JP5441882B2 - 過酸化水素特異的蛍光プローブ - Google Patents
過酸化水素特異的蛍光プローブ Download PDFInfo
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- JP5441882B2 JP5441882B2 JP2010501925A JP2010501925A JP5441882B2 JP 5441882 B2 JP5441882 B2 JP 5441882B2 JP 2010501925 A JP2010501925 A JP 2010501925A JP 2010501925 A JP2010501925 A JP 2010501925A JP 5441882 B2 JP5441882 B2 JP 5441882B2
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- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 title claims description 95
- 239000007850 fluorescent dye Substances 0.000 title description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000004989 dicarbonyl group Chemical group 0.000 claims description 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 4
- 239000007857 degradation product Substances 0.000 claims description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 22
- 229940125898 compound 5 Drugs 0.000 description 15
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 8
- 230000005284 excitation Effects 0.000 description 8
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 7
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 108010093894 Xanthine oxidase Proteins 0.000 description 6
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 6
- -1 organic acid salts Chemical class 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- CMFNMSMUKZHDEY-UHFFFAOYSA-N peroxynitrous acid Chemical compound OON=O CMFNMSMUKZHDEY-UHFFFAOYSA-N 0.000 description 5
- 102000016938 Catalase Human genes 0.000 description 4
- 108010053835 Catalase Proteins 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 4
- 102100037850 Interferon gamma Human genes 0.000 description 4
- 108010074328 Interferon-gamma Proteins 0.000 description 4
- 102000019197 Superoxide Dismutase Human genes 0.000 description 4
- 108010012715 Superoxide dismutase Proteins 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
- 102100033220 Xanthine oxidase Human genes 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 239000002158 endotoxin Substances 0.000 description 4
- 238000002189 fluorescence spectrum Methods 0.000 description 4
- 229920006008 lipopolysaccharide Polymers 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000003642 reactive oxygen metabolite Substances 0.000 description 4
- VTAXRKUQYSTRMC-UHFFFAOYSA-N 3-(9,10-dioxatricyclo[6.2.2.02,7]dodeca-2,4,6,11-tetraen-1-yl)propanoic acid Chemical compound C12=CC=CC=C2C2(CCC(=O)O)C=CC1OO2 VTAXRKUQYSTRMC-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- CHADEQDQBURGHL-UHFFFAOYSA-N (6'-acetyloxy-3-oxospiro[2-benzofuran-1,9'-xanthene]-3'-yl) acetate Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(OC(C)=O)C=C1OC1=CC(OC(=O)C)=CC=C21 CHADEQDQBURGHL-UHFFFAOYSA-N 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229960003130 interferon gamma Drugs 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- LAGNMUUUMQJXBF-UHFFFAOYSA-N 4-ethynylbenzonitrile Chemical compound C#CC1=CC=C(C#N)C=C1 LAGNMUUUMQJXBF-UHFFFAOYSA-N 0.000 description 1
