Compound

Abstract

To provide a compound that has a binding structure to a biological substance and can generate singlet oxygen upon light absorption and excitation, where the maximum absorption wavelength is 700 nm or more.SOLUTION: There is provided a compound represented by formula (1): [X1 is a halogen atom; Ar1 is a substituted or unsubstituted C3-20 (hetero)aryl group; the two Ar1 groups may be the same as or different from each other; Z1 is a direct bond or a divalent aromatic linking group; cases where Ar1 and Z1 are directly bonded include the case where a substituent possessed by Ar1 is bonded to Z1; R1 is a group having at least three or more single bonds, connecting Z1 and an N-hydroxysuccinimide ester group].SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a compound that has a binding structure to biological substances such as nucleic acids, proteins, and polysaccharides and has near-infrared light absorption ability. [Background technology]

[0002] Compounds having near-infrared absorption ability are compounds that absorb light in the near-infrared region of 700 to 2000 nm, and conventionally known compounds include cyanine compounds with an extended polymethine skeleton, phthalocyanine compounds having aluminum or zinc at the center, various naphthalocyanine compounds, nickel dithiolene complexes having a planar tetracoordinate structure, squarylium compounds, quinone compounds, diimmonium compounds, and azo compounds. Among light in the near-infrared region, cyanine dyes and the like are known as dyes that absorb and emit light in the wavelength region of 650 to 1000 nm (near-infrared region), which is called the biological window and is not easily absorbed by substances and water in living organisms (for example, Patent Document 1).

[0003] Compounds with near-infrared absorbing properties are expected to be applied in various fields, such as novel sensors, in vitro and in vivo imaging, and chemotherapy. Among these, chemotherapy utilizing singlet oxygen generated by compounds with near-infrared absorbing properties has attracted attention. For example, Non-Patent Document 1 reports that the introduction of a heavy atom into an appropriate position in the skeleton of a fluorescent dye can promote intersystem crossing of the fluorescent dye from the excited singlet state to the excited triplet state, and that the energy of the excited triplet state of the fluorescent dye is transferred to an oxygen molecule, generating singlet oxygen. Singlet oxygen is highly reactive and is known to destroy harmful tissues around it. Therefore, a therapeutic method that introduces compounds that generate singlet oxygen when irradiated with light into the body and eliminates harmful tissues such as cancer cells has attracted attention.

[0004] As a compound having near-infrared absorbing ability and generating singlet oxygen, the invention described in Patent Document 2 proposes a near-infrared light-absorbing dye compound that has an N-hydroxysuccinimide ester group that serves as a binding site to biological substances and generates singlet oxygen by absorbing and becoming excited by light in a wavelength range known as the biological window. The dye compound has the N-hydroxysuccinimide ester group that serves as a binding site to biological substances linked via a spacer to a skeleton having a structure (azaBODIPY skeleton) having an azadipyrromethene and a boron atom substituted with a halogen atom. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2007 / 005222 [Patent Document 2] Japanese Patent Publication No. 2023-020417 [Non-patent literature]

[0006] [Non-Patent Document 1] Chem.Soc.Rev.,2013,42,77-88 Summary of the Invention [Problem to be solved by the invention]

[0007] The dye compound described in the aforementioned Patent Document 2 can generate singlet oxygen by absorbing light and becoming excited, and has an N-hydroxysuccinimide ester group, which is a binding site for biological substances, so it can be easily introduced into the body and is expected to be used in the diagnosis and treatment of diseases, etc. However, this dye compound has a maximum absorption wavelength of less than 700 nm, and light with wavelengths less than 700 nm has low permeability through the body, making it difficult for light to reach deep inside the body. Therefore, an object of the present invention is to provide a compound that has a binding structure to a biological substance, can absorb light and become excited to generate singlet oxygen, and has a maximum absorption wavelength of 700 nm or more. [Means for solving the problem]

[0008] The present inventors have conducted extensive research in light of the above-mentioned problems and have found that, in a compound having an N-hydroxysuccinimide ester group introduced into a predetermined dye skeleton, if the dye skeleton has an azadipyrromethene substituted with a halogen atom and a boron atom, and has a six-membered ring structure containing NBO having the boron atom, the compound has a maximum absorption wavelength of 700 nm or more, a high extinction coefficient, and is capable of generating singlet oxygen by absorbing light and becoming excited, thereby completing the present invention. That is, the gist of the present invention is as follows.

