Compound

Abstract

To provide a compound that 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): [In formula (1), X1 is a halogen atom; X2 is a halogen atom or a hydrogen 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; R1 is a substituted or unsubstituted C1-20 alkyl group, a substituted or unsubstituted C1-20 alkoxy group, or a substituted or unsubstituted (hetero)aryl group].

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] For example, Patent Document 2 reports that a dye molecule in which a heavy atom is introduced into a structure consisting of azadipyrromethene and a boron atom (azaBODIPY skeleton) generates singlet oxygen upon irradiation with light. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2007 / 005222 [Patent Document 2] U.S. Patent No. 7,220,732 [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 molecules described in the aforementioned Patent Document 2 are capable of generating singlet oxygen when irradiated with light, and are therefore expected to be useful in the diagnosis and treatment of diseases when introduced into living organisms. However, the dye molecules have a maximum absorption wavelength of less than 700 nm, and light with wavelengths less than 700 nm has low transmittance within the body, making it difficult for the light to reach deep within the body. Therefore, an object of the present invention is to provide a compound that can generate singlet oxygen when excited by absorbing light, and that 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, as long as a compound has an azadipyrromethene substituted with a halogen atom and a silicon atom, and a six-membered ring structure containing N-Si-O having the silicon atom, the compound has a maximum absorption wavelength of 700 nm or more and can generate 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): TIFF2025130037000001.tif49170

[0010] In formula (1), X 1 represents a halogen atom. 2 represents a halogen atom or a hydrogen 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. R 1 represents an alkyl group having 1 to 20 carbon atoms which may have a substituent, an alkoxy group having 1 to 20 carbon atoms which may have a substituent, or a (hetero)aryl group which may have a substituent. R 1The substituent that may be possessed by the group is any one of a halogen atom, 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.

[0011] [2] X 1 is an iodine atom or a bromine atom, and 2 is an iodine atom, a bromine atom, or a hydrogen atom.

[0012] [3] X 1 is a bromine atom, and said X 2 is a bromine atom or a hydrogen atom.

[0013] [4] X 1 is a bromine atom, and said X 2 is a hydrogen atom.

[0014] [5] The compound according to any one of [1] to [4], which has a maximum absorption wavelength of 700 nm or more. [Effects of the Invention]

[0015] The compound proposed by the present invention has a halogen-substituted azadipyrromethene and a silicon atom, and a six-membered ring structure containing N-Si-O having the silicon atom. Therefore, the compound has a maximum absorption wavelength of 700 nm or more, and can absorb light and its energy with high transmittance through the body. Furthermore, the compound can generate singlet oxygen by absorbing and exciting light, and is therefore expected to be effectively used in the diagnosis and treatment of diseases. [Brief explanation of the drawings]

[0016] [Figure 1] 1 shows absorption spectrum measurement charts of Compound 1, Compound 2, and Comparative Compound 1 prepared in Examples. DETAILED DESCRIPTION OF THE INVENTION

[0017] 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.

[0018] As used herein, 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, and a silicon atom. Of these, a nitrogen atom is preferred from the viewpoint of durability.

[0019] 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)").

[0020] TIFF2025130037000002.tif49170

[0021] In formula (1), X 1 represents a halogen atom. 2 represents a halogen atom or a hydrogen atom. Ar 1 represents a (hetero)aryl group having 3 to 20 carbon atoms which may have a substituent. Ar 1The 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. R 1 represents an alkyl group having 1 to 20 carbon atoms which may have a substituent, an alkoxy group having 1 to 20 carbon atoms which may have a substituent, or a (hetero)aryl group which may have a substituent. R 1 The substituent that may be possessed by the group is any one of a halogen atom, 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. The dotted line connecting Si and N indicates that Si and N are or may be coordinate bonded.

[0022] The compound of formula (1) has a structure containing azadipyrromethene and a silicon atom, and further has a six-membered ring structure containing N-Si-O having the silicon 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 compound of formula (1) has a six-membered ring structure containing a silicon atom, -Si-O, 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 that the efficiency of generating singlet oxygen in response to the excitation light increases.

[0023] The compound of formula (1) is X 1 One 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. The maximum absorption wavelength is 700 nm or longer, preferably 710 nm or longer. Considering that the excitation light used is often not a single wavelength but has a range, 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.

[0024] <X 1 > X 1represents a halogen atom. X 1 is preferably a bromine atom or an iodine atom from the viewpoint of the heavy atom effect, and more preferably a bromine atom from the viewpoint of the photostability of the compound.

[0025] <X 2 > X 2 represents a halogen atom or a hydrogen atom. X 2 When is a halogen atom, it is preferably a bromine atom or an iodine atom from the viewpoint of the heavy atom effect, and more preferably a bromine atom from the viewpoint of the photostability of the compound. From the viewpoint of the stability of the compound, it is preferably a hydrogen atom. The positions of X1 and X2 can be interpreted as either, so if only one is a halogen atom, it is considered to be X1.

