Compound and labeled biological substance using same

Abstract

A compound having two or more phosphor parts having mutually equivalent light absorption characteristics, wherein adjacent phosphor parts are connected via a group including a structure represented by general formula (I), and a labeled biological substance using the compound. In the formula, X1 to X3 represent-O-,-S-, > NR1, or > CR2R3. And each of R1-R3 and R11 represents a hydrogen atom or a substituent. And R8 represents a hydrogen atom or a substituent. And n is an integer of 2 or more. And * represents a connecting bond.

Description

Technical Field

[0001] The present invention relates to a compound and a labeled biological substance using the compound. Background Art

[0002] To observe changes in vivo in response to various stimuli (diseases, environmental changes, etc.), fluorescently labeled biomaterials, in which biomolecules (antibodies, etc.) that bind to target detection substances are labeled with fluorescent compounds (fluorochromes), are often used.

[0003] For example, immunoblotting (hereinafter also referred to as WB) for detecting a specific protein from a protein mixture utilizes a fluorescent method that uses a fluorescently labeled antibody that binds to the protein to detect the presence or amount of the specific protein.

[0004] Furthermore, in bioimaging technology for analyzing the dynamics and functions of biomolecules, cells, and tissues in a living body, biofluorescence imaging for observing specific parts of a living body visualized by fluorescent labeling is used as one of the biological observation technologies.

[0005] Organic fluorescent dye molecules are commonly used in these fluorescent labels. Brightness (fluorescence intensity) is typically increased by using fluorescently labeled biomaterials with multiple fluorescent dye molecules bonded together. However, most fluorescent organic dyes, such as cyanine and rhodamine, contain highly planar aromatic chromophores, which can easily interact with each other after labeling. This results in a decrease in fluorescence intensity due to interactions such as self-association between the labeled dyes. Furthermore, as the number of fluorescent dye molecules per biomolecule (fluorescent labeling ratio: DOL) increases, the fluorescence intensity due to self-association and other factors tends to decrease further.

[0006] Meanwhile, in a field separate from fluorescent labeling, pigment compounds that utilize the FRET (Fluorescence Resonance Energy Transfer) phenomenon are known. Examples of pigment compounds utilizing this FRET phenomenon include those described in Non-Patent Document 1 and Patent Documents 1 to 4, which link a fluorescent portion I (energy donor) that is excited by excitation light and another fluorescent portion II (energy acceptor) that receives energy from the fluorescent portion I and emits or quenches it, via a group containing proline.

[0007] Previous technical literature

[0008] Non-patent literature

[0009] <Non-patent document 1> Nisha Geng, "Synthesis of Polyproline Spacers between NIRDye Pairs for FRET to Enhance Photoacoustic Imaging", Theses, RIT ScholarWorks, July 2017

[0010] Patent Literature

[0011] Patent Document 1: International Publication No. 2010 / 117420

[0012] Patent Document 2: Japanese Patent Application No. 2003-508080

[0013] Patent Document 3: Japanese Patent Application No. 2004-508838

[0014] Patent Document 4: International Publication No. 99 / 002544 Summary of the Invention

[0015] Technical issues to be solved by the invention

[0016] Pigments used for fluorescent labeling are required to exhibit excellent fluorescence intensity in solution, for example. However, in pigment compounds that utilize the FRET phenomenon described in Non-Patent Document 1 and Patent Documents 1 to 4, energy is transferred to the phosphor portion II instead of emitting fluorescence from the phosphor portion I, resulting in a decrease in the fluorescence intensity of the compound.

[0017] The present invention aims to provide a compound that exhibits excellent fluorescence intensity in a solution state and to provide a labeled biological substance in which the compound is bonded to a biological substance.

[0018] Means for solving technical problems

[0019] That is, the above-mentioned problems of the present invention are solved by the following means.

[0020] [1]

[0021] A compound having two or more phosphor parts having mutually equivalent light absorption characteristics, wherein adjacent phosphor parts are linked via a group having a structure represented by the following general formula (I).

[0022] [Chemical Formula 1]

[0023]

[0024] Where, X 1 ~X 3Indicates -O-, -S-, >NR 1 or >CR 2 R 3 .

[0025] R 1 ~R 3 and R 11 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an acyl group, -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E .

[0026] R 8 ~R 10 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an aryl group, a heteroaryl group, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E .

[0027] L represents an alkylene group, R E With the above R 8 ~R 10 Same meaning, g is 2 to 50. E Can't be -(OL) g R E or -(LO) g R E .

[0028] n is an integer of 2 or greater.

[0029] * indicates a connection key.

[0030] [2]

[0031] The compound according to [1], wherein

[0032] The above n is an integer of 3 or greater.

[0033] 〔3〕

[0034] The compound according to [1] or [2], which is represented by the following general formula (II).

[0035] [Chemical Formula 2]

[0036]

[0037] Where R 4 and R 5 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an amino group, a hydroxyl group, an alkoxy group, a sulfanyl group, an aryl group, or a heteroaryl group.

[0038] R 6 and R 7 represents a hydrogen atom, a hydroxyl group, a sulfanyl group, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, an amino group, an acyl group, a heteroaryl group, or Q.

[0039] Q represents an anionic group, a cationic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E 、-(LO) g R E , a substituent capable of bonding to a biological substance or a substituent capable of bonding to a solid support.

[0040] L 1 ~L 7 represents a single bond or a divalent linking group.

[0041] M represents a phosphor moiety, a physiologically active substance moiety, a prodrug moiety, or a radioactive isotope-containing moiety.

[0042] Y represents a structure represented by the above-mentioned general formula (I).

[0043] m is an integer greater than or equal to 1.

[0044] L, R E and g and the above L, R E and g have the same meaning.

[0045] Here, at least two of M represent phosphor portions having the above-mentioned light absorption characteristics equivalent to each other.

[0046] [4]

[0047] The compound according to [3] is represented by the following general formula (VI).

[0048] [Chemical Formula 3]

[0049]

[0050] Where, X 4 ~X 9 Indicates -O-, -S-, >NR 101 or >CR 102 R 103 .

[0051] Among them, X 4 ~X 6At least one of them is >NL 10 -M or>C(R 102 )-L 10 -M,X 7 ~X 9 At least one of them is >NL 11 -M or>C(R 102 )-L 11 -M.

[0052] Neither -L 10 -M is not -L 11 -M's R 101 ~R 103 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an acyl group, -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E .

[0053] L 10 and L 11 represents a single bond or a divalent linking group.

[0054] n1 is an integer greater than or equal to 2, and q is an integer of 0 or 1.

[0055] R 4 ~R 11 、X 1 ~X 3 , M, L, R E , g and m and the above R 4 ~R 11 、X 1 ~X 3 , M, L, R E , g and m have the same meaning.

[0056] 〔5〕

[0057] The compound according to [4] is represented by the following general formula (VII).

[0058] [Chemical Formula 4]

[0059]

[0060] Where R 6A and R 7A represents a hydrogen atom, a hydroxyl group, a sulfanyl group, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, a heteroaryl group, an amino group, an acyl group, or Q. 6A and R7A At least one of them represents a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support.

[0061] L 12 and L 13 represents a single bond or a linking group.

[0062] na and nb are integers greater than or equal to 0, and r and v are integers of 0 or 1.

[0063] R 4 、R 5 、R 11 , L 10 , L 11 、X 1 ~X 9 , M, Q, q, n1 and m and the above R 4 、R 5 、R 11 , L 10 , L 11 、X 1 ~X 9 , M, Q, q, n1 and m have the same meaning.

[0064] [6]

[0065] The compound according to [5], wherein

[0066] (A) The above na is an integer greater than 1, and the above R 6A is the carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support, and / or (B) the sum of nb and v is an integer greater than 1, and the R 7A It is the above-mentioned carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support.

[0067] In the case of (A) above, the above L 13 The shortest number of atoms connected is 7 or less. In the case of (B), the L 12 The shortest number of connected atoms is less than 7.

[0068] [7]

[0069] The compound according to any one of [1] to [6], wherein

[0070] The structure represented by the above general formula (I) includes X 1 ~X 3 CR 2 R 3 structure.

[0071] 〔8〕

[0072] The compound according to [7], wherein

[0073] The structure represented by the general formula (I) includes X 1 ~X 3 CR 2 R 3 At least one R in the structure 2 -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E .

[0074] 〔9〕

[0075] The compound according to any one of [4] to [6], wherein

[0076] In the above general formula (VI), m is an integer of 3 or less.

[0077]

[10]

[0078] The compound according to any one of [1] to [9], wherein

[0079] The phosphor portion has a structural portion composed of at least one pigment selected from the group consisting of a coumarin pigment, a pyrene pigment, and a rhodamine pigment.

[0080]

[11]

[0081] A labeled biological substance, which is formed by bonding the compound described in any one of [1] to

[10] to a biological substance.

[0082]

[12]

[0083] The labeled biological substance according to

[11] , wherein

[0084] The biological substance is any one of proteins, amino acids, nucleic acids, nucleotides, sugar chains and phospholipids.

[0085] Effects of the Invention

[0086] The compound of the present invention exhibits excellent fluorescence intensity in a solution state. Furthermore, the labeled biological substance of the present invention can be obtained from a compound exhibiting excellent fluorescence intensity in a solution state. DETAILED DESCRIPTION

[0087] In the present invention, when there are multiple substituents, linking groups or structural units (hereinafter referred to as substituents, etc.) represented by specific symbols or formulas, or when multiple substituents, etc. are specified at the same time, unless otherwise specified, each substituent, etc. may be the same or different from each other. The same applies to the number of substituents, etc. Furthermore, when multiple substituents, etc. are close (especially adjacent), unless otherwise specified, they may be connected to each other to form a ring. Furthermore, unless otherwise specified, rings, such as alicyclic rings, aromatic rings and heterocyclic rings may be further fused to form a fused ring.

[0088] For example, in the present invention, the structure represented by the general formula (I) described later means that the structure represented by the general formula (i) below is formed by connecting n (n is an integer greater than 2). In this case, the n structures represented by the general formula (i) may be the same as or different from each other. In addition, X in the general formula (i) below is 1 ~X 3 and R 11 and X in the general formula (I) described below 1 ~X 3 and R 11 This is the same as the meaning of ( s The structure enclosed by () t The structure enclosed by () u The structure enclosed by () m The structure enclosed by () n1 The structure enclosed by () na The structure enclosed by () nb The structures enclosed are also the same. There are s structures that can be the same as or different from each other. There are t structures that can be the same as or different from each other. There are u structures that can be the same as or different from each other. There are m structures that can be the same as or different from each other. There are n1 structures that can be the same as or different from each other. There are na structures that can be the same as or different from each other. There are nb structures that can be the same as or different from each other.

[0089] [Chemical Formula 5]

[0090]

[0091] In the present invention, unless otherwise specified, double bonds, when present in a molecule, may be either E- or Z-type, or a mixture thereof. Furthermore, unless otherwise specified, when a compound contains an asymmetric carbon atom or an asymmetric center, the stereoconfiguration may be either R or S in the expression R,S, or a mixture thereof.

[0092] In the present invention, the representation of compounds and substituents is used to include the meaning of their salts and ions in addition to the compounds themselves and the substituents themselves. For example, dissociative anionic groups such as carboxyl, sulfo and phosphono (-P(=O)(OH)2) can present an ionic structure by hydrogen ion dissociation, or a salt structure. That is, in the present invention, "carboxyl" is used to mean a group containing carboxylate ions or their salts, "sulfo" is used to mean a group containing sulfonate ions or their salts, and "phosphono" is used to mean a group containing phosphonate ions or their salts. The monovalent or polyvalent cations constituting the above-mentioned salt structure are not particularly limited, and examples include inorganic cations, organic cations, and the like. Specifically, Na + 、Li + and K + Alkali metal cations, Mg 2+ , Ca 2+ And Ba 2+ Cations of alkaline earth metals such as alkylammonium cations, organic ammonium cations such as trialkylammonium cations and tetraalkylammonium cations, and organic phosphonium cations such as quaternary phosphonium ions.

[0093] In the case of a salt structure, the salt may be of one type or a mixture of two or more types. A salt type and a free acid structure group may be mixed in the compound, and a salt structure compound and a free acid structure compound may be mixed.

[0094] The compounds of the present invention are all neutral compounds. In the present invention, the neutrality of the compound means electrical neutrality. Specifically, the charge of the compound as a whole is adjusted to 0 by the charged groups or counterions in the compound. For example, in the cyanine pigment represented by the general formula (α) as an example of the pigment constituting the phosphor portion, R 42 The formal charge of the bonded nitrogen atom is +1, and the dissociative groups such as sulfonic groups in the cyanine pigment or other structures in the compound of the present invention have an ionic structure such as a sulfonate ion in pair with the formal charge, thereby making the compound of the present invention a compound with a charge of 0 as a whole.

[0095] In the general formulas related to cyanine dyes defined in the present invention, for convenience, the positive charge of the compound is represented as a structure possessed by a specific nitrogen atom. However, since the cyanine dyes defined in the present invention have a conjugated system, atoms other than the nitrogen atom may actually have a positive charge. However, any cyanine dye that can exhibit the structure represented by each general formula as one of its chemical structures is included in the cyanine dye represented by each general formula. This also applies to negative charges.

[0096] Furthermore, it refers to compounds obtained by modifying a portion of the structure within a range that does not impair the effects of the present invention. Furthermore, compounds not explicitly stating whether they are substituted or unsubstituted may have any substituents within a range that does not impair the effects of the present invention. This also applies to substituents (e.g., groups described as "alkyl," "methyl," "methyl," etc.) and linking groups (e.g., groups described as "alkylene," "methylene," "methylene," etc.). Among these optional substituents, preferred substituents in the present invention are those selected from Substituent Group T described below.

[0097] In the present invention, when the number of carbon atoms in a group is specified, unless otherwise specified in the present invention or this specification, the number of carbon atoms refers to the number of carbon atoms in the group as a whole. In other words, when the group further has a substituent, the number of carbon atoms refers to the total number of carbon atoms including the substituent.

[0098] Furthermore, in the present invention, a numerical range expressed using “to” means a range including the numerical values ​​described before and after “to” as the lower limit and the upper limit.

[0099] The compound of the present invention has two or more phosphor portions whose light absorption characteristics are equivalent to each other, wherein each phosphor portion adjacent to each other is connected via a group comprising a structure represented by general formula (I) described later. Although the details of the reason why the compound of the present invention shows excellent fluorescence intensity in a solution state are not yet clear, it is considered as follows.

[0100] The compound of the present invention has two or more fluorophore parts with mutually equivalent light absorption characteristics, and has a structure in which each fluorophore part adjacent to each other is connected by a group comprising a structure represented by the general formula (I) described later. The structure represented by the general formula (I) has a repeating unit (repeat number is 2 or more) of a nitrogen-containing saturated 5-membered ring such as a ring structure derived from proline, and the two fluorophore parts connected by the group comprising the structure represented by the general formula (I) play the function of a rigid connector, thereby effectively suppressing the quenching caused by the association of the fluorophore part between molecules or within the molecule. As a result, the association of the fluorophore part between molecules or within the molecule under the solution state of the compound (the solution state in which the compound is dissolved in the aqueous medium) can be effectively suppressed. Therefore, it is believed that the labeled biological substance obtained using the compound of the present invention can show excellent fluorescence intensity.

[0101] Hereinafter, the compound of the present invention will be described in detail.

[0102] <Compounds of the present invention>

[0103] The compound of the present invention has two or more phosphor parts having mutually equivalent light absorption characteristics, wherein adjacent phosphor parts are linked via a group including a structure represented by the general formula (I) described below.

[0104] The compound of the present invention may be a compound classified as a polymer or an oligomer.

[0105] In the present invention, “phosphor portions having mutually equivalent light absorption characteristics” means that the difference in the maximum absorption wavelength in the absorption spectrum of each phosphor portion satisfies a relationship of within 15 nm.

[0106] In the present invention, the compound preferably has all phosphor parts such that the difference between the maximum absorption wavelength on the lowest wavelength side and the maximum absorption wavelength on the highest wavelength side in the absorption spectrum of each phosphor part is within 15 nm.

[0107] As mentioned above, compounds with two fluorescent moieties are known to exhibit the FRET phenomenon. The difference in the maximum absorption wavelengths between the absorption spectra of fluorescent moiety I (energy donor), which is excited by excitation light, and fluorescent moiety II (energy acceptor), which receives energy from fluorescent moiety I and emits or quenches light, typically exceeds 15 nm. In such compounds, energy is transferred to fluorescent moiety II instead of emitting fluorescence from fluorescent moiety I, resulting in a decrease in the fluorescence intensity of the compound.

[0108] In contrast, as described above, the compound of the present invention has fluorescent parts having mutually equivalent light absorption characteristics, and therefore does not cause the FRET phenomenon and can exhibit fluorescence intensity proportional to the number of fluorescent parts.

[0109] The chemical structures of the phosphor moieties with mutually equivalent light absorption characteristics are not particularly limited, as long as the aforementioned difference in maximum absorption wavelengths is satisfied. Preferably, the main skeleton structures of the phosphor moieties are identical. The substituents may differ in configuration and chain length, and in the case of anionic or cationic groups, the counterions may also differ. The aforementioned difference in maximum absorption wavelengths is preferably within 10 nm, more preferably within 5 nm.

[0110] The absorption spectrum of the phosphor portion refers to a spectrum measured using a spectrophotometer on a single phosphor constituting the phosphor portion diluted with PBS buffer (Phosphate-buffered saline).

[0111] Furthermore, "a compound in which adjacent phosphor portions are linked via a group including a structure represented by the following general formula (I)" is preferably a compound in which two structures having a phosphor portion as a substituent are linked via a group including a structure represented by the following general formula (I).

[0112] In addition, as long as the adjacent phosphor portions are connected via a group including a structure represented by the following general formula (I), the structure having the above phosphor portion as a substituent is not particularly limited. For example, as described in detail in the general formula (II) described later, 1 With L 2 Combination of L 1 With L 3 Combination of L 4 With L 5 Combination or L 4 With L 6 Combination of carbon atoms, nitrogen atoms and X to form the structure represented by the following general formula (I) 1 ~X 3 The 5-membered ring as the ring-constituting atoms may have a group containing a fluorescent body portion as a substituent. That is, as a structure having a fluorescent body portion as a substituent, as long as each adjacent fluorescent body portion is connected via a group containing a structure represented by the following general formula (I), the carbon atoms, nitrogen atoms and X described in the structure represented by the following general formula (I) are 1 ~X 3 The five-membered ring as the ring-constituting atoms may have a structure having a group including a fluorescent part as a substituent. Examples of such compounds include compounds represented by the general formula (VI) or (VII) described below.

[0113] In the compound of the present invention, the number of the phosphor moieties is 2 or more. The upper limit is not particularly limited; for example, it can be 30 or less, preferably 20 or less, more preferably 15 or less, even more preferably 10 or less, and particularly preferably 4 or less. That is, the number of the phosphor moieties is preferably 2 to 30, more preferably 2 to 20, even more preferably 2 to 15, particularly preferably 2 to 10, and particularly preferably 2 to 4.

[0114] Regarding the phosphor portion possessed by the compound of the present invention, in addition to the above, the description and specific examples of the phosphor portion in the general formula (II) described later can be applied.

[0115] (Structure represented by general formula (I))

[0116] [Chemical Formula 6]

[0117]

[0118] Where, X 1 ~X 3 Indicates -O-, -S-, >NR 1 or >CR 2 R 3 .

[0119] R 1 ~R 3 and R 11 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an acyl group, -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E .

[0120] R 8 ~R 10 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an aryl group, a heteroaryl group, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E .

[0121] L represents an alkylene group, R E With the above R 8 ~R 10 Same meaning, g is 2 to 50. E Can't be -(OL) g R E or -(LO) g R E .

[0122] n is an integer of 2 or greater.

[0123] * indicates a connection key.

[0124] In the present invention, taking stereoisomers into consideration, the structure represented by the above general formula (I) is preferably a structure represented by any one of the following general formulas (IA) or (IB). 1 ~X 3 、R 11 and n and X in the above general formula (I) 1 ~X 3 、R 11 and n have the same meaning.

[0125] [Chemical Formula 7]

[0126]

[0127] X 1 ~X 3 Indicates -O-, -S-, >NR 1 or >CR 2 R 3 , R 1 ~R 3 and R 11 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an aryl group, a heteroaryl group, -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E .

[0128] Can be used as R 1 ~R 3 and R 11 Alkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E and-(LO) g R E and the alkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) in the substituent group T described below. g R E and-(LO) g R E The meanings are the same as those in the preceding text, and the preferred ranges are also the same.

