WO2022176961A1

WO2022176961A1 - Compound and metal complex

Info

Publication number: WO2022176961A1
Application number: PCT/JP2022/006471
Authority: WO
Inventors: 憲史小林; 伸能古志野
Original assignee: 住友化学株式会社
Priority date: 2021-02-19
Filing date: 2022-02-17
Publication date: 2022-08-25
Also published as: JP2024045789A

Abstract

Disclosed is a compound represented by formula (1). In formula (1), n represents an integer of 0-5. Q¹, Q², Q³, and Q⁴ represent a moiety selected from group A, a moiety selected from group B, a moiety represented by formula (C1), or the like. One or more of Q¹, Q², Q³, and Q⁴ is a moiety selected from group A, one or more of Q¹, Q², Q³, and Q⁴ is a moiety selected from group B, and three or more of Q¹, Q², Q³, and Q⁴ are moieties selected from group A, moieties selected from group B, or moieties represented by formula (C1). Group A is a group comprising moieties and the like represented by formula (A1). Group B is a group comprising moieties and the like represented by formula (B1). Z¹, Z², Z³, and Z⁴ represent a single bond or a divalent linking moiety. R represents a divalent linking moiety.

Description

compounds and metal complexes

The present invention relates to compounds and metal complexes.

Compounds capable of 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

An object of the present invention is to provide a compound capable of forming a complex with a plurality of metal species. Another main 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, compounds having a partial structure containing an 8-hydroxyquinoline derivative and a partial structure containing any of carboxylic acid, phosphonic acid, hydroxyl group, or hydroxamic acid can form a complex with a plurality of metal species, leading to the completion of the present invention.

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 5.
Q ¹ , Q ² , Q ³ , and Q ⁴ each independently represent a hydrogen atom, a group selected from Group A, a group selected from Group B, a group represented by formula (C1), or a substituent . provided that at least one of Q ¹ , Q ² , Q ³ and Q ⁴ is a group selected from group A, and at least one of Q ¹ , Q ² , Q ³ and Q ⁴ is from group B a group selected, and at least three of Q ¹ , Q ² , Q ³ , and Q ⁴ are a group selected from group A, a group selected from group B, or a group represented by formula (C1) .
When n is 2 or more, multiple Q ⁴ may be the same or different, and Q ² and Q ³ are bonded to each other or via a divalent linking group to form a ring It may form a structure.
Group A is a group consisting of groups represented by the following formulas (A1), (A2), (A3), (A4), (A5), and (A6).

(In Formula (A1), Formula (A2), Formula (A3), Formula (A4), Formula (A5), and Formula (A6), R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ each independently represents a hydrogen atom, a group represented by formula (C1), or a substituent (* represents a bond).
Group B is a group consisting of groups represented by the following formulas (B1) and (B2).

(In formula (B1), Q ^B1 represents a group represented by formula (C1) or a divalent heterocyclic group which may have a substituent, and X ¹ is a carbon atom or P(OH ), where * represents a bond.)

(In formula (B2), Q ^B2 represents a divalent nitrogen atom-containing monocyclic heterocyclic group that may have a group or substituent represented by formula (C1). Note that * represents a bond.)

(In formula (C1), n2 represents an integer of 1 to 5. L ¹⁰ represents a single bond or a divalent linking group which may have a substituent. R ¹⁶ represents a hydrogen atom or a substituted R ¹⁶ may be combined with any L ¹⁰ to form a ring structure, X ¹⁰ represents -N(OH)C(=O)-, and -N(OH)C (=O)- may be bonded to adjacent groups in any direction, and when n2 is 2 or more, L ¹⁰ present in plurality may be the same or different. ³⁰ represents a single bond or a divalent linking group which may have a substituent (* represents a bond).
Z ¹ , Z ² , Z ³ and Z ⁴ each independently represent a single bond or a divalent linking group which may have a substituent.
When n is 2 or more, multiple Z ⁴ may be the same or different.
R represents a divalent linking group which may have a substituent.
When n is 2 or more, multiple R's may be the same or different. ]

The compound represented by formula (1) is preferably a compound represented by formula (1A) below, a compound represented by formula (1B) below, or a compound represented by formula (1C) below.

[In Formula (1A), Q ¹ , Q ² , Q ³ , Q ⁴ , Z ¹ , Z ² , Z ³ , Z ⁴ and R are as defined above. ]

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

[In Formula (1C), Q ¹ , Q ² , Q ³ , Q ⁴ , Z ¹ , Z ² , Z ³ , Z ⁴ and R are as defined above.
n1 represents an integer of 2-5. ]

The compound represented by the formula (1A) is preferably a compound represented by the following formula (1Aa) or a compound represented by the following formula (1Ab).

[In the formula (1Aa), Q ¹ , Q ² , Q ³ and Q ⁴ have the same meanings as described above.
R ^a represents an optionally substituted hydrocarbylene group, and a portion of —CH ₂ — in the hydrocarbylene group may be substituted with —O—.
Z ^1a , Z ^2a , Z ^3a and Z ^4a each independently represents a single bond or an optionally substituted hydrocarbylene group, and is part of —CH ₂ — in the hydrocarbylene group is optionally substituted with -O-, -C(=O)-, -NHC(=O)-, or -C(=O)NH-. ]

[In Formula (1Ab), Q ¹ , Q ² , Q ³ and Q ⁴ are as defined above.
R ^b is a divalent linking group having a heterocyclic ring, and the linking group may have a substituent.
Z ^1b , Z ^2b , Z ^3b and Z ^4b each independently represents a single bond or an optionally substituted hydrocarbylene group, and is part of —CH ₂ — in the hydrocarbylene group is optionally substituted with -O-, -C(=O)-, -NHC(=O)-, or -C(=O)NH-.
with the proviso that at least one of Z ^1b , Z ^2b , Z ^3b and Z ^4b is such that a portion of —CH ₂ — in the hydrocarbylene group is —O—, —C(=O)—, —NHC( =O)- or a hydrocarbylene group substituted with -C(=O)NH-. The hydrocarbylene group may have a substituent. ]

The group represented by formula (B1) is preferably a compound represented by the following formula (10a), formula (10b), formula (10c), or formula (11) directly to a carbon atom constituting the ring. It is a group from which one bonding hydrogen atom has been removed.

[In formulas (10a) to (10c), R ^7a , R ^8a , R ^9a , R ^7b , R ^8b , R ^9b , R ^7c , R ^8c , and R ^9c each independently represent a hydrogen atom, ) represents a group or a substituent.
However, at least one of R ^7a , R ^8a and R ^9a is a hydrogen atom. At least one of R ^7b , R ^8b and R ^9b is a hydrogen atom. At least one of R ^7c , R ^8c and R ^9c is a hydrogen atom.
^X2 represents a nitrogen atom or ^CR10a .
Each R ^10a independently represents a hydrogen atom, a group represented by formula (C1), or a substituent. ]

[In formula (11), R ¹¹ represents a hydrogen atom, a group represented by formula (C1), or a substituent.
X ³ and X ⁴ each independently represent CR ¹² , N, NR ¹³ , S or O; R ¹² and R ¹³ each independently represent a hydrogen atom, a group represented by formula (C1), or a substituent. When multiple R ¹² and R ¹³ are present, they may be the same or different.
In formula (11), each bond indicated by a double line consisting of a solid line and a broken line is arbitrarily selected from the group consisting of a single bond and a double bond. ]

The group represented by the formula (B2) is preferably a group obtained by removing one hydrogen atom directly bonded to a carbon atom constituting the ring from the compound represented by the following formula (12).

[In Formula (12), X ⁵ , X ⁶ , X ⁷ and X ⁸ each independently represent N, NR ¹⁴ or CR ¹⁵ ; R ¹⁴ and R ¹⁵ each independently represent a hydrogen atom, a group represented by formula (C1), or a substituent. When multiple R ¹⁴ and R ¹⁵ are present, they may be the same or different.
^X9 represents a carbon atom or a nitrogen atom.
^Q10 represents O, OH, or a hydrogen atom.
In formula (12), each bond indicated by a double line consisting of a solid line and a broken line is arbitrarily selected from the group consisting of a single bond and a double bond. ]

The compound represented by Formula (1) is preferably a compound represented by Formula (2) below.

