KR101794695B1 - Functional food composition having anti-inflammatory effect - Google Patents

Abstract

The present invention relates to a composition for effectively preventing, ameliorating, or treating various types of inflammatory diseases owing to excellent anti-inflammatory effects. More specifically, a compound of the present invention suppresses production of nitrogen monoxide (NO) which is an inflammatory mediator as well as expression of interleukin (IL)-6, tumor necrosis factor (TNF)-, and interferon (IFN)-gamma which are inflammatory cytokines. In addition, the compound effectively prevents, ameliorates, or treats inflammatory diseases, and is safe without side effects after injected into human body.

Description

[0001] Functional food composition having an anti-inflammatory effect [

The present invention relates to a composition capable of effectively preventing, ameliorating, or treating various inflammatory diseases because of its excellent anti-inflammatory effect.

Inflammation refers to the tissue response to an injury when external antigens, such as bacteria or viruses, enter the body from outside or when cells or tissue are damaged by some cause. Inflammatory cells release various inflammatory mediators such as active nitrogen and oxygen species that cause DNA damage in the initiation, enhancement of tumor. The inflammation is divided into acute inflammatory and chronic inflammatory. When chronic inflammatory reaction occurs, pre-inflammatory cytokine and chemokine are excessively released, causing damage to surrounding tissues and invasion of tumor cells, And promotes angiogenesis to help tumor growth.

Recently, with the development of molecular biology, attempts have been made to understand inflammatory diseases at the molecular level such as cytokines, and factors affecting these diseases are also being clarified one by one. Among these factors, nitric oxide (NO) is an inflammatory mediator that plays a role in maintaining homeostasis by damaging pathogenic DNA (Kou and Schroder, Ann Sur 221, 220-235, 1995). NO is generated from L-arginine by the three major NOSs, nNOS (neuronal NOS), eNOS (endothelial NOS) and iNOS (inducible NOS), which are isomers of NOS. Of these, NO produced by iNOS excessively reacts with superoxide to form peroxynitrite, which acts as a strong oxidizing agent and damages the cells, thereby activating macrophages by inflammatory stimuli . Macrophages activated by various stimuli and inflammatory mediators produce other inflammatory factors such as tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and prostaglandin E2 (PGE2) And NF-κB are known to be involved in chronic diseases such as inflammation, cancer, and arteriosclerosis (Lawrence et al., Nat Med., 7, 1291-1297, 2001).

Although studies have been actively conducted to treat inflammatory diseases by modulating intracellular levels of the factors involved in the inflammatory response, the initial therapeutic agent was intended to regulate intracellular levels of the factors, but it has disadvantages such as serious side effects, There is no side effect, and studies to control the intracellular levels of the factors are actively under way.

It is an object of the present invention to provide a food composition which is excellent in anti-inflammatory effect and can effectively prevent or ameliorate an inflammatory disease.

Another object of the present invention is to provide a cosmetic composition which is excellent in anti-inflammatory effect and can effectively prevent or ameliorate an inflammatory disease.

Another object of the present invention is to provide a pharmaceutical composition which is excellent in anti-inflammatory effect and can effectively prevent or treat an inflammatory disease.

Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to one embodiment of the present invention, there is provided a food composition for preventing or ameliorating an inflammatory disease, comprising a compound represented by the following formula (1) as an active ingredient:

[Chemical Formula 1]

In Formula 1,

L ₁ is a direct bond or a C _1-6 alkylene group;

R ₁ is hydrogen or C _{1- 6} alkyl group;

R ₂ is -SO ₂ NR ₃ R ₄ ;

R ₃ and R ₄ are each independently hydrogen, C _{1- 6} alkyl or C _{3- 6} cycloalkyl alkyl group;

Wherein R _1, the alkyl group of R ₃ and R _4, the cycloalkyl group of R ₃ and R ₄ are each independently optionally substituted with one or more substituents of C _{1- 6} alkyl group being unsubstituted, substituted, if a plurality of substituents , They may be the same or different from each other.

