FR3030509A1 - 1-PHENYL (3,4-DISUBSTITUTED), 2-PHENYL (3,4-DISUBSTITUTED) ETHANE COMPOUNDS AND THEIR USE - Google Patents

Abstract

The present invention relates to the cosmetic use, in a composition containing a physiologically acceptable medium, of at least one compound of formula (I): in which: R1 signifies a hydrogen atom; a linear or branched, saturated or unsaturated C1-C6 alkyl radical; a benzyl radical; a linear or branched, saturated or unsaturated C1-C6 alkylcarbonyl radical, non-conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C1-C6 alkoxycarbonyl; R2 is a hydrogen atom; a hydroxyl radical; a linear or branched, saturated or unsaturated C1-C6 alkoxy radical; a benzyloxy radical; a linear or branched, saturated or unsaturated, C1-C6 alkylcarbonyloxy radical which is not conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C1-C6 alkoxycarbonyloxy radical; R3 denotes a hydrogen atom or a hydroxyl radical, it being understood that R3 signifies a hydrogen atom in the only cases where R2 also signifies a hydrogen atom; hydrogen, and / or an isomer and / or a solvate of the compound of formula (I), for protecting the skin and / or its integuments from the oxidative stress caused by exposure to UV radiation.

Description

The present invention relates to the field of photoprotective cosmetic compositions, or photoprotective products, and more particularly to compounds used as antioxidants. The present invention relates to the use of 1-phenyl (3,4-disubstituted, 2-phenyl) (3,4-disubstituted) ethane compounds and their use in particular for protecting the skin and its appendages from oxidative stress caused by exposure. to UV radiation, that is to say particularly the skin, including the skin of the scalp.It relates to compositions containing, in a physiologically acceptable medium, at least one 1-phenyl compound (3,4-disubstituted). ), 2-phenyl (3,4-disubstituted) ethane.

Keratinous materials, and in particular the skin and its integuments, are daily exposed to sunlight. However, it is known that prolonged exposure of keratin materials, and in particular of the skin, to this polychromatic light is likely to induce cutaneous disorders or even superficial damage.

This is in particular due to the formation of free radicals, reactive oxygen species such as O 2 and H 0, which can damage DNA, certain lipids and / or proteins, and more generally, which induce cellular aging. These reactive species disrupt biological mechanisms by inducing oxidative stress. This contributes to the development and acceleration of cellular degeneration.

The production of reactive oxygen species thus causes damage to DNA, proteins and / or lipids, and contributes to the acceleration of aging of the cells of the skin and / or its annexes. In particular, the effects of oxidative stress affect cellular respiration and result in an acceleration of aging of the skin, including a dull and / or gray complexion, a heterogeneous complexion, a loss of radiance. and / or the transparency of the skin, the early formation of wrinkles or fine lines, a loss of softness, suppleness and elasticity of the skin. Thus, the UV radiation induces a phenomenon called "photo-aging" of the skin and / or its integuments, which includes as symptoms the appearance of wrinkles / fine lines, a loss of radiance and a heterogeneity of the complexion, a loss firmness, appearance of roughness and yellowing of the skin. The effects of oxidative stress are also manifested by a decrease in the vigor of the hair and / or a deterioration of the appearance of these, in particular the hair can have a dull aspect.

Antioxidants are used in cosmetics to fight free radicals. The role of antioxidants is to capture and neutralize free radicals by converting them into subspecies, safe for keratin materials. Antioxidants can therefore be used in various fields such as anti-aging cosmetics, protection against oxidative stress and in particular that caused by exposure to the sun. Many antioxidants are already known. These include vitamin E (alpha tocopherols and isomers), vitamin C (ascorbic acid) and its derivatives, carotenoids, aminoindoles, melatonin, ubiquinone, coenzyme Q, green tea, thiols and their derivatives (Glutathione, N-acetylcysteine), procyanidolic oligomers (OPC), flavonoids, catechins including epicatechin and its gallic derivatives, polyphenols such as tyrosol, hydroxytyrosol, sesamol, carnosol, gamma orizanol, acids such as dihydrolipoic acid, uric acid, ferulic acid, caffeic acid, rosemarinic acid, carnosic acid.