[In Formula (2), R ² , R ³ , R ⁴ , R ⁵ , Q ² , Q ³ , Q ⁴ , Z ² , Z ³ and Z ⁴ are as defined above.
Z ^1A represents -CH ₂ - or -C(=O)-.
R ^A represents an optionally substituted divalent linking group having 2 to 8 carbon atoms.
-Z ² -Q ² , -Z ³ -Q ³ and -Z ⁴ -Q ⁴ are represented by the following formulas (15a), (15b), (15c), (15d) and (15e) represents a group selected from the group consisting of the represented groups; provided that at least one of -Z ² -Q ² , -Z ³ -Q ³ , and -Z ⁴ -Q ⁴ is a group represented by the following formula (15c), formula (15d), or formula (15e) is.

(In formulas (15a), (15b), (15c), (15d), and (15e), a hydrogen atom directly bonded to a carbon atom constituting the ring is a group or substituent represented by formula (C1) Note that * represents a bond.)]

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

According to the present invention, a compound capable of forming a complex with multiple metal species is provided. The present invention also provides metal complexes having ligands derived from such compounds.

Hereinafter, embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

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").

"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.

"Antigen-affinity structure" 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 (A-1) to (A-12).

In formulas (A-1) to (A-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 (25) 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 (20) 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 cyclooctyne, represented by the following formula (21), or the reaction between a tetrazine group and a terminal alkyne, represented by the following formula (22). be done. Note that * represents a bond.

In addition, 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 a cross-linking agent represented by the following formula (23). 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 (24).

In formula (24), 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". n20 represents an integer of 1 to 10, n21 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 attached to the adjacent group in any direction. good. For example, if the adjacent groups of -C(=O)NR ^e1 - are L ¹ and L ³ , then -L ¹ -C(=O)NR ^e1 -L ³ - may be attached and -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. L ² 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 (A-20) to (A-25). The divalent groups represented by formulas (A-20) to (A-25) may have a substituent. Note that * represents a bond.

n20 is an integer of 1-20, preferably an integer of 1-10, more preferably an integer of 1-6.

n21 is 1 or 2, and n21 is preferably 2 when a cross-linking agent such as the cross-linking agent represented by the above formula (23) is used, and preferably 1 when no cross-linking agent is used.

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 a group represented by the following formula (25) and a group represented by the following formula (26).

In formula (25), L ¹ , L ² and n20 are as defined above. Lk represents the above "crosslinkable site". Note that * represents a bond.

In formula (26), L ¹ , L ² , L ³ , and n20 are as defined above. Lk represents the above "crosslinkable site". Note that * represents a bond.

Substituent C includes, for example, a halogen atom, a hydroxy group, a carboxyl group, an amino group, a sulfonic acid group, a nitro group, a phosphonic acid group, a hydrocarbyl group, a silyl group, a heteroaryl group, an alkyloxy group, an aryloxy group, an aralkyl An oxy group and a silyloxy group are mentioned. Substituent C is preferably a hydroxy 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.

　The 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, the 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, the 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, the 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 the present 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, and Bn represents a benzyl group.

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 description of the group, the number of carbon atoms means the number of carbon atoms excluding the number of carbon atoms of the substituent.

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

[In formula (1), n represents an integer of 0 to 5.
Q ¹ , Q ² , Q ³ , and Q ⁴ each independently represent a hydrogen atom, a group selected from Group A, a group selected from Group B, a group represented by formula (C1), or a substituent . provided that at least one of Q ¹ , Q ² , Q ³ and Q ⁴ is a group selected from group A, and at least one of Q ¹ , Q ² , Q ³ and Q ⁴ is from group B a group selected, and at least three of Q ¹ , Q ² , Q ³ , and Q ⁴ are a group selected from group A, a group selected from group B, or a group represented by formula (C1) . At least three of Q ¹ , Q ² , Q ³ and Q ⁴ are groups selected from Group A or Group B;
When n is 2 or more, multiple Q ⁴ may be the same or different, and Q ² and Q ³ are bonded to each other or via a divalent linking group to form a ring It may form a structure.
Group A is a group consisting of groups represented by the following formulas (A1), (A2), (A3), (A4), (A5), and (A6).

In groups represented by formula (A1), formula (A2), formula (A3), formula (A4), formula (A5), or formula (A6) in group A, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are each independently a hydrogen atom, a group represented by formula (C1), or a substituent. In addition, in the groups represented by formula (A1), formula (A2), formula (A3), formula (A4), formula (A5), or formula (A6), R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ , the total number of hydrogen atoms, groups represented by formula (C1) and substituents is five each. When R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are substituents, the substituents are preferably substituents B or C. In a total of five of R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ , the number of groups represented by formula (C1) and substituents C is preferably 0 to 2. Yes, more preferably 0 or 1. In a total of 5 of R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ , the number of substituents B is preferably 0 or 1. Among five of R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ in total, the number of hydrogen atoms is preferably 4 or 5.

The group selected from Group A is preferably a group selected from the group consisting of groups represented by formula (A1), formula (A2), formula (A3), formula (A4), and formula (A5), A group represented by formula (A1) is preferable.

Groups selected from Group A include, for example, groups represented by the following formulas (AA-1) to (AA-19). The groups represented by formulas (AA-1) to (AA-19) below may have a group represented by formula (C1) or a substituent. Note that * represents a bond, and Sp represents "a structure having affinity with an antigen". Groups selected from Group A are preferably groups represented by formula (AA-1) or formulas (AA-4) to (AA-19).

In the group represented by formula (B1) in group B, X1 is ^a carbon atom or P(OH), preferably a carbon atom.

Q ^B1 is a divalent heterocyclic group optionally having a group represented by formula (C1) or a substituent. Examples of Q ^B1 include heterocyclic compounds such as pyridine, pyrazine, pyrimidine, pyrrole, N-alkylpyrrole, furan, thiophene, thiazole, imidazole, oxazole, benzofuran, benzothiophene, isoquinoline, and quinazoline. Examples include divalent groups in which two hydrogen atoms directly bonded to the constituent carbon atoms are removed. The heterocyclic compound is preferably pyridine, pyrimidine, thiazole or imidazole.

The group represented by formula (B1) in group B is preferably a compound represented by the following formula (10a), formula (10b), formula (10c), or formula (11), and the carbon atoms constituting the ring It is a group excluding one hydrogen atom directly bonded to an atom.

In formula ( ^10a ), X2 is a nitrogen atom or ^CR10a . ^{X2 is preferably CR10a} ^.

R ^7a , R ^8a , R ^9a and R ^10a are each independently a hydrogen atom, a group represented by formula (C1), or a substituent. When R ^7a , R ^8a , R ^9a and R ^10a are substituents, the substituents are preferably substituents B or C. Among R ^7a , R ^8a , R ^9a and R ^10a , the number of groups represented by formula (C1) is preferably 0 or 1, more preferably 0. The number of substituents B in R ^7a , R ^8a , R ^9a and R ^10a is preferably 0 or 1. Among R ^7a , R ^8a , R ^9a and R ^10a , the number of substituents C is preferably 0 or 1, more preferably 0.

The number of hydrogen atoms in R ^7a , R ^8a , R ^9a and R ^10a is preferably 2 to 4.

The group represented by formula (B1) in group B is preferably a group obtained by removing one hydrogen atom from R ^9a of the compound represented by formula (10a), from the viewpoint of improving metal retention.

In formula (10b), R ^7b , R ^8b and R ^9b are each independently a hydrogen atom, a group represented by formula (C1), or a substituent. When R ^7b , R ^8b and R ^9b are substituents, the substituents are preferably substituents B or C. The number of substituents B in R ^7b , R ^8b and R ^9b is preferably 0 or 1.

The number of hydrogen atoms in R ^7b , R ^8b and R ^9b is preferably 2 or 3.

The group represented by formula (B1) in group B is preferably a group obtained by removing one hydrogen atom from R ^9b of the compound represented by formula (10b), from the viewpoint of improving metal retention.

In formula (10c), R ^7c , R ^8c and R ^9c are each independently a hydrogen atom, a group represented by formula (C1), or a substituent. When R ^7c , R ^8c and R ^9c are substituents, the substituents are preferably substituents B or C. Among R ^7c , R ^8c and R ^9c , the number of substituents B is preferably 0 or 1.

