KR101752473B1 - Method for synthesis of novel fluorescence probe library of dansyl scaffold and method for imaging live cells using thereof - Google Patents

Method for synthesis of novel fluorescence probe library of dansyl scaffold and method for imaging live cells using thereof Download PDF

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KR101752473B1
KR101752473B1 KR1020130131502A KR20130131502A KR101752473B1 KR 101752473 B1 KR101752473 B1 KR 101752473B1 KR 1020130131502 A KR1020130131502 A KR 1020130131502A KR 20130131502 A KR20130131502 A KR 20130131502A KR 101752473 B1 KR101752473 B1 KR 101752473B1
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heteroaryl
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이준석
윤창노
김원영
이진각
한원석
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한국과학기술연구원
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C07C311/38—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton
    • C07C311/39—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
    • C07C311/40—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C07C311/38—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton
    • C07C311/39—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
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Abstract

The present invention relates to a novel use of a short-chain derivative, and specifically, a short-chain derivative can be usefully used for imaging living cells. The preparation method of the present invention and the various short-chain derivatives prepared thereby can be used for cell imaging through the method because they are located in the cell upon contact with the cells. Thus, such molecules enable the imaging of living cells and thus can be utilized for a variety of research and industrial applications.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel single-chamber fluorescent compound library and a living cell imaging method using the novel single fluorescence library,

The present invention relates to the synthesis of a novel compound using a monocyclic compound and a method of cell imaging using the same.

Fluorescent compounds have been used in an essay method to measure the activity of various kinds of biogenic enzymes. As a method of making a signal in the essay development, a method of measuring the color or intensity change of a fluorescent substrate or a fluorescence resonance energy transfer (FRET) method using other fluorescent materials surrounding the fluorescent substance is being developed. However, the fluorescence scaffold that produces a fluorescence signal is not largely deviated from some known structures (FIG. 1).

A fluorescent compound is a chemical sensor that generates a signal through interaction with a specific physiologically active substance. It is also called a fluorescence probe in the sense of detecting a biological substance. In early 2000, the development of fluorescent probes based on the structural properties of fluorescent compounds was accelerated. In the beginning, an approach was used to directly link known metal chelators to covalent bonds (J. Am. Chem. Soc., 2005, 127, 10124-0125). However, there was a disadvantage that the kinds of molecules that could be targeted were limited.

The alternative approach is a combination chemistry approach and the New York University team named it the diversity-oriented fluorescence library approach (DOFLA). These have synthesized libraries of fluorescent compounds and developed sensor compounds that recognize specific biomolecules according to their structural diversity ( Mol . BioSyst . 5, 411-421 (2009), J Am Chem Soc 131, 10077-10082 (2009). Angew Chem Int Edit 43, 6331-6335 (2004)). To date, libraries have been developed for structures such as coumarin, dapoxyl, styryl, rosamine, and hemicyanine bodipy. Among them, specific proteins, lipids Have been developed.

Until now, the dansyl structure has not yet been developed as a fluorescent library. Therefore, in order to develop a more diverse fluorescent library, we have developed a method for parallel synthesis of monocylic compounds and have developed a method for imaging living cells using the same.

Mol. BioSyst. 5, 411-421 (2009), J Am Chem Soc 131, 10077-10082 (2009). Angew Chem Int Edit 43, 6331-6335 (2004) Abstract

One aspect provides a short silyl derivative compound. Another aspect provides a composition for cell imaging using a short-chain derivative. Yet another aspect provides a method of cell imaging using a short-chain derivative. Another aspect provides a method for synthesizing a short-chain derivative compound.

An aspect of the present invention is to provide a compound represented by the following formula (1), a hydrate thereof, or a solvate thereof.

