KR20150029273A - New cyclic skin whiteninig agent - Google Patents

Abstract

In the present invention, provided is a skin whitening agent, which is easily synthesized without side effects for skin and has an outstanding effect of inhibiting pigmentation on skin due to an outstanding effect of inhibiting the creation of melanine where a cyclic derivative compound or pharmaceutically acceptable salt thereof has a chemical structure in formula (I) and is accordingly used to achieve the purpose of the present invention. In the present invention, provided is a cyclic derivative compound or pharmaceutically acceptable salt thereof, which has an effect of whitening skin and a chemical structure in formula (I) where A is derived from an aromatic cyclic compound; B is derived from among hydrogen, O which is oxo, NH_2 which is amino, NH which is imino, C1-C10 of saturated or unsaturated straight or branched chain alkyl group, alkoxy, mono alkyl amino group or dialkyl amino group; and C_n, C_n+1 and C_n+2 are three neighboring carbons in the cyclic compound wherein n is a positive integer.

Description

[0001] The present invention relates to a new cyclic skin whitening agent containing a novel cyclic compound,

The present invention relates to a novel skin lightening agent, and more particularly, to an external preparation for skin, specifically, a composition for external application for skin which is excellent in whitening effect.

Skin melanogenesis is a defense mechanism against stimuli such as ultraviolet light in melanocyte-producing cells (melanocyte), and a large amount of melanin produced by the melanin is transferred to keratinocyte and accumulated on the skin surface layer Results. Although melanin protects the skin, hyperpigmentation of the skin causes skin irritation, freckles, darkening of the skin after inflammation of the skin and aging pigmentation spots. This causes the discomfort of the person not only the cosmetic discomfort but also the psychological negative affect on the social activities. . Melanin is produced by tyrosine tyrosine, an enzyme called tyrosinase, converted into DOPA or dopaquinone, and then enzymatically oxidized to form an abnormal deposit in the skin And it is known that it produces spots and black spots. Materials for inhibiting melanin production such as hydroquinone, arbutin, vitamin C and derivatives thereof have been developed for the relief, prevention and treatment of such pigment deposits, stains and spots, and whitening cosmetics containing them have been disclosed And Korean Patent Publication No. 2005-0509848 discloses a whitening cosmetic composition containing a keractone derivative isolated from Korean Patent Publication No. 2005-0509848. Korean Patent Publication No. 2005-0479741 discloses a whitening cosmetic containing a glucose acylated derivative. Of these, hydroquinone is generally recognized for its effectiveness, but is generally limited in its use because of its sensitivity. Ascorbic acid is easily oxidized, the cosmetic compounded with it causes discoloration and irregularities, and the substances derived from plant extracts are difficult to maintain the homogeneity of the product due to the great difference in the effect according to the plant area of the plant, and glucose acylated derivatives The synthesis efficiency is very low.

Therefore, the present inventors continued their research to develop a substance having a high synthesis efficiency and inhibited melanin production, synthesized derivatives of the novel cyclic compounds of the present invention, confirmed their excellent whitening effect, Completed.

It is an object of the present invention to provide a composition for skin whitening which is easy to synthesize, has no adverse effects on the skin, has excellent melanin production inhibiting effect and is excellent in skin pigmentation inhibition effect.

The above object can be achieved by a cyclic derivative compound having a chemical structure represented by the following general formula (I) or a pharmacologically acceptable salt thereof.

는 방향족 고리화합물로부터 유래되고, B는 수소, 옥소(oxo, =O), 아미노(amino, -NH₂), 이미노(imino, =NH), C₁ 내지 C₁₀의 포화 혹은 불포화된 직쇄 또는 분지쇄의 알킬기, 알콕시, 모노알킬아미노기, 또는 디알킬아미노기이고, In the above formula

B is hydrogen, oxo (= O), amino (NH ₂ ), imino (= NH), C ₁ to C ₁₀ saturated or unsaturated straight chain or branched Branched alkyl group, alkoxy, monoalkylamino group, or dialkylamino group,

C _n , C _{n + 1} and C _{n + 2} are three adjacent carbons present in the cyclic compound, and n is a positive integer.

R ₁ is hydrogen, hydroxy, a saturated or unsaturated straight-chain or branched alkyl or alkoxy group,

X and Y are selected from hydrogen, saturated or unsaturated straight or branched chain alkoxy or acyloxy, and one of X and Y is hydrogen.

R ₂ , R _3, R ₄ and R ₅ are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxaldehyde, Lt; / RTI >

The compounds according to the present invention are easy to synthesize, have no adverse effects on the skin, exhibit a melanin inhibitory effect and an inhibitory effect on pigment deposition, so that the composition containing the same can be used as a composition for skin whitening.

The present invention provides a compound having a chemical structure of the following general formula (I) or a pharmacologically acceptable salt thereof, which is excellent in whitening effect:

는 방향족 고리화합물로부터 유래되고, B는 수소, 옥소(oxo, =O), 아미노(amino, -NH₂), 이미노(imino, =NH), C₁ 내지 C₁₀의 포화 혹은 불포화된 직쇄 또는 분지쇄의 알킬기, 알콕시, 모노알킬아미노기, 또는 디알킬아미노기이고, In the above formula

B is hydrogen, oxo (= O), amino (NH ₂ ), imino (= NH), C ₁ to C ₁₀ saturated or unsaturated straight chain or branched Branched alkyl group, alkoxy, monoalkylamino group, or dialkylamino group,

C _n , C _{n + 1} and C _{n + 2} are three adjacent carbons present in the cyclic compound, and n is a positive integer.

R ₁ is hydrogen, hydroxy, a saturated or unsaturated straight-chain or branched alkyl or alkoxy group,

X and Y are selected from hydrogen, saturated or unsaturated straight or branched chain alkoxy or acyloxy, and one of X and Y is hydrogen.

R ₂ , R _3, R ₄ and R ₅ are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxaldehyde, Lt; / RTI >

The cyclic compound is an aromatic compound and may be a structure having one to four or more rings bonded thereto, and may be a homo or heterocyclic compound. The heterocyclic compound preferably contains oxygen or nitrogen in the ring structure, or may contain both oxygen and nitrogen.

화합물로는 특별히 한정되지는 않으나, 예를 들어 벤젠, 피리딘, 피리다진, 피리미딘, 인덴, 인단, 벤조퓨란, 벤조티오펜, 인돌, 벤지미다졸, 벤조티아졸, 퓨린, 나프탈렌, 퀴놀린, 이소퀴놀린, 쿠마린, 시네올린, 퀴녹살린, 플라본, 플라반, 바이벤질, 1,3-디페닐-프로판, 1,3-디페닐-2-프로펜 등을 들 수 있다.The compound of formula (I)

Examples of the compound include, but are not limited to, benzene, pyridine, pyridazine, pyrimidine, indene, indane, benzofuran, benzothiophene, indole, benzimidazole, benzothiazole, purine, naphthalene, quinoline, iso Quinoline, coumarin, cineolein, quinoxaline, flavone, flavan, bibenzyl, 1,3-diphenyl-propane and 1,3-diphenyl-2-propene.

