KR100681911B1 - 5,10,15,20-tetrakis-(2-fluoro-pyridine-3-yl)-porphyrine, 5,10,15,20-tetrakis-(3,5-difluoro-pyridine-4-yl)-porphyrine, and their salts and process for preparing the same - Google Patents

Abstract

A 5,10,15,20-tetrakis-(2-fluoro-pyridine-3-yl)-porphyrine, and 5,10,15,20-tetrakis-(3,5-difluoro-pyridine-4-yl)-porphyrine are provided to be effective as a physiologically active material such as an anti-cancer agent and antibiotics. The 5,10,15,20-tetrakis-(2-fluoro-pyridine-3-yl)-porphyrine is represented by the formula(1) and is prepared by reacting 2-fluoro-pyridine-3-carbaldehyde represented by the formula(5) with pyrrole at a temperature of 20-150 deg.C in the presence of acid such as propanoic acid, butanoic acid, pentanoic acid, hexanoic acid and BF3.

Description

5,10,15,20-tetrakis- (2-fluoro-pyridin- 3-yl) -porphyrin, 5,10,15,20-tetrakis- (3,5-difluoro-pyridine-4- 1)-Porphyrins, N-alkyl salts thereof, and preparation method thereof {5,10,15,20-Tetrakis- (2-fluoro-pyridine-3-yl) -porphyrine, 5,10,15,20-tetrakis -(3,5-difluoro-pyridine-4-yl) -porphyrine, and their salts and process for preparing the same}

Porphyrin compounds are composed of paired double bonds as a whole and have structural features that facilitate coordination bonds with metals . Chem . 1998, 63, 7143.), chiral catalyst (Tetrahedron Lett. 1996, 37, 6291), chiral sensors (J. Am. Chem. Soc. 1997, 119, 5267.), optoelectronic devices (J. Am. Chem. Soc. 1994, 116, 9759.), photoactive therapy of cancer Is a potential photoreceptor (Phtochem. It is a compound constituting pigments such as chlorophyll, which is low in toxicity, has good absorption rate in the human body, and has excellent DNA recognition and selective response to tumor cells, thus preventing dementia through the suppression of specific enzymes (Bioorg. Med. Chem. Lett. 2000, 10, 1435.), Hopkin's disease treatment drug (pharmacological research 2005, 51, 283.), as well as excellent potential photoreceptor in the photoactive treatment of cancer, especially because of its excellent selective response to cancer cells, many studies have been conducted Porphyrin interacts with cells through non-covalent bonds such as hydrophobic interactions, π-π sacking, and electrostatic interactions, and thus continues to develop porphyrin derivatives with more selective interactions with tumor cells. It is done.

The present invention relates to 5,10,15,20-tetrakis- (2-fluoro-pyridin-3-yl) -porphyrin and derivatives thereof 5,10,15,20-tetrakis- (1-alkyl-2). Fluoro-pyridinium-3-yl) -porphyrin salt, 5,10,15,20-tetrakis- (3,5-difluoro-pyridin-4-yl) -porphyrin and its derivatives 5,10, 15,20-tetrakis- (1-alkyl-3,5-difluoro-pyridinium-4-yl) -porphyrin salts, and methods for producing these, more specifically 2-fluoropyridine-3 5,10,15,20-tetrakis comprising a step of forming porphyrin through quantitative reaction with pyrrole in acid condition using carbaldehyde as starting material, and step of forming N-alkyl salt. Fluoro-pyridin-3-yl) -porphyrin and its N-alkyl salt preparation method and 5,10,15,20-tetrakis- (2-fluoro-pyridine) 3-yl) relates to porphyrins and their N- alkyl salt. Also, 5,10 comprising porphyrin formation step through quantitative reaction with pyrrole under acidic conditions using 3,5-difluoropyridine-4-carbaldehyde as a starting material, and N-alkyl salt formation step. , 15,20-tetrakis- (3,5-difluoro-pyridin-4-yl) -porphyrin and its N-alkyl salt production method and 5,10,15,20-tetra prepared by the above production method Kis- (3,5-difluoro-pyridin-4-yl) -porphyrin and its N-alkyl salts.

Compounds having a fluorine group have a high physiological activity, and many studies have been conducted in the development of new drugs in the medical field. Particularly, fluorine-containing porphyrins have a higher third quantum yields due to the strong negative fluorine properties of fluorine, resulting in better photosensitivity than normal porphyrin compounds and strong interactions with cells, DNA, and RNA. Since it shows a strong active action, various developments as pharmaceuticals have been made. One example is Bioorg. Med. Chem. Lett. 1998, 8, 1467) and Bioorg. Med. Chem. Lett. 2000, 10, 1435.) Porphyrin containing fluorine shows strong activity as an inhibitor of acetrylcholinesterase (AChE), which is the cause of Alzheimer's disease. Also, according to (Biochemistry, 2004, 43, 10918.), it shows good activity as a photosensitizer used as a photoactive therapeutic agent for cancer. However, the higher the amount of fluorine groups substituted in porphyrins, the stronger the activity, but the activity is very different depending on the substituted position and the appropriate number of fluorine.

