Stabilization of thiopyridinone compound and composition comprising thiopyridinone compound

Abstract

To provide a composition including a thiopyridinone compound with increased stability of the thiopyridinone compound over time, in particular when the composition is maintained for a relatively long period of time at elevated temperature.SOLUTION: The present invention relates to a composition comprising: (1) at least one thiopyridinone compound; and (2) at least one lipophilic antioxidant. The present invention can provide a composition including the (1) thiopyridinone compound with increased stability of the (1) thiopyridinone compound over time, in particular even when the composition is maintained for a relatively long period of time at elevated temperature.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to the stabilization of thiopyridinone compounds in compositions that include the compounds. [Background technology]

[0002] At various times in life, some people notice darker and / or more colored spots on their skin, more particularly on the face and hands, giving the skin an inhomogeneous appearance. These spots are due to a high concentration of melanin, especially in the keratinocytes located on the surface of the skin.

[0003] For the purpose of treating pigmented blemishes, the use of effective, non-toxic topical depigmenting substances is most particularly desired.

[0004] For example, arbutin, niacinamide and kojic acid are known skin depigmenting agents.

[0005] On the other hand, WO2017 / 102349 discloses a novel depigmenting or whitening agent, namely, a thiopyridinone compound, which can exhibit a strong depigmenting or whitening effect by reducing the production of melanin.

[0006] However, it has been discovered that thiopyridinone compounds tend to become unstable over time in compositions, especially when the compositions containing the thiopyridinone compounds are maintained at elevated temperatures for relatively long periods of time. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] WO2017 / 102349 [Patent Document 2] EP-A-3390363 Summary of the Invention [Problem to be solved by the invention]

[0008] It is therefore an object of the present invention to provide a composition comprising a thiopyridinone compound that exhibits enhanced stability of the thiopyridinone compound over time, particularly when the composition is maintained at elevated temperatures for relatively long periods of time. [Means for solving the problem]

[0009] The above objectives are: (1) A compound of the following formula (I), a tautomer of the following formula (I'):

[0010] [ka]

[0011] (In the formula, R1 is, a) hydrogen atoms, and b) may be the same or different; i) -O-R3 and ii)-S-R3 Saturated linear C1-C optionally substituted with one or more groups selected from 10 Or branched C3~C 10 Alkyl group represents a group selected from R2 is a) a hydrogen atom; b) may be the same or different; i) -O-R3, ii)-SR 3、 iii) -C(O)-O-R3, and iv) C5-C optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups. 12 Aryl Group Saturated linear C1-C optionally substituted with one or more groups selected from 12 Or branched C3~C 12 or a cyclic C3 to C8 hydrocarbon group; c) C5-C optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups 12 Aryl groups and represents a group selected from Where: R3 is a) a hydrogen atom, and b) Saturated linear C1-C 10 Or branched C3~C 10 Alkyl group represents a group selected from At least one compound selected from the group consisting of salts thereof, solvates such as hydrates thereof, optical isomers thereof, racemates thereof, and mixtures thereof; and (2) at least one lipophilic antioxidant This can be achieved by a composition comprising:

[0012] R1 in formulae (I) and (I') represents a hydrogen atom or or R1 in formula (I) and (I') is a linear (C1-C 10 ) Alkyl group or branched (C3-C 10 ) alkyl group, particularly a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably ethyl, and it may be particularly preferred that the alkyl group of R1 is unsubstituted.

[0013] R2 in formulae (I) and (I') represents a hydrogen atom or or R2 in formula (I) and (I') is a straight chain (C1-C 10 ) Alkyl group or branched (C3-C 10 ) alkyl group, in particular a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably a methyl or ethyl group, and it may be preferred that said alkyl group of R2 is unsubstituted.

[0014] R2 in formula (I) and (I') is a straight chain (C1-C 10 ) Alkyl group or branched (C3-C 10 ) an alkyl group, in particular a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl, said alkyl group being substituted with one or more groups selected from i), ii), iii) and iv) as defined above, preferably said alkyl group being substituted with one or two groups selected from i), ii) and iii), more preferably with one or two groups selected from i) and iii), and better still with one group iii) as carboxy.

[0015] R2 in formulae (I) and (I') represents a (C3-C8) cycloalkyl group, preferably a (C5-C7) cycloalkyl group, such as cyclohexyl; or R2 in formula (I) and (I') is a C5-C alkyl group optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups. 12 It may be preferred that it represents an aryl group, preferably an unsubstituted phenyl group.

[0016] R3 in formulae (I) and (I') represents a hydrogen atom or or R3 in formula (I) and (I') is a saturated linear C1-C 10 Or branched C3~C 10 It may be preferred that it represents an alkyl group, in particular a linear (C3-C6) alkyl group or a branched (C3-C6) alkyl group, preferably a (C1-C4) alkyl group, such as a methyl group.

[0017] R1 in formula (I) and (I') is a) hydrogen atoms, and b) may be the same or different; i) -O-R3 and ii)-SR3、 -S-R3, optionally substituted with one or more groups i) A saturated linear C1-C6 or branched C3-C6 alkyl group optionally substituted with one or more groups selected from represents a group selected from R2 in formula (I) and (I') is a) a hydrogen atom; b) may be the same or different; i) -O-R3, ii)-SR 3、 iii) -C(O)-O-R3, and iv) a phenyl group optionally substituted with one or more hydroxyl and / or one or more C1-C4 alkoxy groups, such as methoxy; Preferably, a phenyl group substituted with one or more groups selected from i) and iii), preferably iii) such as carboxy. Saturated linear C1-C optionally substituted with one or more groups selected from 10 Or branched C3~C 10 Or a cyclic C3 to C8 hydrocarbon group such as C5 to C6 represents a group selected from R3 in formula (I) and (I') is a) a hydrogen atom, and b) Saturated linear C1~C6 or branched C3~C6 alkyl group represents a group selected from Preferentially, the compounds of formula (I) and the tautomers (I′), their salts, their solvates, such as their hydrates, their optical isomers, their racemates and mixtures thereof have the following meanings: R1 in formula (I) and (I') is: a) a hydrogen atom, and b) saturated, linear C1-C4 or branched C3-C4 alkyl groups, which may be the same or different, and which are optionally substituted, more preferably unsubstituted, with one or more groups selected from i) -OR3; represents a group selected from R2 in formula (I) and (I') is a) hydrogen atoms, and b) may be the same or different; i) -O-R3, iii) -C(O)-O-R3, and iv) C5-C optionally substituted with one or more hydroxyl and / or one or more C1-C4 alkoxy groups. 12 Aryl Group Saturated linear C1-C optionally substituted with one or more groups selected from 10 Or branched C3~C 10 Or a cyclic C3-C8 hydrocarbon group such as C5-C6 represents a group selected from R3 in formula (I) and (I') is: a) a hydrogen atom, b) saturated linear C1-C4 or branched C3-C4 alkyl groups, such as methyl or ethyl It may be preferred that R represents a group selected from:

[0018] (1) The compound may be selected from the following compounds 1 to 24, tautomers thereof, salts thereof, solvates such as hydrates thereof, optical isomers thereof, racemates thereof, and mixtures thereof, in particular compounds 1, 2, 4, 6, 7, 9, 11, 12, 14, 15, 16, 17, 18, 19, 20, or 21, more particularly 1, 9, 16, 18, 19, 20, or 21, preferably 18, 19, 20, or 21, more preferably 20.