The number of hydrogen atoms in R ^7c , R ^8c and R ^9c is preferably 2 or 3.

The group represented by formula (B1) in group B is preferably a group obtained by removing one hydrogen atom from R ^9c of the compound represented by formula (10c), from the viewpoint of improving metal retention.

In formula (11), X ³ and X ⁴ are each independently CR ¹² , N, NR ¹³ , S, or O. ^X3 is preferably ^CR12 . The combination of X3 and ^X4 is preferably a combination in which X3 is O and ^X4 is ^CR12 ^, or a combination ⁱⁿ which ^X3 is ^CR12 and ^X4 is ^NR13 . A compound in which X ³ is O and X ⁴ is CR ¹² is a compound represented by the following formula (11a), and a compound in which X ³ is CR ¹² and X ⁴ is NR ¹³ is a compound represented by the following formula (11b).

R ¹¹ is a hydrogen atom, a group represented by formula (C1), or a substituent. When R ¹¹ is a substituent, the substituent is substituent B or substituent C, preferably substituent C.

R ¹² is a hydrogen atom, a group represented by formula (C1), or a substituent. When R ¹² is a substituent, the substituent is substituent B or substituent C, preferably substituent C.

R ¹³ is a hydrogen atom, a group represented by formula (C1), or a substituent. When R ¹³ is a substituent, the substituent includes, for example, a hydrocarbyl group, a hydroxy group, a heteroaryl group, etc. in the substituent C. Substituents are preferably hydrocarbyl groups.

The group represented by formula (B1) in group B is preferably a group obtained by removing one hydrogen atom from R ¹¹ of the compound represented by formula (11).

The group represented by formula (B1) in group B is more preferably directly bonded to a carbon atom constituting the ring from the compound represented by formula (10a), formula (10b), or formula (10c). A group in which one hydrogen atom has been removed, more preferably a group in which one hydrogen atom directly bonded to a ring-constituting carbon atom has been removed from the compound represented by formula (10a).

Examples of the group represented by formula (B1) in group B include groups represented by formulas (B1-1) to (B1-51) below. Among these, a group obtained by removing one hydrogen atom directly bonded to a carbon atom constituting a ring from a compound represented by formula (10a), formula (10b), or formula (10c) is represented by formula (B1- 1) ~ formula (B1-9), formula (B1-27) ~ formula (B1-29), formula (B1-32) ~ formula (B1-38), formula (B1-42) ~ formula (B1-44 ), and groups represented by (B1-47) to (B1-51), wherein one hydrogen atom directly bonded to a carbon atom constituting the ring is removed from the compound represented by formula (11) The group is represented by formula (B1-18), formula (B1-19), formula (B1-22) to formula (B1-24), formula (B1-30), formula (B1-31), formula (B1-45 ), and a group represented by the formula (B1-46). Note that * represents a bond, and Sp represents "a structure having affinity with an antigen".

The group represented by formula (B2) is preferably a group obtained by removing one hydrogen atom directly bonded to a carbon atom constituting the ring from the compound represented by formula (12) below.

^X5 , ^X6 , ^X7 , and ^X8 are each independently N, ^NR14 , or ^CR15 . When any of ^X5 , X6, ^X7 or ^X8 is N or ^NR14 , the adjacent ^X5 , ^X6 , ^X7 or ^X8 is ^preferably ^CR15 .

0 to 2 arbitrarily selected from X ⁵ , X ⁶ , X ⁷ and X ⁸ are N and NR ¹⁴ . The number of N and NR ¹⁴ is preferably 0 or 1, more preferably 0.

R ¹⁴ and R ¹⁵ each independently represent a hydrogen atom, a group represented by formula (C1), or a substituent. When R ¹⁴ and R ¹⁵ are substituents, the substituents are preferably substituents B or C. Among R ¹⁴ and R ¹⁵ , the number of substituents B is preferably 0 or 1, more preferably 0. Among R ¹⁴ and R ¹⁵ , the number of groups represented by formula (C1) is preferably 0 or 1, more preferably 0.

^X9 is a carbon atom or a nitrogen atom, preferably a nitrogen atom.

^Q10 is O, OH, or a hydrogen atom, preferably O or OH, more preferably O.

The group represented by formula (B2) is preferably a group obtained by removing one hydrogen atom directly bonded to a carbon atom constituting the ring from the compound represented by formula (12) in which X ⁸ is CH. .

Examples of the group represented by formula (B2) in group B include groups represented by formulas (B2-1) to (B2-29) below. Among these, groups obtained by removing one hydrogen atom directly bonded to a carbon atom constituting a ring from the compound represented by formula (12) are represented by formulas (B2-6) to (B1-29). is a group.

The group represented by formula (B2) is preferably represented by formula (B2-6), formula (B2-10), formula (B2-12) to formula (B2-22), formula (B2-24) to formula ( B2-26), or a group represented by formula (B2-29), more preferably formula (B2-6), formula (B2-10), formula (B2-12) to formula (B2-18), formula (B2-24) to formula (B2-26), or a group represented by formula (B2-29), more preferably formula (B2-6), formula (B2-10), formula (B2-16), or a group represented by formula (B2-17). Note that * represents a bond.

In the group represented by formula (C1), n2 is an integer of 1-5, preferably an integer of 1-4, more preferably 2 or 3.

L ¹⁰ represents a single bond or a divalent linking group optionally having a substituent. Examples of L ¹⁰ include the same groups as L ¹ in the groups represented by formulas (25) and (26).

R ¹⁶ is a hydrogen atom or a substituent, preferably a substituent. Substituents on R ¹⁶ include hydrocarbyl groups on Substituent C. Hydrocarbyl groups as R ¹⁶ are preferably alkyl groups in substituent C. R ¹⁶ may combine with any L ¹⁰ to form a ring structure.

X ¹⁰ represents -N(OH)C(=O)-, and -N(OH)C(=O)- may be bonded to the adjacent group in any direction. For example, if the adjacent groups of -N(OH)C(=O)- are L ¹⁰ and R ¹⁶ , they may be attached at -L ¹⁰ -C(=O)NR ^e1 -R ¹⁶ and R ¹⁶ -C(=O)NR ^e1 -L ¹⁰ - may be used for bonding. When n2 is 2 or more, multiple X ¹⁰ may independently bond to adjacent groups in any direction. The group represented by formula (C1) is preferably a group represented by formula (C1a) or a group represented by formula (C1b), more preferably a group represented by formula (C1a). .

In formulas (C1a) and (C1b), n2, L ¹⁰ , R ¹⁶ and L ³⁰ are as defined above.

L ³⁰ represents a single bond or a divalent linking group which may have a substituent. Examples of L ³⁰ are the same as L ³ in the group represented by formula (26).

Examples of the group represented by formula (C1) include groups represented by formulas (C1-1) to (C1-10). Among these, groups in which R ¹⁶ and L ¹⁰ are not bonded to each other to form a ring structure are groups represented by formulas (C1-1) to (C1-7). Among these, the group represented by formula (C1) is preferably a group represented by formula (C1-2), formula (C1-3), or formula (C1-6). Note that * represents a bond, and ^L30 represents a single bond or a divalent linking group which may have a substituent.

Q ¹ , Q ² , Q ³ , and Q ⁴ each independently represent a hydrogen atom, a group selected from Group A, a group selected from Group B, a group represented by formula (C1), or a substituent . However, at least one of Q ¹ , Q ² , Q ³ and Q ⁴ is a group selected from group A. At least one of Q ¹ , Q ² , Q ³ and Q ⁴ is a group selected from group B, preferably a group represented by formula (B1) in group B. At least three of Q ¹ , Q ² , Q ³ and Q ⁴ are groups selected from group A, groups selected from group B, or groups represented by formula (C1). Q ¹ is preferably a group selected from group A. Q ² and Q ³ are preferably groups selected from group B. ^Q4 is preferably a group selected from group A or group B. When n is 2 or more, multiple ^Q4 's may be the same or different, and are preferably the same.

Q ² and Q ³ may be bonded to each other or form a ring structure via a divalent linking group. Examples of divalent linking groups include alkylene groups such as a methylene group, ethylene group, propylene group, butylene group and pentyl group, and pyridylene groups.