≪ Formula 1 >

Figure 112013099292076-pat00001

Wherein R is hydrogen or a substituted or unsubstituted C 1 -C 30 alkyl, substituted or unsubstituted C 1 -C 30 alkenyl, substituted or unsubstituted C 1 -C 30 alkynyl, substituted Or unsubstituted or substituted C 1 to C 30 cycloalkyl, substituted or unsubstituted C 5 to C 30 Substituted or unsubstituted alkyl, aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted arylalkenyl, substituted or unsubstituted arylalkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, Substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heteroarylalkenyl, substituted or unsubstituted heteroarylalkynyl, carboxylic acid, ester, amide, , Substituted or unsubstituted C 1 -C 30 alkyl amide, hydroxy, halogen, cyano, substituted or unsubstituted C 1 -C 30 hydroxyalkyl, substituted or unsubstituted C 1 -C 30 alkoxy, amino, Substituted or unsubstituted C 1 -C 30 alkylamino, substituted or unsubstituted phenylamino, substituted or unsubstituted carbamoyl, substituted or unsubstituted oxadiazole, and substituted or unsubstituted carbamic acid.

The term " substituted " means that at least one hydrogen is replaced by any one or any combination of the following substituents: halogen such as fluorine, chlorine, bromine and iodine; Hydroxy; Nitro; Cyano; Oxo (= O); Thioxo (= S); Azido; Nitroso; Amino; Hydrazino; Formyl; Alkyl; Alkoxy; Aryl; Haloalkyl groups such as trifluoromethyl, tribromomethyl, trichloromethyl and the like; Haloalkoxy such as -OCH 2 Cl, -OCHF 2 , -OCF 3 , and the like; Arylalkoxy such as benzyloxy, phenylethoxy and the like; Cycloalkyl; -O-cycloalkyl; Heterocyclyl; Heteroaryl; Alkylamino; -O-CH 2 -cycloalkyl; -COOR a ; -C (O) R b ; -C (O) NR a R b ; -NR a C (O) NR b R c ; -NR a C (O) OR b ; -NR a R b ; -NR a C (O) R b ; -0R a; -0R a C (0) 0R b ; -C (O) NR a R b ; -OC (O) R < a >; -R a NR b R c ; -R a R b ; R a , R b and R c are each independently a hydrogen atom; Alkyl; Alkylene; Aryl; Arylalkyl; Cycloalkyl; Heterocyclyl; Heteroaryl and heteroarylalkyl, and R < a >, R < b & gt ; And R < c > are also joined to form a ring of 3 to 7 atoms having 0 to 2 heteroatoms. The substituents may be optionally further substituted.

Here, "alkyl" means a straight or branched aliphatic hydrocarbon group having a certain number of carbon atoms. Preferred alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl,

Here, "halogen" may be any one selected from fluorine, chlorine, bromine and iodine.

Wherein "alkoxy" is selected from, but not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy and t-butoxy.

Herein, "alkenyl" means any one selected from ethenyl, 1-propenyl, 2-propenyl, iso-propenyl, 2-methyl- But is not limited thereto.

Wherein "alkynyl" is ethynyl, propynyl or butynyl, but is not limited thereto.

The term "cycloalkyl" as used herein refers to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, cycloheptyl, perhydronaphthyl, adamantyl, bridged cyclic groups and spirobicyclic groups. But it is not limited thereto.

The term "heterocycloalkyl or heteroaryl group" as used herein refers to a heterocyclyl group such as azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl, benzofuranyl, carbazolyl, cinnolinyl, dioxolanyl, pyridyl, Pyridyl, pyrimidinyl, pyrimidinyl, pyrimidinyl, pyrimidinyl, pyrimidinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrazolyl, imidazolyl, tetrahydroisoquinolinyl, pyrrolyl, Wherein the phenyl ring is optionally substituted with one or more substituents selected from the group consisting of halogen, fluorine, fluorine, fluorine, fluorine, fluorine, fluorine, fluorine, Wherein the heteroaryl is selected from the group consisting of hydrogen, fluorine, fluorine, chlorine, fluorine, fluorine, chlorine, bromine, iodine, Pyridinyl, pyrrolidinyl, 2-oxopyrrolidinyl, and oxazolidinyl. But is not limited thereto.

