Diphenol compounds, their preparation and use

Abstract

The present invention provides a resorcinol-derived compound represented by formula (A), which can be used in the manufacture of drugs to inhibit hyperpigmentation, and in cosmetics and non-therapeutic applications to combat hyperpigmentation. The compounds of the present invention have significant effects on the inhibition of hyperpigmentation caused by ultraviolet and / or visible light radiation, and on the prevention of skin aging. JPEG2025515882000099.jpg73170, R 1 ~R 8 is defined in the specification.

Description

[Technical field]

[0001] The present invention relates to a series of diphenolic compounds, processes for their preparation, pharmaceutical or cosmetic compositions containing such compounds, and their use in medicine and cosmetics, in particular for inhibiting pigmentation and combating hyperpigmentation. [Background technology]

[0002] Melanin, which is present in melanocytes and produced by the conversion of tyrosine catalyzed by tyrosinase, is the pigment that gives skin its color. Excessive production of melanin due to factors such as excessive sun exposure, hormonal imbalance, melasma, diseases, scars left by medical treatments, scars, and age spots can cause skin hyperpigmentation.

[0003] The color of human skin is mainly determined by the amount of melanin in the stratum corneum of the skin. Melanin, which is generally brown or black, is formed in the melanocytes of the skin and transferred to the stratum corneum of the skin to give the skin or hair its color. In mammals, the dark brown eumelanin is mainly formed by hydroxy-substituted aromatic amino acids such as L-tyrosine and L-DOPA, while the yellow to red pheomelanin is formed by sulfur-containing molecules. Starting from L-tyrosine, L-3,4-dihydroxyphenylalanine (L-DOPA) is formed by tyrosinase, which converts it to dopachrome by tyrosinase, and later, in a series of catalytic reactions by various enzymes, finally melanin is formed by oxidation.

[0004] Hyperpigmentation occurs in the skin when excess melanin is concentrated in one area or part of the skin. Hyperpigmentation can also occur due to sun exposure or various inflammatory stimuli. Increased production of melanin commonly results in conditions such as melasma, liver spots or sunspots (senile lentigo), freckles, and seborrheic keratosis. Melasma is a general term used to describe dull skin. Liver spots are commonly used to describe hormone-related skin discoloration. These hormonal changes are commonly due to pregnancy, oral contraceptives, or hormone replacement therapy. Sunspots refer to dark spots on the skin caused by sunlight. These spots are commonly seen in adults with a history of long-term unprotected exposure to sunlight. Although skin damage such as scars, wounds, or skin rashes can also cause hyperpigmentation, the most common cause of dull, brown, or discolored areas on the skin is unprotected sun exposure.

[0005] The prior art discloses methods of using skin whitening agents to address hyperpigmentation. Representative compounds commonly used as skin whitening agents include hydroquinone and vitamin C. One of the mechanisms of action of such agents is to lighten the skin by inhibiting tyrosinase, which is involved in the production of melanin. Commonly used ingredients for skin whitening, skin bleaching or skin brightening include hydroquinone, arbutin, kojic acid, licorice extract, nicotinamide, etc. Hydroquinone is one of the most effective depigmenting agents. Although its effectiveness has already been proven, in the early 2000s, hydroquinone was removed from cosmetics and its use in cosmetics became restricted due to its potential dermatological and systemic side effects. Arbutin (a natural product extracted from plants) is a glycosylated derivative of hydroquinone and is an effective tyrosinase inhibitor that is more stable and less toxic than hydroquinone. However, despite its great potential, arbutin still has insufficient stability and releases hydroquinone upon hydrolysis under various conditions.

[0006] Developing safer and more effective compounds to improve skin pigmentation is a traditional goal of those skilled in the art. By studying the mechanism of action of tyrosinase, we simulate the intermediate product L-DOPA in the process of melanin formation and develop resorcinol-type tyrosinase inhibitors. This idea has increasingly attracted attention from those in the skin whitening field. Resorcinol derivatives such as 4-butylresorcinol, 4-hexylresorcinol, dimethoxytryl-4-propylresorcinol (WO2012 / 129260), phenethylresorcinol (WO2018 / 001485) and isobutyramidothiazolylresorcinol (WO2015 / 090850) have all been proven to have significant effects on skin pigmentation. These results reveal that resorcinol compounds have great potential in inhibiting the activity of tyrosinase. Therefore, developing new compounds with resorcinol structure and investigating their biological functions as tyrosinase inhibitors is of great significance for developing new effective tyrosinase inhibitors and thereafter developing new compound combinations for treating or improving skin hyperpigmentation. Summary of the Invention [Problem to be solved by the invention]

[0007] The present inventors have conducted extensive research and have developed new resorcinol compounds which can be used as tyrosinase inhibitors, particularly in cosmetics or pharmaceuticals, and further, in particular, as depigmenting agents, whitening agents, bleaching agents or brightening agents in cosmetics for treating pigmentation disorders or for alleviating or improving hyperpigmentation. [Means for solving the problem]

[0008] In particular, the present invention provides a compound of formula (A) of the resorcinol class capable of influencing skin pigmentation caused by sunlight, in particular ultraviolet, visible light, and in particular for preventing, treating and / or reducing skin or topical skin pigmentation, the structure of which is as follows: [ka] In the formula, W is [ka] where T is H, [ka] Or, [ka] and In the formula, R 1 is selected from H, an optionally substituted alkyl group, and an optionally substituted arylalkyl group; R 2 , R 6 may be the same or different and are each independently selected from optionally substituted aryl and heteroaryl groups, optionally substituted alkyl groups, optionally substituted amide groups, and optionally substituted ester groups; R 3 , R 4 , R 7 , R 8 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; R 3 , R 4 may combine with the carbon atoms to which they are both attached to form a ring, R 7 , R 8 may be combined with the carbon atom to which they are both attached to form a ring, or a cosmetically or pharma- ceutically or pharma-ceutically acceptable salt thereof, a stereoisomer or a mixture of stereoisomers in any ratio, in particular an enantiomer or a mixture of enantiomers, and more in particular a racemic mixture.

[0009] Furthermore, compound A is a compound of formula (I): [ka] In the formula, R1 ~R 4 is as defined above.

[0010] Furthermore, compound A is a compound of formula (Ia): [ka] In the formula, R 1 ~R 3 is defined above, and Z 1 , Z 2 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; Z 1 , Z 2 may be joined with the carbon atom to which they are both attached to form a ring, which ring may be substituted.

[0011] Furthermore, compound A is a compound of formula (V): [ka] In the formula, R 1 ~R 4 The definition is as above.

[0012] Furthermore, compound A is a compound of formula (Va): [ka] In the formula, R 1 ~R 3 is defined as above, and Z 1 , Z 2 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; Z 1 , Z 2 may be joined with the carbon atom to which they are both attached to form a ring, which ring may be substituted.

[0013] Furthermore, compound A is a compound of formula (VI): [ka] In the formula, R 1 ~R 4 and R 6 ~R 8 The definition is as above.

[0014] Furthermore, compound A is a compound of formula (VIa): [ka] In the formula, R 1 ~R 4 and R 6 , R 7 is defined as above, and Z 1 , Z 2 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; Z 1 , Z 2 may be joined with the carbon atom to which they are both attached to form a ring, which ring may be substituted.

[0015] The present invention also provides a method for producing compound A.

[0016] The present invention also provides pharmaceutical compositions comprising a compound of the present invention or a pharma- ceutically acceptable salt thereof.

[0017] The present invention also provides the use of a compound of the invention, or a pharma- ceutically acceptable salt thereof, in the manufacture of a medicament for the treatment, prevention and / or reduction of hyperpigmentation.

[0018] The present invention also discloses the non-therapeutic, cosmetic use of the compounds of the invention or their salts for combating, preventing and / or reducing hyperpigmentation.

[0019] The present invention also discloses a cosmetic composition containing the compound of the present invention or a salt thereof. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] In the following, the technical solutions of the embodiments of the present invention will be clearly and completely described so as to make the objectives, technical solutions and advantages of the embodiments of the present invention clearer. Needless to say, the described embodiments are only some of the embodiments of the present invention, but not all of the embodiments. All other embodiments that a person skilled in the art can obtain based on the embodiments of the present invention without inventive work are within the scope of protection of the present invention. Unless otherwise clearly stated, in the entire specification and claims, the term "comprises" or its variants such as "comprises" or "contains" shall be understood to include the described components or steps, but not to exclude other material components or steps.

[0021] Moreover, in order to further explain the present invention, numerous specific embodiments are set forth in detail below.

[0022] However, it will be understood by those skilled in the art that the present invention can be similarly practiced even without some of these details. In some examples, in order to enhance the spirit of the present invention, materials, methods, means, etc. familiar to those skilled in the art are not described in detail.

[0023] The endpoints of the ranges and any values ​​disclosed herein are not intended to be limiting to the ranges or values ​​themselves, but rather are understood to include values ​​close to these ranges or values. In the case of numerical ranges, the endpoints of the ranges and single point values, and the single point values ​​can be combined with each other to obtain one or more new numerical ranges, which numerical ranges are considered to be specifically disclosed herein.

[0024] In the present invention, "hyperpigmentation" refers to hyperpigmentation caused by sunlight, especially visible light.

[0025] In the present invention, "cosmetically or pharma- ceutically acceptable" refers to something that may be used in the manufacture of a cosmetic or pharmaceutical composition, and is generally non-toxic, safe and acceptable for use in pharmaceutical and cosmetic applications.

