KR20200095085A - Novel tryptamine azide derivative compounds and skin anti-inflammatory or anti-aging compositions comprising the same - Google Patents

Abstract

To a tryptamine azide derivative compound, its isomer, its pharmaceutically acceptable salt, its hydrate or its solvate, and a composition for skin anti-inflammatory or anti-aging comprising the same as an active ingredient, the compound according to the present specification is IL It has the effect of delaying or alleviating aging by reducing the expression of inflammatory factors such as -8 to lower the incidence of inflammation due to the intensification of aging, and by reducing the expression of beta-galactosidase. Accordingly, the composition containing the tryptamine azide derivative compound of the present specification may be variously used as a pharmaceutical composition or a cosmetic composition.

Description

A novel tryptamine azide derivative compound and a composition for skin anti-inflammatory or anti-aging containing the same {NOVEL TRYPTAMINE AZIDE DERIVATIVE COMPOUNDS AND SKIN ANTI-INFLAMMATORY OR ANTI-AGING COMPOSITIONS COMPRISING THE SAME}

The present specification discloses a novel tryptamine azide derivative compound, its isomer, its pharmaceutically acceptable salt, its hydrate or its solvate, and a composition for skin anti-inflammatory or anti-aging comprising the same.

The most representative substances for improving skin wrinkles are retinol and its derivatives, called retinoids, and are known to have good effects in various fields such as psoriasis, aging, cancer, and acne. In addition, retinoids are known to prevent and restore endogenous and photoaging by inhibiting collagen degrading enzyme (MMP-1) when applied to the skin, preventing loss of collagen and stimulating collagen formation.

However, despite these effects, when applied to the skin, it is known to cause local skin irritation reactions such as erythema, itchiness, psoriasis, and scaling. Therefore, there is an increasing need for substances related to anti-aging and anti-inflammatory that are safe for living body, safer and more effective than conventional substances.

Korean Patent Registration No. 11181362

The present inventors prepared a novel tryptamine azide derivative compound, and the compound reduced the expression of IL-8 and beta-galactosidase, which are very important factors for skin anti-inflammatory or anti-aging applications. By experimentally confirming the present invention was completed.

Accordingly, an object of the present invention is a novel tryptamine azide derivative compound, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate or a solvate thereof, and a composition for skin anti-inflammatory or anti-aging comprising the same as an active ingredient. Is to provide.

In one aspect, the present invention provides a novel tryptamine azide derivative compound, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof.

In another aspect, the present invention provides a method for preparing a novel tryptamine azide derivative compound, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof.

In another aspect, the present invention provides a composition for skin anti-inflammatory or anti-aging comprising a novel tryptamine azide derivative compound, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof as an active ingredient. do.

In one aspect, the novel tryptamine azide derivative compound of the present invention reduces the expression of IL-8, a skin inflammatory factor, and decreases the expression of beta-galactosidase, an aging marker, It may be usefully used as a pharmaceutical composition, cosmetic composition, or external skin preparation for the purpose of skin anti-inflammatory or anti-aging.

1 is an ELISA analysis result showing the degree to which the expression of IL-8, a skin inflammatory factor, is decreased after irradiation with ultraviolet light (Ultraviolet A) on aged cells.
2 is an analysis result showing the degree of reduction in the expression of beta-galactosidase, an aging marker, as a result of treating a substance for about 10 days in senescent cells (passage 20 or more).

Term Definition

In the present specification, when a part "includes" a certain component, it means that other components may be further included rather than excluding other components unless specifically stated to the contrary.

Exemplary Of embodiments Explanation

Hereinafter, the present invention will be described in detail.

In exemplary embodiments of the present invention, the present invention is a tryptamine azide derivative compound represented by Formula 1 below, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof.

[Formula 1]

In Formula 1, L1 and L2 are the same as or different from each other, each independently a C1-5 alkylene group, and X is a halogen group.