[0019] [Table 1A]

[0020] [Table 1B]

[0021] [Table 1C]

[0022] [Table 1D]

[0023] The amount of the (1) compound in the composition according to the present invention may be from 0.01% to 10% by weight, preferably from 0.05% to 5% by weight, more preferably from 0.1% to 3% by weight, based on the total weight of the composition.

[0024] (2) The lipophilic antioxidant may be selected from the group consisting of dibutylhydroxytoluene, ethylhexylmethoxycrylene, tocopherol acetate, oryzanol, pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, dilauryl thiopropionate, and mixtures thereof.

[0025] The amount of (2) lipophilic antioxidant in the composition according to the present invention can be from 0.01% by weight to 10% by weight, preferably from 0.05% by weight to 5% by weight, and more preferably from 0.1% by weight to 3% by weight, relative to the total weight of the composition.

[0026] The composition according to the invention may be for the lightening of keratinous materials, preferably the skin.

[0027] The present invention also relates to a cosmetic method, preferably a whitening method, for keratinous materials, preferably for the skin, comprising the steps of: It also relates to a method comprising the step of applying a composition according to the invention to keratinous materials.

[0028] Another aspect of the present invention is a compound of formula (I) below, a tautomer of formula (I') below:

[0029] [ka]

[0030] (In the formula, R1 is, a) hydrogen atoms, and b) may be the same or different; i) -O-R3 and ii)-S-R3 Saturated linear C1-C optionally substituted with one or more groups selected from 10 Or branched C3~C 10 Alkyl group represents a group selected from R2 is a) a hydrogen atom; b) may be the same or different; i) -O-R3, ii)-SR 3、 iii) -C(O)-O-R3, and iv) C5-C optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups. 12 Aryl Group Saturated linear C1-C optionally substituted with one or more groups selected from 12 Or branched C3~C 12 or a cyclic C3 to C8 hydrocarbon group; c) C5-C optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups 12 Aryl groups and represents a group selected from Where: R3 is a) a hydrogen atom, and b) Saturated linear C1-C 10 Or branched C3~C 10 Alkyl group represents a group selected from The present invention relates to a use of at least one lipophilic antioxidant (2) in a composition comprising at least one compound selected from the group consisting of salts thereof, solvates such as hydrates thereof, optical isomers thereof, racemates thereof, and mixtures thereof, for stabilizing the compound (1). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0031] As a result of extensive investigation, the inventors have discovered that it is possible to provide a thiopyridinone compound, or a composition comprising a thiopyridinone compound, in which the stability of the thiopyridinone compound is enhanced, particularly when the composition is maintained at elevated temperatures for relatively long periods of time.

[0032] Therefore, the composition according to the invention (1) A compound of the following formula (I), a tautomer of the following formula (I'):

[0033] [ka]

[0034] (In the formula, R1 is, a) hydrogen atoms, and b) may be the same or different; i) -O-R3 and ii)-S-R3 Saturated linear C1-C optionally substituted with one or more groups selected from 10 Or branched C3~C 10 Alkyl group represents a group selected from R2 is a) a hydrogen atom; b) may be the same or different; i) -O-R3, ii)-SR 3、 iii) -C(O)-O-R3, and iv) C5-C optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups. 12 Aryl Group Saturated linear C1-C optionally substituted with one or more groups selected from 12 Or branched C3~C 12 or a cyclic C3 to C8 hydrocarbon group; c) C5-C optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups 12Aryl groups and represents a group selected from Where: R3 is a) a hydrogen atom, and b) Saturated linear C1-C 10 Or branched C3~C 10 Alkyl group represents a group selected from These salts, solvates such as hydrates, optical isomers, racemates, and mixtures thereof (hereinafter, the compounds are referred to as "thiopyridinone compounds"); and (2) at least one lipophilic antioxidant Includes.

[0035] The composition according to the present invention can exhibit enhanced stability of the (1) thiopyridinone compound contained therein.

[0036] In other words, the composition according to the present invention can enhance the stability of the (1) thiopyridinone compound therein. The term "stability" of the (1) thiopyridinone compound can be determined by the change in the amount of the (1) thiopyridinone compound in the composition according to the present invention during a specific period of time. Enhanced "stability" means that the change in the amount of the (1) thiopyridinone compound over time is further limited.

[0037] The compositions according to the present invention can exhibit enhanced stability of the (1) thiopyridinone compound therein, even when the compositions are maintained at elevated temperatures, such as 55° C., for relatively long periods of time (e.g., 2 weeks).

[0038] Therefore, the composition according to the present invention can be stored for a long period of time even under high temperature conditions.

[0039] In addition, the enhanced stability of (1) the thiopyridinone compound may lead to improved or enhanced bioavailability of (1) the thiopyridinone compound, which may function as a bleaching or whitening agent. Thus, the composition according to the present invention may provide an enhanced or improved bleaching or whitening effect.

[0040] The composition, use, etc. according to the present invention will be described in detail below.

[0041] [Composition] The composition according to the invention comprises: (1) at least one thiopyridinone compound, and (2) at least one lipophilic antioxidant Includes.

[0042] The (1) thiopyridinone compound and (2) lipophilic antioxidant, as well as other features of the composition according to the present invention, are described below.

[0043] (Thiopyridinone compounds) The composition according to the present invention comprises at least one (1) thiopyridinone compound. Two or more (1) thiopyridinone compounds may be used in combination. Thus, a single type of (1) thiopyridinone compound or a combination of different types of (1) thiopyridinone compounds may be used.

[0044] (1) The thiopyridinone compound is a compound of the following formula (I), a tautomer of the following formula (I'):

[0045] [ka]

[0046] (In the formula, R1 is, a) hydrogen atoms, and b) may be the same or different; i) -O-R3 and ii)-S-R3 Saturated linear C1-C optionally substituted with one or more groups selected from 10 Or branched C3~C 10 Alkyl group represents a group selected from R2 is a) a hydrogen atom; b) may be the same or different; i) -O-R3, ii)-SR 3、 iii) -C(O)-O-R3, and iv) C5-C optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups. 12 Aryl Group Saturated linear C1-C optionally substituted with one or more groups selected from 12 Or branched C3~C 12 or a cyclic C3 to C8 hydrocarbon group; c) C5-C optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups 12 Aryl groups and represents a group selected from Where: R3 is a) a hydrogen atom, and b) Saturated linear C1-C 10 Or branched C3~C 10 Alkyl group represents a group selected from Salts thereof, solvates such as hydrates thereof, optical isomers thereof, racemates thereof, and mixtures thereof is selected from.