In the present invention, the compound represented by the following formula (2) is preferable because it has excellent anti-inflammatory effect, but is not limited thereto:

(2)

In Formula 2,

Each of L ₁ , R ₁ , R ₃ and R ₄ is as defined in the above formula (1).

Wherein L ₁ in the invention is _1- C ₆ alkylene group that may be preferred, more preferably C _1-3 alkylene-date, it is not the most preferably methylene, but may due date, limited.

Wherein R ₁ in the present invention is not that the C _{1- 6} alkyl group, more preferably may be a C _{1- 3} alkyl group, most preferably methyl or ethyl, but date, limited.

Wherein R ₃ and R ₄ in the present invention are each independently preferably a hydrogen or C _{1- 6} alkyl group, and may be more preferably C _{1- 6} alkyl, most preferably methyl, ethyl or propyl but could date , But is not limited thereto.

The compound of the present invention is a compound represented by the following general formula (3): N, N-dimethyl-2- (2 - ((4- (4-methylpiperazin-1-yl) methyl) phenyl) amino) pyrimidin-4-yl) benzenesulfonamide) Most preferably but not exclusively:

(3)

In general, lipopolysaccharide (LPS) interacts with immune cells such as leukocytes among the inducers of inflammatory response, and the increase of nitric oxide concentration by activation of iNOS isoform in monocyte macrophages (Korhonen R. et al., Curr Drug Targets Inflamm Allergy., 4, pp 471-79, 2005). LPS is an endotoxin present in the outer membrane of Gram-negative bacteria. The binding of TLR4 to toll-like receptor 4 (IL-6) and chemokines Ji Y, et al., Cell Physiol Biochem., 25 (2003), pp. 259-348, which is incorporated herein by reference in its entirety. , pp631-640, 2010). In the body inflammation process, excessive NO is formed by NOS (NO synthase). In general, the formation of NO plays an important role in killing bacteria or eliminating tumors (Weis, ZA, Biochem J., 316, p209, 1996). NO produced by iNOS (inducible NO synthase) (Mu, MM, J. Endotoxin Res. 7, p. 431, 2001), which not only promotes inflammatory responses such as inflammation, swelling, and promotes biosynthesis of inflammatory mediators.

In the present invention, the compound represented by the above formula (1) is an inflammatory mediator of nitric oxide (NO) and a variety of inflammatory cytokines such as interleukin-6 (IL-6), TNF- -gamma (IFN-gamma), and thus the prophylactic, ameliorative or therapeutic effect of inflammatory diseases is remarkably excellent.

Inflammatory diseases to be prevented or improved in the present invention include swelling, dermatitis, allergy, atopy, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, sore throat, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, Sjogren's syndrome, and multiple sclerosis, including, but not limited to, osteoarthritis, rheumatoid arthritis, rheumatoid arthritis, fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, shoulder periitis, tendonitis, , ≪ / RTI > but is not limited thereto.

In the present invention, "prevention" means any action that inhibits inflammation or slows the progression of the disease by administration of the composition of the present invention.

In the present invention, "treatment" and "improvement" refer to all actions by which administration of the composition of the present invention improves or alleviates the symptoms of an inflammatory disease.

The food composition of the present invention may be prepared in the form of various foods such as beverage, gum, tea, vitamin complex, powder, granule, tablet, capsule, confection, rice cakes, bread and the like. Since the food composition of the present invention is composed of a plant extract having little toxicity and side effects, it can be safely used for prolonged use even for prophylactic purposes.

When the compound of the present invention is contained in the food composition, the amount thereof may be added in a proportion of 0.1 to 50% of the total weight.

Here, when the food composition is prepared in a beverage form, there are no particular limitations other than those containing the food composition at the indicated ratios and may contain various flavors or natural carbohydrates such as ordinary beverages as an additional ingredient. That is, natural carbohydrates include monosaccharides such as glucose, disaccharides such as fructose, sucrose and the like and sugar sugars such as polysaccharide, dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol can do. Examples of the above-mentioned flavors include natural flavors (such as tau martin and stevia extract (for example, rebaudioside A and glycyrrhizin) and synthetic flavors (for example, saccharine and aspartame).

