WO2006093251A1 - Novel photosensitizer - Google Patents
Novel photosensitizer Download PDFInfo
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- WO2006093251A1 WO2006093251A1 PCT/JP2006/304053 JP2006304053W WO2006093251A1 WO 2006093251 A1 WO2006093251 A1 WO 2006093251A1 JP 2006304053 W JP2006304053 W JP 2006304053W WO 2006093251 A1 WO2006093251 A1 WO 2006093251A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/022—Boron compounds without C-boron linkages
Definitions
- the present invention relates to a novel photosensitizer.
- Photosensitizers are active oxygen species (such as singlet oxygen 0) associated with light irradiation.
- ROS retinal oxidative stress response
- Photodynamic therapy Photodynamic therapy
- pedes a study on the oxidative stress response of cells, functional evaluation of reactive oxygen scavengers, photodynamic therapy (Photodynamic therapy) that performs treatment by loading ROS specifically in tumor tissues It is used in a wide range of applications such as pharmaceuticals.
- Photosensitizer Rose bengal is widely used in the industry.
- many of the existing photosensitizers have problems such as changes in properties as photosensitizers or the occurrence of photofading depending on the environment (solvent polarity, pH, etc.). ing.
- An object of the present invention is to provide a novel compound useful as a photosensitizer capable of exhibiting high active oxygen generation ability without being affected by the type of solvent and pH, and having reduced light fading. It is in this.
- the present inventors solved the above-mentioned problems by using a boron dipyrromethene skeleton as the basic skeleton of the photosensitizer. The present inventors have found that this can be done and have completed the present invention.
- R 1 represents a hydrogen atom, an aryl group optionally having substituent (s), or an alkyl group optionally having substituent (s);
- R 2 , R 4 and R 5 each independently have a C alkyl group that may have a substituent, an aryl group that may have a substituent, or a substituent.
- It may have a c alkoxycarbonyl group, a substituent, and may have a bure group, a substituent.
- R 1 is a hydrogen atom
- R 2 Compounds are provided that are R and R 5 force S methyl groups.
- a photosensitizer comprising the compound represented by the above formula (I) and a compound represented by the above formula (I) are used and activated.
- a method for generating oxygen species is provided.
- a medicament comprising the compound represented by the above formula (I) as an active ingredient, and a method for treating malignant tumor, wherein the compound represented by the above formula (I) is administered to mammals including humans. And a method comprising destroying malignant tumor cells by generating reactive oxygen species in the malignant tumor.
- FIG. 1 Example of the synthesis scheme of the compound of the present invention (A) and ⁇ specific near-infrared emission
- FIG. 6 is a diagram showing the result (B) of measuring the production ability by detecting.
- FIG. 2 is a graph showing the results of comparing the light stability of the compound of the present invention with that of rose bengal.
- examples of the alkyl group include straight chain or branched chain having, for example, carbon number:! To 12, preferably carbon number:! To 6, more preferably 1 to 4 carbon atoms, An alkyl group consisting of a ring or a combination thereof is meant. More specifically, the alkyl group is low A primary alkyl group (an alkyl group having 1 to 6 carbon atoms) is preferred.
- Examples of the lower alkyl group include methinole group, ethyl group, n-propyl group, isopropyl group, cyclopropyl group, n-butyl group, sec-butyl group, isobutyl group, tert-butyl group, cyclopropylmethyl group, n_ Examples thereof include a pentyl group and n_hexynole group.
- aryleno group a monocyclic or polycyclic aryl group may be used, or a vinyl group may be used, but a phenyl group can be preferably used.
- the type, number, and substitution position of the substituent are not particularly limited.
- a halogen atom a fluorine atom, a chlorine atom
- Any of bromine atom and iodine atom a hydroxyl group, an amino group, a force levoxy group, a sulfonic acid group, an alkyl sulfonate group and the like may be used as a substituent.
- Examples of the C alkyl group optionally having substituents represented by R 2 , R 3 , R 4 , and R 5 include
- a methyl group or an ethyl group can be used. Particularly preferred is a methyl group.
- substituent in the case where the alkyl group has a substituent include an amino group, a carboxy group, a sulfonic acid group, an alkyl sulfonate group, and a thiol group.
- a phenyl group is preferable.
- a sulfonic acid group or a sulfonate group is preferred as the substituent, and a sulfonic acid group is particularly preferred.
- An ethoxycarbonyl group is preferred as the luponyl group.