[0047] For purposes of this invention, unless otherwise specified: - Saturated linear C1-C 12 Or branched C3~C 12 The hydrocarbon group is a saturated linear C1-C 12 Or branched C3~C 12 Hydrocarbon group, preferably linear C1-C 10Or branched C3~C 10 More preferably, the term "linear (C1-C6)" corresponds to a linear C1-C6 or branched C3-C6 hydrocarbon group. 12 ) Alkyl or branched (C3-C 12 ) alkyl group". Preferentially, the linear or branched radicals may be selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl. More preferentially, the saturated linear or branched alkyl radicals may be selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl, pentyl, hexyl, heptyl and octyl, e.g. methyl, ethyl, n-pentyl, n-nonyl, isobutyl. - A saturated "cyclic C3-C8" hydrocarbon group is a monocyclic or bicyclic cycloalkyl group containing 3 to 8 carbon atoms, in particular a monocyclic cycloalkyl group in the range C5 to C7, such as a cyclohexyl group. - "Alkoxy group" refers to a group in which the alkyl group is linear or branched C1-C 16 , preferably a C1-C8 hydrocarbon-based group, an alkyloxy group. - when an alkoxy group is optionally substituted, this implies that the alkyl group is optionally substituted as described above. - "aryl" group denotes a fused or non-fused monocyclic or bicyclic carbocyclic group containing 5 to 12 carbon atoms, preferably 6 to 10 carbon atoms, in which at least one ring is aromatic, preferentially the aryl group is a phenyl, biphenyl, naphthyl, more preferably a phenyl group. - The term "at least one" is synonymous with the term "one or more." - the term "inclusive" in relation to a concentration range means that the limits of the range are included within the stated range.

[0048] Salts of the compounds of formula (I), (I'), (II), or (II') below include the conventional non-toxic salts of said compounds formed, for example, from organic or inorganic acids or from organic or inorganic bases.

[0049] As a salt of a compound of formula (I), (I'), (II), or (II'): Compounds of formula (I) or (II) inorganic bases, such as, for example, sodium, potassium, calcium, ammonium, magnesium, lithium hydroxide, and sodium, potassium or calcium carbonate or hydrogen carbonate, or - organic bases such as primary, secondary or tertiary alkylamines, e.g. triethylamine or butylamine The primary, secondary or tertiary alkylamines may contain one or more nitrogen and / or oxygen atoms and therefore may contain, for example, one or more alcohol functions. In particular, 2-amino-2-methylpropanol, ethanolamine, triethanolamine, 2-dimethylaminopropanol, 2-amino-2-(hydroxymethyl)-1,3-propanediol and 3-(dimethylamino)propylamine may be mentioned.

[0050] Mention may also be made of the salts of amino acids, such as lysine, arginine, guanidine, glutamic acid and aspartic acid.Advantageously, the salts of the compounds of formula (I) or (II) (when they contain a carboxy group) may be chosen from the alkali metal or alkaline earth metal salts, for example the sodium, potassium, calcium or magnesium salts, and the ammonium salts.

[0051] As "organic or inorganic acid salts", more specifically: i) hydrochloric acid HCl; ii) hydrobromic acid HBr; iii) sulfuric acid HSO; iv) alkylsulfonic acids: Alk-S(O)OH, such as methanesulfonic acid and ethanesulfonic acid; v) arylsulfonic acids: Ar-S(O)OH, such as benzenesulfonic acid and toluenesulfonic acid; vi) citric acid; vii) succinic acid; viii) tartaric acid; ix) lactic acid; x) alkoxysulfinic acids: Alk-OS(O)OH, such as methoxysulfinic acid and ethoxysulfinic acid; xi) aryloxysulfinic acids, such as tolueneoxysulfinic acid and phenoxysulfinic acid; xii) phosphoric acid HPO; xiii) acetic acid CHC(O)OH; xiv) trifluoromethanesulfonic acid CFSOH; and xv) tetrafluoroboric acid HBF. The salt is selected from salts derived from

[0052] Acceptable solvates of the compounds described herein include conventional solvates, such as those formed during the preparation of the compounds as a result of the presence of a solvent, for example, solvates resulting from the presence of water, or linear or branched alcohols, such as ethanol or isopropanol.

[0053] Optical isomers are in particular enantiomers and diastereoisomers.

[0054] Compound (I') is a tautomeric form of compound (I) when tautomeric equilibrium exists according to the following scheme:

[0055] [ka]

[0056] According to one embodiment of the present invention, R1 represents one hydrogen atom.

[0057] According to another embodiment of the present invention, R1 is a linear (C1-C 10 ) Alkyl group or branched (C3-C10 ) alkyl group, in particular a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably ethyl. In particular, said alkyl group of R1 is unsubstituted.

[0058] According to one embodiment of the present invention, R2 represents one hydrogen atom.

[0059] According to another embodiment of the present invention, R2 is a linear (C1-C 10 ) Alkyl group or branched (C3-C 10 ) an alkyl group, particularly a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably a methyl or ethyl group, wherein the alkyl group of R2 is unsubstituted.

[0060] According to another embodiment of the present invention, R2 is a linear (C1-C 10 ) Alkyl group or branched (C3-C 10 ) an alkyl group, in particular a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl, said alkyl group being substituted with one or more groups selected from i), ii), iii) and iv) above. Preferably, said alkyl group is substituted with one or two groups selected from i), ii) and iii), more preferably with one or two groups selected from i) and iii), and better still with one group iii) as carboxy.

[0061] Another variation of the R2 group is where the alkyl group is substituted with one group iv), in particular with one phenyl group.

[0062] According to another embodiment of the invention, R2 represents a (C3-C8) cycloalkyl group, preferably a (C5-C7) cycloalkyl group, such as cyclohexyl.

[0063] According to another embodiment of the present invention, R2 is a C5-C alkyl group optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups. 12 It represents an aryl group, preferably an unsubstituted phenyl group.

[0064] According to one embodiment, R3 represents a hydrogen atom.

[0065] According to another embodiment, R3 is a saturated linear C1-C 10 Or branched C3~C 10 It represents an alkyl group, particularly a linear (C1-C6) alkyl group or a branched (C3-C6) alkyl group, preferably a (C1-C4) alkyl group, for example a methyl group.

[0066] Preferably, the compounds of formula (I) and the tautomers (I′) or their salts, their optical isomers, their racemates and / or their solvates, such as hydrates, alone or in mixtures, have the following meanings: R1 is, a) hydrogen atoms, and b) may be the same or different; i) -O-R3 and ii)-SR 3、 -S-R3, optionally substituted with one or more groups i) A saturated linear C1-C6 or branched C3-C6 alkyl group optionally substituted with one or more groups selected from represents a group selected from R2 is a) a hydrogen atom, b) may be the same or different; i) -O-R3, ii)-SR 3、 iii) -C(O)-O-R3, and iv) a phenyl group optionally substituted with one or more hydroxyl and / or one or more C1-C4 alkoxy groups (such as methoxy groups); Preferably, a phenyl group substituted with one or more groups selected from i) and iii), preferably iii) such as carboxy. Saturated linear C1-C optionally substituted with one or more groups selected from 10 Or branched C3~C 10 Or a cyclic C3-C8 (C5-C6, etc.) hydrocarbon group represents a group selected from R3 is a) a hydrogen atom, and b) Saturated linear C1~C6 or branched C3~C6 alkyl group represents a group selected from

