A diphenolic compound, a preparation method and application thereof

Abstract

The present application provides a class of resorcinol derivative compounds shown in formula A, which can be used for preparing drugs for inhibiting hyperpigmentation, and cosmetic, non-therapeutic uses for treating hyperpigmentation. The compounds of the present application have significant effects on inhibiting pigment deposition caused by ultraviolet and / or visible light radiation, skin anti-aging, etc. Wherein W is T is H, or R 1 to R 8 The definitions are as defined in the specification.

Description

TECHNICAL FIELD

[0001] The present invention relates to a class of diphenolic compounds, to a process for their preparation, to pharmaceutical or cosmetic compositions containing such compounds, and to their use for pharmaceutical applications and cosmetics, in particular for the inhibition of pigmentation and for the treatment of hyperpigmentation. BACKGROUND

[0002] Melanin, which is present in melanocytes and is produced by the catalytic conversion of tyrosine by tyrosinase, is the pigment responsible for the coloration of the skin. Excessive production of melanin can cause hyperpigmentation of the skin due to factors such as excessive sun exposure, hormonal imbalances, chloasma, diseases, medication injuries, scars, age spots caused by aging, and the like.

[0003] The color of human skin is mainly determined by the amount of melanin in the basal layer of the skin. Melanin, which is usually brown to black, is formed in the melanin-forming cells of the skin, is transferred to the stratum corneum of the skin and imparts its color to the skin or hair. In mammals, the brown-black eumelanin is mainly formed from hydroxyl-substituted aromatic amino acids such as L-tyrosine and L-DOPA, in addition to the yellow to red phaeomelanin from sulfur-containing molecules. Starting from L-tyrosine, L-3,4-dihydroxyphenylalanine (L-DOPA) is formed by tyrosinase and is converted by tyrosinase into dopachrome, which is subsequently oxidized to form melanin by a series of catalytic steps by various enzymes.

[0004] The skin appears hyperpigmented when too much melanin is concentrated in an area or part of the skin. Hyperpigmentation can also occur due to exposure to sunlight or due to different inflammatory stimuli. Increased melanin production is usually accompanied by the manifestations of melasma, chloasma or solar lentigines (age spots), freckles and pigmented keratoses. Melasma is a general term describing darkened skin. Chloasma is usually used to describe a discoloration of the skin caused by hormones. These hormonal changes are usually due to pregnancy, contraceptive medication or estrogen replacement therapy. Solar lentigines refer to dark spots on the skin caused by sunlight. These spots are common in adults with a long history of unprotected sun exposure. Although skin damage, such as scars, wounds or rashes, can also cause hyperpigmentation, the most common cause of darkened areas of the skin, brown spots or discolored areas is unprotected sun exposure.

[0005] The prior art discloses methods for treating hyperpigmentation by using skin lightening agents. Representative compounds of commonly used skin lightening agents include hydroquinone and vitamin C. One of the action pathways of such formulations is to lighten the skin by inhibiting tyrosinase, which is involved in melanin production. The most popular ingredients for skin whitening, skin bleaching or skin lightening include hydroquinone, arbutin, kojic acid, licorice extract, niacinamide, etc. Hydroquinone is one of the most effective depigmentation agents. Although its efficacy has been proven, in the early 21st century, due to its potential dermatological and systemic side effects, hydroquinone began to be removed or its use in cosmetics was limited. 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 is still unstable and undergoes hydrolysis under different conditions, resulting in the release of hydroquinone.

[0006] It has been a long-standing goal to develop compounds that are safer and more effective in improving skin pigmentation. By studying the mechanism of action of tyrosinase and mimicking the intermediate product L-DOPA in the process of melanin formation, the development of resorcinol-type tyrosinase inhibitors has attracted increasing attention from skin whitening-related researchers. 4-Butylresorcinol, 4-hexylresorcinol, dimethoxytolyl-4-propylresorcinol (WO2012 / 129260), phenylethylresorcinol (WO2018 / 001485) and isobutyramidothiazylresorcinol (WO2015 / 090850), a series of resorcinol derivatives, have been proven to have significant effects on skin pigmentation. These results indicate that resorcinol compounds have great potential for inhibiting the activity of tyrosinase. Therefore, developing new compounds with resorcinol structures and exploring their biological functions as tyrosinase inhibitors are of great significance for developing new, efficient tyrosinase inhibitors and further developing new compounds for treating or improving hyperpigmentation. SUMMARY

[0007] The present inventors have developed a new class of resorcinol compounds that can be used as tyrosinase inhibitors, particularly for cosmetic or pharmaceutical applications, and more particularly as depigmentation agents, whitening agents, bleaching agents or lightening agents, and for treating pigmentary disorders or for cosmetic use to slow down or improve hyperpigmentation.

[0008] In particular, the present application provides a class of resorcinol compounds of formula A capable of influencing the pigmentation of skin areas caused by sunlight, in particular ultraviolet, visible light, in particular for preventing, treating and / or reducing the pigmentation of skin areas or skin portions, the compounds of formula A having the following structure:

[0009] Where W is T is H,

[0010] Among them, R 1 Selected from H, optionally substituted alkyl groups, and optionally substituted arylalkyl groups;

[0011] R 2 R 6 They may be the same or different, each independently selected from optionally substituted aryl and heteroaryl groups, optionally substituted alkyl groups, optionally substituted amide groups, optionally substituted ester groups, R 3 R 4 R 7 R 8 They may be the same or different, each independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amide, R 3 R 4 The carbon atoms that can be bonded to them can form a ring, R 7 R 8 It can be linked with the carbon atoms that are connected to it to form a ring; or a cosmetically or pharmaceutically acceptable salt, stereoisomer or mixture of stereoisomers in any proportion, especially enantiomers or mixtures of enantiomers, and even more particularly a mixture of racemic mixtures.

[0012] Furthermore, compound A is a compound of formula (I). Where R 1 To R 4 The definition is as described above.

[0013] Furthermore, compound A is a compound of formula (Ia). Among them, R 1 To R 3 As defined above, Z 1 Z 2 They may be the same or different, each independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amide, Z 1 Z 2 The carbon atoms that can be bonded to them can form a ring, and the ring can be replaced.

[0014] Furthermore, compound A is a compound of formula (V).

[0015] Among them, R 1 To R 4 The definition is as above.

[0016] Furthermore, compound A is a compound of formula (Va). Among them, R 1To R 3 The definition is as above, Z 1 Z 2 They may be the same or different, each independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amide, Z 1 Z 2 The carbon atoms that can be bonded to them can form a ring, and the ring can be replaced.

[0017] Furthermore, compound A is a compound of formula (VI). Among them, R 1 To R 4 and R 6 To R 8 The definition is as above.

[0018] Furthermore, compound A is (VIa). Among them, R 1 To R 4 and R 6 To R 7 The definition is as above, Z 1 Z 2 They may be the same or different, each independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amide, Z 1 Z 2 The carbon atoms that can be bonded to them can form a ring, and the ring can be replaced.

[0019] The present invention also provides a method for preparing compound A.

[0020] The present invention also provides pharmaceutical compositions comprising the compounds of the present invention or pharmaceutically acceptable salts thereof.

[0021] The present invention also provides the use of compounds of the present invention or pharmaceutically acceptable salts thereof in the preparation of medicaments for treating, preventing and / or reducing hyperpigmentation.

[0022] This invention also discloses non-therapeutic and cosmetic uses of compounds of this invention or their salts for treating, preventing, and / or reducing hyperpigmentation.

[0023] The present invention also discloses a cosmetic composition containing the compound of the present invention or a salt thereof. Detailed Implementation

[0024] In order to make the objects, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be described clearly and completely below. Obviously, the described embodiments are only some but not all of the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative efforts should fall into the scope of the present application. Unless otherwise clearly indicated, in the entire specification and claims of the present application, the term "comprise" or its variants such as "contain" or "include" should be understood that the stated components or steps are included but not excluding other components or steps.

[0025] In addition, in order to better illustrate the present application, numerous specific details are given in the following specific embodiments.

[0026] Those skilled in the art should understand that the present application can be implemented without certain specific details. In some embodiments, the raw materials, methods, means and the like which are well known to those skilled in the art are not described in detail, in order to highlight the main idea of the present application.

[0027] The endpoints of the ranges and any values disclosed herein are not limited to the precise values stated. The ranges or values should be construed to be approximations which can be rounded off to the nearest value. The endpoints of the ranges of values will preferentially be read as being inclusive of the other unless explicitly indicated otherwise. For numerical ranges, the endpoints are included in the ranges. For numerical ranges, the endpoints are included in the ranges. For numerical ranges, each intervening value by each endpoint, each separate endpoint value and each separate point value is encompassed. For values which are less than one, one of the enumerated endpoints is also encompassed. For values which are greater than one, one of the enumerated endpoints is also encompassed. The same applies to ranges of integers. For numerical ranges, the endpoints are included in the ranges. For numerical ranges, each intervening value by each endpoint, each separate endpoint value and each separate point value is encompassed. For values which are less than one, one of the enumerated endpoints is also encompassed. For values which are greater than one, one of the enumerated endpoints is also encompassed. The same applies to ranges of integers.