In addition, the food composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants, pectic acid and its salts, alginic acid and its salts, , a pH adjusting agent, a stabilizer, a preservative, a glycerin, an alcohol, a carbonating agent used in a carbonated drink, and the like.

These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0.1 to about 50 parts by weight per 100 parts by weight of the composition of the present invention.

According to another embodiment of the present invention, there is provided a cosmetic composition for preventing or improving an inflammatory disease, comprising a compound represented by the following formula (1) as an active ingredient:

[Chemical Formula 1]

In Formula 1,

L ₁ is a direct bond or C _{1- 6} alkyl group;

R ₁ is hydrogen or C _{1- 6} alkyl group;

R ₂ is -SO ₂ NR ₃ R ₄ ;

R ₃ and R ₄ are each independently hydrogen, C _{1- 6} alkyl or C _{3- 6} cycloalkyl alkyl group;

Wherein R _1, the alkyl group of R ₃ and R _4, the cycloalkyl group of R ₃ and R ₄ are each independently optionally substituted with one or more substituents of C _{1- 6} alkyl group being unsubstituted, substituted, if a plurality of substituents , They may be the same or different from each other.

In the cosmetic composition of the present invention, the above-mentioned compounds overlap with those described above, and the following description is omitted in order to avoid excessive complexity of the description.

However, the type of inflammatory disease to be prevented or improved in the cosmetic composition of the present invention may be edema, dermatitis, allergy or atopy, but is not limited thereto.

The cosmetic composition according to the present invention may be used in cosmetics, nutritional lotions, nutritional essences, massage creams, cosmetic bath additives, body lotions, body milks, bath oils, baby oils, baby powders, shower gels, shower creams, sunscreen lotions, Face and Body Cream, Face and Body Cream, Skin Whitening Cream, Hand Lotion, Hair Lotion, Cosmetic Cream, Jasmine Oil, Face Cream, Skin Cream, Skin Cream, Sunscreen Cosmetics, Bath soap, water soap, soap, shampoo, hand cleanser, medicinal soap {non-medical use}, cream soap, facial wash, whole body cleanser, scalp cleanser, hair rinse, cosmetic soap, tooth whitening gel, . ≪ / RTI > To this end, the composition of the present invention may further comprise a solvent commonly used in the production of a cosmetic composition, or a suitable carrier, excipient or diluent.

For example, water, saline solution, DMSO, or a combination thereof may be used. Examples of the carrier, excipient or diluent include purified water, oil, wax But are not limited to, fatty acids, fatty acid alcohols, fatty acid esters, surfactants, humectants, thickeners, antioxidants, viscosity stabilizers, chelating agents, buffers, lower alcohols and the like. Further, if necessary, it may contain a whitening agent, a moisturizing agent, a vitamin, an ultraviolet screening agent, a perfume, a dye, an antibiotic, an antibacterial agent, and an antifungal agent.

As the oil, hydrogenated vegetable oil, castor oil, cottonseed oil, olive oil, palm oil, jojoba oil and avocado oil may be used. Examples of the wax include wax, wax, carnauba, candelilla, montan, ceresin, liquid paraffin, Can be used.

As the fatty acid, stearic acid, linoleic acid, linolenic acid and oleic acid may be used. As the fatty acid alcohol, cetyl alcohol, octyldodecanol, oleyl alcohol, panthenol, lanolin alcohol, stearyl alcohol and hexadecanol may be used As fatty acid esters, isopropyl myristate, isopropyl palmitate, and butyl stearate may be used. As the surfactant, a cationic surfactant, an anionic surfactant and a nonionic surfactant known in the art can be used, and a surfactant derived from a natural material is preferably used.