 （J. AM. Chem. Soc. 2004, 128, 12833.) and (J. Med. Chem. 2001, 44, 4509.) reported that porphyrins with cations also have the ability to inhibit specific enzymes due to their good interaction with proteins and DNA, but efforts to develop more active porphyrins have been ongoing.

The present invention has been made to solve the above problems, and an object of the present invention is 5,10,15,20-tetrakis (2-fluorofluoropyridine-3), which is effective as a bioactive substance such as an anticancer agent or an antibiotic. (1) — to provide porphyrin.

Another object of the present invention is to provide 5,10,15,20-tetrakis- (2-fluoro-) through quantitative reaction with pyrrole under acidic conditions using 2-fluoropyridine-3-carbaldehyde as starting material. It provides a method for producing pyridin-3-yl) -porphyrin.

Still another object of the present invention is to provide a 5,10,15,20-tetrakis- (1-alkyl-2-fluoropyridinium-3-yl) -porphyrin salt.

Still another object of the present invention is to provide 5,10,15,20-tetrakis- (3,5-difluoro-pyridin-4-yl) -porphyrin.

Another object of the present invention is to provide 5,10,15,20-tetrakis (3) by quantitative reaction with pyrrole under acidic conditions with 3,5-difluoropyridine-4-carbaldehyde as starting material. It is to provide a method for producing, 5-difluoro-pyridin-4-yl) -porphyrin.

Another object of the present invention is to provide a 5,10,15,20-tetrakis- (1-alkyl-3,5-difluoro-pyridinium-4-yl) -porphyrin salt.

5,10,15,20-tetrakis- (2-fluoro-pyridin-3-yl) -porphyrin according to the present invention for achieving the above object is a compound represented by the following formula (1).

 In addition, a method for producing 5,10,15,20-tetrakis (2-fluorofluoropyridin-3-yl) -porphyrin according to the present invention for achieving the above object is 2-fluoropyridine-3-carb. Formation of porphyrin through quantitative reaction with pyrrole under acidic conditions with aldehyde as starting material.

In addition, a 5,10,15,20-tetrakis- (1-alkyl-2-fluoro-pyridinium-3-yl) -porphyrin salt according to the present invention for achieving the above object is represented by the following formula (2) Compound.

(In Formula 2, R is an alkyl group such as methyl or ethyl, propyl, iso -propyl, butyl, iso -butyl, tert -butyl, pentyl, iso -pentyl, benzyl, methylbenzyl, methoxy, ethoxy, Alkoxy groups such as methoxy and pentoxy, ester groups such as acetyloxy, ethylcarbonyloxy, protylcarbonyloxy, butylcarbonyloxy, glucosyloxy derivatives, protosyloxy derivatives, galactosyloxy derivatives, Sugar derivative groups such as nosyloxy derivatives. X ^- anion is a halogen anion ^{(F -, Cl -, Br} -, I -), anion (BF ₄ ^-) tetrafluoroborate, anion (BF ₆ ^-) hexafluoropropane, methyl sulfone benzoate anion (methylsulfonate; CH ₃ SO ₃ ⁻ ), paratoryl sulfoxide anion ( p- tolyl sulfoxide; CH ₃ C ₆ H ₄ SO ⁻ ), trifluoromethanesulfonate; And the like)) ^- CF ₃ SO _3.

Further, in order to achieve the above object, a 5,10,15,20-tetrakis- (1-alkyl-2-fluoropyridinium-3-yl) -porphyrin salt according to the present invention is a 2-fluoropyridine. It is characterized in that it comprises a porphyrin formation step and a N-alkyl salt formation step by quantitative reaction with pyrrole in acid conditions with 3-carbaldehyde as a starting material.

In addition, 5,10,15,20-tetrakis- (3,5-difluoro-pyridin-4-yl) -porphyrin according to the present invention for achieving the above object is a compound represented by the following formula (3).

 In addition, a method for producing 5,10,15,20-tetrakis- (3,5-difluoro-pyridin-4-yl) -porphyrin according to the present invention for achieving the above object is 3,5-difluoro Porphyrin is formed by quantitative reaction with pyrrole under acidic conditions using tropyridine-4-carbaldehyde as a starting material.

In addition, a 5,10,15,20-tetrakis- (1 -alkyl-3,5-difluoro-pyridinium-4-yl) -porphyrin salt according to the present invention for achieving the above object is represented by the following formula (4) It is a compound represented by.