[0129] Can be used as R 1 ~R 3 and R 11 The alkyl group, alkenyl group, alkynyl group, acyl group, aryl group, and heteroaryl group may be unsubstituted or may have a substituent.

[0130] As R 1 ~R 3 and R 11 The substituents that the alkyl, alkenyl, alkynyl, acyl, aryl and heteroaryl groups in the group may have include the substituents in the substituent group T described below, and are preferably halogen atoms, anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R Eor -(LO) g R E .

[0131] Can be used as R 1 ~R 3 and R 11 -NR 8 R 9 AND-OR 10 In, R 8 ~R 10 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an aryl group, a heteroaryl group, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E .

[0132] Can be used as R 8 ~R 10 Alkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E and-(LO) g R E and the alkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) in the substituent group T described below. g R E and-(LO) g R E The meanings are the same as those in the preceding text, and the preferred ranges are also the same.

[0133] Can be used as R 8 ~R 10 The alkyl group, alkenyl group, alkynyl group, acyl group, aryl group, and heteroaryl group may be unsubstituted or may have a substituent.

[0134] As R 8 ~R 10 The substituents that the alkyl, alkenyl, alkynyl, acyl, aryl, and heteroaryl groups in the group may have include the substituents in the substituent group T described later, for example, preferably a halogen atom, a carbamoyl group, an acylamino group, an alkoxy group (preferably an alkoxy group having an anionic group), a heteroaryl group, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E, more preferably a carbamoyl group, an acylamino group, an alkoxy group (preferably an alkoxy group having an anionic group), a heteroaryl group, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E .

[0135] As R 1 , preferably a hydrogen atom, an alkyl group, -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E .

[0136] As R 2 and R 3 , preferably a hydrogen atom, -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E , more preferably R 2 is a hydrogen atom, -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E , and R 3 A hydrogen atom.

[0137] As R 11 , preferably a hydrogen atom, an alkyl group, -NR 8 R 9 、-OR 10 or anionic groups, more preferably hydrogen atoms.

[0138] As R 8 and R 10 , preferably a hydrogen atom, an alkyl group or an acyl group. The alkyl group may be an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E and-(LO)g R E The acyl group may be an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E and-(LO) g R E At least one acyl group.

[0139] As the above-mentioned anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E and-(LO) g R E At least one acyl group in the above-mentioned group preferably has an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E and-(LO) g R E At least one acyl group in, or an anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E and-(LO) g R E The above-mentioned alkyl and acyl groups may have anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E and-(LO) g R E The substituents other than ' and ' include the substituents in the substituent group T described later, and for example, a carbamoyl group or an acylamino group is preferred.

[0140] In addition, -(OL) g R E and-(LO) g R E As can be used as R E The divalent group obtained by removing one hydrogen atom from a hydrogen atom or a substituent is included, and an anionic group, a sulfo group, a phosphono group, a betaine residue, a polyol residue, a sugar residue or a polyamino acid residue may be further bonded. In -(OL) g R E or -(LO) g R E In, as can be used as R E A divalent group obtained by removing one hydrogen atom from a hydrogen atom or a substituent, for example, -(OL)g -、-(OL) g -NHCO-、-(OL) g -CONH-、-(OL) g -CONH alkylene-, -(OL) g -NHCO alkylene-, -(LO) g -、-(LO) g -NHCO-、-(LO) g -CONH-、-(LO) g -CONH alkylene-, -(LO) g -NHCOalkylene-.

[0141] As the above X 1 ~X 3 , preferably at least one of them is >CR 2 R 3 , more preferably at least 2 are >CR 2 R 3 And the remaining one is -O-, -S- or >CR 2 R 3 .

[0142] In the present invention, from the viewpoint of making the structure represented by the general formula (I) more rigid, the structure represented by the general formula (I) preferably includes X 1 ~X 3 CR 2 R 3 The structure represented by the general formula (I) includes X 1 ~X 3 CR 2 R 3 The structure "is a structure in which n structures represented by the general formula (i) are connected to each other. 1 ~X 3 All are>CR 2 R 3 .

[0143] In the structure represented by the general formula (I), the above-mentioned X 1 ~X 3 CR 2 R 3 The ratio of the number of structures of is preferably 30% or more, more preferably 60% or more, and further preferably 80% or more. The upper limit is not particularly limited and can be set to 100% or less. In addition, it is also preferred that all the structures represented by general formula (I) are the above X 1 ~X 3 CR 2 R3 structure.

[0144] From the viewpoint of suppressing the interaction between molecules and, when there are multiple structures within a molecule, between the structures represented by the general formula (I), the above-mentioned X 1 ~X 3 CR 2 R 3 At least one R in the structure 2 Preferably -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E , more preferably -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E , and R 8 ~R 10 At least one of the compounds is an acyl group, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E and-(LO) g R E At least one of the groups.

[0145] In addition, the above “X 1 ~X 3 CR 2 R 3 At least one R in the structure 2 -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E , and R 8 ~R 10 At least one of the compounds is an acyl group, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E and-(LO)g R E At least one group in R 2 -NR 8 R 9 In the case of R 8 and R 9 At least one of the compounds is an acyl group, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E and-(LO) g R E At least one of the groups in R 2 For-OR 10 In the case of R 10 Anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E and-(LO) g R E At least one of the groups.

[0146] And, R 10 Anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E and-(LO) g R E At least one group in 10 Anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E , or anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E and-(LO) g R E At least one of the following is used as a substituent. 8 and R 9 At least one of the residues is an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E and-(LO) g R E The same applies to the case of at least one group in .

[0147] In addition, as the above-mentioned "containing acyl group, anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E and-(LO) g R E "At least one of the groups", for example, preferably "anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E and-(LO) g R E At least one alkyl group in, and anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E and-(LO) g R E At least one acyl group in the group ". Furthermore, acyl groups, anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E As such, it is more preferably an acyl group.

[0148] n is an integer of 2 or greater. In the compound of the present invention, when n is an integer of 2 or greater, rigidity effective in suppressing the association of the dye (phosphor portion) can be imparted to the structure represented by general formula (I), and a decrease in fluorescence intensity can be suppressed.

[0149] In the present invention, when the number of the phosphor portions is 2, from the perspective of further improving the fluorescence intensity (further suppressing the association of the pigment and further suppressing the decrease in fluorescence intensity), the lower limit of n is preferably an integer of 3 or greater, more preferably an integer of 7 or greater, further preferably an integer of 9 or greater, and particularly preferably an integer of 12 or greater. The upper limit is not particularly limited, and for example, it can be an integer of 72 or less, preferably an integer of 36 or less, more preferably an integer of 24 or less, and further preferably an integer of 18 or less. That is, n is preferably an integer of 3 to 72, more preferably an integer of 7 to 36, further preferably an integer of 9 to 24, and particularly preferably an integer of 12 to 18.

[0150] On the other hand, compared to the case where the number of phosphor parts is 2, when the number of phosphor parts is 3 or more, the number of phosphor parts (the number of pigments) per molecule is greater, so a certain number of pigments can be allowed to associate, and as long as it is an integer of 3 or more, the fluorescence intensity can be further improved, which is preferred. Among them, when n is an integer of 6, although there is a certain association inhibition effect, it is not sufficient, so n is more preferably an integer of 7 or more. When the number of phosphor parts is 3 or more, the upper limit of n is, for example, preferably an integer of 72 or less, more preferably an integer of 36 or less, and even more preferably an integer of 24 or less. That is, when the number of phosphor parts is 3 or more, n is preferably an integer of 3 to 72, more preferably an integer of 7 to 36, and even more preferably an integer of 7 to 24.

[0151] <Compound represented by general formula (II)>

[0152] The compound of the present invention is preferably represented by the following general formula (II).

[0153] [Chemical Formula 8]

[0154]

[0155] Where R 4 and R 5 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an amino group, a hydroxyl group, an alkoxy group, a sulfanyl group, an aryl group, or a heteroaryl group.

[0156] R 6 and R 7 represents a hydrogen atom, a hydroxyl group, a sulfanyl group, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, an amino group, an acyl group, a heteroaryl group, or Q.

[0157] Q represents an anionic group, a cationic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E 、-(LO) g R E , a substituent capable of bonding to a biological substance or a substituent capable of bonding to a solid support.

[0158] L 1 ~L 7 represents a single bond or a divalent linking group.

[0159] M represents a phosphor moiety, a physiologically active substance moiety, a prodrug moiety, or a radioactive isotope-containing moiety.

[0160] Y represents a structure represented by the above-mentioned general formula (I).

[0161] m is an integer greater than or equal to 1.

[0162] L, R E and g and the above L, R E and g have the same meaning.

[0163] Here, at least two of M represent phosphor portions having equivalent light absorption characteristics. In other words, this means that at least two of M are phosphor portions, and adjacent phosphor portions are phosphor portions having equivalent light absorption characteristics.

[0164] R 4 and R 5 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an amino group, a hydroxyl group, an alkoxy group, a sulfanyl group, an aryl group, or a heteroaryl group.

[0165] Can be used as R 4 or R 5 The alkyl, alkenyl, alkynyl, acyl, amino, alkoxy, aryl and heteroaryl groups have the same meanings as the alkyl, alkenyl, alkynyl, acyl, amino, alkoxy, aryl and heteroaryl groups in the substituent group T described later, and the preferred scope is also the same.

[0166] Can be used as R 4 or R 5 The alkyl, alkenyl, alkynyl, acyl, amino, alkoxy, aryl and heteroaryl groups may be unsubstituted or may have a substituent. Examples of the substituents that may be substituted include the substituents in the substituent group T described later, and for example, a halogen atom is preferred.

[0167] As R 4 and R 5 From the viewpoint of simplicity of synthesis, a hydrogen atom is preferred. When amino acids are used as raw materials, R 4 and R 5 Most of them become hydrogen atoms, but R 4 and R 5 The substituents in R do not contribute significantly to the excellent association inhibition effect exhibited by the compound of the present invention in a solution state. 4 and R 5 Other substituents (alkyl, alkenyl, alkynyl, acyl, amino, hydroxy, alkoxy, sulfanyl, aryl or heteroaryl) may be present in addition to hydrogen atoms.

[0168] R 6 and R 7 represents a hydrogen atom, a hydroxyl group, a sulfanyl group, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, an amino group, an acyl group, a heteroaryl group, or Q.

[0169] Can be used as R 6 or R 7The alkyl, alkenyl, alkynyl, aryl, alkoxy, amino, acyl and heteroaryl groups have the same meanings as the alkyl, alkenyl, alkynyl, aryl, alkoxy, amino, acyl and heteroaryl groups in the substituent group T described later, and the preferred scope is also the same.

[0170] Can be used as R 6 or R 7 The alkyl group, alkenyl group, alkynyl group, aryl group, alkoxy group, amino group, acyl group, and heteroaryl group may be unsubstituted or may have a substituent.

[0171] As R 6 or R 7 The substituents that the alkyl, alkenyl, alkynyl, aryl, alkoxy, amino, acyl and heteroaryl groups may have include the substituents in the substituent group T described below, preferably alkyl, acyl, alkoxy, amino or Q, or a substituent formed by combining two or more of them, more preferably alkyl, acyl, alkoxy, amino, -(OL) g R E 、-(LO) g R E , a carboxyl group, a substituent capable of bonding to a biological substance or a substituent capable of bonding to a solid support, or a substituent formed by combining two or more of these substituents.

[0172] Can be used as R 6 or R 7 Q represents an anionic group, a cationic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E 、-(LO) g R E , a substituent capable of bonding to a biological substance or a substituent capable of bonding to a solid support.

[0173] Anionic groups, cationic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E and-(LO) g R E and anionic groups, cationic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) in the substituent group T described below. g R E and-(LO) g R E The meanings are the same as those in the preceding text, and the preferred ranges are also the same.

[0174] As the substituent capable of bonding to a biological substance, the description of the substituent capable of bonding to a biological substance described below can be applied, and as the substituent capable of bonding to a solid support, the description of the substituent capable of bonding to a solid support described below can be applied.

[0175] Q is preferably a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support, and more preferably a substituent capable of bonding to a biological substance or a substituent capable of bonding to a solid support.

[0176] As R 6 , preferably, the following one is -L 9 R 6A or -L 13 R 6A The description of the substituent represented by R 7 , preferably, the following one is -L 8 R 7A or -L 12 R 7A Specifically, -L 9 R 6A The description of the substituent represented by means of L 9 The groups and can be used as R 6A This is for -L 13 R 6A 、-L 8 R 7A and -L 12 R 7A Same.

[0177] L 2 ~L 5 and L 7 represents a single bond or a divalent linking group, preferably a single bond or an alkylene group, an alkenylene group, an alkynylene group, an arylene group, a heteroarylene group, -O-, -S-, >C=O, >NR A ,>S=O,>S(=O)2 and>P(=O)OR B A connecting group composed of one or a combination of two or more of the following. A and R B and R A and R B , and represents a hydrogen atom or a substituent.

[0178] L 1 and L 6 represents a single bond or a divalent linking group, preferably a single bond, an alkylene group, an alkenylene group, an alkynylene group, an arylene group, a heteroarylene group, -O-, -S-, >C=O, >NR A,>S=O,>S(=O)2 or>P(=O)OR B . R A and R B and R A and R B , and represents a hydrogen atom or a substituent.

[0179] Can form L 1 ~L 7 The alkylene group has the same meaning as a group obtained by removing one hydrogen atom from an alkyl group selected from the substituent group T described later, and preferred groups are also the same.

[0180] Can form L 1 ~L 7 The alkenylene group has the same meaning as a group obtained by removing one hydrogen atom from an alkenyl group selected from the substituent group T described later, and preferred groups are also the same.

[0181] Can form L 1 ~L 7 The alkynylene group has the same meaning as a group obtained by removing one hydrogen atom from an alkynyl group selected from the substituent group T described later, and preferred groups are also the same.

[0182] Can form L 1 ~L 7 The arylene group has the same meaning as a group obtained by removing one hydrogen atom from an aryl group selected from the substituent group T described later, and preferred groups are also the same.

[0183] Can form L 1 ~L 7 The heteroarylene group has the same meaning as a group obtained by removing one hydrogen atom from a heteroaryl group selected from the substituent group T described later, and preferred groups are also the same.

[0184] Can form L 1 ~L 7 The alkylene group, alkenylene group, alkynylene group, arylene group, and heteroarylene group may be unsubstituted or may have a substituent.

[0185] As can constitute L 1 ~L 7 The substituents that the alkylene, alkenylene, alkynylene, arylene and heteroarylene groups may have are not particularly limited, but are preferably selected from the substituent group T described below, and more preferably include a halogen atom, an alkyl group, an acylamino group or a carbamoyl group. 1 ~L 7The substituent that the above-mentioned alkylene group, alkenylene group, alkynylene group, arylene group and heteroarylene group may have may be further substituted with a substituent selected from the substituent group T described later, and for example, an amino group is preferred.

[0186] And, about the L 1 ~L 7 The number of substituents that the above-mentioned alkylene, alkenylene, alkynylene, arylene and heteroarylene groups may have is not particularly limited as long as they can be used as a structure, and can be set to at least 1 or more as an upper limit, and is not particularly limited. For example, all hydrogen atoms in the alkylene, alkenylene, alkynylene, arylene and heteroarylene groups may be replaced by substituents.

[0187] As can constitute L 1 ~L 7 >NR A R in A and>P(=O)OR B can be used as R B The substituents of R are not particularly limited, but are preferably selected from the substituent group T described below. A , preferably a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group or an anionic group, more preferably a hydrogen atom or an alkyl group, further preferably a hydrogen atom. B , preferably a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heteroaryl group, more preferably a hydrogen atom or an alkyl group, further preferably a hydrogen atom.

[0188] Additionally, it can be used as R A and R B The above-mentioned alkyl, alkenyl, alkynyl, aryl and heteroaryl groups may be unsubstituted or may have a substituent.

[0189] In the form of L 2 ~L 5 and L 7 Alkylene, alkenylene, alkynylene, arylene, heteroarylene, -O-, -S-, >C=O, >NR A ,>S=O,>S(=O)2 and>P(=O)OR B In the connecting group formed by combining two or more of the above, the types of the combined groups are not particularly limited as long as they form a proper chemical structure. For example, 2 to 6 types are preferred, and 2 to 4 types are more preferred. In addition, alkylene, alkenylene, alkynylene, arylene, heteroarylene, -O-, -S-, >C=O, >NR A ,>S=O,>S(=O)2 and>P(=O)OR B Each is counted as 1 type, with a maximum of 12 types.

[0190] In addition, L 2 ~L 5 and L 7 Alkylene, alkenylene, alkynylene, arylene, heteroarylene, -O-, -S-, >C=O, >NR A ,>S=O,>S(=O)2 and>P(=O)OR B In the linking group formed by combining two or more of the above, the number of the combined groups is not particularly limited, and for example, preferably 2 to 10, more preferably 2 to 6, and even more preferably 2 to 4.

[0191] (i)L 1 , L 6

[0192] L 1 and L 6 More preferably, it is a single bond, >C=O, >NR A , arylene, alkylene, -O- or -S-, more preferably a single bond, >C=O, >NR A , arylene or alkylene, particularly preferably a single bond, >C=O or >NR A .

[0193] (ii)L 3 , L 4 , L 7

[0194] L 3 , L 4 and L 7 More preferably, it is a single bond, >C=O, >NR A , alkylene, alkenylene, alkynylene, arylene or heteroarylene, or at least one of alkylene, alkenylene, alkynylene, arylene and heteroarylene and >C=O and >NR A The combination of single bond, >C=O, >NR A , alkylene, alkenylene, alkynylene, arylene or heteroarylene, or connected through at least one of alkylene, alkenylene, alkynylene, arylene and heteroarylene groups -C(=O)NR A - and >C=O or -NR A C(=O)- and >NR A between the groups.

[0195] (iii)L 2 , L 5

[0196] L 2 and L 5 More preferably, they are a single bond, an alkylene group, an alkenylene group, an alkynylene group, an arylene group, a heteroarylene group, -O-, -S-, >C=O, and >NRA One or more of the group consisting of a combination of *-L x -L y -** represents a group.

[0197] L x is a single bond, or a group consisting of one or a combination of two or more of an alkylene group, an alkenylene group, an alkynylene group, an arylene group, and a heteroarylene group, L y is a single bond, -O-, -S-, >C=O or >NR A * indicates L 1 and L 3 The bonded carbon atom or L 4 and L 6 The bond to the carbon atom to which it is bonded, ** represents the bond to M. y When it is a single bond, L x It is a heteroarylene group, or a group consisting of one or a combination of two or more of an alkylene group, an alkenylene group, an alkynylene group, and an arylene group located at the * side, and a heteroarylene group located at the ** side.

[0198] About L 2 and L 5 , in the above by *-L x -L y In the group represented by -**, L is also preferred y is a single bond, -S-, >C=O or >NR A More preferably, L y >C=O or >NR A The group is more preferably L x is an alkylene group and L y >C=O or >NR A group.

[0199] In addition, in the compound represented by the above general formula (II), M and L are connected 1 and L 3 The bonded carbon atom or L 4 and L 6 The connecting chain of carbon atoms to which the bond is attached (including L 2 The connecting chain and the L 5 The shortest number of atoms in each connecting chain of the connecting chain is, for example, 1 to 60, preferably 1 to 40. When M is a fluorescent body part, the shortest number of atoms refers to the number of atoms in the fluorescent body part M that constitutes the conjugated structure part for displaying fluorescence and L. 1 and L 3 The bonded carbon atom or L 4 and L 6 The number of atoms in the shortest chain of carbon atoms to which it is bonded.

[0200] In the compound represented by the above general formula (II), it is also preferred that the conjugated structure of M is represented by a linking group ZZZ-L described later. 2 - In the structure represented by "-", the linking group ZZZ-L 2 Any part of the connecting chain represented by -, and the connecting group ZZZ-L described later in the conjugated structure part of M represented by - 5 - In the structure represented by "-", the linking group ZZZ-L 5 Any part of the connecting chain represented by "-" has the following structure: -(CH2-CH2-O) b -The structure represented by (b is also described later.).

[0201] In the compound represented by the general formula (II), adjacent groups may be bonded to each other to form a ring. As a combination of adjacent groups that may be bonded to each other to form a ring, for example, L 1 With L 2 Combination of L 1 With L 3 Combination of L 2 With R 4 Combination of L 4 With L 5 Combination of L 4 With L 6 Combination or L 5 With R 5 combination.

[0202] The ring formed by bonding the adjacent groups may be any of an aromatic ring and an aliphatic ring, or any of a hydrocarbon ring and a heterocyclic ring, and is preferably a 5- or 6-membered ring.