[0026] For the purposes of the present invention, a "cosmetically or pharma- ceutically acceptable salt" is a cosmetically or pharma- ceutically acceptable salt as defined herein, which retains the pharmaceutical or cosmetic properties and activity of the parent compound. Such salts include, but are not limited to, (1) acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like, or with organic acids such as acetic acid, benzenesulfonic acid, benzoic acid, dl-camphorsulfonic acid, citric acid, ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, hydroxynaphthoic acid, 2-hydroxyethanesulfonic acid, lactic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, muconic acid, 2-naphthalenesulfonic acid, propionic acid, salicylic acid, succinic acid, dibenzoyl-L-tartaric acid, tartaric acid, p-toluenesulfonic acid, trimethylacetic acid, trifluoroacetic acid, and the like; and (2) acid addition salts formed with organic acids such as acetic acid, benzoic acid, benzoic acid, dl-camphorsulfonic acid, citric acid, ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, hydroxynaphthoic acid, 2-hydroxyethanesulfonic acid, lactic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, muconic acid, 2-naphthalenesulfonic acid, propionic acid, salicylic acid, succinic acid, dibenzoyl-L-tartaric acid, tartaric acid, p-toluenesulfonic acid, trimethylacetic acid, trifluoroacetic acid, and the like, in which the acid-derived proton on the parent compound is replaced by a metal ion, e.g., an alkali metal ion (e.g., Na + , K + Or Li + ), alkaline earth metal ions (Ca 2+ Or Mg 2+ The salts may be salts formed when an acid-derived proton on the parent compound is replaced by an ion such as ammonium ion or an aluminum ion, or when an acid-derived proton on the parent compound coordinates with an organic or inorganic base. Acceptable organic bases include, but are not limited to, diethanolamine, ethanolamine, N-methylglucamine, triethanolamine, tris(hydroxymethyl)aminomethane, and the like. Acceptable inorganic bases include, but are not limited to, aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, and sodium hydroxide.

[0027] As used herein, the term "stereoisomer" refers to configurational isomers, including geometric isomers, optical isomers, and conformational isomers.

[0028] Geometric isomers (also called E / Z isomers or cis-trans isomers) arise due to different positions of the substituents on the C=C double bond and may have a Z or E configuration, which are also called cis or trans configuration.

[0029] Optical isomers arise due to the different positions in space of the substituents or lone pairs on an atom (such as a carbon or sulfur atom) that contains four different substituents (which may include lone pairs). The atom is therefore a chiral or asymmetric center. Optical isomers that are not mirror images of one another are called "diastereomers" and optical isomers that are non-superimposable mirror images of each other are called "enantiomers".

[0030] An equimolar mixture of two enantiomers of a chiral compound is called a racemic mixture.

[0031] In the present invention, halogen in all cases denotes fluorine, chlorine, bromine and iodine.

[0032] As used herein, the term "alkyl group" (and other functional groups that contain an alkyl group, e.g., the alkyl group moiety of an alkoxy group, the alkyl group moiety of an arylalkyl group) is in each case a straight-chain or branched-chain alkyl group having typically 1 to 20 carbon atoms, more typically 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, and especially 1 to 3 carbon atoms. 1 ~C 4 Examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a 1-methylpropyl group (sec-butyl group), a 2-methylpropyl group (isobutyl group), and a 1,1-dimethylethyl group (tert-butyl group). 1 ~C 6 Examples of alkyl groups are C 1 ~C 4In addition to the functional groups referred to as alkyl groups, mention may be made of n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl or 1-ethyl-2-methylpropyl groups. 1 ~C 10 Examples of alkyl groups are C 1 ~C 6 In addition to functional groups referred to as alkyl groups, there are included, but are not limited to, n-heptyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 1-ethylhexyl, 2-ethylhexyl, 1,2-dimethylhexyl, 1-propylpentyl, 2-propylpentyl, nonyl, decyl, 2-propylheptyl, and 3-propylheptyl groups. The alkyl groups may be substituted with, but are not limited to, halogens, cyano, nitro, aryl, cycloalkyl, heterocyclyl, amide, and ester groups.

[0033] In the present invention, the term "aryl group" refers to a monovalent monocyclic or bicyclic aromatic hydrocarbon functional group having 6 to 10 ring atoms, such as, but not limited to, a phenyl group or a naphthyl group, particularly a naphthyl group. The aryl group may be substituted with, but not limited to, alkyl groups, halogens, cyano groups, nitro groups, cycloalkyl groups, heterocyclyl groups, amide groups, and ester groups.

[0034] In the present invention, the term "ring" refers to a "cycloalkyl group" or a "heterocyclyl group", and a "cycloalkyl group" refers to a monocyclic monovalent hydrocarbon group having 3 to 6 carbon atoms, which may be saturated or contain one double bond. The cycloalkyl group may be unsubstituted or substituted with one or two substituents independently selected from, but not limited to, alkyl, halogen, alkoxy, hydroxy, or cyano. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyanopropan-1-yl, 1-cyanomethylpropan-1-yl, 3-fluorocyclohexyl, and the like. When a cycloalkyl group contains a double bond, it may be referred to herein as a cycloalkenyl group. A "heterocyclyl group" refers to a monovalent, saturated or unsaturated, monocyclic functional group having 4 to 8 ring atoms, one or two of which are N, O, or S(O). p (wherein p is an integer of 0-2), with the remaining ring atoms being C. In addition, one or two ring carbon atoms of the cyclic heterocyclyl group may be optionally substituted with a -CO- functional group. More specifically, the term "heterocyclyl group" includes, but is not limited to, azetidinyl, oxetanyl, pyrrolidinyl, piperidinyl, homopiperidinyl, 2-oxopyrrolidinyl, 2-oxopiperidinyl, morpholinyl, piperazino, tetrahydropyranyl, and thiomorpholinyl groups. When cycloalkyl groups, heterocyclyl groups, and the like are substituted, they may be substituted with, but is not limited to, alkyl groups, halogens, cyano groups, nitro groups, aryl groups, amide groups, and ester groups.

[0035] The term "optionally substituted" refers to the fact that the associated functional group may or may not be substituted by a substituent.

[0036] When a functional group is substituted, the substituent may be, but is not limited to, an alkyl group, a halogen, a cyano group, a nitro group, a cycloalkyl group, a heterocyclyl group, an amide group, an ester group, an alkoxy group, a halogen, for example, but not limited to, when an alkyl group is substituted with a halogen, a haloalkyl group is formed.

[0037] "Alkoxy" refers to an -OR functional group, where R is an alkyl group as defined above, such as, but not limited to, a methoxy, ethoxy, propoxy, or 2-propoxy, n-butoxy, isobutoxy, or tert-butoxy group.

[0038] The "amide group" of the present invention is "-NHCO-" or " [ka] ", the amide group being, for example, -NHCOCH 3 , -NHCOH, -NHCOCH 2 CH 3 , -NHCOCH 2 CH 2 CH 3 , -NHCOCH(CH 3 ) 2 , -NHCOCH(CH 2 ) 2 , -N(COCH 3 ) 2 , -CONH 2 , -CON(CH 3 ) 2 , -CONHCH 3 , -CONHCH 2 CH 3 , -CON(CH 2 CH 3 ) 2 , -CONHCH(CH 3 ) 2 , -CONHCH 2 CH 2 CH 3 , -CONHCH 2 CH 2CH 2 CH 3 , phthalimide group, succinimide group, glutarimide group, maleimide group, [ka] , [ka] where R 9 is selected from an optionally substituted alkyl or aryl group, a carboxy group or a salt thereof, a cyano group, an optionally substituted amide group, and an optionally substituted ester group, and n is selected from a natural number of 1 to 6, and the ester group is preferably -COOCH 3 , -COOCH 2 CH 3 , -COOCH(CH 3 ) 2 , -COOCH 2 CH 2 CH 3 , -COOCH 2 CH 2 CH 2 CH 3 and n is selected from natural numbers of 1 to 6, and is preferably 1, 2, or 3, but is not limited to these.

[0039] In the present invention, the term "ester group" refers to a functional group containing "-COO-", and the ester group is, for example, -COOCH 3 , -COOCH 2 CH 3 , -COOCH(CH 3 ) 2 , -COOCH 2 CH 2 CH 3 , -COOCH 2 CH 2 CH 2 CH 3 However, the present invention is not limited to these.

[0040] In the present invention, the term "heteroaryl group" covers 5-10 membered aromatic monocyclic rings and aromatic fused rings, in which the aromatic monocyclic rings contain one or more (e.g., 1-4, or in some embodiments, 1-3) heteroatoms selected from N, O, and S, and the remaining atoms are carbon, and the aromatic fused rings contain one or more (e.g., 1-4, or in some embodiments, 1-3) heteroatoms selected from N, O, and S, and the remaining ring atoms are carbon, with at least one heteroatom being in the aromatic ring. For example, heteroaryl groups include 5-10 membered heterocycloalkyl aromatic rings fused with 5-10 membered cycloalkyl groups or heterocycloalkyl rings. In the case where only one ring of the fusion contains one or more heteroatoms, in a bicyclic heteroaromatic ring system, the point of attachment may be located in either ring. In the case where the total number of S and O atoms in the heteroaryl functional group exceeds 1, these heteroatoms are not adjacent to each other. In some embodiments, the total number of S and O atoms in the heteroaryl functional group is no more than 2. In some embodiments, the total number of S and O atoms in the aromatic heterocycle is no more than 1. Examples of heteroaryl functional groups include, but are not limited to, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2,3-pyridazinyl, 3,4-pyridazinyl, 2,4-pyrimidinyl, 3,5-pyrimidinyl, 2,3-pyrazolinyl, 2,4-imidazolinyl, isoxazolinyl, oxazolinyl, thiazolinyl, thiadiazolinyl, tetrazolyl, thienyl, benzothiophenyl, furanyl, benzofuranyl, benzimidazolinyl, indolinyl, pyrazinyl, triazolyl, quinolinyl, pyrazolyl, and 5,6,7,8-tetrahydroisoquinolinyl groups (the bonding position at the 1-position is set arbitrarily). Divalent functional groups derived from monovalent heteroaryl functional groups ending in "radical" by removing a hydrogen atom from the carbon bearing the free valence are named to correspond to the name of the monovalent functional group, e.g., a pyridinyl functional group having two points of attachment would be a pyridinylidene group.Heteroaryl groups do not cover or are identical to aryl, cycloalkyl or heterocycloalkyl groups, as defined herein.

