JP2023022647A - Compound, and metal complex - Google Patents

Abstract

To provide a compound capable of forming a complex having high metal-holding strength in a complexing state.SOLUTION: A compound is represented by a formula (1). In the formula (1), n indicates 0-6, Q1, Q2, and Q3 are a group or the like selected from the group consisting of a group having partial structure including a carboxyl group-substituted quinoline derivative, a group having partial structure including a carboxyl group-substituted pyridine derivative, and a group having partial structure including a carboxyl group-substituted phenanthroline derivative, Y indicates a nitrogen atom or the like, and Z1, Z2, and Z3 indicate a divalent linking group or the like.SELECTED DRAWING: None

Description

The present invention relates to compounds and metal complexes.

Compounds capable of stably forming complexes with various metal ions and metal complexes having ligands derived from such compounds are useful in various applications. Applications of such compounds and metal complexes include, for example, metal removing agents, metal catalysts, luminescent complexes, MRI contrast agents, radionuclide drugs, and separation of radioactive wastes (e.g., Patent Documents 1, 2, Non-Patent Documents 1 and 2).

Japanese Patent No. 2552714 Japanese Patent Publication No. 04-502574

Chem. Soc. Rev. , 2014, 43, 260-290. Inorg. Chem. , 2019, 58, 2275-2285.

An object of the present invention is to provide a compound capable of forming a novel complex with high metal retention in the complexed state. Another object of the present invention is to provide a metal complex having a ligand derived from such a compound.

As a result of intensive studies by the present inventors to solve the above problems, a partial structure containing an 8-hydroxyquinoline-2-carboxylic acid derivative, a partial structure containing a pyridine-2,6-dicarboxylic acid derivative, or 2,2' - discovering that a compound having two or more partial structures selected from the group consisting of partial structures containing a bipyridine-6,6'-dicarboxylic acid derivative can form a complex with a plurality of metal species; The present invention has been completed.

［式（１）中、ｎは、０～６の整数を表す。
Ｑ^１、Ｑ^２、及びＱ^３は、それぞれ独立に、水素原子、群Ａから選ばれる基、群Ｂから選ばれる基、群Ｃから選ばれる基、又は置換基を表す。ただし、Ｑ^１、Ｑ^２、及びＱ^３の少なくとも２個は、群Ａ、群Ｂ、又は群Ｃから選ばれる基である。
ｎが２以上である場合、複数存在するＱ^３は、それぞれ同一であっても異なっていてもよい。
（群Ａ）
群Ａは、下記式（Ａ－１）、式（Ａ－２）、式（Ａ－３）、及び式（Ａ－４）で表される基からなる群である。

（式（Ａ－１）、式（Ａ－２）、式（Ａ－３）、及び式（Ａ－４）中、Ｒ^１ａ、Ｒ^２ａ、Ｒ^３ａ、Ｒ^４ａ、及びＲ^５ａは、それぞれ独立に、水素原子又は置換基を表す。なお、＊は、結合手を表す。）
（群Ｂ）
群Ｂは、下記式（Ｂ－１）及び式（Ｂ－２）で表される基からなる群である。

（式（Ｂ－１）及び式（Ｂ－２）中、Ｒ^１ｂ、Ｒ^２ｂ、及びＲ^３ｂは、それぞれ独立に、水素原子又は置換基を表す。なお、＊は、結合手を表す。）
（群Ｃ）
群Ｃは、下記式（Ｃ－１）、式（Ｃ－２）、式（Ｃ－３）、式（Ｃ－４）、式（Ｃ－５）、及び式（Ｃ－６）で表される基からなる群である。

（式（Ｃ－１）、式（Ｃ－２）、式（Ｃ－３）、式（Ｃ－４）、式（Ｃ－５）、及び式（Ｃ－６）中、Ｒ^１ｃ、Ｒ^２ｃ、Ｒ^３ｃ、Ｒ^４ｃ、Ｒ^５ｃ、及びＲ^６ｃは、それぞれ独立に、水素原子又は置換基を表す。なお、＊は、結合手を表す。）
Ｙは、窒素原子又は置換基を有していてもよい炭化水素基を表す。
ｎが２以上である場合、複数存在するＹは、それぞれ同一であっても異なっていてもよい。
Ｚ^１は、単結合、－Ｃ（＝Ｏ）－、又は置換基を有していてもよい、メチレン基若しくは少なくとも２個の－ＣＨ_２－を有するヒドロカルビレン基を表し、少なくとも２個の－ＣＨ_２－を有する基中の－ＣＨ_２－の一部又は全部は、－Ｏ－、－Ｃ（＝Ｏ）－、－ＮＨＣ（＝Ｏ）－、又は－Ｃ（＝Ｏ）ＮＨ－に置換されていてもよい。
Ｚ^２及びＺ^３は、それぞれ独立に、単結合又は置換基を有していてもよい２価の連結基を表す。
Ｑ^１、Ｑ^２、及びＱ^３がすべて群Ｂから選ばれる基である場合、Ｚ^１、Ｚ^２、及びＺ^３は、末端に－ＣＨ_２－Ｃ（＝Ｏ）ＮＨ－を有する２価の連結基であり、当該連結基は、－ＣＨ_２－Ｃ（＝Ｏ）ＮＨ－中の窒素原子を介してＱ^１、Ｑ^２、及びＱ^３とそれぞれ結合している。
ｎが２以上である場合、複数存在するＺ^２及びＺ^３は、それぞれ同一であっても異なっていてもよく、Ｚ^１及びＺ^２は、互いに結合して環構造を形成していてもよい。］ One aspect of the invention relates to compounds. The compound is a compound represented by the following formula (1).

[In formula (1), n represents an integer of 0 to 6.
Q ¹ , Q ² and Q ³ each independently represent a hydrogen atom, a group selected from group A, a group selected from group B, a group selected from group C or a substituent. However, at least two of Q ¹ , Q ² and Q ³ are groups selected from group A, group B or group C.
When n is 2 or more, multiple ^Q3 's may be the same or different.
(Group A)
Group A is a group consisting of groups represented by the following formulas (A-1), (A-2), (A-3), and (A-4).

(In Formula (A-1), Formula (A-2), Formula (A-3), and Formula (A-4), R ^1a , R ^2a , R ^3a , R ^4a , and R ^5a are each independently represents a hydrogen atom or a substituent.* represents a bond.)
(Group B)
Group B is a group consisting of groups represented by the following formulas (B-1) and (B-2).

(In formulas (B-1) and (B-2), R ^1b , R ^2b and R ^3b each independently represent a hydrogen atom or a substituent. * represents a bond.)
(Group C)
Group C is represented by the following formula (C-1), formula (C-2), formula (C-3), formula (C-4), formula (C-5), and formula (C-6) It is a group consisting of the group

(In formula (C-1), formula (C-2), formula (C-3), formula (C-4), formula (C-5), and formula (C-6), R ^1c , R ^2c , R ^3c , R ^4c , R ^5c and R ^6c each independently represent a hydrogen atom or a substituent, and * represents a bond.)
Y represents a nitrogen atom or a hydrocarbon group optionally having a substituent.
When n is 2 or more, multiple Y's may be the same or different.
Z ¹ represents a single bond, -C(=O)-, or an optionally substituted methylene group or a hydrocarbylene group having at least two -CH ₂ -, and at least two Part or all of -CH ₂ - in a group having -CH ₂ - may be -O-, -C(=O)-, -NHC(=O)-, or -C(=O)NH- may be substituted.
Z ² and Z ³ each independently represent a single bond or a divalent linking group which may have a substituent.
When Q ¹ , Q ² and Q ³ are all groups selected from Group B, Z ¹ , Z ² and Z ³ are divalent groups having -CH ₂ -C(=O)NH- at the ends A linking group, which is linked to Q ¹ , Q ² and Q ³ through the nitrogen atom in -CH ₂ -C(=O)NH-.
When n is 2 or more, multiple Z ² and Z ³ may be the same or different, and Z ¹ and Z ² may combine with each other to form a ring structure. . ]

［式（２）中、Ｑ^１、Ｑ^２、Ｑ^３、Ｚ^１、Ｚ^２、Ｚ^３、及びｎは、前記と同義である。］ The compound represented by Formula (1) is preferably a compound represented by Formula (2) below.

[In formula (2), Q ¹ , Q ² , Q ³ , Z ¹ , Z ² , Z ³ and n are as defined above. ]

［式（２）中、Ｑ^１、Ｑ^２、Ｑ^３、Ｚ^１、Ｚ^２、及びＺ^３は、前記と同義である。
ｎ_１は、０又は１を表す。］ The compound represented by Formula (2) is preferably a compound represented by Formula (3) below.

[In Formula (2), Q ¹ , Q ² , Q ³ , Z ¹ , Z ² and Z ³ are as defined above.
_n1 represents 0 or 1; ]

［式（４）中、Ｑ^１、Ｑ^２、Ｑ^３、及びｎ_１は、前記と同義である。
Ｚ^１Ａは、単結合又は置換基を有していてもよい、メチレン基若しくは少なくとも２個の－ＣＨ_２－を有するヒドロカルビレン基を表し、少なくとも２個の－ＣＨ_２－を有するヒドロカルビレン基中の－ＣＨ_２－の一部又は全部は、－Ｏ－、－Ｃ（＝Ｏ）－、－ＮＨＣ（＝Ｏ）－、又は－Ｃ（＝Ｏ）ＮＨ－に置換されていてもよい。
Ｚ^２Ａ及びＺ^３Ａは、それぞれ独立に、単結合又は置換基を有していてもよいヒドロカルビレン基を表し、ヒドロカルビレン基中の－ＣＨ_２－の一部又は全部は、－Ｏ－、－Ｃ（＝Ｏ）－、－ＮＨＣ（＝Ｏ）－、又は－Ｃ（＝Ｏ）ＮＨ－に置換されていてもよい。
Ｑ^１、Ｑ^２、及びＱ^３がすべて群Ｂから選ばれる基である場合、Ｚ^１Ａ、Ｚ^２Ａ、及びＺ^３Ａは、末端の－ＣＨ_２－が－ＣＨ_２－Ｃ（＝Ｏ）ＮＨ－に置換されたヒドロカルビレン基であり、当該基は、－ＣＨ_２－Ｃ（＝Ｏ）ＮＨ－中の窒素原子を介してＱ^１、Ｑ^２、及びＱ^３とそれぞれ結合している。］ The compound represented by Formula (3) is preferably a compound represented by Formula (4) below.

[In Formula (4), Q ¹ , Q ² , Q ³ , and n ₁ are as defined above.
Z ^1A represents a single bond or optionally substituted methylene group or hydrocarbylene group having at least two —CH ₂ —, hydrocarbylene having at least two —CH ₂ — Part or all of -CH ₂ - in the group may be substituted with -O-, -C(=O)-, -NHC(=O)-, or -C(=O)NH- .
Z ^2A and Z ^3A each independently represent a single bond or an optionally substituted hydrocarbylene group, and part or all of —CH ₂ — in the hydrocarbylene group is —O— , -C(=O)-, -NHC(=O)-, or -C(=O)NH-.
When Q ¹ , Q ² and Q ³ are all groups selected from Group B, Z ^1A , Z ^2A and Z ^3A have -CH ₂ - at the ends of -CH ₂ -C(=O)NH- which is attached to Q ¹ , Q ² and Q ³ respectively through the nitrogen atom in —CH ₂ —C(=O)NH—. ]

［式（５Ａ）、式（５Ｂ）、及び式（５Ｃ）中、Ｒ^１ａ、Ｒ^２ａ、Ｒ^４ａ、Ｒ^５ａ、Ｒ^１ｂ、Ｒ^３ｂ、Ｒ^１ｃ、Ｒ^２ｃ、Ｒ^４ｃ、Ｒ^５ｃ、Ｒ^６ｃ、Ｚ^１Ａ、Ｚ^２Ａ、Ｚ^３Ａ、及びｎ_１は、前記と同義である。
Ｑ^２Ａ及びＱ^３Ａは、それぞれ独立に、下記式（Ａ－２ａ）、式（Ｂ－２ａ）、及び式（Ｃ－３ａ）で表される基からなる群より選ばれる基である。

（（Ａ－２ａ）、式（Ｂ－２ａ）、及び式（Ｃ－３ａ）中、環を構成する炭素原子に直接結合する水素原子は、置換基によって置換されていてもよい。なお、＊は、結合手を表す。）］ The compound represented by Formula (4) is preferably a compound represented by Formula (5A), Formula (5B), or Formula (5C) below.

