FR3073144A1 - PROCESS FOR TREATING KERATINIC MATERIALS FROM DERIVATIVES OF AMIDE C-GLYCOSIDES AND THE COSMETIC COMPOSITION CONTAINING THEM - Google Patents

Abstract

The present invention relates to a process for the cosmetic treatment of keratin materials, comprising the application thereon, such as the skin, of a composition comprising a compound (I) with R1, R2 and R3 as defined in the description and S * a mono or polysaccharide. The invention relates in particular to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined below as a whitening, lightening and / or depigmenting agent for keratinous substances, in particular the skin.

Description

@) The present invention relates to a cosmetic treatment process for keratin materials, comprising the application to them, such as the skin, of a composition comprising a compound (I)

FR 3 073 144 - A1

O (I)

With R1, R2 and R3 as defined in the description and S * a mono or polysaccharide.

The invention relates in particular to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined below as a whitening, lightening and / or depigmenting agent for keratin materials, in particular of the skin.

PROCESS FOR THE TREATMENT OF KERATINIC MATERIALS FROM AMIDE C-GLYCOSIDE DERIVATIVES, AND THE COSMETIC COMPOSITION CONTAINING THEM

The present invention relates to the cosmetic use of compounds derived from glycoside amides, in particular their use for depigmenting and / or bleaching keratin materials and in particular the skin, of new derivatives, the compositions in particular the cosmetic compositions which contain them. . At different times in their life, some people see darker and / or more colored spots appear on the skin and more particularly on the hands and face, giving the skin heterogeneity. These spots are due in particular to a high concentration of melanin in the keratinocytes located on the surface of the skin.

The use of harmless topical depigmenting substances with good efficacy is particularly sought in order to treat pigment spots.

The mechanism for the formation of skin pigmentation, i.e. the formation of melanin, is particularly complex and schematically involves the following main stages:

Tyrosine -> Dopa -> Dopaquinone -> Dopachrome -> Melanin

Tyrosinase (monophenol dihydroxyl phenylalanine: oxygen oxidoreductase EC 1.14.18.1) is the essential enzyme involved in this series of reactions. It catalyzes in particular the reaction of transformation of tyrosine into Dopa (dihydroxyphenylalanine) thanks to its hydroxylase activity and the reaction of transformation of Dopa into dopaquinone thanks to its oxidase activity. This tyrosinase only works when it is maturing under the action of certain biological factors.

A substance is recognized as 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 stages of melanin biosynthesis either by inhibiting one of the enzymes involved in melanogenesis, or by intercalating as a structural analogue of one of the chemical compounds in the melanin synthesis chain, a chain which can then be blocked and thus ensure depigmentation.

Arbutin and kojic acid are known as depigmenting agents for the skin. We have looked for substances which have an effective depigmenting action.

There nevertheless remains the need for a new whitening agent for keratin materials and in particular for human skin which is stable in a composition, easily formulated in particular in aqueous formulations, or alternatively which has a reinforced action so that it can be used in lower amount, which greatly decreases the side effects that can be observed.

In this regard, the Applicant has surprisingly and unexpectedly discovered that amide C-glycoside derivatives exhibited good depigmenting activity, even at low concentration, without showing cytotoxicity.

A first object of the invention is a method of cosmetic treatment of keratin materials, in particular of the skin, using at least one compound of formula (I) as defined below or a cosmetic composition containing 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 (la ¹ ), (la ² ), (IBB) , (lb ¹ ), (lb ² ) and / or (le) and even more particularly of at least one compound 1 to 21 defined below, as a whitening, lightening and / or depigmenting agent for keratin materials, in particular skin.

The subject of the invention is also a method of non-therapeutic cosmetic treatment of depigmentation, lightening and / or bleaching of keratin materials, in particular of 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 (la ¹ ), (la ² ), (IBB), (lb ¹ ), (lb ² ) and / or (le) and even more particularly of at least one compound 1 to 21 as defined below or of a composition containing it.

A subject of the invention is also the dermatological use of at least one compound of formula (I) as defined below, in particular of at least one compound of formula (la ¹ ), (la ² ), (IBB ), (lb ¹ ), (lb ² ) and / or (le) and even more particularly of at least one compound 1 to 21 for them to depigment the skin, to lighten and / or whiten it.

The compounds of formula (I) in accordance with the invention, as defined below, in particular the compounds of formula (la ¹ ), (la ² ), (IBB), (lb ¹ ), (lb ² ) and / or (le) and even more particularly the compounds 1 to 21, make it possible to depigment and / or to lighten effectively, or even to whiten, keratin materials, in particular the skin of human beings. They are in particular intended to be applied to the skin of individuals having brownish pigmentation spots, spots of senescence, or to the skin of individuals wishing to combat the appearance of a brownish color originating from melanogenesis.

By keratin materials within the meaning of the present invention, is meant keratin materials of human beings, and in particular the skin, hair, eyelashes, hair, lips and nails of human beings.

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

More particularly, keratin materials designate the skin of human beings.

A subject of the invention is also the new compounds of formula (la ¹ ), (la ² ), (IBB), (lb ¹ ), (lb ² ) and / or (le) as defined below.

The subject of the invention is likewise a cosmetic composition comprising, in a physiologically acceptable medium, at least one compound of formula (I) as defined below, in particular at least one compound of formula (la ¹ ), (la ² ), (IBB), (lb ¹ ), (lb ² ) and / or (le) and even more particularly at least one compound chosen from compounds 1 to 21 described below.

Compounds of formula (I)

The subject of the invention is therefore the non-therapeutic cosmetic use of at least one compound of formula (I) as a whitening, lightening and / or depigmenting agent for keratin materials, in particular of the skin, said compounds corresponding to formula (I) ) next :

(l) as well as its solvates such as hydrates, its optical, geometric isomers, tautomers and its base or acid salts, organic or inorganic, formula (I) in which:

- S * denotes a monosaccharide sugar radical or denotes a polysaccharide sugar radical comprising from 2 to 5 saccharide unit (s), preferably from 2 to 3 saccharide unit (s) preferentially S * denotes a sugar radical comprising 1 or 2 saccharide unit (s) (monosaccharide or disaccharide), 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 optionally substituted hydroxy groups (s) by a radical R 'chosen from:

i) (Ci-Ce) alkyl; or ii) (C2-Ce) alkenyl; or iii) an acetyl radical; or iv) a protective group (PG) of hydroxy function (s) such as (C2C6) alkyl (thio) carbonyl or benzyl;

said monosaccharide or polysaccharide radical which may also comprise one or more amino groups NRbRc with Rb and R _c , identical or different, representing a hydrogen atom, or an acetyl group, or a group protecting the amino function such as (C2 C6) alkyl (thio) carbonyl;

said mono or polysaccharide radical being linked to the rest of the molecule by a bond between the carbon atom Ci of one of the sugars of said mono or polysaccharide radical, this bond possibly being anomeric a or β;

- R3 represents

i) a hydrogen atom; or ii) a (Ci-Cis) alkyl group; or iii) a (C2-Cis) alkenyl group; or iv) a hydroxy (PG) protecting group such as (C1Ci8) alkyl (thio) carbonyl, such as an acetyl group, (C2Ci8) alkenyl (thio) carbonyl or aryl (Ci-C4) alkyl radical optionally substituted in particular with at least one hydroxy and / or (C1-C4) saturated or unsaturated alkoxy group;

- Ri represents

i) a hydrogen atom; or ii) a (Ci-Cis) alkyl group; or iii) a (C2-Cis) alkenyl group;

- R2 represents

i) an optionally substituted aryl or hereroaryl radical; or ii) a radical of formula (B1):

or :

Rh and Rk independently of one another denote a hydrogen atom or a methyl radical, it being understood that Rh and Rk cannot simultaneously denote a methyl radical y = 1 to 10, limits included iii) a radical of formula (B2):

(B2) in which:

- i = 0 or 1;

R4 represents

i) a hydrogen atom, or ii) a radical chosen from the radicals (a1) to (a32) described below:

me ^ ★ NH AT / ; H, N N ★ 0 • HO O - JV · 'h ₂ n; OH HO. xA  Me (A1) ^H (a2) (A3) (A4) (a5) ( ^a6 )

Me

(A13)

Me (a18)

(a19) (a20) (a21) (a22)

O

(a23) (a24) (θ25)

(A26)

Me

(a27) (a28) (a29) (a30)

Me (a32) or iii) R4 can also form, with Ri and the nitrogen atom which carries Ri, a saturated heterocycle of formula A1, or A2 or A3:

Rô means

i) a hydroxy radical -OH; or ii) an alcoholate -O; M ⁺ with M ⁺ representing a cation such as zinc (Zn ²⁺ ), manganese (Mn ²⁺ ), copper (Cu ²⁺ ), iron (Fe ²⁺ , Fe ³⁺ ), or an alkaline cation such as Na ⁺ , K ⁺ , or an alkaline earth cation such as Mg ²⁺ , Ca ²⁺ ), or an ammonium cation; or iii) a saturated or unsaturated (Ci-Ce) alkoxy radical; or iv) a radical -NRfR _g with Rf and R _g , identical or different, representing a hydrogen atom, or a (Ci-Ce) alkyl group.

In the context of the present invention, the asterix "*" denotes the point of attachment of the radical with the rest of the compound.

Preferably the hydroxy radicals of the radical S * are not substituted or are all substituted by the same group R ’as defined above, in particular by an acetyl group.

Preferably the optional amino group (s) NRbRc of the radical S * denote (s) NHRb with Rb denoting all a hydrogen atom or all an acetyl group.

More preferably, the hydroxy radicals of the S * radical are not substituted, the optional amino group (s) NRbRc of the S * radical denotes NHRb with Rb all denoting a hydrogen atom or all a acetyl group, and R3 represents a hydrogen atom, a (Ci-Cis) alkyl group, a (C2-Cis) alkenyl group, or an acetyl group.

Preferably, S * denotes a monosaccharide sugar radical chosen from glucose and xylose. More particularly, S * denotes a sugar chosen from D-glucose and D-xylose, said radical S * being linked to the rest of the molecule (I) by a bond with the carbon atom C ¹ of the sugar and this bond can be anomeric a or β.

Preferably, R3 represents a hydrogen atom or an acetyl radical; Ri represents a hydrogen radical or a C1-C18 alkyl, linear or branched, saturated or unsaturated, preferably C1-C16 such as methyl.

More preferably, R3 represents a hydrogen atom or an acetyl radical; R 1 represents a hydrogen radical, and R 2 an aryl radical optionally substituted by a phenyl radical substituted by one or more groups chosen from methoxy, hydroxy, carboxy, acetyloxy and / or benzyloxycarbonyl.

In particular, S * denotes a monosaccharide sugar radical chosen from glucose and xylose, in particular chosen from D-glucose and D-xylose; R3 represents a hydrogen atom; Ri represents a hydrogen atom or a C1-C18 alkyl radical, linear or branched, saturated or unsaturated, preferably C1-C16 such as methyl, and R2 denotes a radical of formula (B2):

(B2) in which i = 0 or 1,

R6 represents an ethoxy, hydroxy or NH2 radical,

R4 represents a hydrogen atom, and when i = 0, R4 represents a hydroxymethyl radical of formula (a5)

HO ^ * (a5) or, R4 can form with Ri and the nitrogen atom which carries Ri, a saturated heterocycle of formula A2:

H

A2

In particular, S * denotes a monosaccharide sugar radical chosen from glucose and xylose, preferably having hydroxy groups at C3, and C4 and, where appropriate, C6 substituted by an acetyl group; R3 represents a hydrogen atom; Ri represents a hydrogen atom or a C1-C18 alkyl radical, linear or branched, saturated or unsaturated, preferably C1-C16, more preferably C1-C6 such as methyl, and R2 represents a radical (B2):

in which i = 0 or 1, R6 represents a methoxy or ethoxy radical, R4 represents a hydrogen atom, and when i = 0, R4 represents a hydroxymethyl radical of for

mule (a5) (a5) or, R4 can form with Ri and the nitrogen atom which carries Ri, a saturated heterocycle of formula A2:

H

A2

Within the meaning of the present invention, and unless a different indication is given:

saturated or unsaturated rings, optionally condensed, can also be optionally substituted;

the “alkyl” radicals are saturated, linear or branched hydrocarbon radicals, generally C1-C18, particularly C1-C10, preferably C1-C6 alkyl radicals; as C1-C14 alkyl group, mention may in particular be made of methyl, ethyl, isopropyl, n-propyl, n-butyl, t-butyl, isobutyl, sec-butyl, pentyl, isopentyl, neopentyl, n-hexyl, n- groups. heptyl and octyl;

the “alkenyl” or “alkenyl” radicals are hydrocarbon radicals, linear or branched, C 2 -C 18 unsaturated; preferably comprising one or more double bonds, conjugated or not, such as ethylene, propylene, butylene, pentylene, methyl-2-propylene, prenyl and decylene;

the “aryl” radicals are mono or polycyclic carbon radicals, condensed or not, preferably comprising from 6 to 30 carbon atoms and of which at least one ring is aromatic; preferably chosen from the aryl radical is a phenyl, biphenyl, naphthyl, indenyl, anthracenyl, and tetrahydronaphthyl; more preferably aryl denotes phenyl, the “alkoxy” or “alkoxy” radicals are alkyl-oxy radicals with alkyl as defined above, the alkyl part of the alkoxy is generally C1-C18, preferably CiCw, such as methoxy , ethoxy, propoxy and butoxy, when unsaturated is mentioned this implies that the alkoxy group may represent an alkenyl-oxy group with alkenyl as defined above;

the “cycloalkyl” radicals are C4-C8 cycloalkyl radicals, preferably the cyclopentyl and cyclohexyl radicals; the cycloalkyl radicals can be cycloalkyl radicals substituted, in particular by alkyl, alkoxy, carboxylic acid, hydroxy, amine and ketone groups;

the “heterocycloalkyl” radicals are heterocyclic radicals comprising from 4 to 8 members, saturated or partially unsaturated, non-aromatic, which comprise from 1 to 3 heteroatoms in particular chosen from oxygen, sulfur and nitrogen, preferably morpholino radicals, piperazino and piperidino; the heterocycloalkyl radicals can be radicals substituted, in particular by alkyl, alkoxy, carboxylic acid, hydroxy, amine and ketone groups;

the “aryl” or “heteroaryl” radicals can be substituted by at least one atom or group carried by at least one carbon atom, chosen from:

i) (Ci-Cio) alkyl, preferably Ci-Cs, optionally substituted by one or more radicals chosen from hydroxy radicals, (Ci-C4) optionally unsaturated alkoxy, (poly) hydroxy-C2-C4 alkoxy, acylamino, amino substituted by two identical or different C1-C4 alkyl radicals, optionally carrying at least one hydroxy group or, the two radicals being able to form, with the nitrogen atom to which they are attached, a heterocycle comprising from to 7 chain links, preferably 5 or 6 chain links, saturated or unsaturated optionally substituted optionally comprising another heteroatom identical or different from nitrogen;

ii) halogen;

iii) hydroxy;

iv) C1-C4 alkoxy;

v) C1-C10 alkoxycarbonyl;

vi) C2-C4 (poly) hydroxyalkoxy;

vii) C2-C4 alkylcarbonyloxy, preferably -O-acetyl or acetyloxy;

viii) 5- or 6-membered heterocycloalkyl;

ix) 5 or 6-membered heteroaryl, and optionally substituted by a (C1-C4) alkyl radical, preferably methyl;

x) amino substituted by one or two identical or different C1-C6 alkyl radicals optionally carrying at least: a) a hydroxy group, b) amino optionally substituted by one or two C1-C3 alkyl radicals optionally substituted , said alkyl radicals being able to form, with the nitrogen atom to which they are attached, a heterocycle comprising from 5 to 7 members, saturated or unsaturated optionally substituted optionally comprising at least one other heteroatom different or not from nitrogen, c) a quaternary ammonium group -N ⁺ R'R ”R '”, Q' for which R ', R ”, R'”, identical or different represent a hydrogen atom, or a C1-C4 alkyl group; and Q 'represents the anionic counterion such as the halide, d) a heteroaryl radical with 5 or 6 members, and optionally substituted by a (C1-C4) alkyl radical, preferably methyl;

xi) acylamino (-N (R) -C (O) -R ') in which the radical R is a hydrogen atom, a C1-C4 alkyl radical optionally carrying at least one hydroxy group and the radical R 'is a C1-C2 alkyl radical;

xii) carbamoyl ((R) ₂ NC (O) -) in which the radicals R, which may or may not be identical, represent a hydrogen atom, a C1-C4 alkyl radical optionally carrying at least one hydroxy group;

xiii) alkylsulfonylamino (R'S (O) ₂ -N (R) -) in which the radical R represents a hydrogen atom, a C1-C4 alkyl radical optionally carrying at least one hydroxy group and the radical R 'represents a C1-C4 alkyl radical, a phenyl radical;

xiv) aminosulfonyl ((R) ₂ NS (O) ₂ -) in which the radicals R, which may or may not be identical, represent a hydrogen atom, a C1-C4 alkyl radical optionally carrying at least one hydroxy group, xv ) carboxy in acid or salified form (preferably with an alkali metal or ammonium, substituted or not);

xvi) cyano;

xvii) benzyloxycarbonyl;

xviii) polyhaloalkyl, preferably trifluoromethyl;

xix) a phenylcarbonyloxy group optionally substituted by one or more hydroxy groups; and xx) a phenyl group optionally substituted by one or more hydroxy groups;

the “heteroaryl” radicals are radicals comprising in at least one ring one or more heteroatoms particularly chosen from O, N and S, preferably O or N, optionally substituted by in particular one or more alkyl, alkoxy, carboxy, hydroxy, amine groups or ketone, and at least one cycle of which is aromatic. These rings can contain one or more oxo groups on the heteroaryl carbon atoms; among the heterocyclic radicals which can be used, mention may in particular be made of the furyl, pyrannyl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyridyl, thienyl, pyrimidinyl groups; optionally, the heterocyclic groups are condensed groups such as benzofurannyl, chromenyl, xanthenyl, indolyl, isoindolyl, quinolyl, isoquinolyl, chromannyl, isochromannyl, indolinyl, isoindolinyl, coumarinyl, isocoumarinyl groups, these groups possibly being substituted, in particular by one or several OH groups; the “protective group” or “PG” of the “hydroxy” or “amino” function is known to a person skilled in the art, the two works “Protective Groups in Organic Synthesis”, TW Greene, John Willey & Sons ed ., NY, 1981, pp. 193-217; “Protecting Groups”, P. Kocienski, Thieme, 3 ^rd ed., 2005. In particular, the protective group is chosen from:

(C1-C6) alkyl (thio) carbonyl such as formyl, acetyl or t-butylcarbonyl;

(di) (tri) halo (Ci-C6) alkyl (thio) carbonyl such as trifluoroacethyl (TFA);

(Ci-C6) alkoxy (thio) carbonyl such as methoxycarbonyl, ethoxycarbonyl, isobutyloxycarbonyl, t-butyloxycarbonyl (BOC), vinyloxycarbonyl, allyloxycarbonyl;

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

(C1-C6) alkylthio-thiocarbonyl;

(Di) (tri) halo (Ci-C6) alkylthio-thiocarbonyl;

(di) (C1-C6) (alkyl) aminocarbonyl;

(Di) (Ci-C6) (alkyl) aminothiocarbonyl;

arylcarbonyl optionally substituted as phenylcarbonyl, 2,4,6trimethylphenylcarbonyl;

optionally substituted aryloxycarbonyl such as p-nitrophenoxycarbonyl;

aryl (Ci-C6) optionally substituted alkoxycarbonyl such as benzyloxycarbonyl or Cbz, p-methoxy-benzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, o-nitrobenzyloxycarbonyl, p-nitrobenzyl-oxycarbonyl, 2bromobenzyloxycarbonyl (2-bromo-benzyloxycarbonyl) -oxycarbonyl (2chloro-Z), 4-nitrobenzyloxycarbonyl (nitro-Z), heteroaryl (Ci-C6) alkoxycarbonyl such as 9-fluorenylmethoxycarbonyl (FMOC) or nicotinoyl;

(di) (C1-C6) (alkyl) aminocarbonyl such as dimethylaminocarbonyl;

(C1-C6) (alkyl) arylaminocarbonyl;

carboxy;

optionally substituted aryl such as phenyl, dibenzosuberyl, or 1,3,5-cycloheptatrienyl;

optionally substituted heteroaryl; including in particular the cationic or non-cationic heteroaryl, comprising from 1 to 4 following heteroatoms:

i) 5-, 6- or 7-membered monocyclics such as furanyl or furyl, pyrrolyl or pyrryl, thiophenyl or thienyl, pyrazolyl, oxazolyl, oxazolium, isoxazolyl, isoxazolium, thiazolyl, thiazolium, isothiazolyl, isothiazolium, 1,2,4-triazol 1,2,4-triazolium,

1.2.3- triazolyl, 1,2,3-triazolium, 1,2,4-oxazolyle, 1,2,4-oxazolium, 1,2,4-thiadiazolyle,

1.2.4- thiadiazolium, pyrylium, thiopyridyl, pyridinium, pyrimidinyl, pyrimidinium, pyrazinyl, pyrazinium, pyridazinyl, pyridazinium, triazinyl, triazinium, tetrazinyl, tetrazinium, azepine, azepinium, azepinazinepinazinepinazinepinazinepinazinepinazin, epinephinyl, epinephinyl, epinephine, epinephine

ii) 8 to 11-membered bicyclics such as indolyl, indolinium, benzoimidazolyl, benzoimidazolium, benzoxazolyl, benzoxazolium, dihydrobenzoxazolinyl, benzothiazolyl, benzothiazolium, pyridoimidazolyl, pyridoimidazolium, thienocycloheptadienyl groups, or thienocycloheptadienic groups) C1-C4) alkyl as methyl, or polyhalo (C1-C4) alkyl as trifluoromethyl;

iii) or following tricyclic ABC:

in which the two rings A, Ç optionally comprise a heteroatom, and the ring B is a 5, 6 or 7-membered ring, particularly 6-membered and contains at least one heteroatom such as pypéridyle, pyranyl;

optionally substituted heterocycloalkyl, optionally cationic, the heterocycloalkyl group represents in particular a saturated or partially saturated monocyclic group with 5, 6 or 7 members comprising from 1 to 4 heteroatoms chosen from oxygen, sulfur and nitrogen, such as di / tetrahydrofuranyl , di / tetrahydrothiophenyl, di / tetrahydropyrrolyl, di / tetrahydropyranyl, di / tetra / hexahydrothiopyranyl, dihydropyridyl, piperazinyl, piperidinyl, tetramethylpiperidinyl, morpholinyl, di / tetra / hexahydroetyrin groups tetra / hexahydroazin CI14

C4) alkyl, oxo or thioxo preferably tetrahydropyranyl THP; where the heterocycle represents the following grouping:

<\ JCR ' ^e R'%

N ^k /

R ' ^d

Andans which R ' ^c , R' ^d , R ' ^e , R' ^f , R ' ⁹ and R' ^h , identical or different represent a hydrogen atom or a group (Ci-C4) alkyl, or then two group R ' ⁹ with R' ^h , and / or R ' ^e with R' ^f form an oxo or thioxo group, or else R ' ⁹ with R' ^e together form a cycloalkyl; and v represents an integer inclusive between 1 and 3; preferably R ' ^c to R' ^h represent a hydrogen atom; and An ^- represents a counterion;

isothiouronium -C (NR ' ^c R' ^d ) = N ⁺ R ' ^e R'^f; An ^- with R ' ^c , R' ^d , R ' ^e and R' ^f , identical or different, represent a hydrogen atom or a (CiC4) alkyl group; preferably R ' ^c to R' ^f represent a hydrogen atom; and An ^- represents a counterion;

isothiourea -C (NR ' ^c R' ^d ) = NR '^e; with R ' ^c , R' ^d and R ' ^e as defined above;

(di) aryl (Ci-C4) alkyl or triaryl (Ci-C4) optionally substituted alkyl such as 9-anthracenyl-methyl, phenylmethyl (benzyl), diphenylmethyl or triphenylmethyl optionally substituted by one or more groups chosen in particular from halogen, (Ci -C4) alkyl, (Ci-C4) alkoxy such as methoxy, hydroxy, (Ci-C4) alkylcarbonyl, (di) (Ci-C4) (alkyl) amino such as dimethylamino, nitro;

(di) heteroaryl (Ci-C4) akyl or triheteroaryl (Ci-C4) akyl optionally substituted, the heteroaryl group is in particular, cationic or not, monocyclic, comprising 5 or 6 members and from 1 to 4 heteroatoms chosen from nitrogen, oxygen and sulfur, such as the pyrrolyl, furanyl, thiophenyl, pyridyl, pyridyl N-oxide groups such as 4-pyridyl or 2-pyridyl-Nooxide, pyrylium, pyridinium, triazinyl, optionally substituted by one or more groups such that particularly methyl alkyl, advantageously the (di) heteroaryl (C1-C4) akyl is (di) heteroarylmethyl or (di) heteroarylethyl;

CR ¹ R ² R ³ with R ¹ , R ² and R ³ 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:

- (C1-C4) alkyl such as methyl;

- (Ci-C4) alkoxy;

- optionally substituted aryl such as phenyl optionally substituted by one or more groups such as (Ci-C4) alkyl, (Ci-C4) alkoxy, hydroxy;

- optionally substituted heteroaryl such as thiophenyl, furanyl, pyrrolyl, pyranyl, pyridyl, optionally substituted by a (CiC4) alkyl group;

- P (Z ¹ ) R ' ¹ R' ² R ' ³ with R' ¹ , and R ' ² identical or different represent a hydroxy group, (Ci-C4) alkoxy or alkyl, R' ³ represents a hydroxy group or ( C1-C4) alkoxy, and Z ¹ represents 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-methylethoxy-carbonyl (Adpoc);

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

(tri) (di) halo (C1-C4) alkyl such as 2,2,2-trichloroethyl;

ReRrRgSi- with R _e , Rf, and R _g , identical or different, representing a group (Ci-Ce) alkyl, optionally substituted aryl, (di) aryl (Ci-C4) optionally substituted alkyl, triaryl (Ci-C4) alkyl optionally substituted, such as benzyl, in particular chosen from trimethylsilyl or TMS, triethylsilyl, isopropyldimethylsilyl, terbutyldimethylsilyl or TBDMS, (triphenylmethyl) dimethylsilyl, t-butyldiphenylsilyl, methyldiisopropylsilyl, methyl (di-tyl) triisopropylsilyl, triphenylsilyl;

or then two contiguous hydroxy groups can be protected by an alkylene group * -C (R ') (R ^m ) - (C (R ^k ) (R ^j )) q- * as drawn below:

OH

with R ^j , R ^k , R ¹ , and R ^m , identical or different, representing a hydrogen atom or a (Ci-C4) alkyl, (poly) halo (Ci-C4) alkyl, optionally substituted aryl group such as phenyl, aryl (Ci-C4) alkyl such as benzyl, (poly) halo (Ci-C4) alkoxy, (Ci-C4) alkoxy, halogen, (di) (CiC4) (alkyl) amino, hydroxy, or both groups R ^j and R ^k and / or R ¹ , and R ^m together with the carbon atom which carry them form an oxo group or a (hetero) clycloalkyl 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, cycloheptylidene, benzylidene, p-methoxybenzylidene, 2,4-dimethoxybenzylidene, methoxymethylene and ethoxymethylene;

For the purposes of the present invention, the term “compound of formula (I)” or “compound of formulas (la ¹ ), (la ² ), (IBB), (lb ¹ ), (lb ² ) and / or (le)” means or compound 1 to 21 the compounds as defined in the present description, as well as their solvates such as hydrates, their optical, geometric isomers, their tautomers, their base salts or of organic or inorganic acid.

Acceptable solvates for the compounds used in the present invention include conventional solvates such as those formed in the last step of preparing said compounds due to the presence of solvents. By way of example, mention may be made of solvates due to the presence of water (hydrates) or of linear or branched alcohols such as ethanol or isopropanol.

The salts of the compounds (I) which comprise at least one acid function can be chosen from metal salts, for example aluminum (Al ³⁺ ), zinc (Zn ²⁺ ), manganese (Mn ²⁺ ) or copper (Cu ²⁺ ), alkaline salts, for example lithium (Li ⁺ ), sodium (Na ⁺ ) or potassium (K ⁺ ), or alkaline earth, for example calcium (Ca ²⁺ ) or magnesium (Mg ²⁺ ). It can also be ammonium derivatives of formula NH ₄ ⁺ or organic salts such as ammoniums of formula Y3NIT, NY3 denoting an organic amine, the radicals Y being identical or different, two or three radicals Y being able to form two to two a cycle with the nitrogen atom which carries them or NY3 can designate an aromatic amine. The organic amines are, for example, alkylamines, such as for example methylamine, dimethylamine, trimethylamine, triethylamine or ethylamine, or hydroxyalkylamines, such as for example 2hydroxyethylamine, bis- (2-hydroxyethyl) amine or tri - (2-hydroxyethyl) amine, or cycloalkylamines, for example bicyclohexylamine or glucamine, piperidine, or pyridines and the like, for example collidine, quinine or quinoline, or basic amino acids, such as for example lysine or arginine;

The salts of the compounds of formula (I) which comprise at least one amine function can also be salts of 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 lacking acid.

In the case where the compounds according to the invention are in the form of a salt, the cations are of course found in an amount ensuring the electroneutrality 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 be advantageously chosen from the metal salts Cu ²⁺ , Mn ²⁺ and Zn ²⁺ , the alkaline salts Li ⁺ , Na ⁺ and K ⁺ and the alkaline earth salts Ca ²⁺ and Mg ²⁺ . According to another variant, the salts of the compounds of formula (I) according to the invention which comprise at least one acid function can be advantageously chosen from ammoniums, preferably from amino acid salts of basic character such as for example lysine or arginine or from the salts of diethanolamine or triethanolamine.

Preferably, the compounds (I) which comprise at least one acid function are in the form of sodium salts Na ⁺ .

Preferably, the compounds (I) which comprise at least one acid function are in the form of potassium salts K ⁺ .

Preferably, the compounds (I) which comprise at least one acid function are in the form of calcium salts Ca ²⁺ .

According to a particular embodiment of the invention, the compounds of formula (I) are such that, taken together or separately, R3 represents a hydrogen atom, and Ri represents a hydrogen atom or a group (Ci-Cisjalkyle, preferably methyl, and R2 represents an aryl or hereroaryl radical, optionally substituted, preferably by one or more groups, identical or different, (Ci-C6) alkyl, hydroxy, C1-C4 alkoxy, C1-C6 alkoxycarbonyl, or carboxy.

According to this embodiment, S * preferably also denotes a monosaccharide sugar radical chosen from glucose and xylose, in particular chosen from D-glucose and D-xylose;

According to another particular embodiment of the invention, the compounds of formula (I) are such that, taken together or separately, R3 represents a hydrogen atom, and / or Ri represents a hydrogen atom or a group (Ci -Ci8) alkyl, preferably methyl, and / or R2 represents a radical (B1) as follows:

(B1) where:

Rh and Rk independently of one another denote a hydrogen atom or a methyl radical, it being understood that Rh and Rk cannot simultaneously denote a methyl radical y = 1 to 10, limits included.

According to this embodiment, S * preferably also denotes a monosaccharide sugar radical chosen from glucose and xylose, in particular chosen from D-glucose and D-xylose;

According to another particular embodiment of the invention, the compounds of formula (I) are such that, taken together or separately, R3 represents a hydrogen atom, and Ri represents a hydrogen atom or a group (Ci-Ci8 ) alkyl, preferably methyl, and R2 represents the following radical (B2):

or :

- i = 0 or 1;

R4 represents a hydrogen atom, or is chosen from the radicals (a1) to (a32) described below

Me

(A13)

Me (a18)

O

(a21) (a22)

O

(A23)

Me

(a27) (a28) (a29) (a30)

OH

Me * (a31)

(A32)

F? 4 can also form, with Ri and the nitrogen atom which carries Ri, a saturated heterocycle of formula A1, A2 or A3:

A1 A2 A3

Rô means

i) a hydroxy radical -OH;

ii) an alcoholate -O; M ⁺ with M ⁺ representing a cation such as zinc (Zn ²⁺ ), manganese (Mn ²⁺ ), copper (Cu ²⁺ ), iron (Fe ²⁺ , Fe ³⁺ ), or an alkaline cation such as Na ⁺ , K ⁺ , or an alkaline earth cation such as Mg ²⁺ , Ca ²⁺ , or an ammonium cation;

iii) a saturated or unsaturated (Ci-Ce) alkoxy radical;

iv) a radical -NRfR _g with Rf and R _g , identical or different, representing a hydrogen atom, or a (Ci-Ce) alkyl group.

According to this embodiment, S * preferably also denotes a monosaccharide sugar radical chosen from glucose and xylose, in particular chosen from D-glucose and D-xylose;

It is understood that for the compounds of formula (I) as defined above when S * represents a monosaccharide radical then it may be in pyranose form (the sugar heterocycle which constitutes it is 6-membered) or furanose (the heterocycle sugar which constitutes it is 5-membered); and when S * represents a polysaccharide radical it comprises the chain of 2 to 5 identical or different saccharide units which may be in the form of furanose, or pyranose.

It is understood that for the compounds of formula (I) as defined above when S * represents a polysaccharide radical, preferably the polysaccharide is a disaccharide which results from the chain of 2 pyranose units or the chain of a saccharide unit in furanose form and of a unit in pyranose form or the chain of a saccharide unit in pyranose form and of a unit in furanose form;

whether for the monosaccharide or polysaccharide radical, each saccharide unit can be in the levorotatory L or dextrorotatory form, and in the anomeric form a or β.

According to a preferred embodiment, the sugar radical S * represents a monosaccharide radical of which the heterocycle which constitutes it contains 4 or 5 carbon atoms, of formula S * ’below:

R _a representing a hydrogen atom, a (Ci-C4) alkyl group such as methyl or a (poly) hydroxy (Ci-C ₄ ) alkyl group such as hydroxymethyl or di-hydroxy-1,2ethyl, the hydroxy function (s) of the poly) hydroxy (CiC ₄ ) alkyl group being substituted by A as defined below;

it being understood that the radical R _a is in position Cs if the sugar motif is in pyranose form or in C ₄ if it is in furanose form;

Rb representing a hydrogen atom or a (Ci-C ₄ ) alkyl group preferably hydrogen;

R _c representing a hydrogen atom, or a protecting group for the amine function such as Rd-C (X ') -, identical in the case of several hydroxyl functions, with X' representing an oxygen or sulfur atom, in particular an oxygen atom and Rd representing an (Ci-C ₄ ) alkyl group, preferably R _c representing an acetyl group CH3-C (O) -,

R _e represents a hydrogen atom or a group -CH2-OA;

A representing a hydrogen atom, an (Ci-Ce) alkyl group, or a hydroxy-protecting group such as Rd-C (X ') - as defined above and in particular acetyl CH3-C (O) -, or so when n is greater than or equal to 2 and two groups A-0 are contiguous then two groups A can together form a chain (Ci-Ce) alkylene, linear or branched;

preferably all the protecting groups of A are identical;

n is 1, 2 or 3 and m is 0 or 1.

Preferably, m is 0.

According to another preferred embodiment, the sugar radical S * represents a polysaccharide radical consisting of 2 to 5 saccharide units, in particular 2 to 3, and preferably 2 saccharide units, linked together via an oxygen atom (oxy ) at 1-> 4 (Ci of a saccharide unit -> C4 of the other saccharide unit) or 1-> 3 (Ci of a saccharide unit -> C3 of the other saccharide unit) or 1-> 6 (Ci of a saccharide unit -> Οβ of the other saccharide unit) each saccharide unit of which consists of a heterocycle comprising 4 or 5 carbon atoms, of formula S * ”below:

Formula S * ”in which p and q represent integers inclusive between 0 and 4 with p + q inclusive between 1 and 4, particularly between 1 and 2, preferably p + q = 1; R _a , identical or different, are as defined above, Rb, identical or different, are as defined above, R _c , identical or different, are as defined above, R _e , identical or different, are as defined above , A identical or different, are as defined above, m, identical or different, are as defined above, n, identical or different, are as defined above; it being understood that the two sugar patterns between the hooks q and p can be interchanged, ie represent the following sequence:

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

- S * represents a monosaccharide sugar radical chosen from: glucose, galactose, mannose, xylose, lyxose, fucose, arabinose, rhamnose, quinovose, fructose, sorbose, talose, N -acetylglucosamine, Nacetylgalactosamine, glucosamine, galactosamine; or a disaccharide chosen from: lactose, maltulose, palatinose, lactulose, tonsillosis, turanose, cellobiose, isomaltose, rutinose, maltose; more preferably S * represents a monosaccharide sugar radical chosen from glucose, and xylose. said radical S * comprising one or more radicals -OR _S and optionally one or two radicals -NHR ' _S , more preferably said radical S * comprising one or more radicals -OR _S , said mono or disaccharide radical being linked to the rest of the molecule by a bond between the carbon atom C ¹ of the sugar or of one of the sugars and this bond which can be anomeric a or β;

- R3 represents:

i) a hydrogen atom;

ii) an (Ci-Cis) alkyl group, preferably (Ci-Ce) alkyl such as methyl;

iii) a (C2-Cis) alkenyl radical, preferably (C2-C6) alkenyl such as prenyl;

iv) an aryl (Ci-C4) alkyl radical optionally substituted in particular by at least one hydroxy and / or (Ci-C4) saturated or unsaturated alkoxy group, in particular an aryl (Ci-C4) alkyl radical such as benzyl; or

v) or a (Ci-Cis) alkylcarbonyl radical, preferably (Ci-Ce) alkylcarbonyl, in particular acetyl (CH3-CO-);