[0041] "Arylalkyl" refers to a residue in which an aryl moiety is attached to a parent structure by an alkyl residue. Examples include benzyl, phenethyl, phenylvinyl, phenylallyl, etc. "Heteroaralkyl" refers to a residue in which a heteroaryl moiety is attached to a parent structure by an alkyl residue. Examples include furanylmethyl, pyridinylmethyl, pyrimidinylethyl, etc.

[0042] The following statements regarding the variables of the compounds of formula (A) and preferred embodiments of the variables, features of the uses and methods of the invention, and features of the compositions of the invention may be taken either on their own or in any preferred combination.

[0043] Generally speaking, the present invention provides a compound of the resorcinol class of formula (A): [ka] In the formula, W is [ka] where T is H, [ka] or [ka] and In the formula, R 1 is selected from H, an optionally substituted alkyl group, and an optionally substituted arylalkyl group; R 2 , R 6may be the same or different and are each independently selected from optionally substituted aryl and heteroaryl groups, optionally substituted alkyl groups, optionally substituted amide groups, and optionally substituted ester groups; R 3 , R 4 , R 7 , R 8 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; R 3 , R 4 may combine with the carbon atoms to which they are both attached to form a ring, R 7 , R 8 may combine with the carbon atoms to which they are both attached to form a ring, wherein the amide group is preferably -NHCOCH 3 , -NHCOH, -NHCOCH 2 CH 3 , -NHCOCH 2 CH 2 CH 3 , -NHCOCH(CH 3 ) 2 , -NHCOCH(CH 2 ) 2 , -N(COCH 3 ) 2 , -CONH 2 , -CON(CH 3 ) 2 , -CONHCH 3 , -CONHCH 2 CH 3 , -CON(CH 2 CH 3 ) 2 , -CONHCH(CH 3 ) 2 , -CONHCH 2 CH 2 CH 3 , -CONHCH 2 CH 2 CH 2 CH 3 , phthalimide group, succinimide group, glutarimide group, maleimide group, [ka] , [ka] where R 9 is selected from an optionally substituted alkyl group or an optionally substituted aryl group, a carboxy group or a salt thereof, a cyano group, an optionally substituted amide group, and an optionally substituted ester group, and n is selected from a natural number of 1 to 6, and the ester group is preferably -COOCH 3 , -COOCH 2 CH 3 , -COOCH(CH 3 ) 2 , -COOCH 2 CH 2 CH 3 , -COOCH 2 CH 2 CH 2 CH 3 It is one of the or a cosmetically or pharma- ceutical acceptable salt thereof, a stereoisomer or a mixture of stereoisomers in any ratio, in particular an enantiomer or a mixture of enantiomers, more in particular a racemic mixture.

[0044] Further, the formula (A) provided by the present invention is a compound of the formula (I) or a salt thereof, [ka] In the formula, R 1 is selected from H, an optionally substituted alkyl group, and an optionally substituted arylalkyl group; R 2 is selected from an optionally substituted aryl group, an optionally substituted alkyl group, an optionally substituted amide group, an optionally substituted ester group, an optionally substituted 5-10 membered heteroaryl group, said heteroaryl group containing 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, preferably an optionally substituted alkyl group, [ka] , [ka] where R 9 is selected from an optionally substituted alkyl or aryl group, a carboxy group or a salt thereof, a cyano group, an optionally substituted amide group, and an optionally substituted ester group; n is selected from a natural number of 1 to 6, preferably 1, 2, or 3; R 3 , R 4 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; R 3 , R 4 may combine with the carbon atoms to which they are both attached to form a ring.

[0045] Additionally, in some embodiments of formula (I), R 1 , H, C 1 ~C 6 alkyl group, particularly preferably H or methyl group; Additionally, in some embodiments of formula (I), R 2 teeth, [ka] wherein n is 1, 2 or 3.

[0046] Additionally, in some embodiments of formula (I), R 2 teeth, [ka] Selected from.

[0047] Additionally, in some embodiments of formula (I), R 2 is selected from the group consisting of phenyl groups.

[0048] In some embodiments of formula (I), preferably, R 3 , H, C 1 ~C 6 alkyl groups, particularly preferably H, methyl, ethyl, propyl and butyl groups; In some embodiments of formula (I), preferably, R 4 , H, C 1 ~C 6 alkyl groups, particularly preferably H, methyl, ethyl, propyl and butyl groups; Furthermore, the present invention preferably provides compounds of formula (I) represented by the following formulae (I-1), (I-2), and (I-3): [ka] [ka] [ka] In the formula, R 1 , H, C 1 ~C 6 alkyl group, particularly preferably H or a methyl group; R 2 is selected from a phenyl group, and in some embodiments, preferably, R 3 , H, C 1 ~C 6 alkyl group, particularly preferably H, methyl group, ethyl group, propyl group, and butyl group; R 4 , H, C 1 ~C 6 alkyl group, particularly preferably H, methyl group, ethyl group, propyl group, and butyl group; R 10 is C 1 ~C 18 The alkyl group is preferably an n-dodecyl group, an n-tetradecyl group, or an n-hexadecyl group, where n is selected from 1, 2, and 3.

[0049] Furthermore, the compound of formula (A) provided by the present invention is preferably a compound of formula (Ia): [ka] In the formula, R 1 is selected from H, an optionally substituted alkyl group, and an optionally substituted arylalkyl group; R 2 is selected from an optionally substituted aryl group, an optionally substituted 5-10 membered heteroaryl group, said 5-10 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur, an optionally substituted alkyl group, and an optionally substituted amido group; R 3 is selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; Z 1 , Z 2 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; Z 1 , Z 2 may combine with the carbon atoms to which they are both attached to form a ring, which ring may be substituted by a substituent.

[0050] Furthermore, in the compound of formula (Ia), R 1 , H, C 1 ~C 6 alkyl group, particularly preferably H or methyl group; Additionally, in some embodiments of the compounds of Formula (Ia), R 2 teeth, [ka] (wherein n is a natural number from 1 to 6), [ka] , and a phenyl group.

[0051] Furthermore, the compound of formula (Ia) of the present invention is preferably a compound of the following formula Ia-1 and formula Ia-2. [ka] [ka] In the formula, R 1 , H, C 1 ~C 6 alkyl group, preferably H or methyl group; Z 1 , Z 2 are H and C, respectively. 1 ~C 6 alkyl groups, preferably one of H, methyl, ethyl, propyl and butyl groups, or Z 1 and Z 2 is the bonded carbon atom and C 3 ~C 6 Cycloalkyl groups, 3- to 6-membered heterocyclyl groups, C 3 ~C 6 The cycloalkyl group is preferably a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and the 3- to 6-membered heterocyclyl group is preferably an ethylene oxide group, an azetidinyl group, an oxetanyl group, a pyrrolidinyl group, a piperidinyl group, a homopiperidinyl group, a 2-oxopyrrolidinyl group, a 2-oxopiperidinyl group, a morpholinyl group, a piperazino group, a tetrahydropyranyl group, or a thiomorpholinyl group. n is a natural number selected from 1 to 6, and is preferably 1, 2, or 3.

[0052] Furthermore, in some embodiments, compound A of the present invention is preferably a compound of formula (V): [ka] In the formula, R 1 is selected from H, an optionally substituted alkyl group, and an optionally substituted arylalkyl group; R 2is selected from an optionally substituted aryl group, an optionally substituted alkyl group, an optionally substituted amido group, said amido group being preferably -NHCOCH 3 , -NHCOH, -NHCOCH 2 CH 3 , -NHCOCH 2 CH 2 CH 3 , -NHCOCH(CH 3 ) 2 , -NHCOCH(CH 2 ) 2 , -N(COCH 3 ) 2 , -CONH 2 , -CON(CH 3 ) 2 , -CONHCH 3 , -CONHCH 2 CH 3 , -CON(CH 2 CH 3 ) 2 , -CONHCH(CH 3 ) 2 , -CONHCH 2 CH 2 CH 3 , -CONHCH 2 CH 2 CH 2 CH 3 , phthalimide group, succinimide group, glutarimide group, maleimide group, [ka] , [ka] wherein R 9 is an optionally substituted alkyl or aryl group, a carboxy group or a salt thereof, an optionally substituted ester group (the ester group is preferably -COOCH 3 , -COOCH 2 CH 3 , -COOCH(CH 3 ) 2 , -COOCH 2 CH2 CH 3 , -COOCH 2 CH 2 CH 2 CH 3 a cyano group, or an optionally substituted amide group; n is a natural number selected from 1 to 6; R 3 , R 4 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; R 3 , R 4 may combine with the carbon atoms to which they are both attached to form a ring.