In the compound represented by formula (1), the number of groups selected from group A and group B, and n2 in the group represented by formula (C1) in the compound represented by formula (1) is preferably at least 3, more preferably 3 to 8, more preferably the group represented by formula (C1) in the compound represented by formula (1) is not present, or 4 to 7 when the group represented by formula (C1) in the compound represented by formula (1) is present.

The total number of groups selected from Group A is preferably 1 to 3, more preferably 1 or 2.

The total number of groups selected from Group B is preferably 1 to 3, more preferably 2 or 3.

The total number of groups represented by formula (C1) in the compound represented by formula (1) is preferably 0 to 2, more preferably 0 or 1.

R is a divalent linking group that may have a substituent. The substituent is the substituent B or the substituent C, and the number of the substituent B is preferably 0 or 1.

Examples of the divalent linking group for R include an alkylene group, an arylene group, and a heteroarylene group. The divalent linking group may be a group formed by combining these. The divalent linking group is preferably an alkylene group. The number of carbon atoms in R is not particularly limited, but preferably 1 to 18.

The alkylene group for R is a divalent group in which two hydrogen atoms directly bonded to carbon atoms constituting a 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 arylene group in R is a divalent group excluding two hydrogen atoms directly bonded to the carbon atoms constituting the aromatic hydrocarbon. 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 18.

Heteroarylene groups in R are for example heterocyclic groups such as pyridine, pyrazine, pyrimidine, pyrrole, N-alkylpyrrole, furan, thiophene, thiazole, imidazole, oxazole, benzofuran, benzothiophene, isoquinoline, quinazoline, benzimidazole, quinoline. It is a divalent group in which two hydrogen atoms directly bonded to carbon atoms constituting a compound are removed. A heteroarylene group is preferably a pyridylene group. Although the number of carbon atoms in the heteroarylene group is not particularly limited, it is preferably 3 to 18.

The divalent linking group formed by combining an alkylene group, an arylene group, and a heteroarylene group includes a combination in which a phenylene group, a methylene group, and a phenylene group are linked in order, and a combination in which a methylene group, a phenylene group, and a methylene group are linked in order. A combination, a combination in which a pyridylene group, a methylene group, and a pyridylene group are bonded in order, a combination in which a methylene group, a pyridylene group, and a methylene group are bonded in order, and the like can be mentioned.

Z ¹ , Z ² , Z ³ and Z ⁴ each independently represent a single bond or a divalent linking group which may have a substituent. Examples of divalent linking groups include hydrocarbylene groups. Examples of the hydrocarbylene group include those similar to the hydrocarbylene group for L ¹ . The substituent is the substituent B or the substituent C, and the number of the substituent B is preferably 0 or 1. Some of -CH ₂ - in the hydrocarbylene group may be substituted with -O-, -C(=O)-, -NHC(=O)- or -C(=O)NH- good. The substituents are preferably substituents B, hydrocarbyl groups, aryl groups or heteroaryl groups, more preferably substituents B or hydrocarbyl groups.

The compound represented by the formula (1) is preferably a compound represented by the following formula (1A) where n is 1, a compound represented by the following formula (1B) where n is 0, or n is 2 to 6, more preferably a compound represented by the following formula (1A).

The compound represented by formula (1A) is preferably a compound represented by formula (1Aa) below or a compound represented by formula (1Ab) below.

Examples of the hydrocarbylene group for R ^a are the same as the hydrocarbylene group for L ¹ .

Examples of the hydrocarbylene group for Z ^1a , Z ^2a , Z ^3a and Z ^4a are the same as the hydrocarbylene group for L ¹ .

Examples of compounds represented by formula (1Aa) include compounds represented by formulas (1Aa-1) to (1Aa-23) below. In addition, Sp represents "a structure having an affinity for an antigen".

The bivalent linking group having a heterocyclic ring for R ^b is a bivalent linking group having a heteroarylene group. As the heteroarylene group, the same heteroarylene groups as those for L ¹ can be exemplified. The divalent linking group may be a divalent linking group formed by combining different heteroarylene groups, a divalent linking group formed by combining a heteroarylene group and a hydrocarbylene group, or the like. A heteroarylene group is preferably a pyridylene group.

The divalent linking group formed by combining a heteroarylene group and a hydrocarbylene group includes a combination in which two pyridylene groups are directly linked, a combination in which a pyridylene group, a methylene group, and a pyridylene group are linked in order, and a methylene group. , a pyridylene group and a methylene group combined in that order.

Examples of the hydrocarbylene group for Z ^1b , Z ^2b , Z ^3b and Z ^4b are the same as the hydrocarbylene group for L ¹ .

Examples of compounds represented by formula (1Ab) include compounds represented by formulas (1Ab-1) to (1Ab-8) below. In addition, Sp represents "a structure having an affinity for an antigen".

Examples of compounds represented by formula (1B) include compounds represented by formulas (1B-1) to (1B-4) below.

Examples of the compound represented by formula (1C) include compounds represented by formulas (1C-1) to (1C-13) below. A compound having a cyclic structure having a nitrogen atom in the center is a structure in which Q ² and Q ³ are bonded to each other or via a divalent linking group to form a cyclic structure.

Specific examples of the compound represented by formula (1C-10) include compounds represented by the following formulas (1C-10a) and (1C-10b).

Z ^1A is -CH ₂ - or -C(=O)-, preferably -CH ₂ -.

R ^A is an optionally substituted divalent linking group having 2 to 8 carbon atoms. R ^A is preferably an optionally substituted divalent hydrocarbylene group having 2 to 8 carbon atoms. Examples of the hydrocarbylene group for ^RA are the same as the hydrocarbylene group for ^L1 .

-Z ² -Q ² , -Z ³ -Q ³ , and -Z ⁴ -Q ⁴ are represented by formula (15a), formula (15b), formula (15c), formula (15d), and formula (15e). wherein at least one of -Z ² -Q ² , -Z ³ -Q ³ and -Z ⁴ -Q ⁴ is represented by formula (15c), formula (15d), or a group represented by the formula (15e).

-Z ² -Q ² and -Z ³ -Q ³ are preferably groups represented by formula (15c), formula (15d) or formula (15e), more preferably represented by formula (15c) is the base. In this case, -Z ² -Q ² and -Z ³ -Q ³ may be the same or different.

-Z ⁴ -Q ⁴ is preferably a group represented by formula (15a), formula (15b) or (15c).

In formulas (15a), (15b), (15c), (15d), and (15e), a hydrogen atom directly bonded to a carbon atom constituting the ring is represented by a group or substituent represented by formula (C1). may be substituted. The substituent is preferably substituent B or substituent C.

The compound represented by formula (2) preferably has 0 or 1 substituent B, and since it can be used in combination with the "structure having affinity for the antigen", one substituent B It is more preferable to have

Specific examples of the compound represented by formula (1) include compounds represented by formulas (1-1) to (1-46) below. These compounds may have a substituent. In addition, Sp represents "a structure having an affinity for an antigen". The compound represented by formula (1) is preferably a compound represented by formula (2), formula (1-1) to formula (1-4), formula (1-6) to formula (1 -15), compounds represented by formulas (1-26) to (1-34), formula (1-40), or formula (1-43), more preferably formula (1-1) to formula (1-3), formula (1-7), formula (1-10), formula (1-11), formula (1-27), formula (1-29), formula (1-30), formula ( 1-40), or a compound represented by the formula (1-43).

The compound of this embodiment may form a salt by interacting 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 (1-2), one or two protons in the carboxylic acid may move to the vicinity of the nitrogen atom in the ethylenediamine structure or the nitrogen atom in the hydroxyquinoline structure. good.

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

In the compound represented by formula (1), compounds that can be Q ¹ , Q ² , Q ³ and Q ⁴ can be linked to sites that can be Z ¹ , Z ² , Z ³ and Z ⁴ It can be produced by appropriately combining known methods.

^In ^the ^following ^, ^Q ¹ ^_ ^_ ^_ ^_ , Q ² , Q ³ and Q ⁴ are specifically described.