(In Formula 4, R is an alkyl group such as methyl or ethyl, propyl, iso -propyl, butyl, iso -tilt, tert -butyl, pentyl, iso -pentyl, benzyl, methylbenzyl, methoxy, ethoxy, Alkoxy groups such as methoxy and pentoxy, ester groups such as acetyloxy, ethylcarbonyloxy, protylcarbonyloxy, butylcarbonyloxy, glucosyloxy derivatives, protosyloxy derivatives, galactosyloxy derivatives, Sugar derivative groups such as nosyloxy derivatives. X ^- anion is a halogen anion ^{(F -, Cl -, Br} -, I -), anion (BF ₄ ^-) tetrafluoroborate, anion (BF ₆ ^-) hexafluoropropane, methyl sulfone benzoate anion (methylsulfonate; CH ₃ SO ₃ ⁻ ), paratoryl sulfoxide anion ( p- tolyl sulfoxide; CH ₃ C ₆ H ₄ SO ⁻ ), trifluoromethanesulfonate; And the like)) ^- CF ₃ SO _3.

Further, 5,10,15,20-tetrakis- (1-alkyl-3,5-difluoro-pyridinium-4-yl) -porphyrin salts according to the present invention for achieving the above object are 3,5 Porphyrin formation step through quantitative reaction with pyrrole in acid conditions with -difluoropyridine-4-carbaldehyde as starting material, and N-alkyl salt formation step.

5,10,15,20-tetrakis- (2-fluoro-pyridin-3-yl) -porphyrin and its derivatives 5,10,15,20-tetrakis- (1-alkyl) 2-fluoro-pyridinium-3-yl) -porphyrin salts and 5,10,15,20-tetrakis- (3,5-difluoro-pyridin-4-yl) -porphyrins and derivatives thereof 5 The preparation method and anticancer test of the 10,15,20-tetrakis- (1-alkyl-3,5-difluoro-pyridinium-4-yl) -porphyrin salt are described in more detail at each step.

1.5, 10, 15, 20 Tetrakis -(2- Fluoro -Pyridin-3-yl)-porphyrins and derivatives thereof 5,10,15,20 Tetrakis -(One- Alkyl -2- Fluoro ― Pyridinium -3-day)-a method for producing a porphyrin salt.

Step (1-1): Porphyrin Formation Step

The compound represented by the following Chemical Formula 1 is prepared by reacting 2-fluoropyridine-3-carbaldehyde and pyrrole represented by the following Chemical Formula 5 under acidic conditions.

[Formula 1]

As the acid used, acids such as propanoic acid, butanoic acid, pentanic acid, hexane, and BF ₃ are used. The reaction temperature of the step is preferably carried out at 20 ℃ to 150 ℃.

Step （1-2）: N― Alkyl salt  Forming steps

In the presence of an organic solvent, using an alkyl salt to form an N-alkyl salt in the pyridine group of formula (1) prepared in step (1-1) to prepare a compound represented by the following formula (2).

        [Formula 1]

  [Formula 2]

(In Formula 2, R is an alkyl group such as methyl or ethyl, propyl, iso -propyl, butyl, iso -butyl, tert -butyl, pentyl, iso -pentyl, benzyl, methylbenzyl, methoxy, ethoxy, Alkoxy groups such as methoxy and pentoxy, ester groups such as acetyloxy, ethylcarbonyloxy, protylcarbonyloxy, butylcarbonyloxy, glucosyloxy derivatives, protosyloxy derivatives, galactosyloxy derivatives, Sugar derivative groups such as nosyloxy derivatives. X ^- anion is a halogen anion ^{(F -, Cl -, Br} -, I -), anion (BF ₄ ^-) tetrafluoroborate, anion (BF ₆ ^-) hexafluoropropane, methyl sulfone benzoate anion (methylsulfonate; CH ₃ SO ₃ ⁻ ), paratoryl sulfoxide anion ( p- tolyl sulfoxide; CH ₃ C ₆ H ₄ SO ⁻ ), trifluoromethanesulfonate; And the like)) ^- CF ₃ SO _3.

 The organic solvent is selected from the group consisting of tetrahydrofurane, dimethylformamide, dimethylsulfoxide, ethyl acetate, methyl chloride, methylene chloride, methanol, ethanol, propanol and acetone. It is preferable. The alkyl salt used in this step is R-X. Preferably, the reaction temperature of the N-alkyl salt forming step is 20 ℃ to 100 ℃.

2. 5,10,15,20 Tetrakis ― （3,5― Difluoro -Pyridin-4-yl)-porphyrins and derivatives thereof 5,10,15,20 Tetrakis -(One- Alkyl -3,5 Difluoro ― Pyridi Method for producing the nium-4-yl) -porphyrin salt.

Step (2-1): Porphyrin Formation Step

The compound represented by the following formula (3) is prepared through the reaction of 3,5-difluoropyridine-4-carbaldehyde and pyrrole represented by the following formula (6) under acidic conditions.

