WO2015064939A1

WO2015064939A1 - Method of synthesizing novel fluorescent probe library of dansyl scaffold and method of imaging live cells by using the same

Info

Publication number: WO2015064939A1
Application number: PCT/KR2014/009806
Authority: WO
Inventors: Jun Seok Lee; Chang No Yoon; Won Young Kim; Jin Kak Lee; Won Seok Han
Original assignee: Korea Institute of Science and Technology KIST
Current assignee: Korea Institute of Science and Technology KIST
Priority date: 2013-10-31
Filing date: 2014-10-17
Publication date: 2015-05-07
Anticipated expiration: 2016-04-30
Also published as: KR20150050092A; KR101752473B1

Abstract

Provided is a novel use of adansyl derivative, and, in particular, a dansyl derivative that may be effectively used in imaging live cells. A preparation method of the present invention and various types of dansyl derivatives prepared by using the method may be effectively used in cell imaging since the dansyl derivatives are located in cells when the dansyl derivatives contact with the cells. Thus, the dansyl derivatives enable imaging of live cells and thus may be used in various studies and industrial fields.

Description

METHOD OF SYNTHESIZING NOVEL FLUORESCENT PROBE LIBRARY OF DANSYL SCAFFOLD AND METHOD OF IMAGING LIVE CELLS BY USING THE SAME

One or more aspects of the present invention relate to a method of synthesizing a noble compound by using a dansyl compound and a method of imaging cells by using the synthesized compound.

A fluorescent compound is used in an assay method for measuring the activity of biological enzymes of various types. In the development of assay, a method of producing signals for measuring the activity of the biological enzymes may include a method of measuring a difference of the color or intensity of a substrate of the enzyme with fluorescence, or a fluorescence resonance energy transfer (FRET) method using ambient another fluorescent material. However, a fluorescence scaffold for producing fluorescent signals is not much off from conventionally known structures.

A compound producing signals through an interaction with a specific bioactive material as a fluorescent compound is known as a chemosensor, or as a fluorescent probe in terms of detecting a biomaterial. Since early 2000, the development of a fluorescent probe using a structure of a fluorescent compound has accelerated, and in the early stage of development, for example, an approaching method of connecting the fluorescent compound and a metal chelator by direct covalent bond may be used (J. Am. Chem. Soc., 2005, 127, 10124-0125). However, the method is limited to a type of molecules that may be a target.

Alternatively, a suggested method is an approaching method using combination chemicals which was named diversity-oriented fluorescence library approach (DOFLA) by the NYU research team. The team developed a sensor compound that synthesizes a library of fluorescent compounds and recognizes a specific biomolecule depending on a structure variety (Mol. BioSyst. 5, 411-421 (2009), J Am Chem Soc 131, 10077-10082 (2009), and Angew Chem Int Edit 43, 6331-6335 (2004)). Until now, libraries related to structures of coumarin, dapoxyl, styryl, rosamine, hemicyanine bodipy etc. have been developed, and a compound that interacts with specific protein or lipid therefrom has been developed.

However, a dansyl structure has not been developed in a form of a fluorescence library. Thus, our research team has developed a parallel synthesis method of producing dansyl compounds to develop various fluorescent libraries and a method of imaging biological cells by using the produced dansyl compounds.

The present invention provides a dansyl derivative compound.

The present invention also provides a composition for imaging cells by using a dansyl derivative.

The present invention also provides a method of imaging cells by using a dansyl derivative.

The present invention also provides a method of synthesizing a dansyl derivative compound.

Reference will now be made in detail to aspects, examples of which are illustrated in the accompanying drawings, wherein like reference numerals refer to like elements throughout. In this regard, the present aspects may have different forms and should not be construed as being limited to the descriptions set forth herein. Accordingly, the aspects are merely described below, by referring to the figures, to explain aspects of the present description.

According to one or more aspects of the present invention, a compound represented by Formula 1, or its hydrate or its solvate are provided.