- GZAJOEGTZDUSKS-UHFFFAOYSA-N 5-aminofluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(N)=CC=C21 GZAJOEGTZDUSKS-UHFFFAOYSA-N 0.000 description 1
- NJYVEMPWNAYQQN-UHFFFAOYSA-N 5-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21 NJYVEMPWNAYQQN-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000007323 disproportionation reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical class O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- CKFMJXZQTNRXGX-UHFFFAOYSA-L iron(2+);diperchlorate Chemical compound [Fe+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O CKFMJXZQTNRXGX-UHFFFAOYSA-L 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
- C07D311/82—Xanthenes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N31/00—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods
- G01N31/22—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods using chemical indicators
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N2021/7769—Measurement method of reaction-produced change in sensor
- G01N2021/7786—Fluorescence
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/20—Oxygen containing
- Y10T436/206664—Ozone or peroxide
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
- Pyrane Compounds (AREA)
Description
すなわち、本発明により、下記の一般式(IA)又は(IB):
例1
化合物3をJ. Org. Chem., 2003, 68, 8264-8267を参照して合成した。280 mg (0.516mmol)の化合物3、80 mg (0.629 mmol)の4-エチニルベンゾニトリル、22.8 mg (0.0325 mmol)のジクロロビス(トリフェニルホスフィン)パラジウムおよび28.4 mg (0.149 mmol)のヨウ化銅を20 mlのテトラヒドロフラン (THF)に懸濁し、これに0.27 ml (1.95 mmol)のトリエチルアミンを加え、反応液をアルゴン雰囲気下室温で12時間攪拌した。溶媒を減圧留去し、得られた固体をシリカゲルカラムクロマトグラフィーで精製し、目的化合物216 mg (0.399 mmol;収率 74%)を得た。
72.4 mg (0.137 mmol)の化合物4を1 mlのジメチルスルホキシド (DMSO)に溶解させ、そこに4.37 mg (0.0246 mmol)の塩化パラジウムを加え、反応液をアルゴン雰囲気下100℃で10時間攪拌した。反応液を室温まで冷却した後、10 mlのメタノールと100 mgの炭酸カリウムを加え、室温で30分間攪拌した。反応液中のメタノールを減圧留去し、2N 塩酸を加えて中和してから分取HPLCにより精製し、目的物32.0 mg (0.0654 mmol;収率 48%)を得た。
1H NMR (300MHz, DMSO-d6) δ 10.1 (s, 1H), 8.50 (m, 1H), 8.37 (d, 1H, J = 8.07 Hz), 8.20 (d, 2H, J = 8.25 Hz), 8.10 (d, 2H, J = 8.07 Hz), 7.51 (d, 1H, J = 8.04 Hz), 6.69 (d, 2H, J = 1.65 Hz), 6.63 (d, 2H, J = 8.61 Hz), 6.54 (dd, 2H, J = 8.79, 1.65 Hz)
13C NMR (100MHz, DMSO-d6) δ 191.2, 190.7, 167.5, 159.8, 157.8, 151.8, 136.7, 135.5, 133.8, 133.0, 130.8, 129.3, 127.0, 125.1, 118.0, 116.8, 112.8, 108.5, 102.3
HRMS (ESI-) Calcd for [M-H], 488.07703, Found, 488.07359 (-3.43mmu)
化合物5はキサンテン環からベンジル構造へのPhoto-induced electron Transfer (PeT)機構により消光し、それ自体は弱蛍光性である。一方、過酸化水素との反応により強蛍光性の5-カルボキシフルオレセインを生成する。
(B) 化合物5に過酸化水素、ヒドロキシルラジカル(hydroxylradical)、パーオキシナイトライト(peroxynitrite)、次亜塩素酸イオン(hypochlorite) 、NOC13 、EP-1をそれぞれ添加した場合を比較すると、過酸化水素を添加した場合にのみ蛍光強度の増大が観察され、その他の活性酸素種では蛍光強度の増大を示さないことが確認された。