[In Formula (5A), Formula (5B), and Formula (5C), R ^1a , R ^2a , R ^4a , R ^5a , R ^1b , R ^3b , R ^1c , R ^2c , R ^4c , R ^5c , R ^6c , Z ^1A , Z ^2A , Z ^3A , and n ₁ are as defined above.
Q ^2A and Q ^3A are each independently a group selected from the group consisting of groups represented by the following formulas (A-2a), (B-2a) and (C-3a).

(In (A-2a), formula (B-2a), and formula (C-3a), a hydrogen atom directly bonded to a carbon atom constituting a ring may be substituted by a substituent. Note that * represents a bond.)]

Another aspect of the invention relates to metal complexes. The metal complex has a metal element and a ligand derived from the above compound.

ADVANTAGE OF THE INVENTION According to this invention, the compound which can form a novel complex with high metal retention power in the state of complex formation is provided. The present invention also provides metal complexes having ligands derived from such compounds. Furthermore, the metal complex of the present invention has high metal retention in the complexed state.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

[Substituent]
In this specification, "substituents" are classified into three types, unless otherwise specified.
The first group is a group having a structure that has affinity with an antigen (hereinafter sometimes referred to as "substituent A").
The second group is a group having a site capable of cross-linking with a structure having affinity for an antigen (hereinafter sometimes referred to as "substituent B").
The third group is a group that can generally be taken in the field of organic chemistry (organic ligands) (hereinafter sometimes referred to as "substituent C").

The “antigen” in Substituent A and Substituent B means an antigen that can be used in therapy or diagnosis using radiation. The "antigen" is preferably an antigen derived from cancer cells.

The "structure having affinity with an antigen" in Substituent A and Substituent B means a structure that selectively interacts with a specific antigen. The "structure having affinity with an antigen" is preferably a structure having affinity with an antigen derived from cancer cells. Examples of structures that have affinity for cancer cell-derived antigens include antibodies, antibody fragments, peptide chains, enzymes, nucleic acid base-containing components (e.g., oligonucleotides, DNA vectors, RNA vectors, aptamers), and the like. be done.

Substituent A is a "structure with affinity for an antigen" and a "site capable of cross-linking with a structure having affinity with an antigen" in Substituent B (hereinafter sometimes simply referred to as a "cross-linkable site"). ) is preferably included in the partial structure chemically bonded to.

The "crosslinkable site" in the substituent B is a selective covalent bond to a "specific site" (e.g., thiol group, azide group, terminal amino group, etc.) in the structure that has affinity for the antigen. It means a structure that can be formed. The structure of the "crosslinkable site" is not particularly limited as a group that can generally be taken to selectively form a covalent bond with a specific site in a structure that has affinity with an antigen. Examples of such “crosslinkable sites” include groups represented by the following formulas (D-1) to (D-12).

In formulas (D-1) to (D-12), a straight line extending from the center of the ring structure represents a bond at any position of the ring structure. * represents a bond, which is a binding site with ^L2 in formula (11) described later. These groups may have a substituent.

A preferred embodiment of Substituent A, a partial structure in which a "structure having affinity with an antigen" and a "crosslinkable site" in Substituent B are chemically bonded (hereinafter sometimes referred to as "crosslinked structure"). ) can be formed, for example, by click chemistry. An example of click chemistry includes a reaction in which an azide group and an alkynyl group represented by the following formula (6) are reacted in the presence of a catalyst to form a 1,2,3-triazole ring. Note that * represents a bond.

Another example of click chemistry is the reaction between an azide group and a cyclooctyne group represented by the following formula (7), or the reaction between a tetrazine group and an alkynyl group represented by the following formula (8). mentioned. Note that * represents a bond.

Moreover, in order to form a "crosslinked structure", a crosslinker having two or more sites selected from the group consisting of "crosslinkable sites" and "specific sites" can be used. Examples of such a cross-linking agent include cross-linking agents exemplified by the following formula (9). The cross-linking agent, for example, one of the sites selected from the group consisting of "cross-linkable site" and "specific site", the coordination derived from the metal element in the metal complex described later and the compound represented by formula (1) Bind the other part selected from the group consisting of "crosslinkable site" and "specific site" to the structure-containing site of the child to the structure-containing site of the "structure having affinity for antigen". can be used for reactions.

Examples of the substituent A include groups represented by the following formula (10).

In formula (10), L ¹ represents a direct bond, a hydrocarbylene group optionally having a substituent C, or a heteroarylene group optionally having a substituent C; When multiple L ¹ are present, they may be the same or different. L ² is a direct bond, C(=O)NR ^e1 , C(=S)NR ^e2 , OC(=O)NR ^e3 , OC(=O), C(=O), C(=S), NR represents ^e4 , S, or O; When multiple ^L2 are present, they may be the same or different. ^L3 represents the above "crosslinked structure". When multiple ^L3 are present, they may be the same or different. Sp represents the above-mentioned "structure having affinity with antigen". _n2 represents an integer of 1 to 10, _n3 represents 1 or 2; Note that * represents a bond.

L ¹ is a direct bond, a hydrocarbylene group optionally having a substituent C or a heteroarylene group optionally having a substituent C, preferably a direct bond or having a substituent C is a hydrocarbylene group that may be

Examples of the hydrocarbylene group of the hydrocarbylene group optionally having substituent C in L ¹ include an alkylene group, a cycloalkylene group and an arylene group. L ¹ is preferably an alkylene group or a cycloalkylene group, more preferably an alkylene group.

The alkylene group in the hydrocarbylene group of L ¹ is a divalent group in which two hydrogen atoms directly bonded to the carbon atoms constituting the saturated aliphatic hydrocarbon are removed. Alkylene groups include methylene, ethylene, propylene, isopropylene, butylene, isobutylene, tert-butylene, pentylene, and hexylene groups. A portion of —CH ₂ — in these alkylene groups may be substituted with —O—. Although the number of carbon atoms in the alkylene group is not particularly limited, it is preferably 1 to 8.

The cycloalkylene group in the hydrocarbylene group of L ¹ is a divalent group in which two hydrogen atoms directly bonded to carbon atoms constituting cycloalkane are removed. The cycloalkylene group includes a cyclopropylene group, a cyclobutylene group, a cyclopentylene group, a cyclohexylene group, a cyclooctylene group and the like. Although the number of carbon atoms in the cycloalkylene group is not particularly limited, it is preferably six.

The arylene group in the hydrocarbylene group of ^L1 is a divalent group in which two hydrogen atoms directly bonded to carbon atoms constituting the aromatic hydrocarbon are removed. Arylene groups include phenylene groups, biphenylene groups, terphenylene groups, naphthylene groups, anthracenylene groups and the like. Arylene groups are preferably phenylene groups. Although the number of carbon atoms in the arylene group is not particularly limited, it is preferably 6 to 12.

Heteroarylene groups optionally having a substituent C of L ¹ are, for example, pyridine, pyrazine, pyrimidine, pyrrole, N-alkylpyrrole, furan, thiophene, thiazole, imidazole, oxazole, benzofuran, benzothiophene, isoquinoline, It is a divalent group in which two hydrogen atoms directly bonded to carbon atoms constituting a heterocyclic compound such as quinazoline are removed. A heteroarylene group is preferably a pyridylene group.

L ² is a direct bond, C(=O)NR ^e1 , C(=S)NR ^e2 , OC(=O)NR ^e3 , OC(=O), C(=O), C(=S), NR ^e4 , S, or O, and C(=O)NR ^e1 may be bonded to L ¹ and L ³ via -L ¹ -C(=O)NR ^e1 -L ³ -, -L ³ -C(=O)NR ^e1 -L ¹ - may be used for bonding. The same applies to C(=S)NR ^e2 , OC(=O)NR ^e3 , and OC(=O). R ^e1 , R ^e2 , R ^e3 and R ^e4 each represent a hydrogen atom or a hydrocarbyl group having 1 to 8 carbon atoms. When a plurality of R ^e1 , R ^e2 , R ^e3 and R ^e4 are present, they may be the same or different. ^L2 is preferably a direct bond or C(=O)NH.

Examples of hydrocarbyl groups having 1 to 8 carbon atoms in R ^e1 , R ^e2 , R ^e3 and R ^e4 include alkyl groups, aryl groups and aralkyl groups having 1 to 8 carbon atoms. Hydrocarbyl groups of 1 to 8 carbon atoms are preferably alkyl groups of 1 to 8 carbon atoms.

^L3 is the above "crosslinked structure". Examples of L ³ include divalent groups represented by the following formulas (E-1) to (E-8). The divalent groups represented by formulas (E-1) to (E-8) may have a substituent. Note that * represents a bond.

_n2 is an integer of 1-10, preferably an integer of 1-5, more preferably 1;

n ₃ is 1 or 2. When using a cross-linking agent such as the cross-linking agent exemplified by the above formula (9), n ₃ is preferably 2. When no cross-linking agent is used, n ₃ is preferably 1. is.

Sp is "a structure that has affinity with an antigen". The "structure having an affinity for an antigen" is exemplified by the structures described above.

In the compound and/or metal complex of the present embodiment, when there are a plurality of structures having a substituent A from the viewpoint of intramolecular and intermolecular aspects, one "antigen-affinity structure" has a plurality of It may be bound to the compound and/or metal complex of the present application. In this case, one "antigen-affinity structure" may be shared among a plurality of substituents A.

Examples of the substituent B include groups represented by the following formula (11).

In formula (11), L ¹ , L ² and n ₂ are as defined above. Lk represents the above "crosslinkable site". Note that * represents a bond.

Substituent C includes, for example, halogen atom, hydroxyl group, carboxyl group, amino group, sulfonic acid group, nitro group, phosphonic acid group, hydrocarbyl group, silyl group, heteroaryl group, alkyloxy group, aryloxy group, aralkyl An oxy group and a silyloxy group are mentioned. Substituent C is preferably a hydroxyl group, a carboxyl group, an amino group, a sulfonic acid group, a phosphonic acid group, or an alkyloxy group from the viewpoint of being easily dissolved in an aqueous solution and used. A portion of these groups may be substituted with halogen atoms, for example, a hydrogen atom of a methyl group may be substituted with fluorine to form a trifluoromethyl group.

A halogen atom represented by the substituent C includes a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. A halogen atom is preferably a fluorine atom.

In the amino group represented by substituent C, a hydrogen atom on the nitrogen atom may be substituted with a hydrocarbon group. The amino group includes, for example, unsubstituted amino group, dimethylamino group, diethylamino group, di-n-propylamino group, diisopropylamino group and diphenylamino group. The amino group is preferably an unsubstituted amino group.

Examples of hydrocarbyl groups represented by substituent C include alkyl groups, aryl groups, and aralkyl groups. Hydrocarbyl groups are preferably alkyl groups.

Examples of the alkyl group in the hydrocarbyl group represented by the substituent C include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, tert-butyl group, pentyl group, hexyl group, norbornyl group, Nonyl group, decyl group, 3,7-dimethyloctyl group, dodecyl group, pentadecyl group, octadecyl group, docosyl group and other saturated aliphatic hydrocarbon groups can be mentioned. A portion of —CH ₂ — in these alkyl groups may be substituted with —O—. Although the number of carbon atoms in the alkyl group is not particularly limited, it is preferably 1 to 8 in terms of availability and cost.

Examples of the aryl group in the hydrocarbyl group represented by the substituent C include aromatic hydrocarbon groups such as phenyl group, biphenyl group, terphenyl group, naphthyl group, phenanthryl group and anthracenyl group. Aryl groups are preferably phenyl groups. Although the number of carbon atoms in the aryl group is not particularly limited, it is preferably 6 to 18.

Examples of the aralkyl group in the hydrocarbyl group represented by the substituent C include a benzyl group, (2-methylphenyl)methyl group, (3-methylphenyl)methyl group, (4-methylphenyl)methyl group, (2, 4-dimethylphenyl)methyl group, (ethylphenyl)methyl group and naphthylmethyl group. Aralkyl groups are preferably benzyl groups. Although the number of carbon atoms in the aralkyl group is not particularly limited, it is preferably 7 to 18.