[0067] Preferentially, the compounds of formula (I) and the tautomers (I') alone or in mixtures, or their salts, their optical isomers, their racemates and / or their solvates, such as their hydrates. has the following meaning: R1 is, a) a hydrogen atom, and b) saturated, linear C1-C4 or branched C3-C4 alkyl groups, which may be the same or different, and which are optionally substituted, more preferably unsubstituted, with one or more groups selected from i) -OR3; represents a group selected from R2 is a) hydrogen atoms, and b) may be the same or different; i) -O-R3, iii) -C(O)-O-R3; iv) C5-C optionally substituted with one or more hydroxyl and / or one or more C1-C4 alkoxy groups. 12 Aryl Group Saturated linear C1-C optionally substituted with one or more groups selected from 10 Or branched C3~C 10 Or a cyclic C3-C8 (C5-C6, etc.) hydrocarbon group represents a group selected from R3 is a) a hydrogen atom, and b) saturated linear C1-C4 or branched C3-C4 alkyl groups, such as methyl or ethyl represents a group selected from

[0068] Preferentially, the compounds of formula (I) and the tautomers (I') alone or in mixtures, or their salts, their optical isomers, their racemates and / or their solvates, such as their hydrates. has the following meaning: R1 is a hydrogen atom, R2 is a) a hydrogen atom, and b) may be identical or different, and v) one or more groups selected from -C(O)-O-R3, preferably one group iii) selected from saturated linear C1-C5 or branched C3-C5 or cyclic C3-C8 (such as C5-C6) hydrocarbon groups substituted with one group -C(O)-O-R3, R2 is even more preferably a saturated linear C1-C4 or branched C3-C4 hydrocarbon group substituted with one group iii) -C(O)-OR3, R3 is a) a hydrogen atom, and b) saturated linear C1-C4 or branched C3-C4 alkyl groups, such as methyl or ethyl represents a group selected from

[0069] According to another preferred embodiment, the compounds of formula (I) and the tautomers (I') are selected from among the compounds of formula (II) below and also the tautomers of formula (II') below, their salts, their solvates and their optical isomers, and their racemates, either alone or in mixtures.

[0070] [Table 2]

[0071] R1 and R3 in the formulae (II) and (II') have the same meanings as R1 and R3 in the compounds of the formulae (I) and (I'), and X is an alkylene group -(CH2) n-, where n is an integer in the range of 1 to 10 inclusive, preferably in the range of 1 to 6, more preferably in the range of 1 to 4, for example 1; preferably, R3 represents a hydrogen atom.

[0072] Among the compounds of formula (I), the following compounds are preferably used, either alone or in mixtures, as well as their tautomers or their salts, their optical isomers, their racemates and / or their solvates, such as hydrates:

[0073] [Table 3A]

[0074] [Table 3B]

[0075] [Table 3C]

[0076] [Table 3D]

[0077] Of these compounds, the following compounds are more particularly preferred:

[0078] [Table 4A]

[0079] [Table 4B]

[0080] [Table 4C]

[0081] More preferably, among these compounds, the following compounds are more particularly preferred.

[0082] [Table 5A]

[0083] [Table 5B]

[0084] Even more preferably, among these compounds, the following compounds are more particularly preferred:

[0085] [Table 6]

[0086] In the most preferred embodiment, the compound according to the invention is:

[0087] [Table 7]

[0088] All of the above compounds can be obtained from commercially available reagents by chemical methods known to those skilled in the art.

[0089] (1) Thiopyridinone compounds can be prepared, for example, according to the methods described in EP-A-3390363 or WO2017 / 102349, which are incorporated herein by reference.

[0090] (1) Thiopyridinone compounds may be active ingredients or compounds in cosmetic or dermatological products. The term "active" ingredient or compound as used herein means an ingredient or compound having cosmetic or dermatological active properties, such as antioxidant effect, whitening effect, UV shielding effect and antibacterial effect. (1) Thiopyridinone compounds used in the present invention can function as decolorizing agents, bleaching agents or whitening agents, and therefore the composition according to the present invention can be used as a whitening product or as a cosmetic composition for whitening keratinous materials.

[0091] (1) The thiopyridinone compounds can be used as agents for depigmenting, bleaching or lightening the skin, body hair, eyelashes or hair, as well as the lips and / or nails, preferably the skin, in particular for removing pigmentation or senescence spots and / or as sun protection agents.

[0092] The amount of (1) the thiopyridinone compound in the composition according to the present invention may be 0.01% by weight or more, preferably 0.05% by weight or more, and more preferably 0.1% by weight or more, based on the total weight of the composition.

[0093] On the other hand, the amount of (1) thiopyridinone compound in the composition according to the present invention may be 10% by weight or less, preferably 5% by weight or less, and more preferably 3% by weight or less, based on the total weight of the composition.

[0094] The amount of (1) thiopyridinone compound in the composition according to the present invention may be in the range of 0.01% by weight to 10% by weight, preferably 0.05% by weight to 5% by weight, and more preferably 0.1% by weight to 3% by weight, relative to the total weight of the composition.

[0095] (Lipophilic antioxidant) The composition according to the present invention comprises (2) at least one lipophilic antioxidant. Two or more lipophilic antioxidants may be used in combination. Thus, a single type of lipophilic antioxidant or a combination of different types of lipophilic antioxidants may be used.

[0096] According to the present invention, an antioxidant is a compound capable of inhibiting or reducing oxidation. Antioxidants are capable of scavenging or scavenging reactive oxygen species such as singlet oxygen, hydroxyl radicals, superoxide anion radicals, and hydrogen peroxide.

[0097] Antioxidants are capable of scavenging various forms of radicals that may be present in the skin.

[0098] (2) Lipophilic antioxidants are different from (1) thiopyridinone compounds.

[0099] The reducing agent may be used as (2) a lipophilic antioxidant.

[0100] (2) By lipophilic antioxidant is meant herein that the partition coefficient of the antioxidant between n-butanol and water is >1, more preferably >10, and even more preferably >100.

[0101] (2) Lipophilic antioxidants are hydrophobic and are not hydrophilic antioxidants such as ascorbic acid or glutathione.

[0102] (2) As lipophilic antioxidants, phenolic antioxidants having a hindered phenol structure or a semi-hindered phenol structure in the molecule can be mentioned. Specific examples of such compounds are: 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoic acid, which has the INCI name of pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, 2,6-di-tert-butyl-4-methylphenol, 2,6-di-tert-butyl-4-ethylphenol, 2-tert-butyl-4-methoxyphenol, 3-tert-butyl-4-methoxyphenol, mono- or di- or tri-(α-methylbenzyl)phenol, 2,2'-methylenebis(4-ethyl-6-tert-butylphenol), 2,2'-methylenebis(4-methyl-6-tert-butylphenol), 4,4'-butylidenebis(3-methyl-6-tert-butylphenol), 4,4'-thiobis(3-methyl-6-tert-butylphenol), 2,5-di-tert-butylhydroquinone, 2,5-di-tert-amylhydride Roquinone, tris[N-(3,5-di-tert-butyl-4-hydroxybenzyl)]isocyanurate, 1,1,3-tris(2-methyl-4-hydroxy-5-tert-butylphenyl)butane, butylidene-1,1 bis[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate], octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, tetradecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, Rakis[methylene-3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionato]methane, triethylene glycol bis[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate], 3,9-bis{2-[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionyloxy]-1,1-dimethylethyl}-2,4,8,10-tetraoxaspiro[5.5]Undecane, 1,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzene, 2,2-thiodiethylene bis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate], N,N'-hexamethylene bis(3,5-di-tert-butyl-4-hydroxyhydrocinnamide), 1,6-hexanediol bis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate], 1,3,5-tris[(4-tert-butyl-3-hydroxy-2,6-xylyl)methyl]-1,3,5-triazine-2,4,6-trione, 2,4-bis(n-octylthio)-6-(4-hydroxyphenyl)propionate Examples of the hydroxy-3,5-di-tert-butylanilino)-1,3,5-triazine, 2-tert-butyl-6-(3'-tert-butyl-5'-methyl-2'-hydroxybenzyl)-4-methylphenyl acrylate, 2-[1-(2-hydroxy-3,5-di-tert-pentylphenyl)ethyl]-4,6-di-tert-pentylphenyl acrylate, 4,6-bis[(octylthio)methyl]-o-cresol, 2,4-di-tert-butylphenyl-3,5-di-tert-butyl-4-hydroxybenzoate, and 1,6-hexanediol bis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate] can be mentioned.