[0203] As the aliphatic ring, preferably, a cyclopentane ring, a cyclohexane ring or a structure represented by the general formula (I) above wherein carbon atoms, nitrogen atoms and X are present. 1 ~X 3 The 5-membered ring as the ring-constituting atoms is more preferably a carbon atom, a nitrogen atom and X in the structure represented by the general formula (I). 1 ~X 3 A 5-membered ring as ring-constituting atoms.

[0204] The aromatic ring is preferably a benzene ring or a nitrogen-containing aromatic heterocycle, more preferably a benzene ring or a nitrogen-containing aromatic heterocycle whose ring constituent atoms are carbon atoms and nitrogen atoms, and still more preferably a benzene ring or a pyridine ring.

[0205] These rings may have a substituent. The substituent is not particularly limited and is selected from the substituent group T.

[0206] As through L 2 With R 4 Combination or L 5 With R 5 The ring formed by the combination of may be any of the above-mentioned aliphatic ring and aromatic ring, and is preferably the above-mentioned aliphatic ring.

[0207] As through L 1 With L 2 Combination of L 1 With L 3 Combination of L 4 With L 5 Combination or L 4 With L 6 The ring formed by the combination of may be any of the above-mentioned aliphatic ring and aromatic ring, preferably the carbon atom, nitrogen atom and X described in the structure represented by the general formula (I) 1 ~X 3 A 5-membered ring or a benzene ring as ring-constituting atoms.

[0208] For example, the following structure surrounded by a dotted line of the general formula (II) can be set as,

[0209] [Chemical Formula 9]

[0210]

[0211] The following structures are included. In the following structures, * represents a connecting portion.

[0212] [Chemical Formula 10]

[0213]

[0214] m is an integer greater than or equal to 1. The upper limit is not particularly limited, and for example, it can be an integer less than or equal to 30, preferably an integer less than or equal to 20, more preferably an integer less than or equal to 15, further preferably an integer less than or equal to 10, and particularly preferably an integer less than or equal to 3. That is, m can be an integer of 1 to 30, preferably an integer of 1 to 20, more preferably an integer of 1 to 15, and further preferably an integer of 1 to 10.

[0215] M represents a phosphor moiety, a physiologically active substance moiety, a prodrug moiety, or a radioisotope-containing moiety, wherein at least two of M represent phosphor moieties having equivalent light absorption properties.

[0216] As the phosphor part that can be used as M (hereinafter also referred to as the phosphor part M), as long as it is a structural part composed of an organic compound showing fluorescence, it can be used without particular limitation. In addition, the phosphor part M can be a structural part in which the structural part composed of an organic compound showing fluorescence further has a linking group. Such a linking group is not particularly limited, and for example, the linking group ZZZ described later can be cited. For example, in the compound represented by the general formula (II), the phosphor part M can preferably be linked to L via the linking group ZZZ. 2 or L 5 Bonded compounds.

[0217] Examples of the phosphor portion M include a structural portion composed of at least one dye selected from the group consisting of xanthene dye, rhodamine dye, coumarin dye, cyanine dye, pyrene dye, oxazine dye, squarylium dye, pyridyloxazole dye, and pyrromethene dye.

[0218] As the xanthene dye, rhodamine dye, coumarin dye, cyanine dye, pyrene dye, oxazine dye, squarylium dye, pyridyloxazole dye, and pyrromethene dye, generally known dyes can be used without particular limitation. Among these, those having a hydrophilic group can be preferably used.

[0219] The phosphor portion M preferably has a structural portion composed of at least one of a coumarin dye, a pyrene dye, and a rhodamine dye, and more preferably has a structural portion composed of at least one of a coumarin dye, a pyrene dye, and a rhodamine dye having a hydrophilic group. From the perspective of imparting sufficient hydrophilicity to the compound of the present invention, the number of hydrophilic groups per molecule of each of the coumarin dye, the pyrene dye, and the rhodamine dye is preferably 1 or more, preferably 1 to 8, and more preferably 1 to 4.

[0220] The hydrophilic group is not particularly limited, and examples thereof include an alkoxy group having a substituent, a carboxyl group, a sulfo group, and a phosphono group, with a sulfo group being preferred.

[0221] As a mode, above-mentioned phosphor portion M is preferably a structural part consisting of pyrromethene pigment.As pyrromethene pigment, dipyrromethene boron complex can be cited.As dipyrromethene boron complex, it is possible to use the fluorescent compound (dipyrromethene boron complex) represented by general formula (1) or (4) described in International Publication No. 2019 / 230963, the compound (dipyrromethene boron complex) represented by general formula (1) described in International Publication No. 2021 / 100814, these records can be quoted and incorporated into this specification.

[0222] Furthermore, the pigment constituting the phosphor portion M is incorporated so as not to have a substituent capable of bonding to a biological substance.

[0223] As another embodiment, the phosphor portion M is preferably a structural portion composed of a cyanine dye, and more preferably a structural portion composed of a cyanine dye represented by the following general formula (α).

[0224] [Chemical Formula 11]

[0225]

[0226] Where R 1 ~R 4 represents an alkyl group or -(CH2-CH2-O) b -R 21 b is 1 to 50, R 21 represents an alkyl group.

[0227] R 11 ~R 13 represents a hydrogen atom, an alkyl group, an alkoxy group, an aryloxy group, an alkylthio group, an arylthio group, an amino group or a halogen atom, and adjacent groups may be bonded to each other to form a 5-membered ring or a 6-membered ring.

[0228] R 22 ~R 25 and R 32 ~R 35 represents a hydrogen atom, an alkyl group, an alkoxy group, an aryl group, a sulfo group, a sulfamoyl group, a carboxyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyloxy group, a carbamoyl group, an acylamino group, a nitro group or a halogen atom.

[0229] R 41 and R 42 represents an alkyl group or -(CH2-CH2-O) b -R 21 . R 21 and b and the above R 21 and b have the same meaning. 41 and R 42 They may be bonded to each other to form a ring.

[0230] a is an integer from 1 to 3.

[0231] By using the R 1 ~R 4 、R 11 ~R 13 、R 22 ~R 25 、R 32 ~R 35 、R 41 or R 42One hydrogen atom is removed from any of them to form a monovalent structural portion.

[0232] Among them, the cyanine pigment represented by formula (α) is neutral.

[0233] The cyanine dye represented by the general formula (α) has excitation and absorption wavelengths in the wavelength range of 520 to 600 nm (near 585 nm) when a=1, in the wavelength range of 620 to 700 nm (near 685 nm) when a=2, and in the wavelength range of 740 to 830 nm (near 785 nm) when a=3, depending on the length of the methylene chain (repeating number 2a+3) connected by conjugated double bonds. Therefore, the compound of the present invention having a structural portion composed of the cyanine dye represented by the general formula (α) as the phosphor portion M can be used as a compound exhibiting excellent fluorescence intensity in a fluorescent label using a light source having any wavelength in the wavelength range of approximately 500 to 800 nm (e.g., around 600 nm, 700 nm, or 800 nm) corresponding to the absorption and excitation wavelength of the compound as an excitation light source.

[0234] In polychromatic WB, multiple luminescent colors are detected in the range from the visible region to the near-infrared region. Therefore, it is necessary to select a plurality of pigments in such a way that the absorption waveforms and luminescent waveforms have an appropriate wavelength relationship to avoid mutual interference and crosstalk when exciting the pigments to make them emit light. Ideally, it is adjusted so that only one pigment emits light under a certain excitation light, while the other pigments do not emit light. From this viewpoint, for example, two excitation light sources with a certain degree of interval in the wavelength of the luminescence in the near-infrared region of polychromatic WB are used, such as near 700nm and near 800nm.

[0235] Compared to detection using visible light excitation, fluorescence detection using near-infrared light excitation can suppress membrane autofluorescence, or background fluorescence, thereby easily improving the signal-to-noise ratio (S / N ratio) and enabling highly sensitive detection of target proteins. Consequently, in recent years, the need for fluorescence detection WB using near-infrared light emission has increased in the analysis of trace amounts of proteins.

[0236] However, in the near-infrared region, the fluorescence quantum yield of fluorescent dyes is generally low, making it difficult to obtain a high signal intensity. Even in multicolor WB using the two compounds described above near 700 nm and near 800 nm, compounds of the present invention having a structure composed of a cyanine dye represented by the general formula (α) as the fluorescent moiety M can be used as compounds exhibiting excellent fluorescence intensity. In particular, to meet the demand for more sensitive observation and detection of proteins, they can also exhibit superior fluorescence intensity compared to conventional fluorescent labels using cyanine dyes.

[0237] (i)R 1 ~R 4

[0238] R 1 ~R 4 represents an alkyl group or -(CH2-CH2-O) b -R 21 .

[0239] Can be used as R 1 ~R 4 The alkyl group has the same meaning as the alkyl group in the substituent group T described below.

[0240] The unsubstituted alkyl group preferably has 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, and even more preferably 1 to 2 carbon atoms.

[0241] When the alkyl group has a substituent, the number of carbon atoms in the alkyl portion of the substituted alkyl group is preferably 1 to 10, more preferably 1 to 8, even more preferably 2 to 6, and particularly preferably 2 to 5. Furthermore, the number of atoms constituting the longest chain of the substituted alkyl group is preferably 3 to 35, more preferably 3 to 25, even more preferably 3 to 15, and particularly preferably 3 to 11.

[0242] In the present invention, "the number of carbon atoms in the alkyl portion of an alkyl group having a substituent" means the number of carbon atoms excluding the substituent portion of the alkyl group.

[0243] In the present invention, the term "the number of atoms constituting the longest chain of an alkyl group having a substituent" refers to the number of atoms including the substituent (i.e., the number of atoms obtained by subtracting the number of atoms in the molecular chain that does not constitute the longest chain from the total number of atoms). Furthermore, when a substituent having dissociable hydrogen atoms, such as a sulfo group or a carboxyl group, constitutes the longest chain, the hydrogen atoms are included in the calculation, regardless of whether they are dissociated. Furthermore, the number of atoms in the substituent capable of bonding to biological substances, as described later, is not included.

[0244] As can be used as R 1 ~R 4 The substituents that the alkyl group may have include alkoxy, carboxyl, alkoxycarbonyl, acyloxy, carbamoyl, acylamino, sulfo, phosphono, and -(CH2-CH2-O) b -R 21 , and groups consisting of combinations of these substituents.

[0245] As can be used as R 1 ~R 4 The alkyl group having a substituent is not particularly limited as long as it is an alkyl group having the above-mentioned substituent.

[0246] As can be used as R 1 ~R4 An alkyl group is preferably an unsubstituted alkyl group.

[0247] (-(CH2-CH2-O) b -R 21 )

[0248] Can be used as R 1 ~R 4 -(CH2-CH2-O) b -R 21 In the equation, b is 1 to 50, R 21 represents an alkyl group.

[0249] b refers to an average repeating number (also referred to simply as the repeating number), and is preferably 1 to 24, more preferably 1 to 12, further preferably 1 to 10, particularly preferably 4 to 10, and most preferably 4 to 8.

[0250] Regarding the above average number of repetitions, the compound can be 1 The average repetition number specified in the present invention is the number obtained by rounding off the first decimal place of the average repetition number calculated by the above method.

[0251] R 21 The alkyl group in the above R 1 ~R 4 The record of alkyl.

[0252] As can be used as R 1 ~R 4 -(CH2-CH2-O) b -R 21 and as R 1 ~R 4 The alkyl group may have as a substituent -(CH2-CH2-O) b -R 21 , preferably -(CH2-CH2-O) b - unsubstituted alkyl.

[0253] From the viewpoint of increasing the fluorescence intensity of the fluorescent dye itself, R 1 ~R 4 At least one of them includes -(CH2-CH2-O) b -, more preferably R 1 and R 2 At least one of the R 3 and R 4 At least one of them includes -(CH2-CH2-O) b -The structure represented.

[0254] More preferably, all phosphor moieties M in the compound of the present invention are structural moieties consisting of a cyanine pigment represented by the general formula (α) and R 1 and R 2 At least one of the R 3 and R 4 At least one of them includes -(CH2-CH2-O) b -The structure represented.

[0255] From the above -(CH2-CH2-O) b - is preferably represented by -(CH2-CH2-O) b -R 21 As R 1 ~R 4 Import.

[0256] The above-(CH2-CH2-O) b -b is the same as the above-(CH2-CH2-O) b -R 21 The b in has the same meaning.

[0257] R 1 ~R 4 The substituents extend perpendicularly to the cyanine skeleton (plane), so it is speculated that the substituents are formed by -(CH2-CH2-O) b When the structure represented by - is used as the substituent, the fused ring portion is less likely to undergo π-π interaction (the association suppression effect is enhanced), thereby being able to suppress a decrease in fluorescence intensity due to association.

[0258] (ii)R 11 ~R 13

[0259] R 11 ~R 13 Each independently represents a hydrogen atom, an alkyl group, an alkoxy group, an aryloxy group, an alkylthio group, an arylthio group, an amino group or a halogen atom. Adjacent groups may be bonded to each other to form a 5-membered ring or a 6-membered ring.

[0260] Can be used as R 11 ~R 13 The alkyl group, alkoxy group, aryloxy group, alkylthio group, arylthio group, amino group and halogen atom have the same meanings as the alkyl group, alkoxy group, aryloxy group, alkylthio group, arylthio group, amino group and halogen atom in the substituent group T described below, and the preferred ranges are also the same.

[0261] As R 11 ~R 13 The substituents that the alkyl group, alkoxy group, aryloxy group, alkylthio group, arylthio group, and amino group in the group may have include the substituents in the substituent group T described later.

[0262] In R 11 ~R 13 In the compound, the 5-membered ring or 6-membered ring formed by the adjacent groups bonding to each other can be either aromatic or aliphatic, preferably aliphatic. Furthermore, a 6-membered ring is preferably formed. The number of the 5-membered ring or 6-membered ring in the compound is not particularly limited, but is preferably 1 or 2, more preferably 1.

[0263] For example, taking the case of a=3 as an example, as a 11 ~R 13 The structures of the rings formed by the adjacent groups in the group bonded to each other can preferably include the following structures. In addition, the following examples describe R which does not form a ring structure. 11 ~R 13 The structure in which the ring structure is hydrogen atom and has no substituent is not limited to these. In addition, the structure at the end of the wavy line is omitted in the following description.

[0264] [Chemical Formula 12]

[0265]

[0266] R 11 and the carbon atom bonded to the indolenine ring has R 13 Preferred is a hydrogen atom.

[0267] R 12 And R other than the above 13 A hydrogen atom or an alkyl group is preferred.

[0268] In R 11 ~R 13 In, R 11 and R except for the carbon atom bonded to the indolenine ring 13 Other R 12 ~R 13 The adjacent groups in the group (ie, except for the carbon atom bonded to the indolenine ring) have R 13 Other R 13 and R 12 In some embodiments, the ring of the present invention is preferably a 5- or 6-membered ring, more preferably a 6-membered ring, wherein the adjacent groups in the group (in the group) are preferably bonded to each other and form 5 or 6-membered rings, more preferably form 6-membered rings.And, preferably form above-mentioned 5 or 6-membered rings in the center portion of the key connecting indoline ring and indolenine ring.The ring formed in the center portion of the key connecting indoline ring and indolenine ring refers to the ring of atoms formed from the carbon atom that the bonded atoms number equates from indoline ring and indolenine ring as ring.

[0269] The phosphor portion M is connected to the R 1 ~R 4 、R 11 ~R 13、R 22 ~R 25 、R 32 ~R 35 、R 41 or R 42 One hydrogen atom is removed from any of them to form a monovalent structural portion.

[0270] Specifically, by using 1 ~R 4 、R 11 ~R 13 、R 22 ~R 25 、R 32 ~R 35 、R 41 or R 42 A hydrogen atom is removed from a substituent to form a monovalent structural part, or a hydrogen atom that can be used as R is removed. 11 ~R 13 、R 22 ~R 25 or R 32 ~R 35 The hydrogen atoms in R 11 ~R 13 、R 22 ~R 25 or R 32 ~R 35 The carbon atom to which the group is bonded has a monovalent structural portion having a connecting bond.

[0271] Among them, the phosphor portion M is preferably obtained by 41 and R 42 A monovalent structure is formed by removing one hydrogen atom from the ring formed by bonding, or by removing a hydrogen atom from a ring that can be used as R 12 (Preferably, R is present on carbon atoms with the same number of bonding atoms as the indoline ring and the indolenine ring. 12 ) is formed into a monovalent structural portion by removing one hydrogen atom from a substituent.

[0272] (iii)R 22 ~R 25 and R 32 ~R 35

[0273] R 22 ~R 25 and R 32 ~R 35 represents a hydrogen atom, an alkyl group, an alkoxy group, an aryl group, a sulfo group, a sulfamoyl group, a carboxyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyloxy group, a carbamoyl group, an acylamino group, a nitro group or a halogen atom. 22 ~R 25 and R 32~R 35 , adjacent groups can bond to each other to form a fused ring.

[0274] Can be used as R 22 ~R 25 and R 32 ~R 35 The alkyl group, alkoxy group, aryl group, sulfo group, sulfamoyl group, carboxyl group, alkoxycarbonyl group, aryloxycarbonyl group, acyloxy group, carbamoyl group, acylamino group, nitro group and halogen atom in the substituent group T described below have the same meanings as the alkyl group, alkoxy group, aryl group, sulfo group, sulfamoyl group, carboxyl group, alkoxycarbonyl group, aryloxycarbonyl group, acyloxy group, carbamoyl group, acylamino group, nitro group and halogen atom in the substituent group T described later.

[0275] As R 22 ~R 25 and R 32 ~R 35 The adjacent groups in the condensed ring are bonded to each other and are not particularly limited. For example, a naphthalene ring (a benzene ring formed by bonding the adjacent groups to each other and R 22 ~R 25 The bonded benzene ring or R 32 ~R 35 In addition, from the viewpoint of suppressing association, it is preferred that R 22 ~R 25 and R 32 ~R 35 Adjacent groups in the ring are not bonded to each other and do not form a fused ring.

[0276] From the viewpoint of improving water solubility and suppressing association, R 22 ~R 25 At least one of the R 32 ~R 35 At least one of them has a hydrophilic group, more preferably R 22 ~R 25 Bonded ring and R 32 ~R 35 Each of the bonded rings has at least one hydrophilic group. For example, R 22 ~R 25 and R 32 ~R 35 When adjacent groups in the formula (R) are bonded to each other to form a naphthalene ring as a condensed ring, 22 ~R 25 The number of bonded rings is 2 and R 32 ~R 35 The number of the bonded rings is 2, and more preferably R 22 ~R 25 At least 2 of the above and R32 ~R 35 At least two of them have a hydrophilic group. The upper limit is not particularly limited as long as it is an achievable structure, and can be appropriately adjusted according to the number of hydrophilic groups in the entire compound described later.

[0277] The hydrophilic group is not particularly limited, and examples thereof include an alkoxy group, a carboxyl group, a sulfo group, and a phosphono group having a substituent, with a sulfo group being preferred.

[0278] R 22 ~R 25 and R 32 ~R 35 It is preferably a hydrogen atom, an alkyl group, a sulfo group, a nitro group or a halogen atom, more preferably a hydrogen atom, an alkyl group, a sulfo group or a halogen atom, and still more preferably a hydrogen atom, an alkyl group or a sulfo group.

[0279] (iv)R 41 and R 42

[0280] R 41 and R 42 represents an alkyl group or -(CH2-CH2-O) b -R 21 . R 21 and b and the above R 21 and b have the same meaning.

[0281] As R 41 and R 42 The substituent that the alkyl group in the group may have includes an alkoxy group, a carboxyl group, an alkoxycarbonyl group, an acyloxy group, a carbamoyl group, an acylamino group, a sulfo group, a phosphono group, and a group consisting of a combination of these substituents.

[0282] Can be used as R 41 and R 42 The alkyl group has the same meaning as the alkyl group in the substituent group T described below.

[0283] The unsubstituted alkyl group preferably has 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, and even more preferably 1 to 3 carbon atoms.

[0284] The number of carbon atoms in the alkyl moiety of the substituted alkyl group is preferably 1 to 10, more preferably 1 to 8, even more preferably 1 to 7, even more preferably 1 to 6, and even more preferably 1 to 5. Furthermore, the number of atoms constituting the longest chain of the substituted alkyl group is preferably 3 to 14, more preferably 3 to 12, and even more preferably 3 to 10.