[0028] In the present application, "hyperpigmentation" refers to hyperpigmentation caused by sunlight, more particularly visible light.

[0029] In the present application, "cosmetically or pharmaceutically acceptable" means that it can be used for the preparation of cosmetic or pharmaceutical compositions, and is generally non-toxic, safe and acceptable for pharmaceutical and cosmetic use.

[0030] In the present invention, the "cosmetically or pharmaceutically acceptable salt" is a cosmetically or pharmaceutically acceptable salt as defined herein, and it has the pharmaceutical and cosmetic properties and activities of the original compound. Such a salt can be: (1) an acid addition salt with an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc., or with an organic acid such as acetic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, fumaric acid, gluheptonic 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, etc., but is not limited thereto, and (2) a salt formed when an acid proton present in the parent compound is replaced by a metal ion such as an alkali metal ion (e.g., Na + , K + or Li + ), an alkaline earth metal ion (e.g., Ca 2+ or Mg 2+ ) or an aluminum ion; or a salt formed when an acid proton present in the parent compound is coordinated with an organic base or an inorganic base. Acceptable organic bases include diethanolamine, ethanolamine, N-methylglucamine, triethanolamine, tromethamine, etc., but are not limited thereto. Acceptable inorganic bases include aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate and sodium hydroxide, but are not limited thereto.

[0031] The term "stereoisomer" used in the present invention refers to configurational stereoisomers, which include geometric isomers and optical isomers, as well as conformational isomers.

[0032] Geometric isomers (also referred to as E / Z isomers or cis / trans isomers) are caused by different positions of substituents on a C=C double bond, which can have a Z or E configuration, also referred to as cis or trans configuration.

[0033] Optical isomers are caused by different positions of substituents or lone pairs in space on an atom (such as a carbon atom or a sulfur atom) that contains four different substituents (potentially including a lone pair). Thus, this atom represents a chiral or asymmetric center. Optical isomers that are not mirror images of each other are referred to as "diastereomers", while optical isomers that are non-superimposable mirror images of each other are referred to as "enantiomers".

[0034] An equimolar mixture of the two enantiomers of a chiral compound is referred to as a racemic mixture.

[0035] In the present invention, halogen denotes fluorine, chlorine, bromine and iodine in all cases.

[0036] As used herein, the term "alkyl" (and in other groups containing alkyl, such as the alkyl moiety of alkoxy, the alkyl moiety of arylalkyl) in each case means a straight-chain or branched alkyl group generally having 1-20 carbon atoms, often 1-6 carbon atoms, preferably 1-4 carbon atoms, and especially 1-3 carbon atoms. Examples of C1-C4 alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), and 1,1-dimethylethyl (tert-butyl). Examples of C1-C6 alkyl groups, in addition to those mentioned for C1-C4 alkyl groups, include 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. C1-C 10 Examples of alkyl groups, in addition to those mentioned for C1-C6 alkyl groups, include 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, but are not limited to these. Alkyl groups can be substituted with halogens, cyano, nitro, aryl, cycloalkyl, heterocyclic, amide, ester, etc., but are not limited to these.

[0037] In this invention, "aryl" refers to a monovalent monocyclic or bicyclic aromatic hydrocarbon group with 6 to 10 ring atoms, such as phenyl or naphthyl, especially naphthyl, but not limited thereto. The aryl group can be substituted by alkyl, halogen, cyano, nitro, cycloalkyl, heterocyclic, amide, ester, etc., but is not limited thereto.

[0038] In this invention, "cycloalkyl" refers to a "cycloalkyl" or "heterocyclic group." A "cycloalkyl" group refers to a monocyclic monovalent hydrocarbon group with three to six carbon atoms, which may be saturated or contain a double bond. The cycloalkyl group may be unsubstituted or substituted with one or two substituents independently selected from alkyl, halogen, alkoxy, hydroxy, or cyano groups, but is not limited thereto. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyanocyclopropyl-1-yl, 1-cyanomethylcyclopropyl-1-yl, 3-fluorocyclohexyl, etc. When a cycloalkyl group contains a double bond, it may be referred to herein as a cycloalkenyl group. A "heterocyclic group" refers to a saturated or unsaturated monovalent monocyclic group with 4 to 8 ring atoms, where one or two ring atoms are selected from N, O, or S(O). pwherein p is an integer of 0 to 2, and the remaining ring atoms are C. Further, one or two ring carbon atoms in the heterocyclic group ring can optionally be replaced by a -CO- group. More specifically, the term heterocyclic group includes, but is not limited to, azetidinyl, oxetanyl, pyrrolidinyl, piperidinyl, homopiperidinyl, 2-oxopyrrolidinyl, 2-oxopiperidinyl, morpholinyl, piperazino, tetrahydropyranyl, thiomorpholinyl, and the like, but is not limited thereto. When the cycloalkyl group, heterocyclic group, and the like are substituted, they can be substituted with alkyl, halogen, cyano, nitro, aryl, amido, ester, alkoxy, halogen, and the like, but are not limited thereto, for example, when alkyl is substituted with halogen, haloalkyl is formed, but is not limited thereto.

[0039] The term "optionally substituted" means that the relevant group can be substituted with a substituent, or can not be substituted.

[0040] When a group is substituted, the substituent can be alkyl, halogen, cyano, nitro, cycloalkyl, heterocyclic group, amido, ester, alkoxy, halogen, and the like, but is not limited thereto, for example, when alkyl is substituted with halogen, haloalkyl is formed, but is not limited thereto.

[0041] "Alkoxy" means an -OR group, wherein R is alkyl as defined above, for example, methoxy, ethoxy, propoxy, or 2-propoxy, n-butoxy, isobutoxy, t-butoxy, and the like, but is not limited thereto.

[0042] The "amide group" of the present application means a group containing "-NHCO-" or the amide group, for example, -NHCOCH3, -NHCOH, -NHCOCH2CH3, -NHCOCH2CH2CH3, -NHCOCH(CH3)2, -NHCOCH(CH2)2, -N(COCH3)2, -CONH2, -CON(CH3)2, -CONHCH3, -CONHCH2CH3, -CON(CH2CH3)2, -CONHCH(CH3)2, -CONHCH2CH2CH3, -CONHCH2CH2CH2CH3, phthalimidyl, succinimidyl, glutarimidyl, maleimidyl, wherein R 9 is selected from optionally substituted alkyl or aryl, carboxyl or a salt thereof, cyano, optionally substituted amide group, optionally substituted ester group, n is selected from a natural number of 1 to 6, and the ester group is preferably -COOCH3, -COOCH2CH3, -COOCH(CH3)2, -COOCH2CH2CH3, -COOCH2CH2CH2CH3;

[0043] n is selected from a natural number of 1 to 6, and is preferably 1, 2, or 3, but is not limited thereto.

[0044] The "ester group" of the present application refers to a group containing "-COO-," such as, but not limited to, -COOCH3, -COOCH2CH3, -COOCH(CH3)2, -COOCH2CH2CH3, -COOCH2CH2CH2CH3.

[0045] The "heteroaryl" group in the present application encompasses: 5- to 10-membered aromatic monocyclic, aromatic fused ring, wherein the aromatic monocyclic contains one or more (e.g., 1 to 4, or in certain embodiments, 1 to 3) heteroatoms selected from N, O, and S and the remaining atoms are carbon; aromatic fused ring, which contains one or more (e.g., 1 to 4, or in certain embodiments, 1 to 3) heteroatoms selected from N, O, and S and the remaining ring atoms are carbon, and wherein at least one heteroatom is present in the aromatic ring. For example, heteroaryl includes 5- to 10-membered heterocycloalkyl aromatic rings fused to a 5- to 10-membered cycloalkyl or heterocycloalkyl ring. For the fused rings where only one ring contains one or more heteroatoms, the bicyclic heteroaryl ring system can be attached at either ring. When the total number of S and O atoms in a heteroaryl group exceeds 1, these heteroatoms are not adjacent to each other. In certain embodiments, the total number of S and O atoms in a heteroaryl group does not exceed 2. In certain embodiments, the total number of S and O atoms in an aromatic heterocyclic ring does not exceed 1. Examples of heteroaryl groups include, but are not limited to, (numbering from the point of attachment as the 1-position) 2-pyridyl, 3-pyridyl, 4-pyridyl, 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. A divalent radical derived from a monovalent heteroaryl radical having a free valence on a carbon atom in the name by removal of one hydrogen atom from that carbon atom is named by prefixing the name of the corresponding monovalent radical with "ylidene," e.g., a pyridyl radical having two points of attachment is a pyridylidene. Heteroaryl does not encompass, nor overlap with, aryl, cycloalkyl, or heterocycloalkyl, as defined herein.