For example, as a method for forming a binding site where Z ^x is —CH ₂ —, as exemplified in the following formula (30), a compound having an aldehyde structure and a compound having an amino group are combined in a solvent such as ethanol. and a method of reacting with a reducing agent such as sodium borohydride after mixing inside.

In addition, as another method for forming a bonding site where Z ^x is —CH ₂ —, compounds having a substituent of CH ₂ Cl or CH ₂ Br structure on the aromatic ring, as exemplified in the following formula (31) and a compound having an amino group in a solvent such as acetonitrile or N,N-dimethylformamide (DMF) in the presence of a base such as sodium carbonate or sodium hydrogen carbonate.

In formula (31), the carboxylic acid is protected with an ester structure in the pyridylcarboxylic acid ester moiety of the resulting compound. An ester site can be derived into a carboxylic acid by deprotecting it by performing a generally known de-esterification reaction or the like.

In formula (31), for example, phenol can be derived by protecting the OH site of phenol by benzylation and then debenzylating and deprotecting it. Thus, when 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.

As a method for forming a binding site where Z ^x is -C(=O)-, a compound having a carboxylic acid structure and a compound having an amino group are known to be used, as exemplified in the following formula (32). and mixing in a solvent such as DMF using a condensing agent.

As a method for forming a binding site where Z ^x is -NHC(=O)(CH ₂ )-, compounds having a carboxylic acid structure and compounds having an amino group are exemplified in the following formula (33). are mixed in a solvent such as toluene or dichloromethane using a known carboxylic acid site activator such as oxalyl chloride.

As a method for forming a bonding site where Z ^x is represented by -C(=O)NH(CH ₂ )-, as exemplified by the following formula (34), a compound having a carboxylic acid structure and a compound having an amino group compound in a solvent such as toluene or dichloromethane using a known carboxylic acid site activator such as oxalyl chloride. The structural difference between the compound obtained by the formula (33) and the compound obtained by the formula (34) is the -C(=O)- and -NH- sites of -C(=O)NH(CH ₂ )- The difference is the position of

The compound represented by the formula (1) can be obtained by combining known techniques such as the methods of forming the binding sites exemplified by the above formulas (30) to (34). A compound having a carboxylic acid structure and a compound having an amino group, which are examples of starting materials in each reaction, are also produced by appropriately combining methods for synthesizing known carboxylic acid derivatives and amino compound derivatives. can do.

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 methods.

For example, as a method for producing a compound in which the substituent B has an NSC structure (group represented by formula (A-1)), as exemplified in the following formula (35), ), a compound having a nitro group is used as a diamine compound to synthesize an intermediate product. Subsequently, the nitro moiety is converted to an amine in a solvent such as ethanol by a common reducing agent such as using palladium and hydrogen, and then mixed with thiophosgene in a solvent such as chloroform to obtain formula (A-1 ) can be prepared.

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

In the metal complex of this embodiment, the metal element interacts with the above compound. More specifically, the heteroatom and metal element in the compound interact with each other, and interact with the nitrogen atom and/or oxygen atom in the hydroxyquinoline ring in the compound represented by formula (1). there is 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 8 to 10. The compound of the present embodiment can three-dimensionally exhibit the above 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.

The metal element may be an uncharged or charged ion, preferably a charged ion. 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 counter ion for making 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.

Specific examples of the metal complexes of the present embodiment include metal complexes represented by formulas (K-1) to (K-46). The metal complex preferably has formulas (K-1) to (K-4), formulas (K-6) to (K-15), formulas (K-26) to (K-34), formulas (K-40), or a metal complex represented by formula (K-43), more preferably formula (K-1) to formula (K-3), formula (K-7), formula (K-10) ), formula (K-11), formula (K-27), formula (K-29), formula (K-30), formula (K-40), or a metal complex represented by formula (K-43) is.

In the formula, M represents a metal element. Dashed lines between M and heteroatoms represent possible interactions. Note that dashed lines between M and heteroatoms are for convenience and do not necessarily mean that interactions exist on all dashed lines. 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 imparting agent is preferably carried out in a solvent (that is, 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 imparting agent, and the like.

When isolating and purifying a metal complex, as a purification method after the reaction, an optimal means can be appropriately selected 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.

In addition, since the reaction between a compound and a metal imparting agent is usually a quantitative reaction, a metal complex with a relatively high purity can be obtained in a solution state without special isolation and purification operations.

A metal complex having a substituent A can be obtained by reacting a compound having a substituent A with a metal-donating agent, and a compound having a substituent B is reacted with a metal-donating agent to form a complex. , can also be obtained by performing a binding reaction between a “structure having affinity for an antigen” and a “crosslinkable site” exemplified in formulas (20) to (22) above.

[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 the present embodiment have high metal retention and can form complexes with metals at very low concentrations. 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.

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

The structure of the compound was confirmed by known methods such as nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS).

In the following 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 (a-2)>

The compound (a-2) was prepared according to the non-patent document The Journal of the American Chemical Society, 2018, Vol. 140, p. 15487-15500.

Example 1
<Synthesis of compound (compound (1-2))>

After making the inside of the reaction vessel a nitrogen gas atmosphere, compound (a-2) 121 mg (0.323 mmol), methyl-6-bromomethyl-2-pyridinecarboxylate 163 mg (0.710 mmol), sodium hydrogen carbonate 163 mg (1.94 mmol). ) and 16.1 mL of acetonitrile were added, and the mixture was heated to 80° C. and stirred for 12 hours while refluxing. It was cooled to room temperature (in this specification, room temperature means 25° C.) and the acetonitrile was concentrated to give a crude product. This crude product was purified by gel filtration column chromatography using chloroform as the developing phase, concentrated and dried under reduced pressure to obtain compound (a-3).

79.0 mg (0.117 mmol) of compound (a-3) and 0.78 mL of 6N hydrochloric acid were added to a reaction vessel, and the mixture was heated to 100°C and stirred for 4 hours while refluxing. After the reaction solution was cooled to room temperature, the deposited yellow precipitate was separated by filtration and dried under reduced pressure to obtain compound (1-2) with a yield of 95%. Identification data of the obtained compound (1-2) are shown below.

¹ H-NMR (300 MHz, DMSO-d ₆ ): δ (ppm) = 4.03 (s, 4H), 4.68 (s, 4H), 4.89 (s, 4H), 7.17 (dd , J=7.5 and 1.2 Hz, 2H), 7.40 (dd, J=8.4 and 1.2 Hz, 2H), 7.50 (d, J=7.5 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.79 (dd, J = 8.7 and 4.5 Hz, 2H), 7.87 (d, J = 4.5 Hz, 2H), 7.88 (d, J = 7 .5 Hz, 2 H), 8.36 (d, J=8.7 Hz, 2 H).

Synthesis example 2
<Synthesis of compound (a-6)>

After setting the inside of the reaction vessel to a nitrogen gas atmosphere, 294 mg (1.12 mmol) of 8-(benzyloxy)quinoline-2-carbaldehyde, 336 mg (5.58 mmol) of ethylenediamine, and 11.2 mL of methanol were added and refluxed at 64°C. and stirred for 2 hours. After slowly cooling the reaction vessel to room temperature, 63.0 mg (1.68 mmol) of sodium borohydride was added. After further stirring for 2 hours, 22.3 mL of a saturated sodium bicarbonate aqueous solution was added to terminate the reaction, and the mixture was separated and extracted with chloroform. The chloroform layer was concentrated and dried under reduced pressure to obtain a crude product of compound (a-5).

After making the inside of the reaction vessel a nitrogen gas atmosphere, compound (a-5) 156 mg (0.506 mmol), methyl-6-bromomethyl-2-pyridinecarboxylate 388 mg (1.69 mmol), potassium carbonate 280 mg (2.02 mmol). , and 16.9 mL of acetonitrile was added, and the mixture was heated to 80° C. and stirred for 12 hours while refluxing. It was cooled to room temperature and the acetonitrile was concentrated to give crude product. This crude product was purified by gel filtration column chromatography using chloroform as the developing phase, concentrated and dried under reduced pressure to obtain compound (a-6) with a two-step yield of 58%.

Example 2
<Synthesis of compound (compound (1-1))>

90.9 mg (0.120 mmol) of compound (a-6) and 1.99 mL of 6N hydrochloric acid were added to a reaction vessel, and the mixture was heated to 100°C and stirred for 24 hours while refluxing. The reaction solution was concentrated and dried under reduced pressure to obtain compound (1-1) with a yield of 61%. Identification data of the obtained compound (1-1) are shown below.