In the silyl group represented by substituent C, a hydrogen atom on the silicon atom may be substituted with a hydrocarbon group. Examples of such substituted silyl groups include monosubstituted silyl groups substituted with one hydrocarbon group having 1 to 18 carbon atoms such as methylsilyl group, ethylsilyl group and phenylsilyl group; Silyl group, disubstituted silyl group substituted with two hydrocarbon groups having 1 to 18 carbon atoms such as diphenylsilyl group; trimethylsilyl group, triisopropylsilyl group, tri-n-butylsilyl group, tri-tert- a trisubstituted silyl group substituted with three hydrocarbon groups having 1 to 18 carbon atoms such as a butylsilyl group, a tri-isobutylsilyl group, a tert-butyl-dimethylsilyl group, a tri-n-pentylsilyl group; mentioned. A substituted silyl group is preferably a trimethylsilyl group or a tert-butyldimethylsilyl group.

Examples of the heteroaryl group represented by the substituent C include pyridyl group, pyrazyl group, pyrimidyl group, pyrrolyl group, N-alkylpyrrolyl group, furyl group, thiophenyl group, thiazolyl group, imidazolyl group, oxazolyl group, A benzofuranyl group, a benzothiophenyl group, and an isoquinolinyl group can be mentioned. A heteroaryl group is preferably a pyridyl or pyrimidinyl group.

Examples of the alkyloxy group represented by the substituent C include methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, sec-butoxy group, tert-butoxy group and n-pentyloxy group. , n-octyloxy group and the like. A portion of —CH ₂ — in these alkyloxy groups may be substituted with —O—. Alkyloxy groups are preferably methoxy groups. Although the number of carbon atoms in the alkyloxy group is not particularly limited, it is preferably 1 to 8.

Examples of the aryloxy group represented by the substituent C include phenoxy group, 2-methylphenoxy group, 3-methylphenoxy group, 4-methylphenoxy group, 2,4-dimethylphenoxy group and naphthoxy group. Aryloxy groups are preferably phenoxy groups. Although the number of carbon atoms in the aryloxy group is not particularly limited, it is preferably 6 to 18.

Examples of the aralkyloxy group represented by the substituent C include a benzyloxy group, (2-methylphenyl)methoxy group, (3-methylphenyl)methoxy group, (4-methylphenyl)methoxy group, (2,4 -dimethylphenyl)methoxy group and naphthylmethoxy group. An aralkyloxy group is preferably a benzyloxy group. Although the number of carbon atoms in the aralkyloxy group is not particularly limited, it is preferably 7 to 18.

In the silyloxy group represented by substituent C, a hydrogen atom on the silicon atom may be substituted with a hydrocarbon group. Examples of such substituted silyloxy groups include trimethylsilyloxy, triethylsilyloxy, tri-n-butylsilyloxy, triphenylsilyloxy, triisopropylsilyloxy, and tert-butyldimethylsilyloxy groups. be done. A substituted silyloxy group is preferably a trimethylsilyloxy group or a tert-butyldimethylsilyloxy group.

In this specification, the substituent is preferably the substituent B or the substituent C, more preferably the substituent C, unless otherwise specified.

In this specification, Me represents a methyl group, Et represents an ethyl group, Bn represents a benzyl group, and DMF represents N,N-dimethylformamide.

In the present specification, alkyl groups such as propyl, butyl, pentyl, hexyl and octyl groups; alkylene groups such as propylene, butylene, pentylene, hexylene and octylene groups. If a chain structure or branched structure is not specified, these may be a straight chain structure or a branched structure. These groups preferably have a linear structure.

In this specification, when the number of carbon atoms is stated in the explanation of a group, the number of carbon atoms means the number of carbon atoms not including the number of carbon atoms of the substituent.

[Compound]
A compound of one embodiment is a compound represented by the following formula (1).

［式（１）中、ｎは、０～６の整数を表す。
Ｑ^１、Ｑ^２、及びＱ^３は、それぞれ独立に、水素原子、群Ａから選ばれる基、群Ｂから選ばれる基、群Ｃから選ばれる基、又は置換基を表す。ただし、Ｑ^１、Ｑ^２、及びＱ^３の少なくとも２個は、群Ａ、群Ｂ、又は群Ｃから選ばれる基である。
ｎが２以上である場合、複数存在するＱ^３は、それぞれ同一であっても異なっていてもよい。
（群Ａ）
群Ａは、下記式（Ａ－１）、式（Ａ－２）、式（Ａ－３）、及び式（Ａ－４）で表される基からなる群である。

（式（Ａ－１）、式（Ａ－２）、式（Ａ－３）、及び式（Ａ－４）中、Ｒ^１ａ、Ｒ^２ａ、Ｒ^３ａ、Ｒ^４ａ、及びＲ^５ａは、それぞれ独立に、水素原子又は置換基を表す。なお、＊は、結合手を表す。）
（群Ｂ）
群Ｂは、下記式（Ｂ－１）及び式（Ｂ－２）で表される基からなる群である。

（式（Ｂ－１）及び式（Ｂ－２）中、Ｒ^１ｂ、Ｒ^２ｂ、及びＲ^３ｂは、それぞれ独立に、水素原子又は置換基を表す。なお、＊は、結合手を表す。）
（群Ｃ）
群Ｃは、下記式（Ｃ－１）、式（Ｃ－２）、式（Ｃ－３）、式（Ｃ－４）、式（Ｃ－５）、及び式（Ｃ－６）で表される基からなる群である。

（式（Ｃ－１）、式（Ｃ－２）、式（Ｃ－３）、式（Ｃ－４）、式（Ｃ－５）、及び式（Ｃ－６）中、Ｒ^１ｃ、Ｒ^２ｃ、Ｒ^３ｃ、Ｒ^４ｃ、Ｒ^５ｃ、及びＲ^６ｃは、それぞれ独立に、水素原子又は置換基を表す。なお、＊は、結合手を表す。）
Ｙは、窒素原子又は置換基を有していてもよい炭化水素基を表す。
ｎが２以上である場合、複数存在するＹは、それぞれ同一であっても異なっていてもよい。
Ｚ^１は、単結合、－Ｃ（＝Ｏ）－、又は置換基を有していてもよい、メチレン基若しくは少なくとも２個の－ＣＨ２－を有するヒドロカルビレン基を表し、少なくとも２個の－ＣＨ_２－を有する基中の－ＣＨ_２－の一部又は全部は、－Ｏ－、－Ｃ（＝Ｏ）－、－ＮＨＣ（＝Ｏ）－、又は－Ｃ（＝Ｏ）ＮＨ－に置換されていてもよい。
Ｚ^２及びＺ^３は、それぞれ独立に、単結合又は置換基を有していてもよい２価の連結基を表す。
Ｑ^１、Ｑ^２、及びＱ^３がすべて群Ｂから選ばれる基である場合、Ｚ^１、Ｚ^２、及びＺ^３は、末端に－ＣＨ_２－Ｃ（＝Ｏ）ＮＨ－を有する２価の連結基であり、当該連結基は、－ＣＨ_２－Ｃ（＝Ｏ）ＮＨ－中の窒素原子を介してＱ^１、Ｑ^２、及びＱ^３とそれぞれ結合している。
ｎが２以上である場合、複数存在するＺ^２及びＺ^３は、それぞれ同一であっても異なっていてもよく、Ｚ^１及びＺ^２は、互いに結合して環構造を形成していてもよい。］

[In formula (1), n represents an integer of 0 to 6.
Q ¹ , Q ² and Q ³ each independently represent a hydrogen atom, a group selected from group A, a group selected from group B, a group selected from group C or a substituent. However, at least two of Q ¹ , Q ² and Q ³ are groups selected from group A, group B or group C.
When n is 2 or more, multiple ^Q3 's may be the same or different.
(Group A)
Group A is a group consisting of groups represented by the following formulas (A-1), (A-2), (A-3), and (A-4).

(In Formula (A-1), Formula (A-2), Formula (A-3), and Formula (A-4), R ^1a , R ^2a , R ^3a , R ^4a , and R ^5a are each independently represents a hydrogen atom or a substituent.* represents a bond.)
(Group B)
Group B is a group consisting of groups represented by the following formulas (B-1) and (B-2).

(In formulas (B-1) and (B-2), R ^1b , R ^2b and R ^3b each independently represent a hydrogen atom or a substituent. * represents a bond.)
(Group C)
Group C is represented by the following formula (C-1), formula (C-2), formula (C-3), formula (C-4), formula (C-5), and formula (C-6) It is a group consisting of the group

(In formula (C-1), formula (C-2), formula (C-3), formula (C-4), formula (C-5), and formula (C-6), R ^1c , R ^2c , R ^3c , R ^4c , R ^5c and R ^6c each independently represent a hydrogen atom or a substituent, and * represents a bond.)
Y represents a nitrogen atom or a hydrocarbon group optionally having a substituent.
When n is 2 or more, multiple Y's may be the same or different.
Z ¹ represents a single bond, -C(=O)-, or an optionally substituted methylene group or a hydrocarbylene group having at least two -CH2-, and at least two - Some or all of -CH ₂ - in groups containing CH ₂ - are substituted with -O-, -C(=O)-, -NHC(=O)-, or -C(=O)NH- may have been
Z ² and Z ³ each independently represent a single bond or a divalent linking group which may have a substituent.
When Q ¹ , Q ² and Q ³ are all groups selected from Group B, Z ¹ , Z ² and Z ³ are divalent groups having -CH ₂ -C(=O)NH- at the ends A linking group, which is linked to Q ¹ , Q ² and Q ³ through the nitrogen atom in -CH ₂ -C(=O)NH-.
When n is 2 or more, multiple Z ² and Z ³ may be the same or different, and Z ¹ and Z ² may combine with each other to form a ring structure. . ]

Q ¹ , Q ² and Q ³ each independently represent a hydrogen atom, a group selected from group A, a group selected from group B, a group selected from group C or a substituent. However, at least two of Q ¹ , Q ² and Q ³ are groups selected from group A, group B or group C. Preferably, two or three of Q ¹ , Q ² and Q ³ are groups selected from Group A, Group B or Group C.

When Q ¹ , Q ² and Q ³ are all groups selected from Group B, Z ¹ , Z ² and Z ³ are divalent groups having -CH ₂ -C(=O)NH- at the ends A linking group, which is linked to Q ¹ , Q ² and Q ³ through the nitrogen atom in -CH ₂ -C(=O)NH-. Z ¹ , Z ² and Z ³ have —CH ₂ at the terminal even when Q ¹ , Q ² and Q ³ are each independently a group selected from Group A, Group B or Group C. A divalent linking group having -C(=O)NH-, wherein the linking group is linked to Q ¹ , Q ² and Q ³ via the nitrogen atom in -CH ₂ -C(=O)NH- are preferably combined with each other.

In Group A, R ^1a , R ^2a , R ^3a , R ^4a and R ^5a are each independently a hydrogen atom or a substituent. The substituent is preferably substituent B or substituent C. When the substituent is the substituent B, the number of the substituent B among R ^1a , R ^2a , R ^3a , R ^4a and R ^5a is preferably 0 or 1. When the substituent is substituent C, the number of substituent C among R ^1a , R ^2a , R ^3a , R ^4a and R ^5a is preferably 0 or 1. R ^1a , R ^2a , R ^3a , R ^4a and R ^5a are preferably hydrogen atoms. In each formula of Group A, the total number of R ^1a , R ^2a , R ^3a , R ^4a , and R ^5a is 4, but a total of 4 R ^1a , R ^2a , R ^3a , R ^4a , and The number of hydrogen atoms in R ^5a is preferably 3 or 4.

A group selected from group A is preferably a group selected from the group consisting of groups represented by formula (A-2) and formula (A-3), more preferably represented by formula (A-2) is a group.

Groups selected from Group A include, for example, groups represented by the following formulas (A-1a) to (A-15a). Note that * represents a bond. In the groups represented by the following formulas (A-1a) to (A-15a), when the heterocyclic ring having a bond has a hydrogen atom, the hydrogen atom may be substituted with a substituent. . Since the group selected from Group A is a group represented by the above formula (A-2), it is preferably represented by formula (A-2a) or formula (A-5a) to formula (A-15a). It is a group represented.