- substituents that may be present in a vinyl group having a substituent include a phenyl group, a monoaminophenol group, or a diaminophenyl group (eg, 3,4-diaminophenyl group). it can.
- a substituent having a substituent, Temeyole, a enyl group or a substituent having a substituent, a melenore, or a pyrrolinore group is preferably a 2-phenyl group or a 2-pyrrolyl group, respectively. .
- the method for producing the compound of the present invention represented by the formula (I) is not particularly limited.
- the compound of the present invention can be easily produced by those skilled in the art, for example, according to the production methods specifically disclosed in the examples of the present specification, and the production methods specifically disclosed in the present specification are referred to.
- any compound included in the formula (I) can be easily produced by appropriately selecting starting materials, reagents, and the like and, if necessary, appropriately modifying or modifying the method.
- the compound of the present invention is useful as a photosensitizer. Examples of the reactive oxygen species generated by the compound of the present invention include a force s that can include singlet oxygen 0), and the like.
- the compound of the present invention can be used, for example, as a research reagent for research on oxidative stress response of cells and functional evaluation of active oxygen scavengers. It is also possible to use it as an active ingredient of a medicine for photodynamic 'therapy where oxygen species are loaded to treat.
- a pharmaceutical composition is prepared using one or more general pharmaceutical additives such as excipients as necessary to prepare humans. It is desirable to administer to mammals including it.
- the compound of the present invention is not limited to the function as the photosensitizer of the present invention, and the antibody, ligand, etc. may be introduced via one or more substituents represented by R 1 to R 5.
- Examples of the method of binding the compound of the present invention to an antibody or the like include, for example, a group capable of binding to an antibody or the like such as a carboxy group or an active ester group in a part of the substituents represented by R 1 to R5, A commonly used method such as a bonding method using an agent or an active ester method can be used.
- the thus obtained compound of the present invention can specifically transport the photosensitizer of the present invention to a tumor tissue, for example, during photodynamic therapy.
- 2I-BDPO 10 production ability was measured by detecting specific near-infrared emission.
- 2I-BDP and the existing photosensitizer Rose bengal as a control were prepared by dissolving them in methanol at a concentration of 50 ⁇ mol / L. % Dimethylformamide).
- Table 1 shows the values (1 / ⁇ ) corrected for the emission intensity of m by the molar extinction coefficient.
- the 2I-BDP sample was irradiated with 530 nm light, and the Rose Bengal sample was irradiated with 556 nm light.
- 1,3-Diphenylisobenzofuran has a characteristic absorption power at 410 nm.
- Fig. 2 (A) shows the change in the absorption spectrum when the laser is repeatedly irradiated (the change in the spectrum was traced from 0 to 8 cycles).
- Fig. 2 (B) shows the change in absorbance at the maximum absorption wavelength of each dye with laser irradiation. From this fading speed, it was shown that 2I-BDP has about 4.4 times light stability compared to Rose Bengal.
- the compound of the present invention is useful as a photosensitizer capable of exhibiting high active oxygen generation ability without being affected by the type of solvent and pH, and having reduced photo-fading properties.
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Abstract
Description
明 細 書 Specification
新規光増感剤 New photosensitizer
技術分野 Technical field
[0001] 本発明は新規な光増感剤に関するものである。 [0001] The present invention relates to a novel photosensitizer.
背景技術 Background art
[0002] 光増感剤は光照射に伴レ、一重項酸素 0 )などの活性酸素種（Reactive oxygen s [0002] Photosensitizers are active oxygen species (such as singlet oxygen 0) associated with light irradiation.
2 2
pedes, ROS)を生成する色素化合物であり、細胞の酸化ストレス応答に関する研究、 活性酸素消去剤の機能評価、腫瘍組織特異的に ROSを負荷し治療を行うフォトダイ ナミック 'セラピー (Photodynamic therapy)のための医薬など幅広い用途で用いられて いる。代表的な光増感剤としてはローズベンガル (Rose bengal)が当業界で汎用され ている。し力 ながら、既存の光増感剤の多くは適用する環境 (溶媒の極性や pHなど )に応じて光増感剤としての性質が変化したり、あるいは光褪色を生じるなどの問題 を有している。 pedes, ROS), a study on the oxidative stress response of cells, functional evaluation of reactive oxygen scavengers, photodynamic therapy (Photodynamic therapy) that performs treatment by loading ROS specifically in tumor tissues It is used in a wide range of applications such as pharmaceuticals. As a typical photosensitizer, Rose bengal is widely used in the industry. However, many of the existing photosensitizers have problems such as changes in properties as photosensitizers or the occurrence of photofading depending on the environment (solvent polarity, pH, etc.). ing.
