WO2020002054A1 - Process for treating keratin materials with 5-oxazolidine-2,4-dione c-glycoside compounds, compounds and cosmetic composition containing same - Google Patents

Abstract

The present invention relates to a process for the cosmetic treatment of keratin materials, comprising the application to said materials, such as the skin, of a composition comprising a compound (I) The invention relates in particular to the non-therapeutic cosmetic used of at least one compound of formula (I) as defined below, as an agent for bleaching, lightening and/or depigmenting keratin materials, in particular the skin.

Description

PROCESS FOR TREATING KERATIN MATERIALS WITH 5-OXAZOLIDINE-2,4- DIONE C-GLYCOSIDE COMPOUNDS, COMPOUNDS AND COSMETIC

COMPOSITION CONTAINING SAME

The present invention relates to the cosmetic use of C-glycoside compounds, in particu- lar to the use thereof for depigmenting and/or bleaching keratin materials and in particu- lar the skin, to novel C-glycoside compounds, to the compositions, in particular the cos- metic compositions, which contain them and to a process for treating keratin materials using said C-glycosides. At various periods in their life, some people develop darker and/or more coloured blemishes on the skin, and more especially on the hands and the face, which give the skin heterogeneity. These blemishes are especially due to a high concentration of melanin in the keratinocytes located at the surface of the skin.

The use of highly effective inoffensive topical depigmenting substances is most particu- larly sought for the purpose of treating pigmentary blemishes.

The mechanism of formation of the pigmentation of the skin, i.e. of the formation of mel- anin, is particularly complex and involves, schematically, the following main steps: Tyrosine -» Dopa -» Dopaquinone -» Dopachrome -» Melanin

Tyrosinase (monophenol dihydroxyl phenylalanine: oxygen oxidoreductase EC 1.14.18.1 ) is the essential enzyme involved in this sequence of reactions. In particular, it catalyses the conversion reaction of tyrosine to give dopa (dihydroxyphenylalanine), by virtue of its hydroxylase activity, and the conversion reaction of dopa to give dopaqui- none, by virtue of its oxidase activity. This tyrosinase acts only when it is in mature form under the effect of certain biological factors.

A substance is acknowledged as being depigmenting if it acts directly on the vitality of the epidermal melanocytes where melanogenesis takes place, and/or if it interferes with one of the steps of melanin biosynthesis, either by inhibiting one of the enzymes involved in melanogenesis, or by inserting itself as a structural analogue of one of the chemical compounds of the melanin synthesis chain, which chain can then be blocked, thus en- suring depigmentation.

Arbutin and kojic acid are known as skin depigmenting agents.

Substances which have an efficient depigmenting action have been sought.

There nevertheless remains the need for a new bleaching agent for keratin materials, and in particular for human skin, which is stable in a composition, which can be easily formulated, in particular in aqueous formulations, or else alternatively which has a rein- forced action so that it can be used in a lower amount, thereby considerably reducing the side effects that may be observed.

In this regard, the Applicant has discovered, surprisingly and unexpectedly, that 5-oxa- zolidine-2,4-dione C-glycoside compounds have good depigmenting activity, even at low concentration, without showing any cytotoxicity.

A first subject of the invention is a process for the cosmetic treatment of keratin materials, in particular the skin, using at least one compound of formula (I) as defined below or a cosmetic composition comprising at least one compound of formula (I).

The invention relates to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined below, in particular of at least one compound of formula (G), (I"), (I""), (I'a), (l"a) and/or (l""a) and even more particularly of at least one compound 1a, 1 b, 1c, 1 d and/or 1 to 8 defined below, as an agent for bleaching, lightening and/or depigmenting keratin materials, in particular the skin.

A subject of the invention is also a non-therapeutic cosmetic treatment process for depig- menting, lightening and/or bleaching keratin materials, in particular the skin, comprising the application to the skin of at least one compound of formula (I), in particular of at least one compound of formula (G), (I"), (I""), (I'a), (l"a) and/or (l""a) and even more particu- larly of at least one compound 1a, 1 b, 1c, 1 d and/or 1 to 8 as defined below or of a composition comprising it (them).

Another subject of the invention is the dermatological use of at least one compound of formula (I) as defined below, in particular of at least one compound of formula (G), (I"), (I""), (I'a), (l"a) and/or (l""a) and even more particularly of at least one compound 1a, 1 b, 1 c, 1d and/or 1 to 8, for depigmenting the skin, lightening and/or bleaching it.

The compounds of formula (I) in accordance with the invention, as defined below, in particular the compounds of formula (G), (I"), (I""), (I'a), (l"a) and/or (l""a) and even more particularly of at least one compound 1 a, 1 b, 1 c, 1d and/or 1 to 8 make it possible to efficiently depigment and/or lighten, or even bleach, keratin materials, in particular human skin. They are in particular intended to be applied to the skin of individuals bear- ing brownish pigmentation blemishes or liver spots, or to the skin of individuals wishing to combat the appearance of a brownish colour caused by melanogenesis.

For the purposes of the present invention, the term“keratin materials” means human keratin materials, and in particular human skin, bodily hair, the eyelashes, head hair, the lips and the nails.

The compounds of formula (I) in accordance with the invention may also make it possible to depigment and/or lighten bodily hair, the eyelashes, head hair, and also the lips and/or the nails.

More particularly, the term“keratin materials” denotes human skin.

A subject of the invention is also the novel compounds of formula (I), (G), (I"), (I""), (I'a), (l"a) and/or (l""a) and even more particularly the compounds 1 a, 1 b, 1c, 1d and/or 1 to 8 as defined below.

A subject of the invention is likewise a cosmetic composition comprising, in a physiolog- ically acceptable medium, at least one compound of formula (I) as defined below, in particular at least one compound of formula (G), (I"), (I""), (I'a), (l"a) and/or (l""a) and even more particularly of at least one compound 1a, 1 b, 1 c, 1 d and/or 1 to 8 described below.

Other characteristics, subjects and advantages of the invention will emerge more clearly on reading the description and the examples that follow.

In the text hereinbelow, and unless otherwise indicated, the limits of a range of values are included within that range.

The expression "at least one" is equivalent to the expression "one or more".

For the purposes of the present invention, the term "physiologically acceptable medium" is intended to denote a medium that has no unpleasant odour or appearance, and that is entirely compatible with the topical administration route. In the present case in which the composition is intended for topical administration, i.e. by application to the surface of the keratin material under consideration, such a medium is considered in particular to be physiologically acceptable when it does not cause discomfort, such as stinging or taut- ness that is unacceptable to the user.

In the present invention, the term "keratin material" means a keratin material, preferably a human keratin material, and in particular the skin (preferably human skin), and even more particularly bodily and/or facial skin.

The cutaneous region may be chosen in particular from:

- the hands,

- the face, in particular the forehead, the cheeks or the contour of an eye (periocular), and in particular the crow's feet, the region below the eye (bag), or the eyelids, the arm- pits.

For the purposes of the present invention and unless otherwise indicated:

the saturated or unsaturated and optionally fused rings may also be op- tionally substituted;

- the "alkyl" radicals are saturated, linear or branched, generally C1-C18, particularly C1-C10, hydrocarbon-based radicals, preferably C1-C6 alkyl radicals; as C1 -C14 alkyl group, mention may in particular be made of me- thyl, ethyl, isopropyl, n-propyl, n-butyl, t-butyl, isobutyl, sec-butyl, pentyl, isopentyl, neopentyl, n-hexyl, n-heptyl and octyl groups; the "alkenyP' radicals are linear or branched, unsaturated C2-C18 hydro- carbon-based radicals; preferably comprising one or more conjugated or unconjugated double bonds, such as ethylene, propylene, butylene, pen- tylene, 2-methylpropylene, prenyl and decylene;

the“alkynyl” radicals are linear or branched, unsaturated C2-C18 hydro- carbon-based radicals, preferably comprising one or more triple bonds; the "ary/" radicals are fused or non-fused monocyclic or polycyclic car- bon-based radicals, preferentially comprising from 6 to 30 carbon atoms, and of which at least one ring is aromatic; the aryl radical is preferentially chosen from a phenyl, biphenyl, naphthyl, indenyl, anthracenyl and tet- rahydronaphthyl radical, more preferentially aryl denotes phenyl;

the“ alkoxy” radicals are alkyloxy radicals with alkyl as defined above, the alkyl part of the alkoxy generally being C1-C18, preferably C1-C10, such as methoxy, ethoxy, propoxy and butoxy; when mention is made of un- saturated, this implies that the alkoxy group can represent an alkenyloxy or alkynyloxy group with alkenyl and alkynyl as defined above;

- the“cycloalkyf’ radicals are C₄-C₈ cycloalkyl radicals, preferably cyclo- pentyl and cyclohexyl radicals; the cycloalkyl radicals may be substituted cycloalkyl radicals, in particular substituted with alkyl, alkoxy, carboxylic acid, hydroxyl, amine and ketone groups;

the “heterocycloalkyl” radicals are saturated or partially unsaturated, nonaromatic heterocyclic radicals comprising from 4 to 8 ring members, which comprise from 1 to 3 heteroatoms, in particular chosen from oxy- gen, sulfur and nitrogen, preferably the morpholino, piperazino and pi- peridino radicals; the heterocycloalkyl radicals may be radicals which are substituted, in particular with alkyl, alkoxy, carboxylic acid, hydroxyl, amine and ketone groups;

the“aryf or“heteroaryf radicals can be substituted with at least one atom or group borne by at least one carbon atom, chosen from:

I) (C-i-C io)alkyl, preferably Ci-Ce alkyl, optionally substituted with one or more radicals chosen from the following radicals: hydroxyl, optionally unsaturated (Ci-C₄)alkoxy, (poly)hydroxy(C2-C₄)alkoxy, acylamino, amino substituted with two identical or different Ci-C₄ alkyl radicals optionally bearing at least one hydroxyl group or it being possible for the two radicals to form, with the nitrogen atom to which they are attached, a saturated or unsaturated and optionally substituted 5- to 7-membered, preferably 5- or 6-mem- bered, heterocycle optionally comprising another nitrogen or non-nitrogen heteroatom; ii) halogen; iii) hydroxyl; iv) Ci-C₄ alkoxy; v) C1-C10 alkoxycarbonyl; vi) (poly)hydroxy(C2- C₄)alkoxy; vii) C2-C₄ alkylcarbonyloxy, preferentially -O-acetyl or acetyloxy; viii) 5- or 6- membered heterocycloalkyl; ix) 5- or 6-membered heteroaryl, optionally substituted with a (CrC₄)alkyl radical, preferentially methyl; x) amino substituted with one or two identical or different C1-C6 alkyl radicals optionally bearing at least: a) one hydroxyl group, b) one amino group optionally substituted with one or two optionally substituted C1 -C3 alkyl rad- icals, it being possible for said alkyl radicals to form, with the nitrogen atom to which they are attached, a saturated or unsaturated and optionally substituted 5- to 7-membered heterocycle optionally comprising at least one other nitrogen or non-nitrogen heteroatom, c) one quaternary ammonium group -N⁺R’R”R”’, Q- for which R’, R” and R’”, which may be identical or different, represent a hydrogen atom or a Ci-C₄ alkyl group; and Q- rep- resents the anionic counterion such as the halide, d) one 5- or 6-membered heteroaryl radical, optionally substituted with a (Ci-C₄)alkyl radical, preferentially methyl; xi) acyla- mino (-N(R)-C(0)-R’) in which the radical R is a hydrogen atom or a Ci-C₄ alkyl radical optionally bearing at least one hydroxyl group and the radical R’ is a C1-C2 alkyl radical; xii) carbamoyl ((R)₂N-C(0)-) in which the R radicals, which may be identical or different, represent a hydrogen atom or a Ci-C₄ alkyl radical optionally bearing at least one hy- droxyl group; xiii) alkylsulfonylamino (R’S(0)₂-N(R)-) in which the radical R represents a hydrogen atom or a CrC₄ alkyl radical optionally bearing at least one hydroxyl group and the radical R’ represents a CrC₄ alkyl radical or a phenyl radical; xiv) aminosulfonyl ((R)₂N-S(0)₂-) in which the radicals R, which may be identical or different, represent a hydrogen atom or a CrC₄ alkyl radical optionally bearing at least one hydroxyl group; xv) carboxyl in the acid or salified form (preferably salified with an alkali metal or a sub- stituted or unsubstituted ammonium); xvi) cyano; xvii) benzyloxycarbonyl; xviii) poly- haloalkyl, preferentially trifluoromethyl; xix) a phenylcarbonyloxy group optionally substi- tuted with one or more hydroxyl groups; and xx) a phenyl group optionally substituted with one or more hydroxyl groups;

the "heteroaryl" radicals are radicals comprising, in at least one ring, one or more heteroatoms chosen in particular from O, N and S, preferably O or N, optionally substituted in particular with one or more alkyl, alkoxy, carboxyl, hydroxyl, amine or ketone groups, and at least one ring of which is aromatic. These rings may comprise one or more oxo groups on the carbon atoms of heteroaryl; mention may in particular be made, among the heterocyclic radicals that may be used, of furyl, pyranyl, pyrrolyl, im- idazolyl, pyrazolyl, pyridyl, thienyl, and pyrimidinyl groups; even more preferentially, the heterocyclic groups are fused groups, such as benzo- furanyl, chromenyl, xanthenyl, indolyl, isoindolyl, quinolyl, isoquinolyl, chromanyl, isochromanyl, indolinyl, isoindolinyl, coumarinyl or isocouma- rinyl groups, it being possible for these groups to be substituted, in par- ticular with one or more OH groups;

the "protective group" or "PG" of the "hydroxyl" or "amino" function is known by those skilled in the art; mention may be made of the two books "Protective Groups in Organic Synthesis", T. W. Greene, published by John Wiley & Sons, NY, 1981 , pp.193-217; "Protecting Groups", P. Ko- cienski, Thieme, 3rd ed., 2005.

In particular, the protective group is chosen from:

■ (Ci-C₆)alkyl(thio)carbonyl such as formyl, acetyl or t-butylcarbonyl; ■ (di)(tri)halo(Ci-C₆)alkyl(thio)carbonyl such as trifluoroacetyl (TFA);

■ (Ci-C₆)alkoxy(thio)carbonyl such as methoxycarbonyl, ethoxycarbonyl, iso- butyloxycarbonyl, t-butyloxycarbonyl (BOC), vinyloxycarbonyl, allyloxycar- bonyl;

■ (di)(tri)halo(C-i-C₆)alkoxy(thio)carbonyl such as 2,2,2-trichloroethylcarbonyl;

■ (Ci-C₆)alkylthiothiocarbonyl;

■ (di)(tri)halo(Ci-C₆)alkylthiothiocarbonyl;

■ (di)(Ci-C₆)(alkyl)aminocarbonyl;

■ (di)(Ci-C₆)(alkyl)aminothiocarbonyl;

■ optionally substituted arylcarbonyl such as phenylcarbonyl or 2,4,6-trime- thylphenylcarbonyl;

■ optionally substituted aryloxycarbonyl such as p-nitrophenoxycarbonyl;

■ optionally substituted aryl(Ci-C₆)alkoxycarbonyl such as benzyloxycarbonyl or Cbz, p-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, o-nitro- benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-bromobenzyloxycarbonyl (2- bromo-Z) and 2-chlorobenzyloxycarbonyl (2-chloro-Z), 4-nitrobenzyloxycar- bonyl (nitro-Z),

■ heteroaryl(Ci-C₆)alkoxycarbonyl such as 9-fluorenylmethoxycarbonyl (FMOC) or nicotinoyl;

■ (di)(Ci-C₆)(alkyl)aminocarbonyl such as dimethylaminocarbonyl;

■ (Ci-C₆)(alkyl)arylaminocarbonyl;

■ carboxyl;

■ optionally substituted aryl such as phenyl, dibenzosuberyl or 1 ,3,5-cyclohep- tatrienyl;

■ optionally substituted heteroaryl; especially including the cationic or non-cati- onic heteroaryl comprising from 1 to 4 heteroatoms below:

i) 5-, 6- or 7-membered monocyclic groups such as furanyl or furyl, pyrrolyl or pyrryl, thiophenyl or thienyl, pyrazolyl, oxazolyl, oxazolium, isoxazolyl, isoxazolium, thiazolyl, thiazolium, isothiazolyl, isothiazolium, 1 ,2,4-triazolyl, 1 ,2,4-triazolium, 1 ,2,3-triazolyl, 1 ,2,3-triazolium, 1 ,2,4-oxazolyl, 1 ,2,4-oxazolium, 1 ,2,4-thiadiazolyl, 1 ,2,4-thiadiazolium, pyrylium, thiopyridyl, pyridinium, pyrimidinyl, pyrimidinium, pyrazinyl, pyrazinium, pyri- dazinyl, pyridazinium, triazinyl, triazinium, tetrazinyl, tetrazinium, azepine, azepinium, ox- azepinyl, oxazepinium, thiepinyl, thiepinium, imidazolyl, imidazolium;

ii) 8- to 1 1-membered bicyclic groups such as indolyl, indolinium, benzimidazolyl, ben- zimidazolium, benzoxazolyl, benzoxazolium, dihydrobenzoxazolinyl, benzothiazolyl, benzothiazolium, pyridoimidazolyl, pyridoimidazolium, thienocycloheptadienyl, these monocyclic or bicyclic groups being optionally substituted with one or more groups such as (Ci-C₄)alkyl, for instance methyl, or polyhalo(C-i-C₄)alkyl, for instance trifluoromethyl; iii) or the following tricyclic ABC group:

in which the two rings A and C optionally comprise a heteroatom, and ring B is a 5-, 6- or 7-membered ring, particularly a 6-membered ring, and contains at least one heteroa- tom, for instance piperidyl or pyranyl;