In Group B, R ^1b , R ^2b and R ^3b are each independently a hydrogen atom or a substituent. The substituent is preferably substituent B or substituent C. When the substituent is the substituent B, the number of the substituent B among R ^1b , R ^2b and R ^3b is preferably 0 or 1. When the substituent is C, the number of C substituents in R ^1b , R ^2b and R ^3b is preferably 0 or 1. R ^1b , R ^2b and R ^3b are preferably hydrogen atoms. In each formula of Group B, the total number of R ^1b , R ^2b and R ^3b is 2, and the number of hydrogen atoms among the total of 2 R ^1b , R ^2b and R ^3b is preferably is one or two.

A group selected from group B is preferably a group represented by formula (B-2).

Groups selected from Group B include, for example, groups represented by the following formulas (B-1a) to (B-8a). Note that * represents a bond. In the groups represented by formulas (B-1a) to (B-8a), when the heterocyclic ring having a bond has a hydrogen atom, the hydrogen atom may be substituted with a substituent. The group selected from Group B is a group represented by the above formula (B-2), and therefore is preferably represented by formulas (B-1a) to (B-4a), formula (B-7a) or formula It is a group represented by (B-8a).

In Group C, R ^1c , R ^2c , R ^3c , R ^4c , R ^5c , and R ^6c are each independently a hydrogen atom or a substituent. The substituent is preferably substituent B or substituent C. When the substituent is the substituent B, the number of the substituent B among R ^1c , R ^2c , R ^3c , R ^4c , R ^5c and R ^6c is preferably 0 or 1. When the substituent is C, the number of C substituents among R ^1c , R ^2c , R ^3c , R ^4c , R ^5c , and R ^6c is preferably 0 or 1. R ^1c , R ^2c , R ^3c , R ^4c , R ^5c and R ^6c are preferably hydrogen atoms. In each formula of Group C, the total number of R ^1c , R ^2c , R ^3c , R ^4c , R ^5c , and R ^6c is 5, but a total of 5 R ^1c , R ^2c , R ^3c , R Among ^4c , R ^5c and R ^6c , the number of hydrogen atoms is preferably 4 or 5.

The group selected from Group C is preferably a phenanthroline derivative rather than a bipyridine derivative, from the viewpoint of being able to strongly coordinate to the metal element with a rigid skeleton, the formula (C-4), the formula (C-5), or the formula A group represented by (C-6), more preferably formula (C-5) or formula (C-6).

Groups selected from Group C include, for example, groups represented by the following formulas (C-1a) to (C-9a). Note that * represents a bond. In the groups represented by formulas (C-1a) to (C-9a), when the heterocyclic ring having a bond has a hydrogen atom, the hydrogen atom may be substituted with a substituent. A group selected from Group C is a group represented by the above formula (C-5) or formula (C-6), and therefore is preferably represented by formula (C-5a), formula (C-6a), formula (C-8a), or a group represented by the formula (C-9a).

Y represents a nitrogen atom or a hydrocarbon group optionally having a substituent. Examples of the hydrocarbon group for Y include, for example, a methine group, a trivalent group excluding three hydrogen atoms directly bonded to carbon atoms constituting an aromatic hydrocarbon ring having 6 to 18 carbon atoms, and a number of carbon atoms. 4 to 18 cycloalkanetriyl groups are included. A portion of -CH ₂ - in the cycloalkanetriyl group may be substituted with -O- or -C(=O)-. Y is preferably a nitrogen atom.

Specific examples of the optionally substituted hydrocarbon group for Y include the following formulas (D-1a) to (D-5a). A hydrogen atom in the groups represented by formulas (D-1a) to (D-5a) may be substituted with a substituent. Note that * represents a bond. The optionally substituted hydrocarbon group is preferably represented by formula (D-1a), formula (D-2a), or formula (D-5a).

When n is 2 or more, multiple Y's may be the same or different. When n is 2 or more, a plurality of Y's are preferably the same.

Z ¹ represents a single bond, -C(=O)-, or a hydrocarbylene group having an optionally substituted methylene group or at least two -CH ₂ -. Z ¹ is preferably an optionally substituted hydrocarbylene group having at least two —CH ₂ —. The number of —CH ₂ — in the hydrocarbylene group having at least two —CH ₂ — is preferably 3 or more, more preferably 4 or more.

Z ² and Z ³ each independently represent a single bond or a divalent linking group which may have a substituent. Z ² and Z ³ are preferably divalent linking groups optionally having a substituent.

Divalent linking groups include, for example, hydrocarbylene groups. Examples of hydrocarbylene groups include alkylene groups, cycloalkylene groups, and arylene groups. Specific examples and preferred examples of the cycloalkylene group and the arylene group may be the same as those for L ¹ above.

A hydrocarbylene group is preferably an alkylene group. Examples of the alkylene group in the hydrocarbylene group of Z ² and Z ³ include methylene group, ethylene group, propylene group, isopropylene group, butylene group, isobutylene group, tert-butylene group, pentylene group and hexylene group. . The alkylene group in the hydrocarbylene group having at least two —CH ₂ — of Z ¹ is an alkylene group having at least two —CH ₂ — among the alkylene groups in the hydrocarbylene groups of Z ² and Z ³ is mentioned. The alkylene groups of Z ¹ , Z ² and Z ³ may be linear, branched or cyclic, but are preferably linear. The number of carbon atoms in the alkylene group in the hydrocarbylene group having at least two —CH ₂ — in Z ¹ is preferably 2-30, more preferably 6-30. The number of carbon atoms in the alkylene group in the hydrocarbylene groups of Z ² and Z ³ is preferably 1-30, more preferably 2-30, still more preferably 6-30. The number of carbon atoms in these alkylene groups is a certain number or more because the coordinate bonding site in Q ¹ , Q ² or Q ³ can be at a distance that allows bonding to a single metal element. Preferably. The number of carbon atoms in the main chain connecting between Q ¹ , Q ² and Q ³ of these alkylene groups and Y is preferably 6 or more.

some or all of the —CH ₂ — in the hydrocarbylene groups having at least two —CH ₂ — of Z ¹ and some of —CH ₂ — in the hydrocarbylene groups of Z ² and Z ³ or all may be substituted with -O-, -C(=O)-, -NHC(=O)-, or -C(=O)NH-, solubility in aqueous solution and synthetic For ease of consideration, some of the —CH ₂ — in these hydrocarbylene groups are —O—, —C(=O)—, —NHC(=O)—, or —C(=O) preferably substituted with NH-, more preferably substituted with -O-, -NHC(=O)-, or -C(=O)NH-, -O-, -NHC(= more preferably substituted with 2 or more groups selected from the group consisting of O)- and -C(=O)NH-, and substituted with 4 or more groups selected from the group is particularly preferred.

two ^or more —CH ₂ — in the hydrocarbylene group with at least two —CH ₂ — of Z 1 and two or more —CH ₂ — in the hydrocarbylene groups of Z ² and Z ³ is substituted with -O-, -C(=O)-, -NHC(=O)-, or -C(=O)NH-, two or more of -CH ₂ - are -O It is preferably substituted with at least two selected from the group consisting of -, -C(=O)-, -NHC(=O)-, and -C(=O)NH-. At this time, at least one of the two is preferably -O-.

The methylene group or the group having at least two —CH ₂ — in Z ¹ and the substituent which the divalent linking group in Z ² and Z ³ may have is preferably the substituent B or the substituent is C.

When n is 2 or more, multiple Z ² and Z ³ may be the same or different, and Z ¹ and Z ² may combine with each other to form a ring structure. . n may be 3-6. When n is 3 to 6, Z ¹ and Z ² are preferably bonded together to form a ring structure.

When Z ¹ and Z ² combine with each other to form a ring structure, Q ¹ and Q ² are preferably hydrogen atoms. In the compound represented by the formula (1), the compound in which n is 3 to 6 and Z ¹ and Z ² are bonded to each other to form a ring structure include, for example, the following formulas (E-1) to A compound represented by formula (E-4) can be mentioned. The compound is preferably a compound represented by Formula (E-1) or Formula (E-2).

On the other hand, n may be 0-2, more preferably 0 or 1. When n is 0 to 2, Z ¹ and Z ² are preferably not bonded to each other to form a ring structure. Q ¹ and Q ² are each independently preferably a group selected from group A, a group selected from group B, a group selected from group C, or a substituent. In the compound represented by the formula (1), the compound in which n is 0 to 2 and Z ¹ and Z ² are not bonded to each other to form a ring structure include, for example, the following formulas (F-1) to A compound represented by the formula (F-20) can be mentioned. In addition, Sp represents "a structure having an affinity for an antigen". Since n is 0 or 1, the compounds are preferably compounds represented by formulas (F-1) to (F-18), and have —CH ₂ —C(═O)NH - and is bonded to Q ¹ , Q ² and Q ³ through the nitrogen atom in -CH ₂ -C(=O)NH-, more preferably formula (F-1 ), formula (F-2), formula (F-7), formula (F-9), formula (F-16), or (F-19).

The compound represented by Formula (1) is preferably a compound represented by Formula (2) below. The compound represented by formula (2) is a compound represented by formula (1) in which Y is a nitrogen atom.

［式（２）中、Ｑ^１、Ｑ^２、Ｑ^３、Ｚ^１、Ｚ^２、Ｚ^３、及びｎは、前記と同義である。］

[In formula (2), Q ¹ , Q ² , Q ³ , Z ¹ , Z ² , Z ³ and n are as defined above. ]

The compound represented by Formula (2) is preferably a compound represented by Formula (3) below. The compound represented by formula (3) is a compound represented by formula (2) in which n is 0 or 1.

［式（２）中、Ｑ^１、Ｑ^２、Ｑ^３、Ｚ^１、Ｚ^２、及びＺ^３は、前記と同義である。
ｎ_１は、０又は１を表す。］

[In Formula (2), Q ¹ , Q ² , Q ³ , Z ¹ , Z ² and Z ³ are as defined above.
_n1 represents 0 or 1; ]

The compound represented by Formula (3) is preferably a compound represented by Formula (4) below. The compound represented by formula (4) is a compound represented by formula (3) in which Z ¹ , Z ² and Z ³ are each independently a single bond or a hydrocarbyl group optionally having a substituent. It is a compound that is a rene group.

［式（４）中、Ｑ^１、Ｑ^２、Ｑ^３、及びｎ_１は、前記と同義である。
Ｚ^１Ａは、単結合又は置換基を有していてもよい、メチレン基若しくは少なくとも２個の－ＣＨ_２－を有するヒドロカルビレン基を表し、少なくとも２個の－ＣＨ_２－を有するヒドロカルビレン基中の－ＣＨ_２－の一部又は全部は、－Ｏ－、－Ｃ（＝Ｏ）－、－ＮＨＣ（＝Ｏ）－、又は－Ｃ（＝Ｏ）ＮＨ－に置換されていてもよい。
Ｚ^２Ａ及びＺ^３Ａは、それぞれ独立に、単結合又は置換基を有していてもよいヒドロカルビレン基を表し、ヒドロカルビレン基中の－ＣＨ_２－の一部又は全部は、－Ｏ－、－Ｃ（＝Ｏ）－、－ＮＨＣ（＝Ｏ）－、又は－Ｃ（＝Ｏ）ＮＨ－に置換されていてもよい。
Ｑ^１、Ｑ^２、及びＱ^３がすべて群Ｂから選ばれる基である場合、Ｚ^１Ａ、Ｚ^２Ａ、及びＺ^３Ａは、末端の－ＣＨ_２－が－ＣＨ_２－Ｃ（＝Ｏ）ＮＨ－に置換されたヒドロカルビレン基であり、当該基は、－ＣＨ_２－Ｃ（＝Ｏ）ＮＨ－中の窒素原子を介してＱ^１、Ｑ^２、及びＱ^３とそれぞれ結合している。］

[In Formula (4), Q ¹ , Q ² , Q ³ , and n ₁ are as defined above.
Z ^1A represents a single bond or optionally substituted methylene group or hydrocarbylene group having at least two —CH ₂ —, hydrocarbylene having at least two —CH ₂ — Part or all of -CH ₂ - in the group may be substituted with -O-, -C(=O)-, -NHC(=O)-, or -C(=O)NH- .
Z ^2A and Z ^3A each independently represent a single bond or an optionally substituted hydrocarbylene group, and part or all of —CH ₂ — in the hydrocarbylene group is —O— , -C(=O)-, -NHC(=O)-, or -C(=O)NH-.
When Q ¹ , Q ² and Q ³ are all groups selected from Group B, Z ^1A , Z ^2A and Z ^3A have -CH ₂ - at the ends of -CH ₂ -C(=O)NH- which is attached to Q ¹ , Q ² and Q ³ respectively through the nitrogen atom in —CH ₂ —C(=O)NH—. ]

The compound represented by Formula (4) is preferably a compound represented by Formula (5A), Formula (5B), or Formula (5C) below.