In the present specification, the alkylene group may be a divalent linear or branched alkyl group having two bonding positions, and the number of carbon atoms may be, for example, 1 to 5, or 1 to 3, and specifically methylene group, ethylene Group, a propylene group, and the like, and preferably an ethylene group.

"Isomers" in this specification are in particular optical isomers (eg, essentially pure enantiomers, essentially pure diastereomers or mixtures thereof), as well as conformational isomers ( conformation isomers (i.e., isomers that differ only in the angle of one or more chemical bonds), position isomers (especially tautomers) or geometric isomers (e.g., cis-trans isomers). do.

In the present specification, "essentially pure" means, for example, when used in connection with enantiomers or diaisomers, specific compounds exemplified by enantiomers or diaisomers are at least about 90%, preferably at least about 95%. , More preferably at least about 97% or at least about 98%, even more preferably at least about 99%, even more preferably at least about 99.5% (w/w).

As used herein, "pharmaceutically acceptable" means approval from the government or equivalent regulatory body for use in animals, more specifically in humans, by avoiding significant toxic effects when used in conventional medicinal dosages. It means available or approved, listed in the pharmacopoeia, or recognized as other general pharmacopeia.

In the present specification, "pharmaceutically acceptable salt" refers to a salt according to an aspect of the present invention that is pharmaceutically acceptable and has a desirable pharmacological activity of a parent compound. The salt is (1) formed of an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, or the like; Or acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl) Benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo [2,2,2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert -Acid addition salts formed from organic acids such as butyl acetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid; Or (2) a salt formed when the acidic proton present in the parent compound is substituted.

In the present specification, "hydrate" refers to a compound to which water is bound, and is a broad concept including an inclusion compound having no chemical bonding force between water and the compound.

In the present specification, "solvate" refers to a high-order compound formed between molecules or ions of a solute and molecules or ions of a solvent.

In one embodiment, Formula 1 may be represented by Formula 2 below.

[Formula 2]

The IUPAC name of the tryptamine azide derivative compound of Formula 2 is 3-(1-((1-(2-(1H-indol-3-yl)ethyl)-1H-1,2,3-triazole-4- Yl)methyl)piperidin-4-yl)-6-fluorobenzo[d]isoxazole (3-(1-((1-(2-(1H-indol-3-yl)ethyl)-1H) -1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-6-fluorobenzo[d]isoxazole).

The compound of Formula 2 may exist as a white solid at room temperature.

In exemplary embodiments of the present invention, the present invention is a method for preparing a tryptamine azide derivative compound, characterized in that it comprises a reaction step represented by the following Scheme 1, a method for preparing a tryptamine azide derivative compound.

[Scheme 1]

In Reaction Scheme 1, L1, L2, and X are as defined in Formula 1.

In addition, compound h of Scheme 1 may be prepared by a reaction step represented by Scheme 1-1 below.

[Scheme 1-1]

In Scheme 1-1, L1 and X are as defined in Scheme 1.

Referring to Schemes 1 and 1-1, first, compound h was synthesized using an isoxazole-based compound (Scheme 1-1), and then reacted with a tryptamine azide compound (Scheme 1), and tryptamine of the present invention An azide derivative compound can be prepared.

In one embodiment, the reaction step represented by Scheme 1 may be represented by Scheme 2 below.

[Scheme 2]

Referring to the above formula, compound h'(178.22 mg, 0.69 mM mmol) was dissolved in acetone (5 mL), and then tryptamine azide compound (3-(2-azidoethyl)-1 H -indole) and Cu ( PPh ₃ ) ₃ Br can be added and reacted with microwave (reaction conditions: 65° C., 1 hr).

The reaction can be checked by TLC (DCM/EA=1/1 v/v, R _f =0.1), and after the reaction is confirmed, the solvent is removed by a rotary evaporator, and then silica column chromatography (first developing solvent DCM/EA = 1/1 v/v, secondary developing solvent MC/MeOH=9/1 v/v) to obtain a white solid compound of Formula 2.