[0026] X 1 and X 2 The combination with X 1 is an iodine atom or a bromine atom, and X 2 is preferably an iodine atom, a bromine atom, or a hydrogen atom, and X 1 is a bromine atom, and X 2 is more preferably a bromine atom or a hydrogen atom, and X 1 is a bromine atom, and X 2 It is particularly preferred that is a hydrogen atom.

[0027] <Ar 1 > Ar 1 represents 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.

[0028] Ar 1The 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.

[0029] 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.

[0030] The two Ar in formula (1) 1 may be the same as or different from each other.

[0031] <Substituent> Ar 1Specific 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.

[0032] A specific example of the polyalkyl ether group is a group represented by the following formula (5).

[0033] TIFF2025130037000003.tif40170

[0034] 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, an integer of 3 or more is preferred, and among these, an integer of 4 or more is even more preferred. *Ar 1 represents the bonding position with

[0035] A specific example of the quaternary ammonium group is a group represented by the following formula (6).

[0036] TIFF2025130037000004.tif35170

[0037] 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- (circled - in the figure) 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.

[0038] Examples of the salts of sulfonic acid include sodium salts, potassium salts, and cesium salts.

[0039] <R 1 > R 1 R represents an alkyl group having 1 to 20 carbon atoms which may have a substituent, an alkoxy group having 1 to 20 carbon atoms which may have a substituent, or a (hetero)aryl group which may have a substituent. 1 From the viewpoint of the photostability of the compound, is preferably an alkyl group having 1 to 20 carbon atoms which may have a substituent.

[0040] R 1The substituents optionally contained in the hydroxyl group are any of a halogen atom, 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, and a salt of sulfonic acid, or a combination thereof. Among these substituents, from the viewpoint of solubility, 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, and a salt of sulfonic acid, or a combination thereof, is preferred.

[0041] R 1 Specific examples of the substituent that may be possessed by Ar include the above-mentioned Ar 1 The substituents are the same as those that may be contained in the group X. Among these, a halogen atom is particularly preferable. Specific examples of the halogen atom include a bromine atom and a chlorine atom, and a bromine atom is more preferable, in terms of excellent chemical durability.

[0042] <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.

[0043] TIFF2025130037000005.tif194170

[0044] <Synthesis method> As shown in the following reaction scheme, the compound of the present invention can be synthesized by reacting an azadipyrromethene skeleton with a silicon compound (e.g., a trichlorosilane derivative) to synthesize an intermediate having a structure consisting of an azadipyrromethene and a silicon atom, and then introducing a halogen atom using a halogenating agent (e.g., bromine molecules, N-bromosuccinimide, N-iodosuccinimide, etc.). A specific synthesis method is as shown in the synthesis example of Compound 1 described in the Examples section below. Alternatively, the compound of the present invention can be synthesized by synthesizing an azadipyrromethene intermediate substituted with a halogen atom from an azadipyrromethene skeleton and a halogenating agent, and then reacting the intermediate with a silicon compound.

[0045] TIFF2025130037000006.tif20193

[0046] In the above reaction scheme, X 1 ,X 2 ,Ar 1 ,R 1 has the same meaning as in the above formula (1).

[0047] <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]

[0048] 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.

[0049] <Synthesis of Compound 1> Compound 1 was synthesized via intermediates 1 and 2 as described below.

[0050] TIFF2025130037000007.tif65170

[0051] Intermediate 1 (0.31 g, synthesized according to the method described in Org. Lett., 2008, 10, 21, 4771-4774) was placed in a 100 mL recovery flask and purged with nitrogen. After that, dehydrated pyridine (20 mL) and dodecyltrichlorosilane (0.38 mL) were added and stirred at 85°C for 60 minutes. After cooling to room temperature, the residue obtained after concentration under reduced pressure was purified by silica gel column chromatography (neutral silica gel, dichloromethane / hexane = 5 / 5), yielding 0.23 g of intermediate 2 as a copper-colored solid.

[0052] TIFF2025130037000008.tif66170

[0053] Intermediate 2 (0.22 g) and dichloromethane (30 mL) were placed in a 100 mL recovery flask, and N-bromosuccinimide (58 mg) was added while stirring at room temperature. The mixture was stirred at room temperature for 45 minutes. The solvent was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (neutral silica gel, dichloromethane / hexane = 5 / 5), yielding 0.15 g of compound 1 as a purple solid.

[0054] <Synthesis of Compound 2> Compound 2 was synthesized via intermediates 1 and 3 as described below.