(C) 化合物5に対してHPX/x.o.系を用いてスーパーオキサイド を反応させた場合、コントロール(Hnon)に対して蛍光強度は増大した。HPX/x.o.系にSODを添加しても蛍光強度の増大の程度に大きな変動はなかった。一方、カタラーゼ添加により蛍光強度の増大が抑制されコントロール(Hnon)付近まで低下した。これより、HPX/x.o.系で観察される蛍光強度の増大はスーパーオキサイドの不均化反応産物である過酸化水素によるものであると考えられた。以上の成績より、本発明の化合物5は、過酸化水素特異的蛍光プローブとしての性質を有しており、過酸化水素測定用試薬として使用できると結論された。また、HPX/x.o.系にカタラーゼを共存させた場合の成績より、本発明の化合物は、カタラーゼの活性測定用としても使用できることが確認された。
化合物5は生細胞における過酸化水素の検出にも適用できることを確認した。リポポリサッカライド(LPS)(50μg/ml)およびインターフェロン-γ(IFN-γ)(100 unit/ml)でRAW264.7細胞を12時間刺激した後、化合物5のジアセチル体を細胞にロードし、それから2時間後にオリンパス社製のU-MNIBA2フィルターセット(励起波長470-495 nm、蛍光波長510-550nm)を用い蛍光顕微鏡観察した(図2)。刺激していない細胞に化合物5をロードした場合(A)に比べて、刺激を加えた細胞では蛍光強度の増大が観察された(B)。
Claims (5)
- 下記の一般式(IA)又は(IB):
- R1がベンゼン環上の1個のシアノ基、ハロゲン原子、カルボキシ基、又はスルホ基であり、R2及びR3が水素原子であり、R4及びR5が水素原子であり、R6が水素原子である請求項1に記載の化合物又はその塩。
- キサンテン環に結合するベンゼン環において、R1が置換するフェニル基が結合するジカルボニル基の結合位置がキサンテン環に対してパラ位である請求項1に記載の化合物又はその塩。
- 請求項1に記載の一般式(IA)又は(IB)で表される化合物又はその塩を含む過酸化水素測定用試薬。
- ヒトの生体外において過酸化水素を測定する方法であって、下記の工程:(A)請求項4に記載の試薬と過酸化水素とを反応させる工程、及び(B)上記工程(A)で生成した上記試薬由来の分解物の蛍光を測定する工程を含む方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US3351108P | 2008-03-04 | 2008-03-04 | |
US61/033,511 | 2008-03-04 | ||
PCT/JP2009/054017 WO2009110487A1 (ja) | 2008-03-04 | 2009-03-04 | 過酸化水素特異的蛍光プローブ |
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JPWO2009110487A1 JPWO2009110487A1 (ja) | 2011-07-14 |
JP5441882B2 true JP5441882B2 (ja) | 2014-03-12 |
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US (1) | US8394850B2 (ja) |
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WO (1) | WO2009110487A1 (ja) |
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WO2013113279A1 (en) * | 2012-01-30 | 2013-08-08 | The University Of Hong Kong | Diarylamine-based fluorogenic probes for detection of peroxynitrite |
JP5512764B2 (ja) * | 2012-08-27 | 2014-06-04 | 学校法人同志社 | 複素環化合物、金属錯体及び蛍光プローブ |
US10877051B2 (en) | 2014-01-31 | 2020-12-29 | The University Of Hong Kong | Bistrifilate-based fluorogenic probes for detection of superoxide anion radical |
CN104817530B (zh) * | 2015-04-20 | 2016-11-23 | 济南大学 | 高灵敏选择性比色荧光双通道测定Cu2+的探针及其应用 |
CN106588966B (zh) * | 2016-11-14 | 2018-03-16 | 济南大学 | 一种开型过氧化氢荧光探针化合物的制备与应用 |
CN106928263B (zh) * | 2017-03-31 | 2019-01-01 | 济南大学 | 一种用于快速检测过氧化氢的荧光探针的制备与应用 |
CN107337681B (zh) * | 2017-07-28 | 2019-05-28 | 厦门大学 | 一种超氧阴离子探针及其制备方法和应用 |
FR3110572B1 (fr) * | 2020-05-19 | 2022-10-07 | Arkema France | Dérivé de xanthène, mélanges le comprenant, procédé de fabrication et utilisations correspondants |
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JP4713343B2 (ja) * | 2003-09-05 | 2011-06-29 | 哲雄 長野 | 蛍光プローブ |
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WO2001064664A1 (fr) * | 2000-02-29 | 2001-09-07 | Daiichi Pure Chemicals Co., Ltd. | Reactifs destines au dosage de l'oxygene actif |
JP2005047898A (ja) * | 2003-07-11 | 2005-02-24 | Osaka Industrial Promotion Organization | スルホン酸エステル化合物およびそれを用いた蛍光プローブ |
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WO2009110487A1 (ja) | 2009-09-11 |
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