는 적어도 1개 이상의 히드록시기가 각각 결합된 고리화합물로부터 유래되어질 수 있으며, 바람직하게는 5원환 또는 6원환이 1개 또는 2개가 결합된 고리화합물로 구조 내에 적어도 1개 이상, 바람직하게는 1개 ~ 6개의 인접하는 탄소에 히드록시기가 결합된 화합물로부터 유래될 수 있다. In the above general formula (1)

May be derived from a cyclic compound having at least one hydroxy group bonded thereto, preferably a cyclic compound having one or two of a five-membered ring or six-membered ring bound thereto, and at least one, Lt; RTI ID = 0.0 > 6 < / RTI > adjacent carbons.

In the above general formula (1), B represents hydrogen, oxo, ═O, amino, -NH ₂ , imino, ═NH, C ₁ to C ₁₀ saturated or unsaturated straight- Chain alkyl group, alkoxy, monoalkylamino group, or dialkylamino group.

In the general formula (1), R ₁ is hydrogen, hydroxy, saturated or unsaturated straight-chain or branched alkyl or alkoxy, preferably C ₁ - An alkyl or alkoxy of saturated or unsaturated C ₁₀ straight or branched chain, more preferably the case where R ₁ is alkyl C ₁ to C ₁₀ , more preferably C ₄ - And C ₈ saturated or unsaturated straight-chain or branched-chain alkyl, the case where the R ₁ is alkoxy C ₁ to C ₁₂ , more preferably C ₂ - For C ₁₀ alkoxy of saturated or unsaturated straight or branched chain.

X and Y are hydrogen and a saturated or unsaturated straight-chain or branched alkoxy or acyl group, preferably C ₁ - Alkoxy or acyloxy of the C ₁₀ saturated or unsaturated straight or branched chain, more preferably the case where X and Y are alkoxy C ₂ to C ₁₀ , more preferably C ₄ - If alkoxy of saturated or unsaturated C ₈ straight or branched chain, wherein the X and Y is an acyloxy C ₁ to C ₁₂ , more preferably C ₂ - For C ₁₀ acyloxy is a saturated or unsaturated straight or branched chain. And one of X and Y is hydrogen.

R _2, R ₃ , R ₄ and R ₅ may be the same or different and each represents hydrogen, hydroxy, vinyl, oxo and alkyl, alkoxy, acyloxy, acyloxymethyl, nitrile, Aldehyde, carbonyl chloride, and aldehyde, but is not limited thereto.

가 벤젠으로부터 유래된다면 n은 최대 4의 값을 가질 수 있다.
C _n , C _{n + 1} and C _{n + 2} are adjacent three carbons present in the cyclic compound, and n has a positive number and can be defined within the range of the total number of atoms constituting the ring. For example,

Is derived from benzene, n can have a value of up to 4.

Hereinafter, the present invention will be described in more detail.

The compound of the present invention is an aromatic ring compound, preferably a homo or heterocyclic structure compound in which one or two of a 5-membered ring or 6-membered ring is bonded, as shown in the following reaction formula, wherein a hydroxy group is bonded to at least one carbon in the structure The compound is obtained by dissolving the compound in an appropriate organic solvent and slowly adding dropwise one or more kinds of acyl halide or alkyl halide in a suitable equivalent ratio to effect ester reaction or ether reaction with a hydroxyl group in the cyclic structure , And hydrogenation of the reaction product. The organic solvent usable in the reaction is not particularly limited, and examples thereof include dichloromethane, chloroform, tetrahydrofuran, acetonitrile, dimethylformamide, pyridine, and dimethylformamide. In particular, sodium hydride (NaH) or potassium carbonate (K ₂ CO ₃ ) can be used as a reaction catalyst.

[Reaction Scheme 1]

In the above Reaction Scheme 1, R < ₆ > is a _C1-12 saturated or unsaturated alkyl, both straight-chain and branched.

R ₂ , R _3, R ₄ and R ₅ are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxaldehyde, Lt; / RTI >

[Reaction Scheme 2]

In the above Reaction Scheme 2, R < ₆ > is a _C1-12 saturated or unsaturated alkyl, both straight-chain and branched.

R ₂ , R _3, R ₄ and R ₅ are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxaldehyde, Lt; / RTI >

[Reaction Scheme 3]

In the above Reaction Scheme 3, R ₈ is hydrogen and C _1-12 saturated or unsaturated alkyl, both linear and branched, and R ₇ is a C _1-12 saturated or unsaturated alkyl or acyl, linear or branched Everything is possible.

B is selected from the group consisting of hydrogen, oxo (═O), amino (-NH ₂ ), imino (═NH), C ₁ to C ₁₀ saturated or unsaturated straight or branched chain alkyl groups, An alkylamino group, or a dialkylamino group.

R ₂ , R _3, R ₄ and R ₅ are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxaldehyde, Lt; / RTI >

[Reaction Scheme 4]

In the above Reaction Scheme 4, R ₈ is hydrogen and C _1-12 saturated or unsaturated alkyl, both straight-chain and branched, and R ₇ is C _1-12 saturated or unsaturated alkyl or acyl, straight-chain or branched Everything is possible.

B is selected from the group consisting of hydrogen, oxo (═O), amino (-NH ₂ ), imino (═NH), C ₁ to C ₁₀ saturated or unsaturated straight or branched chain alkyl groups, An alkylamino group, or a dialkylamino group.

R ₂ , R _3, R ₄ and R ₅ are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxaldehyde, Lt; / RTI >

가 벤젠이고, R_2, R_3, R₄ 및 R₅ 가 수소인 경우 제조되어지는 물질명을 예시하면 하기와 같다.As a more specific example of the compound represented by the general formula (I) according to the present invention, a compound of the ring structure

Is benzene, and R _2, R _3, R ₄ and R ₅ are hydrogen, the name of the material to be produced is as follows.

For example, there may be mentioned 2-methoxybenzoic acid methyl ester, 2-ethoxybenzoic acid ethyl ester, 2-propoxybenzoic acid propyl ester, 2-butoxybenzoic acid butyl ester, 2-hexyloxybenzoic acid hexyl ester, 2-octyloxybenzoic acid stearyl ester, 2-decyloxybenzoic acid decyl ester, and the like, but are not limited thereto.

Among the materials prepared through the reaction formula 1, R _{2 ,} R _{3 ,} R ₄ And R < ₅ > are hydrogen and R < ₆ > is pentyl.

For example, 2-pentyloxy-benzoic acid pentaery ester, 3-pentyloxy-benzoic acid pentaery ester, 1-pentyloxy-2-naphthoate acid pentaery ester, 3-pentyloxy- Ester, 3-pentyloxy-4-pyridinecarboxylic acid pentaery ester, 3-pentyloxy-4-quinolinecarboxylic acid pentaery ester, and the like.