[0285] As can be used as R 41 and R 42The alkyl group having a substituent is preferably an alkyl group having at least one of an alkoxy group, a carboxyl group, a sulfo group, and a phosphono group as a substituent, and more preferably an alkyl group having at least one of a carboxyl group and a sulfo group as a substituent, from the viewpoint of further improving water solubility. Alternatively, the alkyl group may be an alkyl group having a substituent consisting of a combination of the preferred substituents (alkoxy group, carboxyl group, sulfo group, and phosphono group) described above and groups other than these substituents.

[0286] Furthermore, the above-mentioned R 1 ~R 4 An alkyl group having a substituent may be used.

[0287] About R 41 and R 42 -(CH2-CH2-O) b -R 21 , the above R can be preferably applied 1 ~R 4 -(CH2-CH2-O) b -R 21 Records of.

[0288] R 41 and R 42 They may be bonded to each other to form a ring.

[0289] In the cyanine pigment represented by the above general formula (α), R 41 and R 42 Preferred examples of structures that are bonded to each other to form a ring include cyanine dyes represented by the following general formula (β).

[0290] [Chemical Formula 13]

[0291]

[0292] Where, L x and L y represents an alkylene group or -(CH2-CH2-O) b -alkylene-*. * indicates the bonding position to U.

[0293] The linking group U represents a divalent linking group having 1 to 100 atoms.

[0294] R 1 ~R 4 、R 11 ~R 13 、R 22 ~R 25 、R 32 ~R 35 , b and a and R in the above general formula (α) 1 ~R 4、R 11 ~R 13 、R 22 ~R 25 、R 32 ~R 35 , b and a have the same meanings, and unless otherwise specified, the preferred ranges are also the same.

[0295] R 1 ~R 4 , L x , L y and at least one of U comprises -(CH2-CH2-O) b - represents a structure. b has the same meaning as b above.

[0296] Among them, the cyanine pigment represented by formula (β) is neutral.

[0297] Can be used as L x and L y The alkylene group is equivalent to the alkylene group which can be used as R 41 and R 42 An alkylene group obtained by removing one hydrogen atom or a substituent from an alkyl group having a substituent.

[0298] Can be used as L x and L y The number of carbon atoms of the alkylene portion of the alkylene group can preferably be applied to R 41 and R 42 The number of carbon atoms in the alkyl portion of the alkyl group having a substituent is described.

[0299] Can be used as L x and L y -(CH2-CH2-O) b -alkylene-* is equivalent to the 41 and R 42 -(CH2-CH2-O) b -R 21 (R 21 represents an alkyl group having a substituent. 21 -(CH2-CH2-O) obtained by removing one hydrogen atom or substituent from an alkyl group b -alkylene.

[0300] Can be used as L x and L y -(CH2-CH2-O) b In -alkylene-*, b is preferably 1 to 10, more preferably 1 to 8, and the number of carbon atoms in the alkylene portion can be preferably adapted to R 41 and R 42The number of carbon atoms in the alkyl portion of the alkyl group having a substituent is described.

[0301] From the viewpoint of further improving the fluorescence intensity, it is preferred that L x and L y All include -(CH2-CH2-O) b -The structure represented.

[0302] The total number of atoms constituting the linking group U is 1 to 100, preferably 10 to 90, more preferably 20 to 90, and even more preferably 30 to 80.

[0303] The linking group U is preferably selected from alkylene, -O-, -NR 50 -、-COO-、-CONR 50 -and-SO2NR 50 - a divalent linking group formed by three or more bonds. 50 represents a hydrogen atom or an alkyl group.

[0304] The number of carbon atoms in the alkylene portion of the alkylene group that can be used as the linking group U is preferably 1-10, more preferably 1-8, further preferably 1-7, particularly preferably 1-6, and most preferably 1-5.

[0305] In the present invention, "the number of carbon atoms in the alkylene portion of the alkylene group" means the number of carbon atoms excluding the substituents possessed by the alkylene group.

[0306] Can be used as R 50 The alkyl group of R 1 ~R 4 The record of alkyl in .

[0307] As R 50 , preferably a hydrogen atom.

[0308] The above-mentioned alkylene, -O-, -NR 50 -、-COO-、-CONR 50 -and-SO2NR 50 The number of - is preferably 3 to 11, more preferably 3 to 7, further preferably 3 to 5, and particularly preferably 3.

[0309] Regarding the linking group U, x and L y The linking portion is preferably -O-, -NR 50 -、-COO-、-CONR 50 -or-SO2NR 50 That is, the linking group U is preferably connected via -O-, -NR 50 -、-COO-、-CONR50 -or-SO2NR 50 -bonded to L x and L y The linking group U is more preferably x and L y The connecting part is -O-, -NR 50 -、-COO-、-CONR 50 -or-SO2NR 50 - A divalent linking group in which the above-mentioned linking portions are linked to each other via an alkylene group.

[0310] The linking group U preferably becomes a monovalent structure part, ie, a phosphor part M, by removing one hydrogen atom. In the linking group U, as the part from which one hydrogen atom is removed, an alkylene group or a group as R 50 The alkyl group is preferably an alkylene group.

[0311] In the linking group U, from alkylene or as R 50 When one hydrogen atom is removed from an alkyl group, it can be directly removed from the alkylene group or as R 50 One hydrogen atom is removed from the alkyl group, and the linker group ZZZ can be bonded to the alkylene group or as R 50 The alkyl group ZZZ becomes the connecting bond.

[0312] Examples of the linking group ZZZ include alkylene, alkenylene, alkynylene, arylene, heteroarylene, -O-, -S-, >C=O, >NR 60 ,>S=O,>S(=O)2,>P(=O)OR 70 、-COO-、-CONR 60 - and -(CH2-CH2-O) p -, and a group consisting of a combination of substituents thereof. The number of combinations is not particularly limited, and can be, for example, 2 to 20, preferably 2 to 7, and more preferably 2 to 5.

[0313] R 60 and R 70 is a hydrogen atom or an alkyl group, preferably a hydrogen atom. 60 and R 70 The alkyl group of R 50 The record of alkyl in .

[0314] p represents the number of repetitions, and is preferably 1-10, more preferably 1-8, and even more preferably 1-4.

[0315] (v)a

[0316] a is an integer of 1 to 3, and preferably an integer of 2 or 3.

[0317] Among the cyanine pigments represented by the above general formula (α), R 1 ~R 4 、R 41 and R 42 At least one of them includes -(CH2-CH2-O) b -represented structure. b has the same meaning as the above b. Thus, it is believed that the compound of the present invention having a structural portion consisting of a cyanine pigment represented by the general formula (α) can have moderate hydrophilicity and moderate excluded volume effect, and the obtained labeled biological substance can show excellent fluorescence intensity.

[0318] Moreover, with respect to the anthocyanine pigment represented by the above-mentioned general formula (α), from the viewpoint of imparting sufficient hydrophilicity as the compound of the present invention, the number of hydrophilic groups per molecule of the anthocyanine pigment represented by the general formula (α) is preferably 2 or more, more preferably 2 to 8, further preferably 2 to 6, and particularly preferably 3 to 6.

[0319] As the hydrophilic group, the aforementioned R 22 ~R 25 and R 32 ~R 35 Description of hydrophilic groups that can be used.

[0320] The position of the hydrophilic group is not particularly limited unless otherwise specified. Preferred examples of the group having the hydrophilic group include R 11 ~R 13 、R 22 ~R 25 、R 32 ~R 35 、R 41 or R 42 .

[0321] In the structure represented by the general formula (α) or (β), a monovalent structural part (phosphor part M) can be formed by removing one hydrogen atom from any substituent, for example, preferably by removing one hydrogen atom from the linking group U to form a monovalent structural part, or by removing one hydrogen atom from a group that can be used as R 12 (Preferably, R is present on carbon atoms with the same number of bonding atoms as the indoline ring and the indolenine ring. 12 ) is formed into a monovalent structural portion by removing one hydrogen atom from a substituent.

[0322] In addition, unless otherwise specified, descriptions of substituents in general formulae (α) and (β) are descriptions of substituents applicable only to general formulae (α) and (β).

[0323] Furthermore, as the phosphor portion M, any component composed of a commercially available fluorescent dye can be used without particular limitation. Examples of such commercially available fluorescent dyes include Alexa Fluor 350, Alexa Fluor 405, Alexa Fluor 430, Alexa Fluor 488, Alexa Fluor 514, Alexa Fluor 532, Alexa Fluor 546, Alexa Fluor 555, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 633, Alexa Fluor 635, Alexa Fluor 647, Alexa Fluor 660, Alexa Fluor 680, Alexa Fluor 700, Alexa Fluor 750, Alexa Fluor 790, DyLight 350, DyLight 405, DyLight 425Q, DyLight 488, DyLight 510-LS, DyLight 515-LS, DyLight 550, DyLight 594, DyLight 633, DyLight 650, DyLight 680, DyLight 730-B1, DyLight 747-B4, DyLight 800, DyLight 650-4xPEG, DyLight 800-4xPEG, etc. (all are product names manufactured by Thermo Fisher Scientific Inc.), ATTO 390, ATTO 425, ATTO 465, ATTO 488, ATTO 495, ATTO 514, ATTO 520, ATTO 532, ATTO 540Q, ATTO 550, ATTO 565, ATTO RHO11, ATTO 580Q, ATTO 590, ATTO 594, ATTO610, ATTO 612Q, ATTO 620, ATTO 633, ATTO RHO14, ATTO 647, ATTO 647N, ATTO 655, ATTO665, ATTO 680, ATTO 700, ATTO 725, ATTO 740, etc. (all product names of ATTO-TEC), Cy3, Cy3B, Cy5, Cy5.5, Cy7, etc. (all products of Global Life Sciences Technologies Japan KKManufactured product name), CF 350, CF 405S, CF 405M, CF 405L, CF 430, CF 440, CF 450, CF 488A, CF503R, CF 514, CF 532, CF 535ST, CF 543, CF 550R, CF 555, CF 568, CF 570, CF 583, CF583R, CF 594, CF 594ST, CF 597R, CF 620R, CF 633, CF 640R, CF 647, CF 660C, CF 660R, CF680, CF 680R, CF 700, CF 750, CF 770, CF 790, CF 800, CF 820, CF 850, CF 870, etc. (all are product names manufactured by Biotium). Furthermore, fluorescent dyes activated by NHS esterification or the like can also be preferably used, so that these commercially available fluorescent dyes can be introduced as the fluorescent body part M in the compound of the present invention (a bond can be formed by a chemical reaction).

[0324] As a physiologically active substance portion that can be used as M, as long as it is a structural portion consisting of a physiologically active substance, it can be used without particular limitation. As a physiologically active substance, for example, vitamins, coenzymes, hormones, antibiotics, neurotransmitters, cytokines, etc. can be cited, more specifically calicheamicin, adriamycin, daunorubicin, mitomycin (Mitomycin) C, bleomycin (Bleomycin), cyclocytidine (Cyclocytidine), vincristine (Vincristine), vinblastine, methotrexate, cisplatin or its derivatives, auristatin or its derivatives, maytansine or its derivatives, paclitaxel (taxol) or its derivatives, camptothecin (Camptothecin) or its derivatives, etc., can be applied to the records of

[0095] to

[0099] sections of Japanese Patent Application Laid-Open No. 2021-020956.

[0325] As a prodrug moiety that can be used as M, any structural moiety consisting of a compound that is metabolized in an organism and converted into a physiologically active substance can be used without particular limitation. As a prodrug, for example, the description in paragraph

[0003] of Japanese Patent Application Laid-Open No. 2020-105187 (prodrug form of 2-pyrroline doxorubicin) can be applied.

[0326] As a radioisotope containing portion that can be used as M, as long as it is a structural part comprising a radioisotope that can be utilized in the medical field, it can be used without particular limitation. As a radioisotope, for example, iodine 131, indium 111, yttrium 90 and lutetium 177, copper 64 can be cited, but are not limited to these. The records of

[0225] section of Japanese Patent Application Laid-Open No. 2021-11483 can be applied. As a structural part comprising a radioisotope, a structural part obtained by bonding or coordination of the above-mentioned radioisotope with a nitrogen atom, a sulfanyl group, an aryl group or a heteroaryl group, etc., of an amino group or a tertiary amine can be cited. Examples of the structural moiety in which a nitrogen atom of a tertiary amine is coordinated to the above-mentioned radioactive isotope include structural moieties such as DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) coordinated to the above-mentioned radioactive isotope to form a complex. Examples of the structural moiety in which a sulfanyl group is coordinated to the above-mentioned radioactive isotope include structural moieties composed of complexes such as diacetylbis(N(4)-methylthiosemicarbazone)copper(II).

[0327] <Compound represented by general formula (III)>

[0328] The compound represented by the above-mentioned general formula (II) is preferably represented by the following general formula (III).

[0329] [Chemical Formula 14]

[0330]

[0331] Where Y 1 ~Y 3 、Z 1 ~Z 3 and W 1 ~W 3 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an amino group, a hydroxyl group, an alkoxy group, a sulfanyl group, an aryl group, a heteroaryl group, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E .

[0332] LL 3 and LL 4 represents a divalent linking group.

[0333] s, t, and u are integers greater than or equal to 0.

[0334] R 4 ~R 7 、R 11 , L 1 , L 2 , L 5 , L 6、X 1 ~X 3 , M, L, R E , g, n and m and R in the above general formula (II) 4 ~R 7 、R 11 , L 1 , L 2 , L 5 , L 6 、X 1 ~X 3 , M, L, R E , g, n and m have the same meaning.

[0335] The structure enclosed by s, t or u cannot be the structure represented by the above general formula (I). 1 Not with W 1 or Z 1 Bonding or Y 2 Not with W 2 or Z 2 Bonding, or Y 3 Not with W 3 or Z 3 The ions are bonded to form a structure represented by the general formula (I).

[0336] Y 1 ~Y 3 、Z 1 ~Z 3 and W 1 ~W 3 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an amino group, a hydroxyl group, an alkoxy group, a sulfanyl group, an aryl group, a heteroaryl group, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E .

[0337] Can be used as Y 1 ~Y 3 、Z 1 ~Z 3 or W 1 ~W 3 Alkyl, alkenyl, alkynyl, acyl, amino, alkoxy, aryl, heteroaryl, anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E and-(LO) g R Eand the alkyl, alkenyl, alkynyl, acyl, amino, alkoxy, aryl, heteroaryl, anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) in the substituent group T described below. g R E and-(LO) g R E The meanings are the same as those in the preceding text, and the preferred ranges are also the same.

[0338] Can be used as Y 1 ~Y 3 、Z 1 ~Z 3 or W 1 ~W 3 The alkyl, alkenyl, alkynyl, acyl, amino, alkoxy, aryl and heteroaryl groups may be unsubstituted or have a substituent. Examples of the substituents that may be substituted include the substituents in the substituent group T described below. For example, an aryl group, a halogen atom, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E .

[0339] And, it can form Y 1 ~Y 3 、Z 1 ~Z 3 or W 1 ~W 3 The substituents that the above-mentioned alkyl, alkenyl, alkynyl, acyl, amino, alkoxy, aryl and heteroaryl groups may have may be further substituted with a substituent selected from the substituent group T described below, for example, preferably an anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E or -(LO) g R E .

[0340] Y 1 ~Y 3 It is preferably a hydrogen atom, an alkyl group, an aryl group or a heteroaryl group, and more preferably a hydrogen atom or an alkyl group.

[0341] W 1 ~W 3 It is preferably a hydrogen atom, an alkyl group, an aryl group or a heteroaryl group, and more preferably a hydrogen atom.

[0342] Z 1 ~Z 3 It is preferably an alkyl group, an aryl group or a heteroaryl group, and more preferably an alkyl group.

[0343] In the compound represented by the general formula (III), in order to suppress the interaction between the structures represented by the general formula (I), a group having a charge repulsive effect is preferred. From this viewpoint, Z 1 ~Z 3 At least one of them preferably contains an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E and-(LO) g R E More preferably, it is a group containing at least one of anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E and-(LO) g R E At least one alkyl group.

[0344] Here, "Z 1 ~Z 3 At least one of the residues is an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E and-(LO) g R E The term "at least one of the groups" refers to a group that satisfies at least one of the following conditions (Z1) to (Z3).

[0345] Condition (Z1): The above s is an integer greater than 1 and the above Z 1 Anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E and-(LO) g R E At least one of the groups.

[0346] Condition (Z2): The above t is an integer greater than 1 and the above Z 2 Anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E and-(LO) g R E At least one of the groups.

[0347] Condition (Z3): u is an integer greater than 1 and Z 3 Anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E and-(LO)g R E At least one of the groups.

[0348] And, "Z 1 ~Z 3 At least one of the residues is an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E and-(LO) g R E At least one alkyl group in the above conditions (Z1) to (Z3) refers to the following: "anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E and-(LO) g R E At least one of the groups)" is replaced by "anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E and-(LO) g R E In addition to being an alkyl group of at least one of the above conditions (Z1) to (Z3), at least one of the above conditions (Z1) to (Z3) is satisfied.

[0349] In addition, Z 1 ~Z 3 Each group may include an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) within the range of obtaining the effect of suppressing the interaction between the structures represented by the general formula (I). g R E and-(LO) g R E 2 or more groups in .

[0350] LL 3 and LL 4 represents a divalent linking group, preferably an alkylene group, an alkenylene group, an alkynylene group, an arylene group, a heteroarylene group, -O-, >C=O and >NR A A connecting group composed of one or more of the following. A represents a hydrogen atom or a substituent.

[0351] As can constitute LL 3 and LL 4 Alkylene, alkenylene, alkynylene, arylene, heteroarylene and>NR A , can preferably apply the above-mentioned can constitute L 1 ~L 7Alkylene, alkenylene, alkynylene, arylene, heteroarylene and>NR A Records of.

[0352] LL 3 Preferably >C=O, >NR A , alkylene, arylene or heteroarylene, more preferably >C=O or NR A In addition, R A Preferred is a hydrogen atom.

[0353] LL 4 Preferably >C=O, >NR A , alkylene, arylene or heteroarylene, more preferably >C=O or >NR A In addition, R A Preferred is a hydrogen atom.

[0354] s, t, and u are integers greater than or equal to 0.

[0355] The upper limit of s, t, and u is not particularly limited, and can be, for example, 20 or less, preferably 10 or less, and more preferably 5 or less.

[0356] In addition, when it is possible to classify it as either a structure enclosed by t or a structure enclosed by u, classification as a structure enclosed by u is given priority.

[0357] <Compound represented by general formula (IV)>

[0358] The compound represented by the above-mentioned general formula (III) is preferably represented by the following general formula (IV).

[0359] [Chemical Formula 15]

[0360]

[0361] Where Y 4 and Y 5 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an amino group, a hydroxyl group, an alkoxy group, a sulfanyl group, an aryl group, a heteroaryl group, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E .

[0362] q is an integer of 0 or 1.

[0363] R 4 ~R 7 、R 11 , L 2 , L 5、X 1 ~X 3 、Y 1 ~Y 3 、Z 1 ~Z 3 、W 1 ~W 3 , M, L, R E , g, n, m, s, t and u and R in the above general formula (III) 4 ~R 7 、R 11 , L 2 , L 5 、X 1 ~X 3 、Y 1 ~Y 3 、Z 1 ~Z 3 、W 1 ~W 3 , M, L, R E , g, n, m, s, t and u have the same meaning.

[0364] Y 4 and Y 5 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an amino group, a hydroxyl group, an alkoxy group, a sulfanyl group, an aryl group, a heteroaryl group, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E .

[0365] Can be used as Y 4 or Y 5 Alkyl, alkenyl, alkynyl, acyl, amino, alkoxy, aryl, heteroaryl, anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E and-(LO) g R E and the alkyl, alkenyl, alkynyl, acyl, amino, alkoxy, aryl, heteroaryl, anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) in the substituent group T described below. g R E and-(LO) g R E The meanings are the same as those in the preceding text, and the preferred ranges are also the same.

[0366] In addition, it can be used as Y 4 or Y 5The above-mentioned alkyl, alkenyl, alkynyl, acyl, amino, alkoxy, aryl and heteroaryl groups may be unsubstituted or may have a substituent.

[0367] Y 4 and Y 5 It is preferably a hydrogen atom or an alkyl group, and more preferably a hydrogen atom.

[0368] q is an integer of 0 or 1, preferably 0.

[0369] <Compound represented by general formula (V)>

[0370] The compound represented by the above-mentioned general formula (IV) is preferably represented by the following general formula (V).

[0371] [Chemical Formula 16]

[0372]

[0373] Where R 6A and R 7A represents a hydrogen atom, a hydroxyl group, a sulfanyl group, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, a heteroaryl group, an amino group, an acyl group, or Q. 6A and R 7A At least one of them represents a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support.