In addition, the compound h'of Scheme 2 may be prepared by a reaction step represented by the following Scheme 2-1.

[Scheme 2-1]

Referring to the above formula, 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole (6-fluoro-3-(piperidin-4-yl)benzo[d] which is an isoxazole-based compound ]isoxazole) was dissolved in DCM (25 mL), then triethyl amine (TEA) was added and stirred for 30 minutes, and propargyl chloride (C ₃ H ₃ Cl) was added, followed by stirring at room temperature for 4 hours.

When the reaction is complete, work-up with DCM and water, the obtained organic layer was filtered under reduced pressure by removing moisture with MgSO ₄ , and then the residue obtained by concentration under reduced pressure was dissolved with a very small amount of EA (Ethyl acetate). Thereafter, an excess of HEX (Hexane) can be recrystallized to obtain compound h'.

However, the reaction temperature, the solvent, and the like are exemplary, and are not limited thereto as long as the reaction can be sufficiently performed.

In exemplary embodiments of the present invention, the present invention is a skin comprising a tryptamine azide derivative compound represented by Chemical Formula 1, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient. It is an anti-inflammatory or anti-aging composition.

In one embodiment, the concentration of the active ingredient may be 0. 0001-5% by weight based on the total weight of the composition.

In one embodiment, the concentration of the active ingredient may be 0.0001-5 wt% based on the total weight of the composition, for example, 0.001 wt% or more, 0.01 wt% or more, 0.1 wt% or more, 1 wt% or more, It may be 9 wt% or less, 8 wt% or less, 7 wt% or less, 6 wt% or less, 5 wt% or less, 4 wt% or less, 3 wt%, 2 wt% or less, or 1 wt% or less. In one embodiment of the present specification, preferably, the concentration of the active ingredient may be 0.3 to 2% by weight.

If the concentration is less than 0.0001% by weight, skin anti-inflammatory or anti-aging effects may be insignificant, and if the concentration is more than 5% by weight, cytotoxicity may occur.

In one embodiment, the composition may be a pharmaceutical composition, a cosmetic composition, an external preparation for skin, or a food composition.

The tryptamine azide derivative compound of Formula 1 according to the present invention can be applied to various fields, and preferably, can be used as an active ingredient of a cosmetic composition. When the tryptamine azide derivative compound is included as an active ingredient, it exhibits an anti-inflammatory effect by inhibiting the expression of IL-8 factor, an inflammatory factor even when irradiated with ultraviolet rays, and beta-galactosidase, a skin aging marker -galactosidase) can be delayed by inhibiting the expression.

The composition according to an embodiment of the present invention may be a pharmaceutical composition for skin anti-inflammatory, and pharmaceutical adjuvants such as preservatives, stabilizers, hydrating agents or emulsifying accelerators, salts and/or buffers for controlling osmotic pressure, and other therapeutic agents. It may further contain useful substances, and may be formulated in various oral or parenteral dosage forms according to conventional methods.

The oral administration agents include, for example, tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, powders, powders, granules, granules, pellets, etc., and these formulations include surfactants in addition to active ingredients. , Diluents (e.g. lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine), lubricants (e.g. silica, talc, stearic acid and magnesium or calcium salts thereof and polyethylene glycol) . Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, optionally starch, agar, alginic acid or sodium salts thereof. It may contain pharmaceutical additives such as disintegrants, absorbents, colorants, flavors, and sweeteners such as. The tablets can be prepared by conventional mixing, granulating or coating methods. In addition, the parenteral dosage form may be a transdermal dosage form, for example, injections, drops, ointments, lotions, gels, creams, sprays, suspensions, emulsions, suppositories, patches, etc. However, it is not limited thereto.

The pharmaceutical composition according to an embodiment of the present invention may be administered parenterally, rectal, topically, transdermally, or subcutaneously.