発明の開示 Disclosure of the invention
発明が解決しょうとする課題 Problems to be solved by the invention
[0003] 本発明の課題は、溶媒の種類や pHなどに影響されずに高い活性酸素生成能を発 揮でき、かつ光褪色性が軽減された光増感剤として有用な新規化合物を提供するこ とにある。 [0003] An object of the present invention is to provide a novel compound useful as a photosensitizer capable of exhibiting high active oxygen generation ability without being affected by the type of solvent and pH, and having reduced light fading. It is in this.
課題を解決するための手段 Means for solving the problem
[0004] 本発明者らは上記の課題を解決すべく鋭意研究を行なった結果、光増感剤の基 本骨格としてボロンジピロメテン（boron dipyrromethene)骨格を用いることにより、上 記の課題を解決できることを見出し、本発明を完成するに至った。 [0004] As a result of diligent research to solve the above-mentioned problems, the present inventors solved the above-mentioned problems by using a boron dipyrromethene skeleton as the basic skeleton of the photosensitizer. The present inventors have found that this can be done and have completed the present invention.
すなわち、本発明により、下記の式 (I) :
(式中、 R1は水素原子、置換基を有していてもよいァリール基、又は置換基を有して いてもよいアルキル基を示し、 R2、
1-6 1-6
てもよレ、c アルコキシカルボニル基、置換基を有してレ、てもよレ、ビュル基、置換基を It may have a c alkoxycarbonyl group, a substituent, and may have a bure group, a substituent.
1-6 1-6
有してレ、てもよレ、チェニル基、又は置換基を有してレ、てもよレ、ピロリル を示す）で表 わされる化合物が提供される。好ましくは、 R1が水素原子であり、 R2、
[0005] また、本発明の別の観点からは、上記の式 (I)で表される化合物からなる光増感剤、 及び上記の式 (I)で表される化合物を用レ、て活性酸素種を発生させる方法が提供さ れる。 [0005] From another aspect of the present invention, a photosensitizer comprising the compound represented by the above formula (I) and a compound represented by the above formula (I) are used and activated. A method for generating oxygen species is provided.
また、本発明のさらに別の観点からは、フォトダイナミックセラピー用の医薬であって From still another aspect of the present invention, it is a pharmaceutical for photodynamic therapy,
、上記の式 (I)で表される化合物を有効成分として含む医薬、及び悪性腫瘍の治療方 法であって、ヒトを含む哺乳類動物に上記の式 (I)で表される化合物を投与し、悪性腫 瘍において活性酸素種を発生させることにより悪性腫瘍細胞を破壊する工程を含む 方法が提供される。 A medicament comprising the compound represented by the above formula (I) as an active ingredient, and a method for treating malignant tumor, wherein the compound represented by the above formula (I) is administered to mammals including humans. And a method comprising destroying malignant tumor cells by generating reactive oxygen species in the malignant tumor.
図面の簡単な説明 Brief Description of Drawings
[0006] [図 1]本発明の化合物の合成スキームの 1例 (A)及び ^特異的な近赤外領域の発光 [0006] [FIG. 1] Example of the synthesis scheme of the compound of the present invention (A) and ^ specific near-infrared emission
2 2
を検出することにより 生成能を測定した結果 (B)を示した図である。 FIG. 6 is a diagram showing the result (B) of measuring the production ability by detecting.
2 2
[図 2]本発明の化合物の光安定性をローズベンガルと比較した結果を示した図である FIG. 2 is a graph showing the results of comparing the light stability of the compound of the present invention with that of rose bengal.