- Ri represents a group chosen from:

i) a hydrogen atom; or ii) a saturated or unsaturated (Ci-Cis) alkyl group, preferably saturated and more preferably saturated with C1-C6 such as methyl;

- R2 represents a group chosen from:

i) an aryl or hereroaryl radical, optionally substituted, preferably by one or more groups, identical or different, (Ci-Ce) alkyl, hydroxy, C1-C4 alkoxy, C1-C6 alkoxycarbonyl, or carboxy; or ii) a radical of formula (B1) below:

Rh and Rk independently of one another denote a hydrogen atom or a methyl radical, it being understood that Rh and Rk cannot simultaneously denote a methyl radical, y = 1 to 10, preferably 1 to 3, bounds included;

iii) a radical of the following formula (B2):

or :

- i = 0 or 1;

R4 represents a hydrogen atom, or is chosen from the radicals (a1) to (a32) described below:

Me

(A13)

Me (a18)

(a19) (a20)

(A21)

(A22)

O

(a23) (a24) (325)

Me

(a27) (a28) (a29) (a30)

Me (a32) or R4 can also form, with Ri and the nitrogen atom which carries Ri, a saturated heterocycle of formula A1, A2 or A3:

Rô means

i) a hydroxy radical -OH; or ii) an alcoholate -O; M ⁺ with M ⁺ representing a cation such as zinc (Zn ²⁺ ), manganese (Mn ²⁺ ), copper (Cu ²⁺ ), iron (Fe ²⁺ , Fe ³⁺ ), or an alkaline cation such as Na ⁺ , K ⁺ , or an alkaline earth cation such as Mg ²⁺ , Ca ²⁺ , or an ammonium cation; or iii) a saturated or unsaturated (Ci-Ce) alkoxy radical; or iv) a radical -NRfR _g with Rf and R _g , identical or different, representing a hydrogen atom, or a (Ci-Ce) alkyl group;

- R _s represents a hydrogen atom or a methyl radical or an acetyl radical, said radicals R _s being preferably all identical and preferably designating a hydrogen atom or an acetyl radical;

- R ' _s represents a radical chosen from a hydrogen atom or an acetyl radical;

More preferably, the compounds of formula (I) are chosen from the compounds of formulas (I '), (I ”), (I” ”), (a), (l” a) and (l ”” a ) following:

9 ^r 3 Ri '

OR ¹ (I ·)

OR ¹

GOLD

(L)

(the)

as well as their solvates such as hydrates, their optical, geometric isomers, tautomers and their base or acid salts, organic or inorganic,

Formulas (! ’), (I”), (! ””), (A), (l ”a) and (l” ”a) in which:

- RT has the same definition as that of Ri for the compounds of formula (I); preferably R’i represents a hydrogen atom; a (Ci-Cis) alkyl radical, preferably C1-C4 alkyl and more preferably methyl; preferably RT represents a hydrogen atom

- R ₂ 'has the same definition as that of R ₂ for the compounds of formula (I); preferably R ' ₂ represents:

i) an aryl radical optionally substituted, preferably by one or more groups, identical or different, chosen from (Ci-Ce) alkyl, hydroxy, C1-C4 alkoxy, C1-C6 alkoxycarbonyl, or carboxy; preferably R ₂ 'represents an aryl radical substituted by one or more methoxy and / or hydroxy and / or carboxy;

ii) a following radical (B’2):

or :

- j = 0 or 1;

R’4 represents a hydrogen atom or is chosen from the radicals (a1) to (a32) described below:

H ₂ N

^H (a2)

Me ^ (a1)

Me

(A13)

Me (a18)

(a 19) (a20)

(A22)

O

(a23) (a24) ( ^a25 )

(A27)

OH

Me '' '' '' '' * (a31)

R’4 can also form with R’1 and the nitrogen atom which carries R’1, a saturated heterocycle of formula A1, A2 or A3:

R6 denotes

i) a hydroxy radical -OH; or ii) an alcoholate -O; M ⁺ with M ⁺ representing a cation such as zinc (Zn ²⁺ ), manganese (Mn ²⁺ ), copper (Cu ²⁺ ), iron (Fe ²⁺ , Fe ³⁺ ), or an alkaline cation such as Na ⁺ , K ⁺ , or an alkaline earth cation such as Mg ²⁺ , Ca ²⁺ , or an ammonium cation; or iii) a saturated or unsaturated (Ci-Ce) alkoxy radical; or iv) a radical -NRfR _g with Rf and R _g , identical or different, representing a hydrogen atom, or a (Ci-Ce) alkyl group.

preferably R'6 represents OH; O ', M ⁺ ; (Ci-Ce) saturated alkoxy, preferably methoxy or ethoxy, or NH ₂ .

- R3 ’has the same definition as that of R3 for the compounds of formula (I); preferably R’3 represents a hydrogen atom or an acetyl radical, and preferably a hydrogen atom;

- R ”represents

i) (Ci-Ce) alkyl; or ii) (C ₂ -Ce) alkenyl; or iii) an acetyl radical; or iv) a protective group (PG) of hydroxy function (s) such as (C ₂ C6) alkyl (thio) carbonyl or benzyl; or

v) a hydrogen atom;

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

- R '”represents a hydrogen atom, or a (Ci-C4) alkyl group, or a CH ₂ -OR” group with R ”as defined above in particular hydrogen or an acetyl radical, and preferably a d atom 'hydrogen.

According to a particular embodiment, the compounds of the invention are of formula (I ’). According to another particular embodiment of the invention, the compounds of the invention are of formula (I ”). According to another particular embodiment of the invention, the compounds of the invention are of formula (I "").

According to another particular embodiment of the invention, the compounds of the invention are of formula (a). According to another particular embodiment of the invention, the compounds of the invention are of formula (l ”a). According to another particular embodiment of the invention, the compounds of the invention are of formula (1 ”).

According to a particular embodiment S * and S * 'represent a monosaccharide radical chosen from glucose, galactose, mannose, xylose, lyxose, fucose, arabinose, rhamnose, ribose, deoxy-ribose , quinovose, fructose, sorbose, talose, threose, erythrose, N-acetylglucosamine, Nacétylgalactosamine, glucosamine, galactosamine, and in particular S * and S * 'represent a monosaccharide radical chosen from glucose, and xylose.

In particular, S * and S * 'represent a monosaccharide radical chosen from Dglucose, D-galactose, D-mannose, D-xylose, L-xylose, D-lyxose, Llyxose, L-fucose , L-arabinose, D-arabinose, L-rhamnose, L-ribose, Dribose, 2-deoxy-D-ribose, 2-deoxy-L-ribose, D-quinovose, D-fructose , Lsorbose, D-talose, D-threose, D-erythrose, L-threose, L-erythrose, Nacétyl-D-glucosamine, N-acetyl- D-galactosamine, D-glucosamine, Dgalactosamine. Preferably, S denotes a monosaccharide chosen from Dglucose, D-galactose, D-mannose, D-xylose, D-lyxose, L-fucose, Larabinose, L-rhamnose, D-ribose, 2-deoxy-D-ribose, D-quinovose, Dfructose, L-sorbose, D-talose, D-threose, D-erythrose, N-acetyl-Dglucosamine, N-acetyl- D- galactosamine, D-glucosamine, D-galactosamine, and in particular, S * and S * 'represent a monosaccharide radical chosen from Dglucose and D-xylose.

Advantageously, S * and S * ’represent a monosaccharide radical chosen from glucose, xylose, rhamnose, mannose and galactose or a disaccharide chosen from lactose, maltose and cellobiose. In particular, S * denotes a monosaccharide chosen from D-glucose, D-xylose, L-rhamnose, D-mannose, Dgalactose or a disaccharide chosen from D-lactose, D-maltose and D-cellobiose.

Preferably, S * and S * ’represent a sugar chosen from glucose, xylose and lactose. More particularly, S * and S * ’denote a sugar chosen from D-glucose, L-xylose and D-lactose. Preferably, S * and S * ’denote glucose or xylose. In particular, S * and S * ’denote D-glucose or D-xylose.

According to another particular embodiment S * and S * ”represent a polysaccharide and in particular a disaccharide chosen from lactose, maltulose, palatinose, lactulose, tonsillosis, turanose, cellobiose, isomaltose, rutinose, maltose.

According to a particular embodiment, the radical S * and S * ”represent a polysaccharide and in particular a disaccharide chosen from D-lactose, maltulose, palatinose, lactulose, tonsillosis, D-turanose, D-cellobiose , isomaltose, rutinose, D-maltose.

According to another particular embodiment, Fù and Fù ’represent respectively a radical (B2), respectively (B’2) such that:

R4 and R’4 independently represent a hydrogen atom or are independently chosen from the radicals (a1) to (a32) described below:

Me

(A13)

Me (a18)

(a19) (a20)

O

(a21) (a22)

O

(a23) (a24) (325)

Me

(a27) (a28) (a29) (a30)

Me (a32)

R4 (respectively R’4) can also form with Ri (respectively R’1) and with the nitrogen atom which carries Ri (respectively R’1) a saturated heterocycle of formula A1, or A2 or A3:

Rô and R’6 independently designate

i) a hydroxy radical -OH; or ii) an alcoholate -O; M ⁺ with M ⁺ representing a cation such as zinc (Zn ²⁺ ), manganese (Mn ²⁺ ), copper (Cu ²⁺ ), iron (Fe ²⁺ , Fe ³⁺ ), or an alkaline cation such as Na ⁺ , K ⁺ , or an alkaline earth cation such as Mg ²⁺ , Ca ²⁺ , or an ammonium cation; or iii) a saturated or unsaturated (Ci-Ce) alkoxy radical; or iv) a radical -NRfR _g with Rf and R _g , identical or different, representing a hydrogen atom, or a (Ci-Ce) alkyl group.

Preferably

R4 and R'4 represent a hydrogen atom when i = 1 or j = 1, and when i = 1 or j = 0, R4 and R'4 independently represent a hydrogen atom or a hydroxymethyl radical (a5): chosen from:

HO

R4 can form, with Ri and the nitrogen atom which carries Ri, a saturated heterocycle of formula A2:

A2

New compounds

The subject of the invention is also the compounds of formula (I) as defined above, with the exception of the following compound (D):

RN = [1087698-42-7]

In particular, the subject of the invention is the new compounds of formulas (la ¹ ), (la ² ), (IBB), (lb ¹ ), and (Ib ² ), and / or (le), as defined below -after.

Thus, the invention relates to the new compounds of formula (la ¹ ), as well as their solvates and / or isomers and / or salts:

(the ¹ )

Formula (la ¹ ) in which S *, Ri and R2 are as defined above.

Among the compounds of structure ( ^1a ), R2 denotes in particular an aryl or heteroaryl radical, optionally substituted (as defined above).

Preferably, S * denotes a sugar radical chosen from glucose or xylose. More particularly, S * denotes a sugar radical chosen from D-glucose or D-xylose.

Preferably, the hydroxy groups of S * are not substituted and the optional amino groups -NRbRc are such that Rb and Rc independently denote a hydrogen atom or an acetyl radical.

Preferably, Ri denotes a hydrogen atom or a C1-C4 alkyl group and more preferably methyl. Preferably, Ri denotes a hydrogen atom.

Preferably, R ₂ denotes an aryl radical, optionally substituted. More preferably, R ₂ denotes a phenyl radical, preferably substituted by one or more groups, identical or different, chosen from: (Ci-Ce) alkyl, hydroxy, C1-C6 alkoxy, C1-C6 alkoxycarbonyl, or carboxy.

In the case of a carboxy group, this can also be in the form of a COO'M ⁺ salt (carboxylate), with M ⁺ representing a cation such as zinc (Zn ²⁺ ), manganese (Mn ^{2 +} ), copper (Cu ²⁺ ), iron (Fe ²⁺ , Fe ³⁺ ) „an alkaline cation such as Na ⁺ , K ⁺ ) or an alkaline earth such as Mg ²⁺ , Ca ²⁺ , or an ammonium cation.

In particular, R ₂ represents a phenyl radical substituted by one or more methoxy and / or hydroxy and / or carboxy.

Among the new compounds of formula (la ¹ ), compound 1 (and / or its solvates and / or its salts) is particularly preferred:

S * compound structure D-slucose 1 OH OH H chiral The ^ O. • ^N / γ ^0Η L , p L ^ \ / OH HO ' OH OH 0

The invention also relates to the new compounds of formulas (la ² ), as well as their solvates and / or isomers and / or salts:

o (the ² )

Formula (la ² ) in which S *, Ri, R ₂ and R3 are as defined above, provided that the hydroxy groups of S * are substituted by the same radical as the radical R3. (R '= RsetRs does not represent a hydrogen atom).

