# US 11,110,186 B2 · Anionic chelate compounds

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- Number: US 11,110,186 B2
- Document ID: US11110186B2
- Status: Granted
- Kind: B2
- Application number: 16/956,995
- Filed: 2018-12-20
- Published: 2020-10-29
- Granted: 2021-09-07
- Earliest claimed: 2017-12-20
- Assignees: General Electric Company
- Applicants: General Electric Company
- Inventors: Brian Christopher Bales; Michael James Rishel
- Web page: https://patentgrep.com/patent/US11110186B2

## CPC

- A61K 49/106: {the complex-forming compound being cyclic, e.g. DOTA}
- C07B 59/004: {Acyclic, carbocyclic or heterocyclic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur, selenium or tellurium}
- C07D 471/08: Bridged systems
- C07F 13/00: Compounds containing elements of Groups 7 or 17 of the Periodic Table
- C07F 13/005: {Compounds without a metal-carbon linkage}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

The invention provides compounds suitable for use as contrast agents in magnetic resonance imaging (MRI). The compounds of the present invention are manganese (II) complexes having advantageous properties as compared with similar known compounds.

## Claims

### Claim 1

A compound of Formula I or a salt or solvate thereof:
wherein:
n is an integer of 1 to 4
R1 is C1-3 alkyl or —(CH2)n+1—C(═O)—NR2R3;
each X is —C(═O)—NR2R3 or —NH—C(═O)—R3;
each R2 is hydrogen, C1-4 alkyl or an anionic substituent;
each R3 is an anionic substituent optionally linked via a C1-4 alkylene; and,
R4 is independently selected from the group comprising hydroxy, halo, amino, amido, C1-6 alkyl and C1-6 hydroxyalkyl and m is between 0-3, wherein each anionic substituent is independently selected from phosphate, phosphonate, hydroxycarboxylate, tetrazole, thiazolidindione, nitromethylsulfonylphenyl, 4-nitrothiophenol, nitromethylcarboxyphenyl, 2,4-dinitrophenol, or malonitrile.

### Claim 2 (depends on 1)

The compound as defined in claim 1 wherein R1 is C1-3 alkyl.

### Claim 3 (depends on 1)

The compound as defined in claim 1 wherein R1 is —(CH2)n−1—C(═O)—NR2R3.

### Claim 4 (depends on 1)

The compound as defined in claim 1 wherein n is 4.

### Claim 5 (depends on 1)

The compound as defined in claim 1 wherein each X is —C(═O)—NR2R3.

### Claim 6 (depends on 1)

The compound as defined in claim 1 wherein each X is —NH—C(═O)—R3.

### Claim 7 (depends on 1)

The compound as defined in claim 1 wherein m is 0.

### Claim 8 (depends on 1)

The compound as defined in claim 1 wherein each anionic substituent has a pKa less than physiological pH.

### Claim 9 (depends on 1)

The compound as defined in claim 1 wherein each of said anionic substituents is over 90% anionic at physiological pH.

### Claim 10 (depends on 1)

The compound as defined in claim 1 which is selected from the following compounds:

### Claim 11 (depends on 1)

A pharmaceutical composition comprising the compound of Formula I as defined in claim 1 together with a biocompatible carrier in a form suitable for mammalian administration.

### Claim 12 (depends on 1)

A method comprising:
(i) administration to a subject of the compound of Formula I as defined in claim 1;
(ii) detection of magnetic resonance (MR) signals from said subject or part of said subject in which said compound has distributed;
(iii) generation of MR images and/or MR spectra from said detected signals.

### Claim 13 (depends on 1)

A method to produce a compound of Formula I as defined in claim 1 comprising reaction of a compound of Formula II:
with a suitable source of manganese.

### Claim 14 (depends on 13)

The method as defined in claim 13 wherein said suitable source of manganese is manganese(II) chloride.