発明を実施するための最良の形態 BEST MODE FOR CARRYING OUT THE INVENTION
[0007] 本明細書において、アルキル基としては、例えば、炭素数:!〜 12個、好ましくは炭素 数:!〜 6個、さらに好ましくは炭素数 1〜4個の直鎖、分枝鎖、環状、又はそれらの組 み合わせからなるアルキル基を意味している。より具体的には、アルキル基として低 級アルキル基（炭素数 1〜6個のアルキル基）が好ましい。低級アルキル基としては、 例えば、メチノレ基、ェチル基、 n—プロピル基、イソプロピル基、シクロプロピル基、 n- ブチル基、 sec-ブチル基、イソブチル基、 tert-ブチル基、シクロプロピルメチル基、 n_ ペンチル基、 n_へキシノレ基などを挙げることができる。ァリーノレ基としては、単環性又 は多環性のァリール基のレ、ずれであってもよレ、が、好ましくはフエ二ル基を用いること ができる。 [0007] In the present specification, examples of the alkyl group include straight chain or branched chain having, for example, carbon number:! To 12, preferably carbon number:! To 6, more preferably 1 to 4 carbon atoms, An alkyl group consisting of a ring or a combination thereof is meant. More specifically, the alkyl group is low A primary alkyl group (an alkyl group having 1 to 6 carbon atoms) is preferred. Examples of the lower alkyl group include methinole group, ethyl group, n-propyl group, isopropyl group, cyclopropyl group, n-butyl group, sec-butyl group, isobutyl group, tert-butyl group, cyclopropylmethyl group, n_ Examples thereof include a pentyl group and n_hexynole group. As the aryleno group, a monocyclic or polycyclic aryl group may be used, or a vinyl group may be used, but a phenyl group can be preferably used.
[0008] 本明細書において、 R1が示すァリール基又はアルキル基が置換基を有する場合、 置換基の種類、個数、置換位置は特に限定されないが、例えば、ハロゲン原子（フッ 素原子、塩素原子、臭素原子、ヨウ素原子のいずれでもよい）、水酸基、アミノ基、力 ノレボキシ基、スルホン酸基、アルキルスルホネート基などを置換基として有していても よい。 In the present specification, when the aryl group or alkyl group represented by R 1 has a substituent, the type, number, and substitution position of the substituent are not particularly limited. For example, a halogen atom (a fluorine atom, a chlorine atom) Any of bromine atom and iodine atom), a hydroxyl group, an amino group, a force levoxy group, a sulfonic acid group, an alkyl sulfonate group and the like may be used as a substituent.
[0009] R2、 R3、 R4、及び R5が示す置換基を有していてもよい C アルキル基としては、例え [0009] Examples of the C alkyl group optionally having substituents represented by R 2 , R 3 , R 4 , and R 5 include
1-6 1-6
ばメチル基又はェチル基などを用いることができる。特に好ましいのはメチル基であ る。アルキル基が置換基を有する場合の該置換基としては、アミノ基、カルボキシ基、 スルホン酸基、アルキルスルホネート基、チオール基などを挙げることができる。置換 基を有していてもよいァリール基としてはフエニル基が好ましい。フエニル基が置換基 を有する場合、該置換基としてはスルホン酸基又はスルホネート基などが好ましぐ 特に好ましいのはスルホン酸基である。置換基を有していてもよい C アルコキシ力 For example, a methyl group or an ethyl group can be used. Particularly preferred is a methyl group. Examples of the substituent in the case where the alkyl group has a substituent include an amino group, a carboxy group, a sulfonic acid group, an alkyl sulfonate group, and a thiol group. As the aryl group which may have a substituent, a phenyl group is preferable. When the phenyl group has a substituent, a sulfonic acid group or a sulfonate group is preferred as the substituent, and a sulfonic acid group is particularly preferred. C alkoxy group optionally having substituent (s)
1-6 1-6
ルポニル基としてはエトキシカルボニル基が好ましレ、。置換基を有してレ、てもよレヽビニ ル基に存在する置換基としてはフエニル基、モノァミノフエ二ノレ基、又はジァミノフエ二 ル基（例えば 3,4-ジァミノフエニル基）などを挙げること力 Sできる。置換基を有してレ、て もよレ、チェニル基又は置換基を有してレ、てもよレ、ピロリノレ基としては、それぞれ 2-チ ェニル基又は 2-ピロリル基が好ましレ、。 An ethoxycarbonyl group is preferred as the luponyl group. Examples of substituents that may be present in a vinyl group having a substituent include a phenyl group, a monoaminophenol group, or a diaminophenyl group (eg, 3,4-diaminophenyl group). it can. As a substituent having a substituent, Temeyole, a enyl group or a substituent having a substituent, a melenore, or a pyrrolinore group is preferably a 2-phenyl group or a 2-pyrrolyl group, respectively. .