[0374] L 8 and L 9 Represents a single bond or a connecting group. 6A When L is a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support 9 For connection>NY 4 and R 6A The shortest number of atoms in the connecting group is 3 or more, R 7A When L is a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support 8 For connection (>C=O) q and R 7A The shortest number of atoms in the linking group is 3 or more.

[0375] R 4 、R 5 、R 11 , L 2 , L 5 、X 1 ~X 3 、Y 1 ~Y 5 、Z 1 ~Z 3 、W 1~W 3 , M, Q, n, m, q, s, t and u and R in the above general formula (IV) 4 、R 5 、R 11 , L 2 , L 5 、X 1 ~X 3 、Y 1 ~Y 5 、Z 1 ~Z 3 、W 1 ~W 3 , M, Q, n, m, q, s, t and u have the same meaning.

[0376] R 6A or R 7A and L 9 or L 8 Determined as R 6A or R 7A is an unsubstituted group, L 9 or L 8 Become the longest group. Among them, in the -L 9 R 6A or -L 8 R 7A When the group represented by has Q, the group located at the most terminal side (-L 9 R 6A R in 6A Side, -L 8 R 7A R in 7A Q on the side becomes R 6A or R 7A Determined by the method.

[0377] R 6A and R 7A represents a hydrogen atom, a hydroxyl group, a sulfanyl group, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, a heteroaryl group, an amino group, an acyl group, or Q. 6A and R 7A At least one of them represents a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support.

[0378] Can be used as R 6A or R 7A The alkyl, alkenyl, alkynyl, aryl, alkoxy, heteroaryl, amino, and acyl groups in the following substituent group T have the same meanings and preferred ranges as the alkyl, alkenyl, alkynyl, aryl, alkoxy, heteroaryl, amino, and acyl groups described later. In addition, all of them are unsubstituted groups.

[0379] Can be used as R 6Aand R 7A Q has the same meaning as Q described above, and the preferred range is also the same.

[0380] R 6A It is preferably an alkyl group, a sulfanyl group, an aryl group, a heteroaryl group or Q, more preferably an alkyl group or Q, and further preferably an alkyl group, a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support.

[0381] R 7A It is preferably an alkyl group, a sulfanyl group, an aryl group, a heteroaryl group or Q, more preferably an alkyl group or Q, and further preferably an alkyl group, a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support.

[0382] L 8 and L 9 represents a single bond or a linking group.

[0383] As can be used as L 8 and L 9 The connecting group is preferably an alkylene group, an alkenylene group, an alkynylene group, an arylene group, a heteroarylene group, -O-, >C=O and >NR A A connecting group composed of one or a combination of two or more of the following. A represents a hydrogen atom or a substituent.

[0384] Can form L 8 or L 9 Alkylene, alkenylene, alkynylene, arylene, heteroarylene and>NR A It is possible to preferably apply the aforementioned L 1 ~L 7 Alkylene, alkenylene, alkynylene, arylene, heteroarylene and>NR A Records of.

[0385] As can constitute L 8 or L 9 The substituents that the alkylene, alkenylene, alkynylene, arylene and heteroarylene groups may have are not particularly limited, but are preferably selected from the substituent group T described below, and more preferably include halogen atoms, aryl groups or alkyl groups. 8 or L 9 The substituents that the above-mentioned alkylene, alkenylene, alkynylene, arylene and heteroarylene groups may have may be further substituted with a substituent selected from the substituent group T described below, for example, preferably an anionic group, a cationic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E .

[0386] And, about the L 8 or L 9 The number of substituents that the above-mentioned alkylene, alkenylene, alkynylene, arylene and heteroarylene groups may have is not particularly limited as long as they can be used as a structure, and can be set to at least 1 or more as an upper limit, and is not particularly limited. For example, all hydrogen atoms in the alkylene, alkenylene, alkynylene, arylene and heteroarylene groups may be replaced by substituents.

[0387] Among them, R 6A When L is a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support 9 For connection>NY 4 and R 6A The shortest number of atoms in the connecting group is 3 or more, R 7A When L is a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support 8 For connection (>C=O) q and R 7A The shortest number of atoms in the linking group is 2 or more.

[0388] Regarding the above-mentioned divalent linking group L 9 , "Connect>NY 4 With R 6A The shortest number of atoms is the number of atoms that make up the connection>NY 4 With R 6A The number of atoms in the shortest chain of the divalent linking group L 8 , "Connect (>C=O) q With R 7A The shortest number of atoms is the number of atoms that form the connection (>C=O) q With R 7A The number of atoms in the shortest chain. In addition, >NY 4 It refers to L 9 Direct bonded>NY 4 , (>C=O) q When q is 1, it means that 8 Direct bond>C=O, when q is 0, it means there is -L bond 5 -M's carbon atom.

[0389] In the compound represented by the above general formula (V), R 6A and R 7A At least one of them is a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support. The carboxyl group, the substituent capable of bonding to a biological substance, or the substituent capable of bonding to a solid support is bonded to (>C=O) through a linking group having at least 2 atoms.q or >NY 4 bonding, thereby connecting R 6A and R 7A The bonding point between the main chain of 5 With R 5 Bonded carbon atom or L 2 With R 4 The distance between the carbon atoms to which the fluorescent part M is bonded) becomes farther, and the steric hindrance around the carboxyl group, the substituent capable of bonding to a biological substance, or the substituent capable of bonding to a solid support is reduced, thereby improving the reactivity of the pigment polymer with a fluorescent part M of 2 or more in the compound to the antibody, and can increase the fluorescence labeling rate (DOL).

[0390] The above R 6A and R 7A At least one of the carboxyl group, the substituent capable of bonding to a biological substance, or the substituent capable of bonding to a solid support, and the carboxyl group, the substituent capable of bonding to a biological substance, or the substituent capable of bonding to a solid support is connected to (>C=O) q or >NY 4 The shortest number of atoms in the connecting group (R 6A When it is a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support, the connection is >NY 4 and R 6A The shortest atomic number and R 7A Connection when it is a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support (>C=O) q and R 7A The shortest number of atoms in the nucleotide sequence (the number of atoms in the shortest sequence) is preferably 2 to 60, more preferably 2 to 40, and further preferably 2 to 20.

[0391] In the present invention, from the viewpoint of ease of synthesis, L 8 and L 9 Any one of them is included -(LO) g -, more preferably L 8 To include - (LO) g -group.

[0392] L 8 More preferably, they are a single bond, an alkylene group, -O-, >C=O, and >NR A The connecting group formed by one or a combination of two or more of the above is more preferably a single bond, an alkylene group, -O-, >C=O, >NR A 、In by-[NR A -NR A-alkylene group, -NR A -(LO) g -alkylene or -C(=O)-(LO) g -alkylene.

[0393] L 9 More preferably, they are a single bond, an alkylene group, -O-, >C=O, and >NR A The connecting group formed by one or a combination of two or more of the above is more preferably a single bond, an alkylene group, -O-, >C=O, >NR A 、In by-[NR A -NR A -alkylene group, -NR A -(LO) g -alkylene or -C(=O)-(LO) g -alkylene.

[0394] <Compound represented by general formula (VI)>

[0395] The compound represented by the above general formula (II) is preferably represented by the following general formula (VI). The compound represented by the following general formula (VI) corresponds to the compound represented by the above general formula (II), wherein L 1 and L 4 is>NH,L 3 C=O,L 6 is a single bond or >C=O, L 7 is a single bond, L 1 With L 2 and L 4 With L 5 These are compounds that are bonded to each other to form a specific 5-membered ring.

[0396] [Chemical Formula 17]

[0397]

[0398] Where, X 4 ~X 9 Indicates -O-, -S-, >NR 101 or >CR 102 R 103 .

[0399] Among them, X 4 ~X 6 At least one of them is >NL 10 -M or>C(R 102 )-L 10 -M,X 7 ~X9 At least one of them is >NL 11 -M or>C(R 102 )-L 11 -M.

[0400] Neither -L 10 -M is not -L 11 -M's R 101 ~R 103 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an acyl group, -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E .

[0401] L 10 and L 11 represents a single bond or a divalent linking group.

[0402] n1 is an integer greater than or equal to 2, and q is an integer of 0 or 1.

[0403] R 4 ~R 11 、X 1 ~X 3 , M, L, R E , g and m and R in the above general formula (II) 4 ~R 11 、X 1 ~X 3 , M, L, R E , g and m have the same meaning.

[0404] As X 4 ~X 6 , except X 4 ~X 6 At least one of them is >NL 10 -M or>C(R 102 )-L 10 Except for -M, unless otherwise specified, X in the above general formula (I) can be applied 1 ~X 3 Records of.

[0405] And, as X 7 ~X 9 , except X 7 ~X 9 At least one of them is >NL 11 -M or>C(R 102)-L 11 Except for -M, unless otherwise specified, X in the above general formula (I) can be applied 1 ~X 3 Records of.

[0406] That is, as X 4 and X 7 Can apply the aforementioned X 1 Records, as X 5 and X 8 Can apply the aforementioned X 2 Records as X 6 and X 9 Can apply the aforementioned X 3 As neither -L 10 -M is not -L 11 -M's R 101 、R 102 and R 103 , can be applied to the R in the aforementioned general formula (I) 1 、R 2 and R 3 Records of.

[0407] In X 4 ~X 9 Does not have -L 10 -M and -L 11 -M>NR 101 and >CR 102 R 103 In, R 101 Preferably, R 102 and R 103 Preferred is a hydrogen atom.

[0408] As in X 4 ~X 6 Does not have the above-L 10 -M, preferably at least one of the two groups is >CR 102 R 103 , more preferably at least one is >CR 102 R 103 And the remaining one is -O-, -S- or >CR 102 R 103 , further preferably both are >CR 102 R 103 .

[0409] As in X 7 ~X 9 Does not have the above-L 11 -M, preferably at least one of the two groups is >CR 102 R 103, more preferably at least one is >CR 102 R 103 And the remaining one is -O-, -S- or >CR 102 R 103 , further preferably both are >CR 102 R 103 .

[0410] In X 4 ~X 6 In, as>NL 10 -M or>C(R 102 )-L 10 -M, preferably >C(R 102 )-L 10 -M, more preferably >CH-L 10 -M.

[0411] In X 7 ~X 9 In, as>NL 11 -M or>C(R 102 )-L 11 -M, preferably >C(R 102 )-L 11 -M, more preferably >CH-L 11 -M.

[0412] X 4 ~X 6 -L 10 The group of -M is not particularly limited, and is preferably X 5 .

[0413] X 7 ~X 9 -L 11 The group of -M is not particularly limited, and is preferably X 8 .

[0414] L 10 and L 11 Preferably, it is a single bond or an alkylene group, an alkenylene group, an alkynylene group, an arylene group, a heteroarylene group, -O-, -S-, >C=O and >NR A alkylene, alkenylene, alkynylene, arylene, heteroarylene, -O-, -S-, >C=O and >NR A One or more of the group consisting of a combination of *-L x1 -L y1 -** represents a group.

[0415] About the L 10 and L 11Alkylene, alkenylene, alkynylene, arylene, heteroarylene and>NR A Unless otherwise specified, the aforementioned L 2 and L 5 Alkylene, alkenylene, alkynylene, arylene, heteroarylene and>NR A Records of.

[0416] L x1 is a single bond, or a group consisting of one or a combination of two or more of an alkylene group, an alkenylene group, an alkynylene group, an arylene group, and a heteroarylene group, L y1 is a single bond, -O-, -S-, >C=O or >NR A In addition, in *-L x1 -L y1 -**, * indicates X 4 ~X 9 , ** represents the connection bond with M.

[0417] About L 10 and L 11 , in the above by *-L x1 -L y1 Among the groups represented by -**, L is also preferred. y1 is a single bond, -S-, >C=O or >NR A More preferably, L y1 >C=O or >NR A The group is further preferably L x1 is a single bond and L y1 >C=O or >NR A group.

[0418] In the compound represented by the above general formula (VI), M and X are connected 4 ~X 9 Any connection chain of L 10 The connecting chain and the L 11 The shortest number of atoms in each connecting chain can be, for example, 1 to 60, preferably 1 to 40. In the case where M is a fluorescent part, the shortest number of atoms refers to the number of atoms that constitute the conjugated structure connecting the fluorescent part and X in the fluorescent part M. 4 ~X 9 The number of atoms in the shortest chain in any of the connected chains.

[0419] In addition, in the compound represented by the above general formula (VI), it is also preferred that the conjugated structure portion of M-the aforementioned linking group ZZZ-L 10 - represented by the structure of "-linking group ZZZ-L 10-" in the connecting chain, and the conjugated structure of M - the aforementioned connecting group ZZZ-L 11 - represented by the structure of "-linking group ZZZ-L 11 Any part of the connecting chain represented by "-" has the aforementioned -(CH2-CH2-O) b -The structure represented by (b is also as mentioned above).

[0420] n1 is an integer greater than or equal to 2.

[0421] The compound represented by the general formula (VI) has a rigid linker main chain connecting the two phosphor moieties compared to the compound represented by any of the general formulas (III) to (V), which can further suppress pigment association. Therefore, the lower limit of n1 is preferably an integer of 3 or greater, and an integer of 5 or greater is more preferred from the perspective of obtaining a sufficient effect of increasing fluorescence intensity. An integer of 9 or greater is further preferred, and an integer of 12 or greater is particularly preferred. This also applies when the number of phosphor moieties is 2 or greater.

[0422] The upper limit of n1 is, for example, preferably an integer of 36 or less, more preferably an integer of 24 or less, and further preferably an integer of 18 or less. That is, n1 is preferably an integer of 2 to 36, more preferably an integer of 3 to 36, further preferably an integer of 5 to 24, particularly preferably an integer of 9 to 24, and particularly preferably an integer of 12 to 18.

[0423] q is an integer of 0 or 1, preferably 0.

[0424] <Compound represented by general formula (VII)>

[0425] The compound represented by the above-mentioned general formula (VI) is preferably represented by the following general formula (VII).

[0426] [Chemical Formula 18]

[0427]

[0428] Where R 6A and R 7A represents a hydrogen atom, a hydroxyl group, a sulfanyl group, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, a heteroaryl group, an amino group, an acyl group, or Q. 6A and R 7A At least one of them represents a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support.

[0429] L 12 and L 13 represents a single bond or a linking group.

[0430] na and nb are integers greater than or equal to 0, and r and v are integers of 0 or 1.

[0431] R 4 、R 5 、R 11 , L 10 , L 11 、X 1 ~X 9 , M, Q, q, n1 and m and R in the above general formula (VI) 4 、R 5 、R 11 , L 10 , L 11 、X 1 ~X 9 , M, Q, q, n1 and m have the same meaning.

[0432] Unless otherwise stated, R 6A and R 7A and R in the aforementioned general formula (V) 6A and R 7A That is, as R 6A and R 7A R in the aforementioned general formula (V) can be applied 6A and R 7A Records of.

[0433] R 6A or R 7A and L 12 or L 13 Determined as R 6A or R 7A is an unsubstituted group, L 12 or L 13 Become the longest group. Among them, in the -L 13 R 6A or -L 12 R 7A When the group represented by has Q, the group located at the most terminal side (-L 13 R 6A R in 6A Side, -L 12 R 7A R in 7A Q on the side becomes R 6A or R 7A Determined by the method.

[0434] L 12 and L 13 represents a single bond or a linking group.

[0435] As can be used as L 12 and L 13The connecting group is preferably an alkylene group, an alkenylene group, an alkynylene group, an arylene group, a heteroarylene group, -O-, >C=O and >NR A A connecting group composed of one or a combination of two or more of the following. A represents a hydrogen atom or a substituent.

[0436] As can constitute L 12 and L 13 Alkylene, alkenylene, alkynylene, arylene, heteroarylene and>NR A , which can be applied to the above general formula (V) and can constitute L 8 or L 9 Alkylene, alkenylene, alkynylene, arylene, heteroarylene and>NR A Records of.

[0437] The compound represented by the above general formula (VII) is preferably one in which (A)na is an integer greater than or equal to 0 (preferably an integer greater than or equal to 1), and R 6A is a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support, and / or the sum of (B)nb and v is an integer greater than or equal to 0 (preferably an integer greater than or equal to 1), and R 7A It is a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support.

[0438] In the case of (A) above, L 13 The shortest number of atoms connected is 7 or less. In the case of (B) above, L 12 The shortest number of connected atoms is less than 7.

[0439] Regarding the above-mentioned divalent linking group L 13 , "L 13 The shortest number of connected atoms is "when na is an integer greater than 1" and refers to the number of atoms that will be connected using () na The bracketed structure shows the N and L 13 Directly bonded N and R 6A The number of atoms in the shortest chain to be connected, when na is 0, refers to the number of atoms that will be connected using () m The bracketed structure shows the N and L 13 Directly bonded N and R 6A The number of atoms in the shortest chain to make the connection.

[0440] Furthermore, regarding the above-mentioned divalent linking group L 12 , and the above “L 13 The shortest number of connected atoms" is the same as "L 12 The shortest number of atoms connecting R 7A and located on the paper relative to L12 L on the left 12 The number of atoms in the shortest chain of bonded atoms.

[0441] For example, in the compound (1) used in the examples described below, L 12 -NHC2H4-, R 7A is -COOH, so L 12 The shortest number of connected atoms is 3.

[0442] In the compound represented by the above general formula (VII), R 6A and R 7A At least one of the substituents is a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support. In particular, it is believed that by satisfying the above-mentioned (A) and / or (B), the mobility of the linker main chain is reduced, thereby further inhibiting pigment association.

[0443] The above L 12 The shortest number of connected atoms and L 13 The shortest linking atoms are preferably 1-5, more preferably 1-4.

[0444] In the present invention, from the viewpoint of ease of synthesis, L 12 and L 13 Any one of them is included -(LO) g -, more preferably L 12 To include - (LO) g -group.

[0445] L 12 More preferably, it is a single bond or a combination of alkylene, -O-, >C=O and >NR A A connecting group composed of one or more of the above, more preferably a single bond, -NR A -alkylene or -NR A -(LO) g -alkylene, more preferably a single bond or -NR A -alkylene.

[0446] L 13 More preferably, it is a single bond or a combination of alkylene, -O-, >C=O and >NR A A connecting group composed of one or more of the above, more preferably a single bond, >NR A Or>C=O.

[0447] na and nb are integers greater than or equal to 0. r and v are integers of 0 or 1.

[0448] In R 6AIn the case of a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support, na is preferably an integer of 0-40, more preferably an integer of 0-20, and even more preferably an integer of 0-15.

[0449] In R 7A In the case of a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support, the total of nb and v is preferably an integer of 0-40, more preferably an integer of 0-20, and even more preferably an integer of 0-15.

[0450] In R 6A When it is not a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support, na is preferably an integer of 0-20, more preferably an integer of 0-10, and even more preferably an integer of 0-5.

[0451] In R 7A When it is not a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support, the total of nb and v is preferably an integer of 0-20, more preferably an integer of 0-10, and even more preferably an integer of 0-5.

[0452] r is preferably 0, and v is preferably 0.

[0453] When the compound represented by any of the general formulae (II) to (VII) among the compounds of the present invention is obtained by peptide synthesis, the right side on the paper is usually the C-terminal structure and the left side on the paper is the N-terminal structure.

[0454] The compound of the present invention preferably contains at least one carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support among the substituents represented by Q.

[0455] The compounds of the present invention can be bonded to biological substances via the carboxyl group or the substituent group capable of bonding to biological substances described later, thereby obtaining target labeled biological substances. In addition, the carboxyl group can be easily derivatized into a substituent group capable of bonding to biological substances by conventional methods.

[0456] Moreover, the compound of the present invention can be bonded to a solid support such as microparticles through a carboxyl group or a substituent capable of bonding to a solid support described later, thereby obtaining target labeled microparticles, etc. As microparticles, there are no particular limitations, and examples include small particles useful for bonding to the compound of the present invention, such as non-polymer beads such as glass beads and magnetic beads, and polymer beads. In a certain embodiment, the microparticles include polystyrene beads. As for small particles, as long as they are of a size commonly used in fluorescent labeling, they are not particularly limited, and typically, the average particle size is 10 nm to 10 μm. In addition, the carboxyl group can be easily derived into a substituent capable of bonding to a solid support by conventional methods.

[0457] In the present invention, for convenience, the substituent capable of bonding to a biological substance and the substituent capable of bonding to a solid support do not include a carboxyl group. The "substituent capable of bonding to a biological substance" includes a substituent capable of bonding to a biological substance derived from a carboxyl group, and the "substituent capable of bonding to a solid support" includes a substituent capable of bonding to a solid support derived from a carboxyl group. However, as described above, bonding to a biological substance or a solid support can also be achieved through a carboxyl group.