□ optionally cationic, optionally substituted heterocycloalkyl, the heterocycloal- kyl group in particular representing a saturated or partially saturated 5-, 6- or 7-membered monocyclic group comprising from 1 to 4 heteroatoms chosen from oxygen, sulfur and nitrogen, such as di/tetrahydrofuranyl, di/tetrahy- drothiophenyl, di/tetrahydropyrrolyl, di/tetrahydropyranyl, di/tetra/hexahy- drothiopyranyl, dihydropyridyl, piperazinyl, piperidinyl, tetramethylpiperidyl, morpholinyl, di/tetra/hexahydroazepinyl, di/tetrahydropyrimidinyl, these groups being optionally substituted with one or more groups such as (Ci-C₄)al- kyl, oxo or thioxo, preferably tetrahydropyranyl THP; or the heterocycle repre- sents the following group:

in which R'^c, R'^d, R'^e, R'^f, R'⁹ and R'^h, which may be identical or different, represent a hydrogen atom or a (Ci-C₄)alkyl group, or alternatively two groups R'⁹ with R'^h, and/or R'^e with R'^f form an oxo or thioxo group, or alternatively R'⁹ with R'^e together form a cy- cloalkyl; and v represents an integer between 1 and 3 inclusive; preferentially, R'^c to R'^h represent a hydrogen atom; and Am represents a counterion;

^■ isothiouronium -C(NR'^cR'^d)=N⁺R'^eR'^f; Am with R'^c, R'^d, R'^e and R'^f, which may be identical or different, representing a hydrogen atom or a (Ci-C₄)al- kyl group; preferentially, R'^c to R'^f represent a hydrogen atom; and Am rep- resents a counterion;

^■ isothiourea -C(NR'^cR'^d)=NR'^e; with R'^c, R'^d and R'^e as defined above; ^■ optionally substituted (di)aryl(Ci-C4)alkyl or triaryl(Ci-C₄)alkyl such as 9-an- thracenylmethyl, phenylmethyl (benzyl), diphenylmethyl or triphenylmethyl op- tionally substituted with one or more groups, in particular chosen from halogen, (Ci-C₄)alkyl, (Ci-C₄)alkoxy such as methoxy, hydroxyl, (Ci-C₄)alkylcarbonyl, (di)(Ci-C₄)(alkyl)amino such as dimethylamino, nitro;

^■ optionally substituted (di)heteroaryl(Ci-C₄)alkyl or triheteroaryl(Ci-C₄)alkyl, the heteroaryl group in particular being cationic or noncationic, 5- or 6-mem- bered monocyclic comprising from 1 to 4 heteroatoms chosen from nitrogen, oxygen and sulfur, such as pyrrolyl, furanyl, thiophenyl, pyridyl, pyridyl N-oxide such as 4-pyridyl or 2-pyridyl-N-oxide, pyrylium, pyridinium or triazinyl groups, optionally substituted with one or more groups such as alkyl, particularly me- thyl; advantageously, the (di)heteroaryl(Ci-C₄)alkyl is (di)heteroarylmethyl or (di)heteroarylethyl;

^■ CR¹R²R³ with R¹, R² and R³, which may be identical or different, representing a halogen atom, such as (tri)(di)halo(Ci-C₄)alkyl such as 2,2,2-trichloroethyl or a group chosen from:

- (Ci-C₄)alkyl such as methyl;

- (Ci-C₄)alkoxy;

- optionally substituted aryl such as phenyl optionally substituted with one or more groups, for instance (Ci-C₄)alkyl, (Ci-C₄)alkoxy or hydroxyl;

- optionally substituted heteroaryl such as thiophenyl, furanyl, pyrrolyl, pyranyl or pyridyl, optionally substituted with a (Ci-C₄)alkyl group;

- P(Z¹)R'¹ R'²R'³ with R'¹ and R'², which may be identical or different, representing a hy- droxyl, (Ci-C₄)alkoxy or alkyl group, R'³ representing a hydroxyl or (Ci-C₄)alkoxy group, and Z¹ representing an oxygen or sulfur atom;

^■ (C2-C6)alkylene, in particular allyl H₂C=CH-CH2-;

^■ optionally substituted arylsulfonyl such as p-toluenesulfonyl (Tos);

^■ sterically hindered cycloalkyl such as the adamantyl group;

^■ sterically hindered cycloalkyloxy(thio)carbonyl such as 1 -adamantyloxycarbonyl (Adoc) or 1-(adamantyl)-1 -methylethoxycarbonyl (Adpoc);

^■ optionally substituted (Ci-C₄)alkoxy(Ci-C₄)alkyl such as methoxymethyl (MOM), ethoxyethyl (EOM) and isobutoxymethyl;

^■ (tri)(di)halo(Ci-C₄)alkyl such as 2,2,2-trichloroethyl;

^■ R_eR_fRgSi- with R_e, R_f, et R_g, which may be identical or different, representing a (Ci-C₆)alkyl group, optionally substituted aryl group, optionally substituted (di)aryl(Ci-C4)alkyl group, optionally substituted triaryl(Ci-C₄)alkyl group, such as benzyl, in particular chosen from trimethylsilyl orTMS, triethylsilyl, isopropyldime- thylsilyl, tert-butyldimethylsilyl or TBDMS, (triphenylmethyl)dimethylsilyl, t-bu- tyldiphenylsilyl, methyldiisopropylsilyl, methyl(di-t-butyl)silyl, tribenzylsilyl, tri-p- xylylsilyl, triisopropylsilyl, triphenylsilyl;

^■ or else two contiguous hydroxyl groups can be protected with an alkylene group *-C(R')(R^m)-(C(R^k)(R^j))q-^* as drawn below:

with R^j, R^k, R', and R^m, which may be identical or different, representing a hydrogen atom or a (Ci-C₄)alkyl, (poly)halo(Ci-C₄)alkyl, optionally substituted aryl such as phenyl, aryl(Ci-C₄)alkyl such as benzyl, (poly)halo(Ci-C₄)alkoxy, (Ci-C₄)alkoxy, halogen, (di)(Ci- C₄)(alkyl)amino or hydroxyl group, or else two R^j and R^k and/or R', and R^m groups form, together with the carbon atom which bears them, an oxo group or a (hetero)cycloalkyl group such as cyclohexyl or cyclopropyl; q is 0, 1 , 2 or 3, preferably ^*-C(R')(R^m)- (C(R^k)(R^j))_q-^* represents a methylene, ethylene, propylene, dimethylmethylene,

^*-C(CH3)2-^* or diphenylmethylene ^*-C(Ph)2-^*, cyclopentylidene, cyclohexylidene, cyclo- heptylidene, benzylidene, p-methoxybenzylidene, 2,4-dimethoxybenzylidene, methox- ymethylene and ethoxymethylene;

the term“hydrogen peroxide-generating system” is intended to mean a chemical compound which is not H2O2 but which can generate hydrogen peroxide and/or which contains hydrogen peroxide, such as a) urea per- oxide; b) polymeric complexes that can release hydrogen peroxide, such as polyvinylpynOlidone/H₂0₂, in particular which is in the form of pow- ders, and the other polymeric complexes described in US 5 008 093, US 3 376 1 10 and US 5 183 901 ; c) oxidases in the presence of an appro- priate substrate (for example glucose in the case of glucose oxidase or uric acid with uricase); d) metal peroxides which, in water, generate hy- drogen peroxide, such as calcium peroxide or magnesium peroxide; e) perborates; or f) percarborates; in particular, they are chosen from a) urea peroxide; b) polymeric complexes that can release hydrogen per- oxide, chosen from polyvinylpyrrolidone/hhC^; c) oxidases; e) perborates and f) percarborates. I- Use of at least one Compound of formula fl)

Therefore, a subject of the invention is the non-therapeutic cosmetic use of at least one compound of formula (I) as an agent for bleaching, lightening and/or depigmenting ker- atin materials, in particular the skin, said compounds corresponding to the following for- mula (l):

and also the solvates thereof such as hydrates, the optical and geometric isomers and tautomers thereof and the organic or mineral base or acid salts thereof,

in which formula (I):

- S* denotes a monosaccharide sugar radical or denotes a polysaccharide sugar radical comprising from 2 to 5 saccharide units, each saccharide unit (the saccharide unit in the case of a monosaccharide or each saccharide unit in the case of polysaccharides) comprising one or more hydroxyl groups optionally substituted with a radical R' chosen from:

i) (Ci-C₆)alkyl or (C2-C6)alkenyl; or

ii) an acetyl radical; or

iii) a protective group (PG) for hydroxyl function(s), such as (C2-C6)alkyl(thio)carbonyl or benzyl;

said monosaccharide radical possibly also being deoxygenated in position 2 (on its C2 carbon atom);

said monosaccharide or polysaccharide radical possibly also comprising one or more amino groups NR_bR_c with R_b and R_c, which may be identical or different, representing a hydrogen atom, or an acetyl group, or a protective group for the amino function, such as (C2-C6)alkyl(thio)carbonyl; said monosaccharide or polysaccharide radical being connected to the rest of the mol- ecule by a bond between the Ci carbon atom of one of the sugars of said monosac- charide or polysaccharide radical, this bond possibly being a or b anomeric;

- R represents

i) a hydrogen atom;

ii) a (Ci-Cis)alkyl group;

iii) an aryl(Ci-C4)alkyl group optionally substituted with at least one hydroxyl and/or (Cr C₄)alkoxy group, such as benzyl;

iv) a cycloalkyl group.