The determination of the dosage of the active ingredient is within the level of those skilled in the art, and the daily dosage of the drug varies depending on various factors such as the degree of progression of the target to be administered, the time of onset, age, health condition, complications, etc. On a basis, the composition may generally be 0.5 mg/kg/day to 10 mg/kg/day, such as 1 mg/Kg to 9 mg/Kg, 2 mg/Kg to 8 mg/Kg, or 3 mg/kg to 7 mg/kg , Preferably, 4mg/kg to 6mg/kg may be dividedly administered 1 to 3 times a day, and the dosage is not intended to limit the scope of the present invention by any method.

The composition according to an embodiment of the present invention may be a cosmetic composition, and the cosmetic composition contains a cosmetically or dermatologically acceptable medium or base. These are all formulations suitable for topical application, such as solutions, gels, solids, dough anhydrous products, emulsions obtained by dispersing the oil phase in an aqueous phase, suspensions, microemulsions, microcapsules, microgranules, or ionic (liposomes) And it may be provided in the form of a nonionic vesicle dispersant, or in the form of a cream, skin, lotion, powder, ointment, spray or conceal stick. These compositions can be prepared according to conventional methods in the art. The composition according to the invention may also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.

The cosmetic composition according to an embodiment of the present invention is not particularly limited in its formulation, for example, softening lotion, astringent lotion, nourishing lotion, nourishing cream, massage cream, essence, eye cream, eye essence, cleansing It can be formulated into cosmetics such as cream, cleansing foam, cleansing water, pack, powder, body lotion, body cream, body oil and body essence.

When the formulation of the present invention is a paste, cream or gel, animal fibers, plant fibers, wax, paraffin, starch, tracant, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide, etc. may be used as a carrier component. Can.

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component. In particular, in the case of a spray, additional chlorofluorohydrocarbon, propane / May contain propellants such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, a solvating agent or an emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.

When the formulation of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline Cellulose, aluminum metahydroxide, bentonite, agar or tracant, and the like may be used.

When the formulation of the present invention is a surfactant containing cleansing, as a carrier component, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linoline derivatives or ethoxylated glycerol fatty acid esters may be used.

The cosmetic composition according to an embodiment of the present invention may further include functional additives and ingredients included in general cosmetic compositions in addition to the active ingredients. The functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingo lipids, and seaweed extract.

In addition to the above functional additives, the cosmetic composition of the present invention may also contain components contained in a general cosmetic composition as necessary. Other components included include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, blood circulation Accelerators, cooling agents, limiting agents, purified water, and the like.

In addition, the composition according to an embodiment of the present invention may be an external preparation for skin, and the external preparation for skin is a generic term that may include anything applied outside the skin, and various formulations of cosmetics and pharmaceuticals may be included therein.

In addition, the composition according to an embodiment of the present invention may be a food composition, the food composition may be a liquid or solid formulation, tablets, capsules, soft capsules, pills, granules, beverages (drinks) , A diet bar, chocolate, caramel formulation or confectionery formulation, and the formulation is not particularly limited. In addition to the above active ingredients, the food composition of the present invention may appropriately contain excipients, sugars, flavors, pigments, fats and oils, proteins, and the like, if necessary.

Hereinafter, the present invention will be described in more detail through the following examples. However, the following implementation is provided only for the purpose of illustration to aid understanding of the present invention, and the scope and scope of the present invention are not limited thereto.

Example : 3-(1-((1-(2-(1H-indol-3-yl)ethyl)-1H-1,2,3- Triazole -4- days) methyl )Piperidin-4-yl)-6-fluorobenzo[d]isooxazole (3-(1-((1-(2-(1H-indol-3-yl)ethyl)-1H-1, Preparation of 2,3-triazol-4-yl)methyl)piperidin-4-yl)-6-fluorobenzo[d]isoxazole)

[Preparation of compound h']

6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole (6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole), an isoxazole-based compound (2 g , 9.08 mmol) was dissolved in DCM (25 mL), TEA (triethyl amine) (4.45 mL, 31.8 mmol) was added and stirred for 30 minutes, and propargyl chloride (C ₃ H ₃ Cl) (1.67 mL, 10 mmol) Was added and stirred at room temperature for 4 hours.