In Formula 1, R is one selected from the group consisting of hydrogen, substituted or unsubstituted C₁-C₃₀ alkyl, substituted or unsubstituted C₁-C₃₀ alkenyl, substituted or unsubstituted C₁-C₃₀ alkynyl, substituted or unsubstituted C₁-C₃₀ cycloalkyl, substituted or unsubstituted C₅-C₃₀ aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted arylalkenyl, substituted or unsubstituted arylalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heteroarylalkenyl, substituted or unsubstituted heteroarylalkynyl, carboxylic acid, ester, amide, substituted or unsubstituted C₁-C₃₀ alkylamide, hydroxy, halogen, cyano, substituted or unsubstituted C₁-C₃₀ hydroxyalkyl, substituted or unsubstituted C₁-C₃₀ alkoxy, amino, substituted or unsubstituted C₁-C₃₀ alkylamino, substituted or unsubstituted phenylamino, substituted or unsubstituted carbamoyl, substituted or unsubstituted oxadiazole, and substituted or unsubstituted carbamic acid.

As used herein, the term "substituted" refers that at least one hydrogen is substituted by one substituent or any combination selected from the following substituents: halogen, such as flourine, chlorine, bromine, or iodine; hydroxy; nitro; cyano; oxo(=O); thioxo(=S); azido; nitroso; amino; hydrazino; formyl; alkyl; alkoxy; aryl; haloalkyl, such as trifluoromethyl, tribromomethyl, or trichloromethyl; haloalkoxy, such as -OCH₂Cl, -OCHF₂, or -OCF₃; arylalkoxy, such as benzyloxy or phenylethoxy; cycloalkyl; -O-cycloalkyl; heterocyclyl; heteroaryl; alkylamino; -0-CH₂-cycloalkyl; -COOR^a; -C(O)R^b; -C(O)NR^aR^b; -NR^aC(O)NR^bR^c; -NR^aC(O)OR^b; -NR^aR^b; -NR^aC(O)R^b; -OR^a; -OR^aC(O)OR^b; -C(O)NR^aR^b; -OC(O)R^a; -R^aNR^bR^c; and -R^aOR^b, wherein R^a, R^b, and R^c are each independently a substituted or unsubstituted group selected from a hydrogen atom; alkyl; alkylene; aryl; arylalkyl; cycloalkyl; heterocyclyl; heteroaryl; and heteroarylalkyl, and R^a, R^b, and R^c are combined to form a 3 to 7 membered ring including 0 to 2 heteroatoms. The substituent may be optionally more substituted.

Here, the term "alkyl" may refer to a linear or branched aliphatic hydrocarbon group having any number of carbon atoms. Examples of the alkyl group include, but not limited to, methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, and heptyl.

Here, the term "halogen" may refer to one selected from the group consisting of flourine, chlorine, bromine, and iodine, but not limited thereto.

Here, the term "alkoxy" may refer to one selected from, but not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, and t-butoxy.

Here, the term "alkenyl" may refer to one selected from the group consisting of ethenyl, 1-propenyl, 2-propenyl, iso-propenyl, 2-methyl-l-propenyl, 1-butenyl, and 2-butenyl, but not limited thereto.

Here, the term "alkynyl" may refer to one selected from the group consisting of ethynyl, propynyl, and butynyl, but not limited thereto.

Here, the term "cycloalkyl" may refer to one selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, cycloheptyl, perhydronaphthyl, adamantyl, cross-linked cyclic groups, and spirobicyclic groups, but not limited thereto.

Here, the term "heterocycloalkyl or heteroaryl" may refer to one selected from the group consisting of azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl, benzopuranyl, carbazolyl, cinnolinyl, dioxolanyl, pyridyl, pteridinyl, purinyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrazolyl, imidazolyl, tetrahydroisoquinolinyl, pyrrolyl, piperonyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, oxazolyl, oxazolinyl, triazolyl, indanyl, isoxazolyl, isoxazolidinyl, decahydroisoquinolyl, benzimidazolyl, indazolyl, phenylpiperidinyl, furyl, tetrahydrofuryl, tetrahydropyranyl, piperazinyl, homopiperazinyl, piperidyl, piperidopiperidyl, morpholinyl, thiomorpholinyl, piperidonyl, 2-oxopiperazinyl, 2-oxopiperidinyl, pyrrolidinyl, 2-oxopyrrolidinyl, and oxazolidinyl, but not limited thereto.

Here, the term "aryl" may refer to one selected from the group consisting of phenyl, naphthyl, anthracenyl, indanyl, and biphenyl, but not limited thereto.

