# US 11,993,618 B2 · Water soluble mono-branched and di-branched complexing agents, and corresponding lanthanide complexes

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- Number: US 11,993,618 B2
- Document ID: US11993618B2
- Status: Granted
- Kind: B2
- Application number: 16/622,123
- Filed: 2018-06-11
- Published: 2023-01-19
- Granted: 2024-05-28
- Earliest claimed: 2017-06-12
- Assignees: Cisbio Bioassays
- Applicants: Cisbio Bioassays
- Inventors: Laurent Lamarque; Jurriaan Zwier; Emmanuel Bourrier
- Web page: https://patentgrep.com/patent/US11993618B2

## CPC

- C07F 5/003: {without C-Metal linkages}
- C07D 401/14: containing three or more hetero rings
- C07F 9/58: Pyridine rings
- C07F 9/65583: {each of the hetero rings containing nitrogen as ring hetero atom}
- C09K 11/06: containing organic luminescent materials
- G01N 33/533: with fluorescent label
- G01N 33/542: with steric inhibition or signal modification, e.g. fluorescent quenching
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C09K: MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention relates to complexing agents of formula (I): wherein Chrom1, Chrom2 and Chrom3 are as defined in the description. The invention also relates to lanthanide complexes obtained from these complexing agents.

## Claims

### Claim 1

A lanthanide complex consisting of a complexing agent of formula (I) and a lanthanide:
wherein:
Chrom1, Chrom2 and Chrom3, independently of one another, represent a group of formula:
provided that the compound of formula (I) comprises (i) one or two groups selected from the groups (Ia) and (Ib) and (ii) at least one L1-CO—R group;
R is a —OR2 or —NH-E group;
R1 is a —CO2H or —P(O)(OH)R3 group;
R2 is H or a (C1-C4)alkyl;
R3 is a (C1-C4)alkyl; phenyl optionally substituted by a —SO3− group; or benzyl;
L1 is a direct bond; a —(CH2)r− group optionally interrupted by at least one atom selected from the group consisting of an oxygen atom, a nitrogen atom and a sulphur atom; a —CH═CH— group; a —CH═CH—CH2— group; a —CH2—CH═CH— group; or a PEG group of formula —CH2—(CH2OCH2)y—CH2OCH3, where y is an integer from 1 to 5;
L2 is selected from the group consisting of:
a direct bond;
a linear or branched C1-C20 alkylene group, optionally containing one or more double or triple bonds;
a C5-C8 cycloalkylene group;
a C6-C14 arylene group;
said alkylene, cycloalkylene or arylene groups optionally containing one or more heteroatoms, or one or more carbamoyl or carboxamido groups, and said alkylene, cycloalkylene or arylene groups being optionally substituted by 1 to 5 C1-C8 alkyl, C6-C14 aryl, sulfonate or oxo groups; and
a divalent group of formula:
wherein n, m, p, q are integers from 1 to 16 and e is an integer from 1 to 6;
G is a reactive group selected from the group consisting of: an acrylamide, an activated ester, an aldehyde, an alkyl halide, an anhydride, an aniline, an azide, an aziridine, a carboxylic acid, a diazoalkane, a haloacetamide, a halotriazine, a hydrazine, an imido ester, an isocyanate, an isothiocyanate, a maleimide, a sulphonyl halide, a thiol, a ketone, an amine which is optionally activated, an acid halide, a succinimidyl ester, a hydroxysuccinimidyl ester, a hydroxysulfosuccinimidyl ester, an azidonitrophenyl, an azidophenyl, a 3-(2-pyridyldithio)-propionamide, a glyoxal, a triazine, and an acetylenic group;
E is a —CH2—(CH2)s—CH2—SO3— or —(CH2)s—NmAlk1Alk2Alk3 group, or a sulfobetaine of formula
where R4 represents a (C1-C6)alkyl, and t is equal to 1, 2, 3, 4, 5 or 6;
r is an integer from 1 to 6;
s is 0, 1 or 2;
Alk1, Alk2, Alk3, which may be identical or different, represent a (C1-C6)alkyl.

### Claim 2 (depends on 1)

The lanthanide complex according to claim 1, wherein the lanthanide is selected from the group consisting of: Eu3+, Sm3+, Tb3+, Gd3+, Dy3+, Nd3+, and Er3+.

### Claim 3 (depends on 2)

The lanthanide complex according to claim 2, wherein the lanthanide is Eu3+ or Tb3+.

### Claim 4 (depends on 3)

The lanthanide complex according to claim 3, wherein the lanthanide is Eu3+.

### Claim 5 (depends on 1)

The lanthanide complex according to claim 1, wherein Chrom1 is a group of formula (Ia) and Chrom2 and Chrom3 are each a group of formula (Ic), identical or different.

### Claim 6 (depends on 5)

The lanthanide complex according to claim 5, wherein Chrom2 and Chrom3 are identical.

### Claim 7 (depends on 1)

The lanthanide complex according to claim 1, wherein Chrom1 and Chrom2 are each a group of formula (Ib), identical or different, and Chrom3 is a group of formula (Id).

### Claim 8 (depends on 7)

The lanthanide complex according to claim 7, wherein Chrom1 and Chrom2 are identical.

### Claim 9 (depends on 1)

The lanthanide complex according to claim 1, wherein R1 is a —CO2H or —P(O)(OH)R3 group wherein R3 is a (C1-C4)alkyl or phenyl.

### Claim 10 (depends on 1)

The lanthanide complex according to claim 1, wherein L1 is a direct bond; a —(CH2)r— group optionally interrupted by at least one atom selected from an oxygen atom and a sulphur atom, and r=2 or 3; a —CH═CH— group; a —CH═CH—CH2— group; or a —CH2—CH═CH— group.

### Claim 11 (depends on 1)

The lanthanide complex according to claim 1, wherein E is a —CH2—(CH2)s—CH2—SO3— group with s=0 or 1; —(CH2)s—N+Alk1Alk2Alk3 with Alk1, Alk2 Alk3, identical or different, representing (C1-C4)alkyl and s=0 or 1; or a group of formula:
wherein R4 is a (C1-C4)alkyl and t is 1 or 2.

### Claim 12 (depends on 1)

The lanthanide complex according to claim 1, wherein the reactive group G is a group of formula:
wherein w varies from 0 to 8 and v is equal to 0 or 1, and Ar is a saturated or unsaturated 5- or 6-membered heterocycle, comprising 1 to 3 heteroatoms, optionally substituted by a halogen atom.

### Claim 13 (depends on 1)

The lanthanide complex according to claim 1, wherein the -L2-G group consists of (i) a reactive group G selected from the group consisting of: a carboxylic acid, an amine, a succinimidyl ester, a haloacetamide, a hydrazine, an isothiocyanate, and a maleimide group, and (ii) a spacer arm L2 consisting of an alkylene chain having from 1 to 5 carbon atoms or a group selected from groups of formula:
where n, m are integers from 1 to 16 and e is an integer from 1 to 6, the group G being linked to either end of these divalent groups.