가 벤젠이고, B가 옥소 이고, R_{2 ,} R_{3 ,} R₄ 및 R₅이 수소이며 R₈이 메틸 일 때 제조되어지는 물질명을 예시하면 하기와 같다.Also, among the materials prepared through Scheme 3,

Is benzene, B is oxo, R _{2 ,} R _{3 ,} R ₄ And when R ₅ is hydrogen and R ₈ is methyl, the name of the material to be produced is as follows.

For example, there may be mentioned, for example, 1- (2-methyloxy-phenyl) -ethanone, 1- (2-pentyloxy- 2-acetyl-phenyl ester, 2-ethylhexanoic acid 2-acetyl-phenyl ester and octanoic acid 2-acetyl-phenyl ester.

The present invention also provides a pharmaceutical composition for the prevention, treatment and whitening of hypercholesterolemia, spots, freckles and black spots, comprising the compound of the general formula (I) or a pharmacologically acceptable salt thereof as an active ingredient .

The compounds of the present invention represented by the above general formula (I) may be prepared as pharmaceutically acceptable salts and solvates according to methods conventional in the art.

Salts are useful as acid addition salts formed by pharmaceutically acceptable free acids. The acid addition salt is prepared by a conventional method, for example, by dissolving the compound in an excess amount of an acid aqueous solution and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. The molar amount of the compound and the acid or alcohol (e.g., glycol monomethyl ether) in water may be heated and then the mixture may be evaporated to dryness, or the precipitated salt may be subjected to suction filtration.

As the free acid, organic acids and inorganic acids can be used. As the inorganic acids, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid and the like can be used. Examples of the organic acids include methanesulfonic acid, p- toluenesulfonic acid, acetic acid, trifluoroacetic acid, (Such as citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid and the like.

In addition, bases can be used to make pharmaceutically acceptable metal salts. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess amount of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, it is preferable for the metal salt to produce sodium, potassium or calcium salt in particular, and the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (for example, silver nitrate).

The pharmaceutically acceptable salts of the above general formula (I) include, unless otherwise indicated, salts of acidic or basic groups which may be present in the compounds of general formula (I). For example, pharmaceutically acceptable salts include the sodium, calcium, and potassium salts of the hydroxy group, and other pharmaceutically acceptable salts of the amino group include hydrobromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate rate, methane sulfonate (mesylate) and p - toluene sulfonate (tosylate) and a salt, the salt manufacturing method or manufacturing process known in the art ≪ / RTI >

The compositions comprising the compounds of the present invention may further comprise suitable carriers, excipients or diluents according to conventional methods.

Examples of carriers, excipients and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The composition containing the compound of the present invention can be formulated in the form of powders, granules, tablets, capsules, oral preparations such as suspensions, emulsions, syrups and aerosols, external preparations, suppositories or sterilized injection solutions, Can be used.

More specifically, when formulating the composition, it can be prepared using a diluent or an excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and the like. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose ), Lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, syrups and the like. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances and preservatives . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.

The compositions for prevention, treatment and whitening of hypercholesterolemia, spots, freckles and black spots, which comprise the compound of general formula (I) of the present invention or a pharmacologically acceptable salt thereof as an active ingredient, The pharmaceutical composition may be formulated as a cream, a gel, a patch, a spray, an ointment, a warning agent, a lotion, a liniment, a pasta agent or a cataplasmatic external preparation for skin, but is not limited thereto.

The preferred dosage of the compound of formula (I) of the present invention or its pharmacologically acceptable salt varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, . However, for the desired effect, the compound of the present invention is preferably administered at 0.0001 to 100 mg / kg per day, preferably 0.001 to 10 mg / kg per day. 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 compounding amount of the compounds according to the present invention in the dermatological pharmaceutical composition is preferably 0.0001 to 20% by weight, more preferably 0.001 to 10% by weight based on the total weight of the composition. If the amount is less than 0.001% by weight, If it exceeds 20% by weight, it is difficult to expect an increase in the effect even if it is blended.

In addition, the pharmaceutical dosage forms of the compounds of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds, as well as in suitable aggregates.

The present invention provides a cosmetic composition for prevention, improvement and whitening of hypercholesterolemia, spots, freckles and black spots, which comprises the compound of general formula (I) or a pharmacologically acceptable salt thereof as an active ingredient.

The composition comprising the compound of formula (I) of the present invention or a pharmacologically acceptable salt thereof as an active ingredient can be variously used for cosmetics and cleansing agents for improving wrinkles of the skin. Examples of products to which the present composition can be added include cosmetics such as various creams, lotions, and skins, and cleansing, cleansing agents, soaps, treatments, and essences.

The cosmetic composition of the present invention comprises a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high molecular weight peptides, polymeric polysaccharides, sphingolipids and seaweed extracts.

The water-soluble vitamin is not particularly limited as long as it can be compounded in cosmetics. Preferably, vitamin B, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, And their salts (thiamine hydrochloride, sodium ascorbate, etc.) or derivatives (sodium ascorbic acid-2-phosphate, magnesium ascorbate-2-phosphate etc.) can also be added to water-soluble vitamins . The water-soluble vitamin can be obtained by a conventional method such as a microorganism conversion method, a purification method from a culture of a microorganism, an enzymatic method, or a chemical synthesis method.

Usable vitamins include vitamins such as vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol) Alpha-tocopherol vitamin E, DL-pantothenyl alcohol, D-pantothenyl alcohol, pantothenyl ethyl laurate, and the derivatives thereof (palmitic acid ascorbin, stearic acid ascorbic acid, dipalmitic acid ascorbin, dl-alpha tocopherol acetate, Ether, etc.) are also included in the usable vitamins used in the present invention. Usability Vitamins can be obtained by a conventional method such as a microorganism conversion method, a purification method from a culture of a microorganism, an enzyme or a chemical synthesis method.

The polymeric peptide may be any compound as long as it can be compounded in cosmetics, and examples thereof include collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, and keratin. The polymeric peptide can be obtained by a conventional method such as purification from a culture broth of a microorganism, an enzymatic method, or a chemical synthesis method, or it can be purified from natural products such as ducks such as pigs and cows and silk fiber of silkworms.

The polymeric polysaccharide may be any compound as long as it can be incorporated in cosmetics, and examples thereof include hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate or a salt thereof (sodium salt, etc.). For example, chondroitin sulfate or a salt thereof can be usually purified from mammals or fish.

Sphingo lipids may be any as long as they can be incorporated into cosmetics, and preferable examples thereof include ceramides, phytosphingosine and sphingoglycolipids. Sphingoid lipids can be purified from ordinary mammals, fish, shellfish, yeast or plants by conventional methods or can be obtained by chemical synthesis.

The seaweed extract may be any of those which can be compounded in cosmetics. Preferably, the seaweed extract is selected from the group consisting of algae extract, red pepper extract, green algae extract and the like. Also, the algae extract may be colored guanine, arginic acid, Potassium alginate and the like are also included in the seaweed extract used in the present invention. Seaweed extract can be obtained from seaweed by a conventional method.

The cosmetic of the present invention may be blended with other essential ingredients, if necessary, in combination with the essential ingredients.