Here, the term "hydroxy alkyl" may refer to hydroxymethyl or hydroxyethyl, but not limited thereto.

Here, the term "amide" may refer to one selected from the group consisting of substituted or unsubstituted C₁-C₃₀ alkylamide, substituted or unsubstituted C₁-C₃₀ benzylamide, substituted or unsubstituted C₁-C₃₀ halobenzylamide, substituted or unsubstituted C₁-C₃₀ phenylamide, or substituted or unsubstituted C₁-C₃₀ phenylalkylamide, wherein at least one hydrogen atom of the phenyl may be independently and selectively substituted with at least one of alkyl, cycloalkyl, alkoxy, cyano, halogen, alkylsulfonyl, alkylthio, -CO₂-alkyl, -COOH, -CONH₂, -CHO, -CH₂OH, hydroxyl, haloalkyl, amino, and nitro, but not limited thereto.

Here, the term "heterocyclylalkyl" may refer to one selected from the group consisting of, oxadiazole, oxadiazolylmethyl, triazolylmethyl, tetrazolylmethyl, morpholinylmethyl, pyrrolidinylmethyl, piperidinylmethyl, and morphonyl, but not limited thereto.

Here, the term "heteroarylalkenyl" may refer to one selected from the group consisting of pyridinylethenyl, thienylethenyl, and triazolylethenyl, but not limited thereto.

Here, the term "heteroarylalkynyl" may refer to pyridinylethynyl or thienylethynyl, but not limited thereto.

Also, R may be one selected from the group consisting of hydrogen, substituted or unsubstituted carboxylic acid methylester, substituted or unsubstituted carboxylic acid, substituted or unsubstituted hydroxy methyl, substituted or unsubstituted amino, substituted or unsubstituted N,N-dimethylamide, substituted or unsubstituted methylamide, substituted or unsubstituted benzylamide, chloro, substituted or unsubstituted 4-chlorobenzylamide, substituted or unsubstituted phenylamide, substituted or unsubstituted phenyl penethylamide, fluoride, substituted or unsubstituted benzylcarbamoyl, substituted or unsubstituted isopropylamide, substituted or unsubstituted 3-methylbutoxy, substituted or unsubstituted methoxy, substituted or unsubstituted 5-methyl-[1,3,4]oxadiazole-2-yl, substituted or unsubstituted tert-butylamide, substituted or unsubstituted sec-butylamide, substituted or unsubstituted cyclopentylamide, substituted or unsubstituted butylamide, substituted or unsubstituted (2-dimethylaminoethyl)-amide, substituted or unsubstituted cyclopropylamide, substituted or unsubstituted cyclohexylamide, substituted or unsubstituted (2-methoxyethyl)-amide, substituted or unsubstituted (1-ethylpropyl)-amide, substituted or unsubstituted isobutylamide, substituted or unsubstituted propylamide, substituted or unsubstituted ethylamide, substituted or unsubstituted cyclopropylmethylamide, substituted or unsubstituted (2-morpholine-4-ylethyl)-amide, substituted or unsubstituted (3-methylbutyl)-amide, substituted or unsubstituted indan-2-ylamide, substituted or unsubstituted (2,2,2-trifluoroethyl)-amide, substituted or unsubstituted methoxycarbonyl methylamide, substituted or unsubstituted 1(R)-methoxycarbonyl ethylamide, substituted or unsubstituted 2-chlorobenzylamide, substituted or unsubstituted 3-chlorobenzylamide, substituted or unsubstituted 2,3-dichlorobenzylamide, substituted or unsubstituted 2,5-dichlorobenzylamide, and substituted or unsubstituted 2-chloro-4-fluorobenzylamide, but R may not be limited thereto.

An example of Formula 1 may be one selected from Formula 2 to Formula 4. Also, a compound represented by one selected from Formula 2 to Formula 4 may exist as a hydrate or a solvate thereof:

,

, and

According to one or more aspects of the present invention, a composition for imaging a cell is provided, wherein the composition includes the compound. Also, the cell may be a live cell. Here, the cell may be an eukaryotic cell or prokaryotic cell. Also, the cells may be a single cell, multicellular cells, or a tissue cell separated from tissue.