[0046] "Arylalkyl" refers to an alkyl radical in which an aryl moiety is attached to the parent structure through an alkyl radical. Examples include benzyl, phenethyl, phenylvinyl, phenylallyl, and the like. "Heteroarylalkyl" refers to an alkyl radical in which a heteroaryl moiety is attached to the parent structure through an alkyl radical. Examples include furanylmethyl, pyridylmethyl, pyrimidinylethyl, and the like.

[0047] The following description of preferred embodiments of the variables of the compounds of formula (A) and of the variables, characteristics of the uses and methods of the present application as well as characteristics of the compositions of the present application is valid per se and preferably in combination with each other.

[0048] In general, the present application provides a resorcinol compound of formula A,

[0049] wherein W is T is H,

[0050] wherein R 1 is selected from H, optionally substituted alkyl and optionally substituted arylalkyl;

[0051] R 2 , R 6 may be the same or different, each independently selected from optionally substituted aryl and optionally substituted heteroaryl, optionally substituted alkyl, optionally substituted amido, optionally substituted ester, R 3 , R 4 , R 7 , R 8 may be the same or different, each independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amido, R 3 , R 4 may be the same or different, each independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amido, R 7 , R 8 may be the same or different, each independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amido, wherein the amido group is preferably -NHCOCH3, -NHCOH, -NHCOCH2CH3, -NHCOCH2CH2CH3, -NHCOCH(CH3)2, -NHCOCH(CH2)2, -N(COCH3)2, -CONH2, -CON(CH3)2, -CONHCH3, -CONHCH2CH3, -CON(CH2CH3)2, -CONHCH(CH3)2, -CONHCH2CH2CH3, -CONHCH2CH2CH2CH3, phthalimido, succinimido, glutarimido, maleimido, wherein R 9 is selected from optionally substituted alkyl or optionally substituted aryl, carboxyl or a salt thereof, cyano, optionally substituted amido, optionally substituted ester, n is selected from natural numbers from 1 to 6, the ester group is preferably one of -COOCH3, -COOCH2CH3, -COOCH(CH3)2, -COOCH2CH2CH3, -COOCH2CH2CH2CH3;

[0052] or a cosmetically or pharmaceutically acceptable salt, a stereoisomer or a mixture of stereoisomers in any ratio, in particular an enantiomer or a mixture of enantiomers, more particularly a racemic mixture thereof.

[0053] Further, the present application provides a compound of formula A:

[0054] wherein R 1 is selected from H, optionally substituted alkyl and optionally substituted arylalkyl;

[0055] R 2 is selected from optionally substituted aryl, optionally substituted alkyl, optionally substituted amido, optionally substituted ester, optionally substituted five- to ten-membered heteroaryl (said heteroaryl comprising 1 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur), preferably optionally substituted alkyl,

[0056] wherein R 9 is selected from optionally substituted alkyl or aryl, carboxyl or a salt thereof, cyano, optionally substituted amido, optionally substituted ester, n is selected from a natural number from 1 to 6, preferably 1, 2, 3; R 3 , R 4 may be the same or different, each independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amido, R 3 , R 4 may be linked together with the carbon atom to which they are jointly attached to form a ring.

[0057] Further, in some embodiments of formula (I), R 1 is selected from H and C1-C6 alkyl, particularly preferably H and methyl;

[0058] Further, in some embodiments of formula (I), R 2 is selected from wherein n is 1, 2 or 3.

[0059] Further, in some other embodiments of formula (I), R 2 is selected from

[0060] Further, in some embodiments of formula (I), R 2 is selected from phenyl.

[0061] In some embodiments of formula (I), preferably, R 3 is selected from H and C1-C6 alkyl, particularly preferably H, methyl, ethyl, propyl and butyl;

[0062] In some embodiments of formula (I), preferably, R 4selected from the group consisting of H and C1-C6alkyl, particularly preferably one of H, methyl, ethyl, propyl and butyl;

[0063] Still further, the present application preferably provides compounds of formula (I) as follows:

[0064]

[0065] wherein R 1 selected from the group consisting of H and C1-C6alkyl, particularly preferably one of H and methyl; R 2 selected from the group consisting of H and C1-C6alkyl, particularly preferably one of H and methyl; R 3 selected from the group consisting of H and C1-C6alkyl, particularly preferably one of H, methyl, ethyl, propyl and butyl; R 4 selected from the group consisting of H and C1-C6alkyl, particularly preferably one of H, methyl, ethyl, propyl and butyl; R 10 selected from the group consisting of C1-C 18 alkyl, preferably n-dodecyl, n-tetradecyl and n-hexadecyl; n is selected from 1, 2 and 3.

[0066] Further, the present application provides compounds of formula A as preferably compounds of formula (la), wherein R 1 selected from the group consisting of H, optionally substituted alkyl and optionally substituted arylalkyl; R 2 selected from the group consisting of optionally substituted aryl, optionally substituted five- to ten-membered heteroaryl (said five- to ten-membered heteroaryl comprising 1 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur), optionally substituted alkyl and optionally substituted amido; R 3 selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amido; Z 1 , Z 2 each independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amido, Z 1 , Z 2 may be linked together with the carbon atom to which they are commonly attached to form a ring, which can be substituted with a substituent.

[0067] Further, in compounds of formula (la), R 1 selected from the group consisting of H and C1-C6alkyl, particularly preferably one of H and methyl;

[0068] Further, in some embodiments of compounds of formula (la), R 2 selected from the group consisting of (wherein n is a natural number from 1 to 6), and phenyl.

[0069] Further, the compounds of formula (Ia) according to the present application are preferably compounds of formulae Ia-1 and Ia-2:

[0070] wherein R 1 is selected from H and C1-C6 alkyl, preferably H and methyl;

[0071] Z 1 and Z 2 are each independently selected from H and C1-C6 alkyl, preferably H, methyl, ethyl, propyl and butyl; or Z 1 and Z 2 together with the carbon atom to which they are attached form a C3-C6 cycloalkyl, 3-6 membered heterocyclyl; C3-C6 cycloalkyl is preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl; 3-6 membered heterocyclyl is preferably oxiranyl, azetidinyl, oxetanyl, pyrrolidinyl, piperidinyl, homopiperidinyl, 2-oxopyrrolidinyl, 2-oxopiperidinyl, morpholinyl, piperazinyl, tetrahydropyranyl, thiomorpholinyl;

[0072] n is selected from natural numbers from 1 to 6, preferably 1, 2 and 3.

[0073] Further, in some embodiments the compound A according to the present application is preferably a compound of formula (V),

[0074]

[0075] wherein R 1 is selected from H, optionally substituted alkyl and optionally substituted arylalkyl;

[0076] R 2 is selected from optionally substituted aryl, optionally substituted alkyl, optionally substituted amido, the amido group is preferably -NHCOCH3, -NHCOH, -NHCOCH2CH3, -NHCOCH2CH2CH3, -NHCOCH(CH3)2, -NHCOCH(CH2)2, -N(COCH3)2, -CONH2, -CON(CH3)2, -CONHCH3, -CONHCH2CH3, -CON(CH2CH3)2, -CONHCH(CH3)2, -CONHCH2CH2CH3, -CONHCH2CH2CH2CH3, phthalimidyl, succinimidyl, glutarimidyl, maleimidyl, one of which is R 9The group is selected from optionally substituted alkyl or aryl groups, carboxyl groups or their salts, optionally substituted ester groups (preferably one of -COOCH3, -COOCH2CH3, -COOCH(CH3)2, -COOCH2CH2CH3, -COOCH2CH2CH2CH3), cyano groups, optionally substituted amide groups, where n is selected from a natural number from 1 to 6; R 3 R 4 They may be the same or different, each independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amide, R 3 R 4 Carbon atoms that can be bonded together with them can form rings.

[0077] Furthermore, in some embodiments, the compound of formula (V) is a compound of formula (Va).