Preferably, the hydroxyl radicals of the radical S* are not substituted or are all substituted with the same group R' as previously defined, in particular with an acetyl group.

Preferably, the optional amino group(s) NR_bRc of the radical S* denote(s) NHR_b with R_b all denoting a hydrogen atom or all denoting an acetyl group.

More preferentially, the hydroxyl radicals of the radical S* are not substituted, and the optional amino group(s) NR_bRc of the radical S* denote(s) NHR_b with R_b all denoting a hydrogen atom or all denoting an acetyl group.

According to one preferred form of the invention, the hydroxyl radicals of the radical S* are not substituted, and the radical S* is not substituted with an amino radical NR_bRc.

According to one advantageous embodiment, R represents

i) a hydrogen atom;

ii) a (Ci-Cis)alkyl group, in particular a (Ci-C₆)alkyl group and more particularly a (Cr C₄)alkyl group such as a methyl group;

It is understood that, for the compounds of formula (I) as defined above, when S* repre- sents a monosaccharide radical, then it can be in pyranose form (the sugar heterocycle which constitutes it comprises 6 ring members) or furanose form (the sugar heterocycle which constitutes it comprises 5 ring members); and when S* represents a polysaccha- ride radical, it comprises the sequence of 2 to 5 saccharide units, which may be identical to or different from one another, which may be in furanose or pyranose form. It is understood that, for the compounds of formula (I) as previously defined, when S* represents a polysaccharide radical, the polysaccharide is preferably a disaccharide which results from the linking of 2 pyranose units or the linking of one saccharide unit in furanose form and one unit in pyranose form or the linking of one saccharide unit in pyranose form and one unit in furanose form;

whether it is for the monosaccharide or polysaccharide radical, each saccharide unit can be in the laevorotatory L form or the dextrorotatory D form, and in a or b anomeric form.

According to one preferred embodiment, the sugar radical S* represents a monosaccha- ride radical in which the heterocycle constituting it contains 4 or 5 carbon atoms, of for- mula S*’ below:

it being understood that the R_a radical is in the Cs position if the sugar unit is in pyra- nose form or in the C₄ position if it is in furanose form;

R_b representing a hydrogen atom or a (Ci-C₄)alkyl group, preferably hydrogen;

R_c representing a hydrogen atom, or a protective group for the amine function, such as R_d-C(X')-, identical in the case of several hydroxyl functions, with X' representing an oxygen or sulfur atom, in particular an oxygen atom, and R_d representing a (Cr C₄)alkyl group, R_c preferably representing an acetyl group CH₃-C(0)-;

R_e represents a hydrogen atom or a -CH₂-0-A group;

A representing a hydrogen atom, a (Ci-C₆)alkyl group or a hydroxyl-function-protect- ing group, such as R_d-C(X')- as defined above and in particular acetyl CH₃-C(0)-, or else, when n is greater than or equal to 2 and two groups A-0 are contiguous, then two A groups can together form a linear or branched (Ci-C₆)alkylene chain;

preferably, when A is different from a hydrogen atom and from a (Ci-C₆)alkyl group, all the protective groups A are identical;

more preferentially, A represents a hydrogen atom; n is equal to 1 , 2 or 3 and m is equal to 0 or 1.

Preferably, m is 0.

According to another preferred embodiment, the sugar radical S* represents a polysac- charide radical constituted of 2 to 5 saccharide units, in particular of 2 to 3 and preferably of 2 saccharide units, linked together via an oxygen atom (oxy), 1 ->4 (Ci of one saccha- ride unit ->C₄ of the other saccharide unit) or 1 ->3 (Ci of one saccharide unit

of the other saccharide unit) or 1 ->6 (Ci of one saccharide unit - Ce of the other saccharide unit), each saccharide unit of which is constituted of a heterocycle comprising 4 or 5 carbon atoms, of formula S*" below:

in which formula S*" p and q represent integers of inclusively between 0 and 4 with p+q inclusively between 1 and 4, particularly between 1 and 2, preferentially p + q =1 ; R_a, which may be identical or different, are as defined above, R_t>, which may be identical or different, are as defined above, R_c, which may be identical or different, are as defined above, R_e, which may be identical or different, are as defined above, A, which may be identical or different, are as defined above, m, which may be identical or different, are as defined above, n, which may be identical or different, are as defined above, it being understood that the two sugar units between the square brackets q and p can be re- versed, i.e. can represent the chain below:

According to one preferred variant of the invention, the compounds of formula (I) are such that:

- S* represents a monosaccharide sugar radical chosen from: glucose, galactose, man- nose, xylose, lyxose, fucose, I'arabinose, rhamnose, quinovose, fructose, sorbose, talose, 2-deoxyglucose, N-acetylglucosamine, N-acetylgalactosamine, glucosamine, ga- lactosamine; or a disaccharide chosen from: lactose, maltulose, palatinose, lactulose, amygdalose, turanose, cellobiose, isomaltose, rutinose, maltose; more preferentially, S* represents a monosaccharide sugar radical chosen from glucose, xylose, rhamnose, ga- lactose or mannose; even more preferentially, S* represents a monosaccharide sugar radical chosen from glucose, xylose, rhamnose, galactose or mannose; even more pref- erentially, S* represents a monosaccharide sugar radical chosen from glucose, rham- nose or xylose, in particular glucose or xylose.

More preferentially, the compounds of formula (I) are chosen from the compounds of formulae (G), (I"), (I""), (I'a), (l"a) and (l""a) below:

and also the solvates thereof such as the hydrates, the optical and geometric isomers thereof, the tautomers thereof and the salts thereof, in which formulae (G), (I"), (I""), (I'a), (l"a) and (l""a):

- R'i has the same definition as that of R for the compounds of formula (I); preferably, R'i represents a hydrogen atom; or a (Ci-C6)alkyl, in particular (Ci-C₄)alkyl, radical, such as a methyl radical;

- R'₂ represents a hydrogen atom or the group -OR" with R" as defined below;

- R" represents

i) (CrC₆)alkyl; or

ii) an acetyl radical; or

iii) a protective group (PG) for hydroxyl function(s), such as (C₂-C₆)alkyl(thio)carbonyl or benzyl; or

iv) a hydrogen atom; preferably, R” represents a hydrogen atom or an acetyl radical, and more particularly a hydrogen atom;

- R'" represents a hydrogen atom, or a (Ci-C₄)alkyl group, or a -CH₂-OR" group with R" as defined previously, in particular hydrogen or an acetyl radical, and preferably a hydro- gen atom.

According to one particular embodiment, the compounds of the invention are of formula

O’)·

According to another particular embodiment of the invention, the compounds of the in- vention are of formula (I”).

According to another particular embodiment of the invention, the compounds of the in- vention are of formula (I””).

According to another particular embodiment of the invention, the compounds of the in- vention are of formula (I’a). According to another particular embodiment of the invention, the compounds of the in- vention are of formula (l”a).

According to another particular embodiment of the invention, the compounds of the in- vention are of formula (l””a).

According to one particular embodiment, S* and S*' represent a monosaccharide radical chosen from glucose, galactose, mannose, xylose, lyxose, fucose, arabinose, rhamnose, ribose, deoxyribose, quinovose, fructose, sorbose, talose, 2-deoxyglucose, threose, erythrose, N-acetylglucosamine, N-acetylgalactosamine, glucosamine and galactosa- mine; in particular, S* and S*' represent a monosaccharide radical chosen from glucose, xylose, rhamnose, galactose or mannose; even more particularly, S* and S*' represent a monosaccharide radical chosen from glucose, xylose or rhamnose; and even more particularly, S* and S*' represent a monosaccharide radical chosen from glucose or xy lose.

In particular, S* and S*’ represent a monosaccharide radical chosen from D-glucose, D- galactose, D-mannose, D-xylose, L-xylose, D-lyxose, L-lyxose, L-fucose, L-arabinose, D-arabinose, L-rhamnose, L-ribose, D-ribose, 2-deoxy-D-ribose, 2-deoxy-L-ribose, D- quinovose, D-fructose, L-sorbose, D-talose, 2-deoxy-D-glucose, D-threose, D-erythrose, L-threose, L-erythrose, N-acetyl-D-glucosamine, N-acetyl- D-galactosamine, D-glucosa- mine and D-galactosamine. Preferably, S* and S*' denote a monosaccharide radical cho- sen from D-glucose, D-galactose, D-mannose, D-xylose or L-rhamnose; in particular, S* and S*' represent a monosaccharide radical chosen from D-glucose, D-xylose or L-rham- nose, and more particularly a D-glucose or D-xylose radical.

According to another particular embodiment, S* and S*" represent a polysaccharide rad- ical and in particular a disaccharide radical chosen from lactose, maltulose, palatinose, lactulose, amygdalose, turanose, cellobiose, isomaltose, rutinose and maltose.