[Formula 3]

As the acid used, acids such as propanoic acid, butanoic acid, pentanic acid, hexane, and BF ₃ are used. The reaction temperature of the step is preferably carried out at 20 ℃ to 150 ℃.

Step (2-2): N Alkyl salt  Forming steps

In the presence of an organic solvent, using an alkyl salt to form an N-alkyl salt in the pyridine group of the formula (3) prepared in step (2-1) to prepare a compound represented by the following formula (4).

        [Formula 3]

  [Formula 4]

(In Formula 4, R is an alkyl group such as methyl, ethyl, propyl, iso -propyl, butyl, iso -butyl, tert -butyl, pentyl, iso -pentyl, benzyl, methylbenzyl, methoxy, ethoxy, Alkoxy groups such as methoxy and pentoxy, ester groups such as acetyloxy, ethylcarbonyloxy, protylcarbonyloxy, butylcarbonyloxy, glucosyloxy derivatives, protosyloxy derivatives, galactosyloxy derivatives, Sugar derivative groups such as nosyloxy derivatives. X ^- anion is a halogen anion ^{(F -, Cl -, Br} -, I -), anion (BF ₄ ^-) tetrafluoroborate, anion (BF ₆ ^-) hexafluoropropane, methyl sulfone benzoate anion (methylsulfonate; CH ₃ SO ₃ ⁻ ), paratoryl sulfoxide anion ( p- tolyl sulfoxide; CH ₃ C ₆ H ₄ SO ⁻ ), trifluoromethanesulfonate; And the like)) ^- CF ₃ SO _3.

 The organic solvent is selected from the group consisting of tetrahydrofurane, dimethylformamide, dimethylsulfoxide, ethyl acetate, methyl chloride, methylene chloride, methanol, ethanol, propanol and acetone. It is preferable. The alkyl salt used in this step is R-X. Preferably, the reaction temperature of the N-alkyl salt forming step is 20 ℃ to 100 ℃.

5,10,15,20-tetrakis- (2-fluoro-pyridin-3-yl) -porphyrin and 5,10,15,20-tetrakis- (3,5-difluoro) Pyridin-4-yl) -porphyrin has antimicrobial, antimicrobial and anticancer effects and is sensitive to light and is effective as a photosensitizer.

In particular, 5,10,15,20-tetrakis- (1alkyl-2-fluoropyridin-3-yl) -porphyrin salts and 5,10,15,20-tetrakis- (1alkyl) according to the present invention The -3,5-difluoro-pyridinium-4-yl) -porphyrin salt is well soluble in aqueous solution, has antimicrobial, antibacterial and anticancer effects, and is sensitive to light, making it effective as a photosensitizer. In particular, since it has cell specificity as an anticancer agent, it can be effectively used for selective cancer treatment.

  Hereinafter, the present invention will be described in more detail with reference to Examples. However, the embodiment is not limited to the present invention.

The molecular structure of the compound obtained in the following examples was confirmed by nuclear magnetic resonance spectrum, ultraviolet spectroscopy, mass spectrometry.

1.5, 10, 15, 20 Tetrakis -(2- Fluoro -Pyridin-3-yl)-porphyrins and derivatives thereof 5,10,15,20 Tetrakis ― （ 1 alkyl -2- Fluoro Synthesis example of -pyridin-3-yl) -porphyrin salt and anticancer test results.

Example  1-1: 5,10,15,20 Tetrakis -(2- Fluoro -Pyridine-3-day-Porphyrin

1 g of 2-fluoro-pyridine-3-carbaldehyde and 0.8 mL of pyrrole were added to 40 mL of propanoic acid and stirred at 120 ° C. for 1 hour. The reaction mixture is cooled to room temperature, distilled under reduced pressure, and saturated aqueous sodium hydroxide (NaOH) solution is added. The product was extracted through methylene chloride and the combined organic layers were dried over sodium sulfate. The dried mixture was distilled under reduced pressure, and then purified by liquid chromatography (1:40 methanol-methane chloride) to give 5,10,15,20-tetrakis- (2-fluoro-pyridin-3-yl) -porphyrin (170 mg). 6%).

¹ H NMR (CD ₂ Cl ₂ , 300 MHz) δ 8.83 (s, 8H), 8.74 (s, 4H), 8.56 (m, 4H), 7.71 (s, 4H), -2.82 (s, 2H); HRMS (FAB): calcd for C ₄₀ H ₂₂ N ₈ F ₄ : 690.1904, found: 690.1874.

Example  1-2: 5,10,15,20 Tetrakis -(One- methyl -2- Fluoro ― Pyridinium -3-day)-porphyrin Tetrafluoroborate

In 30 mL of methylene chloride, 170 mg of 5,10,15,20-tetrakis (2-fluoro-pyridin-3-yl) -porphyrin and 180 mg of trimethoxyoxonium tetrafluoroborate made in Example 1 above were added. ((CH ₃ ) ₃ OBF ₄ ) was added thereto and stirred at 50 ° C. for 1 hour. The resulting precipitate was filtered and washed sequentially with methylene chloride, ethyl acetate and acetone and dried under reduced pressure to give 5,10,15,20-tetrakis- (1-methyl-2-fluoro-pyridinium-3-yl). -Porphyrin tetrafluoroborate (245 mg; 92%) was obtained.