[0010] 式 (I)で表される本発明の化合物の製造方法は特に限定されない。本発明の化合 物は、例えば、本明細書の実施例に具体的に開示された製造方法に従って当業者 が容易に製造でき、また、本明細書に具体的に開示された製造方法を参照しつつ、 出発原料や試薬などを適宜選択し、必要に応じて該方法に適宜の修飾ないし改変 をカロえることにより、式 (I)に包含される任意の化合物を容易に製造できる。 [0011] 本発明の化合物は、光増感剤として有用である。本発明の化合物により生成される 活性酸素種としては、例えば、一重項酸素 0 )などを挙げることができる力 s、これに [0010] The method for producing the compound of the present invention represented by the formula (I) is not particularly limited. The compound of the present invention can be easily produced by those skilled in the art, for example, according to the production methods specifically disclosed in the examples of the present specification, and the production methods specifically disclosed in the present specification are referred to. On the other hand, any compound included in the formula (I) can be easily produced by appropriately selecting starting materials, reagents, and the like and, if necessary, appropriately modifying or modifying the method. [0011] The compound of the present invention is useful as a photosensitizer. Examples of the reactive oxygen species generated by the compound of the present invention include a force s that can include singlet oxygen 0), and the like.
2 2
限定されることはない。本発明の化合物は、例えば、細胞の酸化ストレス応答に関す る研究や活性酸素消去剤の機能評価のための研究用試薬として用いることができる また、本発明の化合物は、腫瘍組織特異的に活性酸素種を負荷して治療を行うフ オトダイナミック 'セラピーのための医薬の有効成分として用いることも可能である。上 記の医薬として本発明の化合物を用いる場合には、必要に応じて、賦形剤などの汎 用の製剤用添加物を 1種又は 2種以上用いて医薬組成物を調製してヒトを含む哺乳 類動物に投与することが望ましい。 There is no limit. The compound of the present invention can be used, for example, as a research reagent for research on oxidative stress response of cells and functional evaluation of active oxygen scavengers. It is also possible to use it as an active ingredient of a medicine for photodynamic 'therapy where oxygen species are loaded to treat. When the compound of the present invention is used as the above-mentioned medicine, a pharmaceutical composition is prepared using one or more general pharmaceutical additives such as excipients as necessary to prepare humans. It is desirable to administer to mammals including it.
[0012] 本発明の化合物は、本発明の光増感剤としての機能を損なわないことを限度として 、 R1乃 至 R5で表される置換基の一つ以上を介して抗体やリガンド等と結合させて使 用すること力 Sできる。本発明の化合物を抗体等と結合させる方法としては、例えば、 R 1乃至 R5で表される置換基の一部にカルボキシ基や活性エステル基など抗体等と結 合可能な基を存在させ、縮合剤や活性エステル法などを用いて結合させる方法等、 通常使用される方法を用いることができる。このようにして得られた本発明の化合物 は、例えば、フォトダイナミック 'セラピーの際に、腫瘍組織へ本発明の光増感剤を特 異的に搬送することができる。 [0012] The compound of the present invention is not limited to the function as the photosensitizer of the present invention, and the antibody, ligand, etc. may be introduced via one or more substituents represented by R 1 to R 5. Can be used in combination with S. Examples of the method of binding the compound of the present invention to an antibody or the like include, for example, a group capable of binding to an antibody or the like such as a carboxy group or an active ester group in a part of the substituents represented by R 1 to R5, A commonly used method such as a bonding method using an agent or an active ester method can be used. The thus obtained compound of the present invention can specifically transport the photosensitizer of the present invention to a tumor tissue, for example, during photodynamic therapy.
実施例 Example
[0013] 以下、実施例により本発明をさらに具体的に説明するが、本発明の範囲は下記の 実施例により限定されることはない。 [0013] The present invention will be described more specifically with reference to the following examples. However, the scope of the present invention is not limited by the following examples.
例 1 Example 1
4，4 -ジフルォ口- 1，3，5，7 -テトラメチル -4-ボラ _3a，4a-ジァザ _s-インダセン (BODIPY 、登録商標、 505/515,モレキユラ一'プローブス社製） (1.0 eq.)をメチレンクロライド及 び無水エタノールに溶解し、ヨウ素（I ) (2.5 eq.)を加えた。その後、水にヨウ素酸（HIO 4,4-difluo-mouth-1,3,5,7-tetramethyl-4-bora _3a, 4a-diaza_s-indacene (BODIPY, registered trademark, 505/515, manufactured by Molecular One Probes) (1.0 eq. ) Was dissolved in methylene chloride and absolute ethanol, and iodine (I) (2.5 eq.) Was added. Then, iodate (HIO in water)
2 2
) (2.0 eq.)を溶解させた水溶液を 20分かけて滴下しながら撹拌した。さらに 60°Cで 20 ) An aqueous solution in which (2.0 eq.) Was dissolved was added dropwise over 20 minutes. 20 at 60 ° C
3 Three
分撹拌した後、溶媒を溜去し、残渣をシリカゲルカラムにより精製した。 n-へキサン/ クロ口ホルムより再結晶して 4,4-ジフルォ口- 2,6-ジィォド -1,3, 5,7-テトラメチル -4-ボ ラ -3a 4a_ジァザ- s-インダセン (2I-BDP)を得た。 After stirring for a minute, the solvent was distilled off and the residue was purified by a silica gel column. Recrystallized from n-hexane / chloroform, 4,4-difluoro-2,6-diodo-1,3,5,7-tetramethyl-4-bo La-3a 4a_diaza-s-indacene (2I-BDP) was obtained.