[0458] In the compounds of the present invention, there is no particular limitation on the position of the carboxyl group, the substituent capable of bonding to a biological substance, or the substituent capable of bonding to a solid support. Preferably, the carboxyl group is present in the structure represented by the general formula (I) and in the structure other than the fluorescent portion. In the compounds represented by the general formula (II), preferably, the substituent is present in R 6 and R 7 At least one of them has.

[0459] The total number of the above-mentioned carboxyl groups, substituents capable of bonding to biological substances, or substituents capable of bonding to solid supports in the compounds of the present invention may be at least one. From the perspective of quantitative determination of the target substance, the total number is preferably 1 to 3, more preferably 1 or 2, and even more preferably 1.

[0460] Furthermore, from the viewpoint of imparting sufficient hydrophilicity to the compound, the compound of the present invention also preferably has an anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL)- g R E or -(LO) g R E For example, it is preferably one or more, more preferably 1 to 8, and even more preferably 1 to 6.

[0461] Regarding anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO)g R E The position of is not particularly limited unless otherwise specified, and may include the above-mentioned anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E For example, in the compound represented by the general formula (III), Z 1 ~Z 3 、X 1 ~X 3 or R 11 Among the compounds represented by the general formula (VI), preferably, X 1 ~X 3 or R 11 .

[0462] Specific examples of the compounds of the present invention are shown below, but the present invention is not limited to these compounds. In the following specific examples, the sulfonic group can dissociate the hydrogen ion and adopt a salt structure. In the case of having a salt structure, it can be used as X + Examples of the monovalent cations and polyvalent cations include the above-mentioned alkali metal cations, alkaline earth metal cations, organic ammonium cations, organic phosphonium cations, and the like.

[0463] In the following specific examples, Dye represents a phosphor portion.

[0464] [Chemical Formula 19]

[0465]

[0466] [Chemical Formula 20]

[0467]

[0468] [Chemical Formula 21]

[0469]

[0470] The compounds of the present invention can bind to biological substances such as proteins (including peptides), amino acids, nucleic acids, nucleotides, sugar chains, and lipids via at least one substituent capable of binding to biological substances, and can be used as labels for biological substances.

[0471] As a substituent capable of bonding to a biological substance, any substituent capable of interacting with (including adhering to) or bonding to a biological substance can be used without particular limitation. For example, substituents described in International Publication No. 2002 / 026891 can be cited. Specifically, the electrophilic groups and nucleophilic groups described in Table 2 of International Publication No. 2002 / 026891, and the reactive groups Rx described on page 18, line 16 to page 19, line 13 of International Publication No. 2002 / 026891 can be applied to the present invention.

[0472] Specific examples of the "substituent capable of bonding to a biological substance" include the following structures.

[0473] [Chemical Formula 22]

[0474]

[0475] X represents a halogen atom such as an iodine atom or a bromine atom. * represents a bond.

[0476] In addition to the above, as the "substituent capable of bonding to a biological substance", a peptide structure (polyamino acid structure), a long-chain alkyl group, etc. can be used.

[0477] Among them, preferred are NHS ester structure (N-hydroxysuccinimide ester structure), succinimide structure, maleimide structure, azide group, acetylene group, peptide structure (polyamino acid structure), long-chain alkyl group (preferably having 12 to 30 carbon atoms), and quaternary ammonium group.

[0478] Specific examples of compounds having at least one substituent capable of bonding to a biological substance include, for example, the aforementioned exemplary compounds of the present invention in which the carboxyl group is appropriately substituted with a substituent capable of bonding to the aforementioned biological substance. The present invention is not limited to these compounds. For example, in these specific examples, groups having dissociable hydrogen atoms, such as carboxyl and sulfo groups, can adopt salt structures by dissociation of the hydrogen atoms.

[0479] The compound of the present invention can be bonded to a solid support such as the above-mentioned fine particles via a substituent capable of bonding to at least one solid support possessed by the compound, and can be used as a solid support reagent.

[0480] As a substituent capable of bonding to a solid support, any substituent capable of acting (including attaching) or bonding to a solid support can be used without particular limitation, and preferably includes the substituents listed above as substituents capable of bonding to a biological substance. Among these, preferably include an NHS ester structure (N-hydroxysuccinimide ester), a succinimide structure, or a maleimide structure.

[0481] In the compounds of the present invention, as specific examples of compounds having at least one substituent capable of bonding to a solid support, for example, the carboxyl group in the exemplary compounds of the present invention described above is appropriately substituted with a substituent capable of bonding to the solid support described above. Furthermore, the present invention is not limited to these compounds. For example, in these specific examples, groups having dissociable hydrogen atoms, such as carboxyl and sulfo groups, can adopt salt structures by dissociation of the hydrogen atoms.

[0482] The compounds of the present invention can be synthesized by conventional methods. For example, they can be synthesized based on peptide synthesis such as peptide solid phase synthesis, and a method using an automatic peptide synthesis apparatus described in International Publication No. 2018 / 174078 can also be preferably applied. The phosphor portion, physiologically active substance portion, prodrug portion, and radioisotope-containing portion can also be synthesized according to conventional methods and introduced into the compounds of the present invention.

[0483] Compounds having a substituent capable of bonding to a biological substance can also be synthesized according to conventional methods. For example, reference can be made to Bioconjugate Techniques (Third Edition, by Greg T. Hermanson).

[0484] <<Marking of biological substances>>

[0485] The labeled biological substance of the present invention is a substance formed by bonding a compound of the present invention to a biological substance. The compound of the present invention has fluorescence caused by the fluorescent body part and exhibits excellent fluorescence intensity in solution, and therefore can be preferably used to label biological substances. The bonding between the compound of the present invention and the biological substance can be a direct bonding method or a method of bonding via a linking group.

[0486] As the above-mentioned biological substances, preferably proteins (including peptides), amino acids, nucleic acids, nucleotides, sugar chains and lipids can be mentioned. As proteins, antibodies can be preferably mentioned, and as lipids, phospholipids, fatty acids and sterols can be preferably mentioned, and phospholipids are more preferred.

[0487] Among the above-mentioned biological substances, substances useful in clinical pathology are not particularly limited. Examples thereof include immunoglobulins such as Ig (Immunoglobulin) G, IgM, IgE, IgA, and IgD, complement, plasma proteins such as C-reactive protein (CRP), ferritin, α1 microglobulin, and β2 microglobulin, and antibodies thereto, tumor markers such as α-fetoprotein, carcinoembryonic antigen (CEA), prostatic acid phosphatase (PAP), CA (carbohydrate antigen) 19-9, and CA-125, and antibodies thereto, hormones such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), estrogen, and insulin, and antibodies thereto, and substances related to viral infection such as hepatitis B virus (HBV)-related antigens (HBs, HBe, and HBc), human immunodeficiency virus (HIV), and adult T-cell leukemia (ATL), and antibodies thereto.

[0488] In addition, bacteria such as diphtheria, Clostridium botulinum, Mycoplasma, and Treponema pallidum and their antibodies, protozoa such as Toxoplasma, Trichomonas, Leishmania, Trypanosoma, and Plasmodium and their antibodies, and ES cells (Embryonic Stem Cells) such as ELM3, HM1, KH2, v6.5, v17.2, and v26.2 (derived from mouse 129, 129 / SV, C57BL / 6, and BALB / c) can also be mentioned. Cells (e.g., embryonic stem cells) and their antibodies, antiepileptic drugs such as phenytoin and phenobarbital, cardiovascular drugs such as quinidine and digoxin, antiasthmatic drugs such as theophylline, antibiotics such as chloramphenicol and gentamicin, and their antibodies, other enzymes, bacterial exotoxins (such as streptolysin O) and their antibodies, etc. Furthermore, antibody fragments such as Fab'2, Fab, and Fv can also be used.

[0489] Specific embodiments of the compound of the present invention and the biological substance interacting and bonding include, for example, the following embodiments.

[0490] Examples include:

[0491] i) non-covalent bonds (e.g., hydrogen bonds, ionic bonds including chelation) or covalent bonds between the peptide in the compound of the present invention and the peptide in the biological substance;

[0492] ii) van der Waals forces between the long-chain alkyl groups in the compounds of the present invention and lipid bilayer membranes and lipids in biological substances;

[0493] iii) generating an amide bond by reaction of an NHS ester (N-hydroxysuccinimide ester) in the compound of the invention with an amino group in a biological substance;

[0494] iv) generating a thioether bond by reaction of a maleimide group in a compound of the invention with a sulfanyl (-SH) group in a biological substance; and

[0495] v) Formation of a triazole ring by a click reaction of an azide group in the compound of the present invention with an acetylene group in a biological substance or based on a click reaction of an acetylene group in the compound with an azide group in a biological substance.

[0496] In the above-mentioned embodiment i), the peptide in the compound of the present invention is not particularly limited as long as it can form a non-covalent bond or a covalent bond with a peptide in a biological substance. As the position of such a peptide, for example, R in the general formula (II) can be preferably mentioned. 6 or R 7 .

[0497] In addition to the above methods i) to v), binding can also be achieved using the method described in, for example, Lucas CDde Rezende and Flavioda Silva Emery, "A Review of the Synthetic Strategies for the Development of BODIPY Dyes for Conjugation with Proteins," Orbital: The Electronic Journal of Chemistry, 2013, Vol. 5, No. 1, pp. 62-83. Furthermore, the methods described in this document can be appropriately referenced in the preparation of the labeled biomaterial of the present invention.

[0498] Among the compounds of the present invention, the labeled biomaterial of the present invention obtained from a compound having a substituent capable of bonding to a biological substance and a biological substance bonded thereto through interaction with the compound includes compounds and products described in paragraph 0038 of JP-A-2019-172826, wherein a portion other than the substituent capable of bonding to a biological substance is substituted with a compound of the present invention, and products thereof. However, the present invention is not limited to these labeled biomaterials and the like.

[0499] <Reagents containing labeled biological substances>

[0500] In the reagent containing the labeled biological substance of the present invention, the labeled biological substance of the present invention is not particularly limited and can be appropriately selected according to the intended use, for example, in the form of a solution dissolved in an aqueous medium such as physiological saline and phosphate buffer, or in the form of a solid such as a microparticle powder or a freeze-dried powder.

[0501] For example, when the labeled biological substance of the present invention is used as a fluorescent labeling reagent, it can also be used as a reagent containing any of the above-mentioned labeled biological substances.

[0502] <Application of labeled biological substances>

[0503] The labeled biological substance of the present invention obtained from the compound of the present invention is believed to exhibit excellent fluorescence intensity due to the excellent fluorescence intensity exhibited by the compound of the present invention, and it is believed that fluorescence emitted by the labeled biological substance excited by light irradiation can be stably detected. Therefore, the labeled biological substance of the present invention can be applied to various techniques using fluorescent labels, and can be preferably used as a fluorescent labeling reagent or a bioluminescent imaging reagent in multicolor Western blotting or dot blotting, for example.

[0504] Fluorescence detection using the labeled biological substance of the present invention generally includes the following steps (i) to (iii) or (iv) to (vii). Fluorescence detection including steps (i) to (iii) is a direct method using a primary antibody fluorescently labeled with a compound of the present invention, while fluorescence detection including steps (iv) to (vii) is an indirect method using a secondary antibody fluorescently labeled with a compound of the present invention.

[0505] (i) Prepare the following steps (a) and (b) separately

[0506] (a) A sample containing a target biological substance (hereinafter also referred to as "target biological substance")

[0507] (b) A labeled biosubstance of the present invention (hereinafter also referred to as "labeled biosubstance A of the present invention") formed by binding a biosubstance capable of binding to the target biosubstance in (a) above (hereinafter also referred to as "primary biosubstance") to the compound of the present invention.

[0508] (ii) preparing a bonded product (hereinafter also referred to as "fluorescently labeled bonded product A") in which the target biomaterial in (a) above is bonded to the primary biomaterial in the labeled biomaterial A of the present invention in (b) above.

[0509] (iii) irradiating the fluorescently labeled linker A with light in a wavelength region absorbed by the labeled biological substance A of the present invention, and detecting the fluorescence emitted by the labeled biological substance A of the present invention

[0510] (iv) Prepare the following steps (c) to (e) respectively

[0511] (c) Sample containing target biological material

[0512] (d) A biomaterial capable of binding to the target biomaterial in (c) above (hereinafter also referred to as "primary biomaterial").

[0513] (e) A labeled biosubstance of the present invention (hereinafter also referred to as "labeled biosubstance B of the present invention") formed by bonding a biosubstance capable of bonding to the primary biosubstance of (d) above (hereinafter also referred to as "secondary biosubstance") to the compound of the present invention.

[0514] (v) A step of preparing a bonded product (hereinafter also referred to as "bonded product b") in which the target biomaterial in (c) and the primary biomaterial in (d) are bonded.

[0515] (vi) A step of preparing a bonded body (hereinafter also referred to as "fluorescently labeled bonded body B2") in which the primary biomaterial in the bonded body b is bonded to the secondary biomaterial in the labeled biomaterial B of the present invention.

[0516] (vii) irradiating the fluorescently labeled linker B2 with light in a wavelength region absorbed by the labeled biological substance B of the present invention, and detecting the fluorescence emitted by the labeled biological substance B of the present invention

[0517] Examples of the biomaterial capable of binding to the target biomaterial (primary biomaterial) and the biomaterial capable of binding to the primary biomaterial (secondary biomaterial) include the biomaterials described above as labeled biomaterials of the present invention. These biomaterials can be appropriately selected depending on the target biomaterial (biomaterial in the subject) or the primary biomaterial, and can be selected to specifically bind to the biomaterial in the subject or the primary biomaterial.

[0518] Among the target biological substances, proteins include so-called disease markers. Examples of disease markers include, but are not particularly limited to, α-fetoprotein (AFP), PIVKA-II (protein induced by vitamin K absence or antagonist II), BCA (breast carcinoma-associated antigen) 225, basic alpha-fetoprotein (BFP), CA (carbohydrate antigen) 15-3, CA19-9, CA72-4, CA125, CA130, CA602, CA54 / 61 (CA546), carcinoembryonic antigen (CEA), DUPAN-2, elastase 1, immunosuppressive acidic protein (IAP), NCC-ST-439, γ-sperm protein (γ-Sm), prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), neuro-specific enolase (NSE), Iba1, amyloid Protein β, Tau, flotillin, squamous cell carcinoma-associated antigen (SCC antigen), sialyl LeX-i antigen (SLX), SPan-1, tissue polypeptide antigen (TPA), sialyl Tn antigen (STN), cytokeratin (CYFRA), pepsinogen (PG), C-reactive protein (CRP), serum amyloid A (SAA), myoglobin, creatine kinase (CK), troponin T, ventricular myosin light chain I, etc.

[0519] The target biological substance may be bacteria. Examples of the bacteria include, but are not particularly limited to, bacteria that are the subject of cell microbiological examinations, such as Escherichia coli, Salmonella, Legionella, and bacteria that cause public health problems.

[0520] The above-mentioned target biological substance can be a viral antigen. The viral antigen is not particularly limited. For example, hepatitis virus antigens such as antigens of hepatitis C and B viruses, p24 protein antigens of HIV virus, pp65 protein antigens of CMV (cytomegalovirus), E6 and E7 proteins of HPV (human papillomavirus), etc. can be cited.

[0521] In the above (i) or (iv), the sample containing the target biological substance is not particularly limited and can be prepared according to a conventional method.

[0522] Furthermore, the labeled biomaterial of the present invention is not particularly limited and can be prepared by bonding a biomaterial capable of bonding to a target biomaterial to the compound of the present invention according to conventional methods. The bond morphology and bond-forming reactions are as described above for the labeled biomaterial of the present invention.

[0523] In (v) above, the target biomaterial and the primary biomaterial may be bonded directly or through a biomaterial different from the target biomaterial and the primary biomaterial. Furthermore, in (vi) above, the primary biomaterial in the bonder b and the secondary biomaterial in the labeled biomaterial B of the present invention may be bonded directly or through a biomaterial different from the primary biomaterial and the secondary biomaterial.

[0524] The labeled biological substance of the present invention can be used as a fluorescently labeled antibody in either the direct method or the indirect method, but is preferably used as a fluorescently labeled antibody in the indirect method.

[0525] In the above (ii) or (v) and (vi), the binding of the labeled biological substance of the present invention to the target biological substance is not particularly limited and can be carried out according to conventional methods.

[0526] In (iii) or (vii) above, the wavelength used to excite the labeled biomaterial of the present invention is not particularly limited as long as it is a wavelength of light capable of exciting the labeled biomaterial of the present invention, but is generally preferably 300 to 1000 nm, more preferably 400 to 800 nm.

[0527] The fluorescence excitation light source used in the present invention is not particularly limited, as long as it emits light of a wavelength capable of exciting the labeled biological substance of the present invention. For example, various laser light sources can be used. Furthermore, various optical filters can be used to obtain a preferred excitation wavelength or to detect only fluorescence.

[0528] The other matters in (i) to (vii) above are not particularly limited, and conditions such as methods, reagents, and apparatuses generally used in fluorescence detection using fluorescent labels can be appropriately selected.

[0529] Furthermore, regarding steps other than the above-mentioned (i) to (vii), conditions such as commonly used methods, reagents, and apparatuses can be appropriately selected according to various methods using fluorescent labels.

[0530] For example, multicolor Western blotting using the labeled biological substance of the present invention can be performed by preparing a blot membrane using methods commonly used for target biological substances (protein separation by electrophoresis, blotting to a membrane, and membrane agglutination). By using the labeled biological substance of the present invention as a labeled antibody (preferably a secondary antibody), the target biological substance can be detected with excellent fluorescence intensity. Dot blots using the labeled biological substance of the present invention can also be performed similarly to multicolor Western blotting. By preparing a blotted nitrocellulose membrane or a blotted PVDF (polyvinylidene fluoride) membrane using methods commonly used for target biological substances, the target biological substance can be detected with excellent fluorescence intensity by using the labeled biological substance of the present invention as a labeled antibody (preferably a secondary antibody).

[0531] -Substituent Group T-

[0532] In the present invention, preferred substituents include substituents selected from the following substituent group T.

[0533] Furthermore, in the present invention, when only a substituent is described, the description of the corresponding substituent in the substituent group T can be referred to and applied. For example, when only "alkyl" is described, the description of "alkyl" in the substituent group T can be referred to and applied. This also applies to substituents other than "alkyl".

[0534] Furthermore, in the present invention, examples of substituents that a certain substituent such as an "alkyl group" may have include substituents selected from the following substituent group T. Furthermore, when a certain substituent such as an "alkyl group" has a substituent and further has a substituent, examples of substituents that the certain substituent may have include a substituent obtained by combining two or more substituents selected from the following substituent group T.

[0535] In addition, in the present invention, when alkyl and cyclic (cyclo) alkyl are distinguished and recorded, alkyl is used to include the meaning of straight-chain alkyl and branched-chain alkyl. On the other hand, when alkyl and cyclic alkyl are not distinguished and recorded and when not otherwise specified, alkyl is used to include the meaning of straight-chain alkyl, branched-chain alkyl and cycloalkyl. This is also the same for groups (alkoxy, alkylthio, alkenyloxy, etc.) that can adopt a cyclic structure, and compounds that include groups that can adopt a cyclic structure. When a group can form a cyclic skeleton, the lower limit of the number of atoms of the group forming the cyclic skeleton is independent of the lower limit of the number of atoms specifically recorded below about the group that can adopt the structure, and is 3 or more, preferably 5 or more.

[0536] In the following description of the substituent group T, for example, in order to clarify a group having a linear or branched structure and a group having a cyclic structure, such as an alkyl group and a cycloalkyl group, these may be described separately.

[0537] The groups included in the substituent group T include the following groups.