In addition, it may contain a hygroscopic agent, a thickening agent, an antioxidant and the like widely known in the field of cosmetics, and the kind and amount thereof are well known in the art.

According to another embodiment of the present invention, there is provided a pharmaceutical composition for preventing or treating an inflammatory disease, comprising a compound represented by the following formula (1) as an active ingredient:

[Chemical Formula 1]

In Formula 1,

L ₁ is a direct bond or C _{1- 6} alkyl group;

R ₁ is hydrogen or C _{1- 6} alkyl group;

R ₂ is -SO ₂ NR ₃ R ₄ ;

R ₃ and R ₄ are each independently hydrogen, C _{1- 6} alkyl or C _{3- 6} cycloalkyl alkyl group;

Wherein R _1, the alkyl group of R ₃ and R _4, the cycloalkyl group of R ₃ and R ₄ are each independently optionally substituted with one or more substituents of C _{1- 6} alkyl group being unsubstituted, substituted, if a plurality of substituents , They may be the same or different from each other.

In the pharmaceutical compositions of the present invention, these compounds are redundant to those described above and the following description is omitted in order to avoid the excessive complexity of the description.

Inflammatory diseases to be prevented or treated in the present invention include edema, dermatitis, allergy, atopy, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, sore throat, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, Sjogren's syndrome, and multiple sclerosis, including, but not limited to, osteoarthritis, rheumatoid arthritis, rheumatoid arthritis, fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, shoulder periitis, tendonitis, , ≪ / RTI > but is not limited thereto.

In the present invention, the pharmaceutical composition may be in the form of a capsule, a tablet, a granule, an injection, an ointment, a powder or a drink, and the pharmaceutical composition may be a human.

The pharmaceutical composition of the present invention may be formulated in the form of oral preparations such as powders, granules, capsules, tablets, aqueous suspensions, etc., external preparations, suppositories and sterilized injection solutions according to a conventional method, . The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may be a binder, a lubricant, a disintegrant, an excipient, a solubilizing agent, a dispersing agent, a stabilizer, a suspending agent, a coloring matter, a perfume or the like in the case of oral administration. A solubilizing agent, an isotonic agent, a stabilizer and the like may be mixed and used. In the case of topical administration, a base, an excipient, a lubricant, a preservative and the like may be used. Formulations of the pharmaceutical compositions of the present invention may be prepared in a variety of ways by mixing with a pharmaceutically acceptable carrier as described above. For example, oral administration may be in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, etc. In the case of injections, they may be formulated in unit dosage ampoules or in multiple dosage forms have. Other, solutions, suspensions, tablets, capsules, sustained-release preparations and the like.

Examples of suitable carriers, excipients and diluents for formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltoditol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil. Further, it may further include a filler, an anticoagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent, an antiseptic, and the like.

The route of administration of the pharmaceutical compositions according to the present invention may be, but is not limited to, oral, intravenous, intramuscular, intraarterial, intramedullary, intradermal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, , Sublingual or rectal. Oral or parenteral administration is preferred.

In the present invention, "parenteral" includes subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intrasynovial, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques. The pharmaceutical compositions of the present invention may also be administered in the form of suppositories for rectal administration.

The pharmaceutical composition of the present invention may be administered orally or parenterally depending on various factors including the activity of the specific compound used, age, weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination, And the dosage of the pharmaceutical composition may be appropriately selected by a person skilled in the art depending on the condition of the patient, the body weight, the degree of disease, the type of drug, the route of administration and the period of time, and is preferably from 0.0001 to 50 mg / kg or 0.001 to 50 mg / kg. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way. The pharmaceutical composition according to the present invention can be formulated into pills, dragees, capsules, solutions, gels, syrups, slurries, suspensions.

The composition of the present invention can be used alone or in combination with conventional therapeutic agents for inflammatory diseases or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers.

The compounds of the present invention inhibit the production of nitric oxide (NO), an inflammatory mediator, and also inhibit the expression of various inflammatory cytokines, interleukin-6 (IL-6), TNF-a and interferon- Can effectively prevent, ameliorate or treat inflammatory diseases, and have no side effects even when administered to human body, and are safe.