'H-NMR (CDC1 , 300 MHz) 2.22, 2.54, 7.10 'H-NMR (CDC1, 300 MHz) 2.22, 2.54, 7.10
3 Three
13C-NMR (CDC1 75 MHz) 13.75, 15.68, 82.00, 120.22, 132.81 144.35, 157.70 13 C-NMR (CDC1 75 MHz) 13.75, 15.68, 82.00, 120.22, 132.81 144.35, 157.70
3 Three
HRMS (ESI-) calcd for C H BF I N 498.91510 (M-H). found 498.91858 HRMS (ESI-) calcd for C H BF I N 498.91510 (M-H) .found 498.91858
13 12 2 2 2 13 12 2 2 2
Anal. Calcd for C H BF I N N 5.60; C 31.24; H 2.62. found: N 5.42; C 31.39 Anal. Calcd for C H BF I N N 5.60; C 31.24; H 2.62. Found: N 5.42; C 31.39
13 13 2 2 2 13 13 2 2 2
H, 2.76 H, 2.76
[0014] 例 2 [0014] Example 2
2I-BDPO10生成能を 特異的な近赤外領域の発光を検出することにより測定し 2I-BDPO 10 production ability was measured by detecting specific near-infrared emission.
2 2 twenty two
た。 It was.
(a)サンプノレ調製 (a) Sampnore preparation
2I-BDP及び対照として既存の光増感剤であるローズベンガル (Rose bengal)を各 50 μ mol/Lになるようにメタノールに溶解した溶液を作成した（2ト BDPは共溶媒として 0. 1%ジメチルホルムアミドを含む）。 2I-BDP and the existing photosensitizer Rose bengal as a control were prepared by dissolving them in methanol at a concentration of 50 μmol / L. % Dimethylformamide).
(b)測定 (b) Measurement
2I-BDP及びローズベンガルを約 0.1 W 514 nmのアルゴンレーザーで励起したとこ ろ、 1268 nm付近に 特異的な発光が観察された (図 1 B)。レーザーの励起波長で When 2I-BDP and Rose Bengal were excited with an argon laser of about 0.1 W 514 nm, specific emission was observed around 1268 nm (Fig. 1B). At the excitation wavelength of the laser
2 2
ある 514 nmにおける各光増感剤の吸光度 (A )、モル吸光係数（ ε )、及び 1268 η The absorbance (A), molar extinction coefficient (ε), and 1268 η of each photosensitizer at a certain 514 nm
514 514 514 514
mの発光強度をモル吸光係数で補正した値 (1/ ε )を表 1に示す。この結果、 2I-BD Table 1 shows the values (1 / ε) corrected for the emission intensity of m by the molar extinction coefficient. As a result, 2I-BD
514 514
Ρはメタノール中でローズベンガルよりも 1.34倍高い ^生成能を持つことが確認でき Ρ can be confirmed to have 1.34 times higher ^^ production capacity in methanol than rose bengal
2 2
た。 It was.
[0015] [表 1] [0015] [Table 1]
例 3 Example 3
様々な有機溶媒中における 2I-BDPの 生成能をジフエ二ルイソべンゾフラン法に Diphenylisobenzofuran method for producing 2I-BDP in various organic solvents
2 2
より測定した。 More measured.
(a)サンプノレ調製 2I-BDP及びローズベンガルを 1 μ mol/Lになるように各有機溶媒に溶解させた (2卜 BDPは共溶媒として 0.1%ジメチルホルムアミドを含む)。さらに 1 ,3-ジフエ二ルイソベン ゾフランを 20 μ mol/L (共溶媒として 0.1%ジメチルホルムアミドを含む)となるように溶 解させた。 (a) Sampnore preparation 2I-BDP and rose bengal were dissolved in each organic solvent so as to be 1 μmol / L (2L BDP contains 0.1% dimethylformamide as a co-solvent). Further, 1,3-diphenylisobenzofuran was dissolved to 20 μmol / L (containing 0.1% dimethylformamide as a co-solvent).