[0538] Examples include alkyl groups (preferably having 1 to 30 carbon atoms, more preferably 1 to 20 carbon atoms, further preferably 1 to 12 carbon atoms, further preferably 1 to 8 carbon atoms, further preferably 1 to 6 carbon atoms, and particularly preferably 1 to 3 carbon atoms), alkenyl groups (preferably having 2 to 30 carbon atoms, more preferably 2 to 20 carbon atoms, further preferably 2 to 12 carbon atoms, further preferably 2 to 6 carbon atoms, further preferably 2 to 4 carbon atoms), and alkynyl groups (preferably having 2 to 30 carbon atoms, further preferably The aryl group preferably has 2 to 20 carbon atoms, more preferably 2 to 12 carbon atoms, more preferably 2 to 6 carbon atoms, and more preferably 2 to 4 carbon atoms), a cycloalkyl group (preferably 3 to 20 carbon atoms), a cycloalkenyl group (preferably 5 to 20 carbon atoms), an aryl group (which may be a monocyclic group or a condensed ring group (preferably a condensed ring group of 2 to 6 rings). In the case of a condensed ring group, it is composed of a 5- to 7-membered ring. The aryl group preferably has 6 to 40 carbon atoms, more preferably 6 to 30 carbon atoms, and more preferably 6 to 8 carbon atoms. ~26, more preferably 6 to 10 carbon atoms), a heterocyclic group (having at least one nitrogen atom, oxygen atom, sulfur atom, phosphorus atom, silicon atom or selenium atom as a ring-constituting atom, which may be a monocyclic group or a condensed ring group (preferably a condensed ring group having 2 to 6 rings). In the case of a monocyclic group, the number of ring members is preferably 5 to 7, more preferably 5 or 6. The number of carbon atoms in the heterocyclic group is preferably 2 to 40, more preferably 2 to 20. The heterocyclic group includes an aromatic heterocyclic group (heteroaryl) and an aliphatic heterocyclic group (aliphatic heterocyclic group). ), alkoxy (preferably having 1 to 20 carbon atoms, more preferably 1 to 12 carbon atoms), alkenyloxy (preferably having 2 to 20 carbon atoms, more preferably 2 to 12 carbon atoms), alkynyloxy (preferably having 2 to 20 carbon atoms, more preferably 2 to 12 carbon atoms), cycloalkyloxy (preferably having 3 to 20 carbon atoms), aryloxy (preferably having 6 to 40 carbon atoms, more preferably 6 to 26 carbon atoms, further preferably 6 to 14 carbon atoms), heterocyclicoxy (preferably having 2 to 20 carbon atoms), polyalkyleneoxy,

[0539] Alkoxycarbonyl (preferably having 2 to 20 carbon atoms), cycloalkoxycarbonyl (preferably having 4 to 20 carbon atoms), aryloxycarbonyl (preferably having 6 to 20 carbon atoms), amino (preferably having 0 to 20 carbon atoms, including unsubstituted amino (-NH2), (mono- or di-) alkylamino, (mono- or di-) alkenylamino, (mono- or di-) alkynylamino, (mono- or di-) cycloalkylamino, (mono- or di-) cycloalkenylamino, (mono- or di-) arylamino, (mono- or di-) heterocyclic amino. Substituted unsubstituted amino Each of the above groups in the group has the same meaning as the corresponding group in the substituent group T. ), sulfamoyl (preferably a sulfamoyl group having 0 to 20 carbon atoms, preferably an alkyl, cycloalkyl or aryl group.), acyl (preferably a group having 1 to 20 carbon atoms, more preferably a group having 2 to 15 carbon atoms, including -C(=O)H, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, and heterocyclic carbonyl.), acyloxy (preferably a group having 1 to 20 carbon atoms), carbamoyl (preferably a carbamoyl group having 1 to 20 carbon atoms, preferably an alkyl, cycloalkyl or aryl group.),

[0540] Acylamino (preferably having 1 to 20 carbon atoms), sulfonamide (preferably having 0 to 20 carbon atoms, preferably an alkyl, cycloalkyl or aryl sulfonamide), alkylthio (preferably having 1 to 20 carbon atoms, more preferably 1 to 12 carbon atoms), cycloalkylthio (preferably having 3 to 20 carbon atoms), arylthio (preferably having 6 to 40 carbon atoms, more preferably 6 to 26 carbon atoms, further preferably 6 to 14 carbon atoms), heterocyclic thio (preferably having 2 to 20 carbon atoms), alkyl, cycloalkyl or arylsulfonyl (preferably having 1 to 20 carbon atoms),

[0541] Silyl group (preferably a silyl group having 1 to 30 carbon atoms, more preferably a silyl group having 1 to 20 carbon atoms, preferably a silyl group substituted by an alkyl group, an aryl group, an alkoxy group or an aryloxy group), silyloxy group (preferably a silyl group having 1 to 20 carbon atoms, preferably a silyloxy group substituted by an alkyl group, an aryl group, an alkoxy group or an aryloxy group), hydroxyl group, cyano group, nitro group, halogen atom (for example, fluorine atom, chlorine atom, bromine atom or iodine atom), oxygen atom (specifically, >CH2 constituting the ring is substituted by >C=O), carboxyl group ( -CO2H), phosphonyl group〔-PO(OH)2〕, phosphonyloxy group〔-O-PO(OH)2〕, sulfonyl group (-SO3H), boric acid group〔-B(OH)2〕, onium group (also referred to as a cationic group. Examples include ammonium groups, sulfonium groups, and phosphonium groups containing cyclic ammonium groups, preferably having 0 to 30 carbon atoms, more preferably 1 to 20 carbon atoms), sulfanyl group (-SH), guanidinium group (-NHC(=NH)NH2), betaine residue, polyol residue, sugar residue or polyamino acid residue.

[0542] (Anionic group)

[0543] In the present invention, the anionic group may be any group having an anion. Examples of such anionic groups include a carboxyl group, a phosphono group (phosphonic acid group, -PO(OH)2), a phosphonooxy group (phosphoric acid group, -OPO(OH)2), and a sulfo group. Preferably, the anionic group is a phosphono group, a phosphonooxy group, or a sulfo group, and more preferably, a phosphonooxy group or a sulfo group.

[0544] The anionic group may dissociate into an ionic structure or a salt structure. When the anionic group has a salt structure, the monovalent or polyvalent cation described above for the salt structure can be preferably used as the monovalent or polyvalent cation.

[0545] (Cationic Group)

[0546] In the present invention, the cationic group can be any group having a cation. Examples of such cationic groups include groups having a quaternary ammonium ion (ammonium group) and groups having a quaternary phosphonium ion (phosphonium group), and preferably groups having a quaternary ammonium ion. + The substituents and P in the group having a quaternary phosphonium ion + The substituents may preferably be alkyl and aryl, more preferably N + and P + All substituents present are alkyl groups.

[0547] In addition to the ionic structure, the cationic group may also have a salt structure. When the cationic group has a salt structure, the monovalent or polyvalent anion may include, for example, F - 、Cl - Halide ions, BF4 - PF6 - , bis(trifluoromethylsulfonyl)imide ion and other monovalent or polyvalent organic anions.

[0548] (Betaine residue)

[0549] In the present invention, a betaine residue refers to a group obtained by removing one hydrogen atom from a compound having a betaine structure. A compound having a betaine structure may be any compound containing both an anionic group and a cationic group in the same molecule. Preferably, the compound contains at least one anionic group selected from the group consisting of a carboxyl group, a phosphonyl group, a phosphonyloxy group, and a sulfonic group, and at least one cationic group selected from the group consisting of an ammonium group and a phosphonium group in the same molecule.

[0550] Furthermore, a group obtained by removing one hydrogen atom from a compound that does not contain an anionic group and a cationic group in the same molecule is not a betaine residue but is classified as an anionic group having a salt structure or a cationic group having a salt structure as described above.

[0551] (polyol residue)

[0552] In the present invention, a polyol residue refers to a group obtained by removing one hydrogen atom from a polyol compound having two or more hydroxyl groups in the molecule, and is not a sugar residue or a polyalkyleneoxy group as described below. The polyol residue may be a chain group or a group having a cyclic structure, and an example thereof includes a cyclodextrin residue.

[0553] (Sugar residue)

[0554] In the present invention, a sugar residue refers to a group obtained by removing one hydrogen atom from a sugar compound. Sugar compounds may include monosaccharides, polysaccharides formed by bonding two or more sugars, sugar alcohols, and chemically modified sugars formed by copolymerizing sugars with epichlorohydrin or the like.

[0555] In addition, residues belonging to sugar residues among polyol residues are classified as sugar residues.

[0556] Examples of the sugar residue include glucose, sucrose, maltose, lactose, trehalose, ribitol, sorbitol, mannitol, maltitol, lactitol, xylitol, fructose, 1-kestose, kestose trihydrate, fucose, dulcitol, galactooligosaccharides, 4'-galactosyl lactose, isomaltooligosaccharides, lactulose, palatinitol, isomaltulose monohydrate, raffinose pentahydrate, dihydroxyacetone dimer, galactose, glyceraldehyde dimer, mannose, ribose, xylose, lactosyl oligosaccharides, Fructoside), Erythritol, Dulcoside A, Isosteviol, Rebaudioside A, Rebaudioside B, Rebaudioside C, Rebaudioside D, Rebaudioside F, Rubusoside, Stevioside, 1-Deoxynojirimycin, Fucoidan, Rhamnose, Threose, Arabinose, Lyxose, Allose A group derived by removing one hydrogen atom from a sugar compound such as hydroxystearic acid, hydroxyethyl ester, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone, thiazolinone,

[0557] (polyamino acid residues)

[0558] In the present invention, a polyamino acid residue refers to a group formed by removing one hydrogen atom from an amino acid compound or a polyamino acid compound formed by bonding two or more amino acids. In the present invention, a polyamino acid residue is a group used to adjust to neutrality (total charge 0) in the use of the compounds and labeled biomaterials of the present invention.

[0559] (Polyalkylene oxide)

[0560] In the present invention, the above-mentioned polyalkyleneoxy group is composed of -(OL) g R E or -(LO)g R E The group represented by .

[0561] In addition, among the polyol residues, residues belonging to a polyalkyleneoxy group are classified as a polyalkyleneoxy group.

[0562] The above-mentioned L represents an alkylene group obtained by removing one hydrogen atom from the alkyl group in the above-mentioned substituent group T, and the number of carbon atoms is preferably 2 to 4, more preferably 2 or 3, and even more preferably 2. The number of carbon atoms contained in the connecting bond of the alkylene group, i.e., the shortest chain connecting two carbon atoms, is preferably 0 to 2, more preferably 0 or 1, and even more preferably 0. That is, L is most preferably a vinyl group.

[0563] The above g refers to the average repeating number (also referred to simply as the repeating number), and is preferably 2 to 50, more preferably 12 to 50, and even more preferably 24 to 50. Even when the repeating number is small, such as g being 2, appropriate hydrophilicity and an appropriate excluded volume effect can be exhibited.

[0564] The above R E With the aforementioned R 8 ~R 10 and have the same meaning as R, and represent a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an aryl group, a heteroaryl group, an anionic group, a betaine residue, a polyol residue, a sugar residue or a polyamino acid residue, preferably a hydrogen atom or an alkyl group. E The alkyl group of the above-mentioned substituent group T can be preferably applied to the alkyl group, and among them, the alkyl group having 1 to 3 carbon atoms is preferred. E The alkyl group may have a substituent.

[0565] In the present invention, the substituent group is described as all or part of the options of the specific substituent: "anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E 、-(LO) g R E ”, unless otherwise specified, the substituent group in the options of the specific substituent is: “anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E 、-(LO) g R E "Preferably substituted with the substituent group: anionic group, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E 、-(LO) g R E", more preferably substituted with the substituent group: "phosphono, phosphonooxy, sulfo, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E 、-(LO) g R E ”.

[0566] This also applies to the case where all or part of the following substituent groups are described as the preferred range of substituents: "anionic group, betaine residue, polyol residue, sugar residue, polyamino acid residue, -(OL) g R E 、-(LO) g R E ”

[0567] Furthermore, as a group formed by combining substituents selected from the substituent group T multiple times, for example, there can be mentioned anionic groups (carboxyl groups, phosphono groups, sulfo groups), cationic groups (onium groups), betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E 、-(LO) g R E As a substituent, the above-mentioned alkyl group, alkenyl group, alkynyl group, cycloalkyl group, cycloalkenyl group, aryl group, heterocyclic group, alkoxy group, alkenyloxy group, alkynyloxy group, cycloalkyloxy group, aryloxy group, heterocyclic group, alkoxycarbonyl group, cycloalkyloxycarbonyl group, aryloxycarbonyl group, amino group, sulfamoyl group, acyl group, acyloxy group, carbamoyl group, acylamino group, sulfonamide group, alkylthio group, cycloalkylthio group, arylthio group, heterocyclicthio group, alkyl group, cycloalkyl group or arylsulfonyl group.

[0568] The substituent selected from the substituent group T is more preferably an alkyl group, an alkenyl group, a cycloalkyl group, an aryl group, a heterocyclic group, an alkoxy group, a cycloalkoxy group, an aryloxy group, an acyl group, an alkoxycarbonyl group, a cycloalkoxycarbonyl group, an amino group, an acylamino group, a carbamoyl group, a cyano group, a halogen atom, an anionic group, a cationic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E , particularly preferably an alkyl group, an alkenyl group, an aryl group, a heterocyclic group, an alkoxy group, an acyl group, an alkoxycarbonyl group, an amino group, an acylamino group, a carbamoyl group, a cyano group, an anionic group, a cationic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E .

[0569] Substituents selected from Substituent Group T include groups formed by combining multiple substituents selected from the above Substituent Group T. Unless otherwise specified, substituents also include groups formed by combining multiple substituents selected from the above Substituent Group T. For example, when a compound or substituent includes an alkyl group, an alkenyl group, etc., these may be substituted or unsubstituted. Furthermore, when an aryl group, a heterocyclic group, etc. is included, these may be monocyclic or condensed rings and may be substituted or unsubstituted.

[0570] Example

[0571] Hereinafter, the present invention will be described in further detail based on Examples, but the present invention is not limited thereto.

[0572] The compounds (1) to (4) of the present invention and comparative compounds (1) to (3) are shown below.

[0573] Furthermore, in each compound, even if not otherwise specified, the sulfonic group may include a salt structure (for example, potassium salt, sodium salt, TEA (triethylammonium) salt, or DIPEA (N,N-diisopropylethylammonium) salt).

[0574] Furthermore, it is believed that the fluorescence intensity of the fluorescent portion in compound (1), i.e., comparative compound (3), and the fluorescent portion in comparative compound (2), i.e., comparative compound (1) alone, are comparable, and that the difference in the structure of the fluorescent portion does not significantly contribute to the evaluation results of the fluorescence intensity of each compound described later.

[0575] [Chemical Formula 23]

[0576]

[0577] [Chemical Formula 24]

[0578]

[0579] The comparative compound (1) is the compound (5) described in International Publication No. 2022 / 025210.

[0580] The comparative compound (3) is a compound (M2-13) in the synthesis example of the compound (M2-1) described later.

[0581] Hereinafter, the synthesis methods of the respective compounds will be described in detail; however, the starting materials, pigment intermediates, and synthesis routes are not limited thereto.

[0582] In addition, the abbreviations used in the synthesis of each compound shown below are as follows.

[0583] DBU: 1,8-diazabicyclo[5.4.0]-7-undecene

[0584] PyAOP: (7-Azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate

[0585] DIC: Diisopropylcarbodiimide

[0586] NHS: N-hydroxysuccinimide

[0587] EDCI: 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride

[0588] HATU: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate

[0589] HOBt: 1-hydroxybenzotriazole

[0590] NMP: N-methyl-2-pyrrolidone

[0591] DMF: dimethylformamide

[0592] DMAP: 4-dimethylaminopyridine

[0593] DIPEA: N-diisopropylethylamine

[0594] TFA: trifluoroacetic acid

[0595] THF: Tetrahydrofuran

[0596] Me:methyl

[0597] Ms:Methylsulfonyl

[0598] Et: ethyl

[0599] tBu: tert-butyl

[0600] Ac:Acetyl

[0601] Fmoc: 9-fluorenylmethoxycarbonyl

[0602] Boc: tert-Butoxycarbonyl

[0603] Ala: alanine

[0604] Lys: lysine

[0605] Tyr: tyrosine

[0606] Pro: Proline

[0607] Resin: Resin

[0608] In addition, %v / v means volume percentage, and %w / v means mass volume percentage.

[0609] Unless otherwise specified, SNAP Ultra C18 (product name, manufactured by Biotage Japan Ltd.) or Sfar C18 (product name, manufactured by Biotage Japan Ltd.) was used as a carrier for reverse-phase column chromatography, and Hi-Flash Column (product name, manufactured by YAMAZEN CORPORATION) was used as a carrier for normal-phase column chromatography.

[0610] The mixing ratio of the eluent used in reverse-phase column chromatography or normal-phase column chromatography is a volume ratio. For example, "acetonitrile:water = 0:100 to 20:80" means changing the eluent from "acetonitrile:water = 0:100" to "acetonitrile:water = 20:80."

[0611] For separation and purification, HPLC (High Performance Liquid Chromatography) 2767 (product name, manufactured by Waters Corporation) was used.

[0612] MS spectra were measured using an ACQUITY SQD LC / MS System [product name, manufactured by Waters Corporation, ionization method: ESI (ElectroSpray Ionization)] or LCMS-2010EV [product name, manufactured by Shimadzu Corporation, ionization method: simultaneous ionization of ESI and APCI (Atmospheric Pressure Chemical Ionization)].

[0613] In addition, when synthesizing each compound, peptide chain synthesis was carried out according to the general method of the peptide solid phase method described in International Publication No. 2018 / 174078.

[0614] [General method for solid-phase peptide synthesis using an automated peptide synthesis apparatus]

[0615] Peptide solid phase synthesis was performed using an automatic peptide synthesizer (manufactured by Biotage Japan Ltd., product name: SyroI). The synthesizer was equipped with Rink Amide-ChemMatrix (registered trademark, manufactured by Biotage Japan Ltd.), a solution of Fmoc amino acid (0.5 mol / L) in N-methyl-2-pyrrolidone (NMP), a solution of cyano-hydroxyimino-ethyl acetate (1.0 mol / L) and diisopropylethylamine (0.1 mol / L) in NMP, a solution of diisopropylcarbodiimide (1.0 mol / L) in NMP, a solution of piperidine (20% v / v) in NMP, and a solution of acetic anhydride (20% v / v) in NMP, and synthesis was performed according to the instructions. Fmoc deprotection (20 minutes), washing with NMP, condensation of Fmoc amino acid (1 hour), and washing with NMP were repeated as one cycle to elongate the peptide chain.

[0616] [Synthesis of Compound (M2-1)]

[0617] Compound (M2-1) was synthesized according to the following scheme. The MS analysis results of compound (M2-13) are shown below.

[0618] MS (ESI m / z): (M+H + ) + =1384,(MH + ) - =1382

[0619] [Chemical Formula 25]

[0620]

[0621] <Synthesis of Compound (1)>

[0622] 1) Synthesis of compound (1-8)

[0623] Compound (1-8) was synthesized according to the following scheme.

[0624] [Chemical Formula 26]

[0625]

[0626] (i) Synthesis of compound (1-1)

[0627] Peptide solid-phase synthesis was performed using H-Pro-Trt(2-Cl)-Resin (manufactured by Watanabe Chemical Industries, Ltd., 0.93 mmol / g, 53.8 mg) as a starting material. N-(9-Fluorenylmethyloxycarbonyl)-L-proline (Fmoc-Pro-OH) and (2S,4S)-(tert-butyloxycarbonyl)-4-amino-1-((9H-fluoren-9-ylmethoxy)carbonyl)-pyrrolidine-2-carboxylic acid (Fmoc-L-Pro(4-NHBoc)-OH(2S,4S)) were stretched. Stretching with N-(9-Fluorenylmethyloxycarbonyl)-L-proline (Fmoc-Pro-OH) was repeated three times. (2S,4S)-(tert-Butyloxycarbonyl)-4-amino-1-((9H-fluoren-9-ylmethoxy)carbonyl)-pyrrolidine-2-carboxylic acid (Fmoc-L-Pro(4-NHBoc)-OH(2S,4S)) was stretched, and stretching with N-(9-fluorenylmethoxycarbonyl)-L-proline (Fmoc-Pro-OH) was repeated three times. (2S,4S)-(tert-Butyloxycarbonyl)-4-amino-1-((9H-fluoren-9-ylmethoxy)carbonyl)-pyrrolidine-2-carboxylic acid (Fmoc-L-Pro(4-NHBoc)-OH(2S,4S)) and N-(9-fluorenylmethoxycarbonyl)-L-proline (Fmoc-Pro-OH) were stretched. After completion of the stretching, the resin was washed with dichloromethane, and the solvent was distilled off under reduced pressure. 2.0 mL of a mixture of TFA:triisopropylsilane:water = 95:2.5:2.5 was added to cleave and deprotect the peptide. After 2 hours, the resin was filtered out, and methyl tert-butyl ether (12 mL) was added to the filtrate to form a solid. The solid was centrifuged to precipitate, and the supernatant was removed. After washing the solid with methyl tert-butyl ether, the solvent was distilled off under reduced pressure to obtain 51.2 mg of compound (1-1) as a white solid.