[0055] TIFF2025130037000009.tif60170

[0056] Intermediate 1 (1.57 g) was placed in a 300 mL recovery flask and the inside of the flask was replaced with nitrogen, after which dehydrated pyridine (40 mL) and (3-bromopropyl)trichlorosilane (1.03 mL) were added and the mixture was stirred for 50 minutes at 85° C. After cooling to room temperature and concentrating under reduced pressure, the resulting residue was purified by silica gel column chromatography (neutral silica gel, dichloromethane only), yielding 0.53 g of Intermediate 3 as a black solid.

[0057] TIFF2025130037000010.tif61170

[0058] Intermediate 3 (0.20 g) and dichloromethane (30 mL) were placed in a 100 mL recovery flask, and N-bromosuccinimide (57 mg) was added while stirring at room temperature. The mixture was stirred 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 = 5 / 5), yielding 0.14 g of compound 2 as a purple solid.

[0059] <Synthesis of Comparative Compound 1> Comparative compound 1 was synthesized in the same manner as intermediate 3 described in paragraphs

[0066] to

[0069] of JP-A-2023-020417.

[0060] <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.

[0061] TIFF2025130037000011.tif67170

[0062] The absorption spectra of the obtained compounds 1 and 2 and comparative compound 1 were measured, and the results are shown in FIG. The maximum absorption wavelength of Compound 1 was 714 nm. The extinction coefficient was 87,000 M -1 cm -1 It was. The maximum absorption wavelength of Compound 2 was 714 nm. The extinction coefficient was 80,000 M -1 cm -1 It was. The maximum absorption wavelength of Comparative Compound 1 was 684 nm. The extinction coefficient was 69600 M -1 cm -1 It was.

[0063] As can be seen from FIG. 1, it was revealed that Compounds 1 and 2 have absorption at longer wavelengths than Comparative Compound 1, with maximum absorption wavelengths of 700 nm or longer.

[0064] <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. A spectrometer (Actes, CSM-330) is used, and a photomultiplier tube (Hamamatsu Photonics, R5509-43) is used as the detector. Measurements are performed at an excitation wavelength of 660 nm.

[0065] The resulting compounds 1 and 2 are measured for singlet oxygen generation. As a result, if luminescence due to singlet oxygen is clearly observed at 1270 nm from the toluene solution of Compound 1, it can be evaluated as having singlet oxygen properties. If luminescence due to singlet oxygen is clearly observed at 1270 nm from a toluene solution of Compound 2, it can be evaluated as having singlet oxygen properties.

[0066] The singlet oxygen generating ability was evaluated by the above-mentioned method for evaluating singlet oxygen generating ability. Specifically, the solvent used for the measurement 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 660 nm.

[0067] From the toluene solution of the above compound 1, luminescence due to singlet oxygen was clearly observed at 1270 nm. From the toluene solution of the compound 2, luminescence due to singlet oxygen was clearly observed at 1270 nm.

[0068] <Consideration> Based on the above examples, the test results so far conducted by the present inventors, and common general technical knowledge, it is expected that a compound represented by the following formula (1) will have a maximum absorption wavelength of 700 nm or more and generate singlet oxygen upon light irradiation.

[0069] TIFF2025130037000012.tif49170

[0070] The compound of formula (1) has a structure consisting of azadipyrromethene and a silicon atom, and further has a six-membered ring structure containing N-Si-O having the silicon 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 compound of formula (1) has a six-membered ring structure containing N-Si-O with a silicon 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 that the efficiency of generating singlet oxygen in response to the excitation light increases.

[0071] 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.

[0072] Considering the above structural features, X 1 If the Br atom 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 compounds 1 and 2 can be obtained. Also, X 2 If is a halogen atom or a hydrogen atom, it is believed that the same effect as that of Br in compounds 1 and 2 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 compounds 1 and 2. Also, R 1 Regarding R 1 is an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkoxy group having 1 to 20 carbon atoms, or an optionally substituted (hetero)aryl group, and is therefore not considered to impair the above structural features, and is therefore considered to be able to solve the problem, similarly to compounds 1 and 2.

Claims

1. A compound represented by the following formula (1): [In formula (1), X １ represents a halogen atom. ２ represents a halogen atom or a hydrogen 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. R １ represents an alkyl group having 1 to 20 carbon atoms which may have a substituent, an alkoxy group having 1 to 20 carbon atoms which may have a substituent, or a (hetero)aryl group which may have a substituent. R １ The substituents which may be substituted are any one of a halogen atom, 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.]

2. The X １ is an iodine atom or a bromine atom, and ２ The compound according to claim 1, wherein is an iodine atom, a bromine atom, or a hydrogen atom.

3. The X １ is a bromine atom, and said X ２ The compound according to claim 1, wherein is a bromine atom or a hydrogen atom.

4. The X １ is a bromine atom, and said X ２ The compound according to claim 1, wherein is a hydrogen atom.

Images