Among the compounds of structure (la ² ), mention may be made in particular of the compounds for which R ₂ denotes an aryl or heteroaryl radical, optionally substituted (as indicated previously in the definitions of radicals).

Among the compounds of structure (la ² ), mention may be made in particular of the compounds for which S * denotes a sugar chosen from glucose or xylose. More particularly, S * denotes a sugar chosen from D-glucose or D-xylose.

The compounds of structure (la ² ) are in particular such that R3 represents an acetyl group, the hydroxy groups of S * and the optional amino groups are substituted by an acetyl group (-CO-CH3) (R3 = R '= R _c = acetyl, and Rb = H).

The compounds of formula (la ² ) are in particular such that R 1 denotes a hydrogen atom or a C1-C4 alkyl group such as methyl. Preferably, Ri denotes a hydrogen atom.

Preferably, R2 denotes an aryl radical. More preferably, R2 denotes a phenyl radical, preferably substituted by one or more groups, identical or different, chosen from: (Ci-Ce) alkyl, C1-C4 alkoxy, C2-C4 alkylcarbonyloxy, preferably-O-acetyl or acetyloxy (CH3-CO-O-), benzyloxycarbonyl, or carboxy. In the case of a carboxy group, this can also be in the form of a COO'M ⁺ salt (carboxylate), with M ⁺ representing a cation such as zinc (Zn ²⁺ ), manganese (Mn ²⁺ ), copper (Cu ²⁺ ), iron (Fe ²⁺ , Fe ³⁺ ), an alkaline cation such as Na ⁺ , K ⁺ , a cation or alkaline earth such as Mg ²⁺ , Ca ²⁺ , or an ammonium cation. In particular R2 represents a phenyl radical substituted by one or more methoxy and / or acetyloxy and / or benzyloxycarbonyl and / or carboxy radicals and more particularly acetyloxy and / or benzyloxycarbonyl and / or carboxy.

Among the compounds of formula (la ² ), the new compounds 2 and 3 (and / or their solvates and / or their salts) are more particularly preferred:

S * compound structure Pz glucose 2 ό ° ^r V'o ⁰ ^ Y ^OH ° <y '° °

Dglucose ο

ο

The invention also relates to the new compounds of formula (IBB):

OR, R

O (IBB) in which S *, Ri and R ₃ have the same definition as in formula (I).

- Rb2 represents

i) a substituted phenyl radical or an optionally substituted heroaryl radical; or ii) a radical of formula (B1):

R

(B1) in which:

Rh and Rk independently of one another denote a hydrogen atom or a methyl radical, it being understood that Rh and Rk cannot simultaneously denote a methyl radical y = 1 to 10, limits included iii) a radical of formula (B2):

(B2) in which:

- i = 0 or 1;

R4 represents a hydrogen atom or a radical chosen from the radicals (a1) to (a32) described below:

Me

(A13)

Me (a18)

(a19) (a20) _(a2 i) (a22)

O

(a23) (a24) ( ^a25 )

(a28) (a29) (a 30)

(A31)

Me (a32)

R4 can form with Ri and the nitrogen atom which carries Ri, a saturated heterocycle of formula A1, A2 or A3:

A1

A2

A3

Rô means

i) a hydroxy radical -OH;

ii) an alcoholate -O; M ⁺ with M ⁺ representing a cation such as zinc (Zn ²⁺ ), manganese (Mn ²⁺ ), copper (Cu ²⁺ ), iron (Fe ²⁺ , Fe ³⁺ ), or an alkaline cation such as Na ⁺ , K ⁺ , or an alkaline earth cation such as Mg ²⁺ , Ca ²⁺ , or an ammonium cation;

iii) a saturated or unsaturated (Ci-Ce) alkoxy radical;

iv) a radical -NRfR _g with Rf and R _g , identical or different, representing a hydrogen atom, or a (Ci-Ce) alkyl group.

Among the compounds of formula (IBB), mention may be made in particular of the compounds for which S * denotes a sugar radical chosen from glucose or xylose and more particularly the compounds for which S * denotes a sugar radical chosen from Dglucose or D-xylose.

According to a particular form of the invention, the new compounds of formula (IBB) are compounds of formula (lb ¹ ), as well as their solvates and / or isomers and / or salts:

(lb ¹ )

Formula (lb ¹ ) in which S *, Ri, R4, R6, and i are as defined above.

In particular, the compounds of formula (lb ¹ ) are such that S * denotes a sugar radical chosen from glucose or xylose and more particularly those for which S * denotes a sugar radical chosen from D-glucose or D-xylose.

Preferably, the hydroxy groups of S * are not substituted and the optional amino groups NRbRc are such that Rb and Rc independently denote a hydrogen atom or an acetyl radical.

Preferably, Ri denotes a hydrogen atom or a C1-C4 alkyl group and more particularly methyl. Preferably, Ri denotes a hydrogen atom.

Preferably R6 denotes a hydroxyl group or forms, with the carbonyl group in the alpha position, a carboxylate radical COO 'M ⁺ with M ⁺ as defined above, or again R6 denotes an alkoxy radical (C1-C4) such as methoxy or ethoxy, or R6 denotes an NH2 radical.

Preferably i = 0.

Preferably R4 represents a hydrogen atom when i = 1, and when i = 0, R4 represents a hydrogen atom or a hydroxymethyl radical (a5) (a5) or alternatively, R4 forms with Ri and the atom of nitrogen carrying Ri. a saturated heterocycle of formula A2:

A2

Among the compounds of structure (IBB) and of structure (lb ¹ ), mention may in particular be made of compounds 4 to 12 (and / or their solvates and / or their salts):

S * compound structure

Ρς glucose 4 OH HO '' ' OH nh ₂ OH O OH Ρς glucose 5 OH _χ Ο OH NOT O Y ^ nh ₂ HO OH s. OH 0 ^ 0 " D- 6 OH I OH glucose s Γ HO ' l k o OH _Ο ^ ^ΝΗ 2 OH Ρς glucose 7 OH ηο ^Λ OH O OH -Ν \ ^ γΝΗ ₂ O OH Ρς glucose 9 OH _x o OH H N ®OH HO '' ' OH ΌΗ O Ρς xvlose 10 J ? OH OH ° OH Ρς 11-dial OH .NOT O AT" xvlose J Y ¹ OH OH ° Ί NH ₂ ΌΗ Ρς xvlose ll-DIA2 i OH Λ AT O Y ^ nh ₂ HO '' Y OH '' 'ΌΗ AT

Pz xvlose 12 r ^o ? ïŸ ^o ^ HO '' γ '^ ΟΗ ⁰ oh OH Pz xvlose 13 OH O HO ^^^^ p ^ OH ⁰ OH OH

Among the new compounds of structure (IBB), mention may be made of the compounds of formula (lb ² ), as well as their solvates and / or isomers and / or salts:

Formula (lb ² ) in which S *, Ri, R3, R4, R6, and i are as defined above, provided that the hydroxy groups of S * are all substituted by the same group as in R3 (R '= R3 and Rs does not represent a hydrogen atom), with the exception of the C2 hydroxy group of S * which remains in free form (-OH).

In particular, the compounds of formula (lb ² ) are such that S * denotes a sugar radical chosen from glucose or xylose and more particularly such that S * denotes a sugar radical chosen from D-glucose or D-xylose.

Preferably, R3 represents an acetyl group, the hydroxy groups of S * and the optional amino groups are substituted by an acetyl group (-CO-CH3) (R3 = R '= R _c = acetyl, and Rb = H), except the C2 hydroxy group which remains in free form (-OH).

Preferably, Ri denotes a hydrogen atom or a C1-C4 alkyl group and more preferably methyl. Preferably, Ri denotes a hydrogen atom or a methyl radical.

Preferably F? 6 denotes a (C1-C4) alkoxy group and more particularly a methoxy or ethoxy radical, preferably ethoxy, or F? 6 denotes an amino radical NH ₂ .

Preferably i = 0.

Preferably R4 represents a hydrogen atom when i = 1, and when i = 0, R4 represents a hydrogen atom or a hydroxymethyl radical (a5):

HO ^ * (a5);

or again, R4 forms with Ri and the nitrogen atom which carries Ri a saturated heterocycle of formula A2:

H

A2

Among the new compounds of formula (IBB) and of formula (lb ² ), mention may in particular be made of compounds 14 to 21 (and / or their solvates and / or their salts):

S * compound structure Pz glucose 14 OO oL 0 ^ 0 _o A- V -OH ⁰ ° γ ° Pz glucose 15 ° L _Ο Λ 0 ^ 0 ₀ '''θ' T -OH ^OH ° γ °

Ρς glucose 16 OO A <A o Ww 0 ^ 0 ^OH HE glucose 17 WHERE? ? H î YïV ^ r ⁰ ^ VA ⁰ ° oO ^OH HE glucose 18 Λ Λ O Cj O i O ° ΑγΑ-'Λ · Μ. ï 1 OH ΟγΟ IT xvlose 19 O ^ 'O 0 ₀ A _O ..U „° ° ^H IT xvlose 20-dial O - ° LyS? '/' ⁰ ^ MAY k Oy ° IT xvlose 20-DIA2 o A ° _u o Α _Ο . · Μ ·, JA i OH θγ °

Among the new compounds of formula (IBB), there may also be mentioned the compounds of formula (Ie), as well as their solvates and / or isomers and / or salts:

CH ₃ (the)

Formula (Ic) in which S *, Ri, Rh, Rk and y are as defined above for the compounds of formula (I).

Preferably, the hydroxy groups of S * are not substituted and the optional amino groups -NRbRc are such that Rb and Rc independently denote a hydrogen atom or an acetyl radical.

Preferably there is between 1 and 5, more preferably between 1 and 3, limits included.

The preferred new compounds are compounds 1 to 21 described above.

Process for the preparation of the compounds of formula (I), in particular (la ¹ ), (la ² ), (lb ¹ ), and (lb ² ), (le), of the invention

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

Preparation process which comprises the following stages:

step 1 consisting in reacting a monosaccharide or a polysaccharide of formula (II) with a derivative of barbituric acid (III), in particular in the presence of an inorganic base such as ΜΌΙΤ, M ⁺ representing a cation such as Na + or K +, or preferably in the presence of a weak base such as (bi) carbonate, in particular with (bi) carbonate of alkali metal, or in the presence of organic base such as triethylamine or diisopropylethylamine,

Formula (II) in which A, R _a , Rb, Rc, Re, n, and m as defined above, p 'and q' representing an integer between 0 and 4 inclusive, with p '+ q' which is included inclusive between 0 and 4, in particular between 0 and 2, preferably p '+ q' = 0 or 1, it being understood that the two patterns in square brackets can be interchanged; the compound of formula (II) being represented in the diagram by:

step 1 being carried out in particular in a polar protic solvent such as water, optionally heating to a temperature between 30 ° C and 100 ° C, in particular to 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; to lead to the compound with a sugar motif (IV);

step 2 which then consists in reacting the compound (IV) with a chemical oxidizing agent such as hydrogen peroxide or a hydrogen peroxide generating agent such as oxone, in particular in a polar solvent of boiling point between 40 ° C and 100 ° C at atmospheric pressure, such as acetone or acetonitrile, or polar protic solvent such as water optionally in basic medium and / or in the presence of a chelating agent such as l ethylene diamine tetraacetic acid (EDTA) in the form of a salt or not, optionally heating to a temperature between 30 ° C. and 70 ° C., to lead to a compound C-glycoside amide (IA),

1) if R3 represents a hydrogen atom and it is desired that it represents a (Ci-Cis) alkyl, (C2-Cis) alkenyl or (C2-Cis) alkynyl group, or that the OH group is protected , then an alkylation step or a step for protecting the hydroxy function is carried out, if on the contrary R3 represents PG then it can be deprotected if it is desired to obtain a free hydroxy function;

2) if A represents a hydrogen atom and it is desired to have a PG then a protection step is added,

3) if Rb and R _c of NRbR _c represent hydrogen atoms and it is desired to protect the amino group (s), a protection step is carried out,

- Step 3 then consists in reacting the amide compound (IA) with an OH'M ⁺ base as defined above to lead to a C-glycoside carboxylate compound (IB); said compound (IB) can then follow 3 synthetic routes:

lane 1 which consists in reacting an anhydride (V) of formula R ^P -C (O) -OC (O) -R ^q with R ^p and R ^q , identical or different, representing a group (Ci-C4) alkyl such as methyl, (such that the anhydride is acetic anhydride), with the compound (IB) to lead by intramolecular reaction between the oxygen atom of group A-0 to C ² of the first motif sugar directly linked to the rest of the molecule on C = O after elimination of water to lead to compound (VI), this compound then being able to react according to step b) with an amine R1R2NH to lead to Cglycoside amide (IC);

lane 2 which consists in reacting the compound (IB) with an arylalkyl halide (VII): Ar (Ci-Ce) alkyl-Hal with Ar representing an aryl and Hal denotes a halide chosen from Cl, Br, F, I preferably (VII) represents a benzyl halide such as benzyl bromide, to lead to the glycoside ester (IE); this compound then being able to react according to step a) by dealkylarylation (debenzylation) such as by catalytic reduction such as hydrogenation with palladium on graphite to lead to acid C-glycoside (IF); this compound can then react according to step c) with an amine R1R2NH to lead to the Cglycoside amide (IC);

- route 3 which consists in neutralizing (IB) with an organic or mineral acid: to lead to the acid C-glycoside (IF);

it is understood that according to the wishes of substituents on the radicals R ′, A and NRbRc the options 1) to 3) mentioned in step 2 also apply to routes 1 and 2 and in steps a), b) and c ); preferably the same GP is used for the entire molecule; the compounds (IC) being contained in formula (I) according to the invention.