[0078] Among them, R 1 Selected from H, optionally substituted alkyl groups, and optionally substituted arylalkyl groups;

[0079] R 2 The amide group is selected from optionally substituted aryl, optionally substituted alkyl, and optionally substituted amide groups, preferably -NHCOCH3, -NHCOH, -NHCOCH2CH3, -NHCOCH2CH2CH3, -NHCOCH(CH3)2, -NHCOCH(CH2)2, -N(COCH3)2, -CONH2, -CON(CH3)2, -CONHCH3, -CONHCH2CH3, -CON(CH2CH3)2, -CONHCH(CH3)2, -CONHCH2CH2CH3, -CONHCH2CH2CH2CH3, phthalimide, succinimide, glutarimide, maleimide, etc. One of them, in which R 9 The group is selected from optionally substituted alkyl or aryl groups, carboxyl groups or their salts, optionally substituted ester groups (preferably one of -COOCH3, -COOCH2CH3, -COOCH(CH3)2, -COOCH2CH2CH3, -COOCH2CH2CH2CH3), cyano groups, optionally substituted amide groups, where n is selected from a natural number from 1 to 6; R 3 Selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amide; Z 1 Z 2 They may be the same or different, each independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amide, Z 1 Z 2 The carbon atoms that can be bonded to them can form a ring, and the ring can be replaced.

[0080] Furthermore, in some embodiments of the present invention, compound A is preferably compound (VI).

[0081] Among them, R 1 Selected from H, optionally substituted alkyl groups, and optionally substituted arylalkyl groups; R 2 R 6 The groups may be the same or different, and each may be independently selected from optionally substituted aryl groups, five- to ten-membered heteroaryl groups (the five- to ten-membered heteroaryl groups comprising 1 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur), optionally substituted alkyl groups, optionally substituted ester groups, and optionally substituted amide groups, wherein the amide groups are preferably -NHCOCH3, -NHCOH, -NHCOCH2CH3, -NHCOCH2CH2CH3, -NHCOCH(CH3)2, -NHCOCH(CH2)2, -N(COCH3)2, -CONH2, -CON(CH3)2, -CONHCH3, -CONHCH2CH3, -CON(CH2CH3)2, -CONHCH(CH3)2, -CONHCH2CH2CH3, -CONHCH2CH2CH2CH3, phthalimide, succinimide, glutarimide, maleimide, etc. One type, in which R 9 The group is selected from optionally substituted alkyl or aryl groups, carboxyl groups or their salts, optionally substituted ester groups (preferably one of -COOCH3, -COOCH2CH3, -COOCH(CH3)2, -COOCH2CH2CH3, -COOCH2CH2CH2CH3), cyano groups, optionally substituted amide groups, where n is selected from a natural number from 1 to 6; R 3 R 4 R 7 R 8 They may be the same or different, each independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amide, R 3 R 4 The carbon atoms that can be bonded to them can form a ring, R 7 R 8 The carbon atoms that can be bonded to them can form a ring, and the ring can be replaced.

[0082] Furthermore, in some embodiments of formula (VI), R 2 and R 6 Selected from n is a natural number from 1 to 6.

[0083] Furthermore, in some embodiments of formula (VI), R 2 and R6 selected from the group consisting of H, C1-C6 alkyl, and C1-C6 haloalkyl.

[0084] Further, the present application provides, in some embodiments, compounds of formula (VI) as follows:

[0085] wherein, R 1 selected from the group consisting of H and C1-C6 alkyl, preferably H and methyl; R 3 selected from the group consisting of H and C1-C6 alkyl, preferably H, methyl, ethyl, propyl, and butyl; R 4 selected from the group consisting of H and C1-C6 alkyl, preferably H, methyl, ethyl, propyl, and butyl; R 7 selected from the group consisting of H and C1-C6 alkyl, preferably H, methyl, ethyl, propyl, and butyl; R 8 selected from the group consisting of H and C1-C6 alkyl, preferably methyl, ethyl, propyl, and butyl; n is selected from the group consisting of 1, 2, and 3, and m is selected from the group consisting of 1, 2, and 3.

[0086] Further, the present application provides, in some embodiments, compounds of formula (VI) as follows: wherein, R 1 selected from the group consisting of H, optionally substituted alkyl, and optionally substituted arylalkyl; R 2 , R 6 , R 9 may be the same or different, each independently selected from the group consisting of optionally substituted aryl, five- to ten-membered heteroaryl (said five- to ten-membered heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, or sulfur), optionally substituted alkyl, optionally substituted ester, and optionally substituted amide, wherein the amide is preferably -NHCOCH3, -NHCOH, -NHCOCH2CH3, -NHCOCH2CH2CH3, -NHCOCH(CH3)2, -NHCOCH(CH2)2, -N(COCH3)2, -CONH2, -CON(CH3)2, -CONHCH3, -CONHCH2CH3, -CON(CH2CH3)2, -CONHCH(CH3)2, -CONHCH2CH2CH3, -CONHCH2CH2CH2CH3, phthalimido, succinimido, glutarimido, maleimido, , R 9 may be the same or different, each independently selected from the group consisting of optionally substituted alkyl or aryl, carboxyl or a salt thereof, optionally substituted ester (said ester is preferably one of -COOCH3, -COOCH2CH3, -COOCH(CH3)2, -COOCH2CH2CH3, -COOCH2CH2CH2CH3), cyano, optionally substituted amide, n is selected from the group consisting of natural numbers from 1 to 6; R 3 , R 4 , R 7each independently of one another selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted acylamino, R 3 , R 4 may be linked to form a ring with the carbon atoms to which they are jointly attached; Z 1 , Z 2 each independently of one another selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted acylamino, Z 1 , Z 2 may be linked to form a ring with the carbon atoms to which they are jointly attached, which ring can be substituted.

[0087] In particular, the compounds of the present application are selected from the group consisting of:

[0088]

[0089] N-(1 -(2,4-dihydroxyphenyl)ethyl)-2-piperidinone;

[0090]

[0091] N-(1 -(2,4-dihydroxyphenyl)ethyl)-2-piperidinone;

[0092]

[0093] N-(1 -(2,4-dihydroxyphenyl)ethyl)-2-piperidinone;

[0094]

[0095] N-(1 -(2,4-dihydroxyphenyl)ethyl)-2-piperidinone;

[0096]

[0097] N-(1 -(2,4-dihydroxyphenyl)ethyl)-2-piperidinone;

[0098]

[0099] N-(1 -(2,4-dihydroxyphenyl)ethyl)-2-piperidinone;

[0100]

[0101] 1,1 '-((4,6-dihydroxy-1,3-benzylidene)bis(ethane-1,1 -diyl))bis(pyrrolidin-2-one);

[0102]

[0103] 1,1'-((4,6-dihydroxy-1,3-benzene)bis(propane-1,1-ylidene))bis(pyrrolidine-2- one);

[0104]

[0105] 1,1'-((4,6-dihydroxy-1,3-benzene)bis(propane-1,1-ylidene))bis(pyrrolidine-2- one);

[0106]

[0107] 1,1'-((4,6-dihydroxy-1,3-benzene)bis(propane-1,1-ylidene))bis(pyrrolidine-2- one);

[0108]

[0109] 1,1'-((4,6-dihydroxy-1,3-benzene)bis(propane-1,1-ylidene))bis(pyrrolidine-2- one);

[0110]

[0111] 1,1'-((4,6-dihydroxy-1,3-benzene)bis(propane-1,1-ylidene))bis(pyrrolidine-2- one);

[0112]

[0113] 4,6-bis(1-phenylethyl)-1,3-benzenediol.

[0114] The present application also provides a preparation method of the above-mentioned compound of formula (I), the synthetic route of which is as follows: wherein R 1 , R 2 , R 3 and R 4 are defined as above, and wherein R 5 is selected from leaving groups, and the leaving groups are selected from one of OH, H2O, OTs, OMs, Cl, Br, and I;

[0115] In the above reaction, the reaction temperature is 40-110 degrees, preferably 70-90 degrees;

[0116] In the above reaction, the molar ratio of formula II to formula IVa is 1:1-1.5, preferably 1:1.01-1.05;

[0117] The above reaction is carried out in a solvent selected from one or more of toluene, hexanenitrile, dioxane, DMF, DMAc, DMSO, NMP, DMI, ethyl acetate, isopropyl acetate, dichloroethane, and the like, preferably toluene.

[0118] The above reaction can be carried out in the presence of a catalyst selected from a protic acid or a Lewis acid, such as hydrochloric acid, HBr, HI, HF, sulfuric acid, phosphoric acid, oxalic acid, methanesulfonic acid, trifluoromethanesulfonic acid, boric acid, benzenesulfonic acid, p-toluenesulfonic acid, and the like, preferably p-toluenesulfonic acid.