According to one particular form of the invention, S* and S*" represent a polysaccharide radical, in particular a disaccharide radical chosen from lactose, maltose and cellobiose. In particular, S* and S*" represent a disaccharide radical chosen from D-lactose, D- maltose and D-cellobiose. By way of examples of novel compounds of formulae (G), (I"), (I""), (I'a), (l"a) and (l""a) according to the invention, mention may be made of the compounds 1a, 2a, 3a and 4a, and 1 to 8, and also the isomers thereof and/or the solvates thereof and/or the salts thereof and/or the tautomers thereof:

and in particular the compounds 1_, 2, 3, 4 and/or the solvates thereof and/or the salts thereof and/or the tautomers thereof. The acceptable solvates of the compounds used in the present invention comprise con- ventional solvates such as those formed during the last step of the preparation of said compounds due to the presence of solvents. Mention may be made, by way of example, of the solvates due to the presence of water (hydrates) or of linear or branched alcohols, such as ethanol or isopropanol.

The salts of the compounds of formula (I) which comprise at least one amine function can be salts of an organic acid such as citric acid, lactic acid, tartaric acid, aspartic acid, glutamic acid, acetic acid, formic acid, trifluoroacetic acid, hydrochloric acid, glycolic acid or malic acid.

The salts of the compounds of formula (I) which comprise at least one acid function can also be chosen from metal salts, for example aluminium (Al³⁺), zinc (Zn²⁺), manganese (Mn²⁺) or copper (Cu²⁺); alkali metal salts, for example lithium (Li⁺), sodium (Na⁺) or po- tassium (K⁺); or alkaline-earth metal salts, for example calcium (Ca²⁺) or magnesium (Mg²⁺). They can also be ammonium derivatives of formula NH₄ ⁺ or organic salts such as ammoniums of formula U₃NI- , NY₃ denoting an organic amine, the Y radicals being identical or different, it being possible for two or three Y radicals to form, in pairs, a ring with the nitrogen atom which carries them or it being possible for NY₃ to denote an aro- matic amine. The organic amines are for example alkylamines, for instance methylamine, dimethylamine, trimethylamine, triethylamine or ethylamine, or hydroxyalkylamines, for instance 2-hydroxyethylamine, bis(2-hydroxyethyl)amine or tris(2-hydroxyethyl)amine, or cycloalkylamines, for instance bicyclohexylamine or glucamine, piperidine, or pyri- dines and the like, for example collidine, quinine or quinoline, or amino acids which are basic in nature, for instance lysine or arginine. In the case where the compounds according to the invention are in salt form, the anions or the cations are of course in an amount which ensures the electro-neutrality of the compounds of formula (I).

The salts of the compounds of formula (I) according to the invention which comprise at least one acid function can advantageously be chosen from the metal salts Cu²⁺, Mn²⁺ and Zn²⁺, the alkali metal salts Li⁺, Na⁺ and K⁺ and the alkaline-earth metal salts Ca²⁺ and Mg²⁺.

According to another variant, the salts of the compounds of formula (I) according to the invention which comprise at least one acid function can advantageously be chosen from ammoniums, preferably from the salts of amino acids which are basic in nature, for in- stance lysine or arginine or from diethanolamine salts or triethanolamine salts.

II- Novel compounds

A subject of the invention is also the compounds of formula (I) as defined above.

In particular, a subject of the invention is the novel compounds of formulae (G), (I"), (I""), (I'a), (l"a) and (l""a), as defined below.

The preferred novel compounds are the compounds 1a, 2a, 3a and 4a, 1 to 8 described above.

III. Obtaining of the 5-oxazolidine-2,4-dione C-qlvcoside compounds

1) Process for the synthesis of the novel compounds of formula (I)

Another subject of the invention is a process for preparing, or a process for the chemical synthesis of, the compounds of formula (I) as defined above, according to scheme (1 ) below:

in which (II) denotes a monosaccharide represented by:

or a polysaccharide PS-OH, in which A, R_a, Rt_>, R_c, Re, n, and m are as defined above, p' and q' representing an integer inclusively between 0 and 4, with p’ + q’ inclusively between 0 and 4, in particular between 0 and 2, preferably p'+q' = 0 or 1 , it being under- stood that the two units between square brackets can be reversed; PS-OH denoting a polysaccharide having the structure (gg) below:

(gg)

step 1 consisting in reacting a monosaccharide or a polysaccharide PS- OH of formula (II) with a barbituric acid derivative (III), in particular in the presence of a mineral base such as IVTOH , M⁺ representing a cationic counterion or preferably a weak base such as (bi)carbonate, in particular with alkali metal (bi)carbonate, or in the presence of an organic base such as triethylamine or diisopropylethylamine; in particular in a polar protic solvent such as water, by heating optionally at a temperature of between 30°C and 100°C, in particular at 80°C, preferably for a period of between 1 hour and 24 hours, in particular between 3 hours and 10 hours, such as 5 hours, so as to give the compound comprising a sugar unit (IV);

step 2 consisting in reacting the compound (IV) with a chemical oxidizing agent such as hydrogen peroxide or a hydrogen peroxide-generating agent such as oxone or else a biological agent such as an enzyme of oxidase type, in particular in a polar solvent (or solvent mixture) with a boiling point of between 40°C and 100°C at atmospheric pressure, such as acetone or acetonitrile, or a polar protic solvent such as water, option- ally in a basic medium and/or in the presence of a chelating agent such as ethylenediaminetetraacetic acid (EDTA) optionally in salt form, so as to give a C-glycoside compound (I) according to the invention,

^■ it being understood that, if A represents a hydrogen atom and it is desired to have a protective group PG, then a protection step is added,

^■ that if R_b and R_c of NR_bR_c optionally present on the monosaccharide or the poly- saccharide (II) represent hydrogen atoms and it is desired to protect the amino group(s), a protection step is carried out,

^■ that if the group R comprises a function sensitive to these synthesis steps, it will be advisable to add a protection/deprotection sequence.

Under certain reaction temperature and time conditions during step 2, it is possible to isolate the intermediate (V) according to step 2a:

Step 2b consists in treating the compound (V) in a polar solvent (or solvent mixture) with a boiling point of between 40°C and 100°C at atmospheric pressure, such as acetone or acetonitrile, or a polar protic solvent such as water, optionally in a medium that is basic, in particular by addition of a mineral base such as sodium hydroxide or potassium hy- droxide, and/or in the presence of a chelating agent such as ethylenediaminetetraacetic acid (EDTA) optionally in salt form, and optionally in the presence of a chemical oxidizing agent, such as hydrogen peroxide or else a hydrogen peroxide-generating agent, such as oxone, or else a biological agent such as an enzyme of oxidase type, to give a C- glycoside compound (I) according to the invention.

The compounds of formula (V), and also the solvates and/or isomers and/or salts thereof, are novel. They can also be represented by the general formula below

with S* and R as described above.

A subject of the invention is also the compounds of formula (V).

Thus, when the process described above uses D-glucose, it is possible to isolate, after step 1 , then the oxidation step 2 carried out for a limited period of time, the novel com- pound 9 (and/or the solvates thereof and/or the salts thereof):

All the reagents are obtained by conventional methods known by those skilled in the art. In particular, the compounds (III) are commercially available or can be prepared, for ex- ample by the following method:

The amines (VI) are reacted with the isocyanates (VII) to form symmetrical urea, which then reacts with an activated malonyl derivative (VIII), such as malonyl chloride (Y = Cl), to give the compounds (III), the reaction being carried out in an aprotic polar solvent such as dichloromethane, THF, ether or acetonitrile, at temperatures ranging from 20°C to 160°C.

Those skilled in the art will take care to protect or deprotect the sensitive functions ac- cording to the synthesis steps.

As compounds of formula (I), in particular (G), (I"), (I""), (I'a), (l"a) and (l""a), use may be made of the compounds la, 2a, 3a and 4a, and 1 to 8 described above.

IV - Compositions

The compounds of formula (I) according to the invention have a most particular applica- tion in the cosmetics field.

A subject of the invention is also a composition containing at least one compound of formula (I), and preferably at least one compound of formulae (G), (I"), (I""), (I'a), (l"a) and (l""a) defined above, and more particularly at least one compound 1a, 2a, 3a and 4a, and 1 to 8 as defined above.

The composition according to the invention is advantageously a cosmetic composition. The composition according to the invention is advantageously a composition intended for topical application. The composition according to the invention advantageously comprises, in a physiologi- cally acceptable medium, at least one compound of formula (I) as described above, and preferably at least one compound of formulae (G), (I"), (I""), (I'a), (l"a) and (l""a) defined above, and more particularly at least one compound 1a, 2a, 3a and 4a, and 1 to 8 as defined above.

The term“physiologically acceptable medium” is intended to mean a medium that is compatible with human keratin materials such as bodily or facial skin, the lips, mucous membranes, the eyelashes, the nails, the scalp and/or the hair.