[0103] (2) Lipophilic antioxidants may also include BHA (butylated hydroxyl anisole = 2-tert-butyl-4-methoxyphenol and / or 3-tert-butyl-4-methoxyphenol) and BHT (butylated hydroxyl toluene = di-tert-butyl-4-hydroxytoluene).

[0104] (2) Lipophilic antioxidants can also include vitamin E (or tocopherols and tocotrienols) and its derivatives, such as tocopherol acetate.

[0105] (2) As a lipophilic antioxidant, diphenyl acrylate, preferably having the following general formula:

[0106] [ka]

[0107] (In the formula, One or both of R1 and R2 are independently straight or branched chain C 1~30 is an alkoxy group, and any non-alkoxy R1 or R2 group is hydrogen; R3 is a straight or branched chain C 1~30 (It is alkyl) Mention may also be made of α-cyanodiphenyl acrylate, which may be represented by:

[0108] Alternatively, one or both of R1 and R2 are independently C 1~8 R is an alkoxy group, any non-alkoxy R or R group is hydrogen, and R is a straight or branched chain C 2~20 It is an alkyl.

[0109] Alternatively, one or both of R1 and R2 are independently methoxy, any non-methoxy R1 or R2 is hydrogen, and R3 is a straight or branched chain C 2~20 It is an alkyl.

[0110] A suitable α-cyanodiphenylacrylate is ethylhexyl methoxycrylene, or 2-ethylhexyl 2-cyano-3-(4-methoxyphenyl)-3-phenylpropenoate, where R1 is methoxy, R2 is hydrogen, and R3 is 2-ethylhexyl.

[0111] (2) As lipophilic antioxidants, ferulic acid and its derivatives (esters, salts, etc.) can also be mentioned. In particular, ferulic acid and C1-C 30 Mention may be made of the esters with alcohols, in particular methyl ferulate, ethyl ferulate, isopropyl ferulate, and octyl ferulate, and also oryzanol, in particular γ-oryzanol, such as oryzanol-A, oryzanol-C, and campesteryl ferulate.

[0112] (2) The lipophilic antioxidant may include a non-phenolic antioxidant, such as a sulfur-containing non-phenolic compound containing at least one sulfur atom, particularly thiodipropionic acid and its derivatives (esters, salts, etc.), such as dilauryl thiodipropionate, dimyristyl thiodipropionate, and distearyl thiodipropionate.

[0113] (2) The lipophilic antioxidant is preferably selected from the group consisting of dibutylhydroxytoluene (BHT), ethylhexyl methoxycrylene, tocopherol acetate, oryzanol, pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, dilauryl thiopropionate, and mixtures thereof.

[0114] The amount of (2) lipophilic antioxidant in the composition according to the present invention may be 0.01% by weight or more, preferably 0.05% by weight or more, more preferably 0.1% by weight or more, relative to the total weight of the composition.

[0115] On the other hand, the amount of (2) lipophilic antioxidant in the composition according to the present invention may be 10% by weight or less, preferably 5% by weight or less, more preferably 3% by weight or less, based on the total weight of the composition.

[0116] The amount of (2) lipophilic antioxidant in the composition according to the present invention may range from 0.01% by weight to 10% by weight, preferably from 0.05% by weight to 5% by weight, more preferably from 0.1% by weight to 3% by weight, relative to the total weight of the composition.

[0117] In the composition according to the present invention, the weight ratio of the amount of (1) the thiopyridinone compound to the amount of (2) the lipophilic antioxidant may be 0.1 or more, preferably 0.4 or more, and more preferably 0.6 or more.

[0118] On the other hand, the weight ratio of the amount of (1) the thiopyridinone compound to the amount of (2) the lipophilic antioxidant in the composition according to the present invention may be 4 or less, preferably 3 or less, and more preferably 2 or less.

[0119] In the composition according to the present invention, the weight ratio of the amount of (1) the thiopyridinone compound to the amount of (2) the lipophilic antioxidant may be in the range of 0.1-4, preferably 0.4-3, and more preferably 0.6-2.

[0120] (pH adjuster) The composition according to the present invention may comprise (3) at least one pH adjusting agent (pH adjuster). Two or more pH adjusting agents may be used in combination. Thus, a single type of pH adjusting agent or a combination of different types of pH adjusting agents may be used.

[0121] (3) At least one acidifying agent and / or at least one basifying agent (alkaline agent) may be used as a pH adjusting agent.

[0122] The acidifying agent may be a mono- or poly-, e.g. di-, acid.

[0123] The acidifying agent may, for example, be a mineral acid (inorganic acid), such as hydrochloric acid, sulfuric acid, phosphoric acid, or an organic acid, such as a carboxylic acid, for example tartaric acid, citric acid and lactic acid, and a sulfonic acid.

[0124] The basifying agent may be a mono- or polyvalent, e.g. divalent, base.

[0125] The basifying agents can be mineral (inorganic) or organic or hybrid.

[0126] The inorganic basifying agent may be selected from aqueous ammonia, alkali metal carbonates or bicarbonates such as sodium or potassium carbonate and bicarbonate, alkali metal hydroxides such as sodium or potassium hydroxide, and mixtures thereof.

[0127] The organic basifying agent may be selected from organic amines having a pKb at 25° C. of less than 12, preferably less than 10, and even more advantageously less than 6. It should be noted that this is the pKb that corresponds to the highest basicity function. In addition, the organic amine does not include any alkyl or alkenyl fatty chains containing more than 10 carbon atoms.

[0128] Organic basifying agents are, for example, alkanolamines, oxyethylenated and / or oxypropylenated ethylenediamines, amino acids, and amine compounds of the following formula (III):

[0129] [ka]

[0130] (In the formula, W represents a C1-C6 divalent alkylene group optionally substituted with one or more hydroxyl groups or C1-C6 alkyl groups and optionally interrupted by one or more heteroatoms such as O and N; R x , R y , R z , and R t may be the same or different and represent a hydrogen atom, a C1-C6 alkyl group, a C1-C6 hydroxyalkyl group, or a C1-C6 aminoalkyl group. You can choose from.