Fig. 1 is a graph showing the nitrogen oxide formation inhibitory effect of the compound (U02-A015) according to one embodiment of the present invention in Example 1. Fig.
FIG. 2 is a graph showing the effect of inhibiting the expression of interleukin-6 (IL-6) according to the treatment of the compound (U02-A015) according to an embodiment of the present invention in Example 2. FIG.
FIG. 3 is a graph showing the inhibitory effect of TNF-α on the treatment of the compound (U02-A015) according to one embodiment of the present invention in Example 2. FIG.
FIG. 4 is a graph showing the effect of suppressing the expression of interferon-gamma (IFN-gamma) according to the treatment of the compound (U02-A015) according to one embodiment of the present invention in Example 3. FIG.
FIG. 5 is a graph showing the cytotoxicity evaluation results of the compound (U02-A015) according to one embodiment of the present invention in Example 4. FIG.

Hereinafter, the present invention will be described in more detail with reference to Examples. It will be apparent to those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

Example

[ Synthetic example  One] N, N - dimethyl-2- (2 - ((4 - ((4- Methylpiperazine -1 day) methyl ) Phenyl) amino) pyrimidin-4-yl) benzenesulfonamide

Step 1) Preparation of 2- (2-chloropyrimidin-4-yl) -N, N-dimethybenzenesulfonamide

A mixture of 2,4-dichloropyrimidine (100 mg, 0.671 mmol), (2- (N, N-dimethylsulfamoyl) phenyl) boronic acid compound 14 (184 mg, 0.805 mmol) in an aqueous toluene solution (3 ml) Was added K ₂ CO ₃ (185 mg, 1.34 mmol) and Pd (PPh ₃ ) ₄ (77.6 mg, 0.067 mmol) in EtOH (1 mL) and H 2 O (1 mL) at 60 ° C overnight. The reaction mixture was diluted with water (10 mL), extracted with EtOAc (3 X 10 mL) and cooled to room temperature. The combined organic layers were concentrated in vacuo then dried over Na ₂ SO4, filtered. The residual compound was purified by flash column chromatography on SiO ₂ (1: 4 EtOAc = hexane) to give 2- (2-chloropyrimidin-4-yl) -N, N- dimethylbenzenesulfonamide Mg, 77%).

_{^{1 H NMR (CDCl 3, 400MHz}} ): δ 8.66 (1H, d, J = 4.0 Hz), 8.01 (1H, d, J = 8.0 Hz), 7.65-7.69 (2H, m), 7.54 (1H, d, J = 4.0 Hz), 7.44 (1H, dd, J = 8.0, 4.0 Hz), 2.65 (6H, s).

Step 2) Synthesis of N, N-dimethyl-2- (2 - ((4- (4-methylpiperazin-1-yl) methyl) phenyl) amino) pyrimidin- )

(145 mg, 0.487 mmol) and 4- ((4-methylpiperazin-1-yl) -N, N-dimethylbenzenesulfonamide (100 mg, 0.487 mmol) was added to a mixture of K ₂ CO ₃ (100 mg, 0.731 mmol), Xantphos (14.1 mg, 0.024 mmol) and Pd (dba) 3 0.024 mmol) was refluxed overnight in a suspension of t-BuOH (5 mL). The reaction mixture was diluted with water (10 mL), extracted with EtOAc (3 x 10 mL) and cooled to room temperature. The combined organic layers were concentrated in vacuo then dried over Na ₂ SO _4, filtered. The residue was purified by Prep-TLC (10: 1 CH ₂ Cl ₂ = methanol) to give N, N-dimethyl-2- (2- ((4- ( Methyl) phenyl) amino) pyrimidin-4-yl) benzenesulfonamide (71 mg, 31%).