After the reaction was completed, the resulting organic layer was worked-up with DCM and water, and the obtained organic layer was filtered under reduced pressure by removing moisture with MgSO ₄ , and then the residue obtained by concentration under reduced pressure was converted into a very small amount of EA (Ethyl acetate). After dissolving, 6-fluoro-3-(1-(prop-2-ynyl)piperidin-4-yl)benzo[d]isoxazole (6-fluoro-3) was recrystallized with an excess of HEX (Hexane). -(1-(prop-2-ynyl)piperidin-4-yl)benzo[d]isoxazole)(Compound h') was obtained (white solid, 1.83 g, 7.1 mmol, yield 78.03%).

TLC confirmation: EA: HEX = 1: 1, R _f =0.6

¹ H NMR (CDCl ₃ , 400MHz) δ 2.09 (m, 4H), 2.27 (m, 1H), 2.42 (m, 2H), 3.05 (m, 3H), 3.37 (d, 2.4Hz, 2H), 7.03 ( td, 8.8Hz, 2.0Hz, 1H), 7.22 (dd, 8.8Hz, 2.0Hz, 1H), 7.67 (dd, 8.8Hz, 5.2Hz, 1H)

(3-(1-((1-(2-(1H-indol-3-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl) -6-Fluorobenzo[d]isooxazole (3-(1-((1-(2-(1H-indol-3-yl)ethyl)-1H-1,2,3-triazol-4-yl) ) Preparation of methyl)piperidin-4-yl)-6-fluorobenzo[d]isoxazole)]

Compound h'(178.22 mg, 0.69 mmol) was dissolved in acetone (5 mL), then tryptamine azide compound (3-(2-azidoethyl)-1 H- indole) (141.33 mg, 0.76 mmol) and Cu (PPh ₃ ) ₃ Br (64 mg, 0.069 mmol) was added and reacted with microwave (reaction conditions: 65° C., 1 hr).

The reaction was checked by TLC (DCM/EA=1/1 v/v, R _f =0.1), and after the reaction was confirmed, the solvent was removed with a rotary evaporator, and then silica column chromatography (first developing solvent DCM/EA= Purified by 1/1 v/v, secondary developing solvent MC/MeOH=9/1 v/v), 3-(1-((1-(2-(1H-indol-3-yl)ethyl)- 1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-6-fluorobenzo[d]isoxazole (a compound of Formula 2) was obtained (white solid, 290 mg, yield 94.9%). The melting point and NMR results are as follows.

Melting point: 87℃

¹ H NMR (DMSO, 400MHz) δ 1.75(m, 2H), 1.96(d, J =11.2Hz, 2H), 2.07(t, J =11.2Hz, 2H), 2.84(d, J =11.2Hz, 2H ), 3.06(m, 1H), 3.24(t, J =6.6Hz, 2H), 3.54(s, 2H), 4.59(d, J =6.6Hz, 2H), 6.93(t, J =6Hz, 1H) , 7.02(t, J =6Hz, 1H), 7.04(s, 1H), 7.28(d, J =8.2Hz, 1H), 7.47(d, J =8.2Hz, 1H), 7.66(d, J =9.2 Hz, 1H), 7.89 (s, 1H), 7.97 (q, J =9.2H, 5.6 Hz, 1H), 10.82 (s, 1H); ¹³ C NMR (DMSO, 100MHz) δ 26.64, 30.39, 34.26, 50.85, 53.01, 53.51, 97.32, 97.58, 111.24, 111.46, 112.26, 112.51, 117.28, 118.24, 119.71, 122.32, 122.57, 122.64, 126.68, 123.26 , 136.29, 161.08; ESI-HRMS: [MH] ⁺ 445.8 (calcd 445.5).