Examples of the compounding ingredients that may be added include organic solvents such as a preservative component, a moisturizer, an emollient, a surfactant, an organic and inorganic pigment, an organic powder, an ultraviolet absorbent, a preservative, a bactericide, an antioxidant, a plant extract, a pH adjuster, A blood circulation accelerator, a cold agent, an antiperspirant agent, and purified water.

Examples of the oil retaining component include ester-based oil retaining, hydrocarbon-based oil retaining, silicone-based oil retaining, fluoric oil retaining, animal retention and plant retention.

Examples of ester-based fats include glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isostearyl isostearate, Butyl isopropyl myristate, isopropyl myristate, isopropyl myristate, isopropyl myristate, isopropyl myristate, isopropyl myristate, butyl, ethyl linoleate, isopropyl linoleate, ethyl oleate, isosilyl myristate, isostearic acid isostearyl, isostearyl palmitate, octyldodecyl myristate, Trimethylol propane, triisostearic acid trimethylol propane, tetra 2-ethylhexanoic acid pentaerythritol tetra (2-ethylhexanoate) , Decyl caprylate, decyl laurate, hexyl laurate, myristate decyl, myristyl myristate, myristine monoethyl stearate, stearyl stearate, decyl oleate, ricinoleic acid tri , Isostearyl stearate, isostearyl stearate, isodecyl stearate, octyldodecyl oleate, octyldodecyl linoleate, isopropyl isostearate, isopropyl stearate, isopropyl stearate, isopropyl stearate, -Hexyl stearate, stearyl ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicaprate, di (capryl, capric acid) propylene glycol, Propyleneglycol propionate, propyleneglycol propionate, dicaproic acid neopentyl glycol, dioctanoic acid neopentyl glycol, tricarboxylic acid glyceryl, triunsaturated glyceryl, triisopalmitic acid glyceryl, triisostearic acid glyceryl, neopentanoic acid octyldodecyl Octanoic acid octanoate, octanoic acid octanoate, octanoic acid octanoate, octanoic acid octanoate, octanoic acid octanoate, octanoic acid octanoate, Octyldecyl lactate, octyldecyl lactate, octyldecyl lactate, polyglycerin oleic acid ester, polyglycerin isostearic acid ester, triisocetyl citrate, triisobutyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, But are not limited to, ethyl, acetyltriethyl citrate, acetyltributyl citrate, trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, But are not limited to, dioctyl sebacate, stearic acid cholesteryl, isostearic acid cholesteryl, hydroxystearic acid cholesteryl, oleic acid cholesteryl, oleic acid dihydrocholesteryl, isostearic acid pitostearyl, Stearoyl hydroxystearic acid isostearyl, 12-stearoyl stearyl hydroxystearate, 12-stearo And monohydroxystearic acid and esters such as sostearyl.

Examples of the hydrocarbon hydrocarbon-based fats include hydrocarbon fats and oils such as squalene, liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, floating isoparaffin, polybutene, microcrystalline wax and vaseline.

Examples of silicone based oils include polymethyl silicone, methylphenyl silicone, methyl cyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane-methylcetyloxysiloxane copolymer, dimethylsiloxane-methylstarchoxysiloxane copolymer, alkyl Modified silicone oils, and amino-modified silicone oils.

Examples of the fluorine-based oil include perfluoropolyether and the like.

Examples of animal or vegetable oils include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, new flower oil, soybean oil, corn oil, rape oil, apricot kernel oil, palm kernel oil, palm oil, castor oil, , Corn oil, palm oil, palm oil, cucumber nut oil, wheat germ oil, rice germ oil, shea butter, coltsfoot colostrum, marker daisy nut oil, mead home oil, egg oil, , Canned wax, carnauba wax, liquid lanolin, hardened castor oil, and the like.

Examples of the moisturizing agent include water-soluble low-molecular moisturizing agents, oil-soluble molecular moisturizing agents, water-soluble polymers, and oil-soluble polymers.

Examples of the water-soluble low-molecular moisturizing agent include serine, glutamine, sorbitol, mannitol, sodium pyrrolidone-carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol B Glycol (polymerization degree n = 2 or more), polyglycerin B (polymerization degree n = 2 or more), lactic acid, lactic acid salt and the like.

Examples of the lipid-soluble low-molecular moisturizing agent include cholesterol and cholesterol ester.

Examples of the water-soluble polymer include carboxyvinyl polymer, polyaspartic acid, tragacanth, xanthan gum, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, water-soluble chitin, chitosan, dextrin, etc. .

Examples of the oil-soluble polymer include polyvinylpyrrolidone / eicosene copolymer, polyvinylpyrrolidone / hexadecene copolymer, nitrocellulose, dextrin fatty acid ester, and polymer silicone.

Examples of the emollients include long chain acyl glutamic acid cholesteryl ester, hydroxystearic acid cholesteryl, 12-hydroxystearic acid, stearic acid, rosin acid and lanolin fatty acid cholesteryl ester.

Examples of the surfactant include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants.

Examples of the nonionic surfactant include self emulsifying monostearate glycerin, propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE (polyoxyethylene) sorbitan fatty acid ester, POE sorbit fatty acid ester, POE (Polyoxyethylene / polyoxypropylene) copolymer, POE.POP alkyl ether, polyether-modified silicone, polyether-modified silicone, polyoxyethylene-polyoxypropylene (POE) Alkanolamides, alkylamine oxides, hydrogenated soybean phospholipids, and the like.

Examples of the anionic surfactant include fatty acid soap, alpha-acylsulfonate, alkylsulfonate, alkylallylsulfonate, alkylnaphthalenesulfonate, alkylsulfate, POE alkylether sulfate, alkylamide sulfate, alkyl phosphate, POE alkyl phosphate, alkylamide phosphate , Alkyloyl taurine salts, N-acyl amino acid salts, POE alkyl ether carboxylates, alkylsulfosuccinates, sodium alkylsulfoacetates, acylated hydrolyzed collagen peptide salts, and perfluoroalkyl phosphate esters .

Examples of the cationic surfactant include alkyl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride, stearyl trimethyl ammonium bromide, cetostearyl trimethyl ammonium chloride, distearyl dimethyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, behenyl trimethyl ammonium chloride, Benzalkonium, diethylaminoethylamide stearate, dimethylaminopropylamide stearate, quaternary ammonium salts of lanolin derivatives, and the like.

Examples of the amphoteric surfactant include carboxybetaine type, amide betaine type, sulfobetaine type, hydroxysulfobetaine type, amidosulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type and amide amine type Amphoteric surfactants and the like.

Examples of the organic and inorganic pigments include inorganic pigments such as silicic acid, silicic anhydride, magnesium silicate, talc, sericite, mica, kaolin, Bengala, clay, bentonite, titanium mica, titanium oxide, bismuth chloride, zirconium oxide, magnesium oxide, Inorganic pigments such as calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, chromium oxide, chromium oxide, chromium hydroxide, But are not limited to, polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin, fluororesin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, Silk powder, cellulose, CI Pigment Yellow, CI Pigment Orange, and composite pigments of inorganic pigments and organic pigments thereof.