¹ H-NMR (300 MHz, D ₂ O): δ (ppm) = 3.53 (t, J = 5.7 Hz, 2H), 3.82 (t, J = 5.7 Hz, 2H), 4.25 (s, 2H) 4.46 (s, 2H) 4.67 (s, 4H), 7.25 (dd, J = 7.8 and 0.9 Hz, 1H), 7.49 (dt, J = 7.5 and 1 .2Hz, 3H), 7.61 (t, J = 7.8Hz, 1H), 7.68 (dd, J = 7.8 and 0.9Hz, 1H), 7.74 (d, J = 8.4Hz, 1H), 7.77-7.82 (m, 3H), 7.83-7.88 (m, 2H), 7.96 (t, J = 7.8Hz, 1H), 8.60 (d, J=8.4Hz, 1H).

Synthesis example 3
<Synthesis of compound (compound (a-7))>

After dissolving 77.0 mg (0.115 mmol) of compound (a-3) in 1.00 g (16.7 mmol) of acetic acid, 10.3 mg (0.149 mmol) of sodium nitrite was added at room temperature and stirred for 10 minutes. A nitroso derivative reaction solution was obtained. In a separate container, 1.61 g (19.2 mmol) of sodium hydrogencarbonate and 598 mg (3.43 mmol) of sodium hyposulfite were added and dissolved in 24.0 mL of water, and the above nitroso derivative reaction solution was added dropwise thereto. After foaming subsided, a brown precipitate was collected by filtration, and the filtrate was washed with 50 mL of water to obtain a brown powder. The resulting brown powder was dissolved in 1.5 mL of chloroform, added to 8.0 g of diethyl ether, the brown precipitate generated was removed by filtration, and the filtrate was evaporated to remove the solvent and dried. was dissolved in 120 mg of chloroform and added dropwise to a mixture of 3.0 g of heptane and 3.0 g of diethyl ether. obtained at 9.1%. Identification data of the obtained compound (a-7) are shown below.

¹ H-NMR (300 MHz, CDCl ₃ ): δ (ppm) = 3.82 (brs, 4H), 3.93 (brs, 8H), 3.97 (s, 6H), 6.73 (d, J = 8.1Hz, 1H), 6.98 (d, J = 8.1Hz, 1H), 7.13-7.16 (m, 1H), 7.24-7.27 (m, 1H), 7 .38-7.47 (m, 3H), 7.63-7.66 (m, 4H), 7.90-8.00 (m, 4H).

Synthesis example 4
<Synthesis of compound (compound (a-8))>

To 2.40 mg (3.49 μmol) of compound (a-7) was added 0.60 mL of heavy chloroform in which 0.81 mg (3.49 μmol) of di-2-pyridyl thionocarbonate was dissolved at room temperature, and the mixture was stirred for 2 hours. The reaction mixture was concentrated, the yellow solid residue was washed with diethyl ether and water, and the remaining residue was dried under reduced pressure to obtain a yellow powder compound (a-8) with a yield of 86%. Identification data of the obtained compound (a-8) are shown below.

¹ H-NMR (300 MHz, THF-d ₈ ): δ (ppm) = 2.88 (s, 4H), 3.84-3.85 (br, 6H), 3.88-3.90 (br, 4H), 3.96-3.99 (br, 4H), 7.00-7.06 (m, 2H), 7.23-7.89 (m, 11H), 8.03 (d, J = 8.7 Hz, 1 H), 8.22 (d, J=8.7 Hz, 1 H).

Reference example 1
<Method for Synthesizing Compound (Compound (1-40))>

Compound (a-7) is subjected to a deprotection reaction of the methyl ester moiety generally known in the field of synthetic organic chemistry to synthesize compound (a-9) in which the methyl ester moiety is a carboxylic acid. be able to. Specific examples of the deprotection reaction of the methyl ester moiety include the method of mixing sodium hydroxide in a mixed solvent of water and tetrahydrofuran, the method described in Example 3 below, and the like. Further, compound (1-40) can be synthesized by subjecting compound (a-9) to an isothiocyanation reaction of an amine moiety, which is generally known in the field of synthetic organic chemistry. Specific examples of the isothiocyanate conversion reaction of the amine site include the method of mixing thiophosgene in a dichloromethane solvent, the method described in Synthesis Example 4 above, and the like.

Synthesis example 5
<Synthesis of compound (compound (a-11))>

1.70 mg (2.33 μmol) of compound (a-8) was dissolved in 520 mg of heavy tetrahydrofuran, and 1.22 mg (1.86 μmol) of compound (a-10) (reagent purchased from Sigma-Aldrich) and 0 triethylamine were dissolved at room temperature. 35.7 mg of heavy water mixed with 21 mg (2.10 μmol) was added and stirred for 4 days. The solvent was distilled off from the reaction solution, and the residue was washed with water. The pale-yellow residue was dissolved in 520 mg of heavy tetrahydrofuran, and 74.0 mg of heavy water obtained by mixing 1.00 mg (1.52 μmol) of compound (a-10) and 0.17 mg (1.68 μmol) of triethylamine was added at room temperature. Stirred for an hour. The solvent was distilled off from the reaction solution, and the residue was suspended in water and filtered. The filtrate was dried under reduced pressure to obtain compound (a-11) as a yellow solid with a yield of 67%. The formation of the resulting compound (a-11) was confirmed by mass spectrometry as described below.

HRMS (ESI) m/z ₍ M+H) ⁺ calcd for _{C64H84N13O14S} : _1290.6 , found: _1290.7 .

Example 3
<Synthesis of compound (compound (1-43))>

2.00 mg (1.55 μmol) of compound (a-11) was dissolved in a mixture of 250 mg of heavy THF and 318 mg of heavy water, and ice-cooled to 0°C. To this yellow solution was added 54.8 mg of heavy water containing 0.520 mg (12.4 μmol) of lithium hydroxide monohydrate. The solution turned orange immediately after the addition. Five minutes after the addition, the reaction was allowed to warm to room temperature. When the mixture was stirred for 40 minutes after the addition, 50.2 mg of heavy water containing 12.1 μmol of hydrogen chloride was added to obtain a pale orange homogeneous solution with a pH of 7-8. After distilling off the solvent, the residue was washed with water, and the remaining residue was dried under reduced pressure to obtain compound (1-43) as a pale brown solid with a yield of 54%.

Comparison of the ¹ H-NMR (300 MHz, THF-d ₈ /D ₂ O) measurement results of the solution before and after the reaction of compound (a-11) revealed that 3 The peak assigned to the methyl group of the ester site (methyl group of -C(=O)OCH ₃ site) 6H observed at 0.82 ppm disappeared in ¹ H-NMR after the reaction. From the above measurement results, it was determined that compound (1-43) was obtained.

Example 4
<La complex synthesis of compound (1-2)>
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 (1-2) was dissolved in buffer solution 1 at a concentration of 30 μmol/L to prepare solution 1A. In a separate container, LaCl ₃ was dissolved in buffer 1 at a concentration of 3 mmol/L to prepare solution 2. Then, Solution 2 was added to Solution 1A so that the compound (1-2) and LaCl ₃ were in the same molar amount to obtain Solution 3A. Ultraviolet-visible absorption spectroscopy was carried out before and after the addition of solution 2, and a peak with a maximum absorption wavelength of 264 nm appeared with the addition of LaCl ₃ . This confirmed the formation of a La complex.

Example 5
<Zr Complex Synthesis of Compound (1-2)>
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 (1-2) was dissolved in buffer solution 2 at a concentration of 30 μmol/L to prepare solution 4A. A solution 5 was prepared by dissolving ZrCl ₄ at a concentration of 3 mmol/L in a 0.1 mol/L hydrochloric acid aqueous solution in another container. Next, solution 6A was obtained by adding solution 5 to solution 4A so that compound (1-2) and ZrCl ₄ were in the same molar amount. Ultraviolet-visible absorption spectroscopy was performed before and after the addition of solution 5, and a shoulder peak at 274 nm appeared with the addition of _ZrCl4 . This confirmed the formation of a Zr complex.