As used herein, the term "a composition for imaging cells" refers to a material that allows the composition to be attached on a surface of a cell by having the cell as a target object or to penetrate into the cell, and make the cell be visibly recognizable. The cell may be visibly recognizable by fluorescence. Also, the composition for imaging cells may penetrate into a cell. Particularly, the composition may be located in cytoplasm. Also, the compound may absorb light at a certain wavelength and may emit the absorbed light back. The cell may be imaged by detecting a wavelength of the emitted light.

According to one or more aspects of the present invention, a method of imaging cells is provided, wherein the method includes contacting a cell with the compound. Also, the method may further include irradiating light for fluorescent excitation and detecting fluorescence emitted by the light.

The method of imaging cells will be described in detail as follows:

First, the method may include contacting a cell with the compound. The compound may be a compound having a structure of Formula 1. For example, the compound may be a compound represented by one selected from Formula 2 to Formula 4. A concentration of the compound may be in a range of 0.1 μM to 1,000 μM, for example, 1 μM to 500 μM, or 1 μM to 100 μM.

Next, the method may further include irradiating light for fluorescence excitation. Here, a wavelength of the light irradiated on the compound for fluorescence excitation may be in a range of 300 nm to 500 nm, for example, 315 nm to 400 nm, or 330 nm to 350 nm. For example, most preferably, a wavelength of the light may be in a range of 338 nm to 341 nm. The light may be any light emitted from a light source for fluorescence excitation. For example, most preferably, the light source may be a laser light source.

Then, the method may further include detecting emitted fluorescence. A wavelength of the emitted fluorescence may be in a range of 500 nm to 560 nm, for example, 510 nm to 555 nm, or 520 nm to 550 nm. For example, most preferably, a wavelength of the emitted fluorescence may be in a range of 531 nm to 546 nm.

According to one or more aspects of the present invention, a method of preparing a dansyl derivative is provided, wherein the method includes heatinga dansyl-halogen and a primary amine in the presence of tetrahydrofuran to produce the dansyl derivative. Here, the preparing process may be performed in the same manner shown in Reaction scheme 1. Also, the dansyl derivative may be a compound represented by Formula 1. For example, the dansyl derivative may be a compound represented by one of Formula 2 to Formula 4.

Various types of dansyl derivatives may be synthesized in the same manner shown in Reaction scheme 1. When the parallel synthesis method is used, a fluorescence compound library including dansyl derivatives of various structures may be synthesized. Here, the description of R is as defined in the present specification. Also, the halogen may be chlorine.

In some aspects, a fluorescent dansyl compound may be prepared by using a substitution reaction of a dansyl chloride and a primary amine. The substitution may be performed by heating. That is, when 5-(dimethylamino)naphthalene-1-sulfonyl chloride compound represented by a dansyl-chloride and a primary amine are dissolved in THF and heated, a product of Formula 1 may be prepared. Also, the product may be purified by column chromatography.

INDUSTRIAL APPLICABILITY

Developing a cell imaging technique is an on-going process, but various fluorescence materials still need to be developed. According to one or more aspects of the present invention, various types of dansyl derivatives may be used as a novel fluorescent composition for imaging cells, and thus it enabled variation of types of fluorescent materials. The molecules enable imaging of live cells and thus have a high possibility in being used for various researches and industrial purposes.

ADVANTAGEOUS EFFECTS

As described above, according to the one or more of the above aspects of the present invention, provided are a preparation method capable of parallel synthesizing a derivative of 5-(dimethylamino)naphthalene-1-sulfonamide , which is a dansyl derivative that is produced by a preparation process of Reaction scheme 1 from 5-(dimethylamino)naphthalene-1-sulfonyl chloride, i.e., a compound represented by Formula 1; and a real-time molecule imaging method using the compound. The synthesis method and the molecule imaging method may be applied to development of molecule imaging and assaying methods of a novel fluorescent compound.