It is also understood that during the preparation of the reagent (II) steps 2), and 3) mentioned above can be applied to it.

Thus, for example, when the saccharide (II) is a D-glucose, the synthesis scheme for the corresponding amides (IC) (IC) gluc is as follows:

D-glucose 1,3-dimethylbarbituric acid

NaHCO ,,

H ₂ O

(IA) gluc

i. HN ^ Rj ii. possible protection

i. NaOH (il. H ⁺ )

(IB) gluc (or acid form) (IV) gluc

OH OH O * 1 ^N r ₂ ^ O HO OH OH

(IC) gluc

In this scheme, the intermediate (IB) gluc or the corresponding acid form obtained after acidification, denotes in particular the following compound (IB) glucose:

OH OH

OH (IB) glucose (or acid form) the compound (Vl) gluc designates in particular the following compound (Vl) glucose:

(VI) qlucose and the compound (IC) denotes in particular the following compound (IC) glucose:

(IC) glucose

According to the same principle, when the saccharide (II) is a D-xylose, the diagram of synthesis of the corresponding amides (IC) (IC) xyl, is as follows:

OH O

D-xylose 1,3-dimethylbarbituric acid

(IB) xyl (or acid)

NaHCO ,,

H ₂ O

In this scheme, the intermediate (IB) xyl or the corresponding acid form obtained after acidification, denotes in particular the following compound (IB) xylose:

ONa (IB) xylose (or acid) the compound (Vl) xyl denotes in particular the following compound (Vl) xylose

(Vl) xylose and the compound (IC) denotes in particular the following compound (IC) xylose:

(IC) xylose

Similarly, when the saccharide (II) is an L-rhamnose, the synthesis scheme of the corresponding amides (IC), of formula (IC) rhamn is as follows:

i. NaOH (ii. H ⁺ )

L-rhamnose

HO

h ₂ o ₂ or oxone

(LA) rhamn

i. hnr, r ₂ ii. possible protection

(IC) rhamn

In this scheme, the intermediate (IB) rhamn or the corresponding acid form obtained after acidification, denotes in particular the following compound (IB) rhamnose:

(IB) rhamnose (or acid) the compound (Vl) rhamn denotes in particular the compound (Vl) rhamnose following

and the compound (IC) denotes in particular the following compound (IC) rhamnose:

(IC) rhamnose

When the saccharide (II) is a D-galactose, the synthesis scheme of the corresponding amides (IC) of formula (ICd) galac is as follows:

NaHCO ,,

H ₂ O

D-galacose 1,3-dimethylbarbituric acid

i. NaOH (ü · H ⁺ )

(IB) galac (or acid form)

i. HN ^ Rj ii. possible protection

(LA) Galac

OH OH O * 1 ^NR 2 ^ O HO ' OH OH

(IC) Galac

In this scheme, the galac intermediate (IB) or the corresponding acid form obtained after acidification, denotes in particular the following galactose compound (IB):

(IB) galactose (or acid) the compound (Vl) galac designates in particular the compound (Vl) galactose following

(VI) galactose and the compound (IC) denotes in particular the following compound (IC) galactose:

(IC) galactose

When the saccharide (II) is a D-mannose, the synthesis scheme of the corresponding amides (IC), of formula (IC) mann, is as follows:

(IV) mann

(IA) mann

i. HN ^ Rj ii. possible protection

OH OH O * 1 ^NR 2 ^ O HO OH OH

(IC) mann

In this scheme, the intermediate (IB) mann or the corresponding acid form obtained after acidification, denotes in particular the following compound (IB) mannose:

ONa (IB) mannose (or acid) the compound (Vl) mann denotes in particular the following compound (Vl) mannose:

(Vl) mannose and the compound (IC) designates in particular the following compound (IC) mannose:

(IC) mannose

Similarly, when the saccharide (II) is a D-lactose, the synthesis scheme for the corresponding amides, of formula (IC) lact, is as follows:

OH OH O

(IV) lact

H ^N -.

D-lactose acid 1,3-dimethy Ibarbituric

OH OH (IC) lact

In this diagram, the lact intermediate (IB) or the corresponding acid form obtained after acidification, denotes in particular the following lactose compound (IB):

OH HO _K Γ ° 1 o Â.ONa HO Ol? OH OH

(IB) lactose (or acid ') the compound (Vl) lact designates in particular the following compound (Vl) lactose:

and the compound (IC) denotes in particular the following compound (IC) lactose:

OH R, HO Γ ° T o HO ' Ol? OH OH

(IC) lactose

According to another object of the invention, the invention also relates to the lactonic compounds as well as their solvates and / or isomers and / or salts chosen from the following compounds:

(VI) galac

(Vl) xylose

(Vl) mann

(Vl) mannose

(Vl) lact

(Vl) lactose

According to a preferred embodiment, an object of the invention, the invention also relates to the lactonic compounds as well as their solvates and / or isomers and / or salts chosen from the compounds (Vl) xyl, (Vl) rhamn, ( Vl) galac, (Vl) mann and (Vl) lact and in particular the compounds (Vl) xylose, (Vl) rhamnose, (Vl) galactose, (Vl) mannose and (Vl) lactose, and especially the compounds (Vl ) rhamnose, (Vl) galactose, (Vl) mannose and / or (Vl) lactose, as defined above.

Special case of the compounds of formulas (la ¹ ) and (la ² ):

The compounds of formulas (la ¹ ) and (la ² ) can be obtained via the synthetic route below (scheme 2), from compound (IF), the preparation process of which is described above:

hnr, r ₂

N-acylation

The compound (IF), whose hydroxy groups are preferably substituted or protected (groups A and R3), undergoes an N-acylation reaction with an aromatic amine HNR1R2, to obtain a family of compounds (VIII) including the compounds of formula (the ² ).

A step of deprotection of the hydroxy functions of the sugar unit (groups A) and of the possible other functions present in the groups Ri and / or R2, leads to the group of compounds (XI) which include the compounds of formula (la ¹ ).

Special case of the compounds of formulas (lb ¹ ) and (lb ² ):

The compounds formulas (lb ¹ ) and (lb ² ) can be obtained via the synthetic route below (scheme 3), from compound (VI), the preparation process of which is described above:

Ri R R O

deprotection hydrolysis aminolysis

An opening of the lactone (VI) is effected by attack of the compound (X). Two variants are possible:

the use of a single equivalent of the amine (X) preferentially leads to the group of compounds (XI), which includes the compounds of formula (lb ² ); the reaction is generally carried out in a polar aprotic solvent such as dichloromethane (DCM), THF, or DMF, at a temperature between 20 ° C. and 150 ° C., optionally in the presence of a base such as diisopropylethylamine ( DIEA) or triethylamine (TEA);

- the use of an excess of amine (X), possibly itself as a solvent, can lead directly to compound (XII), which includes the compounds of formula (lb ¹ ), provided that the group R3 either cleavable by the action of an amine, this is particularly the case for the acetyl group.

Depending on the nature of the groups A, R3, R ”i, R” 4, R ”s and R” 6, different deprotection and / or hydrolysis and / or aminolysis reactions, in particular of ester function (s) ( s), can make it possible to convert the compounds (XI) into compounds (XII), to finally lead to the compounds of formula (lb ¹ ).

All the reagents are obtained by conventional methods known to those skilled in the art. The latter will take care to protect or unprotect according to the synthesis steps. For example :

The compounds can be obtained from:

of a sugar (II) of scheme 1 with free OH group (s) or substituted by a C1-C6 alkyl group or by a C1-C6 alkylcarbonyl group, or with OH protected by a PG accessible according to the methods described by Peter GM Wuts and Theodora W. Greene, in Greene's Protective Groups in Organic Synthesis, Fourth Edition, Wiley, 2006; processes for the alkylation, acylation or protection of the hydroxyls of sugars are known and in particular described in Durantie, Estelle et al, Chemistry - A European Journal, 18 (26), 8208-8215 (2012).

The sugar (II) of scheme 1 can also contain one or more amino group (s) substituted by the same C1-C6 alkylcarbonyl group, or by a PG such as those described by Peter GM Wuts and Theodora W. Greene, in Greene's Protective Groups in Organic Synthesis, Fourth Edition, Wiley, 2006. The processes for alkylation, acylation or protection of sugar hydroxyls are known to those skilled in the art and notably described in: Durantie, Estelle et al, Chemistry - A European Journal, 18 (26), 8208-8215 (2012). N-acylation methods are also well known to those skilled in the art and consist of reacting the amine with either a reactive derivative of carboxylic acid such as an anhydride or an acid halide (acid chloride ), or a carboxylic acid activated in situ via a coupling agent such as HOBt, EDCI, CDI, DCC, HATU, PyBOP, in the optional presence of an organic base such as DIEA or TEA, or a mineral base such as NaOH, and optionally DMAP in equimolar or catalytic amount, in a polar aprotic solvent such as DCM, THF, DMF, or acetonitrile, or optionally protic like water.

The barbituric acid derivative (III) optionally N-disubstituted by the radicals Ri corresponding to the (Ci-Cis) alkyl, aryl or aryl (Ci-C4) alkyl groups, the aryl radical being optionally substituted in particular by OMe, OEt , and / or hydroxyl protected by a PG as defined above; (III) can be prepared for example according to the method described by Guoyao Xia et al., J. Med. Chem. 2011, 54, 2409-2421.

The hydroxy group of (IA) in alpha of the group C = O can be alkylated or alkylated to yield the compound (IA ') in which R' is different from H, and corresponds to the (CiCis) alkyl, (C2-Cis) alkenyl groups , (Ci-Cis) alkynyle, aryl (Ci-C4) alkyl, the aryl radical being optionally substituted by a group (Ci-C4) alkoxy such as OMe, OEt, and / or hydroxy optionally protected by a PG (preferably identical to that optionally present on the aryl radical of the group Ri), or (Ci-Ci8) alkylcarbonyl, or (Ci

Cisjalkénylcarbonyle. R ’and / or R3 may also correspond to a hydroxy protecting group which may be necessary in the course of subsequent steps. The alkylation step of the hydroxy group is generally carried out by treatment with a base, often relatively strong, of NaH type, tBuOK, tBuONa, in the presence of an alkylating agent such as an alkyl halide, in a polar aprotic solvent. such as DMF, NMP, THF, acetonitrile, acetone. The hydroxy group acylation step is generally carried out by treatment with either a reactive carboxylic acid derivative such as an anhydride or an acid halide (acid chloride), or a carboxylic acid activated in situ. via a coupling agent such as HOBt, EDCI, CDI, DCC, optionally in the presence of a base such as pyridine, triethylamine or diisopropylethylamine, sodium acetate, soda, and optionally DMAP in equimolar or catalytic amount , in a polar aprotic solvent such as acetonitrile, pyridine, dichloromethane, THF, acetone, or optionally protic like water. Alternatively, the hydroxy can be treated with a carboxylic acid in an acid medium (APTS, anhydrous HCl, H2SO4), with a device for removing the water formed, such as the presence of a desiccant, such as silica gel. , Na2SO4, MgSCU, P2O5 or a Dean Stark apparatus using a volatile solvent forming an azeotrope with water, such as toluene or cyclohexane.

If the hydroxy of the sugar unit (II) and the alpha hydroxy of C = O are substituted by the same group then we start directly from the reagent (II) with unprotected sugar unit, in order to then carry out the acylation step or alkylation of all of the hydroxyls in a single step on the compound (IA).