Test example : IL-8 factor and beta-galactosidase (beta- galactosidase ) For analysis

Fibroblast culture, UV irradiation and material treatment

Fibroblasts (normal human fibroblast) (Lonza, Switzerland) were grown in a 60 mm culture dish (cultured in a CO ₂ incubator) with 10% FBS-DMEM culture medium, and then 10 J/cm ² Ultraviolet A was irradiated, and the example compound And the compounds of Table 1 were treated by 10 μM, respectively, and grown for 24 hours in a culture medium without serum, and then the culture medium and the treated cells were collected, respectively.

Sample No Structure MW IUPAC name HBU-226

393.5 (E)-isopropyl 3-(allylthio)-2-(3-(3,4-dimethoxyphenyl)acrylamido)propanoate HBU-259

343.37 (E)-3-(3,4-dimethoxyphenyl)-N-(4-hydroxy-3-methoxybenzyl)acrylamide HBU-375

376.41 1-(4-((1-(2-(1H-indol-3-yl)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-hydroxyphenyl)ethanone HBU-376

390.44 1-(2-((1-(2-(1H-indol-3-yl)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-methoxyphenyl)ethanone HBU-454

374.46 N-((1-(2-(1H-indol-3-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)benzo[d]thiazol-2-amine HBU-463

251.28 (E)-3-(3,4-dimethoxyphenyl)-N-(2-hydroxyethyl)acrylamide

ELISA (enzyme-linked immunosorbent assay) assay (according to Kit Protocol)

Capture antibody of each IL-8 (4 ug/ml) and (procollagen) (4 μg/ml) was diluted in PBS (Phosphate buffered saline) medium and treated in a 96 well plate. Reaction for 12 hours. After aspiration from each well, wash three times with a wash buffer (400 μl), and then use a reagent diluent (1% Bovine Serum Albumin, PBS, 300 μl) for each standard. (standard) and the culture medium sample (100 μl) collected after the fibroblast culture, ultraviolet irradiation, and material treatment were each treated and reacted at room temperature for 2 hours. After aspiration from each well, after washing three times with a wash buffer (400 μl), each detection antibody (100 μl) was reacted at room temperature for 2 hours. .

After aspiration from each well, after washing three times with a wash buffer (400 μl), Streptavidin-HRP (100 μl) was added, and then during reaction for 20 minutes at room temperature, Blocked the light. Thereafter, aspiration was performed from each well, washed three times with a wash buffer (400 μl), and then a substrate solution containing a substrate was added and reacted at room temperature for 20 minutes. Finally, a stop solution (50 μl) was added to stop further reaction, and then measured with a microplate reader (450 nm to 570 nm).

The results of ELISA analysis for IL-8 according to the above ELISA assay (UVA), and the results of changes in the expression of IL-8 when treated with 10 μM of each substance compared to the irradiation group are shown in FIG. 1, and each substance is shown in the following table. Same as 1.

Referring to Figure 1, compared to the ultraviolet-treated control group (UVA), #226 (4% increase), #259 (2% decrease), #375 (1% decrease), #376 (8% increase), # Values of 384 (Example compound) (22% decrease), #454 (5% increase), and #463 (2% decrease) were shown, indicating that the Example compound significantly inhibited the expression of IL-8.

In addition, compared to the positive control group (indicated by UVA+PC on the drawing, Qurecetin) treated with ultraviolet (UVA) together, the inflammatory factor was reduced to a level similar to that of the tryptamine azide derivative according to the present invention. It was confirmed that the compound exhibits an anti-inflammatory effect by having an effect of reducing IL-8, an inflammatory factor that increases by UV irradiation.

Beta-galactosidase (beta- galactosidase ) Aging Marker Staining assay

(According to Kit Protocol)

After culturing the aged fibroblasts (passage at least 25 or more) at a ratio of about 50% (60 mm culture dish), each of the substances in Table 1 was treated with 10 μM for 10 days, and then experimented as follows. Proceeded.