However, there is a need to identify novel compounds having antioxidant properties, which make it possible in particular to protect keratinous substances (especially the skin of the scalp and / or the integuments) of individuals against the harmful effects of oxidative stress. induced by the sun's rays. We therefore understand the need to have products that reduce or even inhibit the phenomenon of oxidative stress resulting from the exposure of the skin, including the scalp, to UV rays. In this respect the Applicant has surprisingly and unexpectedly discovered that certain 1-phenyl (3,4-disubstituted), 2-phenyl (3,4-disubstituted) ethane derivatives have the property of preventing or at least reducing the production of reactive oxygen species which is induced by the exposure of skin cells to UV radiation, and thus to protect the skin, scalp and integuments such as hair, eyelashes and nails, oxidative stress, in particular caused by exposure to UV radiation. In particular, the 1-phenyl (3,4-disubstituted), 2-phenyl (3,4-disubstituted) ethanes defined in the present description can be used to cosmetically treat the skin, including the scalp, against oxidative stress caused by exposure to UV radiation. By "prevention" or "prevention" is meant according to the invention the fact of reducing the risk of occurrence or slowing the occurrence of a given phenomenon, namely, according to the present invention, the cutaneous signs of photoaging.

The subject of the invention is therefore the cosmetic use, in a composition containing a physiologically acceptable medium, of at least one 1-phenyl (3,4-disubstituted), 2-phenyl (3,4-disubstituted) ethane derivative. formula (I): (I) wherein: - R1 signifies a hydrogen atom; a linear or branched, saturated or unsaturated C1-C6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical, saturated or unsaturated, non-conjugated with the carbonyl ("acyl"); or a linear or branched, saturated or unsaturated ("carbonate") C1-C6 alkoxycarbonyl radical; R2 represents a hydrogen atom; a hydroxyl radical; a linear or branched, saturated or unsaturated C1-C6 alkoxy radical; a benzyloxy radical; a linear or branched, saturated or unsaturated, C1-C6 alkylcarbonyloxy radical which is not conjugated with the carbonyl; or a linear or branched, saturated or unsaturated ("carbonate") C1-C6 alkoxycarbonyloxy radical, - R3 represents a hydrogen atom or a hydroxyl radical, it being understood that R3 signifies a hydrogen atom in the only cases where R2 also means hydrogen, or one of its solvates or one of its optical isomers, stereoisomers, or diastereoisomers, to protect the skin and / or its integuments from the oxidative stress caused by exposure to UV radiation.

Certain compounds of 1-phenyl (3,4-disubstituted), 2-phenyl (3,4-disubstituted) ethane of formula (I), the use of which is defined in the present description, are known. Certain other compounds of 1-phenyl (3,4-disubstituted), 2-phenyl (3,4-disubstituted) ethane of formula (I), the use of which is defined in the present description, are novel compounds which have been specially formulated for the purpose of carrying out the invention.

Thus, the present invention also relates to certain compounds of 1-phenyl (3,4-disubstituted), 2-phenyl (3,4-disubstituted) ethane of formula (I) defined in the present description, which compounds, to the knowledge of the applicant, have not been described in the state of the art.

The subject of the invention is therefore also a novel compound of formula (Ta): ORi in which: R1 represents a saturated or unsaturated C3-05 linear alkyl radical; a saturated or unsaturated C 3 -C 6 branched alkyl radical; a saturated or unsaturated C2-C6 linear alkylcarbonyl radical, non-conjugated with the carbonyl; a saturated or unsaturated C4-C6 branched alkylcarbonyl radical, non-conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C1-C6 alkoxycarbonyl radical, its (optical, stereoisomeric, or diastereoisomeric) isomers and its solvates.