［式（５Ａ）、式（５Ｂ）、及び式（５Ｃ）中、Ｒ^１ａ、Ｒ^２ａ、Ｒ^４ａ、Ｒ^５ａ、Ｒ^１ｂ、Ｒ^３ｂ、Ｒ^１ｃ、Ｒ^２ｃ、Ｒ^４ｃ、Ｒ^５ｃ、Ｒ^６ｃ、Ｚ^１Ａ、Ｚ^２Ａ、Ｚ^３Ａ、及びｎ_１は、前記と同義である。
Ｑ^２Ａ及びＱ^３Ａは、それぞれ独立に、下記式（Ａ－２ａ）、式（Ｂ－２ａ）、及び式（Ｃ－３ａ）で表される基からなる群より選ばれる基である。

[In Formula (5A), Formula (5B), and Formula (5C), R ^1a , R ^2a , R ^4a , R ^5a , R ^1b , R ^3b , R ^1c , R ^2c , R ^4c , R ^5c , R ^6c , Z ^1A , Z ^2A , Z ^3A , and n ₁ are as defined above.
Q ^2A and Q ^3A are each independently a group selected from the group consisting of groups represented by the following formulas (A-2a), (B-2a) and (C-3a).

（（Ａ－２ａ）、式（Ｂ－２ａ）、及び式（Ｃ－３ａ）中、環を構成する炭素原子に直接結合する水素原子は、置換基によって置換されていてもよい。なお、＊は、結合手を表す。）］

(In (A-2a), formula (B-2a), and formula (C-3a), a hydrogen atom directly bonded to a carbon atom constituting a ring may be substituted by a substituent. Note that * represents a bond.)]

^Q2A and ^Q3A may be the same or different, and are preferably the same at sites other than the optionally substituted substituents.

In the compound represented by formula (5A), formula (5B), or formula (5C), 0 or 1 hydrogen atoms directly bonded to carbon atoms constituting the ring are substituted with substituent B. More preferably, one substitution is possible because it can be used in combination with a "structure having affinity for an antigen."

Examples of compounds represented by formula (5A), formula (5B), or formula (5C) include compounds represented by the following formulas (G-1) to (G-16). These compounds may have a substituent. In addition, Sp represents "a structure having an affinity for an antigen".

The compound of this embodiment may form a salt upon interaction with an acid or base, or may be hydrated. Examples of acids that may form salts include hydrochloric acid, bromic acid, iodic acid, phosphoric acid, acetic acid, sulfuric acid, nitric acid, perchloric acid, trifluoroacetic acid, trifluoromethanesulfonic acid, and tetrafluoroboric acid. , hexafluorophosphoric acid, tetraphenylboric acid, and the like. The acid is preferably hydrochloric acid or bromic acid. The salt structure with an acid includes, for example, a salt structure in which the nitrogen site in the compound of the present embodiment interacts with an acid.

Examples of the base that may form a salt include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide; substances; quaternary ammonium hydroxides such as tetramethylammonium hydroxide and tetrabutylammonium hydroxide; alkali metal carbonates such as lithium carbonate, sodium carbonate and potassium carbonate; lithium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate and the like and alkali metal hydrogen carbonate. The salt structure with a base includes, for example, a salt structure in which the proton of the carboxylic acid site in the compound of the present embodiment is replaced with another cation.

In the compound of this embodiment, some protons may move within the molecule. For example, in the compound represented by formula (G-1), one or two protons in the carboxylic acid may move to the vicinity of the nitrogen atom in the quinoline structure.

[Method for producing compound]
Next, a method for producing the compound of the present embodiment will be described.

The compound represented by formula (1) can be obtained by appropriately combining known methods that can link compounds that can be Q ¹ , Q ² and Q ³ to sites that can be Z ¹ , Z ² and Z ³ . can be manufactured by

^{In the following , Q 1 ,} Q ² and ^Q A method for forming a binding site that connects the sites that can be ³ will be specifically described.

Z ^x is a hydrocarbylene group in _which the terminal —CH ₂ — is replaced with —CH ₂ —C(=O)NH—, and the group is When each of Q ¹ , Q ² , and Q ³ is bonded via a nitrogen atom, a method for forming a bonding site with such a hydrocarbylene group is as exemplified by the following formula (10). A compound having a carboxylic acid group bonded to a hydrocarbylene group and a compound having an amino group are reacted with a known carboxylic acid site activator such as oxalyl chloride or a condensing agent using DMF, toluene, dichloromethane, or the like. and a method of mixing in a solvent of

Further, for example, in the case where Z ^x is an alkylene group, the method for forming a bonding site with such an alkylene group includes a compound having an aldehyde structure and a compound having an amino group, as exemplified in the following formula (11) compound in a solvent such as ethanol, and then reacting with a reducing agent such as sodium borohydride.

In formulas (10) and (11), the carboxylic acid in the resulting compound is protected with an ester structure. An ester site can be derived into a carboxylic acid by deprotecting it by performing a generally known de-esterification reaction or the like. Thus, in the step of forming the binding site of ^Zx , the compound of the present embodiment can be produced by appropriately introducing a protecting group and then deprotecting it.

The compound represented by formula (1) can be obtained by combining known techniques exemplified above. A compound having a carboxylic acid structure and a compound having an amino group, which are examples of starting materials in each reaction, can be obtained by appropriately combining known methods for synthesizing carboxylic acid derivatives and amino compound derivatives. can be manufactured.

As for the compound represented by the formula (1) having the substituent B having "the site capable of cross-linking with the structure having affinity for the antigen", a compound partially having the structure of the substituent B is synthesized. It can be produced by appropriately combining known techniques.

For example, as a method for producing a compound in which the substituent B has a —C ₆ H ₅ NCS structure (a group represented by the formula (D-1)), any of the raw materials in the above formula (10) or (11) A compound having a nitrophenyl group is used to perform a reaction to form a binding site by Z ^x . Subsequently, an appropriate deprotection reaction was performed to convert the ester site to a carboxylic acid, and then the nitro site was converted to an amine in a solvent such as ethanol using a common reducing agent such as a combination of a palladium catalyst and hydrogen. Compounds having the —C ₆ H ₅ NCS structure can be prepared by subsequent mixing with thiophosgene in a solvent such as chloroform.

[Metal complex]
Next, a metal complex having a ligand derived from the compound of this embodiment will be described.

In the metal complex of the present embodiment, the metal element interacts with the above compound. More specifically, the heteroatom in the compound interacts with the metal element, and the nitrogen atom in the nitrogen-containing heterocycle and/or the oxygen-containing functional group in the compound represented by formula (1) It interacts with oxygen atoms. Interactions are usually coordinate bonds.

The metal complex is a heteroatom of the compound represented by formula (1) (e.g., a nitrogen atom in a nitrogen-containing heterocyclic group, a nitrogen atom in a primary to tertiary amine, -OH (including -O ^- ) an oxygen atom, an oxygen atom in —CO ₂ H (including —CO ₂ ^— ), and the number of coordinate bonds is preferably 4 to 12, more preferably 6 to 10. The compound of the present embodiment can three-dimensionally exhibit the above-described interaction when a metal element is bonded. The presence or absence of formation of coordinate bonds can be confirmed by specifying the distance between the metal element and the heteroatom by structural optimization calculation using software that can simulate the 3D molecular structure that is widely used.

In the ligand derived from the compound represented by formula (1), at least two of Q ¹ , Q ² and Q ³ are groups selected from group A, group B or group C. Here, in all groups selected from Group A, Group B, or Group C, preferably at least one heteroatom interacts with the metal element, and at least two heteroatoms interact with the metal element. More preferably, at least three interact with the metal element.

The metal elements may be uncharged or charged ions, preferably charged ions. When the metal element is charged, it preferably has a valence of 1 to 4, more preferably 2 to 4.

The metal element may be a typical metal element, an alkali metal element, an alkaline earth metal element, a transition metal element, or a rare earth element, and may be a radioactive element or a non-radioactive element.

Examples of metal elements that are non-radioactive elements include Mg, Al, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Ge, Sr, Y, Zr, Nb, Mo, Ru, Rh, Pd, Ag, Cd, In, Sn, Sb, Te, Ba, La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, La, Hf, Ta, W, Re, Os, Ir, Pt, Au, Hg, Tl, Pb, and Bi. The metal element, which is a non-radioactive element, is preferably a metal element that can be stably used as a divalent to tetravalent metal cation.

Examples of metal elements that are radioactive elements include ⁴⁴ Sc, ⁴⁷ Sc, ⁵¹ Cr, ⁵⁹ Fe, ⁵⁷ Co, ⁵⁸ Co, 60 Cu, ⁶¹ Cu, ⁶² Cu, ⁶⁴ Cu ^{, 67 Cu} , ⁶⁶ Ga, ⁶⁷ Ga, ⁶⁸ Ga, ⁷⁵ Se, ^{83 Sr} , ⁸⁶ Y, ⁹⁰ Y, ⁸⁹ Zr, ⁹⁹ Mo, 94m Tc, ^99m Tc, ⁹⁷ Ru, ¹⁰³ Ru, ¹⁰⁵ Rh, ¹⁰⁹ Pd, ¹¹¹ Ag, 110 In, ¹¹¹ In, ^{114m In} , ¹³² La, ¹³⁵ La, ¹⁵³ Sm, ¹⁴⁹ Tb, ⁶⁰ Tb, ¹⁶¹ Tb, ¹⁶⁶ Ho, ¹⁶⁷ Tm, ¹⁶⁹ Yb, ¹⁷⁷ Lu, ¹⁸⁶ Re, ¹⁸⁸ Re, ¹⁹⁹ Au, ²⁰¹ Tl, ²¹² Pbi, ^{212 B} Bi, ²³³ Ra, ²²⁵ Ac, ²²⁷ Th, ²⁴¹ Am, ²⁴⁴ Cm. The metal element, which is a radioactive element, is preferably a metal element that can be used as a divalent to tetravalent metal cation.

The number of metal elements present in one molecule of the metal complex may be one or more. The number of metal elements present in one molecule of the metal complex is preferably 1 or 2, more preferably 1.

The number of metal elements present in one molecule of the metal complex may be one or two or more. The number of metal elements present in one molecule of the metal complex is preferably one.

The metal complex may contain a counterion to render the metal complex electrically neutral. If the metal complex is positively charged, an anion is chosen to neutralize it. Anions include, for example, fluoride ion, chloride ion, bromide ion, iodide ion, sulfide ion, oxide ion, hydroxide ion, hydride ion, phosphate ion, acetate ion, sulfate ion, nitric acid ions, bicarbonate ions, trifluoroacetate ions, trifluoromethanesulfonate ions, tetrafluoroborate ions, and the like. The anion is preferably hydrochloride or acetate. If the metal complex is negatively charged, a cation is chosen to neutralize it. Examples of cations include protons, ammonium ions, tetraalkylammonium ions, tetraarylphosphonium ions, and the like. A plurality of counterions may be present, and they may be the same or different.

The metal complex may contain neutral molecules such as the solvent used during the metal complexation reaction or purification. Examples of neutral molecules include water, methanol, ethanol, n-propanol, N,N-dimethylformamide, N-methyl-2-pyrrolidone, dimethylsulfoxide, acetone, chloroform, acetonitrile, benzonitrile, triethylamine, pyridine. , diethyl ether, acetic acid, propionic acid, hydrochloric acid, and the like. A plurality of neutral molecules may exist, and they may be the same or different.