[0053] Further, in some embodiments, the compound of formula (V) is a compound of formula (Va): [ka] In the formula, R 1 is selected from H, an optionally substituted alkyl group, and an optionally substituted arylalkyl group; R 2 is selected from an optionally substituted aryl group, an optionally substituted alkyl group, an optionally substituted amido group, said amido group being preferably -NHCOCH 3 , -NHCOH, -NHCOCH 2 CH 3 , -NHCOCH 2 CH 2 CH 3 , -NHCOCH(CH 3 ) 2 , -NHCOCH(CH 2 ) 2 , -N(COCH 3 ) 2 , -CONH 2 , -CON(CH 3 ) 2 , -CONHCH 3 , -CONHCH 2 CH 3 , -CON(CH 2 CH 3 )2 , -CONHCH(CH 3 ) 2 , -CONHCH 2 CH 2 CH 3 , -CONHCH 2 CH 2 CH 2 CH 3 , phthalimide group, succinimide group, glutarimide group, maleimide group, [ka] , [ka] wherein R 9 is an optionally substituted alkyl or aryl group, a carboxy group or a salt thereof, an optionally substituted ester group (the ester group is preferably -COOCH 3 , -COOCH 2 CH 3 , -COOCH(CH 3 ) 2 , -COOCH 2 CH 2 CH 3 , -COOCH 2 CH 2 CH 2 CH 3 a cyano group, or an optionally substituted amide group; n is a natural number selected from 1 to 6; R 3 is selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; Z 1 , Z 2 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; Z 1 , Z 2 may be joined with the carbon atom to which they are both attached to form a ring, which ring may be substituted.

[0054] Furthermore, the compound of formula (A) provided by some embodiments of the present invention is preferably a compound of formula (VI): [ka] In the formula, R 1 is selected from H, an optionally substituted alkyl group, and an optionally substituted arylalkyl group; R 2 , R 6 may be the same or different and are each independently selected from an optionally substituted aryl group, a 5-10 membered heteroaryl group, said 5-10 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur, an optionally substituted alkyl group, an optionally substituted ester group, an optionally substituted amido group, wherein said amido group is preferably -NHCOCH 3 , -NHCOH, -NHCOCH 2 CH 3 , -NHCOCH 2 CH 2 CH 3 , -NHCOCH(CH 3 ) 2 , -NHCOCH(CH 2 ) 2 , -N(COCH 3 ) 2 , -CONH 2 , -CON(CH 3 ) 2 , -CONHCH 3 , -CONHCH 2 CH 3 , -CON(CH 2 CH 3 ) 2 , -CONHCH(CH 3 ) 2 , -CONHCH 2 CH 2 CH 3 , -CONHCH 2 CH 2 CH 2 CH 3 , phthalimide group, succinimide group, glutarimide group, maleimide group, [ka] , [ka] wherein R 9 is an optionally substituted alkyl or aryl group, a carboxy group or a salt thereof, an optionally substituted ester group (the ester group is preferably -COOCH 3 , -COOCH 2 CH 3 , -COOCH(CH 3 ) 2 , -COOCH 2 CH 2 CH 3 , -COOCH 2 CH 2 CH 2 CH 3 a cyano group, or an optionally substituted amide group; n is a natural number selected from 1 to 6; R 3 , R 4 , R 7 , R 8 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; R 3 , R 4 may combine with the carbon atoms to which they are both attached to form a ring, R 7 , R 8 may be joined with the carbon atom to which they are both attached to form a ring, which ring may be substituted.

[0055] Further, in some embodiments of formula (VI), R 2 , R 6 teeth, [ka] where n is a natural number from 1 to 6.

[0056] Further, in some embodiments of formula (VI), R 2 , R6 is selected from the group consisting of phenyl groups.

[0057] Furthermore, the compound represented by formula (VI) of the present invention is preferably provided as a compound represented by the following formula (VI-1) and formula (VI-2). [ka] [ka] In the formula, R 1 , H, C 1 ~C 6 alkyl group, preferably H or methyl group; R 3 , H, C 1 ~C 6 alkyl group, preferably one of H, methyl, ethyl, propyl and butyl groups; R 4 , H, C 1 ~C 6 alkyl group, preferably one of H, methyl, ethyl, propyl and butyl groups; R 7 , H, C 1 ~C 6 alkyl group, preferably H, methyl group, ethyl group, propyl group, butyl group, R 8 , H, C 1 ~C 6 and m is selected from the group consisting of alkyl groups, preferably methyl, ethyl, propyl and butyl groups; n is selected from 1, 2 and 3;

[0058] Furthermore, in some embodiments of the present invention, formula (VI) is preferably formula (VIa): [ka] In the formula, R 1 is selected from H, an optionally substituted alkyl group, and an optionally substituted arylalkyl group; R 2 , R 6may be the same or different and are each independently selected from an optionally substituted aryl group, a 5- to 10-membered heteroaryl group, said 5- to 10-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur, an optionally substituted alkyl group, an optionally substituted ester group, and an optionally substituted amide group, wherein the amide group is preferably -NHCOCH 3 , -NHCOH, -NHCOCH 2 CH 3 , -NHCOCH 2 CH 2 CH 3 , -NHCOCH(CH 3 ) 2 , -NHCOCH(CH 2 ) 2 , -N(COCH 3 ) 2 , -CONH 2 , -CON(CH 3 ) 2 , -CONHCH 3 , -CONHCH 2 CH 3 , -CON(CH 2 CH 3 ) 2 , -CONHCH(CH 3 ) 2 , -CONHCH 2 CH 2 CH 3 , -CONHCH 2 CH 2 CH 2 CH 3 , phthalimide group, succinimide group, glutarimide group, maleimide group, [ka] , [ka] wherein R 9 is an optionally substituted alkyl or aryl group, a carboxy group or a salt thereof, an optionally substituted ester group (the ester group is preferably -COOCH3 , -COOCH 2 CH 3 , -COOCH(CH 3 ) 2 , -COOCH 2 CH 2 CH 3 , -COOCH 2 CH 2 CH 2 CH 3 a cyano group, or an optionally substituted amide group; n is a natural number selected from 1 to 6; R 3 , R 4 , R 7 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; R 3 , R 4 may combine with the carbon atoms to which they are both attached to form a ring; Z 1 , Z 2 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; Z 1 , Z 2 may be joined with the carbon atom to which they are both attached to form a ring, which ring may be substituted.

[0059] Particularly preferably, the compound of the present invention is selected from the following compounds: [ka] N-(1-(2,4-dihydroxyphenyl)ethyl)-2-pyrrolidone [ka] N-(1-(2,4-dihydroxyphenyl)propyl)-2-pyrrolidone [ka] N-(1-(2,4-dihydroxyphenyl)ethyl)-2-piperidone [ka] N-(1-(2,4-dihydroxyphenyl)propyl)-2-piperidone [ka] N-(1-(2,4-dihydroxyphenyl)ethyl)-2-hexamethyleneiminone [ka] N-(1-(2,4-dihydroxyphenyl)propyl)-2-hexamethyleneiminone [ka] 1,1'-((4,6-dihydroxy-1,3-phenylidene)bis(ethane-1,1-diyl))bis(pyrrolidin-2-one) [ka] 1,1'-((4,6-dihydroxy-1,3-phenylidene)bis(prop-1,1-diyl))bis(pyrrolidin-2-one) [ka] 1,1'-((4,6-dihydroxy-1,3-phenylidene)bis(ethane-1,1-diyl))bis(piperidin-2-one) [ka] 1,1'-((4,6-dihydroxy-1,3-phenylidene)bis(prop-1,1-diyl))bis(piperidin-2-one) [ka] 1,1'-((4,6-dihydroxy-1,3-phenylidene)bis(ethane-1,1-diyl))bis(hexamethyleneimin-2-one) [ka] 1,1'-((4,6-dihydroxy-1,3-phenylidene)bis(prop-1,1-diyl))bis(hexamethyleneimin-2-one) [ka] 4,6-Bis(1-phenylethyl)-1,3-benzenediol

[0060] The present invention also provides a method for preparing the compound of formula (I) above, the synthetic route being as follows: [ka] In the formula, R 1 , R 2 , R 3 and R 4 is defined above, where R 5 is selected from leaving functional groups, the leaving functional groups being OH, H 2 One of O, OTs, OMs, Cl, Br, and I is selected. In the above reaction, the reaction temperature is 40 to 110°C, preferably 70 to 90°C. In the above reaction, the molar ratio of the compounds of formula II and formula IVa charged in the reaction is 1:1-1.5, preferably 1:1.01-1.05; The above reaction is carried out in a solvent, and the solvent is one or a combination of two or more selected from toluene, acetonitrile, dioxane, DMF, DMAc, DMSO, NMP, DMI, ethyl acetate, isopropyl acetate, dichloroethane, etc., and preferably toluene.

[0061] The above reaction may be promoted by a catalyst, the catalyst being a protic acid or a Lewis acid selected from hydrochloric acid, HBr, HI, HF, sulfuric acid, phosphoric acid, oxalic acid, methanesulfonic acid, trifluoromethanesulfonic acid, boric acid, benzenesulfonic acid, p-toluenesulfonic acid, etc., preferably p-toluenesulfonic acid.

[0062] The present invention also provides a method for preparing the compound of formula (Ia) above, the synthetic route being as follows: [ka] In the formula, R 1 , R 2 , R 3 is defined above, and Z 1 , Z 2 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; Z 1 , Z 2 may combine with the carbon atoms to which they are both attached to form a ring, In the above reaction, the reaction temperature is 40 to 110°C, preferably 70 to 90°C. In the above reaction, the molar ratio of the reaction of formula II and formula IIIa is 1:1-1.5, preferably 1:1.01-1.05; The above reaction is carried out in a solvent, and the solvent is one or a combination of two or more selected from toluene, acetonitrile, dioxane, DMF, DMAc, DMSO, NMP, DMI, ethyl acetate, isopropyl acetate, dichloroethane, etc., and preferably toluene.

[0063] The above reaction may be promoted by a catalyst, the catalyst being a protic acid or a Lewis acid selected from hydrochloric acid, HBr, HI, HF, sulfuric acid, phosphoric acid, oxalic acid, methanesulfonic acid, trifluoromethanesulfonic acid, boric acid, benzenesulfonic acid, p-toluenesulfonic acid, etc., preferably p-toluenesulfonic acid.