[0017] (b)測定 [0017] (b) Measurement
2I-BDPのサンプルには 530 nm、ローズベンガルのサンプルには 556 nmの光を照 射した。 1，3 -ジフエ二ルイソべンゾフランは 410 nmに特徴的な吸光を持つ力 との The 2I-BDP sample was irradiated with 530 nm light, and the Rose Bengal sample was irradiated with 556 nm light. 1,3-Diphenylisobenzofuran has a characteristic absorption power at 410 nm.
2 反応によりこの吸収がなくなる。この吸収の消失から 生成能を評価した。表 2に 1 ,3 2 This absorption is eliminated by the reaction. The production ability was evaluated from the disappearance of this absorption. 1 and 3 in Table 2
2 2
-ジフヱニルイソべンゾフランの退色の速度（slope)、照射した光の波長における光増 感剤の吸光度（relative number of absorbed photons) ,及びその吸光度で退色の速 度を補正した値である relative efficiency ϊ ιΟ generationを示す。この結果から、 21--The rate of fading of diphenylisobenzofuran, the absorbance of the photosensitizer at the wavelength of the irradiated light (relative number of absorbed photons), and the value obtained by correcting the rate of fading by the absorbance relative efficiency ϊ ι Ο Indicates generation. From this result, 21-
2 2
BDPはどの溶媒においても効率よく を生成することが示された。また、参考として BDP has been shown to efficiently produce in any solvent. Also as a reference
2 2
各溶媒における の寿命を付記した。 2I-BDPの各溶媒における 生成能（relative The lifetime of in each solvent is noted. 2I-BDP production ability in each solvent (relative
2 2 twenty two
efficiency of 'θ generation)と各溶媒における の寿命との間には相関があること There is a correlation between the efficiency of 'θ generation) and the lifetime of
2 2 twenty two
から、 2I-BDP©10生成能は各溶媒で変化せず、様々な環境で安定した 生成能 Therefore, 2I-BDP © 10 production ability does not change with each solvent, and production ability is stable in various environments.
2 2 を持つことが示された。 It was shown to have 2 2.
[0018] [表 2] [0018] [Table 2]
2I-BDP ロース、'へ、、ン； Γル 2I-BDP Loin, 'To, N;
CH3CN CH30H アセトン CH2C12 CHCI3 CH3OH slope (x lO4 s—リ 128 44 130 129 142 29 relat ive number of CH 3 CN CH 3 0H Acetone CH 2 C1 2 CHCI3 CH3OH slope (x lO 4 s—li 128 44 130 129 142 29 relat ive number of
absorbed photons 0. 11 0. 12 0. 12 0. 096 0. 086 0. 13 relative effi c iency absorbed photons 0. 11 0. 12 0. 12 0. 096 0. 086 0. 13 relative effi c iency
of ]02 generation 0. 11 0. 037 0. 11 0. 14 0. 17 0. 022of ] 0 2 generation 0. 11 0. 037 0. 11 0. 14 0. 17 0. 022
Lifetime (x lO—6 sec. ) * 30-77 5- 12 26-65 59-100 60-260 Lifetime (x lO— 6 sec.) * 30-77 5- 12 26-65 59-100 60-260
*文献値 (Singlet 02 Volume I : Phys i cal-Chemi cal Aspect) * Literature value (Singlet 0 2 Volume I: Phys i cal-Chemi cal Aspect)
[0019] 例 4 [0019] Example 4
2I-BDPの光安定性をローズベンガルと比較した。 The light stability of 2I-BDP was compared with Rose Bengal.