[0119] The present application also provides a method for preparing the compound of formula (Ia) as described above, and the synthetic route is as follows: wherein R 1 , R 2 , R 3 are defined as defined above, and Z 1 , Z 2 may be the same or different, and each is independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, and optionally substituted amido, and Z 1 , Z 2 may be linked to form a ring with the carbon atom to which they are both attached;

[0120] In the above reaction, the reaction temperature is 40-110°C, preferably 70-90°C;

[0121] In the above reaction, the molar ratio of the reactants in the reaction of formula II with formula IIIa is 1:1-1.5, preferably 1:1.01-1.05;

[0122] The above reaction is carried out in a solvent selected from one or more of toluene, hexanenitrile, dioxane, DMF, DMAc, DMSO, NMP, DMI, ethyl acetate, isopropyl acetate, dichloroethane, and the like, preferably toluene.

[0123] The above reaction can be carried out in the presence of a catalyst selected from a protic acid or a Lewis acid, such as hydrochloric acid, HBr, HI, HF, sulfuric acid, phosphoric acid, oxalic acid, methanesulfonic acid, trifluoromethanesulfonic acid, boric acid, benzenesulfonic acid, p-toluenesulfonic acid, and the like, preferably p-toluenesulfonic acid.

[0124] The present application also provides a method for preparing the compound of formula (V), and the synthetic route is as follows:

[0125] wherein R 1 , R 2 , R 3 , R 4 are defined as defined above, and R 5selected from the group consisting of OH, H2O, OTs, OMs, Cl, Br, I, and the like.

[0126] The reaction temperature in the above reaction is 40-110°C, preferably 70-90°C.

[0127] The reaction temperature in the above reaction is 40-110°C, preferably 70-90°C.

[0128] The reaction is carried out in a solvent selected from the group consisting of toluene, hexanenitrile, dioxane, DMF, DMAc, DMSO, NMP, DMI, ethyl acetate, isopropyl acetate, dichloroethane, and the like, alone or in combination, preferably toluene.

[0129] The reaction can be promoted by a catalyst selected from the group consisting of protonic acids or Lewis acids, such as hydrochloric acid, HBr, HI, HF, sulfuric acid, phosphoric acid, oxalic acid, methanesulfonic acid, trifluoromethanesulfonic acid, boric acid, benzenesulfonic acid, p-toluenesulfonic acid, and the like, preferably p-toluenesulfonic acid.

[0130] The present application also provides a method for preparing a compound of formula (Va), the synthetic route of which is as follows:

[0131] wherein R 1 , R 2 , R 3 are defined as defined above, and Z 1 , Z 2 may be the same or different, and are each independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, and optionally substituted amido, and Z 1 , Z 2 may be linked to form a ring with the carbon atom to which they are both attached;

[0132] The reaction temperature in the above reaction is 40-110°C, preferably 70-90°C.

[0133] The reaction temperature in the above reaction is 40-110°C, preferably 70-90°C.

[0134] The reaction is carried out in a solvent selected from the group consisting of toluene, hexanenitrile, dioxane, DMF, DMAc, DMSO, NMP, DMI, ethyl acetate, isopropyl acetate, dichloroethane, and the like, alone or in combination, preferably toluene.

[0135] The above reaction can be promoted by a catalyst, which is a protonic acid or 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 and the like, preferably p-toluenesulfonic acid.

[0136] The present application also provides a preparation method of the compound of formula (VI), and the synthetic route is as follows:

[0137]

[0138] wherein, R 1 , R 2 , R 3 , R 4 , R 6 , R 7 and R 8 are defined as defined above, wherein R 5 is selected from leaving groups selected from OH, H2O, OTs, OMs, Cl, Br, I and the like.

[0139] In the above reaction, the reaction temperature is 40-110 degrees, preferably 70-90 degrees;

[0140] In the above reaction, the molar ratio of formula I to formula IVb is 1:1-1.5, preferably 1:1.01-1.05;

[0141] The above reaction is carried out in a solvent selected from toluene, hexanenitrile, dioxane, DMF, DMAc, DMSO, NMP, DMI, ethyl acetate, isopropyl acetate, dichloroethane and the like, or a combination of one or more thereof, preferably toluene.

[0142] The above reaction can be promoted by a catalyst, which is a protonic acid or 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 and the like, preferably p-toluenesulfonic acid.

[0143] The present application also provides a preparation method of the compound of formula (VIa), and the synthetic route is as follows:

[0144]

[0145] wherein, R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , Z 1 and Z 2 are defined as defined above.

[0146] In the above reaction, the reaction temperature is 40-110°C, preferably 70-90°C;

[0147] In the above reaction, the molar ratio of the reactants of formula I and formula IIIb is 1:1-1.5, preferably 1:1.01-1.05;

[0148] The above reaction is carried out in a solvent selected from one or a combination of toluene, hexanenitrile, dioxane, DMF, DMAc, DMSO, NMP, DMI, ethyl acetate, isopropyl acetate, dichloroethane, etc., preferably toluene.

[0149] The above reaction can be carried out with the promotion of a catalyst selected from a protonic acid or a Lewis acid, such as 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.

[0150] The compound of the present application can be used for the preparation of a medicament or a cosmetic for the treatment, prevention and / or alleviation of hyperpigmentation. The use is in particular by topical application to the skin, such as human skin.

[0151] The present application also provides a cosmetic or pharmaceutical composition containing the compound of formula (A) of the present application or a salt thereof.

[0152] Further, the above cosmetic composition can be prepared in a suitable form such as a cream, an emulsion, a paste, a capsule, a lotion, a foam, a gel, a dispersion, a suspension, a spray, an essence, a pack, etc.

[0153] Further, the pharmaceutical / cosmetic composition of the present application can further contain one or more additives such as an antioxidant, an emollient, a humectant, a thickening agent, a fragrance, a preservative, a pigment or a colorant, or a sunscreen. These additives are conventional for those skilled in the art.

[0154] An antioxidant can be used to protect the ingredients of the composition against oxidizing agents contained in or to be contacted with the composition. Examples of antioxidants include ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, potassium propyl gallate, octyl gallate, dodecyl gallate, phenyl-alpha-naphthylamine, and tocopherols such as alpha-tocopherol.

[0155] 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 waxes), phospholipids and sterols, isopropyl palmitate or glyceryl stearate, in particular almond oil or fatty alcohols (such as cetyl alcohol, stearyl alcohol and / or myristyl alcohol).

[0156] Silicones are particularly preferred emollients. Silicones that can be used in the present application include, but are not limited to, dimethicone, methyl cyclomethicone, phenyl trimethicone, phenyl dimethicone, cetyl dimethicone, stearyl dimethicone, amino-terminated dimethicone, C 30-45 alkyl dimethicone, C 30-45 alkyl methicone, cetyl stearyl methicone, dimethicone copolyol, cyclopentyl siloxane, cyclohexyl siloxane, or any combination thereof. In particular, amino-terminated dimethicone can be used in the present application as an emollient.

[0157] Humectants are used to increase and maintain moisture in the skin. Examples of humectants include propylene glycol, butylene glycol, polyethylene glycols (PEG) (such as PEG-4 to PEG-32), glycerin (also known as glycerol), sorbitol, xylitol, maltitol, mannitol, polydextrose, hyaluronic acid and its salts (such as sodium or potassium salt), urea, aloe vera juice, honey, and the like.

[0158] Thickeners are used to increase the viscosity and consistency of the composition. Examples of thickeners include lipid thickeners such as cetyl alcohol, stearyl alcohol, myristyl alcohol, carnauba wax, or stearic acid; naturally derived thickeners such as cellulose derivatives, such as hydroxyethyl cellulose, guar gum, locust bean gum, xanthan gum, or gelatin; mineral thickeners such as silica, bentonite, or magnesium aluminum silicate; synthetic thickeners such as carbomers; ionic thickeners such as NaCl.

[0159] Examples of fragrances or perfumes include peppermint, rose oil, rose water, aloe vera juice, clove oil, menthol, camphor, eucalyptus oil, and other plant extracts. In order to eliminate certain odors of the composition, masking agents can be used.

[0160] Preservatives can be used to protect the composition from degradation. Examples of preservatives include phenoxyethanol, methyl paraben, benzalkonium chloride, benzethonium chloride, propyl paraben, benzoic acid, benzyl alcohol, and mixtures thereof. In particular, it can be phenoxyethanol, methyl paraben, or mixtures thereof.

[0161] Pigments or colorants are used to change the color of the composition. In addition to the above-mentioned soluble substances, insoluble light-protective dyes, in particular finely divided metal oxides or salts, are also suitable for this purpose. In the case of compositions which are to be white, titanium dioxide can be chosen. In clear or transparent compositions, light-protective agents such as titanium oxide are used in order to make them opaque. Examples of particularly suitable metal oxides are also zinc, iron, zirconium, silicon, manganese, aluminum and cerium oxides and mixtures thereof. Silicates (talc), barium sulfate or zinc stearate can be used as examples of suitable salts. Oxides and salts are used in the form of pigments which are used in skin care and skin protection emulsions and decorative cosmetics. In this case, the particles should have an average diameter of less than 100 nm, preferably between 5 and 50 nm, particularly preferably between 15 and 30 nm. They can be spherical, but particles having an elliptical shape or other shapes which are not spherical can also be used. The pigments can also be surface-treated, i.e. hydrophilized or hydrophobized. Typical examples are coated titanium dioxides. Suitable hydrophobic coating agents in this case are first and foremost organosilicon compounds, in particular trialkyloxysilanes or trisiloxanes. So-called micro- or nano-dyes are preferably used in sunscreen preparations, preferably using micronized zinc oxide.