[0064] The present invention also provides a method for preparing a compound of formula (V), the synthetic route being as follows: [ka] In the formula, R 1 , R 2 , R 3 , R 4is defined above, where R 5 is selected from leaving functional groups, the leaving functional groups being OH, H 2 Selected from O, OTs, OMs, Cl, Br, I, etc.

[0065] In the above reaction, the reaction temperature is 40 to 110°C, preferably 70 to 90°C. In the above reaction, the molar ratio of the compounds of formula II and formula IVa charged in the reaction is 1:2.0-3.0, preferably 1:2.01-2.10; The above reaction is carried out in a solvent, and the solvent is one or a combination of two or more selected from toluene, acetonitrile, dioxane, DMF, DMAc, DMSO, NMP, DMI, ethyl acetate, isopropyl acetate, dichloroethane, etc., and preferably toluene.

[0066] The above reaction may be promoted by a catalyst, the catalyst being a protic acid or a Lewis acid selected from hydrochloric acid, HBr, HI, HF, sulfuric acid, phosphoric acid, oxalic acid, methanesulfonic acid, trifluoromethanesulfonic acid, boric acid, benzenesulfonic acid, p-toluenesulfonic acid, etc., preferably p-toluenesulfonic acid.

[0067] The present invention also provides a method for preparing a compound of formula (Va), the synthetic route being as follows: [ka] In the formula, R 1 , R 2 , R 3 is defined above, and Z 1 , Z 2 may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; Z 1 , Z 2 may combine with the carbon atoms to which they are both attached to form a ring, In the above reaction, the reaction temperature is 40 to 110°C, preferably 70 to 90°C. In the above reaction, the molar ratio of the compounds of formula II and formula IIIa charged in the reaction is 1:2.0-3.0, preferably 1:2.01-2.10; The above reaction is carried out in a solvent, and the solvent is one or a combination of two or more selected from toluene, acetonitrile, dioxane, DMF, DMAc, DMSO, NMP, DMI, ethyl acetate, isopropyl acetate, and dichloroethane, and preferably toluene.

[0068] The above reaction may be promoted by a catalyst, the catalyst being a protic acid or a Lewis acid selected from hydrochloric acid, HBr, HI, HF, sulfuric acid, phosphoric acid, oxalic acid, methanesulfonic acid, trifluoromethanesulfonic acid, boric acid, benzenesulfonic acid, p-toluenesulfonic acid, etc., preferably p-toluenesulfonic acid.

[0069] The present invention also provides a method for preparing a compound of formula (VI), the synthetic route being as follows: [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R 6 , R 7 and R 8 is defined above, where R 5 is selected from leaving functional groups, the leaving functional groups being OH, H 2 Selected from O, OTs, OMs, Cl, Br, I, etc.

[0070] In the above reaction, the reaction temperature is 40 to 110°C, preferably 70 to 90°C. In the above reaction, the molar ratio of the components of formula I and formula IVb charged to the reaction is 1:1-1.5, preferably 1:1.01-1.05; The above reaction is carried out in a solvent, and the solvent is one or a combination of two or more selected from toluene, acetonitrile, dioxane, DMF, DMAc, DMSO, NMP, DMI, ethyl acetate, isopropyl acetate, dichloroethane, etc., and preferably toluene.

[0071] The above reaction may be promoted by a catalyst, the catalyst being a protic acid or a Lewis acid selected from hydrochloric acid, HBr, HI, HF, sulfuric acid, phosphoric acid, oxalic acid, methanesulfonic acid, trifluoromethanesulfonic acid, boric acid, benzenesulfonic acid, p-toluenesulfonic acid, etc., preferably p-toluenesulfonic acid.

[0072] The present invention also provides a method for preparing a compound of formula (VIa), the synthetic route being as follows: [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , Z 1 and Z 2 is as defined above.

[0073] In the above reaction, the reaction temperature is 40 to 110°C, preferably 70 to 90°C. In the above reaction, the molar ratio of the compounds of formula I and formula IIIb charged to the reaction is 1:1-1.5, preferably 1:1.01-1.05; The above reaction is carried out in a solvent, and the solvent is one or a combination of two or more selected from toluene, acetonitrile, dioxane, DMF, DMAc, DMSO, NMP, DMI, ethyl acetate, isopropyl acetate, dichloroethane, etc., and preferably toluene.

[0074] The above reaction may be promoted by a catalyst, the catalyst being a protic acid or a Lewis acid selected from hydrochloric acid, HBr, HI, HF, sulfuric acid, phosphoric acid, oxalic acid, methanesulfonic acid, trifluoromethanesulfonic acid, boric acid, benzenesulfonic acid, p-toluenesulfonic acid, etc., preferably p-toluenesulfonic acid.

[0075] The compounds of the invention may be used to manufacture a drug or cosmetic product for treating, preventing and / or reducing hyperpigmentation, in particular topically on the skin, for example human skin.

[0076] The present invention also provides a cosmetic or pharmaceutical composition containing the compound of formula (A) of the present invention or a salt thereof.

[0077] Furthermore, the above cosmetic composition may be prepared in any suitable form, such as a cream, emulsion, paste, capsule, lotion, foam, gel, dispersion, suspension, spray, essence, pack, or the like.

[0078] Additionally, the pharmaceutical / cosmetic compositions of the present invention may further comprise one or more additives such as antioxidants, emollients, moisturizers, thickeners, fragrances, preservatives, pigments or colorants, or sunscreens, which additives are well known to those skilled in the art.

[0079] Antioxidants may be used to protect the components of the composition from oxidizing agents contained in or in contact with the composition. Examples of antioxidants include ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, potassium propyl gallate, octyl gallate, dodecyl gallate, phenyl-α-naphthylamine, and tocopherols (such as α-tocopherol).

[0080] Emollients are agents that soften and smooth the skin.Examples of emollients include oils and waxes (such as microcrystalline wax, polyethylene), triglycerides (such as castor oil, cocoa butter, safflower oil, corn oil, olive oil, cod liver oil, almond oil, palm oil, soybean oil), squalene, acetylated monoglycerides, ethoxylated glycerides, fatty acids, alkyl esters of fatty acids, alkenyl esters of fatty acids, fatty alcohols, fatty alcohol ethers, ether esters, lanolin and lanolin derivatives, polyol esters, wax esters (such as beeswax, vegetable wax), phospholipids and sterols, isopropyl palmitate or glyceryl stearate, especially almond oil or fatty alcohols (such as cetyl alcohol, stearyl alcohol and / or myristyl alcohol).

[0081] Silicones are particularly preferred emollients. Silicones that can be used in the present invention include dimethicone, methylcyclosiloxane, phenyl polytrimethicone, phenyl polydimethicone, cetyl dimethicone, stearyl dimethicone, amino-blocked dimethicone, C 30~45 Alkyl dimethicone, C 30~45 In particular, amino-blocked dimethicones may be used as emollients in the present invention, including but not limited to alkyl methicones, cetostearyl methicones, dimethicone copolyols, cyclopentyl siloxanes, cyclohexyl siloxanes, or any combination thereof.

[0082] Moisturizers are used to maintain or increase moisture in the skin. Examples of moisturizers include propylene glycol, butylene glycol, polyethylene glycol (PEG) (such as PEG-4 to PEG-32), glycerol (also called glycerin), sorbitol, xylitol, maltitol, mannitol, polydextrose, hyaluronic acid and its salts (such as sodium salt or potassium salt), urea, aloe vera juice, honey, etc.

[0083] Thickener is used to increase the viscosity or consistency of the composition.Examples of thickener include lipid thickener such as cetyl alcohol, stearyl alcohol, myristyl alcohol, carnauba wax or stearic acid, natural thickener such as cellulose derivative (e.g. hydroxyethyl cellulose), guar gum, locust bean gum, xanthan gum or gelatin, mineral thickener such as silica, bentonite or magnesium aluminum silicate, synthetic thickener such as carbomer, ionic thickener such as NaCl.

[0084] Examples of fragrances or flavorings include peppermint, rose oil, rose water, aloe vera juice, clove oil, menthol, camphor, eucalyptus oil, and other plant extracts. To eliminate some of the odors of the composition, a masking agent may be used.

[0085] Preservatives may be used to protect the composition from degradation. Examples of preservatives include phenoxyethanol, methylparaben, benzalkonium chloride, benzethonium chloride, propylparaben, benzoic acid, benzyl alcohol, and mixtures thereof. In particular, phenoxyethanol, methylparaben, or mixtures thereof may be used.

[0086] Pigments or colorants are used to change the color of the composition. Besides the soluble substances mentioned above, insoluble light-protecting pigments, especially finely dispersed metal oxides or salts, are also suitable for this purpose. To obtain a white composition, titanium dioxide may be chosen. The clear or transparent composition is rendered opaque by the use of a light-blocking agent such as the oxide of titanium. Examples of particularly suitable metal oxides include zinc oxide, iron, zirconium, silicon, manganese, aluminum, cerium oxide and mixtures thereof. Silicates (talc), barium sulfate or zinc stearate are examples of suitable salts. The oxides and salts are used as pigments in emulsions for skin care and skin protection, decorative cosmetics. In this case, the particles have an average diameter of less than 100 nm, preferably between 5 and 50 nm, particularly preferably between 15 and 30 nm. They may be spherical, or particles with other shapes than ellipsoidal or spherical may be used. The pigments may be subjected to a surface treatment, i.e. hydrophilized or hydrophobized. A typical example is coated titanium dioxide. In this case, the first choice of suitable hydrophobic coating agents are silicones, in particular trialkoxyoctylsilanes or trisiloxanes. So-called micro- or nanopigments are preferably used in sunscreen formulations, preferably using micronized zinc oxide.

