Fluorescent probe

Patent metadata

Field	Value
Publication number	US-9329184-B2
Application number	US-201213985185-A
Country	US
Kind code	B2
Filing date	Feb 17, 2012
Priority date	Feb 18, 2011
Publication date	May 3, 2016
Grant date	May 3, 2016

Abstract

A compound represented by the formula (I) (R 1 represents a substituent on the benzene ring; R 2 represents a monovalent substituent; R 3 and R 4 represent hydrogen atom, or an alkyl group; R 5 and R 6 represent an alkyl group, or an aryl group; R 7 and R 8 represent hydrogen atom, or an alkyl group; R 9 and R 10 represent hydrogen atom, or a monovalent substituent; and X represents silicon atom, germanium atom, or tin atom), or a salt thereof.

First claim

What is claimed is:

1. A compound of formula (I) or a salt thereof:

wherein, R 1 represents the same or different 1 to 4 monovalent substituents; R 2 represents a monovalent substituent; R 3 and R 4 independently represent a hydrogen atom, or an alkyl group having 1 to 6 carbon atoms; R 5 and R 6 independently represent an alkyl group having 1 to 6 carbon atoms, or an aryl group; R 7 and R 8 independently represent a hydrogen atom, or an alkyl group having 1 to 6 carbon atoms; R 9 and R 10 independently represent a hydrogen atom, or a monovalent substituent; and X represents a silicon atom, a germanium atom, or a tin atom.

2. The compound or a salt thereof according to claim 1 , wherein X is a silicon atom or a germanium atom.

3. The compound or a salt thereof according to claim 1 , wherein R 1 or R 2 is a trapping group that can trap a proton, a metal ion, a reactive oxygen species, a hypoxic environment, an enzyme activity, or glutathione, and R 9 and R 1 are hydrogen atoms.

4. The compound or a salt thereof according to claim 1 , wherein at least one of R 9 and R 10 is a trapping group that can trap a proton, a metal ion, a reactive oxygen species, a hypoxic environment, an enzyme activity, or glutathione, and R 1 and R 2 are hydrogen atoms.

5. The compound or a salt thereof according to claim 4 , wherein at least one of R 9 and R 10 is a trapping group that can trap an activity of an enzyme selected from the group consisting of a peptidase, a protease, a lactamase, a glycoside hydrolase, a transferase, and an oxidoreductase.

6. The compound or a salt thereof according to claim 4 , wherein at least one of R 9 and R 10 is a trapping group that is cleaved by an enzyme selected from the group consisting of a peptidase, a protease, and a lactamase.

7. The compound or a salt thereof according to claim 4 , wherein at least one of R 9 and R 10 is a trapping group that is cleaved by a peptidase or a protease selected from the group consisting of caspase, prostate-specific antigen, leucine aminopeptidase, and γ-glutamyl transpeptidase.

8. A fluorescent probe comprising the compound or salt thereof according to claim 1 .

9. The compound or a salt thereof according to claim 1 , wherein R 1 or R 2 is a trapping group that can trap a proton, a metal ion, a reactive oxygen species, a hypoxic environment, an enzyme activity, or glutathione, provided that R 1 and R 2 are not simultaneously trapping groups, and at least one of R 9 and R 10 is a trapping group that can trap a proton, a metal ion, a reactive oxygen species, a hypoxic environment, an enzyme activity, or glutathione.

10. A method for measuring an object substance for measurement, comprising:
(a) contacting the compound or a salt thereof according to claim 1 with the object substance for measurement, and
(b) measuring fluorescence intensity of a compound generated in (a) after trapping of the object substance for measurement.

11. A method for preparing the compound or a salt thereof according to claim 1 wherein R 3 and R 4 represent a hydrogen atom, R 5 and R 6 independently represent an alkyl group having 1 to 6 carbon atoms, or an aryl group; R 7 and R 8 represent hydrogen atom; R 9 and R 10 represent hydrogen atom; and X represents a silicon atom, a germanium atom, or a tin atom, comprising:
(a) preparing a compound of formula (II):

wherein R 11 represents a halogen atom, from a 3-halogenated N,N-diallylaniline prepared from a 3-halogenated aniline and an allyl halide, and formaldehyde,
(b) reacting the compound of formula (II) with a dichlorodialkylsilane, and then subjecting the resultant to an oxidation reaction to prepare an N,N,N′,N′-tetrallyl-diamino-Si-xanthone mentioned as shown below,

(c) preparing a compound of formula (III):

wherein, R 1 represents the same or different 1 to 4 monovalent substituents and R 2 represents a monovalent substituent wherein R 1 and R 2 optionally include protective groups for the preparation of the compound of formula (III), from N,N,N′,N′-tetrallyl-diamino-X-xanthone and a halogenated benzene derivative,
(d) deallylating the compound of formula (III) to prepare the compound according to claim 1 , wherein when R 1 and R 2 include protective groups for the preparation of the compound of the general formula (III), removal of the protective group may be performed before or after, or simultaneously with the deallylation.

12. A compound of formula (III) or a salt thereof:

wherein, R 1 represents the same or different 1 to 4 monovalent substituents and R 2 represents a monovalent substituent; R 5 and R 6 independently represent an alkyl group having 1 to 6 carbon atoms, or an aryl group; and X represents a silicon atom, a germanium atom, or a tin atom.

Assignees

• Nagano Tetsuo
• Hanaoka Kenjiro
• Koide Yuichiro
• Egawa Takahiro
• KUSHIDA Yu
• Univ Tokyo

Inventors

• Nagano Tetsuo
• Hanaoka Kenjiro
• Koide Yuichiro
• Egawa Takahiro
• KUSHIDA Yu

Classifications

• C07F7/0812 Primary

  comprising a heterocyclic ring · CPC title

• C07F7/0818

  Chemistry & Metallurgy · mapped topic

• C07F7/10

  containing nitrogen {having a Si-N linkage} · CPC title

• G01N33/582 Primary

  with fluorescent label · CPC title

• G01N33/533

  with fluorescent label · CPC title