¹ H NMR (CDCl ₃ , 500 MHz) d 9.53 (m, 8H), 9.37 (s, 4H), 8.53 (m, 4H), -3.01 (s, 1H), -3.18 (s, 1H); HRMS (FAB): calcd for C ₄₄ H ₃₄ N ₈ F ₄ : 750.2843, found: 750.2824.

Example  1-3: 5,10,15,20 Tetrakis -(One- methyl -2- Fluoro ― Pyridinium  -3-day)-porphyrin Of tetrafluoroborate  Anticancer activity test result （IC ₅₀ (ΜM)）

HL-60 A172 Hela A549 HepG2 89.1 ± 1.4 ＞ 150 5.2 ± 0.1 84.8 ± 2.9 5.2 ± 0.2

HL-60: human promyelocytic leukemia cell

A172: human gliobalstoma cell

Hela: human cervix epithelial carcinoma cell

A549: human lung epithelial carcinoma cell

HepG2: human hpathoma cell

2. 5,10,15,20 Tetrakis ― （3,5― Difluoro Examples of the synthesis of -pyridin-4-yl) -porphyrin and its derivatives 5,10,15,20-tetrakis- (1 -alkyl-3,5-difluoro-pyridin-4-yl) -porphyrin salts and anticancer Test results.

Example  2-1: 5,10,15,20 Tetrakis ― （3,5― Difluoro -Pyridine-4-day)-porphyrin

1 g of 3,5-difluoropyridine-4-carbaldehyde and 0.5 mL of pyrrole were added to 40 mL of propanoic acid and stirred at 120 ° C. for 1 hour. The reaction mixture is cooled to room temperature, distilled under reduced pressure, and saturated aqueous sodium hydroxide (NaOH) solution is added. The product was extracted through methylene chloride and the combined organic layers were dried over sodium sulfate. The dried mixture was distilled under reduced pressure, and then purified by liquid chromatography (1:40 methanol-methane chloride) to give 5,10,15,20-tetrakis- (3,5-difluoro-pyridin-4-yl)-. Porphyrin (63 mg; 8%).

¹ H NMR (CD ₂ Cl ₂ , 300 MHz) δ 8.91 (s, 8H), 8.90 (d, J = 2.7 Hz, 8H), −2.58 (s, 2H); UV (MC, λmasz, log ε): 412, 508, 542, 584, 652 nm; HRMS (FAB): calcd for C ₄₀ H ₁₈ N ₈ F ₈ : 762.1527, found: 762.1497.

Example  2-2: 5,10,15,20 Tetrakis -(One- methyl -3,5 Difluoro ― Pipe Dinium-4th-porphyrin Tetrafluoroborate

In 20 mL of methylene chloride, 63 mg of 5,10,15,20-tetrakis- (3,5-difluoro-pyridin-4-yl) -porphyrin and 60 mg of trimethoxyoxo made in Example 2-1 above Added tetrafluoroborate ((CH ₃ ) ₃ OBF ₄ ) and stirred at 50 ° C. for 1 hour. The resulting precipitate was filtered and washed sequentially with methylene chloride, ethyl acetate and acetone and dried under reduced pressure to give 5,10,15,20-tetrakis- (1 -methyl-3,5-difluoro-pyridinium-4 -Yl) -pyrroline tetrafluoroborate (87 mg; 90%） was obtained.

¹ H NMR (CDCl ₃ , 500 MHz) d 10.06 (s, 8H), 9.54 (s, 8H), 4.79 (s, 12H), -3.18 (s, 2H); HRMS (FAB): calcd for C ₄₄ H ₃₀ N ₈ F ₈ : 822.2466, found: 822.2423.

Example  2-3: 5, 10, 15, 20 Tetrakis -(One- methyl ―3,5― Difluoro ― Pyridinium -4-day)-porphyrin Of tetrafluoroborate  Anticancer activity test result （IC ₅₀ (ΜM)）

HL-60 A172 Hela A549 HepG2 11.4 ± 0.6 130.1 ± 6.8 112.4 ± 5.8 115.6 ± 6.2 41.2 ± 0.3