Here, "aryl" may be selected from phenyl, naphthyl, anthracenyl, indanyl, and biphenyl, but is not limited thereto.

Here, "hydroxyalkyl" may be hydroxymethyl or hydroxyethyl, but is not limited thereto.

The term "amide group" means a substituted or unsubstituted C 1 -C 30 alkyl amide, a substituted or unsubstituted C 1 -C 30 benzyl amide, a substituted or unsubstituted C 1 -C 30 halobenzyl amide, hwandoen C 1 ~ C 30 phenylamide, or a substituted or an unsubstituted C 1 ~ C 30 phenylalkyl amide, where one or more hydrogen atoms of said phenyl group is alkyl, cycloalkyl, alkoxy, cyano, halogen, alkylsulfonyl , alkylthio, -CO 2 alkyl, -COOH, -CONH 2, -CHO, -CH 2 OH, hydroxyl, haloalkyl, amino, but may have been independently and optionally substituted by one or more of nitro, this limited It is not.

Here, "heterocyclylalkyl" may be oxadiazole, oxadiazolylmethyl, triazolylmethyl, tetrazolylmethyl, morpholinylmethyl, pyrrolidinylmethyl, piperidinylmethyl or morphonyl, It is not.

Here, "heteroarylalkenyl" may be pyridinylethenyl, thienylethenyl or triazolylethenyl, but is not limited thereto.

Here, "heteroarylalkenyl" may be pyridinylethynyl or thienylethynyl, but is not limited thereto.

Also, the substituent R may be hydrogen, a substituted or unsubstituted carboxylic acid methyl ester, a substituted or unsubstituted carboxylic acid, a substituted or unsubstituted hydroxymethyl, a substituted or unsubstituted amino, a substituted or unsubstituted N, N-di Substituted or unsubstituted benzyl amide, chloro, substituted or unsubstituted 4-chlorobenzyl amide, substituted or unsubstituted phenyl amide, substituted or unsubstituted phenylphenylethyl amide, substituted or unsubstituted amide amide, 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] oxadiazol-2-yl, substituted or unsubstituted tert-butyl amide, substituted or unsubstituted sec-butyl amide, substituted or unsubstituted cyclopentyl amide, 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 isobutyl amide, substituted or unsubstituted propyl amide, substituted or unsubstituted ethyl amide, substituted or unsubstituted cyclopropyl Substituted or unsubstituted (2-morpholin-4-ylethyl) -amide, substituted or unsubstituted (3-methylbutyl) -amide, substituted or unsubstituted indan- Substituted or unsubstituted methoxycarbonylmethyl amide, substituted or unsubstituted 1 (R) -methoxycarbonylethyl amide, substituted or unsubstituted (meth) 2-chlorobenzene Amide, substituted or unsubstituted 3-chlorobenzyl amide, substituted or unsubstituted 2,3-dichlorobenzyl amide, substituted or unsubstituted 2,5-dichlorobenzyl amide, and substituted or unsubstituted 2-chloro -4-fluorobenzylamide, but the present invention is not limited thereto.

Specific examples of the formula (1) may be any one selected from the following formulas (2) to (4). In addition, any one compound selected from the formulas (2) to (4) may exist as a hydrate or a solvate thereof:

(2)

Figure 112013099292076-pat00002

(3)

Figure 112013099292076-pat00003

≪ Formula 4 >

Figure 112013099292076-pat00004
.

Another aspect provides a composition for cell imaging comprising the compound. The cell may also be a live cell. At this time, the cells include prokaryotes and eukaryotes. In addition, the cells may be single cells or multicellular cells, and may be tissue cells isolated from tissues.

As used herein, the term "composition for cell imaging" means a substance that allows the composition to target a cell, bind to the surface of the cell, or penetrate the inside of the cell to visually recognize the cell. One embodiment of a visually recognizable method can be fluorescence. In addition, the composition for cell imaging can penetrate into cells. In particular, it may be located within the cytoplasm. In addition, the compound can absorb light of a specific wavelength and emit the absorbed light again. Such a cell can be imaged by detecting the emission wavelength.