[0009] [1] A compound represented by the following formula (1):

[0010] TIFF2025130036000002.tif52170

[0011] In formula (1), X 1 represents a halogen atom. Ar 1 represents a (hetero)aryl group having 3 to 20 carbon atoms which may have a substituent. Ar 1 The substituent that may be possessed by the group is any one of an alkyl group having 1 to 20 carbon atoms, an alkenyl group having 2 to 20 carbon atoms, an alkoxy group having 1 to 20 carbon atoms, a (hetero)aryloxy group having 3 to 20 carbon atoms, an alkylcarbonyl group having 2 to 20 carbon atoms, an arylcarbonyl group having 7 to 20 carbon atoms, an alkylamino group having 2 to 20 carbon atoms, an arylamino group having 6 to 20 carbon atoms, an alkylamide group having 2 to 20 carbon atoms, a (hetero)aryl group having 3 to 20 carbon atoms, a polyalkyl ether group having 4 to 16 carbon atoms, a quaternary ammonium group, a sulfonic acid group, or a salt of sulfonic acid, or a combination thereof. In addition, the two Ar in formula (1)1 may be the same as or different from each other. Z 1 represents a direct bond or a divalent aromatic linking group. Z 1 is any part of the chemical structure enclosed in brackets and R 1 Any structure that bonds Ar 1 and Z 1 When Ar and Ar are directly bonded, 1 The substituents on and Z 1 This includes cases where the compound is combined with R 1 is Z 1 and the N-hydroxysuccinimide ester group, and has at least three single bonds.

[0012] [2] The compound according to [1] above, wherein the compound represented by formula (1) is a compound represented by the following formula (2):

[0013] TIFF2025130036000003.tif45170

[0014] In formula (2), Ar 1 , X 1 , Z 1 , R 1 represents Ar in the formula (1). 1 , X 1 , Z 1 , R 1 is synonymous with.

[0015] [3] The compound according to [2] above, wherein the compound represented by formula (2) is a compound represented by the following formula (3):

[0016] TIFF2025130036000004.tif46170

[0017] In formula (3), Ar 1 , Z 1 , R 1 represents Ar in the formula (1). 1 , Z 1 , R 1 is synonymous with.

[0018] [4] The compound according to any one of [1] to [3], which has a maximum absorption wavelength of 700 nm or more. [Effects of the Invention]

[0019] The compound proposed by the present invention is a compound having an N-hydroxysuccinimide ester group introduced into a specific dye skeleton, and the dye skeleton has an azadipyrromethene substituted with a halogen atom and a boron atom, and a six-membered ring structure containing NBO having the boron atom. As a result, the compound has a maximum absorption wavelength of 700 nm or more and a high extinction coefficient, allowing it to efficiently absorb light and its energy, which has high transmittance within the body. Furthermore, because the compound has an N-hydroxysuccinimide ester group that can function as a binding site for biological substances, it can absorb light and generate singlet oxygen upon excitation, and is therefore expected to be effectively used in the diagnosis and treatment of diseases. [Brief explanation of the drawings]

[0020] [Figure 1] 1 is a chart showing absorption spectrum measurements of Compound 1 prepared in an example and Comparative Compound 1. DETAILED DESCRIPTION OF THE INVENTION

[0021] The following describes in detail the embodiments of the present invention. However, the present invention is not limited to the following embodiments and can be practiced in various modifications within the scope of the present invention.

[0022] In this specification, the term "(hetero)aryloxy group" refers to an aryloxy group which may contain a heteroatom, and the term "(hetero)aryl group" refers to an aryl group which may contain a heteroatom. The phrase "may contain a heteroatom" means that one or more of the carbon atoms forming the main skeleton of the aryl group or aryloxy group are substituted with a heteroatom, and examples of the heteroatom include a nitrogen atom, an oxygen atom, a sulfur atom, a phosphorus atom, a silicon atom, etc. Among these, a nitrogen atom is preferred from the viewpoint of durability.

[0023] The compound of the present invention is a compound represented by the following formula (1) (hereinafter, may be referred to as "compound of formula (1)").

