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WO2006093251A1 - Nouveau photosensibilisateur - Google Patents

Nouveau photosensibilisateur Download PDF

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Publication number
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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WO
WIPO (PCT)
Prior art keywords
group
substituent
optionally substituted
compound
present
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Application number
PCT/JP2006/304053
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English (en)
Japanese (ja)
Inventor
Tetsuo Nagano
Yasuteru Urano
Takatoshi Yogo
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Tokyo NUC
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University of Tokyo NUC
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Filing date
Publication date
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Publication of WO2006093251A1 publication Critical patent/WO2006093251A1/fr
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Classifications

    • 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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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L’invention décrit un composé représenté par la formule (I) suivante. (I) (dans la formule, R1 représente un atome d'hydrogène, un groupe aryle éventuellement substitué ou un groupe alkyle éventuellement substitué ; et R2, R3, R4 et R5 représentent indépendamment un groupe alkyle éventuellement substitué en C1-C6, un groupe aryle éventuellement substitué, un groupe alcoxycarbonyle éventuellement substitué en C1-C6, un groupe vinyle éventuellement substitué, un groupe thiényle éventuellement substitué ou un groupe pyrrolyle éventuellement substitué. L’invention décrit également un photosensibilisateur constitué d'un tel composé.
PCT/JP2006/304053 2005-03-04 2006-03-03 Nouveau photosensibilisateur Ceased WO2006093251A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US65817605P 2005-03-04 2005-03-04
US60/658,176 2005-03-04

Publications (1)

Publication Number Publication Date
WO2006093251A1 true WO2006093251A1 (fr) 2006-09-08

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2006/304053 Ceased WO2006093251A1 (fr) 2005-03-04 2006-03-03 Nouveau photosensibilisateur

Country Status (1)

Country Link
WO (1) WO2006093251A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009298720A (ja) * 2008-06-12 2009-12-24 National Institute Of Advanced Industrial & Technology ボロンジピロロメタン誘導体及びそれを用いた過酸化脂質測定試薬
JP2012128207A (ja) * 2010-12-15 2012-07-05 Canon Inc 音響装置及びその制御方法、プログラム
WO2016143699A1 (fr) * 2015-03-06 2016-09-15 国立研究開発法人科学技術振興機構 Complexe bore-dipyrrine et produit pharmaceutique le contenant

Citations (4)

* Cited by examiner, † Cited by third party
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 (ja) * 1998-07-22 2000-02-08 Kansai Paint Co Ltd ポジ型可視光感光性樹脂組成物及びその用途
JP2002236360A (ja) * 2001-02-09 2002-08-23 Mitsui Chemicals Inc 感光性樹脂組成物及び該用途

Patent Citations (4)

* Cited by examiner, † Cited by third party
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 (ja) * 1998-07-22 2000-02-08 Kansai Paint Co Ltd ポジ型可視光感光性樹脂組成物及びその用途
JP2002236360A (ja) * 2001-02-09 2002-08-23 Mitsui Chemicals Inc 感光性樹脂組成物及び該用途

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009298720A (ja) * 2008-06-12 2009-12-24 National Institute Of Advanced Industrial & Technology ボロンジピロロメタン誘導体及びそれを用いた過酸化脂質測定試薬
JP2012128207A (ja) * 2010-12-15 2012-07-05 Canon Inc 音響装置及びその制御方法、プログラム
WO2016143699A1 (fr) * 2015-03-06 2016-09-15 国立研究開発法人科学技術振興機構 Complexe bore-dipyrrine et produit pharmaceutique le contenant
JPWO2016143699A1 (ja) * 2015-03-06 2017-12-28 国立研究開発法人科学技術振興機構 ジピリンホウ素錯体及びこれを含有する医薬

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