As the organic powder, metallic soap such as calcium stearate; Metal salts of alkyl phosphates such as sodium zinc cetylate, zinc laurylate and calcium lauryl laurate; Acylamino acid polyvalent metal salts such as N-lauroyl-beta-alanine calcium, N-lauroyl-beta-alanine zinc and N-lauroylglycine calcium; Amidosulfonic acid multivalent metal salts such as N-lauroyl-taurine calcium and N-palmitoyl-taurine calcium; Such as N-epsilon-lauroyl-L-lysine, N-epsilon-palmitoylidene, N-alpha-paratyylnitine, N-alpha-lauroyl arginine, Acyl basic amino acids; N-acylpolypeptides such as N-lauroylglycylglycine; Alpha-amino fatty acids such as alpha-aminocaprylic acid, alpha-aminoaurauric acid, and the like; Polyethylene, polypropylene, nylon, polymethylmethacrylate, polystyrene, divinylbenzene-styrene copolymer, ethylene tetrafluoride, and the like.

Examples of ultraviolet absorbers include paraaminobenzoic acid, ethyl parnamobenzoate, amyl paranobenzoate, octyl paranobenzoate, ethyleneglycol salicylate, phenyl salicylate, benzyl salicylate, benzyl salicylate, butylphenyl salicylate, homomenthyl salicylate, benzyl cinnamate , Octyl methoxycinnamate, dioctyl methoxycinnamate, mono-2-ethylhexane glyceryl dipyrromethoxycinnamate, isopropyl paratumoxycinnamate, diisopropyl-diisopropyl cinnamate ester mixture, Carninoic acid, ethyl urocanoate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and salts thereof, dihydroxymethoxybenzophenone, sodium dihydroxymethoxybenzophenone disulfonate, dihydroxybenzophenone , Tetrahydroxybenzophenone, 4- tert -butyl-4'-methoxydibenzoylmethane, 2,4,6-trianylino- p- (carbo-2'-ethylhexyl-1'- , 3,5-triazine, 2- (2- And the like can be mentioned hydroxy-5-methylphenyl) benzotriazole.

Examples of the disinfectant include hinokitiol, trichloroacid, trichlorohydroxydiphenyl ether, crohexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid, zinc filitione, benzalkonium chloride, No. 301, mononitro and eicol sodium, and undecylenic acid.

Examples of the antioxidant include butylhydroxyanisole, gallic acid propyl, and eicosorbic acid.

Examples of the pH adjuster include citric acid, sodium citrate, malic acid, sodium malate, fumaric acid, sodium fumarate, succinic acid, sodium succinate, sodium hydroxide, sodium monohydrogenphosphate and the like.

Examples of the alcohol include higher alcohols such as cetyl alcohol.

In addition, any of the above-mentioned components may be blended within the range not to impair the objects and effects of the present invention, but it is preferably 0.01 to 5% by weight based on the total weight, More preferably from 0.01 to 3% by weight.

The cosmetic of the present invention may take the form of a solution, an emulsion, a viscous mixture or the like.

The ingredients contained in the cosmetic composition of the present invention may contain, as an active ingredient, the ingredients commonly used in cosmetic compositions in addition to the compounds of formula (I), for example, stabilizers, solubilizers, vitamins, pigments And customary adjuvants and carriers such as perfumes.

The cosmetic composition of the present invention can be prepared into any formulation conventionally produced in the art, and examples thereof include emulsions, creams, lotions, packs, foundations, lotions, essences, and hair cosmetics.

Specifically, the cosmetic composition of the present invention can be used as a skin lotion, a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, a nutrition lotion, a massage cream, a nutrition cream, a moisturizing cream, a hand cream, Packs, soaps, cleansing foams, cleansing lotions, cleansing creams, body lotions and body cleansers.

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

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In the case of a spray, in particular, / Propane or dimethyl ether.

In the case of the solution or emulsion of the present invention, a solvent, a solvent or an emulsifier is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

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

When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolenic derivatives or ethoxylated glycerol fatty acid esters.

Hereinafter, the present invention will be described in detail with reference to the following examples and experimental examples.

However, the following examples and experimental examples are illustrative of the present invention, and the content of the present invention is not limited by the following examples and experimental examples.

Example 1. Preparation of 2-ethoxy benzoic acid ethyl ester

10 mmol of 2-hydroxybenzoic acid was added to a 2-neck round flask at room temperature, and 50 ml of dimethylformamide was added thereto. 24 mmol of potassium carbonate (K 2 CO 3) was added as a catalyst, and 24 mmol of bromoethane was slowly added dropwise. After addition, the reaction was allowed to proceed at room temperature for 6 hours. 500 ml of purified water was added to the reaction mixture and extracted with 100 ml of n-hexane. The hexane layer was dried under reduced pressure and then separated and purified by silica gel column chromatography (ethyl acetate: hexane = 1: 50) 2-ethoxybenzoic acid ethyl ester was obtained and identified using fast atom impact mass spectrometry (hereinafter FAB-MS).

FAB mass: 195 [M + H] < ⁺ >

Example 2. Preparation of 2-propoxy benzoic acid propyl ester

2-propoxybenzoic acid propyl ester having the following physical properties was obtained by the same method as in Example 1 except that bromopropane was used in place of bromoethane.

FAB mass: 223 [M + H] < ⁺ >

Example 3. Preparation of 2-butoxy benzoic acid butyl ester

Butoxybenzoic acid butyl ester having the following physical data was obtained by the same method as in Example 1 except that bromobutane was used in place of bromoethane.

FAB mass: 251 [M + H] < ⁺ >

Example 4. Preparation of 2-pentyloxy benzoic acid pentyl ester

2-pentyloxybenzoic acid pentyl ester having the following physical data was obtained by the same method as in Example 1 except that bromopentane was used in place of bromoethane.

FAB mass: 279 [M + H] < ⁺ >

Example 5. Preparation of 2-hexyloxy benzoic acid hexyl ester

Was synthesized in the same manner as in Example 1, except that bromohexane was used instead of bromoethane to obtain 2-hexyloxybenzoic acid hexyl ester having the following physical properties.

FAB mass: 307 [M + H] < ⁺ >

Example 6. Preparation of 2-octyloxy benzoic acid octyl ester

Octyloxybenzoic acid octyl ester having the following physical properties was synthesized in the same manner as in Example 1 except that bromo octane was used instead of bromoethane to give the following characteristics.

FAB mass: 363 [M + H] < ⁺ >

Example 7. Preparation of 2-decyloxy benzoic acid decyl ester 2-decyloxy benzoic acid decyl ester

Synthesis was conducted in the same manner as in Example 1 except that bromodecane was used instead of bromoethane to obtain 2-decyloxybenzoic acid decyl ester having the following physical properties.

FAB mass: 419 [M + H] < ⁺ >

Example 8. Preparation of 3-ethoxy benzoic acid ethyl ester

Was synthesized in the same manner as in Example 1, except that 3-hydroxybenzoic acid was used instead of 2-hydroxybenzoic acid to obtain 3-ethoxybenzoic acid ethyl ester having the following physical data.