[0024] TIFF2025130036000005.tif52170

[0025] In formula (1), X 1 represents a halogen atom. Ar 1 represents a (hetero)aryl group having 3 to 20 carbon atoms which may have a substituent. Ar 1 The substituent that may be possessed by the group is any one of an alkyl group having 1 to 20 carbon atoms, an alkenyl group having 2 to 20 carbon atoms, an alkoxy group having 1 to 20 carbon atoms, a (hetero)aryloxy group having 3 to 20 carbon atoms, an alkylcarbonyl group having 2 to 20 carbon atoms, an arylcarbonyl group having 7 to 20 carbon atoms, an alkylamino group having 2 to 20 carbon atoms, an arylamino group having 6 to 20 carbon atoms, an alkylamide group having 2 to 20 carbon atoms, a (hetero)aryl group having 3 to 20 carbon atoms, a polyalkyl ether group having 4 to 16 carbon atoms, a quaternary ammonium group, a sulfonic acid group, or a salt of sulfonic acid, or a combination thereof. In addition, the two Ar in formula (1) 1 may be the same as or different from each other. Z 1 represents a direct bond or a divalent aromatic linking group. Z 1 represents a combination of any part of the chemical structure enclosed in brackets (also referred to as the "dye skeleton of the present invention") and R 1 Any structure that bonds Ar 1 and Z 1 When Ar and Ar are directly bonded, 1The substituents on and Z 1 This includes cases where the compound is combined with R 1 is Z 1 and the N-hydroxysuccinimide ester group, and has at least three single bonds. The dotted line connecting B and N indicates that B and N are or may be coordinate bonded.

[0026] The compound of formula (1) has a structure containing azadipyrromethene and a boron atom, and further has a six-membered ring structure containing NBO having the boron atom. As a result, the compound has a maximum absorption wavelength of 700 nm or more and a high extinction coefficient, and can efficiently absorb light that is highly permeable within the body and its energy. In this case, since the dye skeleton of the present invention has a six-membered ring structure containing NBO having a boron atom, it is presumed that the conjugation is expanded, the absorption wavelength becomes longer, and further, the extinction coefficient becomes larger. It can also be presumed that a large extinction coefficient efficiently absorbs light corresponding to the absorption wavelength, making it easier to enter an excited state, and increasing the efficiency of generating singlet oxygen in response to excitation light. The maximum absorption wavelength is 700 nm or longer, preferably 710 nm or longer, more preferably 720 nm or longer, even more preferably 730 nm or longer, and most preferably 740 nm or longer. Considering that the excitation light used often has a range rather than a single wavelength, a longer wavelength is preferable because less energy is wasted (absorbed by the body surface, etc.). Furthermore, those with high singlet oxygen generation efficiency can be identified by the emission of light at 1270 nm when, for example, they are dissolved in toluene and irradiated with light (excitation light) near the maximum absorption wavelength, and those that can observe this emission are preferred.

[0027] The compound of formula (1) is X 1One of the characteristics of this compound is that a halogen atom (H) is bonded to the 4-position of the azadipyrromethene moiety (the β-position of the pyrrole ring). Because the HOMO (highest occupied molecular orbital) is widely distributed at this 4-position, the direct bonding of the halogen atom at this position maximizes the interaction between the azadipyrromethene skeleton and the halogen atom. Therefore, when irradiated with light corresponding to the absorption wavelength of the compound of formula (1), the compound of formula (1) is excited to a singlet state, and the heavy atom effect of the halogen atom presumably facilitates intersystem crossing to an excited triplet state. Because of these photophysical properties, singlet oxygen is generated when oxygen molecules coexist under light irradiation. Specifically, energy is transferred from the compound of formula (1) to the oxygen molecules, and the oxygen molecules are excited to singlet oxygen. Singlet oxygen can inactivate, for example, cancer cells in a living body. Therefore, it is believed that by binding the compound of the present invention, which is a compound of formula (1), to, for example, an antibody, and generating singlet oxygen in a living body, cancer cells can be inactivated more effectively.

[0028] Furthermore, in the compound of formula (1), the dye skeleton of the present invention and the N-hydroxysuccinimide ester group are connected by R 1 and Z 1 The N-hydroxysuccinimide ester group, which can function as a binding site to a biological substance, is located away from the π-conjugated structure of the dye skeleton of the present invention, and therefore, the dye can be more easily bound to a biological substance and can be easily introduced into a living body while maintaining the above-mentioned optical properties.