[0087] In a preferred embodiment, the light-protecting pigment is selected from micronized titanium dioxide, zinc oxide, and micronized zinc oxide. When titanium dioxide is selected as the light-protecting pigment, its total amount is advantageously between 0.1 and 10.0% by weight of the formulation. When zinc oxide is selected as the light-protecting pigment, its total amount is advantageously between 0.1 and 10.0% by weight of the formulation, and when one or more triazine organic pigments are selected, their total amount is advantageously between 0.1 and 10.0% by weight, based on the total amount of the formulation. In a preferred embodiment, the pharmaceutical or cosmetic composition according to the invention may further contain at least one skin-lightening agent, such as sclareolide.

[0088] The present invention also relates to the use of the compounds of formula (A) according to the invention in cosmetics, in particular as depigmenting, whitening, bleaching or brightening agents, and more particularly in cosmetics for the skin, such as human skin.

[0089] The present invention also relates to the use of the cosmetic composition according to the invention in cosmetics, in particular as a depigmenting, whitening, bleaching or brightening composition, more particularly in cosmetics for topical application to the skin, such as human skin.

[0090] The present invention also relates to the use of a compound of formula (A) according to the invention for preparing a cosmetic composition, said cosmetic composition being used in particular for depigmenting, lightening, bleaching or brightening the skin, such as human skin.

[0091] The present invention also relates to the use of the compounds of formula (A) according to the invention as depigmenting, whitening, bleaching or brightening agents, more particularly on the skin (such as human skin).

[0092] The present invention also relates to a method for achieving depigmentation, lightening, bleaching or brightening of skin (such as human skin) by applying to human skin in need thereof an effective amount of a compound according to the present invention or a cosmetic composition according to the present invention.

[0093] The present invention also relates to the use of the compounds according to the invention as a medicament, in particular in the treatment of pigmentation disorders, and more particularly said use by topical application to the skin, such as human skin.

[0094] The present invention also relates to the use of a pharmaceutical composition, in particular a dermatological composition, according to the invention as a medicament, in particular in the treatment of pigmentation disorders, and more particularly said use by topical application to the skin, such as human skin.

[0095] The present invention also relates to the use of the compounds according to the invention for preparing a pharmaceutical composition, in particular a dermatological composition, which is in particular used for treating pigmentation disorders and further in particular for topical application to the skin (human skin).

[0096] The present invention also relates to the use of the compounds according to the invention for treating pigmentation disorders, more particularly said use by topical application to the skin, such as human skin.

[0097] The present invention also relates to a method for treating pigmentation disorders of the skin (such as human skin) by applying to the skin of a human in need thereof an effective amount of a compound according to the present invention or a pharmaceutical composition, in particular a dermatological composition, according to the present invention.

[0098] Said pigmentation disorders are furthermore hyperpigmentation, especially such as small birthmarks, melasma, freckles, post-inflammatory hyperpigmentation, drug-, chemical- or sun-induced hyperpigmentation.

[0099] The present invention also relates to the use of the compounds according to the invention as antioxidants, in particular for reducing or inhibiting oxidative stress, in particular UV-induced oxidative stress, more particularly in the skin.

[0100] The present invention also relates to a method for reducing or inhibiting oxidative stress, in particular UV-induced oxidative stress, more particularly oxidative stress in the skin, which comprises administering, in particular topically administering, to a human in need thereof an effective amount of a compound according to the invention.

[0101] When the composition of the present invention is administered to human skin, the combination of the compound of the present invention and the UV filter is well tolerated, does not cause redness, whitening or browning of the skin, is not irritating, does not dry the skin, does not cause moisture, does not form a scaly, powdery or sticky film, and does not cause the skin to crack. These UV filters may be UV-A filters, UV-B filters, photoprotective pigments or mixtures thereof. Among them, the UV filter refers to an organic substance (light filter) that is, for example, liquid or crystalline at room temperature and can absorb ultraviolet radiation and release the absorbed energy in the form of long-wave radiation such as heat. Generally, the content of the UV filter is 0.05-50% by weight, preferably 0.5-40% by weight.

[0102] The UV filter may be either oil-soluble or water-soluble.

[0103] Suitable oil-soluble substances include the following: 3-benzylidene camphor and its derivatives, e.g. 3-(4-methylbenzylidene) camphor 4-Aminobenzoic acid derivatives, preferably 2-ethylhexyl 4-(dimethylamino)benzoate, 2-octyl 4-(dimethylamino)benzoate, pentyl 4-(dimethylamino)benzoate Esters of cinnamic acid, preferably 2-ethylhexyl 4-methoxycinnamate, propyl 4-methoxycinnamate, isoamyl 4-methoxycinnamate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate (octocrylene) Esters of salicylic acid, preferably 2-ethylhexyl salicylate, homosalate, menthyl salicylate Benzophenone derivatives, preferably 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2-hydroxy-4-methoxy-benzophenone, 2,2'-dihydroxy-4-methoxybenzophenone Esters of benzylmalonic acid, preferably bis-2-ethylhexyl 4-methoxybenzylmalonate Triazine derivatives, such as 2,4,6-tris(p-2-ethylhexylaniline)-1,3,5-triazine, bis(octylbutamide triazine) Benzoylmethane derivatives, preferably 4-tert-butyl-4'-methoxydibenzoylmethane Carbonyl-containing polycyclic compounds, such as tricyclo(5.2.1.0)decan-one derivatives

[0104] Examples of suitable water-soluble substances include the following: 2-Phenylbenzimidazole-5-sulfonic acid, and its alkali metal salts, alkaline earth metal salts, ammonium salts, alkylammonium salts, alkanol salts, and glucosamine salts Disodium salt of 2,2'-bis-(1,4-phenylene) 1H-benzimidazole-4,6-disulfonic acid Sulfonic acid derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its salts Sulfonic acid derivatives of 3-benzylidene camphor, preferably benzylidene dl-camphorsulfonic acid, 2-methyl-5-(2-oxo-3-bornylidene)sulfonic acid and its salts

[0105] Typical examples of particularly suitable UV-A filters include benzoylmethane derivatives such as 4-tert-butyl-4'-methoxy-dibenzoylmethane, 2-(4-diethylamino-2-hydroxybenzoyl)-hexyl benzoate, 1-phenyl-3-(4'-isopropylphenyl)propane-1,3-dione, enamine compounds. Of course, UV-A and UV-B filters may be used in combination, for example diphenylmethane derivatives and / or benzoylmethane derivatives 4-tert-butyl-4'-methoxy-dibenzoylmethane in combination with cinnamic acid derivatives, preferably 2-cyano-3,3-diphenylacrylic acid 2-ethylhexyl (octocrylene) and / or 4-methoxycinnamate 2-ethylhexyl and / or 4-methoxycinnamate isoamyl and / or 4-methoxycinnamate propyl. Such combinations of cinnamic acid ester derivatives may be replaced with water-soluble filters, such as 2-phenylbenzimidazole-5-sulfonic acid and its alkali metal, alkaline earth metal, ammonium, alkylammonium, alkanol, and glucosamine salts and / or 4-(2-oxo-3-bornylidenemethyl)benzenesulfonic acid and 2-methyl-5-(2-oxo-3-bornylidene)sulfonic acid and its alkali metal, alkaline earth metal, ammonium, alkylammonium, alkanol, and glucosamine salts.

[0106] In a preferred embodiment, the preparation according to the invention (cosmetic or pharmaceutical) contains at least one additional UV-absorbing substance selected from the following group: Camphor benzalkonium methosulfate Terephthalidenedicamphorsulfonic acid and its salts Menthyl Salicylate Benzylidene dl-camphorsulfonic acid and its salts 2-Ethylhexyl 2-cyano-3,3-diphenylacrylate Ethyl p-aminobenzoate Isoamyl p-methoxycinnamate 2-Phenylbenzimidazole sulfonic acid and its salts 2,4,6-Tris(p-2-ethylhexylaniline)-1,3,5-triazine 2-(2H-benzotriazol-2-yl)-4-methyl-6-(2-methyl-3-(1,3,3,3-tetramethyl-1-(trimethylsilyl-oxy)-disiloxanyl)-propyl)phenol Methylenebis-benzotriazolyltetramethylbutylphenol 4,4'-[(6-[4-(1,1-dimethyl)-aminocarbonyl]phenylamino)-1,3,5-triazine-2,4-diyl]diimino]-di-(2-ethylhexyl benzoate) 3-(4'-Methylbenzylidene)-D,L-camphor 3-Benzylidene camphor 2-Ethylhexyl Salicylate 2-Ethylhexyl 4-dimethylaminobenzoate 4-Hydroxy-4-methoxybenzophenone-5-sulfonic acid and its salts Malonate benzylidene polysiloxane Menthyl Anthranilate Polyacrylamide methyl benzylidene camphor 2-Ethylhexyl p-Methoxycinnamate or mixtures thereof