It is understood that when it is necessary to protect the hydroxy and / or amino functions which could react and interfere with the following reaction, these are protected according to the methods known by a person skilled in the art mentioned above, then the reaction in question is carried out, then the hydroxy and / or amine groups are deprotected by the methods known by a person skilled in the art, mentioned above, to make the hydroxy and / or amines free again.

For example, the following reactions can be carried out by protecting, then carrying out the desired reaction, then deprotected:

(VI ')

Ac ₂ O

(VII ')

r _a . OH R ', 1 i group B: deprotection NHR R'2 ([c, K ^R 1 r ^ 2X ^c 2 ° then / or N-acylation HO n (B) _m or protection (VII ') ---------------- (the') --------------------- (the')

group B: deprotection then / or N-acylation or protection

O-acylation or O-alkylation

groups A: O-acylation, O-alkylation or protection (la ”)

(the'")

(the")

i. protection R ₃ ii. O-acylation or O-alkylation (la ”)

Schemes in which B denotes an amino radical NRbRc as defined above; R’i, respectively R’2, denotes a group Ri, respectively R2, substituted by a protective group, Ri and R2 having the same definitions given above.

deprotection (s) (la ’) or (la”) or (la ’”) ------------- s

As compounds of formula (I), it is possible to use the compounds 1 to 21 described above.

The compounds of formula (I) according to the invention find a very particular application in the cosmetic field.

The subject of the invention is also a composition containing at least one compound of formula (I), and preferably at least one compound of formula (la ¹ ), (la ² ), (IBB), (lb ¹ ), (lb ² ) and / or (the) defined above, and more particularly at least one compound 1 to 21 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 physiologically acceptable medium, at least one compound of formula (I) as described above, and preferably at least one compound of formula (la ¹ ), (la ² ), (IBB ), (lb ¹ ), (lb ² ) and / or (le) defined above, and more particularly at least one compound 1 to 21 as defined above.

By physiologically acceptable medium is meant a medium compatible with human keratin materials such as the skin of the body or of the face, the lips, the mucous membranes, the eyelashes, the nails, the scalp and / or the hair.

The compound of formula (I), and in particular the compound of formula (la ¹ ), (la ² ), (IBB), (lb ¹ ), (lb ² ) and / or (le), or even 1 to 21 defined above, (each compound of formula (I) and in particular each compound of formula (la ¹ ), (la ² ), (IBB), (lb ¹ ), (lb ² ) and / or (le) and more particularly a compound 1 to 21 if the composition comprises several) 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 to 5% by weight, in particular between 0.5 to 3% by weight, relative to the total weight of the composition.

The composition according to the invention is advantageously a cosmetic composition: it can comprise adjuvants usually used in the cosmetic field. The composition can be an aqueous composition, that is to say containing water or a mixture of water and water-miscible solvents such as C2C6 alcohols.

Mention may in particular be made of; organic solvents, in particular C2-C6 alcohols; oils, in particular hydrocarbon oils, silicone oils; waxes, pigments, fillers, dyes, surfactants, emulsifiers; cosmetic active ingredients, polymers, thickeners, preservatives, perfumes, bactericides, odor absorbers, antioxidants.

According to an advantageous form of the invention, the cosmetic composition contains at least one compound of formula (I), and in particular at least one compound of formula (la ¹ ), (la ² ), (IBB), (lb ¹ ), (lb ² ) and / or (le), as defined above and at least one additive chosen from perfumes, oils, waxes, surfactants, thickeners, dyes, bactericides, preservatives.

In a preferred embodiment, the cosmetic composition according to the invention contains at least one compound chosen from compounds 1 to 21 defined above, as well as their solvates such as hydrates, and their base or acid salts, organic or inorganic.

These optional cosmetic adjuvants may be present in the composition in an amount of 0.001 to 80% by weight, in particular 0.1 to 40% by weight, relative to the total weight of the composition. In any event, these adjuvants, as well as their proportions, will be chosen by a person skilled in the art so that the advantageous properties of the compounds according to the invention are not, or not substantially, altered by the addition envisaged.

As active agents, it will be advantageous to introduce into the composition according to the invention at least one compound chosen from: desquamating agents; soothing agents, organic or inorganic photoprotective agents, moisturizing agents; depigmenting agents other than those which are the subject of the present invention; anti-glycation agents; NO synthase inhibitors; agents stimulating the synthesis of dermal or epidermal macromolecules and / or preventing their degradation; agents stimulating the proliferation of fibroblasts and / or keratinocytes or stimulating the differentiation of keratinocytes; dermo-relaxing agents; tensing agents; anti-pollution and / or anti-radical agents; agents acting on the microcirculation; ceramides; agents acting on the energy metabolism of cells; and their mixtures.

The composition according to the invention can in particular be presented in all the galenical forms normally used in the cosmetic field, and in particular in the form of an aqueous or hydroalcoholic solution, optionally gelled, of a dispersion of the lotion type possibly biphasic, of an oil-in-water or water-in-oil or multiple emulsion ((W / O / W or O / W / W for example), of an aqueous gel, of an oil dispersion in an aqueous phase to using spherules, these spherules possibly being polymeric nanoparticles such as nanospheres and nanocapsules or, better still, lipid vesicles of ionic and / or nonionic type, of aqueous or oily gel. These compositions are prepared according to the usual methods The composition according to the invention can constitute a skin care composition, and in particular a cream for cleaning, protecting, treating or caring for the face, for the hands, for the feet, for large folds. anatomical or for the body (for example day creams, night creams, makeup remover creams, foundation creams, sunscreen creams); a fluid foundation, a cleansing milk, a body milk for protection or care, an anti-sun milk; a skin care lotion, gel or foam, such as a cleansing lotion.

The subject of the invention is also a method of cosmetic treatment of the skin, comprising the application to the skin, of a composition comprising at least one compound of formula (I), and preferably at least one compound of formula (la ¹ ), (la ² ), (IBB), (Ib ¹ ), (Ib ² ) and / or (le) defined above, and more particularly at least one compound 1 to 21 as defined above.

The subject of the invention is also a non-therapeutic cosmetic process for depigmentation, lightening and / or bleaching of keratin materials, in particular of the skin, comprising the application of the cosmetic composition described above comprising at least one compound of formula (I and preferably at least one compound of formula (la ¹ ), (la ² ), (IBB), (lb ¹ ), (lb ² ) and / or (le) defined above, and more particularly at least a compound 1 to 21 as defined previously, 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 formula (la ¹ ), (la ² ), (IBB), (lb ¹ ), (lb ² ) and / or (le) defined above, and more particularly at least one compound 1 to 21 as defined above, as a whitening, lightening and / or depigmenting agent for keratin materials, in particular of the skin.

The different examples below describe different synthetic routes making it possible to obtain the compounds of formula (I).

In these diagrams "t.a. "Means room temperature.

The invention is illustrated in more detail by the following nonlimiting examples.

EXAMPLES

Example 1:

Synthesis of compounds 1, 2 and 3

1.2 eq

I2

D-glucose (5 g), dissolved in water (56 mL), is introduced into a 250 mL single-flask. The 1,3-dimethylbarbituric acid (4.33 g) is added with stirring, then NaHCCh is added until pH 7. After neutralization, the flask is equipped with a condenser and the mixture is heated at 80 ° C for 5 h . The reaction is followed by TLC in 1: 1 Dichloromethane (DCM) / MeOH. The reaction mixture is concentrated in vacuo. The residue obtained is taken up in water then precipitated in acetone, filtered and the solid 11 obtained is dried under vacuum. It is isolated in the form of an orange powder, (9.3 g, 98% yield). The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure.

g of product 11 are dissolved in 10 ml of water at room temperature, then 30% H2O2 (3 ml) are added. The reaction mixture is stirred at room temperature for 2 days. Then are added 0.21 equiv. of a 20% aqueous solution of sodium metabisulfite, and the stirring is continued for 1 h at ambient temperature. The absence of peroxide is checked, then the reaction mixture is poured into 300 ml of ethanol. The precipitate formed is filtered, and the filtrate concentrated to a minimum volume. A new precipitate forms, which is collected and dried under vacuum at 30 ° C (First product fraction, 1.6 g). The filtrate is again taken up in ethanol, the precipitate formed is filtered, and the filtrate concentrated to dryness to give another fraction of product (0.8 g). 2 batches of product I2 are therefore recovered in the form of a white solid (2.4 g, yield 65%). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Compound I2 (2.56 g, 10 mmol) was added to a solution of NaOH (4 g, 100 mmol) in 50 ml of water. After stirring at 100 ° C for 5 h, the reaction mixture is cooled to room temperature then adjusted to pH ~ 4 by addition of an ion exchange resin. The resin is then removed by filtration. The filtrate is concentrated to obtain 2.3 g of the acid salt I3 in the form of a gray solid (quantitative rdt). The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure.

A mixture of salt I3 (3.3 g, 12.6 mmol), benzyl bromide (2.6 g, 15.2 mmol), 12.6 ml of / 7-BU4NF in 1 M solution in THF, and 20 ml of DMF, is stirred at room temperature for 16 h. The mixture is then concentrated to dryness. The residue is purified by chromatography on a silica column (dichloromethane / methanol = 10/1) to give 2.4 g of benzyl ester I4 in the form of a white solid (yield 58%). The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure.

To a solution of compound I4 (6.3 g, 19.2 mmol) in dichloromethane (30 mL) are added acetic anhydride (19.6 g, 192 mmol) and pyridine (7.6 g, 96 mmol). The reaction mixture is stirred for 16 h at room temperature, then the acetic anhydride is evaporated and 50 ml of water are added. The mixture is extracted with dichloromethane 3 times. The organic phases are combined, washed with a saturated aqueous solution of NaHCCh, dried over Na2SC> 4, filtered and evaporated. The residue is purified by chromatography on silica gel (ethyl acetate / petroleum ether 1: 2) to give compound I5 (white viscous solid, 2 g, yield = 21% over the 5 steps starting from D-glucose ).

To a solution of compound I5 (2 g, 3.7 mmol) in a methanol / ethyl acetate mixture 1: 1 (20 mL) is added Pd / C 10% (0.2 g). The mixture is hydrogenated under a hydrogen atmosphere for 16 h at room temperature. After filtration, the filtrate is evaporated to dryness to give compound I6 (white solid, 1.5 g, yield = 90%).

To a solution of compound I6 (2 g, 4.5 mmol) in dichloromethane (10 ml_) are added oxalyl chloride (0.68 g, 5.4 mmol) and a drop of DMF. The reaction mixture is stirred for 2 h at room temperature, then evaporated to dryness. The residue obtained I7 is used directly in the next step.

To a solution of compound I8 ([1444836-72-9], 1.27 g, 4.5 mmol) in dichloromethane (10 mL) was added triethylamine (0.9 g, 8.9 mmol),. then a solution of crude I7 (2.08 g, 4.5 mmol) in dichloromethane (10 mL) was added dropwise. At the end of the addition, the reaction mixture was stirred for 16 h at room temperature, then evaporated to dryness. The residue obtained was purified by chromatography on silica gel (ethyl acetate / petroleum ether 1: 2) to give compound 3 (white solid, 2 g, Yield = 65% over 2 steps).

To a solution of compound 3 (2 g, 2.8 mmol) in a methanol / ethyl acetate mixture 2: 1 (15 mL) is added Pd / C 10% (0.2 g). The mixture is hydrogenated under a hydrogen atmosphere for 16 h at room temperature. After filtration, the filtrate is evaporated to dryness to give compound 2 (white solid, 1.66 g, yield = 95%).

To a solution of compound 2 (1.66 g, 2.7 mmol) in methanol (10 mL) is added K2CO3 (0.733 g, 5.3 mmol). The reaction mixture is stirred for 24 h at room temperature and then Amberlite IR-120 resin is added. The suspension is stirred for 1 h at room temperature. After filtration, the filtrate is evaporated to dryness. A precipitate forms after adding 10 ml of ethyl acetate. The solid is filtered, washed with ethyl acetate and dried under vacuum to give compound 1 (white solid, 0.69 g, Yield = 70%). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

The MS and NMR spectra are in accordance with the desired product.

Synthesis of compounds 4 to 21

Synthesis of compounds 14 and 4

Ac ₂ O, AcONa 110 ° C, 4 p.m.

A mixture of the acid salt I3 (2.5 g, 10 mmol), AcONa (2 g, 10 mmol), and 20 ml of Ac20 is stirred at 110 ° C for 16 h then the mixture is concentrated to dryness. The residue is taken up in 200 ml of NaHCOs aq. sat. and extracted 3 times with ethyl acetate. The organic phases are combined, concentrated under vacuum, and the residue obtained is purified by chromatography on silica (petroleum ether / ethyl acetate = 2/1) to give 1.9 g of the lactone intermediate L1 in the form of a solid white, 50% yield. The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure.