Example 6
<Sr Complex Synthesis of Compound (1-2)>
A 0.01 mol/L HEPES aqueous solution was prepared as a buffer (hereinafter referred to as "buffer 3"). Compound (1-2) was dissolved in buffer solution 3 at a concentration of 50 μmol/L to prepare solution 7A. In a separate container, SrCl ₂ was dissolved in buffer 3 at a concentration of 3 mmol/L to prepare solution 8 . Next, solution 9A was obtained by adding solution 8 to solution 7A so that compound (1-2) and SrCl ₂ were in the same molar amount. Ultraviolet-visible absorption spectrum analysis was performed before and after addition of solution 8, and a peak with a maximum absorption wavelength of 307 nm appeared with the addition of _SrCl2 . This confirmed the formation of an Sr complex.

Example 7
<In Complex Synthesis of Compound (1-2)>
Solution 1A was prepared. In a separate container, InCl ₃ was dissolved in a 0.1 mol/L hydrochloric acid aqueous solution at a concentration of 3 mmol/L to prepare a solution 10 . Next, solution 10 was added to solution 1A so that the compound (1-2) and InCl ₃ were in the same molar amount to obtain solution 11A. Ultraviolet-visible absorption spectroscopy was performed before and after the addition of solution 10, and a peak with a maximum absorption wavelength of 264 nm appeared with the addition of InCl ₃ . This confirmed the formation of an In complex.

Example 8
<Gd Complex Synthesis of Compound (1-2)>
Solution 1A was prepared. In a separate container, GdCl ₃ was dissolved in buffer 1 at a concentration of 3 mmol/L to prepare solution 12 . Next, solution 12 was added to solution 1A so that the compound (1-2) and GdCl ₃ were in the same molar amount to obtain solution 13A. Ultraviolet-visible absorption spectroscopy was performed before and after the addition of solution 12, and a peak with a maximum absorption wavelength of 265 nm appeared with the addition of _GdCl3 . This confirmed the formation of a Gd complex.

Reference example 2
<Metal Retention Power of La Complex of Compound (1-2)>
To the above solution 3A, 10 equivalents of ethylenediaminetetraacetic acid (hereinafter referred to as EDTA) relative to compound (1-2) was added and stirred to dissolve EDTA. Ultraviolet-visible absorption spectroscopy was performed before and after the addition of EDTA. From the absorption intensity change at 264 nm, which is the maximum absorption wavelength, it was confirmed that 90% of the La complex of compound (1-2) remained.

Reference example 3
<Metal Retention Power of Zr Complex of Compound (1-2)>
To the above solution 6A was added 10 equivalents of EDTA relative to compound (1-2), and the mixture was stirred to dissolve EDTA. Ultraviolet-visible absorption spectroscopy was performed before and after the addition of EDTA. From the change in absorption intensity at 274 nm, which is a shoulder peak due to the Zr complex, it was confirmed that 90% of the Zr complex of compound (1-2) remained.

Reference example 4
<Metal Retention Power of Sr Complex of Compound (1-2)>
1 equivalent of EDTA was added to the above solution 9A with respect to compound (1-2), and the mixture was stirred to dissolve the EDTA. Ultraviolet-visible absorption spectroscopy was performed before and after the addition of EDTA. From the change in absorption intensity at 307 nm, which is the maximum absorption wavelength, it was confirmed that 93% of the Sr complex of compound (1-2) remained.

Reference example 5
<Metal Retention Power of In Complex of Compound (1-2)>
To the above solution 11A, 10 equivalents of EDTA was added to compound (1-2) and stirred to dissolve EDTA. Ultraviolet-visible absorption spectroscopy was performed before and after the addition of EDTA. From the change in absorption intensity at 264 nm, which is the maximum absorption wavelength, it was confirmed that 98% of the In complex of compound (1-2) remained.

Reference example 6
<Metal Retention Power of Gd Complex of Compound (1-2)>
To the above solution 13A, 10 equivalents of EDTA was added to compound (1-2) and stirred to dissolve EDTA. Ultraviolet-visible absorption spectroscopy was performed before and after the addition of EDTA. From the absorption intensity change at 265 nm, which is the maximum absorption wavelength, it was confirmed that 85% of the Gd complex of compound (1-2) remained.

Example 9
<La complex synthesis of compound (1-1)>
Solution 1B was prepared using compound (1-1) instead of compound (1-2) used in Example 4 above. Solution 3B was obtained in the same manner as in Example 4 except that Solution 1A was changed to Solution 1B. Ultraviolet-visible absorption spectroscopy was performed before and after the addition of solution 2, and a peak with a maximum absorption wavelength at 267 nm appeared with the addition of LaCl ₃ . This confirmed the formation of a La complex.

Example 10
<Zr Complex Synthesis of Compound (1-1)>
Solution 4B was prepared using compound (1-1) instead of compound (1-2) used in Example 5 above. Solution 6B was obtained in the same manner as in Example 5 except that Solution 4A was changed to Solution 4B. Ultraviolet-visible absorption spectrum analysis was performed before and after addition of solution 5, and a peak with a maximum absorption wavelength of 265 nm appeared with the addition of _ZrCl4 . This confirmed the formation of a Zr complex.

Example 11
<Sr Complex Synthesis of Compound (1-1)>
Solution 7B was prepared using compound (1-1) instead of compound (1-2) used in Example 6 above. Solution 9B was obtained in the same manner as in Example 6, except that solution 7A was changed to solution 7B. Ultraviolet-visible absorption spectroscopy was performed before and after the addition of Solution 8, and a shoulder peak at 282 nm appeared with the addition of _SrCl2 . This confirmed the formation of an Sr complex.

Reference example 7
<Metal Retention Power of La Complex of Compound (1-1)>
The same operation as in Reference Example 2 was performed, except that 10 equivalents of EDTA with respect to compound (1-1) was added to the above solution 3B. From the absorption intensity change at 267 nm, which is the maximum absorption wavelength, it was confirmed that 93% of the La complex of compound (1-1) remained.

Reference example 8
<Metal Retention Power of Zr Complex of Compound (1-1)>
The same operation as in Reference Example 3 was performed, except that 10 equivalents of EDTA relative to compound (1-1) was added to the above solution 6B. From the change in absorption intensity at 265 nm, which is the maximum absorption wavelength, it was confirmed that 80% of the Zr complex of compound (1-1) remained.

Reference example 9
<Metal Retention Power of Sr Complex of Compound (1-1)>
The same operation as in Reference Example 4 was performed, except that 1 equivalent of EDTA relative to compound (1-1) was added to the above solution 9B. From the change in absorption intensity at 282 nm, which is a shoulder peak due to the Sr complex, it was confirmed that 96% of the Sr complex of compound (1-1) remained.

Example 12
<La Complex Synthesis of Compound (1-43)>
Solution 1C was prepared using compound (1-43) in place of compound (1-2) used in Example 4 above. Solution 3C was obtained in the same manner as in Example 4 except that Solution 1A was changed to Solution 1C. Ultraviolet-visible absorption spectroscopy was performed before and after the addition of solution 2, and a peak with a maximum absorption wavelength at 271 nm appeared with the addition of _LaCl3 . This confirmed the formation of a La complex.

Reference example 8
<Metal Retention Power of La Complex of Compound (1-43)>
The same procedure as in Reference Example 2 was performed, except that 10 equivalents of EDTA relative to compound (1-43) was added to solution 3C. From the change in absorption intensity at 271 nm, which is the maximum absorption wavelength, it was confirmed that 82% of the La complex of compound (1-43) remained.

Comparative example 1
<Synthesis of La complex of compound (a-2) and its metal retention>
Compound (a-2) was dissolved in buffer solution 3 at a concentration of 50 μmol/L to prepare solution 1a. A solution 3a was obtained in the same manner as in Example 4 except that the solution 1A was changed to the solution 1a. Ultraviolet-visible absorption spectroscopy was performed before and after addition of Solution 2, and a peak with a maximum absorption wavelength of 360 nm appeared with the addition of LaCl ₃ . This confirmed the formation of a La complex. To solution 3a, 1 equivalent of EDTA relative to compound (a-2) was added, and ultraviolet-visible absorption spectrum analysis was performed before and after the addition. Absorption at 360 nm, which is the maximum absorption wavelength, completely disappeared, confirming that the La complex of compound (a-2) did not remain.