The metal complex preferably has one substituent A or one substituent B.

Examples of the metal complex of this embodiment include metal complexes represented by the following formulas (H-1) to (H-16). These metal complexes may have a substituent.

In the formula, M represents a metal element. Dashed lines between M and heteroatoms represent possible interactions. Note that the dashed lines between M and heteroatoms are for convenience and do not necessarily mean that interactions exist in all dashed lines, while the dashed lines between M and heteroatoms are not shown. The points may be partially interacting. Also, part of the moieties represented as oxygen anions may combine with protons to form an OH structure. Further, the metal complex represented by the above formula may have a counterion and/or a neutral molecule as described above, and the ligand derived from the above compound may have a substituent. good. In addition, Sp represents "a structure having an affinity for an antigen".

[Method for producing metal complex]
Next, a method for producing the metal complex of this embodiment will be described. The method for producing a metal complex according to the present embodiment includes a step of mixing a reactant that imparts a metal element and the compound represented by formula (1).

For example, the metal complex of the present embodiment is obtained by organically synthesizing the compound of the present embodiment, and then using the obtained compound as a reactant for imparting a metal element (hereinafter, sometimes referred to as a "metal imparting agent". ) and reacted. The amount of the metal-providing agent to be reacted can be appropriately adjusted according to the desired metal complex.

Examples of the metal imparting agent include acetates, fluorides, chlorides, bromides, iodides, sulfates, carbonates, nitrates, acetates, hydroxides, perchlorates, and tris of the metal elements exemplified above. fluoroacetate, trifluoromethanesulfonate, tetrafluoroborate, hexafluorophosphate, tetraphenylborate and the like. The metal donating agent is preferably a chloride or acetate of a metal element. The metal imparting agent may be a hydrate.

The reaction between the compound and the metal donating agent is preferably carried out in a solvent (ie reaction solvent).

Examples of reaction solvents include water, acetic acid, propionic acid, hydrochloric acid, aqueous ammonia, methanol, ethanol, n-propanol, N,N-dimethylformamide, N-methyl-2-pyrrolidone, dimethylsulfoxide, acetone, and chloroform. , acetonitrile, benzonitrile, triethylamine, pyridine, diethyl ether and the like. The reaction solvent may be used singly or in combination of two or more. The reaction solvent may contain other components such as acids, bases and buffers for adjusting the pH of the reaction solution.

The reaction temperature is usually -10 to 200°C, preferably 0 to 100°C, more preferably 10 to 40°C. The reaction time is generally 1 minute to 1 week, preferably 1 minute to 24 hours, more preferably 1 minute to 6 hours.

Conditions such as the reaction solvent, reaction temperature, and reaction time can be appropriately optimized according to the type of compound, the type of metal-providing agent, and the like.

In the case of isolating and purifying the metal complex, as a purification method after the reaction, an optimum method can be appropriately selected and used from known recrystallization methods, reprecipitation methods, chromatography methods, and the like. Depending on the conditions, the produced metal complex may precipitate, and the metal complex can be isolated and purified by separating the precipitated metal complex by filtration.

A metal complex having substituent A can be obtained by reacting a compound having substituent A with a metal-donating agent. In addition, after reacting a compound having a substituent B with a metal-donating agent to form a complex, the "structure having affinity for the antigen" and the "crosslinking" exemplified in the above formulas (6) to (8) It can also be obtained by performing a binding reaction with "possible sites".

[Utility of compound and/or metal complex]
Next, usefulness of the compound and/or metal complex of the present embodiment will be described.

The compound of the present embodiment is used as a catalyst for reactions such as decomposition of hydrogen peroxide, an electrode catalyst for carbon dioxide reduction, etc., by forming a complex with a metal element having oxidation-reduction activity such as Co, Fe, Ni, etc. be able to.

Some forms of the compounds of this embodiment have high metal retention and can form complexes with very low concentrations of metals. Therefore, for example, valuable metal elements can be collected from radioactive waste or seawater. Some forms of the compound form strong coordination bonds with metal elements, and therefore can be used, for example, as surface coating materials for metal particles. Some forms of the compound of the present embodiment can be given luminescent properties by using a specific metal element, and can be used as a luminescent material. Furthermore, when some forms of the compounds of this embodiment are used as ligands, they can be used in radiopharmaceuticals because of their high retention of radiometal elements.

EXAMPLES The present invention will be specifically described below based on examples, but the present invention is not limited to these.

The structures of the compounds were confirmed by known methods such as nuclear magnetic resonance (NMR) spectroscopy and mass spectroscopy (MS).

In the following medium-pressure preparative column chromatography, EPCLC-AI-580S manufactured by Yamazen Co., Ltd. and ODS M W917 and ODS-SM L UW113 manufactured by Yamazen Co., Ltd. connected as reversed-phase columns were used.
For gel filtration column chromatography, JAIGEL-2H-40 and JAIGEL-1H-40 manufactured by Nippon Analytical Industry Co., Ltd. were connected to LC-9104 manufactured by Nippon Analytical Industry Co., Ltd. as columns.
An AV NEO 300 MHz NMR spectrometer manufactured by BRUKER was used for the NMR measurement.
UV-visible absorption spectrum analysis was performed using Shimadzu UV-2400PC.

Synthesis example 1
<Synthesis of Compound (S-2)>

After the inside of the reaction vessel was replaced with a nitrogen gas atmosphere, 0.250 g (0.788 mmol) of 3,6,9-trioxaundecane-1,11-dioic acid, 6.00 g (47.3 mmol) of oxalyl chloride, and 0.00 g (47.3 mmol) of DMF were added. 0600 mL was added, and the mixture was heated to 65° C. and stirred for 1 hour while refluxing, and then unreacted oxalyl chloride and DMF were concentrated under reduced pressure. After creating a nitrogen gas atmosphere in another reaction vessel, 0.455 g (1.97 mmol) of compound (S-1) was dissolved in 11.0 mL of DMF at room temperature. This solution was added dropwise to the above reaction solution, and after stirring for 15 minutes at room temperature, 0.239 g (2.36 mmol) of triethylamine was added dropwise. After the above reaction solution was further stirred for 2 hours, it was concentrated to dryness under reduced pressure. The crude product was redissolved in methanol and purified by reverse phase chromatography using water/methanol and acetonitrile/methanol mobile phases. The collected solution was concentrated under reduced pressure and dried under reduced pressure to obtain compound (S-2) with a yield of 41%. Identification data of the obtained compound (S-2) are shown below.

¹ H-NMR (300 MHz, DMSO-d6): δ (ppm) = 3.74 (d, J = 3.3 Hz, 8H), 3.96 (s, 6H), 4.14 (s, 4H), 7.16 (d, J = 8.6 Hz, 2H), 7.51 (d, J = 8.2 Hz, 2H), 8.08 (d, J = 8.6 Hz, 2H), 8.36 (d , J=8.2 Hz, 2H), 9.69 (s, 2H), 10.0 (br, 2H).

Example 1
<Synthesis of compound (G-1)>

After the inside of the reaction vessel was replaced with a nitrogen gas atmosphere, 130 mg (0.205 mmol) of compound (S-2) was dissolved in a mixed solvent of 3.06 mL of methanol and 1.53 mL of water. 1.52 mL of a 4.0 M sodium hydroxide aqueous solution was added dropwise thereto, and the mixture was stirred at room temperature for 30 minutes. Next, 0.530 mL of a 36% hydrochloric acid aqueous solution was added dropwise to the above reaction solution, and after stirring for 30 minutes, the solution was concentrated under reduced pressure to dryness. The crude product was redissolved in water and purified by reverse phase chromatography using water/methanol and acetonitrile/methanol mobile phases. The separated solution was concentrated under reduced pressure and dried under reduced pressure to confirm the production of compound (G-1) by NMR. Identification data of the obtained compound (G-1) are shown below.

¹ H-NMR (300 MHz, DMSO-d6): δ (ppm) = 3.94 (br, 8H), 4.25 (s, 4H), 6.92 (d, J = 8.1 Hz, 2H), 7.19 (d, J=8.1 Hz, 2H), 7.83 (d, J=8.7 Hz, 2H), 8.00 (d, J=8.7 Hz, 2H).

Synthesis example 2
<Synthesis of compound (S-4)>

After the inside of the reaction vessel was replaced with a nitrogen gas atmosphere, 80.0 mg (0.252 mmol) of 3,6,9-trioxaundecane-1,11-dioic acid, 1.92 g (15.1 mmol) of oxalyl chloride, and 0.92 g (15.1 mmol) of DMF were added. 0190 mL was added, and the mixture was heated to 65° C. and stirred for 1 hour while refluxing, and then unreacted oxalyl chloride and DMF were concentrated under reduced pressure. After making the inside of another reaction vessel a nitrogen gas atmosphere, 0.135 g (0.630 mmol) of dimethyl-4-aminopyridine-2,6-dicarboxylate (compound (S-3)) was added to 3.53 mL of DMF at room temperature. Dissolved. This solution was added dropwise to the above reaction solution, and after stirring for 10 minutes at room temperature, 0.0770 g (0.756 mmol) of triethylamine was added dropwise. After the above reaction solution was further stirred for 3 hours, it was concentrated to dryness under reduced pressure. The crude product was redissolved in methanol and purified by reverse phase chromatography using water/methanol and acetonitrile/methanol mobile phases. The collected solution was concentrated under reduced pressure and dried under reduced pressure to obtain compound (S-4) with a yield of 54%. Identification data of the obtained compound (S-4) are shown below.

¹ H-NMR (300 MHz, DMSO-d6): δ (ppm) = 3.70 (m, 8H), 3.91 (s, 12H), 4.19 (s, 4H), 8.56 (s, 4H), 10.5(s, 2H).

Example 2
<Synthesis of compound (G-10)>

After the inside of the reaction vessel was replaced with a nitrogen gas atmosphere, 68.0 mg (0.110 mmol) of compound (S-4) was dissolved in a mixed solvent of 1.61 mL of methanol and 1.61 mL of water. 0.410 mL of a 4.0 M sodium hydroxide aqueous solution was added dropwise thereto, and the mixture was stirred at room temperature for 30 minutes. Next, 0.142 mL of a 36% hydrochloric acid aqueous solution was added dropwise to the above reaction solution, and after stirring for 30 minutes, the solution was concentrated under reduced pressure to dryness. The crude product was redissolved in water and purified by reverse phase chromatography using water/methanol and acetonitrile/methanol mobile phases. The collected solution was concentrated under reduced pressure and dried under reduced pressure to confirm the production of compound (G-10) by NMR. Identification data of the obtained compound (G-10) are shown below.

¹ H-NMR (300 MHz, DMSO-d6): δ (ppm) = 3.64 (m, 8H), 4.20 (s, 4H), 8.54 (s, 4H), 10.9 (s, 2H).

Synthesis example 3
<Synthesis of Compound (S-5)>

After making the inside of the reaction vessel a nitrogen gas atmosphere, 80.0 mg (0.166 mmol) of 4,7,10,13,16-pentaoxanonadecane-1,19-dioic acid and 1.26 g (9.93 mmol) of oxalyl chloride were added. ), and 0.0130 mL of DMF were added, and the mixture was heated to 65° C. and stirred for 1 hour while refluxing, and then unreacted oxalyl chloride and DMF were concentrated under reduced pressure. After creating a nitrogen gas atmosphere in another reaction vessel, 0.0890 g (0.414 mmol) of compound (S-3) was dissolved in 3.36 mL of DMF at room temperature. This solution was added dropwise to the above reaction solution, and after stirring for 5 minutes at room temperature, 0.0500 g (0.497 mmol) of triethylamine was added dropwise. After the above reaction solution was further stirred for 3 hours, it was concentrated to dryness under reduced pressure. The crude product was redissolved in methanol and purified by reverse phase chromatography using water/methanol and acetonitrile/methanol mobile phases. The collected solution was concentrated under reduced pressure and dried under reduced pressure to obtain compound (S-5) with a yield of 40%. Identification data of the obtained compound (S-5) are shown below.

¹ H-NMR (300 MHz, CDCl ₃ ): δ (ppm) = 2.68 (t, J = 6.0 Hz, 4H), 3.64 (m, 16H), 3.79 (t, J = 6.0 Hz). 0 Hz, 4H), 3.97 (s, 12H), 8.56 (s, 4H), 9.66 (s, 2H).