FAB mass: 195 [M + H] < ⁺ >

Example 9. Preparation of 3-propoxy benzoic acid propyl ester

Was synthesized in the same manner as in Example 2 except that 3-hydroxybenzoic acid was used instead of 2-hydroxybenzoic acid to obtain 3-propoxybenzoic acid propyl ester having the following physical data.

FAB mass: 223 [M + H] < ⁺ >

Example 10. Preparation of 3-butoxy benzoic acid butyl ester

Butoxybenzoic acid ester was obtained in the same manner as in Example 3, except that 3-hydroxybenzoic acid was used instead of 2-hydroxybenzoic acid, to obtain 3-butoxybenzoic acid butyl ester having the following physical data.

FAB mass: 251 [M + H] < ⁺ >

Example 11. Preparation of 3-pentyloxy benzoic acid pentyl ester

Was synthesized in the same manner as in Example 4, except that 3-hydroxybenzoic acid was used instead of 2-hydroxybenzoic acid to obtain 3-pentyloxybenzoic acid pentyl ester having the following physical properties.

FAB mass: 279 [M + H] < ⁺ >

Example 12. Preparation of 3-hexyloxy benzoic acid hexyl ester

Was synthesized in the same manner as in Example 5, except that 3-hydroxybenzoic acid was used in place of 2-hydroxybenzoic acid to obtain 3-hexyloxybenzoic acid hexyl ester having the following physical properties.

FAB mass: 307 [M + H] < ⁺ >

Example 13. Preparation of 3-octyloxy benzoic acid octyl ester

Was synthesized in the same manner as in Example 6, except that 3-hydroxybenzoic acid was used in place of 2-hydroxybenzoic acid to obtain 3-octyloxybenzoic acid octyl ester having the following physical properties, Respectively.

FAB mass: 363 [M + H] < ⁺ >

Example 14. Preparation of 3-decyloxy benzoic acid decyl ester.

Was synthesized in the same manner as in Example 7, except that 3-hydroxybenzoic acid was used instead of 2-hydroxybenzoic acid to obtain 3-decyloxybenzoic acid decyl ester having the following physical properties.

FAB mass: 419 [M + H] < ⁺ >

Example 15: Preparation of 5-acetyl-2-pentyloxy benzoic acid pentyl ester 5-acetyl-2-pentyloxybenzoic acid pentaery ester

Acetyl-2-hydroxybenzoic acid instead of 2-hydroxybenzoic acid was used to synthesize 5-acetyl-2-pentyloxybenzoic acid pentaerythritol Ester.

FAB mass: 321 [M + H] < ⁺ >

Example 16. 1-Pentyloxy-2-naphthoic acid pentaerythritol (1-pentyloxy-2-naphthoic acid pentyl ester)

Was synthesized in the same manner as in Example 4 except that 1-hydroxy-2-naphthoic acid was used in place of 2-hydroxybenzoic acid to obtain 1-pentyloxy-2-naphthoic acid pentaery ester having the following physical properties .

FAB mass: 329 [M + H] < ⁺ >

Example 17. 3-Pentyloxy-2-naphthoic acid pentaerythritate (3-pentyloxy-2-naphthoic acid pentyl ester)

Was synthesized in the same manner as in Example 4, except that 3-hydroxy-2-naphthoic acid was used in place of 2-hydroxybenzoic acid to obtain 3-pentyloxy-2-naphthoic acid pentaery ester having the following physical properties .

FAB mass: 329 [M + H] < ⁺ >

Example 18. 3-Pentyloxy-4-pyridinecarboxylic acid Pentyl ester (3-pentyloxy-4-pyridinecarboxylic acid pentyl ester)

Was synthesized in the same manner as in Example 4, except that 3-hydroxy-4-pyridinecarboxylic acid was used instead of 2-hydroxybenzoic acid, to obtain 3-pentyloxy-4-pyridinecarboxylic acid pentyl Ester.

FAB mass: 280 [M + H] < ⁺ >

Example 19. 3-Pentyloxy-quinoline-4-carboxylic acid pentaerythritol (3-pentyloxy-quinoline-4-carboxylic acid pentyl ester)

Was synthesized in the same manner as in Example 4, except that 3-hydroxy-quinoline-4-carboxylic acid was used in place of 2-hydroxybenzoic acid to obtain 3-pentyloxy-quinoline- Acid penthyl ester.

FAB mass: 330 [M + H] < ⁺ >

Example 20. Preparation of 1- (2-pentyloxy-phenyl) -ethanone (1- (2-pentyloxy-phenyl) -ethanone)

Was synthesized in the same manner as in Example 4, except that 1- (2-hydroxy-phenyl) -ethanone was used in place of 2-hydroxybenzoic acid to obtain 1- (2-pentyloxy-phenyl) -Ethanone. ≪ / RTI >

FAB mass: 207 [M + H] < ⁺ >

Example 21. Preparation of 1- (3-pentyloxy-phenyl) -ethanone (1- (3-pentyloxy-phenyl) -ethanone)

Synthesis was conducted in the same manner as in Example 4, except that 1- (3-hydroxy-phenyl) -ethanone was used in place of 2-hydroxybenzoic acid to obtain 1- (3-pentyloxy-phenyl) -Ethanone. ≪ / RTI >

FAB mass: 207 [M + H] < ⁺ >

Example 22: Preparation of 1- (3-pentyloxy-naphthalen-2-yl) -ethanone

Was synthesized in the same manner as in Example 4, except that 1- (3-hydroxy-naphthalen-2-yl) -ethanone was used in place of 2-hydroxybenzoic acid to obtain 1- Oxy-naphthalen-2-yl) -ethanone.

FAB mass: 257 [M + H] < ⁺ >

Example 23. Preparation of acetic acid 2-acetyl-phenyl ester

10 mmol of 1- (2-hydroxy-phenyl) -ethanone was added to a 2-neck round flask at room temperature, and 50 ml of chloroform was then added. 12 mmol of triethylamine was added as a catalyst, and 12 mmol of acetyl chloride was slowly added dropwise thereto. After addition, the reaction was allowed to proceed at room temperature for 2 hours. 500 ml of purified water was added to the reaction mixture to carry out liquid-liquid fractionation. The chloroform layer was dried under reduced pressure and then purified by silica gel column chromatography (ethyl acetate: hexane = 1: 30) Acetic acid 2-acetyl-phenyl ester was obtained and identified using fast atom impact mass spectrometry (hereinafter FAB-MS).

FAB mass: 179 [M + H] < ⁺ >

Example 24. Preparation of 2-ethylhexanoic acid 2-acetyl-phenyl ester 2-ethylhexanoic acid 2-acetyl-phenyl ester

Ethylhexanoyl chloride instead of acetyl chloride was used to synthesize 2-ethylhexanoic acid 2-acetyl-phenyl ester having the following physical data ≪ / RTI >

FAB mass: 263 [M + H] < ⁺ >

Example 25. Preparation of 1-pentyloxy-2-propyl-benzene

Was synthesized in the same manner as in Example 4, except that 2-ethyl-phenol was used instead of 2-hydroxybenzoic acid to obtain 1-pentyloxy-2-propyl-benzene having the following physical properties.