(a)サンプノレ調製 (a) Sampnore preparation
2I-BDP及びローズベンガルを 1 /i mol/Lとなるようにメタノールに溶解した（2I-BDP は共溶媒として 0.1%ジメチルホルムアミドを含む）。 (b)測定 2I-BDP and rose bengal were dissolved in methanol to 1 / i mol / L (2I-BDP contains 0.1% dimethylformamide as a co-solvent). (b) Measurement
各サンプル溶液を 2I-BDP及びローズベンガルがほぼ同じ吸光度を持つ 546 nm ( 約 0.11 W)で励起した。励起には 546 nmの可変レーザーを用い 128回（emission inter val 0.1 se ）のレーザー照射 10回を 1サイクルとした。レーザーを繰り返し照射したと きの吸光スペクトルの変化を図 2(A)に示す（0〜8サイクルまでスペクトル変化を追跡 した）。その結果、ローズベンガルでは光照射に伴い顕著に褪色し、吸光スペクトル が大きく変化していくのに対し、 2I-BDPの褪色は非常に小さいことが確認できた。レ 一ザ一照射に伴う各色素の極大吸収波長における吸光度の変化を図 2(B)に示す。 この褪色の速度から、 2I-BDPはローズベンガルと比較して約 4.4倍の光安定性を持 つことが示された。 Each sample solution was excited at 546 nm (approximately 0.11 W), where 2I-BDP and Rose Bengal had approximately the same absorbance. For excitation, a variable laser of 546 nm was used, and 10 laser irradiations of 128 times (emission interval 0.1 se) were taken as one cycle. Fig. 2 (A) shows the change in the absorption spectrum when the laser is repeatedly irradiated (the change in the spectrum was traced from 0 to 8 cycles). As a result, in Rose Bengal, it was confirmed that the discoloration of 2I-BDP was very small while the absorption spectrum changed greatly with light irradiation. Fig. 2 (B) shows the change in absorbance at the maximum absorption wavelength of each dye with laser irradiation. From this fading speed, it was shown that 2I-BDP has about 4.4 times light stability compared to Rose Bengal.
産業上の利用可能性 Industrial applicability
本発明の化合物は、溶媒の種類や pHなどに影響されずに高い活性酸素生成能を 発揮でき、かつ光褪色性が軽減された光増感剤として有用である。 The compound of the present invention is useful as a photosensitizer capable of exhibiting high active oxygen generation ability without being affected by the type of solvent and pH, and having reduced photo-fading properties.
Claims
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009298720A (en) * | 2008-06-12 | 2009-12-24 | National Institute Of Advanced Industrial & Technology | Boron dipyrrolomethane derivative and reagent for measuring peroxylipid using the same |
| JP2012128207A (en) * | 2010-12-15 | 2012-07-05 | Canon Inc | Acoustic device, control method thereof, and program |
| WO2016143699A1 (en) * | 2015-03-06 | 2016-09-15 | 国立研究開発法人科学技術振興機構 | Boron-dipyrrin complex and pharmaceutical product containing same |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4774339A (en) * | 1987-08-10 | 1988-09-27 | Molecular Probes, Inc. | Chemically reactive dipyrrometheneboron difluoride dyes |
| US5869689A (en) * | 1995-10-17 | 1999-02-09 | Molecular Probes, Inc | Stains for acidic organelles |
| JP2000039716A (en) * | 1998-07-22 | 2000-02-08 | Kansai Paint Co Ltd | Positive type visible light sensitive resin composition and its use |
| JP2002236360A (en) * | 2001-02-09 | 2002-08-23 | Mitsui Chemicals Inc | Photosensitive resin composition and its use |
-
2006
- 2006-03-03 WO PCT/JP2006/304053 patent/WO2006093251A1/en not_active Ceased
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4774339A (en) * | 1987-08-10 | 1988-09-27 | Molecular Probes, Inc. | Chemically reactive dipyrrometheneboron difluoride dyes |
| US5869689A (en) * | 1995-10-17 | 1999-02-09 | Molecular Probes, Inc | Stains for acidic organelles |
| JP2000039716A (en) * | 1998-07-22 | 2000-02-08 | Kansai Paint Co Ltd | Positive type visible light sensitive resin composition and its use |
| JP2002236360A (en) * | 2001-02-09 | 2002-08-23 | Mitsui Chemicals Inc | Photosensitive resin composition and its use |
Non-Patent Citations (1)
| Title |
|---|
| YOGO T. ET AL.: "Highly Efficient and Photostable Photosensitizer Based on BODIPY Chromophore", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 127, no. 35, 7 September 2005 (2005-09-07), pages 12162 - 12163, XP003002850 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009298720A (en) * | 2008-06-12 | 2009-12-24 | National Institute Of Advanced Industrial & Technology | Boron dipyrrolomethane derivative and reagent for measuring peroxylipid using the same |
| JP2012128207A (en) * | 2010-12-15 | 2012-07-05 | Canon Inc | Acoustic device, control method thereof, and program |
| WO2016143699A1 (en) * | 2015-03-06 | 2016-09-15 | 国立研究開発法人科学技術振興機構 | Boron-dipyrrin complex and pharmaceutical product containing same |
| JPWO2016143699A1 (en) * | 2015-03-06 | 2017-12-28 | 国立研究開発法人科学技術振興機構 | Dipyrine boron complex and pharmaceutical containing the same |
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