The subject of the invention is also a novel compound of formula (Ib): ## STR2 ## in which R 1 and R 2 are chosen from the following combinations: R 1 signifies a hydrogen atom and R 2 signifies a hydroxyl radical; a linear or branched C2-C6 alkoxy radical, saturated or unsaturated; a benzyloxy radical; a linear or branched, saturated or unsaturated, C1-C6 alkylcarbonyloxy radical which is not conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C1-C6 alkoxycarbonyloxy radical; - R1 is a methyl radical and R2 is a linear or branched C2-C6 alkoxy radical, saturated or unsaturated; a linear or branched, saturated or unsaturated, C1-C6 alkylcarbonyloxy radical which is not conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C 1 -C 6 alkoxycarbonyloxy radical; R1 represents a linear or branched, saturated or unsaturated C 2 -C 6 alkyl radical; a benzyl radical; a linear or branched, saturated or unsaturated C1-C6 alkylcarbonyl radical, non-conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C1-C6 alkoxycarbonyl radical, and R2 denotes a hydroxyl radical; a linear or branched, saturated or unsaturated C1-C6 alkoxy radical; a benzyloxy radical; a linear or branched, saturated or unsaturated (C1-C6) alkylcarbonyloxy, unconjugated with carbonyl radical; or a linear or branched, saturated or unsaturated C1-C6 alkoxycarbonyloxy radical, their (optical, stereoisomeric, or diastereoisomeric) isomers and their solvates.

Also, the present invention provides processes for the preparation of the 1-phenyl (3,4-disubstituted), 2-phenyl (3,4-disubstituted) ethane compounds of formula (I), the use of which is defined herein. description, including 1-phenyl (3,4-disubstituted), 2-phenyl (3,4-disubstituted) ethane compounds of formula (Ta) or (Ib). The invention also relates to a cosmetic composition comprising, in a physiologically acceptable medium, at least one compound chosen from compounds of formula (I), and compounds of formula (Ta) as defined above. The subject of the invention is also a process for non-therapeutic cosmetic treatment of the skin, comprising the application to the skin of a cosmetic composition comprising at least one of the compounds as defined above.

The invention also relates to a cosmetic process for protecting the skin and / or its integuments from an oxidative stress caused by exposure to UV radiation, comprising at least one step of topical application to the skin or its appendices, particularly on the scalp, of a composition as defined above.

Protection of the skin and / or its integuments from oxidative stress "caused by exposure to UV radiation" Skin "refers to the entire skin, including the scalp and mucous membranes. By dander, we mean all integumentary appendages including nails, hair, hair, eyelashes and eyebrows.

The term "oxidative stress" refers to all the damage caused by an increase in the free radicals of oxygen in a subject, and in particular in his skin, and its appendages, more particularly in the scalp. Oxygen free radicals include: - singlet oxygen .0-0. (or '02); superoxide radical anion 02--; the hydroxyl radical HO; the hydroperoxyl H02 radical; the radicals peroxide (R00), alkoxy radical (RO), where R is a carbon chain.

These highly reactive derivatives induce oxidative stress that contributes to the development and acceleration of cellular degeneration. This oxidative stress can be generated by non-photosensitive mechanisms, for example NADPH oxidase generates superoxide radicals, or by exposure to certain components of sunlight.

The present application relates more specifically to oxidative stress caused by exposure to ultraviolet (UV) radiation, including UVA radiation. The so-called 'antioxidant' compounds also known as 'anti-radical compounds' are compounds capable of capturing and neutralizing free radicals by converting them into less reactive chemical subspecies.