Comparative example 2
<Study on Synthesis of Sr Complex of Compound (a-2)>
Solution 7a was prepared using compound (a-2) instead of compound (1-2). The same operation as in Example 6 was performed except that solution 7A was changed to solution 7a. Ultraviolet-visible absorption spectrum analysis was performed before and after addition of solution 8, and no change was observed in the ultraviolet-visible absorption spectrum, and formation of an Sr complex was not confirmed.

From the above results, the compound of the present invention is effective against a plurality of 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 a complex. 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. Furthermore, the metal complexes of the present invention retained the metal even when EDTA was added to the complex. Since EDTA is a strong chelating agent having four carboxylic acid sites, it was found that the metal complex of the present invention can stably retain a metal even when a substance that interacts with the metal coexists.

Claims

A compound represented by the following formula (1).

[In formula (1), n represents an integer of 0 to 5.
Q 1 , Q 2 , Q 3 , and Q 4 each independently represent a hydrogen atom, a group selected from Group A, a group selected from Group B, a group represented by formula (C1), or a substituent . provided that at least one of Q 1 , Q 2 , Q 3 and Q 4 is a group selected from group A, and at least one of Q 1 , Q 2 , Q 3 and Q 4 is from group B a group selected, and at least three of Q 1 , Q 2 , Q 3 , and Q 4 are a group selected from group A, a group selected from group B, or a group represented by formula (C1) .
When n is 2 or more, multiple Q 4 may be the same or different, and Q 2 and Q 3 are bonded to each other or via a divalent linking group to form a ring It may form a structure.
Group A is a group consisting of groups represented by the following formulas (A1), (A2), (A3), (A4), (A5), and (A6).

(In Formula (A1), Formula (A2), Formula (A3), Formula (A4), Formula (A5), and Formula (A6), R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 each independently represents a hydrogen atom, a group represented by formula (C1), or a substituent (* represents a bond).
Group B is a group consisting of groups represented by the following formulas (B1) and (B2).

(In formula (B1), Q B1 represents a group represented by formula (C1) or a divalent heterocyclic group which may have a substituent, and X 1 is a carbon atom or P(OH ), where * represents a bond.)

(In formula (B2), Q B2 represents a divalent nitrogen atom-containing monocyclic heterocyclic group that may have a group or substituent represented by formula (C1). Note that * represents a bond.)

(In formula (C1), n2 represents an integer of 1 to 5. L 10 represents a single bond or a divalent linking group which may have a substituent. R 16 represents a hydrogen atom or a substituted R 16 may be combined with any L 10 to form a ring structure, X 10 represents -N(OH)C(=O)-, and -N(OH)C (=O)- may be bonded to adjacent groups in any direction, and when n2 is 2 or more, L 10 present in plurality may be the same or different. 30 represents a single bond or a divalent linking group which may have a substituent (* represents a bond).
Z 1 , Z 2 , Z 3 and Z 4 each independently represent a single bond or a divalent linking group which may have a substituent.
When n is 2 or more, multiple Z 4 may be the same or different.
R represents a divalent linking group which may have a substituent.
When n is 2 or more, multiple R's may be the same or different. ]
2. The compound according to claim 1, wherein the compound represented by the formula (1) is a compound represented by the following formula (1A).

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

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

[In Formula (1C), Q 1 , Q 2 , Q 3 , Q 4 , Z 1 , Z 2 , Z 3 , Z 4 and R are as defined above.
n1 represents an integer of 2-5. ]
3. The compound according to claim 2, wherein the compound represented by the formula (1A) is a compound represented by the following formula (1Aa) or a compound represented by the following formula (1Ab).

[In the formula (1Aa), Q 1 , Q 2 , Q 3 and Q 4 have the same meanings as described above.
R a represents an optionally substituted hydrocarbylene group, and a portion of —CH 2 — in the hydrocarbylene group may be substituted with —O—.
Z 1a , Z 2a , Z 3a and Z 4a each independently represents a single bond or an optionally substituted hydrocarbylene group, and is part of —CH 2 — in the hydrocarbylene group is optionally substituted with -O-, -C(=O)-, -NHC(=O)-, or -C(=O)NH-. ]

[In Formula (1Ab), Q 1 , Q 2 , Q 3 and Q 4 are as defined above.
R b is a divalent linking group having a heterocyclic ring, and the linking group may have a substituent.
Z 1b , Z 2b , Z 3b and Z 4b each independently represents a single bond or an optionally substituted hydrocarbylene group, and is part of —CH 2 — in the hydrocarbylene group is optionally substituted with -O-, -C(=O)-, -NHC(=O)-, or -C(=O)NH-.
with the proviso that at least one of Z 1b , Z 2b , Z 3b and Z 4b is such that a portion of —CH 2 — in the hydrocarbylene group is —O—, —C(=O)—, —NHC( =O)- or a hydrocarbylene group substituted with -C(=O)NH-. The hydrocarbylene group may have a substituent. ]
The group represented by the formula (B1) is directly bonded to a carbon atom constituting the ring from the compound represented by the following formula (10a), formula (10b), formula (10c), or formula (11). The compound according to any one of claims 1 to 5, which is a group with one hydrogen atom removed.

[In formulas (10a) to (10c), R 7a , R 8a , R 9a , R 7b , R 8b , R 9b , R 7c , R 8c , and R 9c each independently represent a hydrogen atom, ) represents a group or a substituent.
However, at least one of R 7a , R 8a and R 9a is a hydrogen atom. At least one of R 7b , R 8b and R 9b is a hydrogen atom. At least one of R 7c , R 8c and R 9c is a hydrogen atom.
X2 represents a nitrogen atom or CR10a .
Each R 10a independently represents a hydrogen atom, a group represented by formula (C1), or a substituent. ]

[In formula (11), R 11 represents a hydrogen atom, a group represented by formula (C1), or a substituent.
X 3 and X 4 each independently represent CR 12 , N, NR 13 , S or O; R 12 and R 13 each independently represent a hydrogen atom, a group represented by formula (C1), or a substituent. When multiple R 12 and R 13 are present, they may be the same or different.
In formula (11), each bond indicated by a double line consisting of a solid line and a broken line is arbitrarily selected from the group consisting of a single bond and a double bond. ]
The group of claims 1 to 6, wherein the group represented by the formula (B2) is a group from the compound represented by the following formula (12) excluding one hydrogen atom directly bonded to the carbon atoms constituting the ring. A compound according to any one of clauses.

[In Formula (12), X 5 , X 6 , X 7 and X 8 each independently represent N, NR 14 or CR 15 ; R 14 and R 15 each independently represent a hydrogen atom, a group represented by formula (C1), or a substituent. When multiple R 14 and R 15 are present, they may be the same or different.
X9 represents a carbon atom or a nitrogen atom.
Q10 represents O, OH, or a hydrogen atom.
In formula (12), each bond indicated by a double line consisting of a solid line and a broken line is arbitrarily selected from the group consisting of a single bond and a double bond. ]
The compound according to any one of claims 1 to 7, wherein the compound represented by the formula (1) is a compound represented by the following formula (2).

[In Formula (2), R 2 , R 3 , R 4 , R 5 , Q 2 , Q 3 , Q 4 , Z 2 , Z 3 and Z 4 are as defined above.
Z 1A represents -CH 2 - or -C(=O)-.
R A represents an optionally substituted divalent linking group having 2 to 8 carbon atoms.
-Z 2 -Q 2 , -Z 3 -Q 3 and -Z 4 -Q 4 are represented by the following formulas (15a), (15b), (15c), (15d) and (15e) represents a group selected from the group consisting of the represented groups; provided that at least one of -Z 2 -Q 2 , -Z 3 -Q 3 , and -Z 4 -Q 4 is a group represented by the following formula (15c), formula (15d), or formula (15e) is.

(In formulas (15a), (15b), (15c), (15d), and (15e), a hydrogen atom directly bonded to a carbon atom constituting the ring is a group or substituent represented by formula (C1) Note that * represents a bond.)]
A metal complex having a metal element and a ligand derived from the compound according to any one of claims 1 to 8.