These and/or other aspects will become apparent and more readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings in which:

FIG. 1 illustrates a dye of FITC channel of Formula 4 (Dansyl-3 dye);

FIG. 2 illustrates a dye of DAPI channel of Formula 4 (Hoechst dye);

FIG. 3 illustrates a dye of FITC channel of Formula 3 (Dansyl-2 dye);

FIG. 4 illustrates a dye of DAPI channel of Formula 3 (Hoechst dye);

FIG. 5 illustrates a dye of FITC channel of Formula 2 (Dansyl-1 dye); and

FIG. 6 illustrates a dye of DAPI channel of Formula 2 (Hoechst dye)

Hereinafter, the embodiments are described in greater detail. However, the embodiments are for illustrative purposes only and do not limit the scope of the present invention.

Example 1. N-(5-chloro-2-hydroxyphenyl)-5-(dimethylamino)naphthalene -1-sulfonamide (Dansyl-1)

7.2 mg (0.0266 mmol) of 5-(dimethylamino)naphthalene-1-sulfonyl chloride was added to a round-bottom flask and nitrogen was filled in the flask. Then 18 ml of tetrahydrofuran (THF) (dried) was added to the flask to dissolve sufficiently the 5-(dimethylamino)naphthalene-1-sulfonyl chloride in the THF. 2-amino-4-chloro phenol was dissolved in 1 ml of THF and slowly added to the flask. Then, the resultant was stirred for 90 minutes while heating at 60℃. A degree of the reaction was confirmed by using thin layer chromatography (TLC). After completing the reaction, a solvent in the reaction mixture was immediately removed by reduced pressure distillation, and then the resultant was purified through column chromatography (EtOAc : n-Hexane = 1:2) to obtain 6.7 mg of N-(5-chloro-2-hydroxyphenyl)-5-(dimethylamino)naphthalene-1-sulfonyl amide (yield 66.6%).

¹H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 8.4 Hz, 1H), 8.34 (d, J = 8.4 Hz, 1H), 8.15 (d, J= 7.6 Hz, 1H), 7.64 (dd, 1H), 7.47 (dd, 1H), 7.24 (d, 1H), 6.93 (d, J = 8.8 Hz, 1H), 6.75 (d, J = 8.8 Hz, 1H), 6.6 (s, 1H), 2.92 (s, 6H)

Example 2. N-(2,4-dihydroxyphenyl)-5-(dimethylamino)naphthalene-1-sulfonamide (Dansyl-2)

6.7 mg (0.0248 mmol) of 5-(dimethylamino)naphthalene-1-sulfonyl chloride was added to a round-bottom flask and nitrogen was filled in the flask. Then, 18 ml of THF (dried) was added to the flask to dissolve sufficiently the 5-(dimethylamino)naphthalene-1-sulfonyl chloride in the THF. 4-aminobenzene-1,3-diol was dissolved in 1 ml of methanol and slowly added thereto. Then, the resultant was stirred for 90 minutes while heating at 60℃. A degree of the reaction was confirmed by using TLC. After completing the reaction, a solvent in the reaction mixture was immediately removed by reduced pressure distillation, and then the resultant was purified through column chromatography (EtOAc : n-Hexane = 1:1) to obtain 7.4 mg of N-(2,4-dihydroxyphenyl)-5-(dimethylamino)naphthalene-1-sulfoneamide (yield 83.1%).

¹H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 8.8 Hz, 1H), 8.36 (d, J = 8.4 Hz, 1H), 8.06 (d, J= 7.6 Hz, 1H), 7.65 (dd, 1H), 7.43 (dd, 1H), 7.25 (d, 1H), 6.37 (s, 1H), 6.36 (s, 1H) 6.07 (d, 1H), 5.97 (d, 1H), 2.94 (s, 6H)

Example 3. N-(3-chloro-4-fluorobenzene)-5-(dimethylamino)naphthalene-1-sulfoneamide (Dansyl-3)

6.9 mg (0.0248 mmol) of 5-(dimethylamino)naphthalene-1-sulfonyl chloride was added to a round-bottom flask and nitrogen was filled in the flask. Then 18 ml of THF (dried) was added in the flask to dissolve sufficiently the 5-(dimethylamino)naphthalene-1-sulfonyl chloride in the THF. (3-chloro-4-fluorophenyl)methaneamine was dissolved in 1 ml of THF and slowly added to the flask. Then, the resultant was stirred for 90 minutes while heating at 60℃. A degree of the reaction was confirmed by using TLC. After completing the reaction, a solvent in the reaction mixture was immediately removed by reduced pressure distillation, and then the resultant was purified through column chromatography (EtOAc:n-Hexane = 1:2) to obtain 6.8 mg of N-(2,4-dihydroxyphenyl)-5-(dimethylamino)naphthalene-1-sulfoneamide (yield 67.7%).

