds may be used as an MRI contrast imaging agent.

Claims (33)

1 . A compound having the structure:

wherein each chiral carbon atom has a stereochemistry that is either R or S,

or a tautomer, a hydrate, a solvate, or a salt thereof, or a mixture of same.

2 . The compound of claim 1 , wherein the structure comprises a stereochemistry selected from the group consisting of:

and combinations and mixtures of any thereof.

3 . The compound of claim 2 , wherein the structure of the compound is:

4 . The compound of claim 2 , wherein the structure of the compound is:

5 . The compound of claim 2 , wherein the structure of the compound is:

6 . The compound of claim 2 , wherein the structure of the compound is:

7 . The compound of claim 2 , wherein the structure of the compound is:

8 . A compound selected from the group consisting of:

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2R,16R)-3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis({[{{(2R)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate,

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2S,16S)-3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis ({[{{(2S)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate,

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2R,16S)-3,6,12,15-tetraox9.0-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis({[({(2S)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate,

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2R,16R)-3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis ({[{{(2S)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate, and

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2S,16R)-3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis({[{{(2R)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate,

or a tautomer, a hydrate, a solvate, or a salt thereof, or a mixture of same.

9 . The compound of claim 8 , wherein the compound is:

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2R,16R)-3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis({[{{(2R)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate.

10 . The compound of claim 8 , wherein the compound is:

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2S,16S)-3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis ({[({(2S)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate.

11 . The compound of claim 8 , wherein the compound is:

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2R,16R)-3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis({[{{(2S)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate.

12 . The compound of claim 8 , wherein the compound is:

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2R,16S)-3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis ({[({(2S)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate.

13 . The compound of claim 8 , wherein the compound is:

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2S,16R)-3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis ({[{{(2R)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate.

14 . The compound of claim 8 , wherein the compound is a mixture of two or more compounds selected from the group consisting of:

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2R,16R)-3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis ({[{{(2R)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate,

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2S,16S)-3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis ({[{{(2S)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate,

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2R,16S)-3,6,12,15-tetraox9.0-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis({[{{(2S)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate,

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2R,16R)-3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis ({[{{(2S)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate, and

Tetragadolinium [4,10-bis (carboxylatomethyl)-7-{(2S,16R)-3,6,12,15-tetraoxo-16-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis({[({(2R)-2-[4,7,10-tris-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]propanoyl}amino) acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 18, 2025
From: BERGER, MARKUS; LOHRKE, JESSICA; HILGER, CHRISTOPH-STEPHAN; JOST, GREGOR; FRENZEL, THOMAS; SUELZLE, DETLEV; PLATZEK, JOHANNES; PANKNIN, OLAF; PIETSCH, HUBERTUS
To: BAYER PHARMA AKTIENGESELLSCHAFT
Reel/Frame 070238/0198 →
Priority Claims (1)
EP 15170658 · Jun 4, 2015 · regional
Continuity (5)
Continuation 17979367 · Nov 2, 2022
Continuation 16947272 · Jul 27, 2020
Continuation 16192185 · Nov 15, 2018
Continuation 15578687
Related Publication 20250114485A1 · Apr 10, 2025
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