FAB mass: 207 [M + H] < ⁺ >

Example 26. Preparation of 2-ethylhexanoic acid 2-propyl-phenyl ester 2-ethylhexanoic acid 2-propyl-phenyl ester

Ethylhexanoic acid 2-propyl-phenyl ester having the following physical data was synthesized in the same manner as in Example 24, except that 2-propyl-benzene was used instead of 1- (2-hydroxy-phenyl) ≪ / RTI >

FAB mass: 263 [M + H] < ⁺ >

Example 27. Preparation of 2-ethylhexanoic acid 3-propyl-phenyl ester 2-ethylhexanoic acid 3-propyl-phenyl ester

Ethylhexanoic acid 3-propyl-phenyl ester having the following physical data was synthesized in the same manner as in Example 24, except that 3-propyl-benzene was used instead of 1- (2-hydroxy-phenyl) ≪ / RTI >

FAB mass: 263 [M + H] < ⁺ >

Experimental Example 1. Measurement of inhibitory effect on melanin formation

The whitening effect at the cellular level was examined by adding the compounds prepared according to the methods described in Examples 1 to 27 and hydroquinone to the culture solution of mouse melanoma cells of B-16 (Lotan R , Lotan D. Cancer Res., 40 , pp. 3345-3350, 1980). The final concentrations of the compounds prepared above were added to the culture medium of B-16 melanoma cells so that the final concentrations were 5 μg / ml and 10 μg / ml, respectively. After culturing for 3 days, the cells were treated with trypsin Melanin was extracted after centrifugation from the container. Was added 1 N sodium hydroxide solution, 1ml the extract dissolved melanin boiled for 10 minutes, using a spectrophotometer 475 nanometers (nm) in the amount of the produced melanin unit cell allowance by measuring the absorbance at (10 ⁶ cell) absorbance (Repeated three times). The relative amount of melanin production relative to the control group was calculated as the inhibition rate (%), and the results are shown in Table 1.

All of the above compounds showed a melanin production inhibitory effect comparable to that of hydroquinone in melanoma cells of cultured rats. Although hydroquinone has a strong inhibitory effect on melanin production at low concentrations, it can not be tested at concentrations of 1 μg / ml or more. However, the compounds do not exhibit cytotoxicity even at a concentration of 20 μg / ml and thus produce melanin higher than hydroquinone Inhibiting effect can be obtained.

Inhibition of melanin formation at the cellular level sample Concentration (ug / ml) Inhibition rate (%) Control group - - Hydroquinone One 48 5 Death The material of Example 1 5 31 20 46 The material of Example 2 5 41 20 52 The material of Example 3 5 45 20 64 The material of Example 4 5 54 20 65 The material of Example 5 5 52 20 67 The material of Example 6 5 41 20 52 The material of Example 7 5 22 20 35 The material of Example 8 5 27 20 42 The material of Example 9 5 29 20 48 The material of Example 10 5 38 20 54 The material of Example 11 5 49 20 62 The substance of Example 12 5 46 20 61 The material of Example 13 5 29 20 41 The material of Example 14 5 21 20 32 The material of Example 15 5 39 20 57 The material of Example 16 5 41 20 52 The material of Example 17 5 38 20 52 The material of Example 18 5 42 20 71 The material of Example 19 5 38 20 59 The material of Example 20 5 24 20 41 The material of Example 21 5 25 20 45 The material of Example 22 5 19 20 37 The material of Example 23 5 27 20 41 The material of Example 24 5 19 20 38 The material of Example 25 5 16 20 31 The material of Example 26 5 24 20 35 The material of Example 27 5 23 20 41

Production Example 1. Production of softening longevity

Formulation 1 and Comparative Formulation 1 were prepared with the compositions shown in Table 2 below.

Composition (% by weight) Formulation 1 Comparative Formulation 1 a b c d The material of Example 4 0.1   -   -   -   - The material of Example 11   - 0.1   -   -   - The material of Example 16   -   - 0.1   -   - The material of Example 18   -   -   - 0.1   - ethanol 10.0 10.0 10.0 10.0 10.0 Polyoxyethylene hardened castor oil 1.0 1.0 1.0 1.0 1.0 Methyl paraoxybenzoate 0.2 0.2 0.2 0.2 0.2 glycerin 5.0 5.0 5.0 5.0 5.0 1,3-butylene glycol 6.0 6.0 6.0 6.0 6.0 incense Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount Purified water to 100 to 100 to 100 to 100 to 100

Production Example 2. Preparation of nutrition lotion

Formulation 2 and Comparative Formulation 2 were prepared with the compositions shown in Table 3 below.

Composition (% by weight) Formulation 2 Comparative Formulation 2 a b c d The material of Example 4 0.1   -   -   -   - The material of Example 11   - 0.1   -   -   - The material of Example 16   -   - 0.1   -   - The material of Example 18   -   -   - 0.1   - Polyoxyethylene hardened castor oil 1.0 1.0 1.0 1.0 1.0 Methyl paraoxybenzoate 0.2 0.2 0.2 0.2 0.2 glycerin 6.0 6.0 6.0 6.0 6.0 1,3-butylene glycol 5.0 5.0 5.0 5.0 5.0 Carbomer 0.2 0.2 0.2 0.2 0.2 Triethanolamine 0.3 0.3 0.3 0.3 0.3 Propylene glycol 5.0 5.0 5.0 5.0 5.0 ethanol 3.2 3.2 3.2 3.2 3.2 Carboxyvinyl polymer 0.1 0.1 0.1 0.1 0.1 incense Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount Purified water to 100 to 100 to 100 to 100 to 100

Preparation Example 3. Preparation of cream

Formulation 3 and Comparative Formulation 3 were prepared with the compositions shown in Table 4 below.

Composition (% by weight) Formulation 3 Comparative Formulation 3 a b c d The material of Example 4 0.1   -   -   -   - The material of Example 11   - 0.1   -   -   - The material of Example 16   -   - 0.1   -   - The material of Example 18   -   -   - 0.1   - Cetanol 2.0 2.0 2.0 2.0 2.0 Figure-20 1.0 1.0 1.0 1.0 1.0 Sobutan monostearate 1.0 1.0 1.0 1.0 1.0 Mineral oil 10.0 10.0 10.0 10.0 10.0 Trioctanoate 5.0 5.0 5.0 5.0 5.0 Triethanolamine 0.5 0.5 0.5 0.5 0.5 Carbomer 0.2 0.2 0.2 0.2 0.2 glycerin 5.0 5.0 5.0 5.0 5.0 Propylene glycol 3.0 3.0 3.0 3.0 3.0 antiseptic Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount incense Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount Purified water to 100 to 100 to 100 to 100 to 100

Production Example 4. Preparation of ointment for skin

Formulation 4 and Comparative Formulation 4 were prepared with the compositions of Table 5 below.