[0162] In a preferred embodiment, the light-protective dye is selected from the group consisting of finely divided titanium dioxide, zinc oxide, finely divided zinc oxide. When titanium dioxide is chosen as the light-protective dye, it is advantageous for its total amount to be from 0.1 to 10.0% by weight of the preparation. When zinc oxide is chosen as the light-protective dye, it is advantageous for its total amount to be from 0.1 to 10.0% by weight of the preparation, and when one or more triazine organic pigments are chosen, it is advantageous for their total amount to be from 0.1 to 10.0% by weight, based on the total amount of the preparation. In a preferred embodiment, the pharmaceutical or cosmetic composition according to the application also contains at least one skin lightening agent, for example sclareolide.

[0163] The present application also relates to the cosmetic use of a compound of formula (A) according to the application, in particular as depigmenting, whitening, bleaching or lightening agent, more particularly for the skin, such as human skin.

[0164] The present application also relates to the cosmetic use of a cosmetic composition according to the application, in particular as depigmenting, whitening, bleaching or lightening agent composition, more particularly intended for topical application to the skin, such as human skin.

[0165] The present application also relates to the use of a compound of formula (A) according to the application for the preparation of a cosmetic composition, in particular intended for depigmenting, whitening, bleaching or lightening the skin, such as human skin.

[0166] The present application also relates to a compound of formula (A) according to the present application for use as depigmenting, whitening, bleaching or lightening agent, more particularly for use in skin, such as human skin.

[0167] The present application also relates to a method of depigmenting, whitening, bleaching or lightening skin, such as human skin, by applying to the skin of a person in need thereof an effective amount of a compound according to the present application or of a cosmetic composition according to the present application.

[0168] The present application also relates to a compound according to the present application for use as a medicament, more particularly in the treatment of hyperpigmentation disorders, more particularly by topical application to the skin, such as human skin.

[0169] The present application also relates to a pharmaceutical composition, in particular a dermatological composition, according to the present application for use as a medicament, more particularly in the treatment of hyperpigmentation disorders, more particularly by topical application to the skin, such as human skin.

[0170] The present application also relates to the use of a compound according to the present application for the manufacture of a pharmaceutical composition, in particular a dermatological composition, which is intended more particularly for use in the treatment of hyperpigmentation disorders, more particularly by topical application to the skin, such as human skin.

[0171] The present application also relates to the use of a compound according to the present application for the treatment of hyperpigmentation disorders, more particularly by topical application to the skin, such as human skin.

[0172] The present application also relates to a method of treating hyperpigmentation disorders of the skin, such as human skin, by applying to the skin of a person in need thereof an effective amount of a compound according to the present application or of a pharmaceutical composition, in particular a dermatological composition, according to the present application.

[0173] The hyperpigmentation disorders will more particularly be hyperpigmentations, including lentigo, melasma, freckles, post-inflammatory hyperpigmentation and hyperpigmentation induced by drugs, chemicals or sunlight.

[0174] The present application also relates to a compound according to the present application for use as an antioxidant, in particular for inhibiting or reducing oxidative stress, more particularly oxidative stress due to UV, more particularly oxidative stress in the skin.

[0175] The present application also relates to a method for inhibiting or reducing oxidative stress, more particularly oxidative stress due to UV, more particularly oxidative stress in the skin, comprising administering, in particular topically administering, to a person in need thereof an effective amount of a compound according to the present application.

[0176] When the compositions of the present invention are applied to human skin, the combination of the compounds and UV filter substances is well tolerated, without causing redness, whitening, or browning of the skin. They are non-irritating, do not dry out the skin, do not form a damp, scaly, powdery, or sticky film, and do not cause skin cracking. These UV filter substances can be UV-A filter substances, UV-B filter substances, photoprotective dyes, or mixtures thereof. Specifically, UV filter substances refer to organic substances (light filter substances) that are, for example, liquid or crystalline at room temperature, capable of absorbing ultraviolet radiation and releasing the absorbed energy in the form of long-wave radiation, such as heat. Typically, the content of the UV filter substance is from 0.05% to 50% by weight, preferably from 0.5% to 40% by weight.

[0177] UV filter materials can be oil-soluble or water-soluble.

[0178] Suitable oil-soluble substances include:

[0179] • 3-Benzyl camphor and its derivatives, such as 3-(4-methylbenzylidene)camphor;

[0180] ·4-Aminobenzoic acid derivatives, preferably 2-ethylhexyl 4-(dimethylamino)benzoate, 2-octyl 4-(dimethylamino)benzoate and pentyl 4-(dimethylamino)benzoate;

[0181] • Esters of cinnamic acid, preferably 2-ethylhexyl 4-methoxycinnamic acid, propyl 4-methoxycinnamic acid, isoamyl 4-methoxycinnamic acid, or 2-ethylhexyl 2-cyano-3,3-diphenylacrylate (occrylene).

[0182] • Esters of salicylic acid, preferably 2-ethylhexyl salicylate, homosalyl salicylate, and menthyl salicylate;

[0183] Benzophenone derivatives, preferably 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2-hydroxy-4-methoxy-benzophenone, or 2,2'-dihydroxy-4-methoxybenzophenone;

[0184] • Benzyl malonate, preferably bis-2-ethylhexyl 4-methoxybenzyl malonate.

[0185] • Triazine derivatives, such as 2,4,6-tris(p-2-ethylhexylaniline)-1,3,5-triazine and bis(octylbutyramide)triazinone;

[0186] Benzoylmethane derivatives, preferably 4-tert-butyl-4'-methoxydibenzoylmethane;

[0187] • Carbonyl-containing polycyclic compounds, such as ketone tricyclic (5.2.1.0) decane derivatives, etc.

[0188] Suitable examples of water-soluble substances include:

[0189] • 2-phenylbenzimidazole-5-sulfonic acid and alkali metal, alkaline earth metal, ammonium, alkylammonium, alkanolammonium, glucammonium salts thereof;

[0190] • disodium salt of 2,2'-bis-(1,4-phenylene)-1 H-benzimidazole-4,6-disulfonic acid;

[0191] • sulfonic acid derivatives of benzophenone, preferably 2-hydroxy-4- methoxybenzophenone-5-sulfonic acid and salts thereof;

[0192] • sulfonic acid derivatives of 3-benzylidene camphor, preferably benzylidene camphor sulfonic acid and 2-methyl-5-(2-oxo-3-antiradicalyl) sulfonic acid and salts thereof.

[0193] Typical examples of particularly suitable UV-A light filter substances include derivatives of benzoylmethane, such as 4-tert-butyl-4'-methoxy-dibenzoylmethane, 2-(4-diethylamino-2-hydroxybenzoyl)-benzoic acid hexyl ester, 1-phenyl-3-(4'-isopropylphenyl)propane-1,3-dione, and also enamine compounds. Of course, UV-A and UV-B filters can also be used in mixtures, for example, in combination of diphenylmethane derivatives and / or benzoylmethane derivatives 4-tert-butyl-4'-methoxy-dibenzoylmethane and cinnamic acid derivatives, the cinnamic acid derivatives being preferably 2-cyano-3,3-diphenylacrylic acid 2-ethylhexyl ester (octocrylene) and / or 4-methoxycinnamic acid 2-ethylhexyl ester and / or 4-methoxycinnamic acid isoamyl ester and / or 4-methoxycinnamic acid propyl ester. The cinnamic acid ester derivatives of such combinations can also be replaced by water-soluble filters such as 2-phenylbenzimidazole-5-sulfonic acid and alkali metal, alkaline earth metal, ammonium, alkylammonium, alkanolammonium, glucammonium salts thereof and / or 4-(2-oxo-3-antiradicalylmethyl)benzenesulfonic acid and 2-methyl-5-(2-oxo-3-antiradicalyl)sulfonic acid and alkali metal, alkaline earth metal, ammonium, alkylammonium, alkanolammonium, glucammonium salts thereof.