[0131] Examples of amine compounds of formula (III) that may be mentioned include 1,3-diaminopropane, 1,3-diamino-2-propanol, spermine and spermidine.

[0132] The term "alkanolamine" refers to an organic amine containing a primary, secondary or tertiary amine functional group and one or more linear or branched C1-C8 alkyl groups bearing one or more hydroxyl groups.

[0133] Alkanolamines such as monoalkanolamines, dialkanolamines or trialkanolamines containing one to three identical or different C1-C4 hydroxyalkyl groups may be suitable for the present invention. Among compounds of this type, mention may be made of monoethanolamine (MEA), diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine, N-dimethylaminoethanolamine, 2-amino-2-methyl-1-propanol, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 3-amino-1,2-propanediol, 3-dimethylamino-1,2-propanediol and tris(hydroxymethylamino)methane.

[0134] The amino acids that may be used are of natural or synthetic origin, in their L-, D- or racemic form, and more particularly contain at least one acid function chosen from carboxylic, sulfonic, phosphonic or phosphoric functions. The amino acids may be in neutral or ionic form.

[0135] Among the amino acids that may be used in the present invention, mention may in particular be made of aspartic acid, glutamic acid, alanine, arginine, ornithine, citrulline, asparagine, carnitine, cysteine, glutamine, glycine, histidine, lysine, isoleucine, leucine, methionine, N-phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine and valine.

[0136] It may be preferred that the amino acid is a basic amino acid that optionally contains an additional amine function contained in the ring or a ureido function.

[0137] Such basic amino acids preferably have the following formula (IV):

[0138] [ka]

[0139] (In the formula, R is

[0140] [ka]

[0141] -(CH2)3-NH2, -(CH2)2-NH2, -(CH2)2-NH-CO-NH2, and

[0142] [ka]

[0143] represents a group selected from can be selected from those equivalent to

[0144] Compounds corresponding to formula (IV) include histidine, lysine, arginine, ornithine and citrulline.

[0145] The organic basifying agent can be chosen from organic amines of the heterocyclic type, in addition to histidine, already mentioned among the amino acids, mention may in particular be made of pyridine, piperidine, imidazole, triazole, tetrazole and benzimidazole.

[0146] The organic basifying agent may also be selected from amino acid dipeptides. Among the dipeptides of amino acids that may be used in the present invention, mention may be made in particular of carnosine, anserine and baleine.

[0147] The organic basifying agent can also be selected from compounds containing a guanidine function.Amines of this type that can be used in the present invention, in addition to arginine already mentioned as an amino acid, can in particular be creatine, creatinine, 1,1-dimethylguanidine, 1,1-diethylguanidine, glycocyamine, metformin, agmatine, N-amidinoalanine, 3-guanidinopropionic acid, 4-guanidinobutyric acid and 2-([amino(imino)methyl]amino)ethane-1-sulfonic acid.

[0148] In a preferred embodiment of the present invention, the organic basifying agent may be selected from amino acids, preferably basic amino acids, more preferably arginine, lysine, histidine, or mixtures thereof. Even more preferentially, the organic basifying agent may be arginine.

[0149] Hybrid compounds that may be mentioned include the salts of acids such as carbonic or hydrochloric acid with the aforementioned amines. In particular, guanidine carbonate or monoethanolamine hydrochloride may be used.

[0150] (3) The pH adjuster may be present in an amount of 0.01% by weight or more, preferably 0.05% by weight or more, and more preferably 0.1% by weight or more, based on the total weight of the composition.

[0151] (3) The pH adjuster may be present in an amount of up to 15% by weight, preferably up to 10% by weight, and more preferably up to 5% by weight, based on the total weight of the composition.

[0152] (3) The pH adjuster may be present in an amount ranging from 0.01% to 15% by weight, preferably from 0.05% to 10% by weight, and more preferably from 0.1% to 5% by weight, relative to the total weight of the composition.

[0153] Compositions according to the invention preferably have a pH of 4.5 or greater, more preferably 5 or greater.

[0154] Compositions according to the invention preferably have a pH of 6.5 or less, more preferably 6 or less.

[0155] The compositions according to the invention preferably have a pH of from 4.5 to 6.5, more preferably from 5 to 6.

[0156] The pH of the composition means the pH of the aqueous phase of the composition according to the present invention. The pH can be measured according to JIS Z 8802 (2011).

[0157] In order to stabilize the pH of the composition according to the invention, it may be preferred that at least one buffer or buffering agent is also used as (3) a pH adjusting agent in combination with the acidifying agent and / or basifying agent.

[0158] As the buffer, any commonly known buffer may be used. For example, a salt of an acid or base, preferably a salt of a weak acid or base, may be used. For example, when citric acid or lactic acid is used as the acidifying agent, sodium citrate or sodium lactate may be used as the buffer.

[0159] (water) The composition according to the present invention may contain (4) water.

[0160] The amount of (4) water in the composition according to the present invention may be 30% by weight or more, preferably 35% by weight or more, and more preferably 40% by weight or more, based on the total weight of the composition.

[0161] On the other hand, the amount of (4) water in the composition according to the present invention may be 99% by weight or less, preferably 95% by weight or less, and more preferably 90% by weight or less, based on the total weight of the composition.

[0162] The amount of (4) water in the composition according to the present invention may be 30% by weight to 99% by weight, preferably 35% by weight to 95% by weight, and more preferably 40% by weight to 90% by weight, based on the total weight of the composition.

[0163] (Other optional additives) The composition according to the present invention may also comprise any of the other optional additives commonly used in the cosmetic field, for example selected from solvents, chelating agents, cosmetic active agents other than component (1), such as oils, preservatives, and mixtures thereof.

[0164] It is routine for a person skilled in the art to adjust the nature and amounts of the abovementioned optional additives which may be present in the composition according to the invention so that the desired cosmetic properties are not affected by said additives.

[0165] The solvent may include one or several cosmetically acceptable organic solvents, which may be alcohols, especially monohydric alcohols such as ethyl alcohol, isopropyl alcohol, benzyl alcohol and phenylethyl alcohol; diols such as ethylene glycol, propylene glycol and butylene glycol; other polyols such as glycerol, sugars and sugar alcohols; and ethers such as ethylene glycol monomethyl, monoethyl and monobutyl ether, propylene glycol monomethyl, monoethyl and monobutyl ether, and butylene glycol monomethyl, monoethyl and monobutyl ether.

[0166] The organic solvent may be present in a concentration of from 0.01% to 30% by weight, preferably from 0.1% to 20% by weight, more preferably from 1% to 10% by weight, relative to the total weight of the composition.

[0167] [Preparation] The compositions according to the present invention can be prepared by mixing the essential and optional ingredients described above in a conventional manner.

[0168] For example, the composition according to the present invention comprises: (1) at least one thiopyridinone compound, and (2) at least one lipophilic antioxidant The composition can be prepared by a method comprising the step of mixing

[0169] Any of the optional ingredients can be further mixed.

[0170] The mixing can be carried out at any temperature, such as room temperature (e.g., 20 to 25° C., preferably 25° C.), preferably at a temperature of 30° C. or higher, preferably at 40° C. or higher, more preferably at 50° C. or higher, etc. It is preferable to further mix with any of the above-mentioned optional components, such as a pH adjuster.