Another aspect provides a method of imaging a cell comprising contacting the compound with a cell. In addition, it may further comprise the step of irradiating light for fluorescence excitation and the step of detecting fluorescence emitted.

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

First, the cell may be contacted with the compound. The compound may be a compound having the structure of Formula (1). Preferably a compound selected from the formulas (2) to (4). The concentration of the compound may be from 0.1 [mu] M to 1,000 [mu] M. Also, it may be 1 μM to 500 μM, and may be 1 μM to 100 μM.

The following can further include irradiating light for fluorescent excitation. At this time, the wavelength irradiated to the compound for fluorescence excitation may be 300 nm to 500 nm. In addition, the wavelength of the light to be irradiated may be 315 nm to 400 nm, or 330 nm to 350 nm. Most preferably from 338 nm to 341 nm. Any light may be used as far as it is emitted from a light source for fluorescence excitation. A laser light source may be used as the most preferable light source.

The following can further include the step of detecting emitted fluorescence. The wavelength of the emitted fluorescence may be from 500 nm to 560 nm. Further, the wavelength may be 510 nm to 555 nm, or 520 nm to 550 nm. Most preferably from 531 nm to 546 nm.

Another aspect provides a process for preparing a short-chain derivative comprising reacting a short-chain halogen and a primary amine in the presence of tetrahydrofuran to react. At this time, the preparation step can be carried out according to the following Reaction Scheme 1. At this time, the short-chain derivative may be a compound represented by the general formula (1). Preferably, the monocylic derivative may be any compound selected from the above formulas (2) to (4).

<Reaction Scheme 1>

Figure 112013099292076-pat00005

Various types of short-chain derivatives can be synthesized by the above reaction scheme. When such a parallel synthesis method is used, a fluorescent compound library containing a short-chain derivative of various structures can be synthesized. Wherein R is as described herein. Further, the halogen may be chlorine.

In one embodiment, as shown in Scheme 1, a dansyl-chloride that does not fluoresce and a primary amine can be substituted to produce a fluorescent monocyclic compound. Such a method is carried out through a heating reaction. That is, when the 5- (dimethylamino) naphthalene-1-sulfonyl chloride compound represented by the short-chain chloride and the primary amine are dissolved in THF and heated, the product of the above formula 1 can be prepared. In addition, such products can be purified using column chromatography.

The present invention is 5 5- (dimethylamino) naphthalene-1-sulfonyl chloride (5- (dimethylamino) naphthalene-1-sulfonyl chloride) with dansil derivative produced from the compound through a manufacturing step of Scheme 1 of the formula (1) - (dimethylamino) naphthalene-1-sulfonamide compound derivatives and a real time molecular imaging method using these compounds. These synthetic methods and molecular imaging methods can be applied to the development of molecular imaging and essay methods of novel fluorescent compounds.

Figure 1 is a schematic for the fluorescent structure known to date.
Figure 2 shows the staining of the FITC channel of formula (3) (Dansyl-3 staining).
Figure 3 shows the staining of the DAPI channel of formula (3) (Hoechst staining).
Figure 4 shows the staining of the FITC channel of formula (2) (Dansyl-2 staining).
Figure 5 shows the staining of the DAPI channel of formula (2) (Hoechst staining).
Figure 6 shows the staining of the FITC channel of formula (1) (Dansyl-1 staining).
Figure 7 shows the staining of the DAPI channel of formula (1) (Hoechst staining).

Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example  1. N- (5- Chloro -2- Hydroxyphenyl ) -5- (dimethylamino) naphthalene-1-yl Von amay De ( Dansyl -One)

&Lt; Formula 1 >

Figure 112013099292076-pat00006

5- (Dimethylamino) naphthalene-1-sulfonyl chloride (7.2 mg, 0.0266 mmol) was added to a round bottom flask, which was filled with nitrogen and dissolved in THF (18 ml, dried). 2-Amino-4-chlorophenol was dissolved in 1 ml of THF and added slowly. Heated to 60 &lt; 0 &gt; C and stirred for 90 minutes. The extent of the reaction was confirmed by TLC. After the completion of the reaction, the reaction mixture was immediately distilled under reduced pressure to remove the solvent, and then purified by column chromatography (EtOAc: n-Hexane = 1: 2) to obtain N- (5-chloro-2-hydroxyphenyl) Amino) naphthalene-1-sulfonylamide (6.7 mg, yield 66.6%).