HL-60: human promyelocytic leukemia cell

A172: human gliobalstoma cell

Hela: human cervix epithelial carcinoma cell

A549: human lung epithelial carcinoma cell

HepG2: human hpathoma cell

As described above, according to the present invention, 5,10,15,20-tetrakis (2-fluorofluoropyridin-3-yl) using 2-fluoro-pyridine-3-carbaldehyde as a starting material. -The effect of preparing a porphyrin and its derivative 5,10,15,20-tetrakis- (1-alkyl-2-fluoro-pyridinium- 3-yl) -porphyrin salt can be attained. Further, 5,10,15,20-tetrakis (3,5-difluoropyridin-4-yl) -porphyrin and derivatives thereof, starting from 3,5-difluoropyridine-4-carbaldehyde The effect of producing the phosphorus 5,10,15,20-tetrakis- (1-alkyl-3,5-difluoro-pyridinium-4-yl) -porphyrin salt can be achieved. 5,10,15,20-tetrakis- (2-fluoro-pyridin-3-yl) -porphyrin according to the present invention and 5,10,15,20-tetrakis- (3,5-difluoro- Pyridin-4-yl) -porphyrin has antimicrobial, antibacterial and anticancer activity and functions as a photosensitizer. Furthermore, 5,10,15,20-tetrakis- (1-alkyl-2-fluoro-pyridinium-3-yl) -porphyrin salt and 5,10,15,20-tetrakis- (1) according to the present invention -Alkyl-3,5-difluoro-pyridinium-4-yl) -porphyrin salts have high solubility in aqueous solutions, have antibiotic, antibacterial and anticancer effects, and function as photosensitizers. By using this, it can be used as bioactive substances such as antibacterial agents, antibiotics and anticancer agents, and can be effectively used for photoactive therapy as a photosensitive agent. In particular, as an anticancer agent has a selective activity for each cancer cell can be effectively used in cancer treatment. In addition, it can be effectively used as a material having a photoresist function when developing electronic materials.

While specific embodiments of the present invention have been described above, the present invention is not limited to the above-described specific embodiments and the technical field to which the present invention pertains without departing from the gist of the present invention as claimed in the claims. Anyone of ordinary skill in the art can make various modifications, as well as such modifications are within the scope of the claims.

Claims (22)

5,10,15,20-tetrakis- (2-fluoro-pyridin-3-yl) -porphyrin represented by the following general formula (1).  [Formula 1]

5,10,15,20-tetrakis, characterized in that 2-fluoro-pyridine-3-carbaldehyde represented by the following formula (5) is prepared under the acid condition by the reaction of pyrrole with the following formula (1). -(2-fluoro-pyridin- 3-yl)-porphyrin.  [Formula 5]

 [Formula 1]

The acid used in the preparation step is propanoic acid, butanoic acid, pentanic acid, hexane, BF ₃ A method for producing 5,10,15,20-tetrakis- (2-fluoro-pyridin-3-yl) -porphyrin, which is selected from an acid such as an acid. The process for preparing 5,10,15,20-tetrakis- (2-fluoro-pyridin-3-yl) -porphyrin according to claim 2, wherein the reaction temperature in the step is 20 ° C to 150 ° C. A 5,10,15,20-tetrakis- (1 -alkyl-2 -fluoro-pyridin-3 -yl) -porphyrin salt represented by the following formula (2).           [Formula 2]

(In Formula 2, R is an alkyl group such as methyl or ethyl, propyl, iso -propyl, butyl, iso -butyl, tert -butyl, pentyl, iso -pentyl, benzyl, methylbenzyl, methoxy, ethoxy, Alkoxy groups such as methoxy and pentoxy, ester groups such as acetyloxy, ethylcarbonyloxy, protylcarbonyloxy, butylcarbonyloxy, glucosyloxy derivatives, protosyloxy derivatives, galactosyloxy derivatives, Sugar derivative groups such as nosyloxy derivatives. X ^- anion is a halogen anion ^{(F -, Cl -, Br} -, I -), tetrafluoroborate anion lane (BF ₄ ^-), hexafluoro-Lobo Lane anion (BF ₆ ^-), methyl sulfone anion (methylsulfonate; CH ₃ SO ₃ ^-), para-tolyl sulfoxide anion (p -tolyl sulfoxide; CH ₃ C ₆ H ₄ SO ⁻ ), trifluoromethanesulfonate; And the like)) ^- CF ₃ SO _3. (B) preparing a compound represented by the following Chemical Formula 1 by reacting 2-fluoro-pyridine-3-carbaldehyde represented by the following Chemical Formula 3 with pyrrole under acidic conditions; and N forming an N-alkyl salt in the pyridine group of the compound prepared in step 하에서 in the presence of an organic solvent to prepare a compound represented by the following formula (2); 5, 10, 15, 20 A method for preparing a tetrakis- (1-alkyl-2-fluoro-pyridin-3-yl) -porphyrin salt.         [Formula 3]

[Formula 1]

[Formula 2]