_{^{1 H NMR (CDCl 3, 400MHz}} ): δ 8.46 (1H, d, J = 8.0 Hz), 8.03 (1H, dd, J = 8.0, 4.0 Hz), 7.57-7.687 (4H, m), 7.46 (1H, dd, J = 8.0, 4.0 Hz), 7.24-7.28 (2H, m), 7.19 (1H, br s), 6.98 ), 2.30-2.56 (8H, m), 2.28 (3H, s).

[ Example  1] Nitrogen oxide (NO) production inhibitory effect

(LPS) - induced nitric oxide (NO) production in Raw264.7 cells, a macrophage of mice.

Specifically, Fetal Bovine Serum (Fetal Bovine Serum) was added to a medium containing phenol-Red free DMEM (Dulbecco's Modified Eagle Medium, Gibco), Raw 264.7 cells were seeded at 4 × 10 ⁵ cells / And then inoculated into a 24-well plate. After 1 day, the compound (U02-A015) prepared in Synthesis Example 1 was treated at a concentration of 0, 10, 25 and 50 μM for 1 hour. One hour later, the cells were treated with 1 μg / ml of LPS and further cultured for 24 hours. Then, the culture was centrifuged at 4 ° C at 2,000 rpm for 5 minutes. Thereafter, 200 μl of the supernatant was collected and dispensed into a new 24-well plate, and the same amount of a grease reagent (Sigma) was added thereto. The mixture was reacted at room temperature for 10 minutes, and then transferred to a microplate reader The absorbance was measured at a wavelength of 540 nm. Calibration curves were prepared using sodium nitrite, and the amount of nitrogen oxides produced in the culture was calculated based on this. The inhibition rate of each sample was calculated by calculating the amount of nitrogen oxides in the LPS-treated group as 100% The results are shown in Fig. DMSO was used as a negative control, and resveratrol (Res) was treated at a concentration of 5 μM instead of the compound of Synthesis Example 1 as a positive control.

As shown in FIG. 1, in the cells treated with LPS alone, the amount of nitrogen oxides (NO) produced increased sharply. On the other hand, the amount of nitrogen oxides (NO) was significantly decreased when the compound of the present invention (U02-A015) , And when the compound was treated at a concentration of 50 μM, an inhibitory effect on NO production of about 50% was confirmed. On the other hand, resveratrol treated with a positive control showed almost no inhibitory effect.

Thus, it was found that the compounds according to the present invention effectively inhibited the production of nitrogen oxides which act as mediators of the inflammatory reaction.

[ Example  2] IL-6 and TNF -α production inhibitory effect

Raw 264.7 cells (4 × 10 ⁵ cells / ml) were inoculated into a 24-well plate and after 1 day The compound (U02-A015) prepared in Synthesis Example 1 was treated at a concentration of 0, 10, 25 and 50 μM for 1 hour. After 1 hour, a portion of the cells were treated with 1 ㎍ / ml of LPS and further cultured for 24 hours. After that, the culture was centrifuged at 2,000 rpm for 5 minutes at 4 DEG C, and 200 mu l of the supernatant was collected separately. The secretion pattern of IL-6 and TNF-α in the supernatant was confirmed by enzyme-linked immunosorbent assay (ELISA). The inhibition rates of IL-6 and TNF-a in the LPS-treated group were calculated as 100%, and the results are shown in Figs. 2 and 3.

As shown in FIGS. 2 and 3, the level of IL-6 and TNF-a expression, which are inflammatory cytokines in the cells, increased sharply when LPS was treated. However, treatment with the compound (U02-A015) And TNF- [alpha] expression levels were decreased in a concentration-dependent manner.

This suggests that the compound of the present invention inhibits the expression of inflammatory cytokines.