1 H NMR (400 MHz, CDCl 3) 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, 6 H).

Example  2. N- (2,4- Dihydroxyphenyl ) -5- (dimethylamino) naphthalene-1- Sulfonamide  ( Dansyl -2)

(2)

Figure 112013099292076-pat00007

5- (Dimethylamino) naphthalene-1-sulfonyl chloride (6.7 mg, 0.0248 mmol) was added to a round bottom flask, which was then filled with nitrogen and dissolved in THF (18 ml, dried). The 4-aminobenzene-1,3-diol was dissolved in 1 ml of methanol and then slowly added. Heated to 60 &lt; 0 &gt; C and stirred for 90 minutes. The extent of the reaction was confirmed by TLC. After the completion of the reaction, the reaction mixture was immediately distilled under reduced pressure to remove the solvent, and then purified by column chromatography (EtOAc: n-Hexane = 1: 1) to obtain N- (2,4-dihydroxyphenyl) ) Naphthalene-1-sulfonamide (7.4 mg, yield 83.1%).

1 H NMR (400 MHz, CDCl 3) 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 (D, IH), 7.46 (d, IH), 7.25 (d, IH), 6.37 (s, IH), 6.36 .

Example  3. N- (3- Chloro -4- Fluorobenzene ) -5- (dimethylamino) naphthalene-1-yl Von amay De ( Dansyl -3)

(3)

Figure 112013099292076-pat00008

5- (Dimethylamino) naphthalene-1-sulfonyl chloride (6.9 mg, 0.0248 mmol) was added to a round bottom flask, which was then charged with nitrogen and dissolved in THF (18 ml, dried). (3-chloro-4-fluorophenyl) methanamine was dissolved in 1 ml of THF and then slowly added. Heated to 60 &lt; 0 &gt; C and stirred for 90 minutes. The extent of the reaction was confirmed by TLC. After completion of the reaction, the reaction mixture was immediately distilled under reduced pressure to remove the solvent, and then purified through column chromatography (EtOAc: n-Hexane = 1: 2) to obtain N- (2,4-dihydroxyphenyl) ) Naphthalene-1-sulfonamide (6.8 mg, yield 67.7%).

1 H NMR (400 MHz, CDCl 3 )? 8.56 (d, J = 8.8 Hz, 1 H), 8.26 2H), 7.59 (dd, IH), 7.52 (dd, IH), 7.22 (d, IH), 7.03 (d, ) 2.93 (s, 6H).

Example  4. Dansyl  Optical properties of compounds

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

Example  5. The biological cell of the compound Imaging

5.1. Cell culture and fluorescent staining

For real-time fluorescence staining of live cells, HEK293 cells were used and cultured on a culture dish in a 5% incubator at 37 DEG C according to the protocol provided by ATCC. HEK293 cells were cultured in Dulbecco's Modified Eagle Medium (DMEM), 10% Fetal Bovine Serum (FBS) and 1X Pen / Strep.

5.2. Fluorescence image measurement

Live cells in each cell culture were treated with 100 uM (DMSO 1%) Dansyl compound and 1x Hoechst and incubated in a 37 ° C incubator for 15 min. Fluorescence images were obtained using a fluorescence microscope (Olympus-IX51 DP71, Olympus) filter capable of detecting DAPI staining and a filter capable of detecting FITC staining. As shown in the above examples, in the staining of HEK293 cell lines, it was shown that Dansyl compounds were permeable to living cells and fluorescence imaging was possible (see FIG. 2 to FIG. 7).