The compound of formula (I), and in particular the compound of formulae (G), (I"), (I""), (I'a), (l"a) and (l""a) or else 1a, 2a, 3a and 4a, and 1 to 8 defined above (each corn- pound of formula (I) and in particular each compound of formulae (G), (I"), (I""), (I'a), (l"a) and (l""a) and more particularly a compound 1a, 2a, 3a and 4a, and 1 to 8 if the composition comprises several thereof) may be present in the composition according to the invention in an amount which may be between 0.01 % and 10% by weight, preferably between 0.1 % and 5% by weight, in particular between 0.5% and 3% by weight, relative to the total weight of the composition.

The composition according to the invention is advantageously a cosmetic composition: it may comprise adjuvants usually used in the cosmetic field. The composition may be an aqueous composition, that is to say containing water or a mixture of water and water miscible solvents such as C2-C6 alcohols.

Mention may be made in particular of organic solvents, especially C2-C6 alcohols; oils, in particular hydrocarbon-based oils and silicone oils; waxes, pigments, fillers, dyes, sur- factants, emulsifiers; cosmetic active agents, polymers, thickeners, preservatives, fra- grances, bactericides, odour absorbers, antioxidants.

According to one advantageous form of the invention, the cosmetic composition contains at least one compound of formula (I), and in particular at least one compound of formulae (G), (I"), (I""), (I'a), (l"a) and (l""a), as defined above, and at least one additive chosen from fragrances, oils, waxes, surfactants, thickeners, dyes, bactericides and preserva- tives. In one preferred embodiment, the cosmetic composition according to the invention con- tains at least one compound chosen from the compounds 1a, 2a, 3a and 4a, and 1 to 8 defined above, and also the solvates thereof such as hydrates, and the organic or min- eral acid or base salts thereof.

These optional cosmetic adjuvants may be present in the composition in a proportion of from 0.001 % to 80% by weight and especially from 0.1 % to 40% by weight, relative to the total weight of the composition. In any case, these adjuvants, and the proportions thereof, will be chosen by those skilled in the art such that the advantageous properties of the compounds according to the invention are not, or are not substantially, adversely affected by the envisaged addition.

As active agents, it will be advantageous to introduce into the composition according to the invention at least one compound chosen from: desquamating agents; calmatives, organic or mineral photoprotective agents, moisturizers; depigmenting agents other than those which are the subject of the present invention; anti-glycation agents; NO-synthase inhibitors; agents for stimulating the synthesis of dermal or epidermal macromolecules and/or for preventing their degradation; agents for stimulating fibroblast and/or keratino- cyte proliferation or for stimulating keratinocyte differentiation; dermo-decontracting agents; tensioning agents; anti-pollution agents and/or free-radical scavengers; agents acting on the microcirculation; ceramides; agents acting on the energy metabolism of cells; and mixtures thereof.

The composition according to the invention may in particular be in any presentation form normally used in the cosmetic field, and especially in the form of an aqueous or aqueous- alcoholic solution, which is optionally gelled, a dispersion of the lotion type, which is op- tionally a two-phase lotion, an oil-in-water or water-in-oil or multiple (for example W/O/W or O/W/O) emulsion, an aqueous gel, a dispersion of oil in an aqueous phase by means of spherules, these spherules possibly being polymer nanoparticles such as nano- spheres and nanocapsules or, better still, lipid vesicles of the ionic and/or non-ionic type; aqueous or oily gels. These compositions are prepared according to the usual methods. The composition according to the invention may constitute a skincare composition, and especially a cleansing, protecting, treating or care cream for the face, the hands, the feet, the major anatomical folds or the body (for example day creams, night creams, makeup- removing creams, foundation creams or antisun creams); a fluid foundation, a makeup- removing milk, a protective or care body milk or an antisun milk; a skincare lotion, gel or foam, such as a cleansing lotion.

V. Treatment process

A subject of the invention is also a process for the cosmetic treatment of the skin, corn- prising the application to the skin of a composition comprising at least one compound of formula (I), and preferably at least one compound of formulae (G), (I"), (I""), (I'a), (l"a) and (l""a) defined above, and more particularly at least one compound 1a, 2a, 3a and 4a, and 1 to 8 as defined above.

A subject of the invention is also a non-therapeutic cosmetic process for depigmenting, lightening and/or bleaching keratin materials, in particular the skin, comprising the appli cation of the cosmetic composition described above comprising at least one compound of formula (I) and preferably at least one compound of formulae (G), (I"), (I""), (I'a), (l"a) and (l""a) defined above, and more particularly at least one compound 1a, 2a, 3a and 4a, and 1 to 8 as defined above.

More preferably, it is the process for depigmenting, lightening and/or bleaching the skin.

The invention also relates to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined above, and preferably at least one compound of formulae (G), (I"), (I""), (I'a), (l"a) and (l""a) defined above, and more particularly at least one corn- pound 1a, 2a, 3a and 4a, and 1 to 8 as defined above, as an agent for bleaching, light ening and/or depigmenting keratin materials, in particular the skin.

The various examples below describe various synthesis routes making it possible to ob- tain the compounds of formula (I).

In these schemes, "a.t" signifies ambient temperature.

The invention is illustrated in greater detail by the following non-limiting examples.

EXAMPLES Al Synthesis examples

4.1 Synthesis of compounds 1, 2, 3, 4 and 9

Example 1 : Synthesis of compound 1

compound 1

Step 1. Barbituric acid (10.7 g, 83 mmol) is added, with stirring, to a solution of D-glu- cose (15 g, 83 mmol) in water (170 ml), then NaHCOs is added to pH 7. After neutrali- zation, the mixture is heated at 80°C for 5 h. The reaction is monitored by TLC in di- chloromethane/MeOH 6:4 + 1% acetic acid. The reaction mixture is added dropwise to acetone (850 ml) with rigourous stirring. The precipitate obtained is filtered off and then washed 3 times in acetone, and the solid 10 obtained is dried under vacuum. It is iso- lated in the form of a yellow powder. The ¹H NMR spectra and the mass spectrometry are in accordance with the expected structure.

Step 2. Hydrogen peroxide at 50% (137 mmol) is added, with stirring, to a solution of compound 10 (21.4 g, 68.5 mmol) in water (60 ml). The reaction mixture is brought to 70°C for 4 h 30. The reaction is monitored by TLC (BUOH/H2O/ACOH 6:2:2). The mixture is then added dropwise at ambient temperature to 600 ml of acetone. The residue formed is filtered off, then dissolved in water and the solution is concentrated to dryness. The powder obtained is washed twice in acetone, to give the compound 1 in the form of a pale yellow powder. The ¹H NMR spectra and the mass spectrometry are in accord- ance with the expected structure. Example 2: Synthesis of compound 2

compound 2

Step 1. According to the process described in example 1 , the intermediate 11 is ob- tained from D-xylose and barbituric acid. The ¹H NMR spectra and the mass spectrom- etry are in accordance with the expected structure 11.

Step 2. 15 g of 11 (0.053 mol) in 35 ml of water were placed in a 100 ml three-necked flask equipped with a condenser, an argon inlet, a bubbler, a thermometer and a mag- netic stirrer. 10.9 ml of 30% aqueous hydrogen peroxide in water (0.106 mol) were then added. The reaction medium is stirred at ambient temperature and the reaction is mon- itored by TLC with water/acetonitrile 8:2.

After stirring overnight, the starting product is consumed, but the peroxide test is posi- tive. The reaction medium is heated at 80°C for 3 hours (negative peroxide test), cooled to ambient temperature and then poured into a round-bottomed flask containing 250 ml of ethanol, before being concentrated to dryness in a rotary evaporator.

The paste obtained is taken up with acetone using a mortar, to give the compound 2 in the form of a light beige powder. The ¹H NMR spectra and the mass spectrometry are in accordance with the expected structure.

Example 3: Synthesis of compound 3

compound 3

Step 1. According to the process described in example 1 , the intermediate 12 is ob- tained from D-glucose and 1 ,3-dimethylbarbituric acid. The ¹H NMR spectra and the mass spectrometry are in accordance with the expected structure 12.

Step 2. An aqueous solution of Na EDTA (13 mg in 90 ml of water, C = 4.10^-4 M, 0.036 mmol) is added, with stirring, to a solution of 12 (10.0 g, 32.0 mmol) in 140 ml of ace- tonitrile. After a few minutes, the mixture is cooled in an ice bath and then 25 ml of acetone are added. An oxone (48.0 g, 78.1 mmol) / NaHCOs (20.0 g, 238 mmol) mixture is then slowly added. Stirring is continued overnight at ambient temperature, then the reaction mixture is filtered. After evaporation under vacuum, the residue is taken up in methanol, and the insoluble matter is filtered off. The filtrate is evaporated under vac- uum and then purified on silica gel (dichloromethane/MeOH 8:2). The compound 3 is obtained in the form of a white solid. The ¹H NMR spectra and the mass spectrometry are in accordance with the expected structure.

Example 4: Synthesis of compound 4

compound 4

Step 1. According to the process described in example 1 , the intermediate 13 is ob- tained from L-rhamnose and 1 ,3-dimethylbarbituric acid. The ¹H NMR spectra and the mass spectrometry are in accordance with the expected structure 13.