(In Formula 2, R is an alkyl group such as methyl or ethyl, propyl, iso -propyl, butyl, iso -butyl, tert -butyl, pentyl, iso -pentyl, benzyl, methylbenzyl, methoxy, ethoxy, Alkoxy groups such as methoxy and pentoxy, ester groups such as acetyloxy, ethylcarbonyloxy, protylcarbonyloxy, butylcarbonyloxy, glucosyloxy derivatives, protosyloxy derivatives, galactosyloxy derivatives, Sugar derivative groups such as nosyloxy derivatives. X ^- anion is a halogen anion ^{(F -, Cl -, Br} -, I -), tetrafluoroborate anion lane (BF ₄ ^-), hexafluoro-Lobo Lane anion (BF ₆ ^-), methyl sulfone anion (methylsulfonate; CH ₃ SO ₃ ^-), para-tolyl sulfoxide anion (p -tolyl sulfoxide; CH ₃ C ₆ H ₄ SO ⁻ ), trifluoromethanesulfonate; And the like)) ^- CF ₃ SO _3. The method of claim 6, wherein the acid used in step ( _iii) is propanoic acid, butanoic acid, pentanic acid, hexane, BF ₃ A method for producing a 5,10,15,20-tetrakis- (1-alkyl-2-fluoropyridin-3-yl) -porphyrin salt, characterized in that it is selected from acids such as these. 7. The 5,10,15,20-tetrakis- (1 -alkyl-2 -fluoro-pyridin-3 -yl) according to claim 6, characterized in that the reaction temperature of step (iii) is from 25 deg. C to 150 deg. -Preparation of porphyrin salts. The organic solvent of claim 6, wherein the organic solvent used in step (v) is tetrahydrofurane, dimethylformamide, dimethylsulfoxide, ethyl acetate, methyl chloride, methylene chloride, methanol, A process for preparing a 5,10,15,20-tetrakis- (1 -alkyl-2 -fluoro-pyridin-3 -yl) -porphyrin salt, characterized in that it is selected from the group consisting of ethanol, propanol and acetone. 7. The 5,10,15,20-tetrakis- (1 -alkyl-) according to claim 6, wherein the alkyl salt used in the formation of the N-alkyl salt in step (iii) uses a salt of type R-X. Method for preparing 2-fluoro-pyridin-3-yl) -porphyrin salt. Where R is methyl or ethyl, propyl, iso -propyl, butyl, iso -butyl, tert -butyl, pentyl, iso -pentyl, benzyl, methylbenzyl and the like, and methoxy, ethoxy, protoxy, Alkoxy groups such as pentoxy, ester groups such as acetyloxy, ethylcarbonyloxy, protylcarbonyloxy, butylcarbonyloxy, glucosyloxy derivatives, protosyloxy derivatives, galactosyloxy derivatives, mannosyloxy derivatives Sugar derivative groups such as; X ^- anion is a halogen anion ^{(F -, Cl -, Br} -, I -), anion (BF ₄ ^-) tetrafluoroborate, anion (BF ₆ ^-) hexafluoropropane, knitted anion of methyl sulfone (methylsulfonate; CH ₃ SO ₃ ⁻ ), paratoryl sulfoxide anion ( p- tolyl sulfoxide; CH ₃ C ₆ H ₄ SO ⁻ ), trifluoromethanesulfonate; And the like)) ^- CF ₃ SO _3. 7. The 5,10,15,20-tetrakis- (1 -alkyl-2 -fluoro-pyridin-3 -yl) according to claim 6, wherein the reaction temperature in step (iii) is from 20 deg. C to 100 deg. -Preparation of porphyrin salts. 5,10,15,20-tetrakis- (3,5-difluoro-pyridin-4-yl) -porphyrin represented by the following general formula (3).  [Formula 3]

3,5-difluoropyridine-4-carbaldehyde represented by the following formula (6) under acid conditions is prepared by the following formula (3) by reaction with pyrrole (5,10,15,20) A method for producing tetrakis- (3,5-difluoro-pyridin-4-yl) -porphyrin.  [Formula 6]

 [Formula 3]

The method of claim 13, wherein the acid used in the preparation step is propanoic acid, butanoic acid, pentanic acid, hexane, BF ₃ A method for producing 5,10,15,20-tetrakis- (3,5-difluoro-pyridin-4-yl) -porphyrin, which is selected from acids such as these. The 5,10,15,20-tetrakis- (3,5-difluoro-pyridin-4-yl) -porphyrin according to claim 13, wherein the reaction temperature in the step is 20 ° C to 150 ° C. Manufacturing Method 5,10,15,20-tetrakis- (1-alkyl-3,5-difluoro-pyridinium-4-yl) -porphyrin salt represented by the following general formula (4).           [Formula 4]