[0171] The form of the composition according to the present invention is not particularly limited and may take various forms such as a W / O emulsion, an O / W emulsion, a gel, a solution, etc. It is preferred that the composition according to the present invention is in the form of an emulsion, preferably an O / W emulsion, more preferably an O / W gel emulsion.

[0172] [Beauty method] The composition according to the invention can be used as a cosmetic or dermatological composition, preferably a cosmetic composition, more preferably a cosmetic composition for keratinous materials, such as the skin, scalp, hair, mucous membranes such as the lips, and nails.

[0173] The composition according to the invention can be used as a bleaching, bleaching or whitening product for keratinous materials such as the skin. In particular, the composition according to the invention can be used as a whitening product.

[0174] The composition according to the invention may preferably be intended for application to keratinous materials, such as the skin, the scalp and / or the lips, preferably the skin.

[0175] The composition according to the invention can therefore be used in a cosmetic method for keratinous materials, preferably skin. In one embodiment, the invention relates to a cosmetic method, preferably a whitening method, for keratinous materials, preferably skin, comprising the step of applying a composition according to the invention to the keratinous materials.

[0176] The composition according to the invention can be used as a topical cosmetic composition in the form of a lotion, milk, cream, gel, paste, serum, foam or spray.

[0177] [use] The present invention also relates to a compound of formula (I) below, a tautomer of formula (I') below:

[0178] [ka]

[0179] (In the formula, R1 is, a) hydrogen atoms, and b) may be the same or different; i) -O-R3 and ii)-S-R3 Saturated linear C1-C optionally substituted with one or more groups selected from 10 Or branched C3~C 10 Alkyl group represents a group selected from R2 is a) a hydrogen atom; b) may be the same or different; i) -O-R3, ii)-SR 3、 iii) -C(O)-O-R3, and iv) C5-C optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups. 12 Aryl Group Saturated linear C1-C optionally substituted with one or more groups selected from 12 Or branched C3~C 12 or a cyclic C3 to C8 hydrocarbon group; c) C5-C optionally substituted with one or more hydroxyl and / or one or more C1-C8 alkoxy groups 12 Aryl groups and represents a group selected from Where: R3 is a) a hydrogen atom, and b) Saturated linear C1-C 10 Or branched C3~C 10 Alkyl group represents a group selected from (2) use of at least one lipophilic antioxidant in a composition comprising at least one compound selected from the salts thereof, solvates such as hydrates thereof, optical isomers thereof, racemates thereof, and mixtures thereof, (1) It also relates to the use for stabilizing a compound.

[0180] The term "stabilize" has the same meaning as enhancing stability.

[0181] The use according to the present invention can enhance the stability of (1) a thiopyridinone compound in a composition containing the (1) thiopyridinone compound.

[0182] Therefore, the use according to the present invention can enable the composition containing (1) a thiopyridinone compound to be stored for a long period of time, especially under high temperature conditions.

[0183] The above statements regarding (1) the thiopyridinone compound and (2) the lipophilic antioxidant for the composition according to the invention may also apply to those used in the use according to the invention.

[0184] The composition in use according to the invention may comprise any of the optional ingredients described above in relation to the composition according to the invention. EXAMPLES

[0185] The present invention will be described in a more detailed manner by means of examples. However, these examples should not be construed as limiting the scope of the present invention.

[0186] (Examples 1 to 6 and Comparative Example 1) [Preparation] Each of the compositions according to Examples 1 to 6 and Comparative Example 1 was prepared by mixing the components shown in Table 1. All figures for component amounts are based on "wt %" as active material.

[0187] [Table 8A]

[0188] [Table 8B]

[0189] N-[(2-thioxo-1,2-dihydropyridin-3-yl)carbonyl]glycine (2-mercaptonicotinoylglycine): Compound 20

[0190] [evaluation] (Residual rate of thiopyridinone compounds) The amount of thiopyridinone in each of the compositions according to Examples 1 to 6 and Comparative Example 1 was determined by HPLC-UV assay at the following times. Timing (1) Immediately after the composition was prepared (T0) Timing (2) The composition was kept in a sealed, light-shielded container at 55°C for 2 weeks after preparation.

[0191] The details of the HPLC-UV assay are as follows.

[0192] Equipment / Reagents

[0193] [Table 9]

[0194] HPLC conditions

[0195] [Table 10]

[0196] The residual rate of the thiopyridinone compound was determined by the following formula. Residual rate (%) of thiopyridinone compound = amount of thiopyridinone compound at timing (2) / amount of thiopyridinone compound at timing (1)

[0197] The results are shown in the row "Residual rate (%) of thiopyridinone compound" in Table 2 below.

[0198] The residual rate of thiopyridinone compounds was classified according to the following criteria. Very good: 90% or more Good: More than 85% to less than 90% Defective: 85% or less

[0199] The results are shown in the "Stability" row in Table 2 below.

[0200] [Table 11]

[0201] (result) The compositions according to Examples 1 to 6, each of which contained a thiopyridinone compound and various lipophilic antioxidants, were more stable at high temperatures, with a greater amount of the thiopyridinone compound remaining, compared to the composition according to Comparative Example 1, which did not contain any lipophilic antioxidants.

Claims

1. (1) A compound of the following formula (I), a tautomer of the following formula (I'): 【Chemical 1】 (wherein, R 1 is a) a hydrogen atom, and b) groups selected from those which may be the same or different, i)-O-R 3 and ii)-S-R 3 optionally substituted by one or more groups selected from saturated straight-chain C 1 ~C 10 or branched C 3 ~C 10 alkyl group are shown, R 2 is a) a hydrogen atom and b) groups selected from those which may be the same or different, i)-O-R 3 、 ii)-S-R 3、 iii)-C(O)-O-R 3 and iv) one or more hydroxyl and / or one or more C 1 -C 8 aryl group optionally substituted with a C 5 -C 12 alkoxy group optionally substituted by one or more groups selected from a saturated straight-chain C 1 ~C 12 or branched C 3 ~C 12 or cyclic C 3 ~C 8 hydrocarbon group, and c) one or more hydroxyls and / or one or more C 1 -C 8 -C optionally substituted with an alkoxy group 5 -C 12 -aryl group and are shown, here, R 3 is a) a hydrogen atom, and b) Saturated straight-chain C 1 ~C 10 or branched C 3 ~C 10 alkyl group groups selected from) At least one compound selected from these salts, solvates such as these hydrates, these optical isomers, these racemates, and mixtures thereof, and (2) At least one lipophilic antioxidant comprising a composition, preferably a cosmetic composition.

2. R of formula (I) and (I') 1 represents a hydrogen atom or or R of formula (I) and (I') 1 is a linear (C 1 ~C 10 ) alkyl group or a branched (C 3 ~C 10 ) alkyl group, particularly a linear (C 1 ~C 6 ) alkyl group or a branched (C 3 ~C 6 ) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably ethyl, and particularly the alkyl group of R 1 is unsubstituted, the composition according to claim 1.