After washing 3 times with 1X PBS (Phosphate buffered saline), 1.5 ml of 1X fixation buffer was treated, wait at least 10 minutes, and then wash 3 times with 1X PBS (Phosphate buffered saline). I did. Afterwards, 1 ml of a dye prepared according to the kit protocol (based on 10 ml-Reagent B (125 μl), Reagent C (125 μl), X-gal solution (0.25 ml), 8.5 ml of distilled water) was treated on the fixed senescent cells. It was kept for at least 2 hours.

Subsequently, it was determined whether or not the amount of expression of beta galactosidase (aged cells appeared blue) in the cell group treated with each substance was decreased with an optical microscope.

The results of the analysis on the degree of staining of the stomach beta-galactosidase are shown in FIG. 2. Referring to Figure 2, despite the treatment of the substance for about 10 days in senescent cells (passage 20 or more), when the compound of the present invention (represented by #384) is treated together, significantly beta-galactosidase ( beta-galactosidase) expression was inhibited.

Specifically, there is little difference between #226, #259, #375, #376, #454, and #463 compared to the negative control group, whereas when the example compound (#384) was treated, the amount of aged cells It was confirmed that this decreased by more than 40%.

In conclusion, it was possible to predict the aging delay or anti-aging effect of the trypta azide derivative compound according to the present invention.

Claims (15)

A tryptamine azide derivative compound represented by the following Formula 1, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof:
[Formula 1]

In Formula 1,
L1 and L2 are the same as or different from each other, and are each independently an alkylene group having 1 to 5 carbon atoms,
X is a halogen group. The method of claim 1,
Formula 1 is a tryptamine azide derivative compound represented by the following Formula 2, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof:
[Formula 2]

A method for preparing a tryptamine azide derivative compound according to claim 1 or 2, characterized in that it comprises a reaction step represented by the following Scheme 1, wherein the method for preparing a tryptamine azide derivative compound:
[Scheme 1]

In Scheme 1,
L1, L2 and X are as defined in Formula 1. The method of claim 3,
Compound h of Scheme 1 is a method for preparing a tryptamine azide derivative compound, characterized in that it is prepared by a reaction step represented by the following Scheme 1-1:
[Reaction Scheme 1-1]

In Scheme 1-1,
L1 and X are as defined in Scheme 1. The method of claim 3,
The reaction step represented by Scheme 1 is a method for preparing a tryptamine azide derivative compound, characterized in that it is represented by the following Scheme 2:
[Scheme 2]

The method of claim 5,
Compound h'of Scheme 2 is a method for preparing a tryptamine azide derivative compound, characterized in that it is prepared by a reaction step represented by the following Scheme 2-1:
[Scheme 2-1]

A composition for skin anti-inflammatory or anti-aging comprising the tryptamine azide derivative compound according to claim 1 or 2, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof as an active ingredient. The method of claim 7,
Composition, characterized in that the concentration of the active ingredient is 0. 0001-5% by weight based on the total weight of the composition. The method of claim 7,
The composition is a composition for skin anti-inflammatory, a composition characterized in that it reduces the expression of IL-8 factor. The method of claim 7,
The composition is a composition for skin anti-aging, characterized in that it reduces the expression of beta-galactosidase (beta-galactosidase). The method of claim 7,
The composition is a composition, characterized in that the pharmaceutical composition for skin anti-inflammatory. The method of claim 7,
The dosage of the tryptamine azide derivative compound according to claim 1 or 2, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof according to claim 1 or 2 by administration of the composition is 5 mg/kg/day to 10 mg Composition, characterized in that / kg / day. The method of claim 7,
The composition is a composition for skin anti-inflammatory or anti-aging, characterized in that the cosmetic composition. The method of claim 7,
The composition is a composition for external use for skin. The method of claim 7,
The composition is characterized in that the food composition.

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