[0029] <X 1 > X 1 represents a halogen atom. X 1 is preferably a bromine atom or an iodine atom from the viewpoint of the heavy atom effect, and is more preferably a bromine atom from the viewpoint of the photostability of the compound.

[0030] <Ar 1 > Ar 1represents a (hetero)aryl group having 3 to 20 carbon atoms which may have a substituent. Note that the number of carbon atoms in the (hetero)aryl group having 3 to 20 carbon atoms which may have a substituent does not include the number of carbon atoms of the substituent.

[0031] Ar 1 The substituents that may be present are any one of an alkyl group having 1 to 20 carbon atoms, an alkenyl group having 2 to 20 carbon atoms, an alkoxy group having 1 to 20 carbon atoms, a (hetero)aryloxy group having 3 to 20 carbon atoms, an alkylcarbonyl group having 2 to 20 carbon atoms, an arylcarbonyl group having 7 to 20 carbon atoms, an alkylamino group having 2 to 20 carbon atoms, an arylamino group having 6 to 20 carbon atoms, an alkylamide group having 2 to 20 carbon atoms, a (hetero)aryl group having 3 to 20 carbon atoms, a polyalkyl ether group having 4 to 16 carbon atoms, a quaternary ammonium group, a sulfonic acid group, or a salt of sulfonic acid, or a combination thereof. Among these substituents, from the viewpoint of solubility, any one of an alkyl group having 1 to 20 carbon atoms, an alkoxy group having 1 to 20 carbon atoms, a polyalkyl ether group having 4 to 10 carbon atoms, a quaternary ammonium group, a sulfonic acid group, or a salt of sulfonic acid, or a combination thereof, is preferred. In the present invention, when a (hetero)aryl group having 3 to 20 carbon atoms is contained as a substituent, if the (hetero)aryl group has a portion that satisfies the above-mentioned "optionally substituted (hetero)aryl group having 3 to 20 carbon atoms", that portion is defined as the "optionally substituted (hetero)aryl group having 3 to 20 carbon atoms", and the remaining portion is defined as the substituent (hetero)aryl group having 3 to 20 carbon atoms.

[0032] Ar 1 In terms of absorption wavelength, the Ar group is preferably a phenyl group which may have a substituent. The substituent which the phenyl group may have is the Ar group. 1 Among these, from the viewpoint of solubility, it is preferable to use an alkyl group having 1 to 20 carbon atoms, an alkoxy group having 1 to 20 carbon atoms, a polyalkyl ether group having 4 to 10 carbon atoms, a quaternary ammonium group, a sulfonic acid group, or a salt of sulfonic acid, or a combination thereof.

[0033] The two Ar in formula (1) 1 may be the same as or different from each other. One of the two Ar in formula (1) 1 is Z 1 and the Ar 1 has a substituent Z 1 It may be combined with

[0034] <Substituent> Ar 1 Specific examples of the substituent that may be possessed by are as follows: Specific examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isopentyl group, a neopentyl group, a tert-pentyl group, an n-hexyl group, a 1-methylpentyl group, a 4-methyl-2-pentyl group, a 3,3-dimethylbutyl group, a 2-ethylbutyl group, an n-heptyl group, a 1-methylhexyl group, an n-octyl group, and a tert-octyl group. Specific examples of the alkoxy group include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy group, a hexyloxy group, a heptyloxy group, and an octyloxy group. Specific examples of the (hetero)aryl group include a phenyl group, a naphthyl group, a biphenyl group, a terphenyl group, and a pyridyl group.

[0035] A specific example of the polyalkyl ether group is a group represented by the following formula (5).

[0036] TIFF2025130036000006.tif40170

[0037] In formula (5), U represents a hydrogen atom, a methyl group, or an ethyl group, and from the viewpoint of solubility, U is preferably a methyl group. n represents an integer of 2 or more and 7 or less, and from the viewpoint of solubility, it is preferably an integer of 3 or more, and more preferably an integer of 4 or more. *Ar 1 represents the bonding position with

[0038] A specific example of the quaternary ammonium group is a group represented by the following formula (6).