[ Example  3] IFN -gamma formation inhibitory effect

Raw 264.7 cells (4 × 10 ⁵ cells / ml) were inoculated into a 24-well plate, and after 1 day passed, the compound (U02-A015) prepared in Synthesis Example 1 was treated at a concentration of 0, 50 μM Lt; / RTI > for 1 hour. One hour later, the cells were treated with 1 ㎍ / ml of LPS and further cultured for 24 hours. After that, the culture was centrifuged at 2,000 rpm for 5 minutes at 4 DEG C, and 200 mu l of the supernatant was collected separately. The expression level of IFN-gamma in the supernatant was confirmed by enzyme-linked immunosorbent assay (ELISA), and the result is shown in FIG.

As shown in FIG. 4, when LPS was treated, the expression level of IFN-gamma, an inflammatory cytokine, in the cells was rapidly increased, Treatment of the compound (U02-A015) according to the present invention revealed that the expression level of IFN-gamma was significantly reduced.

This suggests that the compound of the present invention inhibits the expression of inflammatory cytokines.

[ Example  4] Evaluation of cytotoxicity

Raw264.7 cells were suspended in DMEM medium supplemented with 10% fetal bovine serum (FBS) at a concentration of 3 × 10 ⁴ cells / mL and inoculated on a 24-well plate in 200 μl each. Then, 1 μg / ml of LPS and the compound (U02-A015) (10, 15, 50 μM) prepared in Synthesis Example 1 or LPS and the compound of Synthesis Example 1 were treated and cultured for 20 hours, respectively. 5 mg / ml of MTT solution was added at a rate of 20 μl per well, followed by further incubation for 4 hours. After removal of the supernatant, 100 μl of DMSO was added and the absorbance was measured at 570 nm. Cell viability was calculated according to the following equation with 100% negative control group treated with PBS. The results are shown in Fig.

Cell survival rate (%) = (extract group treated absorbance value / negative control absorbance value) X 100

As shown in FIG. 5, although the cell survival rate was decreased during LPS treatment, it was confirmed that the compound (U02-A015) of the present invention was not toxic to Raw264.7 cells.

Thus, the compounds according to the present invention were found to be safe without side effects.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (11)

N, N-dimethyl-2- (2 - ((4 - ((4-methylpiperazin-1-yl) methyl) phenyl) amino) pyrimidin- A food composition for preventing or improving an inflammatory disease, comprising 2- (2 - ((4 - ((4-methylpiperazin-1-yl) methyl) phenyl) amino) pyrimidin-4-yl) benzenesulfonamide. delete delete delete delete delete The method according to claim 1,
The inflammatory disease is selected from the group consisting of edema, dermatitis, allergy, atopy, asthma, conjunctivitis, periodontitis, rhinitis, otitis, sore throat, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, Wherein the food composition is at least one disease selected from the group consisting of fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, shoulder joint inflammation, tendonitis, nephritis, myositis, hepatitis, cystitis, nephritis, sjogren's syndrome and multiple sclerosis . N, N-dimethyl-2- (2 - ((4 - ((4-methylpiperazin-1-yl) methyl) phenyl) amino) pyrimidin- A cosmetic composition for preventing or ameliorating an inflammatory disease, comprising 2- (2 - ((4 - (4-methylpiperazin-1-yl) methyl) phenyl) amino) pyrimidin-4-yl) benzenesulfonamide. 9. The method of claim 8,
Wherein said inflammatory disease is edema, dermatitis, allergy or atopy. N, N-dimethyl-2- (2 - ((4 - ((4-methylpiperazin-1-yl) methyl) phenyl) amino) pyrimidin- A pharmaceutical composition for the prophylaxis or treatment of inflammatory diseases, comprising 2- (2 - ((4 - (4-methylpiperazin-1-yl) methyl) phenyl) amino pyrimidin-4-yl) benzenesulfonamide as an active ingredient. . 11. The method of claim 10,
The inflammatory disease is selected from the group consisting of edema, dermatitis, allergy, atopy, asthma, conjunctivitis, periodontitis, rhinitis, otitis, sore throat, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, Which is at least one disease selected from the group consisting of fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, shoulder joint inflammation, tendonitis, nephritis, myositis, hepatitis, cystitis, nephritis, sjogren's syndrome and multiple sclerosis Composition.

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