[0194] In a preferred embodiment, the (cosmetic or pharmaceutical) preparation according to the application contains at least one additional UV-absorbing substance selected from the group comprising:

[0195] • camphor benzalkonium methosulfate

[0196] • p-phenylene-bis-dimethylbenzyl sulfonic acid and salts

[0197] • homomethyl salicylate

[0198] • benzylidene camphor sulfonic acid and salts

[0199] • 2-cyano-3,3-diphenylacrylic acid-2-ethylhexyl ester

[0200] • ethyl p-aminobenzoate

[0201] • isopropyl methylphenyl glycidate

[0202] • 2-phenylbenzimidazole sulfonic acid and salts thereof

[0203] • 2,4,6-tris(p-2-ethylhexylphenylamine)-1,3,5-triazine

[0204] • 2-(2H-benzotriazol-2-yl)-4-methyl-6-(2-methyl-3-(1,3,3,3-tetramethyl-1- (trimethylsilyl-oxy)-disiloxanyl)-propyl)phenol

[0205] • methylene bis-benzotriazolyl tetramethylbutylphenol

[0206] • 4,4'-[(6-[4-(1,1-dimethyl)-aminocarbonyl]phenylamino)-1,3,5-triazine-2,4- diyl]bisimino]-bis-(benzoic acid 2-ethylhexyl ester)

[0207] • 3-(4'-methylbenzylidene)-D,L-camphor

[0208] • 3-benzylidene camphor

[0209] • salicylic acid-2-ethylhexyl ester

[0210] • 4-dimethylaminobenzoic acid-2-ethylhexyl ester

[0211] • 4-hydroxy-4-methoxybenzophenone-5-sulfonic acid and salts thereof

[0212] • benzalmalonate-polysiloxane

[0213] • menthyl anthranilate

[0214] • polyacrylamidomethyl benzylidene camphor

[0215] • p-methoxycinnamic acid-2-ethylhexyl ester

[0216] or mixtures thereof.

[0217] The compositions of the present application, when applied to human skin, can be used simultaneously with skin lightening agents to enhance the effect of reducing hyperpigmentation. Suitable skin lightening agents for use in the present application include: kojic acid derivatives (preferably kojic dipalmitate), arbutin, ascorbic acid and ascorbic acid derivatives (preferably magnesium ascorbyl phosphate), hydroquinone and hydroquinone derivatives, senkyunen, amino acids (preferably cyclohexyl glycinate, N-acetyl tyrosine and derivatives thereof, undecylenoyl phenylalanine), sulfur-containing molecules (preferably glutathione, cysteine, thiourea derivatives, thioctic acid), alpha-hydroxy acids (preferably citric acid, lactic acid, malic acid, salts and esters thereof), gluconic acid, chromone derivatives (preferably aloe-emodin), 1-aminoethyl phosphinic acid, flavonoids, ellagic acid, nicotinamide, thujaplicin and derivatives thereof, triterpenes (preferably maslinic acid), sterols (preferably dihydrobrassicasterol), benzofuranones (preferably senkyunen), 4-vinylguaiacol, 4-ethylguaiacol, zinc salts (preferably zinc chloride or zinc gluconate), diacids (preferably octadecene diacid and / or azelaic acid), nitric oxide synthesis inhibitors (preferably L-nitroarginine and derivatives thereof, 2,7-dinitroindazole or thio-L-citrulline), metal chelators (preferably alpha-hydroxy fatty acids, phytic acid, cholic acid, bile extracts, humic acid, EGTA, EDTA and derivatives thereof), soy milk and extracts thereof, retinoids, serine protease inhibitors, other synthetic or extracted natural active ingredients (preferably used in the form of plant extracts, for example, bearberry extract, grape extract, mulberry extract, sweet potato extract, rice extract, papaya extract, turmeric extract, cyperus rotundus extract, licorice root extract (preferably glabridin or glycyrrhetinol), artocarpus lakoocha extract, sorrel extract, pine (pinus) extract, vitis extract or stilbene derivatives isolated or concentrated therefrom, saxifrage extract, scutellaria extract, microalgae extract (preferably tetraselmis suecica extract), ginseng extract.

[0218] The present application will now be described in detail by way of examples. However, it is to be understood that the examples are not intended to limit the scope of the protection in any way.

[0219] In the following examples:

[0220] The amounts of reactants and products were measured by liquid chromatography (Agilent HPLC 1260).

[0221] The conversion and selectivity of the reaction were calculated by the following formula:

[0222] Conversion = (molar amount of raw material input - molar amount of raw material remaining in the product) / molar amount of raw material input x 100%.

[0223] Selectivity = Actual moles of target product / Theoretical moles of target product x 100%

[0224] The raw materials used were commercially available products, and the room temperature was 25 ± 5°C, unless otherwise specified.

[0225] Example 1

[0226]

[0227] A 1000ml four-necked flask was charged with 250g of toluene, 1.0g of catalyst p-toluenesulfonic acid, 110g of resorcinol, and 125g of N-vinylpiperidone, heated, and reacted at 90°C for 10 hours. The reaction was completed as detected by liquid phase. After the solvent was removed under reduced pressure, the product was obtained by recrystallization using a mixed solvent of ethyl acetate / petroleum ether, with a yield of 90% and a purity of 99%.

[0228] Example 2

[0229]

[0230] A 1000ml four-necked flask was charged with 250g of toluene, 1.0g of catalyst p-toluenesulfonic acid, 110g of resorcinol, and 202g of 6-methoxy-2-naphthylethanol, heated, and reacted at 90°C for 10 hours. The reaction was completed as detected by liquid phase. After the solvent was removed under reduced pressure, the product was obtained by recrystallization using a mixed solvent of ethyl acetate / petroleum ether, with a yield of 92% and a purity of 99%.

[0231] Example 3

[0232]

[0233] A 1000ml four-necked flask was charged with 250g of toluene, 1.0g of catalyst p-toluenesulfonic acid, 110g of resorcinol, and 222g of N-vinylpyrrolidone, heated, and reacted at 90°C for 10 hours. The reaction was completed as detected by liquid phase. After the solvent was removed under reduced pressure, the product was obtained by recrystallization using a mixed solvent of ethyl acetate / petroleum ether, with a yield of 85% and a purity of 96%.

[0234] Example 4

[0235]

[0236] A 1000ml four-necked flask was charged with 250g of toluene, 1.0g of catalyst p-toluenesulfonic acid, 110g of resorcinol, and 244g of 1-phenylethanol, heated, and reacted at 90°C for 10 hours. The reaction was completed as detected by liquid phase. After the solvent was removed under reduced pressure, the product was obtained by separation and purification using a silica gel column (eluted with a mixed solvent of ethyl acetate / petroleum ether), with a yield of 82% and a purity of 97%.

[0237] Example 5

[0238]

[0239] In a 1000 ml four-necked flask, add toluene 150 g, catalyst p-toluene sulfonic acid 0.50 g, resorcinol pyrrolidine derivative 110 g, N-vinyl pyrrolidine 56 g, heat, react at 90 °C for 10 hours, liquid phase detection reaction is complete, after the solvent is removed under reduced pressure, add ethyl acetate / petroleum ether mixed solvent recrystallization to obtain the product, yield 84%, purity 97%.

[0240] Example 6

[0241]

[0242] In a 1000 ml four-necked flask, add toluene 250 g, catalyst p-toluene sulfonic acid 1.0 g, resorcinol benzyl ethyl derivative 214 g, 1-phenyl ethanol 122 g, heat, react at 90 °C for 10 hours, liquid phase detection reaction is complete, after the solvent is removed under reduced pressure, separate and purify by silica gel column (eluted with ethyl acetate / petroleum ether mixed solvent), after the solvent is removed by concentration to obtain the product, yield 80%, purity 95%.

[0243] The following compounds in Tables 1-3 are prepared according to the methods described in the above examples.

[0244]

[0245] Table 1: Compounds of structure I

[0246]

[0247]

[0248]

[0249] Table 2: Compounds of structure VI

[0250]

[0251]

[0252] Table 3: NMR data of compounds I-a to I-g

[0253]

[0254]

[0255]

[0256] Test Example: Evaluation of tyrosinase inhibitory activity

[0257] 1.1 Test Method A: Test the inhibitory activity of the sample on tyrosinase by light absorption method

[0258] The compound of the present application is respectively prepared into 5 μg / mL, 3 μg / mL, 1 μg / mL, 0.5 μg / mL, 0.01 μg / mL solution. The positive control kojic acid is respectively prepared into 25, 20, 10, 7.5, 5, 2.5 μg / mL concentration solution. Take 50 μL of the above five kinds of concentration solution, and prepare 1 mL with 950 μL of pH 6.8 phosphate buffer solution, add 1 mL of 0.1 mg / mL tyrosine, then add 1 mL of tyrosinase (200 U / mL) prepared by pH 6.8 phosphate buffer solution, incubate at 37°C for 20 min, and measure the absorbance at 490 nm.