[0039] TIFF2025130036000007.tif35170

[0040] In formula (6), R 11 ~R 13 may be the same or different, and each independently represents an alkyl group having 1 to 4 carbon atoms. From the viewpoint of solubility, it is preferably a methyl group or an ethyl group. T- (in the figure, - is circled) represents a counter ion, and * represents Ar 1 or Ar 2 represents the bonding position with Specific examples of T- include a chlorine atom, a bromine atom, an iodine atom, tetrafluoroboric acid (BF4), and hexafluorophosphoric acid (PF6). Among these, a chlorine atom, a bromine atom, and an iodine atom are preferred from the viewpoint of the stability of the compound.

[0041] Examples of the salts of sulfonic acid include sodium salts, potassium salts, and cesium salts.

[0042] <Z 1 > Z 1 represents a direct bond or a divalent aromatic linking group. Z 1 is preferably a direct bond in terms of ease of production. Z 1is preferably a divalent aromatic linking group in that it can further distance the N-hydroxysuccinimide ester group from the dye skeleton of the present invention, and is preferably any one of a phenylene group, a biphenylene group, a terphenylene group, and a fluorenediyl group in that it prevents the absorption wavelength from becoming shorter.

[0043] <R 1 > R 1 is Z 1 and the N-hydroxysuccinimide ester group, and has at least three single bonds. By having three or more single bonds, it is possible to ensure a distance from the N-hydroxysuccinimide ester group, which can function as a binding site for biological substances, and the functions of each site can be fully exerted. Preferably, it has three or more consecutive single bonds. R 1 is preferably represented by the following formula (7):

[0044] TIFF2025130036000008.tif29170

[0045] In formula (7), Q represents any group selected from the group consisting of -CH2-, -O-, -CO-, -NH-, and -S-. m is preferably an integer of 2 or more, more preferably an integer of 3 or more, even more preferably an integer of 5 or more, even more preferably an integer of 7 or more. On the other hand, the upper limit is preferably an integer of 30 or less. The m Qs may be the same group or different groups. Among these, Q preferably contains either -CH2- or -O- in terms of excellent chemical durability.

[0046] <Z 1 Binding point of > Z 1 may be bonded to any position of the chemical structure enclosed in parentheses in formula (1), i.e., the dye skeleton of the present invention having an azadipyrromethene structure. 1 Ar1 Alternatively, they may be bonded to the 4-position of the azadipyrromethene structure (the β-position of the pyrrole ring) as shown in formula (2) below. From the viewpoint of ease of production, bonding at the position shown in formula (2) is preferred.

[0047] <Suitable Compounds> The compound of formula (1) is a compound represented by the formula (1) 1 The substitution position of is preferably the 4-position of the azadipyrromethene structure (the β-position of the pyrrole ring). That is, it is preferably a compound represented by the following formula (2), and particularly preferably a compound represented by the following formula (2): 1 is preferably a compound represented by the following formula (3), in which is a bromine atom.

[0048] TIFF2025130036000009.tif45170

[0049] In formula (2), Ar 1 , X 1 , Z 1 , R 1 represents Ar in the formula (1). 1 , X 1 , Z 1 , R 1 is synonymous with.

[0050] TIFF2025130036000010.tif46170

[0051] In formula (3), Ar 1 , Z 1 , R 1 represents Ar in the formula (1). 1 , Z 1 , R 1 is synonymous with.

[0052] <Example> Preferred specific examples of the compound of formula (1) of the present invention are shown below, but the present invention is not limited to these.

[0053] TIFF2025130036000011.tif198170

[0054] <Synthesis method> As shown in the following reaction scheme, the compound of the present invention can be synthesized by synthesizing an intermediate in which a halogen atom and a protected carboxylic acid are substituted on a structure consisting of an azadipyrromethene and a boron atom, then deprotecting the protecting group of the carboxylic acid to convert it into a carboxylic acid intermediate or a carboxylate intermediate, and then converting the carboxylic acid intermediate or the carboxylate intermediate into an N-hydroxysuccinimide ester group. A specific synthesis method is as shown in the synthesis example of Compound 1 described in the Examples section below.

[0055] TIFF2025130036000012.tif23772

[0056] In the above reaction scheme, X 1 ,Ar 1 ,Z 1 ,R 1 has the same meaning as in the above formula (1).