Composition (% by weight) Formulation 4 Comparative Formulation 4 a b c d The material of Example 4 0.1   -   -   -   - The material of Example 11   - 0.1   -   -   - The material of Example 16   -   - 0.1   -   - The material of Example 18   -   -   - 0.1   - Diethyl sebacate 8.0 8.0 8.0 8.0 8.0 Nonsense 5.0 5.0 5.0 5.0 5.0 Polyoxyethylene oleyl ether phosphate 6.0 6.0 6.0 6.0 6.0 Sodium benzoate Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount vaseline to 100 to 100 to 100 to 100 to 100

Production Example 5. Preparation of essence

Formulation 5 and Comparative Formulation 5 were prepared with the compositions shown in Table 6 below.

Composition (% by weight) Formulation 5 Comparative Formulation 5 a b c d The material of Example 4 0.5   -   -   -   - The material of Example 11   - 0.5   -   -   - The material of Example 16   -   - 0.5   -   - The material of Example 18   -   -   - 0.5   - Propylene glycol 10.0 10.0 10.0 10.0 10.0 glycerin 10.0 10.0 10.0 10.0 10.0 Sodium hyaluronate aqueous solution (1%) 5.0 5.0 5.0 5.0 5.0 ethanol 5.0 5.0 5.0 5.0 5.0 Polyoxyethylene hardened castor oil 1.0 1.0 1.0 1.0 1.0 Methyl paraoxybenzoate 0.1 0.1 0.1 0.1 0.1 Carbomer 0.4 0.4 0.4 0.4 0.4 incense Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount Purified water to 100 to 100 to 100 to 100 to 100

Production Example 6. Production of pack

Formulation 6 and Comparative Formulation 6 were prepared with the compositions of Table 7 below.

Composition (% by weight) Formulation 6 Comparative Formulation 6 a b c d The material of Example 4 0.1   -   -   -   - The material of Example 11   - 0.1   -   -   - The material of Example 16   -   - 0.1   -   - The material of Example 18   -   -   - 0.1   - glycerin 5.0 5.0 5.0 5.0 5.0 Propylene glycol 4.0 4.0 4.0 4.0 4.0 Polyvinyl alcohol 15.0 15.0 15.0 15.0 15.0 ethanol 8.0 8.0 8.0 8.0 8.0 Polyoxyethylene hardened castor oil 1.0 1.0 1.0 1.0 1.0 Polyoxyethylene oleyl ether phosphate 1.0 1.0 1.0 1.0 1.0 Methyl paraoxybenzoate 0.2 0.2 0.2 0.2 0.2 incense Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount Purified water to 100 to 100 to 100 to 100 to 100

EXPERIMENTAL EXAMPLE 2 Confirmation of Pigmentation Inhibitory Effect

Experiments were carried out in the following manner to verify the effect of inhibiting pigmentation according to Formulations 1 to 6 and Comparative Formulations 1 to 6 prepared in Preparation Examples 1 to 6.

Eighty healthy subjects were selected and aluminum foil having a diameter of 7 mm and having a diameter of 7 mm and having 2 lines was attached to the lower part of both arms. Using an ORIEL solar simulator 1000W at a distance of 10 cm from the arm, / cm < ² > Before irradiation, the irradiated sites were washed well with 70% aqueous ethanol solution. Formulations 1 to 6 and Comparative Formulations 1 to 6 were applied in pairs on the same row from 3 days before irradiation to 8 weeks after irradiation, twice a day. The packs of Formulation 6 and Comparative Formulation 6 were detached after 15 minutes of application.

 The panel was divided into 20 groups in group 1 and tested in 4 groups. The determination of the whitening effect was made by visually determining the degree of discoloration of the formulations and the comparative formulations, and the degree of inhibition of the pigmentation by the formulation compared to the comparative formulations was evaluated in three steps of marked effect, effect, and no difference , And the results are shown in Table 8 below.

As shown in Table 8, the cosmetics of formulations 1 to 6 containing the substances of the present invention showed an excellent skin whitening effect as compared with the conventional cosmetics.

Pigment inhibition effect Experimental material Distinct effect (n.) Effective (persons) No difference (persons) Comparative Formulation 1 0 One 19 Formulation 1 a 5 8 7 b 5 9 6 c 5 8 7 d 4 9 7 Comparative Formulation 2 0 3 17 Production Example 2 a 6 9 5 b 4 10 6 c 5 9 6 d 6 9 5 Comparative Formulation 3 0 2 18 Formulation 3 a 7 9 4 b 8 6 6 c 6 8 6 d 7 7 6 Comparative Formulation 4 0 2 18 Formulation 4 a 5 10 5 b 7 9 4 c 4 8 8 d 7 9 4 Comparative Formulation 5 0 3 17 Formulation 5 a 5 8 7 b 7 6 7 c 8 7 5 d 7 9 4 Comparative Formulation 6 0 2 18 Formulation 6 a 8 7 5 b 7 6 7 c 7 8 5 d 6 9 5

Claims (9)

A derivative of a cyclic compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof:

In the above formula

B is hydrogen, oxo (= O), amino (NH ₂ ), imino (= NH), C ₁ to C ₁₀ saturated or unsaturated straight chain or branched Branched alkyl group, alkoxy, monoalkylamino group, or dialkylamino group,
C _n , C _{n + 1} and C _{n + 2} are three adjacent carbons present in the cyclic compound, and n is a positive integer.
R ₁ is hydrogen, hydroxy, a saturated or unsaturated straight-chain or branched alkyl or alkoxy group,
X and Y are selected from hydrogen, saturated or unsaturated straight or branched chain alkoxy or acyloxy, and one of X and Y is hydrogen.
R ₂ , R _3, R ₄ and R ₅ are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxaldehyde, Lt; / RTI > The method according to claim 1,

Is derived from a cyclic compound in which 1 to 3 rings of a pentagonal or hexagonal ring are bonded. The derivative or pharmacologically acceptable salt thereof according to claim 1, wherein the cyclic compound is a homo or heterocyclic compound. 4. The derivative or pharmacologically acceptable salt thereof according to claim 3, wherein the heterocyclic compound is a compound containing oxygen, nitrogen or oxygen and nitrogen in its structure. The method according to claim 1,

Is derived from a cyclic compound selected from the group of benzene, pyridine, naphthalene, quinoline, flavone, isoflavone, flavan, flavanone, stilbene, and coumarin or a pharmacologically acceptable salt thereof. A derivative or pharmacologically acceptable salt thereof according to claim 1, wherein R ₁ is hydrogen, hydroxy, C 1 to C ₁₂ saturated or unsaturated straight-chain or branched alkyl or acyl. 7. A composition for preventing, treating and whitening hyperpigmentation, spots, freckles and black spots comprising a compound according to any one of claims 1 to 6 or a pharmacologically acceptable salt thereof as an active ingredient. The dermatological pharmaceutical composition according to claim 7, wherein the composition is a cream, a gel, a patch, a spray, an ointment, an alarm, a lotion, a liniment, a pasta or a catarcoma. A cosmetic composition for preventing, improving and whitening hyperpigmentation, spots, freckles and black spots, comprising the compound according to any one of claims 1 to 6 as an active ingredient.