[0628] (ii) Synthesis of compound (1-2)

[0629] To a 50 mL eggplant-shaped flask, 352 mg of compound (1-1), 3.5 mL of chloroform (CHCl₃), 423 μL of N-diisopropylethylamine (DIPEA), and 115 μL of acetic anhydride (Ac₂O) were added and stirred at room temperature for 1 hour. The reaction solution was then concentrated and purified by HPLC, followed by freeze-drying to obtain 314 mg of compound (1-2).

[0630] (iii) Synthesis of Compound (1-3)

[0631] To a 50 mL eggplant-shaped flask, 500 mg of compound (4-1) described in International Publication No. 2020 / 175473 as compound (2-1), 5 mL of tetrahydrofuran (THF), 254 mg of N-[(9H-fluoren-9-ylmethoxy)carbonyl]-β-alanine (Fmoc-βAla-OH), 128 μL of diisopropylcarbodiimide, and 13.3 mg of 4-dimethylaminopyridine were added and stirred at room temperature for 2 hours. Acetonitrile (50 mL) was added, the precipitated solid was filtered, and dried under reduced pressure to obtain 593 mg of compound (1-3).

[0632] (iv) Synthesis of Compound (1-4)

[0633] To a 50 mL eggplant-shaped flask, 108 mg of compound (1-3), 2.2 mL of chloroform (CHCl₃), and 26.8 μL of 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) were added and stirred at 35°C for 1 hour. Then, 11.7 μL of methanesulfonic acid (MsOH), 93.3 μL of N,N-diisopropylethylamine (DIPEA), 169 mg of compound (1-2), and 141 mg of (7-azabenzotriazol-1-yloxy)tripyrrolidinylphosphonium hexafluorophosphate (PyAOP) were added and stirred at 35°C for 3 hours. Acetonitrile (10 mL) was added, and the precipitated solid was filtered and dried under reduced pressure to obtain 219 mg of compound (1-4).

[0634] (v) Synthesis of Compound (1-5)

[0635] In the synthesis of the above-mentioned compound (1-4), 233 mg of the above-mentioned compound (1-5) was synthesized from 219 mg of the compound (1-4) in the same manner, except that (2S,4S)-(tert-butoxycarbonyl)-4-amino-1-((9H-fluoren-9-ylmethoxy)carbonyl)-pyrrolidine-2-carboxylic acid (Fmoc-L-Pro(4-NHBoc)-OH(2S,4S)) was used instead of the compound (1-2), and the compound (1-4) was used instead of the compound (1-3).

[0636] (vi) Synthesis of Compound (1-6)

[0637] The same operation as in the synthesis of the above-mentioned compound (1-4) and compound (1-5) was repeated twice to synthesize 190 mg of compound (1-6) from 100 mg of compound (1-5).

[0638] (vii) Synthesis of Compound (1-7)

[0639] To a 10 mL eggplant-shaped flask, 97.5 mg of compound (1-6), 975 μL of N,N-dimethylformamide (DMF), and 8.9 μL of 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) were added and stirred at 35°C for 1 hour. 3.7 μL of acetic anhydride (Ac2O) was added and stirred at 35°C for 1 hour. The precipitated solid, which was precipitated by the addition of acetonitrile (50 mL), was filtered and dried under reduced pressure to obtain 74.1 mg of compound (1-7).

[0640] (viii) Synthesis of Compound (1-8)

[0641] To a 10 mL eggplant flask, 30.1 mg of compound (1-7) and 1.0 mL of TFA were added and stirred at room temperature for 1 hour. 10 mL of methanol (MeOH) was added to the reaction mixture to generate a solid, which was then removed by filtration. The filtrate was concentrated, purified by HPLC, and freeze-dried to obtain 10.6 mg of compound (1-8).

[0642] 2) Synthesis of compound (1)

[0643] Compound (1) was synthesized according to the following scheme.

[0644] [Chemical Formula 27]

[0645]

[0646] In a 10 mL eggplant-shaped flask, 1.5 mg of compound (1-8), 150 μL of N,N-dimethylformamide (DMF), 1 μL of triethylamine (Et3N), and 3.75 mg of compound (M2-1) were added and stirred at room temperature for 1 hour. The reaction solution was then concentrated and purified by HPLC, followed by freeze-drying to obtain 0.85 mg of compound (1). The MS analysis results of compound (1) are shown below.

[0647] MS (ESI m / z): (M+H + ) + =8571、(MH + ) - =8569

[0648] <Synthesis of Compound (2)>

[0649] In the synthesis of the above compound (1), 0.88 mg of the above compound (2) was synthesized from 1.8 mg of the compound (1-8) in the same manner except that Alexa Fluor 350 NHS ester (product name, manufactured by ThermoFisher Scientific Inc.) was used instead of the compound (M2-1). The MS measurement results of the compound (2) are as follows.

[0650] MS (ESI m / z): (M+H + ) + =5360,(MH + ) - =5358

[0651] <Synthesis of Compound (3)>

[0652] In the synthesis of the above compound (1), 0.72 mg of the above compound (3) was synthesized from 1.1 mg of the compound (1-8) in the same manner except that Alexa Fluor 405 NHS ester (product name, manufactured by ThermoFisher Scientific Inc.) was used instead of the compound (M2-1). The MS measurement results of the compound (3) are as follows.

[0653] MS (ESI m / z): (M+H + ) + =6302, (MH + ) - =6300

[0654] <Synthesis of Compound (4)>

[0655] In the synthesis of the above compound (1), 1.0 mg of the above compound (4) was synthesized from 4.5 mg of the compound (1-8) in the same manner except that Alexa Fluor 488 NHS ester (product name, manufactured by ThermoFisher Scientific Inc.) was used instead of the compound (M2-1). The MS measurement results of the compound (4) are as follows.

[0656] MS (ESI m / z): (M+H + ) + =6021、(MH + ) - =6023

[0657] <Synthesis of Comparative Example Compound (2)>

[0658] 1) Synthesis of compound (c2-7)

[0659] Compound (c2-7) was synthesized according to the following scheme.

[0660] [Chemical Formula 28]

[0661]

[0662] (i) Synthesis of compound (c2-3)

[0663] To a 50 mL eggplant-shaped flask, 750 mg of Nε-(1-(4,4-dimethyl-2,6-dioxocyclohexan-1-ylidene)-3-methylbutyl)-Nα-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-lysine (Fmoc-Lys(ivDde)-OH), 15 mL of tetrahydrofuran (THF), 461 mg of tert-butyl 1-amino-3,6,9,12-tetraoxapentadecan-15-ate, 595 mg of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) and 273 μL of N,N-diisopropylethylamine (DIPEA) were added, and the mixture was stirred at room temperature for 4 hours. Thereafter, the mixture was separated between ethyl acetate and saturated brine, and the organic layer was distilled off under reduced pressure to obtain compound (c2-2) as a crude product.

[0664] Compound (c2-2), 7.5 mL of tetrahydrofuran (THF), and 258 μL of piperidine were added to a 50 mL eggplant-shaped flask and stirred at room temperature for 12 hours. The mixture was then separated using ethyl acetate and saturated brine, and the organic layer was removed by distillation under reduced pressure. The mixture was purified by normal phase column chromatography to obtain 855 mg of compound (c2-3).

[0665] (ii) Synthesis of compound (c2-4)

[0666] To a 50 mL eggplant-shaped flask, 300 mg of compound (c2-3), 7.7 mL of dichloromethane (CH2Cl2), 83.2 μL of acetic anhydride (Ac2O), and 139 μL of triethylamine (Et3N) were added and stirred at room temperature for 1 hour. After separation using chloroform (CHCl3) and saturated brine, the organic layer was removed by vacuum distillation to obtain a crude product.

[0667] 3.5 mL of the obtained crude product and trifluoroacetic acid (TFA) were added to a 50 mL eggplant flask, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was then concentrated, purified by reverse phase column chromatography, and freeze-dried to obtain 287 mg of compound (c2-4).

[0668] (iii) Synthesis of compound (c2-5)

[0669] To a 50 mL eggplant-shaped flask were added 287 mg of compound (c2-4), 5.7 mL of tetrahydrofuran (THF), 172 mg of tert-butyl 1-amino-3,6,9,12-tetraoxapentadecan-15-ate, 255 mg of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU), and 117 μL of N,N-diisopropylethylamine (DIPEA). The mixture was stirred at room temperature for 4 hours. The mixture was then separated between ethyl acetate and saturated brine, and the organic layer was removed under reduced pressure to obtain the compound as a crude product.

[0670] 2.5 mL of the obtained crude product and trifluoroacetic acid (TFA) were added to a 50 mL eggplant flask, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was then concentrated, purified by reverse phase column chromatography, and freeze-dried to obtain 281 mg of compound (c2-5).

[0671] (iv) Synthesis of compound (c2-6)

[0672] To a 50 mL eggplant-shaped flask, 140 mg of compound (c2-5), 2.8 mL of tetrahydrofuran (THF), 103 mg of compound (c2-3), 71.9 mg of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU), and 33.0 μL of N,N-diisopropylethylamine (DIPEA) were added and stirred at room temperature for 4 hours. The mixture was then separated between ethyl acetate and saturated brine, and the organic layer was removed under reduced pressure to obtain the compound as a crude product.

[0673] To a 50 mL eggplant-shaped flask, 2.8 mL of the obtained crude product, tetrahydrofuran (THF), and 30.6 μL of hydrazine hydrate were added and stirred at room temperature for 12 hours. The reaction solution was then concentrated, purified by reverse-phase column chromatography, and freeze-dried to obtain 152 mg of compound (c2-6).

[0674] (v) Synthesis of Compound (c2-7)

[0675] To a 50 mL eggplant flask, 108 mg of compound (c2-6) and 3 mL of trifluoroacetic acid (TFA) were added and stirred at room temperature for 1.5 hours. The reaction solution was then concentrated, purified by reverse phase column chromatography, and freeze-dried to obtain 100 mg of compound (c2-7).

[0676] 2) Synthesis of comparative compound (2)

[0677] In the synthesis of the above-mentioned compound (1), 3.9 mg of the above-mentioned comparative compound (2) was synthesized from 2.2 mg of compound (c2-7) in the same manner, except that compound (c2-7) was used instead of compound (1-8), and compound (5-NHS) described in International Publication No. 2022 / 025210 (equivalent to the NHS ester compound of the above-mentioned comparative compound (1)) was used instead of compound (M2-1). The MS measurement results of the comparative compound (2) are as follows.

[0678] MS (ESI m / z): (M+H + ) + =4466、(MH + ) - =4464

[0679] <Example 1>

[0680] The solutions of each dye prepared as described above in PBS(-) (product name, manufactured by FUJIFILM Wako Pure Chemical Corporation) as a solvent were prepared so as to measure the ε value using an ultraviolet-visible spectrophotometer (product name: UV-2550, manufactured by SHIMADZU CORPORATION). max The absorbance at the wavelength of (maximum molar absorptivity) is 0.1.

[0681] The solutions of each prepared pigment were irradiated with excitation light of the excitation wavelengths listed in the following table using a spectrofluorimeter (product name: RF-5300, manufactured by Shimadzu Corporation) under uniform exposure conditions, and the integrated value of the fluorescence intensity in the fluorescence intensity measurement area listed in the following table was calculated. The fluorescence intensity ratio of the pigment in each table was calculated by setting the integrated value of the fluorescence intensity of the specific comparative compound in the table as the reference value (1.0) and calculating the ratio relative to this reference value (integral value of the fluorescence intensity of the pigment / integral value of the fluorescence intensity of the comparative compound as the reference) and evaluating the results according to the following evaluation criteria. Alexa Fluor 350, 405, and 488 (product names) in the following table are all fluorescent compounds manufactured by Thermo Fisher Scientific Inc.

[0682] The results are summarized in Tables 1 to 5.

[0683] -Evaluation Criteria for Fluorescence Intensity (Integral Value)-

[0684] A: The ratio of fluorescence intensity to the reference value is 0.95 times or more and 1.0 times or less

[0685] B: The ratio of fluorescence intensity to the reference value is 0.90 times or more and less than 0.95 times

[0686] C: The ratio of fluorescence intensity to the reference value is 0.85 times or more and less than 0.90 times

[0687] D: The ratio of fluorescence intensity to the reference value is 0.80 times or more and less than 0.85 times

[0688] E: The ratio of fluorescence intensity to the reference value is 0.75 times or more and less than 0.80 times

[0689] F: The ratio of fluorescence intensity to the reference value is 0.70 times or more and less than 0.75 times

[0690] G: The ratio of fluorescence intensity to the reference value is less than 0.70 times

[0691] [Table 1]

[0692] No. pigment Excitation wavelength Fluorescence intensity measurement area Fluorescence intensity ratio r101 Comparative Compound (2) 785nm 810~840nm D rc11 Comparative compound (1) 785nm 810~840nm 1.0 (baseline value)

[0693] [Table 2]

[0694] No. pigment Excitation wavelength Fluorescence intensity measurement area Fluorescence intensity ratio 201 Compound (1) 785nm 810~840nm A c21 Comparative Compounds (3) 785nm 810~840nm 1.0 (baseline value)

[0695] [Table 3]

[0696] No. pigment Excitation wavelength Fluorescence intensity measurement area Fluorescence intensity ratio 301 Compound (2) 350nm 365~420nm A c31 Alexa Fluor 350 350nm 365~420nm 1.0 (baseline value)

[0697] [Table 4]

[0698] No. pigment Excitation wavelength Fluorescence intensity measurement area Fluorescence intensity ratio 401 Compound (3) 405nm 420~500nm B c41 Alexa Fluor 405 405nm 420~500nm 1.0 (baseline value)

[0699] [Table 5]

[0700] No. pigment Excitation wavelength Fluorescence intensity measurement area Fluorescence intensity ratio 501 Compound (4) 495nm 500~700nm B c51 Alexa Fluor 488 495nm 500~700nm 1.0 (baseline value)

[0701] The following can be seen from the results of Tables 1 to 5 above.

[0702] Comparative compound (2) is not a compound specified in the present invention in that the two phosphor portions composed of cyanine pigments (Comparative compound (1)) having equivalent light absorption characteristics are not connected via a group comprising a structure represented by general formula (I). The fluorescence intensity of a solution of the comparative compound (2) is 0.80 times or more and less than 0.85 times that of a solution of the comparative compound (1) as a single pigment, and the fluorescence intensity is significantly reduced by forming a pigment multimer (No. r101 relative to No. rc11).

[0703] In contrast, compounds (1) to (4) are compounds specified in the present invention, wherein two phosphor moieties composed of a cyanine dye, a coumarin dye, a pyrene dye, or a rhodamine dye having equivalent light absorption characteristics are linked via a group having a structure represented by general formula (I). The fluorescence intensity of the solutions of these compounds (1) to (4) is 0.90 times or more higher than the fluorescence intensity of the solution of the pigment alone (reference value 1.0), and the decrease in fluorescence intensity due to the formation of pigment multimers is suppressed compared to the comparative compound (2), resulting in excellent fluorescence intensity (No. 201 relative to No. c21, No. 301 relative to No. c31, No. 401 relative to No. c41, and No. 501 relative to No. c51).

[0704] In this way, the compound of the present invention has two or more phosphor parts with mutually equivalent light absorption characteristics, and the adjacent phosphor parts are connected via a group including a specific structure represented by general formula (I), thereby effectively inhibiting the self-association and association quenching of the compound of the present invention in the solution state and imparting excellent fluorescence intensity.

[0705] The present invention has been described together with its embodiments. Unless otherwise specified, there is no intention to limit the present invention to any details in the description, and it is considered that it should be broadly interpreted without departing from the spirit and scope of the invention as shown in the appended claims.

[0706] This application claims priority based on Japanese Patent Application No. 2023-028798 filed in Japan on February 27, 2023, which is hereby incorporated by reference, and the contents of which are incorporated into this specification as a part of what is described in this specification.

Claims

1. A compound having two or more phosphor parts having mutually equivalent light absorption characteristics, wherein: The adjacent phosphor portions are linked via a group having a structure represented by the following general formula (I), [Chemical Formula 1] Where, X 1 ~X 3 Indicates -O-, -S-, >NR 1 or >CR 2 R 3 , R 1 ~R 3 and R 11 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an acyl group, -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E , R 8 ~R 10 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an aryl group, a heteroaryl group, an anionic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E or -(LO) g R E , L represents an alkylene group, R E With the above R 8 ~R 10 Same meaning, g is 2 to 50, among which R E Can't be -(OL) g R E or -(LO) g R E , n is an integer greater than or equal to 2, * indicates a connection key.

2. The compound according to claim 1, wherein The n is an integer greater than or equal to 3.

3. The compound according to claim 1, which is represented by the following general formula (II): [Chemical Formula 2] Where R 4 and R 5 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an acyl group, an amino group, a hydroxyl group, an alkoxy group, a sulfanyl group, an aryl group or a heteroaryl group, R 6 and R 7 represents a hydrogen atom, a hydroxyl group, a sulfanyl group, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, an amino group, an acyl group, a heteroaryl group or Q, Q represents an anionic group, a cationic group, a betaine residue, a polyol residue, a sugar residue, a polyamino acid residue, -(OL) g R E 、-(LO) g R E , a substituent capable of bonding to a biological substance or a substituent capable of bonding to a solid support, L 1 ~L 7 represents a single bond or a divalent linking group, M represents a phosphor moiety, a physiologically active substance moiety, a prodrug moiety, or a radioisotope-containing moiety, Y represents a structure represented by the general formula (I), m is an integer greater than or equal to 1, L, R E and g and the above L, R E and g have the same meaning, in, At least two of M represent phosphor portions having mutually equivalent light absorption characteristics.

4. The compound according to claim 3, which is represented by the following general formula (VI): [Chemical Formula 3] Where, X 4 ~X 9 Indicates -O-, -S-, >NR 101 or >CR 102 R 103 , in, X 4 ~X 6 At least one of them is >NL 10 -M or>C(R 102 )-L 10 -M,X 7 ~X 9 At least one of them is >NL 11 -M or>C(R 102 )-L 11 -M, Neither -L 10 -M is not -L 11 -M's R 101 ~R 103 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an acyl group, -NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E , L 10 and L 11 represents a single bond or a divalent linking group, n1 is an integer greater than or equal to 2, q is an integer of 0 or 1, R 4 ~R 11 、X 1 ~X 3 , M, L, R E , g and m and the above R 4 ~R 11 、X 1 ~X 3 , M, L, R E , g and m have the same meaning.

5. The compound according to claim 4, which is represented by the following general formula (VII): [Chemical Formula 4] Where R 6A and R 7A represents a hydrogen atom, a hydroxyl group, a sulfanyl group, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, a heteroaryl group, an amino group, an acyl group, or Q, wherein R 6A and R 7A At least one of the groups represents a carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support, L 12 and L 13 represents a single bond or a linking group, na and nb are integers greater than or equal to 0, r and v are integers of 0 or 1, R 4 、R 5 、R 11 , L 10 , L 11 、X 1 ~X 9 , M, Q, q, n1 and m and the above R 4 、R 5 、R 11 , L 10 , L 11 、X 1 ~X 9 , M, Q, q, n1 and m have the same meaning.

6. The compound according to claim 5, wherein (A) na is an integer greater than 1, and R 6A is the carboxyl group, the substituent capable of bonding to a biological substance, or the substituent capable of bonding to a solid support, and / or (B) the sum of nb and v is an integer greater than 1, and the R 7A is the carboxyl group, a substituent capable of bonding to a biological substance, or a substituent capable of bonding to a solid support, Wherein, in the case of (A) above, the L 13 The shortest number of atoms connected is 7 or less. In the case of (B) above, the L 12 The shortest number of connected atoms is less than 7.

7. The compound according to claim 1, wherein The structure represented by the general formula (I) includes X 1 ~X 3 CR 2 R 3 structure.

8. The compound according to claim 7, wherein The structure represented by the general formula (I) includes X 1 ~X 3 CR 2 R 3 At least one R in the structure 2 Yes-NR 8 R 9 、-OR 10 , anionic groups, betaine residues, polyol residues, sugar residues, polyamino acid residues, -(OL) g R E or -(LO) g R E .

9. The compound according to claim 4, wherein In the general formula (VI), m is an integer of 3 or less.

10. The compound according to claim 1, wherein The phosphor portion has a structural portion composed of at least one pigment selected from the group consisting of a coumarin pigment, a pyrene pigment, and a rhodamine pigment.

11. A labeled biological substance, which is formed by bonding the compound according to any one of claims 1 to 10 to a biological substance.

12. The labeled biological substance according to claim 11, wherein The biological substance is any one of proteins, amino acids, nucleic acids, nucleotides, sugar chains and phospholipids.

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