[0057] <Explanation of terms, etc.> In the present invention, when it is written "α to β" (α and β are arbitrary numbers), unless otherwise specified, it means "not less than α and not more than β", and also means "preferably greater than α" or "preferably smaller than β". Furthermore, when it is stated that "α or more" or "α≦" (α is any number), it also means "preferably greater than α" unless otherwise specified, and when it is stated that "β or less" or "≦β" (β is any number), it also means "preferably smaller than β" unless otherwise specified. [Example]

[0058] The present invention will be described in more detail below with reference to examples. The present invention is not limited to the following examples, and the present invention can be practiced with any modifications without departing from the gist of the present invention.

[0059] <Synthesis of Compound 1> Compound 1 was synthesized via intermediates 1, 2, 3, 4, 5, 6, 7, and 8 as described below.

[0060] TIFF2025130036000013.tif56170

[0061] Intermediate 1 (4.00 g, synthesized according to the method described in Org. Lett., 2008, 10, 21, 4771-4774) and N,N-dimethylformamide (100 mL) were placed in a 300 mL recovery flask and cooled in an ice bath under a nitrogen atmosphere. Imidazole (2.26 g) and tert-butyldimethylsilyl chloride (5.36 g) were added and stirred at room temperature for 2 hours. Water (200 mL) and ethyl acetate (200 mL) were then added for separation and washing. The oil phase was collected and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (neutral silica gel, dichloromethane / hexane = 3 / 7) to obtain 5.36 g of Intermediate 2 as a dark blue solid.

[0062] TIFF2025130036000014.tif55170

[0063] Intermediate 2 (5.36 g) and dichloromethane (100 mL) were placed in a 300 mL recovery flask, and N-bromosuccinimide (2.69 g) was added while stirring at room temperature, followed by stirring at room temperature for 1.5 hours. The solvent was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (neutral silica gel, dichloromethane / hexane = 3 / 7), yielding 6.16 g of Intermediate 3 as a purple solid.

[0064] TIFF2025130036000015.tif54170

[0065] Intermediate 3 (3.70 g), tetrahydrofuran (100 mL), acetic acid (0.54 mL), and 1 M tetra-n-butylammonium fluoride / tetrahydrofuran solution (9.38 mL) were added to a 300 mL recovery flask and stirred at room temperature for 15 minutes. The residue obtained after concentration under reduced pressure was purified by silica gel column chromatography (neutral silica gel, dichloromethane only), yielding 2.73 g of Intermediate 4 as a black-brown solid.

[0066] TIFF2025130036000016.tif54170

[0067] Intermediate 4 (0.75 g), toluene (100 mL), and N,N-diisopropylethylamine (2.00 mL) were placed in a 300 mL recovery flask. Boron trifluoride diethyl ether complex (1.47 mL) was added while stirring at room temperature, and the mixture was stirred at 110 °C for 2.5 hours. After cooling to room temperature, dichloromethane (150 mL) and deionized water (150 mL) were added for separation and washing. The oil phase was recovered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (neutral silica gel, dichloromethane / hexane = 6 / 4), yielding 0.27 g of Intermediate 5 as a black-purple solid.

[0068] TIFF2025130036000017.tif46170

[0069] Under a nitrogen atmosphere, a 100 mL flask was charged with intermediate 5 (0.17 g), intermediate 6 (0.14 g, synthesized according to the method described in JP 2023-020417 A), toluene (100 mL), tetrahydrofuran (60 mL), and 2 mol / L aqueous potassium phosphate solution (0.8 mL) and stirred. A catalyst solution prepared by stirring palladium acetate (6 mg), 2-dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl (22 mg), and tetrahydrofuran (3 mL) at room temperature for 10 minutes was added to the solution in a 30 mL Schlenk flask and stirred at 75 °C for 1.5 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (neutral silica gel, dichloromethane / ethyl acetate = 8 / 1), yielding 42 mg of intermediate 7 as a black-purple solid.

[0070] TIFF2025130036000018.tif43170

[0071] Intermediate 7 (42 mg), tetrahydrofuran (40 mL), and trifluoroacetic acid (0.2 mL) were placed in a 100 mL flask and stirred at room temperature for 1.5 hours. The mixture was concentrated under reduced pressure to give 40 mg of Intermediate 8 as a black-blue solid.