3. R of formula (I) and (I') 2 represents a hydrogen atom, or or R of formula (I) and (I') 2 is a linear (C 1 ~C 10 ) alkyl group or a branched (C 3 ~C 10 ) alkyl group, particularly a linear (C 1 ~C 6 ) alkyl group or a branched (C 3 ~C 6 ) alkyl group, for example methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably a methyl or ethyl group, and the alkyl group of R 2 is unsubstituted, the composition according to claim 1.

4. R of formula (I) and (I') 2 is a linear (C 1 ~C 10 ) alkyl group or a branched (C 3 ~C 10 ) alkyl group, particularly a linear (C 1 ~C 6 ) alkyl group or a branched (C 3 ~C 6 ) alkyl group, such as methyl, ethyl, n-pentyl, n-nonyl, isobutyl, more preferably methyl or ethyl, and the alkyl group is substituted with one or more groups selected from i), ii), iii) and iv) defined above, preferably the alkyl group is substituted with one or two groups selected from i), ii) and iii), more preferably one or two groups selected from i) and iii), and more preferably substituted with one group iii) as carboxy. The composition according to claim 1.

5. R of formula (I) and (I') 2 is a (C 3 -C 8 ) cycloalkyl group, preferably a (C 5 -C 7 ) cycloalkyl group, for example, represents cyclohexyl, or or R of formula (I) and (I') 2 is a C 1 to C 8 aryl group optionally substituted with one or more hydroxyls and / or one or more C 5 to C 12 alkoxy groups, and is preferably an unsubstituted phenyl group, the composition according to claim 1.

6. R of formula (I) and (I') 3 represents a hydrogen atom, or or R of formula (I) and (I') 3 is a saturated straight-chain C 1 to C 10 or branched C 3 to C 10 alkyl group, particularly a straight-chain (C 3 to C 6 ) alkyl group or a branched (C 3 to C 6 ) alkyl group, preferably a (C 1 to C 4 ) alkyl group, for example, a methyl group, the composition according to claim 1.

7. R of formula (I) and (I') 1 is a) a hydrogen atom, and b) groups selected from those which may be the same or different, i)-O-R 3 and ii)-S-R 3、 -S-R optionally substituted by one or more groups i) 3 optionally substituted by one or more groups selected from saturated straight-chain C 1 ~C 6 or branched C 3 ~C 6 alkyl group are represented, R of formula (I) and (I') 2 is a) a hydrogen atom and b) groups selected from those which may be the same or different, i)-O-R 3 、 ii)-S-R 3、 iii)-C(O)-O-R 3 and iv) a phenyl group optionally substituted with one or more hydroxyl and / or one or more C alkoxy groups such as methoxy 1 ~C 4 ​ preferably one or more groups selected from i) and iii), preferably a phenyl group substituted with iii) such as carboxy optionally substituted by one or more groups selected from saturated linear C 1 to C 10 or branched C 3 to C 10 or C 5 to C 6 such as cyclic C 3 to C 8 hydrocarbon group and are represented, R of formula (I) and (I') 3 is a) a hydrogen atom, and b) Saturated straight-chain C 1 ~C 6 or branched C 3 ~C 6 alkyl group groups selected from are represented, Preferentially, the compound of formula (I) and the tautomer (I'), these salts, these solvates such as these hydrates, these optical isomers, these racemates, and mixtures thereof have the following meanings: R of formula (I) and (I') 1 is: a) a hydrogen atom, and b) which may be the same or different, i) -OR 3 optionally substituted by one or more groups selected from, more preferably unsubstituted, saturated straight-chain C 1 ~C 4 or branched C 3 ~C 4 alkyl group groups selected from are represented, R of formula (I) and (I') 2 is a) a hydrogen atom, and b) groups selected from those which may be the same or different, i)-O-R 3 、 iii)-C(O)-O-R 3 and iv) one or more hydroxyl and / or one or more C 1 to C 4 aryl group optionally substituted with a C 5 to C 12 alkoxy group A saturated linear C optionally substituted by one or more groups selected from 1 -C 10 or a branched C 3 -C 10 or a C 5 -C 6 such as a cyclic C 3 -C 8 hydrocarbon group are represented, R of formula (I) and (I') 3 is: a) a hydrogen atom, b) Saturated straight-chain C 1 ~C 4 or branched C 3 ~C 4 alkyl group, such as methyl or ethyl groups selected from are represented, The composition according to claim 1.

8. (1) The compound is selected from the following Compounds 1-24, their tautomers, their salts, their solvates such as hydrates, their optical isomers, their racemates, and mixtures thereof, particularly Compounds 1, 2, 4, 6, 7, 9, 11, 12, 14, 15, 16, 17, 18, 19, 20, or 21, more specifically 1, 9, 16, 18, 19, 20, or 21, preferably 18, 19, 20, or 21, more preferably 20, The composition according to claim 1. 【Table 1A】 【Table 1B】 【Table 1C】 【Table 1D】

9. The amount of the compound (1) in the composition is 0.01% by weight to 10% by weight, preferably 0.05% by weight to 5% by weight, more preferably 0.1% by weight to 3% by weight based on the total weight of the composition. The composition according to claim 1.

10. The composition according to claim 1, wherein the (2) lipophilic antioxidant is selected from the group consisting of dibutylhydroxytoluene, ethylhexyl methoxycinnamate, tocopheryl acetate, oryzanol, pentaerythrityl tetra-di-t-butylhydroxyhydrocinnamate, dilauryl thiodipropionate, and mixtures thereof.

11. The composition according to claim 1, wherein the amount of the (2) lipophilic antioxidant in the composition is 0.01% by weight to 10% by weight, preferably 0.05% by weight to 5% by weight, more preferably 0.1% by weight to 3% by weight, based on the total weight of the composition.

12. The composition according to claim 1, for whitening keratinous substances, preferably the skin.

13. A cosmetic method, preferably a whitening method, for keratinous substances, preferably for the skin, comprising: applying the composition according to any one of claims 1 to 12 to the keratinous substance.

14. (1) A compound of the following formula (I), a tautomer of the following formula (I'): [Chemical 2] (wherein, R 1 is a) represents a hydrogen atom, and b) represents a group selected from the group consisting of, which may be the same or different, i)-O-R 3 and ii)-S-R 3 optionally substituted with one or more groups selected from a saturated straight-chain C 1 ~C 10 or branched C 3 ~C 10 alkyl group and R 2 is a) represents a hydrogen atom, and b) represents a group selected from the group consisting of, which may be the same or different, i)-O-R 3 、 ii)-S-R 3、 iii)-C(O)-O-R 3 and iv) one or more hydroxyl and / or one or more C 1 -C 8 aryl group optionally substituted with a C 5 -C 12 alkoxy group optionally substituted by one or more groups selected from saturated linear C 1 ~C 12 or branched C 3 ~C 12 or cyclic C 3 ~C 8 hydrocarbon group, and c) one or more hydroxyl and / or one or more C 1 -C 8 aryl group optionally substituted with a C 5 -C 12 aryl group and wherein, a) represents a hydrogen atom, and R 3 is a group selected from the group consisting of) b) Saturated straight-chain C 1 ~C 10 or branched C 3 ~C 10 alkyl group Use of at least one lipophilic antioxidant in a composition selected from at least one compound selected from these salts, solvates such as hydrates thereof, optical isomers thereof, racemates thereof, and mixtures thereof, for stabilizing the (1) compound. ​

Images