Example 3
<Synthesis of compound (G-12)>

After a nitrogen gas atmosphere was created in the reaction vessel, 48.0 mg (0.0650 mmol) of compound (S-5) was dissolved in a mixed solvent of 1.14 mL of methanol and 1.14 mL of water. 0.195 mL of 4.0 M sodium hydroxide aqueous solution was added dropwise thereto, and the mixture was stirred at room temperature for 1 hour. Next, 0.0670 mL of a 36% hydrochloric acid aqueous solution was added dropwise to the above reaction solution, and after stirring for 30 minutes, the solution was concentrated under reduced pressure to dryness. The crude product was redissolved in water and purified by reverse phase chromatography using water/methanol and acetonitrile/methanol mobile phases. The collected solution was concentrated under reduced pressure and dried under reduced pressure to confirm the production of compound (G-12) by NMR. Identification data of the obtained compound (G-12) are shown below.

¹ H-NMR (300 MHz, DMSO-d6): δ (ppm) = 2.63 (t, J = 6.0 Hz, 4H), 3.46 (m, 16H), 3.71 (t, J = 6 .0Hz, 4H), 8.45(s, 4H), 10.8(s, 2H).

Synthesis example 4
<Synthesis of compound (S-6)>

After creating a nitrogen gas atmosphere in the reaction vessel, 50.0 mg (0.160 mmol) of 5-nitro-1,10-phenanthroline-2,9-dioic acid hydrate, 0.406 g (3.19 mmol) of oxalyl chloride, and 0.588 mL of methanol were added. After stirring for 1 hour at room temperature, 3.00 mL of water was added and the precipitated yellow precipitate was filtered. The resulting filtrate was washed with 3.00 mL of water and then dried under reduced pressure to obtain compound (S-6) with a yield of 83%. Identification data of the obtained compound (S-6) are shown below.

¹ H-NMR (300 MHz, CDCl ₃ ): δ (ppm)=4.05 (s, 6H), 8.53 (d, J=8.4 Hz, 1H), 8.56 (d, J=9. 0 Hz, 1 H), 9.01 (d, J = 8.4 Hz, 1 H), 9.10 (d, J = 9.0 Hz, 1 H), 9.24 (s, 1 H).

Synthesis example 5
<Synthesis of Compound (S-7)>

After the inside of the reaction vessel was filled with a nitrogen gas atmosphere, 42.0 mg (0.123 mmol) of compound (S-6), 33.6 mg of Pd/fibroin, and 10.6 mL of methanol were added. After the inside of the reaction vessel was replaced with nitrogen gas again, the atmosphere was made into a hydrogen atmosphere. After stirring at room temperature for 2 days, filtration was performed to obtain a filtrate. The resulting filtrate was concentrated and dried under reduced pressure to obtain compound (S-7) with a yield of 37%. Identification data of the obtained compound (S-7) are shown below.

¹ H-NMR (300 MHz, CD ₃ OD): δ (ppm) = 4.08 (s, 6H), 7.09 (s, 1H), 8.30 (d, J = 9.0Hz, 1H), 8.32 (d, J=9.0 Hz, 1 H), 8.48 (d, J=9.0 Hz, 1 H), 8.89 (d, J=9.0 Hz, 1 H).

Synthesis example 6
<Synthesis of Compound (S-8)>

After making the inside of the reaction vessel a nitrogen gas atmosphere, 9.15 mg (0.0190 mmol) of 4,7,10,13,16-pentaoxanonadecane-1,19-dioic acid and 0.142 g (0.0960 mmol) of oxalyl chloride were added. ), and 1 μL of DMF were added, and the mixture was heated to 65° C. and stirred for 30 minutes while refluxing, and then unreacted oxalyl chloride and DMF were concentrated under reduced pressure. After creating a nitrogen gas atmosphere in another reaction vessel, 15.0 mg (0.0470 mmol) of compound (S-7) was dissolved in 0.397 mL of DMF at room temperature. This solution was added dropwise to the above reaction solution, and after stirring for 10 minutes at room temperature, 10 mg (0.0560 mmol) of triethylamine was added dropwise. The above reaction solution was further stirred for 1 hour and then concentrated to dryness under reduced pressure. The crude product was redissolved in methanol and purified by reverse phase chromatography using water/methanol and acetonitrile/methanol mobile phases. The separated solution was concentrated under reduced pressure and dried under reduced pressure to obtain compound (S-8). The production of compound (S-8) was confirmed by mass spectrometry as described below.

HRMS ₍ ESI) m/z (M+H) ⁺ calcd for _C40H36N6O13 : _809.2 , _found : 809.2.

Example 4
<Synthesis of compound (G-13)>

Compound (G-13) was synthesized in the same manner as in Example 3 using compound (S-8) instead of compound (S-5) described in Example 3. The production of compound (G-13) was confirmed by mass spectrometry as described below.

HRMS ₍ ESI) m/z (M+H) ⁺ calcd for _C36H28N6O13 : _753.2 , _found : 753.2.

Synthesis example 7
<Synthesis of Compound (S-9)>

After creating a nitrogen gas atmosphere in the reaction vessel, 0.110 g (0.272 mmol) of N,N′,N″-tris(carboxyethoxyethyl)amine hydrochloride, 1.55 g (12.2 mmol) of oxalyl chloride, and After adding 0.0190 mL of DMF and stirring for 2 hours, unreacted oxalyl chloride and DMF were concentrated under reduced pressure. After creating a nitrogen gas atmosphere in another reaction vessel, 0.297 g (1.36 mmol) of compound (S-1) was dissolved in 2.72 mL of DMF at room temperature. This solution was added dropwise to the above reaction solution, and after stirring for 10 minutes at room temperature, 0.138 g (1.36 mmol) of triethylamine was added dropwise. After the above reaction solution was further stirred for 20 hours, it was concentrated to dryness under reduced pressure. The crude product was redissolved in methanol and purified by reverse phase chromatography using water/methanol and acetonitrile/methanol mobile phases. The collected solution was concentrated under reduced pressure and dried under reduced pressure to obtain compound (S-9) with a yield of 38%.

Example 5
<Synthesis of compound (G-5)>

0.013 g (0.016 mmol) of compound (S-9) was dissolved in a mixed solvent of 0.16 mL of methanol and 0.16 mL of water. 0.06 mL of a 4.0 M sodium hydroxide aqueous solution was added dropwise thereto, and the mixture was stirred at room temperature for 2 hours. After cooling to 0° C. in an ice water bath, 6M hydrochloric acid was added dropwise, and the precipitated white solid was filtered to obtain compound (G-5). Identification data of the obtained compound (G-5) are shown below.

¹ H-NMR (300 MHz, DMSO-d6): δ (ppm) = 2.69 (t, J = 6.6 Hz, 6H), 3.45 (t, J = 6.6 Hz, 6H), 3.73 (t, J = 6.6 Hz, 6H), 3.75 (t, J = 6.6 Hz, 6H), 7.16 (d, J = 7.8 Hz, 3H), 7.60 (d, J = 7.8Hz, 3H), 8.15 (d, J = 7.8Hz, 3H), 8.50 (d, J = 7.8Hz, 3H), 9.96 (s, 3H), 10.18 ( s, 3H), 13.00 (s, 3H).

Synthesis example 8
<Synthesis of compound (S-10)>

After creating a nitrogen gas atmosphere in the reaction vessel, 0.130 g (0.322 mmol) of N,N′,N″-tris(carboxyethoxyethyl)amine hydrochloride, 1.84 g (14.5 mmol) of oxalyl chloride, and After adding 0.0190 mL of DMF and stirring for 2 hours, unreacted oxalyl chloride and DMF were concentrated under reduced pressure. After creating a nitrogen gas atmosphere in another reaction vessel, 0.245 g (1.13 mmol) of compound (S-3) was dissolved in 3.22 mL of DMF at room temperature. This solution was added dropwise to the above reaction solution, and after stirring for 10 minutes at room temperature, 0.114 g (1.13 mmol) of triethylamine was added dropwise. After the above reaction solution was further stirred for 20 hours, it was concentrated to dryness under reduced pressure. The crude product was redissolved in methanol and purified by reverse phase chromatography using water/methanol and acetonitrile/methanol mobile phases. The collected solution was concentrated under reduced pressure and dried under reduced pressure to obtain compound (S-10) with a yield of 20%. Identification data of the obtained compound (S-10) are shown below.

¹ H-NMR (300 MHz, DMSO-d6): δ (ppm) = 2.73 (t, J = 6.3 Hz, 6H), 2.89 (t, J = 6.3 Hz, 6H), 2.36 (t, J = 6.3 Hz, 6H), 3.77 (t, J = 6.3 Hz, 6H), 3.87 (s, 18H), 7.40 (s, 6H), 10.60 (s , 3H).

Example 6
<Synthesis of compound (G-6)>

3.0 mg (0.004 mmol) of compound (S-10) was dissolved in a mixed solvent of 0.036 mL of methanol and 0.036 mL of water. 0.014 mL of 4M sodium hydroxide aqueous solution was added dropwise thereto, and the mixture was stirred at room temperature for 2 hours. After cooling to 0° C. in an ice water bath, 6M hydrochloric acid was added dropwise, and the precipitated white solid was filtered to obtain compound (G-6). The production of compound (G-6) was confirmed by mass spectrometry as described below.

HRMS ( _ESI ) m/z (M+H) ⁺ calcd for _C36H40N7O18 : _858.2 , _found : 858.2.

Example 7
<La Complex Synthesis of Compound (G-1)>
A 0.1 mol/L HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) aqueous solution was prepared as a buffer (hereinafter referred to as "buffer 1"). Compound (G-1) was dissolved in buffer solution 1 at a concentration of 30 μmol/L to obtain solution 1a. In a separate container, LaCl ₃ was dissolved in buffer 1 at a concentration of 3 mmol/L to obtain solution 1b. Next, solution 1c was obtained by adding solution 1b to solution 1a so that the compound (G-1) and LaCl ₃ were in the same molar amount. Ultraviolet-visible absorption spectroscopy was performed before and after the addition of solution 1a and solution 1c, and a peak with a maximum absorption wavelength of 390 nm appeared with the addition of LaCl ₃ . This confirmed the formation of a La complex.

Example 8
<Metal Retention Power of La Complex of Compound (G-1)>
To the above solution 1c was added 1 equivalent of ethylenediaminetetraacetic acid (hereinafter referred to as EDTA) relative to compound (G-1), and UV-visible absorption spectrum analysis was performed before and after the addition. From the amount of change in absorption intensity at 390 nm, which is the maximum absorption wavelength, it was confirmed that 96% of the La complex of compound (G-1) remained. Subsequently, EDTA was added to this solution so that the total amount of EDTA added was 10 equivalents relative to compound (G-1). Ultraviolet-visible absorption spectrum analysis was performed, and it was confirmed that 91% of the La complex of compound (G-1) remained by the same analysis method as when 1 equivalent of EDTA was added.

Example 9
<La complex synthesis of compound (G-5)>
The same operation as in Example 7 was performed except that compound (G-1) in Example ₇ was changed to compound (G-5). Appeared. This confirmed the formation of a La complex.

Example 10
<Metal Retention Power of La Complex of Compound (G-5)>
The same operation as in Example 8 was performed except that compound (G-1) in Example 8 was changed to compound (G-5), and 1 equivalent of EDTA was added to compound (G-5). , confirmed that 92% of the La complex of the compound (G-5) remained. Subsequently, EDTA was added to this solution, and the total amount of EDTA added was 10 equivalents relative to compound (G-5), and 63% of the La complex of compound (G-5) remained. It was confirmed.

Example 11
<La Complex Synthesis of Compound (G-6)>
The same operation as in Example 7 was performed except that compound (G-1) in Example ₇ was changed to compound (G-6). Appeared. This confirmed the formation of a La complex.

Example 12
<Metal Retention Power of La Complex of Compound (G-6)>
The same operation as in Example 8 was performed except that compound (G-1) in Example 8 was changed to compound (G-6), and 1 equivalent of EDTA was added to compound (G-6). , confirmed that 80% of the La complex of the compound (G-6) remained. Subsequently, EDTA was added to this solution, and the total amount of EDTA added was 10 equivalents relative to compound (G-6), and 72% of the La complex of compound (G-6) remained. It was confirmed.