[0072] TIFF2025130036000019.tif49170

[0073] Intermediate 8 (40 mg), N-hydroxysuccinimide (5.1 mg), and dry dichloromethane (40 mL) were placed in a 100 mL recovery flask, and N,N'-diisopropylcarbodiimide (5.6 mg) was added while stirring at room temperature. The mixture was then stirred at room temperature for 1.5 hours. The residue obtained after concentration under reduced pressure was purified by silica gel column chromatography (neutral silica gel, dichloromethane / ethyl acetate = 8 / 1) to obtain 20 mg of compound 1 as a black-purple solid.

[0074] <Synthesis of Comparative Compound 1> Comparative compound 1 was synthesized in the same manner as intermediate 9 described in paragraphs

[0055] to

[0071] of JP 2022-081719 A.

[0075] <Evaluation of absorption spectrum> Using a Hitachi U-3900H spectrophotometer, 5 × 10 -6 The absorption spectrum of each solution was measured in the wavelength range of 400 nm to 900 nm.

[0076] TIFF2025130036000020.tif59170

[0077] The absorption spectrum of the obtained compound 1 was measured using a toluene solution, and the results are shown in Figure 1. The maximum absorption wavelength of compound 1 was 749 nm. The extinction coefficient was 148,000 M -1 cm -1 It was. On the other hand, the absorption spectrum of Comparative Compound 1 was measured and the results are shown in Figure 1. The maximum absorption wavelength of Comparative Compound 1 was 690 nm. The extinction coefficient was 55,000 M -1 cm -1 It was. As can be seen from FIG. 1, Compound 1 is a useful compound that has absorption at longer wavelengths, with a maximum absorption wavelength of 700 nm or more, and a molar absorption coefficient that is 2.69 times higher than that of Comparative Compound 1.

[0078] <Evaluation of singlet oxygen generation ability> The singlet oxygen generating ability can be evaluated by detecting the emission of singlet oxygen. For example, the measurement solvent is toluene, and the concentration of each compound is adjusted so that the absorbance at the excitation wavelength in a 1 cm square cell is 2. For example, a spectrometer (Actes, CSM-330) is used, and a photomultiplier tube (Hamamatsu Photonics, R5509-43) is used as the detector. Measurement is performed at an excitation wavelength of 660 nm. However, if the maximum absorption wavelength exceeds 700 nm, it is preferable to measure at 785 nm.

[0079] Singlet oxygen generation is measured for the obtained Compound 1. If luminescence due to singlet oxygen is clearly observed at 1270 nm from a toluene solution of Compound 1, it can be evaluated as having singlet oxygen generating ability.

[0080] The singlet oxygen generating ability was evaluated by the above-mentioned method for evaluating singlet oxygen generating ability. Specifically, the measurement solvent was toluene, and the concentration of each compound was adjusted so that the absorbance at the excitation wavelength in a 1 cm square cell was 2. The emission of singlet oxygen was detected using the above-mentioned spectrometer and the above-mentioned InGaAs detector. The measurement was performed at an excitation wavelength of 785 nm.

[0081] From the toluene solution of the above compound 1, luminescence due to singlet oxygen was clearly observed at 1270 nm. Emission due to singlet oxygen was clearly observed at 1270 nm from the toluene solution of the above-mentioned Comparative Example Compound 1. The emission intensity was 0.2, when the emission intensity of emission due to singlet oxygen from the above-mentioned toluene solution of Compound 1 was set to 1.

[0082] <Consideration> Taking into account the above examples, the test results that have been carried out by the present inventors so far, and common general technical knowledge, it can be found that a compound represented by the following formula (1) has a maximum absorption wavelength of 700 nm or more, a high extinction coefficient, and is capable of absorbing light and generating singlet oxygen by excitation.

[0083] TIFF2025130036000021.tif52170

[0084] In the compound of formula (1), the structure enclosed in parentheses, i.e., the dye skeleton of the present invention, has a six-membered ring structure containing NBO having a boron atom, and therefore, it is presumed that the conjugation is expanded, the absorption wavelength becomes longer, and further, the extinction coefficient becomes larger, so that the compound has a maximum absorption wavelength of 700 nm or more and a high extinction coefficient. Furthermore, it is presumed that a high extinction coefficient efficiently absorbs light corresponding to the absorption wavelength, easily becomes excited, and increases the efficiency of generating singlet oxygen in response to excitation light.