[0259] Enzyme activity inhibition rate = [(A2-A1)-(B2-B1)] / (A2-A1) x 100%

[0260] A1 is the absorbance at 0 min without inhibitor; A2 is the absorbance after 20 min without inhibitor;

[0261] B1 is the absorbance at 0 min with inhibitor; B2 is the absorbance after 20 min with inhibitor.

[0262] The test results show that the compound of the present application has good inhibitory effect on inhibiting tyrosinase at IC50 of 10 μM, and preferred compounds I-a, I-b, I-c, I-d, I-e, I-f, I-g, I-h, V-a, V-b and V-c have good inhibitory effect at 0.05 μM-1 μM, and the IC50 of the control sample kojic acid is 47.0 μM. The above results show that the compound of the present application has strong tyrosinase inhibitory activity; the present application can be used alone or in combination as a tyrosinase inhibitor for the inhibition of enzymatic browning of fruits and vegetables, for whitening in whitening cosmetics, and for preparing various preparations for preventing and treating human hypermelanosis, melanoma and other diseases requiring inhibition of tyrosinase activity.

[0263] 1.3 Test Method B:

[0264] 1.3.1 Cytotoxicity test

[0265] 1) Cell inoculation: inoculate cells into 96-well plates at a seeding density of 1 x 10 4 Inoculate cells into 96-well plates at a seeding density of 1 x 10

[0266] 2) Experimental grouping: zero setting group, control group, positive control group and sample group. In the sample group, different concentration gradients are set for each sample, and 3 repeated wells are set under each concentration gradient.

[0267] 3) Liquid preparation: prepare sample working solutions with different concentrations according to the test concentration setting table.

[0268] 4) Drug administration: when the cell plating rate in the 96-well plate reaches 40% to 60%, drug administration is performed. The control group is added with 200 μL of culture medium containing 10% PBS (Gibco) per well; the positive control group is added with 200 μL of culture medium containing 10% DMSO per well; the sample group is added with 200 μL of culture medium containing the corresponding concentration of samples per well; the zero setting group is not inoculated with cells, and only 200 μL of cell culture medium is added. After drug administration is completed, the 96-well plate is placed in the incubator (37°C, 5% CO2) for culture.

[0269] 5) Detection: after 24 h of cell incubation and culture, the supernatant is discarded, MTT working solution (0.5 mg / mL) is added, and incubation is performed at 37°C in the dark for 4 h. After incubation, the supernatant is discarded, 100 μL of DMSO is added to each well, and the OD value is read at 490 nm.

[0270] 6) Calculation of cell relative viability:

[0271]

[0272] Cell viability test data example:

[0273]

[0274] * Control sample: phenylethyl resorcinol

[0275] The cell viability data show that the structure of the compound of the present application has low cytotoxicity.

[0276] 1.3.2 Cell melanin synthesis inhibition test

[0277] According to the cytotoxicity test data, the cell melanin synthesis inhibition test is carried out within the range allowed by cytotoxicity. The sample is grouped according to different concentrations, the detection index is the melanin content, the detection model is melanocyte, and the detection is carried out by colorimetry. The logarithmic growth phase cells are collected, the cell density is 2×105 per bottle, and is inoculated into a 24-well plate, and after being cultured in an incubator (37℃, 5% CO2) for 24h, according to the cytotoxicity result, the drug is added according to the concentration requirement, and the untreated cells are used as a blank control, and 3 parallel groups are set. After adding the drug, continue to culture in an incubator (37℃, 5% CO2) for 48h, discard the supernatant, add 1mL of 10% DMSO in 1M NaOH, and place in a 60℃ constant temperature oven for incubation for 1h, after recovering to room temperature, transfer 200μL per hole to a 96-well plate, use 10% DMSO in 1M NaOH as a blank control, read the absorbance value at 405nm, and calculate the relative inhibition rate of cell melanin.

[0278]

[0279] Cell melanin synthesis inhibition rate results

[0280] Sample Concentration (%, g / ml) Cell melanin synthesis inhibition rate (%) I-a 0.10 71.10 I-a 0.050 50.22 I-a 0.025 18.55 I-d 0.10 67.80 I-d 0.050 50.40 I-d 0.025 33.54 I-e 0.10 34.99 I-f 0.05 48.15 I-g 0.05 43.26 I-h 0.10 46.30 V-a 0.010 73.80 V-a 0.0050 47.60 V-a 0.0025 28.89 V-b 0.10 32.05 V-c 0.10 54.85 PC* 0.30 66.37

[0281] Note: PC sample is kojic acid.

[0282] The test results show that the compounds I-a, I-d, I-e, I-f, I-g, I-h, V-a, V-b, V-c of the present application have cell melanin synthesis inhibition effect at a lower concentration (not more than 0.10% g / ml), and the selected I-a, I-d, V-a all show better cell melanin synthesis inhibition effect than kojic acid, and can even inhibit cell melanin synthesis at very low concentration.

[0283] The above results show that: the compounds of the present application all have strong tyrosinase inhibition activity; the present application can be used alone or mixed as a tyrosinase inhibitor for whitening in whitening cosmetics, and various preparations for preventing and treating human pigment deposition diseases, melanoma and other diseases requiring inhibition of tyrosinase activity.

[0284] Although the present application has been disclosed as above with preferred embodiments, it is not intended to limit the present application, and any person skilled in the art can make various modifications and modifications without departing from the spirit and scope of the present application, therefore the protection scope of the present application should be defined by the claims.

Claims

1. A compound of formula (I-1) or a salt thereof, in, n is a natural number selected from 1 to 6; R 1 Selected from H or C1-C6 alkyl groups; When R 1 When selected from H, R 3 Selected from H or C1-C6 alkyl groups, R 4 Selected from C1-C6 alkyl groups; when R 1 When selected from C1-C6 alkyl groups, R 3 Selected from H or C1-C6 alkyl groups, R 4 Selected from H or C1-C6 alkyl groups.

2. The compound or its salt according to claim 1, characterized in that, R 1 Selected from H or methyl; R 3 Selected from one of H, methyl, ethyl, propyl, and butyl; R 4 It is selected from H, methyl, ethyl, propyl and butyl; n is selected from 1, 2 and 3.

3. Compounds of formula (I-3) or their salts, in, R 1 Selected from H or C1-C6 alkyl; R 3 Selected from H or C1-C6 alkyl; R 4 Selected from H or C1-C6 alkyl groups.

4. The compound or its salt according to claim 3, characterized in that, R 1 Selected from H or methyl; R 3 Selected from one of H, methyl, ethyl, propyl, and butyl; R 4 It is selected from one of H, methyl, ethyl, propyl and butyl.

5. A compound of formula (VI-2) or a salt thereof, in, R 1 Selected from H or C1-C6 alkyl; R 3 Selected from H or C1-C6 alkyl; R 4 Selected from H or C1-C6 alkyl; R 7 Selected from H or C1-C6 alkyl; R 8 Selected from H or C1-C6 alkyl; n is selected from 1, 2, and 3; m is selected from 1, 2, and 3, under the condition that R 3 R 4 R 7 and R 8 They are not both hydrogen.

6. A compound, characterized in that, 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-piperidinone; N-(1-(2,4-dihydroxyphenyl)propyl)-2-piperidinone; N-(1-(2,4-dihydroxyphenyl)ethyl)-2-cyclohexylimine; N-(1-(2,4-dihydroxyphenyl)propyl)-2-cyclohexylimine; 1,1'-((4,6-dihydroxy-1,3-phenylenemethyl)bis(ethyl-1,1-imide))bis(pyrrolidone-2-one); 1,1'-((4,6-dihydroxy-1,3-benzoxyl)bis(propyl-1,1-pyrrolidone))bis(pyrrolidone-2-one); 1,1'-((4,6-dihydroxy-1,3-phenylenemethyl)bis(ethyl-1,1-imide))bis(piperidin-2-one); 1,1'-((4,6-dihydroxy-1,3-phenylenemethyl)bis(propyl-1,1-imide))bis(piperidin-2-one); 1,1'-((4,6-dihydroxy-1,3-phenylidene)bis(ethyl-1,1-idene))bis(cycloheximine-2-one); 1,1'-((4,6-dihydroxy-1,3-benzoxyl)bis(propyl-1,1-pyridyl))bis(cycloheximine-2-one).

7. A pharmaceutical composition comprising the compound of any one of claims 1-6 or a pharmaceutically acceptable salt thereof.

8. Use of the compound according to any one of claims 1-6 in the preparation of a medicament for treating, preventing and / or reducing hyperpigmentation.

9. The non-therapeutic cosmetic use of the compound or a salt thereof according to any one of claims 1-6 for treating, preventing and / or reducing hyperpigmentation.

10. A cosmetic composition comprising the compound of any one of claims 1-6 or a salt thereof.

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