[0107] When the composition of the present invention is administered to human skin, it may be used in combination with a skin lightening agent to enhance the effect of alleviating hyperpigmentation. Suitable skin lightening agents for use in the present invention include kojic acid derivatives (preferably kojic dipalmitate), arbutin, ascorbic acid and ascorbic acid derivatives (preferably magnesium ascorbyl phosphate), hydroquinone and hydroquinone derivatives, sclareolide, amino acids (preferably cyclohexylcarbamates, N-acetyltyrosine and its derivatives, undecylenoylphenylalanine), sulfur-containing molecules (preferably glutathione, cysteine, thiourea derivatives, lipoic acid), α-his(OH)-1,1-trimethylsiloxyphenylalanine, ... hydroxy acids (preferably citric acid, lactic acid, malic acid, salts and esters thereof), gluconic acid, chromone derivatives (preferably aloesin), 1-aminoethylphosphinic acid, flavonoids, ellagic acid, nicotinamide, thujaplicin and its derivatives, triterpenes (preferably maslinic acid), sterols (preferably ergosterol), benzofuranones (preferably senkyunolide), 4-vinylguaiacol, 4-ethylguaiacol, zinc salts (preferably zinc chloride or gluconic acid zinc), diacids (preferably octadecenedioic acid and / or azelaic acid), nitric oxide synthesis inhibitors (preferably L-nitroarginine and its derivatives, 2,7-dinitroindazole or thio-L-citrulline), metal chelators (preferably α-hydroxy fatty acids, phytic acid, cholic acid, bile extract, humic acid, EGTA, EDTA and its derivatives), soy milk and its extracts, retinoids, serine protease inhibitors, other synthetic or extracted natural active ingredients (preferably bearberry extract Examples of the plant extracts include grape extract, sorrel extract, jicama extract, rice extract, papaya extract, ginseng extract, magnolia extract, licorice root extract (preferably glabridin or licochalcone A), cinnamon extract, sorrel extract, pinus (pine) extract, grape extract, or a stilbene derivative separated or concentrated therefrom, saxifrage extract, Scutellaria root extract, microalgae extract (preferably Tetraselmis extract), and ginseng extract). EXAMPLES

[0108] The present invention will now be described in detail with reference to the following examples, although it will be understood that the relevant examples do not impose any limitations on the scope of protection.

[0109] In the following examples, The amounts of reactants and products are determined by liquid chromatography (Agilent HPLC 1260).

[0110] The conversion and selectivity of the reaction are calculated by the following formulas. Conversion rate = (number of moles of raw material input - number of moles of raw material remaining in the product) / number of moles of raw material input × 100% Selectivity = actual moles of desired product / theoretical moles of desired product x 100%

[0111] Unless otherwise stated, all materials used were commercially available products and the room temperature was 25±5°C.

[0112] Example 1 [ka] 250g toluene, 1.0g p-toluenesulfonic acid catalyst, 110g resorcinol, and 125g N-vinylpiperidone were added to a 1000mL four-neck flask, heated, and reacted at 90℃ for 10 hours, and the completion of the reaction was detected by liquid chromatography. After removing the solvent under reduced pressure, a mixed solvent of ethyl acetate / petroleum ether was added and the product was recrystallized to obtain a product with a yield of 90% and a purity of 99%.

[0113] Example 2 [ka] 250g of toluene, 1.0g of p-toluenesulfonic acid catalyst, 110g of resorcinol, and 202g of 6-methoxy-2-naphthylethanol were added to a 1000mL four-neck flask, and the mixture was heated and reacted at 90℃ for 10 hours. The completion of the reaction was detected by liquid chromatography, and the solvent was removed under reduced pressure. After that, a mixed solvent of ethyl acetate / petroleum ether was added and the product was recrystallized to obtain a product with a yield of 92% and a purity of 99%.

[0114] Example 3 [ka] 250g toluene, 1.0g p-toluenesulfonic acid catalyst, 110g resorcinol, and 222g N-vinylpyrrolidone were added to a 1000mL four-neck flask, heated, and reacted at 90℃ for 10 hours, and the completion of the reaction was detected by liquid chromatography. After removing the solvent under reduced pressure, a mixed solvent of ethyl acetate / petroleum ether was added and the product was recrystallized to obtain a product with a yield of 85% and a purity of 96%.

[0115] Example 4 [ka] 250g of toluene, 1.0g of p-toluenesulfonic acid catalyst, 110g of resorcinol, and 244g of 1-phenylethanol were added to a 1000mL four-neck flask, heated, and reacted at 90℃ for 10 hours, and the completion of the reaction was detected by liquid chromatography, and the solvent was removed under reduced pressure. The product was purified by separation using a silica gel column (eluted with a mixed solvent of ethyl acetate / petroleum ether), and the product was obtained after concentration and removal of the solvent. The yield was 82% and the purity was 97%.

[0116] Example 5 [ka] In a 1000mL four-neck flask, 150g of toluene, 0.50g of p-toluenesulfonic acid catalyst, 110g of pyrrolidone derivative of resorcinol, and 56g of N-vinylpyrrolidone were added and heated to react at 90℃ for 10 hours, and the completion of the reaction was detected by liquid chromatography. After removing the solvent under reduced pressure, a mixed solvent of ethyl acetate / petroleum ether was added and the product was recrystallized to obtain a product with a yield of 84% and a purity of 97%.

[0117] Example 6 [ka] 250g of toluene, 1.0g of p-toluenesulfonic acid catalyst, 214g of phenethyl-substituted derivative of resorcinol, and 122g of 1-phenylethanol were added to a 1000mL four-neck flask, heated, and reacted at 90℃ for 10 hours, the completion of the reaction was detected by liquid chromatography, the solvent was removed under reduced pressure, and then the product was purified by separation using a silica gel column (eluted with a mixed solvent of ethyl acetate / petroleum ether), and the product was obtained after concentration and removal of the solvent. The yield was 80% and the purity was 95%.

[0118] The compounds in Tables 1 to 3 below were produced by referring to the methods in the above examples. [ka] [Table 1] [ka] [Table 2] [Table 3]

[0119] Application test example: Evaluation of tyrosinase inhibitory activity 1.1 Test method A The sample is tested for its inhibitory activity against tyrosinase using an absorption spectrophotometric method. The compounds of the present invention were prepared as solutions with five concentrations of 5 μg / mL, 3 μg / mL, 1 μg / mL, 0.5 μg / mL, and 0.01 μg / mL, respectively. Kojic acid, a positive control, was prepared as solutions with concentrations of 25 μg / mL, 20 μg / mL, 10 μg / mL, 7.5 μg / mL, 5 μg / mL, and 2.5 μg / mL, respectively. 50 μL of each of the solutions with the above five concentrations was taken out, and supplemented with 950 μL of pH 6.8 phosphate buffer to 1 mL, and 1 mL of 0.1 mg / mL tyrosine was added, followed by addition of 1 mL of tyrosinase (200 U / mL) prepared with pH 6.8 phosphate buffer, and incubated at 37° C. for 20 minutes, and the absorbance was measured at 490 nm. Enzyme activity inhibition rate = [(A2-A1)-(B2-B1)] / (A2-A1)×100% A1 was the absorbance at 0 min without the addition of any inhibitor, and A2 was the absorbance after 20 min without the addition of any inhibitor. B1 was the absorbance when the inhibitor was added at 0 min, and B2 was the absorbance when the inhibitor was added after 20 min.

[0120] As can be seen from the test results, the compounds of the present invention have an IC 50 The preferred compounds Ia, Ib, Ic, Id, Ie, If, Ig, Ih, Va, Vb and Vc have good inhibitory effects on tyrosinase even at 0.05-1 μM, and the IC of kojic acid in the control sample is 50 The mean tyrosinase inhibitory activity was 47.0 μM. The above results show that the compounds of the present invention all have high tyrosinase inhibitory activity. The present invention, alone or mixed with others, can be used as a tyrosinase inhibitor to inhibit catalytic browning of fruits and vegetables, used in whitening cosmetics for whitening, and used to manufacture various preparations of drugs for preventing and treating human pigmentation disorders caused by excess melanin, malignant melanoma, and other conditions requiring inhibition of tyrosinase activity.

[0121] 1.3 Test method B 1.3.1 Cytotoxicity tests 1) Cell inoculation: 1×10 4 Seed the cells into 96-well plates at a seeding density of 10 cells / well and place in an incubator (37 °C, CO 2 5%) overnight.

[0122] 2) Grouping of the test. The test included a blank group, a control group, a positive control group, and a sample group. In the sample group, different concentration gradients were set for each sample, and each concentration gradient was set in three replicate wells.

[0123] 3) Preparation: Sample working solutions of different concentrations were prepared according to the test concentration settings.

[0124] 4) Addition of drugs. Drugs were added when the cell seeding rate in the 96-well plate reached 40-60%. In the control group, 200 μL of culture medium containing 10% PBS (Gibco) was added to each well. In the positive control group, 200 μL of culture medium containing 10% DMSO was added to each well. In the sample group, 200 μL of culture medium containing the corresponding concentration of sample was added to each well. In the blank group, no cells were seeded and only 200 μL of cell culture medium was added. After completing the addition of drugs, the 96-well plate was placed in an incubator (37°C, CO 2 5%) and cultured.

[0125] 5) Measurement: After incubating the cells for 24 hours, the supernatant was discarded, MTT working solution (0.5 mg / mL) was added, and the cells were incubated in the dark at 37°C for 4 hours. After the incubation was completed, the supernatant was discarded, 100 μL of DMSO was added to each well, and the OD value was read at 490 nm.

[0126] 6) Calculation of relative cell viability. Relative cell viability = (OD of sample wells - OD of blank wells) / (OD of solvent control wells - OD of blank wells) x 100% [Table 4]

[0127] Cell viability data demonstrates that compounds of the invention have low cytotoxicity.