Cell imaging technology is continuously being developed, but development of various fluorescent materials is still required. In the case of the present invention, various kinds of short-chain derivatives can be used as a composition for a new fluorescence imaging, thereby making it possible to diversify kinds of fluorescent substances. These molecules enable the imaging of living cells, so they are likely to be used for various research and industrial applications.

Claims (8)

1. A composition for cell imaging, which is a living cell comprising a compound of the formula (1), a hydrate thereof or a solvate thereof,
Wherein said composition comprises contacting said composition with a cell, followed by incubation at < RTI ID = 0.0 > 37 C &lt; / RTI &
&Lt; Formula 1 &gt;
Figure 112017045405808-pat00009

Wherein R is hydrogen or a substituted or unsubstituted C 1 to C 30 alkyl, substituted or unsubstituted C 1 to C 30 alkenyl, substituted or unsubstituted C 1 to C 30 alkynyl, hwandoen a substituted or unsubstituted C 1 to C 30 cycloalkyl, substituted or unsubstituted C 5 to C 30 aryl, substituted or unsubstituted C 5 to C 30 aryl, substituted or unsubstituted C 5 to C 30 Substituted or unsubstituted C 1 to C 30 arylalkynyl, substituted or unsubstituted C 5 to C 30 heteroaryl, substituted or unsubstituted C 1 to C 30 heterocyclyl, substituted or unsubstituted C 1 to C 30 heterocycloalkyl, substituted or unsubstituted C 1 to C 30 heterocyclyloalkyl, substituted or unsubstituted C 5 to C 30 heteroarylalkyl, substituted or unsubstituted C 5 to C 30 heteroaryl alkenyl, substituted or unsubstituted C 5 to C 30 heteroaryl, alkynyl, carboxylic acid, S Le, amide, hydroxy, halogen, cyano, substituted or unsubstituted C 1 to C 30 hydroxyalkyl, substituted or unsubstituted C 1 to C 30 alkoxy, amino, substituted or unsubstituted phenylamino, substituted or Unsubstituted carbamoyl, substituted or unsubstituted oxadiazole, and substituted or unsubstituted carbamic acid;
The substituent is selected from the group consisting of hydroxy, nitro, cyano, oxo (= O), thioxo (= S), azido, nitroso, hydrazino, formyl, alkyl, alkoxy, aryl, haloalkyl, haloalkoxy, -O-cycloalkyl, heterocyclyl, heteroaryl, -O-CH 2 -cycloalkyl, -C (O) R b , -C (O) NR a R b , -NR a C ) NR b R c, -NR a c (O) OR b, -NR a R b, -NR a c (O) R b, -0R a, -0R a c (0) 0R b, -C (0 ) NR a R b, -OC ( O) R a, -R a NR b R c, -R a and b of the one selected 0R;
Wherein R a , R b and R c are each independently a substituted or unsubstituted group selected from hydrogen, alkyl, alkylene, aryl, arylalkyl, cycloalkyl, heterocyclyl, heteroaryl and heteroarylalkyl, To form a ring of 3 to 7 atoms with 0 to 2 heteroatoms. CLAIMS 1. A composition for cell imaging which is a living cell comprising a compound of formula (III), a hydrate thereof or a solvate thereof,
Wherein said composition comprises contacting said composition with a cell, followed by incubation at < RTI ID = 0.0 > 37 C &lt; / RTI &
(3)
Figure 112016125300046-pat00011
. delete delete Contacting the cell with the compound of claim 1 or 2; And incubating said cells at &lt; RTI ID = 0.0 &gt; 37 C. &lt; / RTI &gt; 6. The method of claim 5, further comprising the step of illuminating light for fluorescence excitation and detecting emitted fluorescence. Adding a short-chain halogen and a primary amine in the presence of tetrahydrofuran; 60 C &lt; / RTI &gt; for 90 minutes; Removing the solvent by vacuum distillation of the reaction mixture; Lt; RTI ID = 0.0 &gt; 1, &lt; / RTI &gt; 8. The method of claim 7, wherein the halogen is chlorine.
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