Example 13
<La Complex Synthesis of Compound (G-12)>
The same operation as in Example 7 was performed except that compound (G-1) in Example ₇ was changed to compound (G-12). Appeared. This confirmed the formation of a La complex.

Example 14
<Metal Retention Power of La Complex of Compound (G-12)>
The same operation as in Example 8 was performed except that compound (G-1) in Example 8 was changed to compound (G-12), and 1 equivalent of EDTA was added to compound (G-12). , confirmed that 89% of the La complex of the compound (G-12) remained. Subsequently, EDTA was added to this solution, and the total amount of EDTA added was 10 equivalents relative to compound (G-12), and 45% of the La complex of compound (G-12) remained. It was confirmed.

Example 15
<La complex synthesis of compound (G-10)>
The same operation as in Example 7 was performed except that compound (G-1) in Example 7 was changed to compound (G-10), and the maximum absorption wavelength of 250 nm decreased significantly with the addition of LaCl ₃ . bottom. This confirmed the formation of a La complex.

Example 16
<Metal Retention Power of La Complex of Compound (G-10)>
The same operation as in Example 8 was performed except that compound (G-1) in Example 8 was changed to compound (G-10), and 1 equivalent of EDTA was added to compound (G-10). , confirmed that 90% of the La complex of the compound (G-10) remained. Subsequently, EDTA was added to this solution, and the total amount of EDTA added was 10 equivalents relative to compound (G-10), and 83% of the La complex of compound (G-10) remained. It was confirmed.

Example 17
<Zr Complex Synthesis of Compound (G-10)>
As a buffer solution, a 1:1 (volume ratio) mixed solution of 0.1 mol/L sodium acetate aqueous solution and dimethylsulfoxide was prepared (hereinafter referred to as “buffer solution 2”). Compound (G-10) was dissolved in buffer solution 2 at a concentration of 30 μmol/L to prepare solution 2a. In another container, ZrCl ₄ was dissolved in a 0.1 mol/L hydrochloric acid aqueous solution at a concentration of 3 mmol/L to obtain a solution 2b. Next, solution 2c was obtained by adding solution 2b to solution 2a so that the compound (G-10) and ZrCl ₄ were in the same molar amount. Ultraviolet-visible absorption spectroscopy of Solution 2a and Solution 2c revealed an absorption peak at 272 nm with the addition of _ZrCl3 . This confirmed the formation of a Zr complex. Subsequently, the solution 2b was added so that the total amount of ZrCl ₄ to the compound (G-10) was 3 equivalents to the solution 2c, to obtain the solution 2d.

Example 18
<Metal Retention Power of Zr Complex of Compound (G-10)>
To the above solution 2d was added 1 equivalent of ethylenediaminetetraacetic acid (hereinafter referred to as EDTA) relative to compound (G-10), and UV-visible absorption spectrum analysis was performed before and after the addition. The absorption intensity at 272 nm, which is the maximum absorption wavelength, did not decrease. Subsequently, EDTA was added to this solution so that the total amount of EDTA added was 10 equivalents relative to compound (G-10). Ultraviolet-visible absorption spectrum analysis was performed, and since the absorption intensity at 272 nm did not decrease as in the case of adding 1 equivalent of EDTA, it was confirmed that 100% of the Zr complex of compound (G-10) remained. bottom.

Example 19
<Sr Complex Synthesis of Compound (G-6)>
The same operation as in Example 7 was performed except that a 0.01 mol/L HEPES aqueous solution was used as the buffer solution, SrCl ₂ was used as the metal salt, and the concentration of the compound (G-6) was 50 μmol/L. Obtained. A significant decrease in absorbance at 285 nm was observed with the addition of _SrCl2 . This confirmed the formation of an Sr complex.

<Metal Retention Power of Sr Complex of Compound (G-6)>
To the above solution 3a was added 1 equivalent of EDTA with respect to compound (G-6), and UV-visible absorption spectrum analysis was performed before and after the addition. From the absorption intensity change at 285 nm, which is the maximum absorption wavelength, it was confirmed that 50% of the Sr complex of compound (G-6) remained.

Comparative example 1
<Synthesis of La complex of compound (a-2) and its metal retention>

A 0.1 mol/L ammonium acetate aqueous solution was prepared as a buffer (hereinafter referred to as "buffer 4"). 8-Hydroxyquinoline-2-carboxylic acid (compound (HQA)) was dissolved in buffer solution 4 at a concentration of 30 μmol/L to prepare solution 4a. In a separate container, LaCl ₃ was dissolved in buffer 4 at a concentration of 3 mmol/L to obtain solution 4b. Solution 4c was then obtained by adding solution 4b to solution 4a so that the compound (HQA) and LaCl ₃ were in the same molar amount. Ultraviolet-visible absorption spectroscopy was performed before and after the addition of solution 4a and solution 4c, and a peak with a maximum absorption wavelength at 270 nm appeared with the addition of _LaCl3 . This confirmed the formation of a La complex.

To the above solution 4c, 1 equivalent of EDTA was added to the compound (HQA), and UV-visible absorption spectrum analysis was performed before and after the addition. From the amount of change in absorption intensity at 270 nm, which is the maximum absorption wavelength, it was confirmed that only 23% of the La complex of the compound (HQA) remained. Subsequently, EDTA was added to this solution so that the total amount of EDTA added was 10 equivalents relative to the compound (HQA). Ultraviolet-visible absorption spectrum analysis was performed, and it was confirmed by the same analysis method as when adding 1 equivalent of EDTA that no La complex of the compound (HQA) remained.

Comparative example 2
<Synthesis of La complex of compound (PyDA) and its metal retention>

A 0.01 mol / L HEPES aqueous solution was used as a buffer solution, 2,6-pyridinedicarboxylic acid (compound (PyDA)) was used as a compound, and the concentration of the compound (PyDA) at the time of measurement was 200 μmol / L. As in Example 1, the compound (PyDA) was mixed with the same molar amount of LaCl ₃ to obtain the La complex of the compound (PyDA). A peak with a maximum absorption wavelength at 280 nm appeared with the addition of LaCl ₃ . This confirmed the formation of a La complex.

To the above solution, 1 equivalent of EDTA was added to the compound (PyDA), and UV-visible absorption spectroscopy was performed before and after the addition. From the amount of change in absorption intensity at 280 nm, which is the maximum absorption wavelength, it was confirmed that only 22% of the La complex of the compound (PyDA) remained.

From the above results, the compound of the present invention formed a complex with La and retained the metal even when EDTA was added as the third component to the La complex. Since EDTA is a strong chelating agent having four carboxylic acid moieties, it was found that the metal complex of the present invention can stably retain metals even in the presence of a third component that strongly interacts with metals. In addition, the compounds of the present invention are complexes with multivalent metal species including Zr ⁴⁺ which is a tetravalent metal species, La ³⁺ which is a trivalent metal species, and Sr ²⁺ which is a divalent metal species. It was confirmed that it is possible to form Zr ⁴⁺ , La ³⁺ , and Sr ²⁺ are all metal elements whose outermost electron shells have closed-shell structures, and metal elements with such closed-shell structures are generally known to be difficult to form complexes. . Since the compound of the present invention can form a complex with a metal element having a closed-shell structure, it is presumed that it can easily form a complex with many other metal elements that do not have a closed-shell structure.

Claims (6)

A compound represented by the following formula (1).

[In formula (1), n represents an integer of 0 to 6.
Q ¹ , Q ² and Q ³ each independently represent a hydrogen atom, a group selected from group A, a group selected from group B, a group selected from group C or a substituent. However, at least two of Q ¹ , Q ² and Q ³ are groups selected from group A, group B or group C.
When n is 2 or more, multiple ^Q3 's may be the same or different.
(Group A)
Group A is a group consisting of groups represented by the following formulas (A-1), (A-2), (A-3), and (A-4).

(In Formula (A-1), Formula (A-2), Formula (A-3), and Formula (A-4), R ^1a , R ^2a , R ^3a , R ^4a , and R ^5a are each independently represents a hydrogen atom or a substituent.* represents a bond.)
(Group B)
Group B is a group consisting of groups represented by the following formulas (B-1) and (B-2).

(In formulas (B-1) and (B-2), R ^1b , R ^2b and R ^3b each independently represent a hydrogen atom or a substituent. * represents a bond.)
(Group C)
Group C is represented by the following formula (C-1), formula (C-2), formula (C-3), formula (C-4), formula (C-5), and formula (C-6) It is a group consisting of the group

(In formula (C-1), formula (C-2), formula (C-3), formula (C-4), formula (C-5), and formula (C-6), R ^1c , R ^2c , R ^3c , R ^4c , R ^5c and R ^6c each independently represent a hydrogen atom or a substituent, and * represents a bond.)
Y represents a nitrogen atom or a hydrocarbon group optionally having a substituent.
When n is 2 or more, multiple Y's may be the same or different.
Z ¹ represents a single bond, -C(=O)-, or an optionally substituted methylene group or a hydrocarbylene group having at least two -CH ₂ -, and at least two Part or all of -CH ₂ - in a group having -CH ₂ - may be -O-, -C(=O)-, -NHC(=O)-, or -C(=O)NH- may be substituted.
Z ² and Z ³ each independently represent a single bond or a divalent linking group which may have a substituent.
When Q ¹ , Q ² and Q ³ are all groups selected from Group B, Z ¹ , Z ² and Z ³ are divalent groups having -CH ₂ -C(=O)NH- at the ends A linking group, which is linked to Q ¹ , Q ² and Q ³ through the nitrogen atom in -CH ₂ -C(=O)NH-.
When n is 2 or more, multiple Z ² and Z ³ may be the same or different, and Z ¹ and Z ² may combine with each other to form a ring structure. . ] 2. The compound according to claim 1, wherein the compound represented by the formula (1) is a compound represented by the following formula (2).

[In formula (2), Q ¹ , Q ² , Q ³ , Z ¹ , Z ² , Z ³ and n are as defined above. ] 3. The compound according to claim 2, wherein the compound represented by the formula (2) is a compound represented by the following formula (3).

[In Formula (2), Q ¹ , Q ² , Q ³ , Z ¹ , Z ² and Z ³ are as defined above.
_n1 represents 0 or 1; ] 4. The compound according to claim 3, wherein the compound represented by the formula (3) is a compound represented by the following formula (4).

[In Formula (4), Q ¹ , Q ² , Q ³ , and n ₁ are as defined above.
Z ^1A represents a single bond or optionally substituted methylene group or hydrocarbylene group having at least two —CH ₂ —, hydrocarbylene having at least two —CH ₂ — Part or all of -CH ₂ - in the group may be substituted with -O-, -C(=O)-, -NHC(=O)-, or -C(=O)NH- .
Z ^2A and Z ^3A each independently represent a single bond or an optionally substituted hydrocarbylene group, and part or all of —CH ₂ — in the hydrocarbylene group is —O— , -C(=O)-, -NHC(=O)-, or -C(=O)NH-.
When Q ¹ , Q ² and Q ³ are all groups selected from Group B, Z ^1A , Z ^2A and Z ^3A have -CH ₂ - at the ends of -CH ₂ -C(=O)NH- which is attached to Q ¹ , Q ² and Q ³ respectively through the nitrogen atom in —CH ₂ —C(=O)NH—. ] 5. The compound according to claim 4, wherein the compound represented by formula (4) is a compound represented by formula (5A), formula (5B), or formula (5C) below.

[In Formula (5A), Formula (5B), and Formula (5C), R ^1a , R ^2a , R ^4a , R ^5a , R ^1b , R ^3b , R ^1c , R ^2c , R ^4c , R ^5c , R ^6c , Z ^1A , Z ^2A , Z ^3A , and n ₁ are as defined above.
Q ^2A and Q ^3A are each independently a group selected from the group consisting of groups represented by the following formulas (A-2a), (B-2a) and (C-3a).

(In (A-2a), formula (B-2a), and formula (C-3a), a hydrogen atom directly bonded to a carbon atom constituting a ring may be substituted by a substituent. Note that * represents a bond.)] A metal complex comprising a metal element and a ligand derived from the compound according to any one of claims 1 to 5.