A solution of lactone L1 (1.50 g, 3.86 mmol), L-glycine ethyl ester hydrochloride (0.54 g, 3.86 mmol) and DIEA (1.50 g, 11.59 mmol) in THF (50 mL) is stirred for 14 h at 80 ° C . After evaporation of the solvent, 5 ml of ethyl acetate are added to dissolve the residue. The organic phase is washed twice with 0.1 M aq. HCl. The aqueous phase is extracted with ethyl acetate. The organic phases are combined, dried over MgSO4, filtered and evaporated. The residue is purified by chromatography on silica gel (ethyl acetate / n-heptane 2: 1) to give 14 (beige solid, 1.15 g, mdt = 61%). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Product 14 (569 mg, 1.16 mmol) is dissolved in a solution of 7 M ammonia in methanol (15 mL). The reaction mixture is stirred for 17 h at room temperature. After evaporation of the solvent, 5 ml of methanol are added to dissolve the residue. A precipitate forms after adding 50 ml of ethyl acetate. The solid is filtered, washed with ethyl acetate and n-heptane, and dried under vacuum to give compound 4 (white solid, 333 mg, yield = 98%). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Synthesis of compounds 15 and 5

Compound 15 is obtained according to the procedure described for compound 14, from lactone L1 (1.80 g, 4.64 mmol), L-serine ethyl ester hydrochloride (0.79 g, 4.64 mmol) and DIEA (1.80 g, 13.91 mmol) . Compound 15 is in the form of a beige solid (1.47 g, mdt = 61%). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Compound 5 is obtained according to the procedure described for compound 4, starting from 15 (1.47 g, 2.82 mmol). It is in the form of a beige solid (857 mg, 94%). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Synthesis of compounds 16 and 6

Compound 16 is obtained according to the procedure described for compound 14, from lactone L1 (1.0 g, 2.58 mmol), L-proline ethyl ester (0.37 g, 2.58 mmol) and DIEA (3.33 g, 25.75 mmol). It is in the form of a yellow solid (640 mg, Yield = 49%). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Compound 6 is obtained according to the procedure described for compound 4, from 16 (640 mg, 1.20 mmol). Compound 6 is in the form of a beige solid (291 mg, Yield = 72%). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Synthesis of compounds 17 and 7

Compound 17 is obtained according to the procedure described for compound 14, from lactone L1 (1.50 g, 3.86 mmol), β-alanine ethyl ester hydrochloride (0.68 g, 3.86 mmol) and DIEA (1.50 g, 11.59 mmol) . It is in the form of a yellow solid (794 mg, Yield = 35%). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Compound 7 is obtained according to the procedure described for compound 4, starting from 17 (794 mg, 1.57 mmol). It is in the form of a beige solid (243 mg, Yield = 50%). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Synthesis of Compound 78

Compound 18 is obtained according to the procedure described for compound 14, from lactone L1 (1.0 g, 2.58 mmol), L-sarcosine ethyl ester (0.39 g, 2.58 mmol) and DIEA (3.33 g, 25.75 mmol). Yellow solid (650 mg, 50%). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Compound 9 synthesis

O O O O O O o aq. HCl A ·· © ¹ ' ⁰ ° EtOH where V o 14 9 To a solution of compound 14 (50 mg, 0.10 mmol) in ethanol (5 mL) are added

fairies 10 drops of HCl conc. After stirring for 17 h at room temperature, the mixture is evaporated to dryness to give compound 9 (colorless solid, 45 mg, quantitative yield.). The ¹ H NMR spectra and mass spectrometry are in agreement with the expected structure.

Synthesis of compounds 19 and 10 +

70%

i. NaOH, reflux, 5 h

NaHCO ₃ , H ₂ O ° C, 5 h

NHJMeOH

DIEA, THF, 80 ° C

1,3-dimethylbarbituric acid

1.2 eq

Ac ₂ O, AcONa ° C, 8 p.m.

In a 5 L double jacket reactor equipped with a condenser, a nitrogen inlet and a bubbler, D-xylose (225 g, 1.50 mol) is dissolved in 3 L under an inert atmosphere. The 1,3-dimethylbarbituric acid (1.2 equiv., 281 g, 1.80 mol) is added with stirring, per portion followed by the addition of. sodium bicarbonate (2.1 equiv., 264 g, 3.15 mol) up to pH = 7. The solution is then heated at 90 ° C for 5 h and then partially concentrated, under vacuum. Acetone is then added to the concentrated aqueous solution to precipitate the compound which is then filtered, washed with an acetone / water mixture approximately 4/1, then dried under vacuum. 593.5 g of crude compound I9 are thus isolated (61% NMR purity) in the form of a beige powder.

In a 5 L double jacket reactor, compound I9 (286 g crude, 61% pure or 0.56 mol), under an inert atmosphere, is dissolved in 1.5 L of water and stirred at room temperature. The 30% hydrogen peroxide in water (n _t h = 2 equiv., 188 mL, 1.84 mol) is added dropwise via a dropping funnel. The reaction medium is then heated at 70 ° C for 5 h, then concentrated to dryness (after having verified the absence of residual peroxides) to give a pale yellow powder which is then used in the next step without purification (110, 249 g crude, 43% NMR purity,).

In a 5 L double jacket reactor, the compound 110 (159.5 g crude, 43% pure or 0.32 mol), under an inert atmosphere, is dissolved in 2.5 L of water and with mechanical stirring at 20 ° C. 1M sodium hydroxide (225 mL, 2.26 mol) is added via a dropping funnel. The reaction medium is then heated at 90 ° C for 5 h. The reaction medium (2.7 L) containing the 111 carboxylate (285 g, 26% NMR purity) is then purified.

The above reaction medium (26% NMR purity, corresponding to 49.0 g of product in acid form 111) is acidified. Compound 111 is then fixed on a basic resin and the impurities are removed by aqueous washes. Compound 111 is then released from the basic resin with 0.5 M hydrochloric acid. After lyophilization, a beige powder was obtained (21.45 g, compound 111 at 84% NMR purity, 38% rdt).

A mixture of acid 111 (8.5 g, 38 mmol), AcONa (3.2 g, 38 mmol), and 73 ml of Ac2O is stirred at 55 ° C for 20 h, then the mixture is treated with ether diisopropyl to recover a white solid after filtration. This solid is treated by fractional precipitation in ethyl acetate to obtain different fractions of a single diastereoisomer of lactone L2, denoted dial. The filtrates were concentrated and purified by chromatography on silica (n-heptane / ethyl acetate 8: 2) to give two fractions other lactone L2 as mixtures enriched dial or DIA2 ^(2nd diastereoisomer). A total of 6.11 g of lactone are obtained (white powder, 56% rdt). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Compound 19 is obtained according to the procedure described for compound 14, from lactone L2 (1.5 g, 4.7 mmol), L-glycine ethyl ester hydrochloride (662 mg, 4.7 mmol) and DIEA (2.5 mL, 14 mmol) : Yellow oil, 1.07 g, Yield = 56%. ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Compound 10 is obtained according to the procedure described for compound 4, from 19 (800 mg, 1.9 mmol). Ethyl acetate is replaced by acetone for precipitation. It is isolated in the form of a white powder, 435 mg, Yield = 86%.

Synthesis of compounds 20-dia1 and 11-dia1

Compound 2Q-dia1 is obtained according to the procedure described for compound 19, from lactone L2-dia1 (1.34 g, 4.2 mmol), L-serine ethyl ester hydrochloride (719 mg, 4.24 mmol) and DIEA (3.7 mL , 21 mmol). Yellow oil (1 g, 45%). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Compound 11-d / 'a7 is obtained according to the procedure described for compound 10, from 2Q-dia1 (550 mg, 1.23 mmol). Yellow oil (160 mg, 44%). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Synthesis of compounds 20-dia2 and 11-dia2

Compound 20-dia2 is obtained according to the procedure described for compound 19, from lactone L2-dia2 (1.5 g, 4.7 mmol), L-serine ethyl ester hydrochloride (804 mg, 4.7 mmol) and DIEA (4.1 mL , 24 mmol). Sticky white powder (860 mg, ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Compound 11-dia2 is obtained according to the procedure described for compound 10, from 20-dia2 (810 mg, 1.8 mmol). Yellow oil (380 mg, 72% 2 steps). ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Compound 21 synthesis

Compound 21 is obtained according to the procedure described for compound 19, from lactone L2 (1.07 g, 3.4 mmol), L-sarcosine ethyl ester (520 mg, 3.4 mmol) and DIEA (7.1 mL, 41 mmol). Orange hard wax. ¹ H / ¹³ C NMR spectra and mass spectrometry are in agreement with the expected structure.

Example 2: Demonstration of depigmenting activity

The measurement of the depigmenting activity (reduction in the production of melanin) of compounds of formula (I) was carried out by assaying normal human melanocytes in vitro as follows.

First, normal human melanoycts are grown and distributed in wells. After 24 hours, the culture medium was replaced by a medium containing compounds of formula (I) to be evaluated. The cells were incubated 72 hours before the measurement of the final optical density which measures the quantity of melanin produced by the melanocytes. The compounds are tested at 100 μΜ after calibration. .

Different test campaigns have been carried out and the results are collated in the following table.

Compound No. % depigmentation at 100 μΜ (countryside) % depigmentation at 100 μΜ (campaign 2) 1 13% 4 19% 5 31% 6 29% 7 34% 10 20% 11-c // a1 28% 11-c // a2 32% 12 20% (28% at the maximum dose tested 200 μΜ) 19 15% (43% at the maximum dose tested 200 μΜ) 20-dia1 23%

The compounds of formula (I) have shown a depigmenting effect.

Example 3 Cosmetic Composition

A depigmenting composition for the skin is prepared comprising (in grams): Compound No. 102 g

PEG40068 g

Ethanol30 g

The composition applied to the skin helps to remove dark spots.

A similar composition is prepared with compound 11 (trans or cis isomers or mixture of the two).

Example 5: gel

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

Compound # 10 0.25%

Carbomer (Carbopol 981 from Lubrizol) 1% preservative qs water qs 100%

The composition applied to the skin helps to remove dark spots.

A similar composition is prepared with compound 11 (trans or cis isomers or mixture of the two).

Claims (1)

1. Non-therapeutic cosmetic process for depigmentation, lightening and / or bleaching of keratin materials, comprising the application of a compound of formula (I) or of a composition comprising one or more compounds of formula (I): OR, R. (I) in which: - S * denotes a monosaccharide sugar radical or denotes a polysaccharide sugar radical comprising from 2 to 5 saccharide unit (s), preferably from 2 to 3 saccharide unit (s) preferentially S * denotes a sugar radical comprising 1 or 2 saccharide unit (s) (monosaccharide or disaccharide), 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 optionally substituted hydroxy groups (s) by a radical R 'chosen from: i) (Ci-Ce) alkyl; or ii) (C2-Ce) alkenyl; or iii) an acetyl radical; or iv) a protective group (PG) of hydroxy function (s) such as (C2C6) alkyl (thio) carbonyl or benzyl; said monosaccharide or polysaccharide radical which may also comprise one or more amino groups NRbR _c with Rb and R _c , identical or different, representing a hydrogen atom, an acetyl group, or a group protecting the amino function such as (C2 C6) alkyl (thio) carbonyl; said mono or polysaccharide radical being linked to the rest of the molecule by a bond between the carbon atom Ci of one of the sugars of said mono or polysaccharide radical, this bond possibly being anomeric a or β; - R3 represents i) a hydrogen atom; or ii) a (Ci-Cis) alkyl group; or iii) a (C2-Cis) alkenyl group; or iv) a hydroxy (PG) protecting group such as (CiCi8) alkyl (thio) carbonyl, such as an acetyl group, (C2- Ci8) alkenyl (thio) carbonyl or aryl radical (Ci-C4) alkyl optionally substituted in particular by at least one hydroxy and / or (Ci-C4) alkoxy saturated or unsaturated; - Ri represents i) a hydrogen atom; or ii) a (Ci-Cis) alkyl group; or iii) a (C2-Cis) alkenyl group; - R2 represents i) an optionally substituted aryl or hereroaryl radical; or ii) a radical of formula (B1): Rh (Bl) where: Rh and Rk independently of one another denote a hydrogen atom or a methyl radical, it being understood that Rh and Rk cannot simultaneously denote a methyl radical - y = 1 to 10; iii) a radical of formula (B2): (B2) in which: - i = 0 or 1; R4 represents i) a hydrogen atom, or ii) a radical chosen from the radicals (a1) to (a32) described below: me ^ ★ NH AT / ; H, N N ★ 0 • HO O - TV- 'h ₂ n; OH HO. AT  Me (A1) ^H (a2) (A3) (A4) (a5) ( ^a6 )