[0128] 1.3.2 Cellular melanin synthesis inhibition test Based on the cytotoxicity test data, a cellular melanin synthesis inhibition test was conducted within the permissible range of cytotoxicity. The samples were grouped according to concentration, the measurement index was melanin content, the measurement model was melanocytes, and the measurement was performed using a color development method. Logarithmic growth phase cells were collected and 2 × 10 5 Seed the cells into 24-well plates at a cell density of 10 cells / bottle and place in an incubator (37 °C, CO 2 After culturing for 24 hours in a 5% CO incubator, drugs were added according to the concentration requirements based on the cytotoxicity results, and untreated cells served as blank control, with three parallel groups for each group. After drug addition, the cells were incubated in an incubator (37°C, CO 2 The cells were then cultured in 10% DMSO-containing 1M NaOH for 48 hours, the supernatant was discarded, 1 mL of 1M NaOH containing 10% DMSO was added, and the cells were incubated in a constant temperature oven at 60°C for 1 hour. After the cells were returned to room temperature, 200 μL of each well was transferred to a 96-well plate, and the absorbance was read at 405 nm using 1M NaOH containing 10% DMSO as a blank control to calculate the relative inhibition rate of cellular melanin synthesis. Cellular melanin synthesis inhibition rate % = (1 - (OD of drug-added well - OD of blank well) / (OD of control well - OD of blank well)) x 100% [Table 5]

[0129] As can be seen from the test results, the compounds Ia, Id, Ie, If, Ig, Ih, Va, Vb, and Vc of the present invention have the effect of inhibiting cellular melanin synthesis at low concentrations (0.10% or less, g / mL), and the selected compounds Ia, Id, and Va all exhibit superior inhibitory effects on cellular melanin synthesis to kojic acid, and can inhibit cellular melanin synthesis even at very low concentrations.

[0130] The above results show that the compounds of the present invention all have high tyrosinase inhibitory activity. The compounds of the present invention, alone or mixed with others, can be used in whitening cosmetics for whitening as tyrosinase inhibitors, and can be used to manufacture various preparations of drugs for preventing and treating human pigmentation diseases caused by excess melanin, malignant melanoma, and other conditions that require the inhibition of tyrosinase activity.

[0131] Although the present invention has been disclosed as above in the preferred embodiment, the present invention is not limited thereto. Those skilled in the art can make various modifications and adaptations without departing from the spirit and scope of the present invention. Therefore, the protection scope of the present invention is governed by the following claims.

Claims

1. A compound of formula (A) or a cosmetically or pharma- ceutically acceptable salt thereof, a stereoisomer or a mixture of stereoisomers in any ratio, in particular an enantiomer or a mixture of enantiomers, more in particular a racemic mixture, 【Chemistry 1】 (Wherein, W is 【Chemistry 2】 where T is H, 【Chemistry 3】 or 【Chemistry 4】 and In the formula, R １ is selected from H, an optionally substituted alkyl group, and an optionally substituted arylalkyl group; R ２ , R ６ may be the same or different and are each independently selected from optionally substituted aryl and optionally substituted heteroaryl groups, optionally substituted alkyl groups, optionally substituted amide groups, and optionally substituted ester groups; R ３ , R ４ , R ７ , R ８ may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; R ３ , R ４ may combine with the carbon atoms to which they are both attached to form a ring, R ７ , R ８ may combine with the carbon atoms to which they are both attached to form a ring, wherein the amide group is preferably -NHCOCH ３ , -NHCOH, -NHCOCH ２ CH ３ , -NHCOCH ２ CH ２ CH ３ , -NHCOCH(CH ３ ) ２ , -NHCOCH(CH ２ ) ２ , -N(COCH ３ ) ２ , -CONH ２ , -CON(CH ３ ) ２ , -CONHCH ３ , -CONHCH ２ CH ３ , -CON(CH ２ CH ３ ) ２ , -CONHCH(CH ３ ) ２ , -CONHCH ２ CH ２ CH ３ , -CONHCH ２ CH ２ CH ２ CH ３ , phthalimide group, succinimide group, glutarimide group, maleimide group, 【Chemistry 5】 、 【Chemistry 6】 Wherein R ９ is selected from an optionally substituted alkyl group or an optionally substituted aryl group, a carboxy group or a salt thereof, a cyano group, an optionally substituted amide group, and an optionally substituted ester group, and n is selected from a natural number of 1 to 6, and the ester group is preferably -COOCH ３ , -COOCH ２ CH ３ , -COOCH(CH ３ ) ２ , -COOCH ２ CH ２ CH ３ , -COOCH ２ CH ２ CH ２ CH ３ It is.)

2. 2. The compound according to claim 1, characterized in that compound A is a compound of formula (I). 【Chemistry 7】 (In the formula, R １ ~R ４ is defined in claim 1.

3. 3. The compound according to claim 1 or 2, characterized in that compound A is a compound of formula (Ia). 【Chemistry 8】 (In the formula, R １ ~R ３ is defined in claim 1 or 2, Z １ , Z ２ may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; Z １ , Z ２ may combine with the carbon atoms to which they are both attached to form a ring, which may be substituted.

4. The compound according to claim 1, characterized in that compound A is a compound of formula (V). 【Chemistry 9】 (In the formula, R １ ~R ４ is defined in claim 1.

5. The compound according to claim 4, characterized in that compound A is a compound of formula (Va). 【Chemistry 10】 (In the formula, R １ ~R ３ is defined in claim 4, Z １ , Z ２ may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; Z １ , Z ２ may combine with the carbon atoms to which they are both attached to form a ring, which may be substituted.

6. The compound according to claim 1, characterized in that compound A is a compound of formula (VI). 【Chemistry 11】 (In the formula, R １ ~R ４ and R ６ ~R ８ is defined in claim 1.

7. The compound according to claim 6, characterized in that compound A is of formula (VIa). 【Chemistry 12】 (In the formula, R １ ~R ４ and R ６ , R ７ is defined in claim 1, Z １ , Z ２ may be the same or different and are each independently selected from hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, and an optionally substituted amido group; Z １ , Z ２ may combine with the carbon atoms to which they are both attached to form a ring, which may be substituted.

8. A compound according to any one of claims 1 to 7, characterized in that it is selected from the following compounds: (N-(1-(2,4-dihydroxyphenyl)ethyl)-2-pyrrolidone N-(1-(2,4-dihydroxyphenyl)propyl)-2-pyrrolidone N-(1-(2,4-dihydroxyphenyl)ethyl)-2-piperidone N-(1-(2,4-dihydroxyphenyl)propyl)-2-piperidone N-(1-(2,4-dihydroxyphenyl)ethyl)-2-hexamethyleneiminone N-(1-(2,4-dihydroxyphenyl)propyl)-2-hexamethyleneiminone 1,1'-((4,6-dihydroxy-1,3-phenylidene)bis(ethane-1,1-diyl))bis(pyrrolidin-2-one) 1,1'-((4,6-dihydroxy-1,3-phenylidene)bis(prop-1,1-diyl))bis(pyrrolidin-2-one) 1,1'-((4,6-dihydroxy-1,3-phenylidene)bis(ethane-1,1-diyl))bis(piperidin-2-one) 1,1'-((4,6-dihydroxy-1,3-phenylidene)bis(prop-1,1-diyl))bis(piperidin-2-one) 1,1'-((4,6-dihydroxy-1,3-phenylidene)bis(ethane-1,1-diyl))bis(hexamethyleneimine-2-one) 1,1'-((4,6-dihydroxy-1,3-phenylidene)bis(prop-1,1-diyl))bis(hexamethyleneimine-2-one) 4,6-bis(1-phenylethyl)-1,3-benzenediol)

9. A method for preparing a compound of formula (I), comprising reacting a compound of formula (II) with a compound of formula (IVa), the synthesis route being as follows: 【Chemistry 13】 (In the formula, R １ , R ２ , R ３ and R ４ is defined in claim 1, where R ５ is selected from leaving functional groups, and the leaving functional groups are preferably OH, H ２ O, OTs, OMs, Cl, Br, or I.

10. A method for preparing a compound of formula (Ia), comprising reacting a compound of formula (II) with a compound of formula (IIIa), the synthesis route being as follows: 【Chemistry 14】 (In the formula, R １ , R ２ , R ３ is defined in claim 1, Z １ , Z ２ is defined in claim 3.

11. A method for preparing a compound of formula (V), comprising reacting a compound of formula (II) with a compound of formula (IVa), the synthesis route being as follows: 【Chemistry 15】 (In the formula, R １ , R ２ , R ３ , R ４ is defined in claim 1, where R ５ is selected from leaving functional groups, and the leaving functional groups are preferably OH, H ２ O, OTs, OMs, Cl, Br, or I.

12. A method for preparing a compound of formula (Va), comprising reacting a compound of formula (II) with a compound of formula (IIIa), the synthesis route being as follows: 【Chemistry 16】 (In the formula, R １ , R ２ , R ３ , Z １ and Z ２ is defined in claim 5.

13. A method for preparing a compound of formula (VI), comprising reacting a compound of formula (I) with a compound of formula (IVb), the synthesis route being as follows: 【Chemistry 17】 (In the formula, R １ , R ２ , R ３ , R ４ , R ６ , R ７ and R ８ is defined in claim 1, where R ５ is selected from leaving functional groups, the leaving functional groups being OH, H ２ One selected from O, OTs, OMs, Cl, Br, and I.

14. A method for preparing a compound of formula (VIa), comprising reacting a compound of formula (I) with a compound of formula (IIIb), the synthesis route being as follows: 【Chemistry 18】 (In the formula, R １ , R ２ , R ３ , R ４ , R ６ , R ７ is defined in claim 1, Z １ and Z ２ is defined in claim 7.

15. A pharmaceutical composition comprising a compound according to any one of claims 1 to 8 or a pharma- ceutically acceptable salt thereof.

16. Use of a compound according to any one of claims 1 to 8 in the manufacture of a medicament for the treatment, prevention and / or reduction of hyperpigmentation.

17. 10. Use of a compound or salt thereof according to any one of claims 1 to 8 in a non-therapeutic cosmetic product for combating, preventing and / or reducing hyperpigmentation.

18. A cosmetic composition comprising the compound or salt thereof according to any one of claims 1 to 8.

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