¹H NMR (400 MHz, CDCl3) δ 8.56 (d, J = 8.8 Hz, 1H), 8.26 (m, 2H), 7.59 (dd, 1H), 7.52 (dd, 1H), 7.22 (d, 1H), 7.03 (d, 1H), 6.89 (m, 2H), 5.04 (dd, 1H), 4.07 (d, 2H) 2.93 (s, 6H)

Example 4. Optical properties of dansyl compound

Table 1

	λem (nm)	λem (nm)
Dansyl-1	341	546
Dansyl-2	338	540
Dansyl-3	341	531

Example 5. Biological cell imaging of compound

5.1. Cell culture and fluorescent dye method

A real-time fluorescent dye method of live cells uses HEK293 cells and cultures the cells on a culture dish in an 5% CO₂ incubator by following a protocol provided from ATCC. HEK293 cells used Dulbecco's Modified Eagle Medium (DMEM) and 10% Fetal Bovine Serum (FBS), 1X Pen/Strep as a culture media.

5.2. Measurement of fluorescent image

Live cells contained in each of the cell culturing media were treated with 100 μM (DMSO 1%) Dansyl compound and 1x Hoechst and incubated in a 37℃ incubator for 15 minutes. A filter capable of detecting DAPI dye and a filter capable of detecting FITC dye from a fluorescence microscope (Olympus-IX51 DP71, Olympus) were used to obtain a fluorescent image. As shown in the examples above, in the case of using dye in a HEK293 cell strain, the dansyl compound is transmitted through living cells, and thus fluorescent imaging was made possible (see FIG. 1 to FIG. 6)

It should be understood that the exemplary embodiments described therein should be considered in a descriptive sense only and not for purposes of limitation. Descriptions of features or aspects within each embodiment should typically be considered as available for other similar features or aspects in other embodiments.

While one or more embodiments of the present invention have been described with reference to the figures, it will be understood by those of ordinary skill in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present invention as defined by the following claims.

Claims

A compound, or a hydrate or a solvate thereof, wherein the compound is represented by Formula 1:

<Formula 1>

wherein R is one selected a group consisting of from hydrogen, substituted or unsubstituted C₁-C₃₀ alkyl, substituted or unsubstituted C₁-C₃₀alkenyl, substituted or unsubstituted C₁-C₃₀ alkynyl, substituted or unsubstituted C₁-C₃₀ cycloalkyl, substituted or unsubstituted C₅-C₃₀ aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted arylalkenyl, substituted or unsubstituted arylalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heteroarylalkenyl, substituted or unsubstituted heteroarylalkynyl, carboxylic acid, ester, amide, substituted or unsubstituted C₁-C₃₀ alkylamide, hydroxy, halogen, cyano, substituted or unsubstituted C₁-C₃₀ hydroxyalkyl, substituted or unsubstituted C₁-C₃₀ alkoxy, amino, substituted or unsubstituted C₁-C₃₀ alkylamino, substituted or unsubstituted phenylamino, substituted or unsubstituted carbamoyl, substituted or unsubstituted oxadiazole, and substituted or unsubstituted carbamic acid.
A compound, or a hydrate or a solvate thereof, wherein the compound is represented by one selected from the group consisting of Formula 2, Formula 3, and Formula 4:

<Formula 2>

,

<Formula 3>

, and

<Formula 4>

.
A composition for a imaging cell, wherein the composition comprises the compound of claim 1 or 2.
The composition of claim 3, wherein the cell are a live cell.
A method of imaging a cell, the method comprising contacting the compound of claim 1 or 2, and the cell.
The method of claim 5, further comprising irradiating light for fluorescent excitation and detecting fluorescence emitted by the light.
A method of producing the compound of claim 1, the method comprising heating a dansyl-halogen and a primary amine in the presence of tetrahydrofuran to produce the compound of claim 1.
The method of claim 7, wherein the halogen is chlorine.