Step 2. An aqueous solution of Na EDTA (7 mg in 46 ml of water, 0.019 mmol) is added, with stirring, to a solution of 13 (5.0 g, 15.4 mmol) in 80 ml of acetonitrile. After a few minutes, the mixture is cooled in ice and then 13 ml of acetone are added. An oxone (25.2 g, 41.0 mmol) / NaHCOs (10.5 g, 125 mmol) mixture is then carefully added at a rate of approximately 2/3 of a spatula every 10 min. The pH is stabilized at approxi- mately 7.3. Stirring is continued overnight at ambient temperature, then the reaction mixture is filtered. After evaporation under vacuum, the residue is purified on silica gel by elution with an increasing gradient of MeOH in dichloromethane. The compound 4 is obtained in the form of a yellow oil. The ¹H NMR spectra and the mass spectrometry are in accordance with the expected structure.

Example 5: Synthesis of compound 9

compound 9

An aqueous solution of Na2EDTA (0.4 mM, 1 ml, 0.35 pmol) is added, with stirring, to a solution of 12 (100 mg, 0.294 mmol) in 1.5 ml of acetonitrile. After a few minutes, the mixture is cooled in ice and then 0.26 ml of acetone are added. An oxone (0.5 g, 0.814 mmol) / NaHCOs (0.2 g, 2.38 mmol) mixture is then carefully added all at once. The pH is stabilized at approximately 8. After 2 h of stirring, the reaction mixture is filtered and concentrated under vacuum so as to obtain 70 mg of compound 9 in the form of a white paste. The ¹H NMR spectra and mass spectrometry are in accordance with the expected structure 9.

B) Demonstration of the depigmenting activity

The measurement of the depigmenting activity (reduction of melanin production) of com- pounds of formula (I) was performed by assaying normal human melanocytes in vitro as follows.

First of all, normal human melanocytes are cultured and dispensed into wells. After 24 hours, the culture medium was replaced with a medium containing compounds of formula (I) to be evaluated. The cells were incubated 72 hours before measurement of the final optical density, which measures the amount of melanin produced by the melanocytes. The compounds are tested at 100 mM after calibration. Lucinol (n-butyl resorcinol) at 100 mM is used as positive reference, and corresponds to 100% depigmentation.

The compounds of formula (I) showed a depigmenting effect.

Example 3: Cosmetic composition

A skin depigmenting composition is prepared, comprising (in grams):

Compound No. 2 2 g

PEG400 68 g

Ethanol 30 g

The composition applied to the skin makes it possible to attenuate brown blemishes. A similar composition is prepared with the compound 3.

Example 4: gel

A skin depigmenting gel is prepared, comprising (% by weight):

Compound No. 2 0.25%

Carbomer (Carbopol 981 from Lubrizol) 1%

preservative qs

water qs 100% The composition applied to the skin makes it possible to attenuate brown blemishes.

A similar composition is prepared with the compound 3.

Claims

1. Non-therapeutic cosmetic process for depigmenting, lightening and/or bleaching keratin materials, comprising the application of a compound of formula (I) or of a compo- sition comprising one or more compounds of formula (I):

and also the solvates thereof such as hydrates, the optical and geometric isomers and tautomers thereof and the organic or mineral base or acid salts thereof,

in which formula (I):

- S* denotes a monosaccharide sugar radical or denotes a polysaccharide sugar radical comprising from 2 to 5 saccharide units, each saccharide unit (the saccharide unit in the case of a monosaccharide or each saccharide unit in the case of polysaccharides) corn- prising one or more hydroxyl groups optionally substituted with a radical R' chosen from: i) (Ci-C₆)alkyl or (C2-C6)alkenyl; or

ii) an acetyl radical; or

iii) a protective group (PG) for hydroxyl function(s), such as (C2-C6)alkyl(thio)carbonyl or benzyl;

said monosaccharide radical possibly also being deoxygenated in position 2 (on its C2 carbon atom);

said monosaccharide or polysaccharide radical possibly also comprising one or more amino groups NR_bR_c with R_b and R_c, which may be identical or different, representing a hydrogen atom, or an acetyl group, or a protective group for the amino function, such as (C2-C6)alkyl(thio)carbonyl;

said monosaccharide or polysaccharide radical being connected to the rest of the mole- cule by a bond between the C1 carbon atom of one of the sugars of said monosaccharide or polysaccharide radical, this bond possibly being a or b anomeric; - R represents

i) a hydrogen atom;

ii) a (Ci-Cis)alkyl group;

iii) an aryl(Ci-C₄)alkyl group optionally substituted with at least one hydroxyl and/or (Ci- C₄)alkoxy group, such as benzyl;

iv) a cycloalkyl group.

2. Process according to the preceding claim, in which the compound(s) of formula (I) comprise(s) a radical R chosen from:

i) a hydrogen atom;

ii) a (CrC ie)alkyl group, in particular a (Ci-C₆)alkyl group and more particularly a (Cr C₄)alkyl group such as a methyl group.

3. Process according to either one of the preceding claims, in which the compound(s) of formula (I) comprise(s) a sugar radical S^* which represents a monosaccharide radical in which the heterocycle which forms it contains 4 or 5 carbon atoms, of formula S*' below:

R_a representing a hydrogen atom a (Ci-C₄)al-

it being understood that the R_a radical is in the Cs position if the sugar unit is in pyranose form or in the C₄ position if it is in furanose form;

R_b representing a hydrogen atom or a (Ci-C₄)alkyl group, preferably hydrogen;

R_c representing a hydrogen atom, or a protective group for the amine function, such as R_d-C(X')-, identical in the case of several hydroxyl functions, with X' representing an ox- ygen or sulfur atom, in particular an oxygen atom, and R_d representing a (Ci-C₄)alkyl group, R_c preferably representing an acetyl group CH₃-C(0)-;

R_e represents a hydrogen atom or a -Chh-O-A group;

A representing a hydrogen atom, a (Ci-C₆)alkyl group or a hydroxyl-function-protective group, or else, when n is greater than or equal to 2 and two groups A-0 are contiguous, then two A groups can together form a linear or branched (Ci-C₆)alkylene chain; preferably, when A is different from a hydrogen atom and from a (Ci-C₆)alkyl group, all the protective groups A are identical;

n is equal to 1 , 2 or 3 and m is equal to 0 or 1 , preferably m is equal to 0.

4. Process according to any one of Claims 1 to 3, in which the compound(s) of formula (I) comprise(s) a sugar radical S* which represents a polysaccharide radical con- stituted of 2 to 5 saccharide units, in particular of 2 to 3 and preferably of 2 saccharide units, linked together via an oxygen atom (oxy), 1 ->4 (Ci of one saccharide unit ->C₄ of the other saccharide unit) or 1 ->3 (Ci of one saccharide unit

of the other saccharide unit) or 1 ->6 (Ci of one saccharide unit - Ce of the other saccharide unit), each saccha- ride unit of which is constituted of a heterocycle comprising 4 or 5 carbon atoms, of formula S*" below:

in which formula S*":

- p and q represent integers inclusively between 0 and 4, with p + q inclusively between 1 and 4, particularly between 1 and 2, preferentially p + q = 1 ;

- R_a, R_b, R_c, R_e, A m, and n, which may be identical or different, are as defined in any one of the preceding claims, it being understood that the two sugar units between the square brackets q and p can be reversed, i.e. can represent the following sequence:

5. Process according to any one of Claims 1 to 3, in which the compound(s) of formula (I) comprise(s) a sugar radical S* or S*' which represents a monosaccharide radical cho- sen from glucose, galactose, mannose, xylose, lyxose, fucose, arabinose, rhamnose, ribose, deoxyribose, quinovose, fructose, sorbose, talose, 2-deoxyglucose, threose, erythrose, N-acetylglucosamine, N-acetylgalactosamine, glucosamine and galactosa- mine; in particular, S* or S*' represents a monosaccharide radical chosen from D-glu- cose, D-galactose, D-mannose, D-xylose, L-xylose, D-lyxose, L-lyxose, L-fucose, L- arabinose, D-arabinose, L-rhamnose, L-ribose, D-ribose, 2-deoxy-D-ribose, 2-deoxy-L- ribose, D-quinovose, D-fructose, L-sorbose, D-talose, 2-deoxy-D-glucose, D-threose, D- erythrose, L-threose, L-erythrose, N-acetyl-D-glucosamine, N-acetyl- D-galactosamine, S*-glucosamine and D-galactosamine. Preferably, S* or S*' denotes a monosaccharide radical chosen from D-glucose, D-galactose, D-mannose, D-xylose, D-lyxose, L-fucose, L-arabinose, L-rhamnose, D-ribose, 2-deoxy-D-ribose, D-quinovose, D-fructose, L-sor- bose, D-talose, 2-deoxy-D-glucose, D-threose, D-erythrose, N-acetyl-D-glucosamine, N- acetyl- D-galactosamine, D-glucosamine and D-galactosamine, advantageously chosen from glucose, xylose, rhamnose, mannose and galactose; in particular, S* or S*' denotes a monosaccharide radical chosen from D-glucose, D-xylose, L-rhamnose, D-mannose and D-galactose, in particular S^* and S^*’ represent a monosaccharide radical chosen from D-glucose, D-xylose and L-rhamnose, and more particularly a D-glucose or D-xy- lose radical.