(In Formula 4, R is an alkyl group such as methyl, ethyl, propyl, iso -propyl, butyl, iso -butyl, tert -butyl, pentyl, iso -pentyl, benzyl, methylbenzyl, methoxy, ethoxy, Alkoxy groups such as methoxy and pentoxy, ester groups such as acetyloxy, ethylcarbonyloxy, protylcarbonyloxy, butylcarbonyloxy, glucosyloxy derivatives, protosyloxy derivatives, galactosyloxy derivatives, Sugar derivative groups such as nosyloxy derivatives. X ^- anion is a halogen anion ^{(F -, Cl -, Br} -, I -), tetrafluoroborate anion lane (BF ₄ ^-), hexafluoro-Lobo Lane anion (BF ₆ ^-), methyl sulfone anion (methylsulfonate; CH ₃ SO ₃ ^-), para-tolyl sulfoxide anion (p -tolyl sulfoxide; CH ₃ C ₆ H ₄ SO ⁻ ), trifluoromethanesulfonate; And the like)) ^- CF ₃ SO _3. Preparing a compound represented by the following Chemical Formula 3 by reacting 3,5-difluoropyridine-4-carbaldehyde represented by the following Chemical Formula 6 with pyrrole under acidic conditions; and N forming an N-alkyl salt in the pyridine group of the compound prepared in step 하에서 in the presence of an organic solvent to produce a compound represented by the following formula (4); 5, 10, 15, 20 A method for producing a tetrakis- (1-alkyl-3,5-difluoro-pyridinium-4-yl) -porphyrin salt.         [Formula 6]

[Formula 3]

[Formula 4]

(In Formula 4, R is an alkyl group such as methyl, ethyl, propyl, iso -propyl, butyl, iso -butyl, tert -butyl, pentyl, iso -pentyl, benzyl, methylbenzyl, methoxy, ethoxy, Alkoxy groups such as methoxy and pentoxy, ester groups such as acetyloxy, ethylcarbonyloxy, protylcarbonyloxy, butylcarbonyloxy, glucosyloxy derivatives, protosyloxy derivatives, galactosyloxy derivatives, Sugar derivative groups such as nosyloxy derivatives. X ^- anion is a halogen anion ^{(F -, Cl -, Br} -, I -), tetrafluoroborate anion lane (BF ₄ ^-), hexafluoro-Lobo Lane anion (BF ₆ ^-), methyl sulfone anion (methylsulfonate; CH ₃ SO ₃ ^-), para-tolyl sulfoxide anion (p -tolyl sulfoxide; CH ₃ C ₆ H ₄ SO ⁻ ), trifluoromethanesulfonate; And the like)) ^- CF ₃ SO _3. 18. The process of claim 17, wherein the acid used in step _iii is propanoic acid, butanoic acid, pentanic acid, hexane, BF ₃ A method for producing a 5,10,15,20-tetrakis- (1-alkyl-3,5-difluoro-pyridinium-4-yl) -porphyrin salt, characterized in that it is selected from acids such as these. 18. The 5,10,15,20-tetrakis (1-alkyl-3,5-difluoro-pyridinium) of claim 17, wherein the reaction temperature of step (iii) is from 25 ° C to 150 ° C. 4-yl)-A method for producing a porphyrin salt. 18. The method of claim 17, wherein the organic solvent used in step (v) is tetrahydrofurane, dimethylformamide, dimethylsulfoxide, ethyl acetate, methyl chloride, methylene chloride, methanol, Preparation of 5,10,15,20-tetrakis (1-alkyl-3,5-difluoro-pyridinium-4-yl) -porphyrin salts, characterized in that it is selected from the group consisting of ethanol, propanol and acetone Way. 18. The 5,10,15,20-tetrakis- (1-alkyl-) characterized in claim 17, wherein the alkyl salt used in the formation of the N-alkyl salt in step (iii) uses a salt of type R-X. Method for preparing 3,5-difluoro-pyridinium-4-yl) -porphyrin salt. Where R is methyl or ethyl, propyl, iso -propyl, butyl, iso -butyl, tert -butyl, pentyl, iso -pentyl, benzyl, methylbenzyl and the like, and methoxy, ethoxy, protoxy, Alkoxy groups such as pentoxy, ester groups such as acetyloxy, ethylcarbonyloxy, protylcarbonyloxy, butylcarbonyloxy, glucosyloxy derivatives, protosyloxy derivatives, galactosyloxy derivatives, mannosyloxy derivatives Sugar derivative groups such as; X ^- anion is a halogen anion ^{(F -, Cl -, Br} -, I -), anion (BF ₄ ^-) tetrafluoroborate, anion (BF ₆ ^-) hexafluoropropane, knitted anion of methyl sulfone (methylsulfonate; CH ₃ SO ₃ ⁻ ), paratoryl sulfoxide anion ( p- tolyl sulfoxide; CH ₃ C ₆ H ₄ SO ⁻ ), trifluoromethanesulfonate; And the like)) ^- CF ₃ SO _3. 18. The 5,10,15,20-tetrakis- (1-alkyl-3,5-difluoro-pyridinium--characterized in claim 17, wherein the reaction temperature in step (iii) is between 20 and 100 ° C. 4-yl)-A method for producing a porphyrin salt.