[0085] The compound of formula (1) is X 1The compound has a unique feature in that a halogen atom (H) is bonded to the 4-position of the azadipyrromethene moiety (the β-position of the pyrrole ring). Because the HOMO (highest occupied molecular orbital) is widely distributed at this 4-position, the direct bonding of the halogen atom at this position maximizes the interaction between the azadipyrromethene skeleton and the halogen atom. Therefore, when irradiated with light corresponding to the absorption wavelength of the compound of formula (1), the compound of formula (1) is excited to a singlet state, and the heavy atom effect of the halogen atom presumably facilitates intersystem crossing to an excited triplet state. Because of these photophysical properties, singlet oxygen is generated when oxygen molecules coexist under light irradiation. Specifically, energy is transferred from the compound of formula (1) to the oxygen molecules, and the oxygen molecules are excited to singlet oxygen.

[0086] Considering the above structural features, X 1 If the compound is a halogen atom, it is presumed that the heavy atom effect will make it easier for intersystem crossing to occur to the excited triplet state, and therefore it is thought that the same effect as that of Br in compound 1 can be obtained. Ar 1 is a (hetero)aryl group having 3 to 20 carbon atoms which may have a substituent, it is not considered to impair the above structural features, and therefore it is considered to be able to solve the problem in the same way as compound 1. Furthermore, no matter where the N-hydroxysuccinimide ester group is bonded to the dye skeleton of the present invention, it is not considered that the above structural features are impaired, and therefore, it is considered that the problem can be solved in the same way as in Compound 1. 1 Z 1 or Ar 1 has a substituent Z 1 It is thought that it may be combined with

[0087] In the compound of formula (1), the dye skeleton of the present invention and the N-hydroxysuccinimide ester group are bonded to each other by R 1 and Z 1The N-hydroxysuccinimide ester group, which can function as a binding site for a biological substance, is located away from the π-conjugated structure of the dye skeleton of the present invention, and therefore it is expected that binding to a biological substance will be easier. From this viewpoint, R constituting the bonding site between the dye skeleton of the present invention and the N-hydroxysuccinimide ester group 1 and Z 1 R of 1 has at least three single bonds, and Z 1 is considered to be any direct bond or divalent aromatic linking group.

Claims

1. A compound represented by the following formula (1): [In formula (1), X １ represents a halogen atom. Ar １ represents a (hetero)aryl group having 3 to 20 carbon atoms which may have a substituent. Ar １ The substituent that may be possessed by the formula (I) is any one of an alkyl group having 1 to 20 carbon atoms, an alkenyl group having 2 to 20 carbon atoms, an alkoxy group having 1 to 20 carbon atoms, a (hetero)aryloxy group having 3 to 20 carbon atoms, an alkylcarbonyl group having 2 to 20 carbon atoms, an arylcarbonyl group having 7 to 20 carbon atoms, an alkylamino group having 2 to 20 carbon atoms, an arylamino group having 6 to 20 carbon atoms, an alkylamide group having 2 to 20 carbon atoms, a (hetero)aryl group having 3 to 20 carbon atoms, a polyalkyl ether group having 4 to 16 carbon atoms, a quaternary ammonium group, a sulfonic acid group, or a salt of sulfonic acid, or a combination thereof. In addition, two Ar in formula (1) １ may be the same as or different from each other. Z １ represents a direct bond or a divalent aromatic linking group. Z １ is a combination of any part of the chemical structure enclosed in brackets and R １ Any structure that bonds Ar and １ and Z １ and are directly bonded, Ar １ The substituents of Z １ This includes cases where the compound is combined with R １ Is Z １ and the N-hydroxysuccinimide ester group, and has at least three single bonds.]

2. The compound according to claim 1, wherein the compound represented by formula (1) is a compound represented by the following formula (2): [In formula (2), Ar １ , X １ , Z １ , R １ represents Ar in the formula (1). １ , X １ , Z １ , R １ is equivalent to the above.]

3. The compound according to claim 2, wherein the compound represented by formula (2) is a compound represented by the following formula (3): [In formula (3), Ar １ , Z １ , R １ represents Ar in the formula (1). １ , Z １ , R １ is equivalent to the above.]

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