6. Process according to any one of Claims 1 to 3 and 5, in which the compound(s) of formula (I) comprise(s) a sugar radical S* or S*' which represents a monosaccharide radical chosen from glucose, xylose and rhamnose; particularly, S* or S*' denotes a sugar radical chosen from D-glucose, D-xylose and L-rhamnose, more particularly S* or S*' denote a glucose or xylose radical, preferentially S* or S*' denote a D-glucose or D- xylose radical .

7. Process according to any one of Claims 1 to 4, in which the compound(s) of for- mula (I) comprise(s) a sugar radical S* or S*" which represents a polysaccharide radical and in particular a disaccharide radical preferably chosen from lactose, maltulose, palati- nose, lactulose, amygdalose, turanose, cellobiose, isomaltose, rutinose and maltose; more particularly chosen from D-lactose, maltulose, palatinose, lactulose, amygdalose, turanose, D-cellobiose, isomaltose, rutinose and D-maltose, in particular a disaccharide radical chosen from lactose, maltose and cellobiose, in particular, S^* and S^*" represent a disaccharide radical chosen from D-lactose, D-maltose and D-cellobiose. 8. Process according to any one of the preceding claims, in which the corn- pound^) of formula (I) is (are) chosen from the compounds of formulae (G), (I"), (I""), (I'a), (l"a) and (l""a) below:

and also the solvates thereof such as the hydrates, the optical and geometric isomers thereof, the tautomers thereof and the salts thereof, in which formulae (G), (I"), (I""), (I'a), (l"a) and (l""a):

- R'i has the same definition as that of R for the compounds of formula (I); preferably, R'i represents a hydrogen atom; or a (CrC₆)alkyl, in particular (CrC4)alkyl, radical, such as a methyl radical;

- R'2 represents a hydrogen atom or the group -OR" with R" as defined below;

- R" represents

i) (Ci-C₆)alkyl; or

ii) an acetyl radical; or

iii) a protective group (PG) for hydroxyl function(s), such as (C2-C6)alkyl(thio)carbonyl or benzyl; or

iv) a hydrogen atom;

preferably, R” represents a hydrogen atom or an acetyl radical, and more particularly a hydrogen atom;

- R'" represents a hydrogen atom, or a (Ci-C₄)alkyl group, or a -CH2-OR" group with R" as defined previously, in particular hydrogen or an acetyl radical, and preferably a hydro- gen atom.

9. Process according to any one of the preceding claims, in which the com- pound(s) of formula (I) are chosen from the following compounds:

and also the solvates thereof such as hydrates, and the organic or mineral base or acid salts thereof. 10. Composition comprising one or more compounds of formula (I) as defined in any one of the preceding claims, preferably at least one compound of formula (I) cho- sen from (G), (I"), (I""), (I'a), (l"a) and (l""a) as defined in Claim 8 and compounds 1a, 1 b, 1 c, 1 d and 1 to 8 as defined in the preceding claim. 11. Composition according to Claim 10, in which the compound(s) of formula (I) are present in amounts ranging from 0.01 % to 10% by weight, preferentially from 0.1 % to 5% by weight, relative to the total weight of the composition.

12. Composition according to either of Claims 10 and 1 1 , characterized in that it com- prises at least one adjuvant chosen from the group formed by organic solvents, es- pecially C2-C6 alcohols; oils, especially hydrocarbon-based oils and silicone oils; waxes, pigments, fillers, dyes, surfactants, emulsifiers; cosmetic active agents, or- ganic or mineral photoprotective agents, polymers, thickeners, preservatives, fra- grances, bactericides, ceramides, odour absorbers, antioxidants.

13. Compounds of formula (I)

and also the solvates thereof such as hydrates, the optical and geometric isomers and tautomers thereof and the organic or mineral base or acid salts thereof,

in which formula (I):

- S* denotes a monosaccharide sugar radical or denotes a polysaccharide sugar radical comprising from 2 to 5 saccharide units, each saccharide unit (the saccharide unit in the case of a monosaccharide or each saccharide unit in the case of polysaccharides) corn- prising one or more hydroxyl groups optionally substituted with a radical R' chosen from: i) (Ci-C₆)alkyl or (C2-C6)alkenyl; or

ii) an acetyl radical; or

iii) a protective group (PG) for hydroxyl function(s), such as (C2-C6)alkyl(thio)carbonyl or benzyl;

said monosaccharide radical possibly also being deoxygenated in position 2 (on its C2 carbon atom);

said monosaccharide or polysaccharide radical possibly also comprising one or more amino groups NR_bR_c with R_b and R_c, which may be identical or different, representing a hydrogen atom, or an acetyl group, or a protective group for the amino function, such as (C2-C6)alkyl(thio)carbonyl;

said monosaccharide or polysaccharide radical being connected to the rest of the molecule by a bond between the C1 carbon atom of one of the sugars of said monosac- charide or polysaccharide radical, this bond possibly being a or b anomeric; - R represents

i) a hydrogen atom;

ii) a (Ci-Cis)alkyl group;

iii) an aryl(Ci-C₄)alkyl group optionally substituted with at least one hydroxyl and/or (Ci- C₄)alkoxy group, such as benzyl;

iv) a cycloalkyl group.

14. Compound of formula (I) according to the preceding claim, comprising a radical R chosen from:

i) a hydrogen atom;

ii) a (Ci-Cis)alkyl group, in particular a (Ci-C₆)alkyl group and more particularly a (Ci- C₄)alkyl group such as a methyl group.

15. Process according to any one of Claims 1 to 9, for depigmenting, lightening and/or bleaching the skin.

16. Non-therapeutic cosmetic use of a compound of formula (I) as defined according to any one of Claims 1 to 8, and compounds 1a, 2a, 3a and 4a, and 1 to 8 as defined in Claim 9, as an agent for bleaching, lightening and/or depigmenting keratin mate- rials, in particular the skin.

17. Process for the synthesis of compounds of formula (I) as defined in any one of Claims 1 to 9 according to scheme (1 ) below:

in which (II) denotes a monosaccharide represented by:

or a polysaccharide PS-OH, in which A, R_a, R_t>, R_c, R_e, n, and m are as defined above, p' and q' representing an integer inclusively between 0 and 4, with p’ + q’ inclusively between 0 and 4, in particular between 0 and 2, preferably p'+q' = 0 or 1 , it being under- stood that the two units between square brackets can be reversed; PS-OH denoting a polysaccharide having the structure (gg) below:

(99)

step 1 consisting in reacting a monosaccharide or a polysaccharide PS- OH of formula (II) with a barbituric acid derivative (III), in particular in the presence of a mineral base such as IVTOH , M⁺ representing a cationic counterion or preferably a weak base such as (bi)carbonate, in particular with alkali metal (bi)carbonate, or in the presence of an organic base such as triethylamine or diisopropylethylamine; in particular in a polar protic solvent such as water, by heating optionally at a temperature of between 30°C and 100°C, in particular at 80°C, preferably for a period of between 1 hour and 24 hours, in particular between 3 hours and 10 hours, such as 5 hours, so as to give the compound comprising a sugar unit (IV);

step 2 consisting in reacting the compound (IV) with a chemical oxidizing agent such as hydrogen peroxide or a hydrogen peroxide-generating agent such as oxone or else a biological agent such as an enzyme of oxidase type, in particular in a polar solvent (or solvent mixture) with a boiling point of between 40°C and 100°C at atmospheric pressure, such as acetone or acetonitrile, or a polar protic solvent such as water, option- ally in a basic medium and/or in the presence of a chelating agent such as ethylenediaminetetraacetic acid (EDTA) optionally in salt form, so as to give a C-glycoside compound (I) according to the invention,

■ it being understood that, if A represents a hydrogen atom and it is desired to have a protective group PG, then a protection step is added,

■ that, if R_b and R_c of NR_bR_c optionally present on the monosaccharide or the polysaccharide (II) represent hydrogen atoms and it is desired to protect the amino group(s), a protection step is carried out,

■ that if the group R comprises a function sensitive to these synthesis steps, it will be advisable to add a protection/deprotection sequence. wherein, under certain reaction temperature and time conditions during step 2, it is pos- sible to isolate the intermediate (V) according to step 2a:

wherein step 2b consists in treating the compound (V) in a polar solvent (or solvent mix- ture) with a boiling point of between 40°C and 100°C at atmospheric pressure, such as acetone or acetonitrile, or a polar protic solvent such as water, optionally in a medium that is basic, in particular by addition of a mineral base such as sodium hydroxide or potassium hydroxide, and/or in the presence of a chelating agent such as ethylenedia- minetetraacetic acid (EDTA) optionally in salt form, and optionally in the presence of a chemical oxidizing agent, such as hydrogen peroxide or else a hydrogen peroxide-gen- erating agent, such as oxone, or else a biological agent such as an enzyme of oxidase type, to give a C-glycoside compound (I) according to the invention.

18. Compounds of formula (V), and also the solvates and/or isomers and/or salts

thereof, having the general formula below

with S* and R as described in Claims 1 to 9.

19. Compounds according to the preceding claim