Derivatives of 1-phenyl (3,4-disubstituted), 2-phenyl (3,4-disubstituted) ethane The compounds described below comprise, within the meaning of the invention, the compounds as such as well as their solvates and their isomers. The term "solvates" refers to conventional solvates, such as those formed during the last stage of the preparation of these compounds due to the presence of solvents. By way of example, mention may be made of solvates due to the presence of water or linear or branched alcohols such as ethanol or isopropanol. Preferably, the isomers according to the invention are stereoisomers, in particular enantiomers, diastereoisomers, as well as their mixtures, including racemic mixtures. The present invention relates to the cosmetic use, in a composition containing a physiologically acceptable medium, of at least one compound of formula (I): (I) in which: R1 signifies a hydrogen atom; a linear or branched, saturated or unsaturated C1-C6 alkyl radical; a benzyl radical; a linear or branched, saturated or unsaturated C1-C6 alkylcarbonyl radical, non-conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C1-C6 alkoxycarbonyl radical; R2 represents a hydrogen atom; a hydroxyl radical; a linear or branched, saturated or unsaturated C1-C6 alkoxy radical; a benzyloxy radical; a linear or branched, saturated or unsaturated, C1-C6 alkylcarbonyloxy radical which is not conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C 1 -C 6 alkoxycarbonyl radical; R 3 signifies a hydrogen atom or a hydroxyl radical, it being understood that R 3 signifies a hydrogen atom in the only cases where R 2 also signifies a hydrogen atom; hydrogen, and / or an isomer and / or a solvate of the compound of formula (I), for protecting the skin and / or its integuments from the oxidative stress caused by exposure to UV radiation. For the purposes of the invention, an alkyl radical is a linear or branched saturated aliphatic group. C1-C6 alkyl is an alkyl radical comprising from 1 to 6 carbon atoms, that is to say that the alkyl radical can comprise 1, 2, 3, 4, 5 or 6 carbon atoms. As examples of alkyl radicals, mention may be made of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl and the like. Within the meaning of the invention, a benzyl radical is an aromatic group of formula C6H5-CH2- and of structural formula (X1): CH2- (X1) Within the meaning of the invention, an alkylcarbonyl radical is a group of formula ( X 2) 0 AL K 20 (X 2), wherein "Alk" means an alkyl radical as defined above. Within the meaning of the invention, an alkoxy radical is a -O-alkyl group where the alkyl group is as defined above. C1-C6 alkoxy is a -O-alkyl group wherein the alkyl group comprises 1 to 6 carbon atoms, i.e. the alkyl group may include 1, 2, 3, 4, 5 or 6 carbon atoms. A C1-C6 alkoxy radical includes especially methoxy, ethoxy, propoxy, butoxy, pentoxy and hexyloxy radicals.

Within the meaning of the invention, a benzyloxy radical is a group of formula -O-benzyl (X3) as shown below: CH, O- * (X3) Within the meaning of the invention, an alkoxycarbonyl radical is a group of formula (X4): ## STR5 ## wherein the group "Alk-O" means an alkoxy group as defined above. Within the meaning of the invention, an alkylcarbonyloxy radical is a group of formula (X5): ## STR5 ## in which "Alk" signifies an alkyl group as defined above. For the purposes of the invention, an alkoxycarbonyloxy radical is a group of formula (X6): Wherein the group "Alk-O" means an alkoxy group as defined above. According to one particular aspect of the invention, the compound of formula (I) is characterized in that: R1 denotes a hydrogen atom or a linear or branched, saturated or unsaturated C1-C6 alkyl radical, preferably a radical linear or branched C1-C4 alkyl, saturated, and even more preferably a methyl radical; and R2 denotes a hydrogen atom or a linear or branched, saturated or unsaturated C1-C6 alkyl radical, preferably a linear or branched, saturated C1-C4 alkyl radical, and even more preferably a methyl radical.

According to another aspect of the invention, the compound of formula (I) is characterized in that: - R1 denotes a methyl radical; and - R2 and R3 signify a hydrogen atom.

The structural formula of this particular compound, hereinafter referred to as the compound text (A), is shown below: According to another aspect of the invention, the compound of formula (I) is characterized in that: - R1 means a hydrogen atom, - R2 signifies a methoxy radical, and - R3 signifies a hydroxyl radical. The structural formula of this particular compound, hereinafter referred to as the compound text (B), is represented below: The present invention also relates to novel chemical compounds of formula (Ta): R 10 ° R 1 (la) wherein: - R1 is a saturated or unsaturated C3-05 linear alkyl radical; a saturated or unsaturated C 3 -C 6 branched alkyl radical; a saturated or unsaturated C2-C6 linear alkylcarbonyl radical, non-conjugated with the carbonyl; a saturated or unsaturated C4-C6 branched alkylcarbonyl radical, non-conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C1-C6 alkoxycarbonyl radical, their isomers and their solvates. Also disclosed is another compound of formula (Ib): wherein R1 and R2 are selected from the following combinations: A. R1 is hydrogen and R2 is hydroxyl; a linear or branched C2-C6 alkoxy radical, saturated or unsaturated; a benzyloxy radical; a linear or branched, saturated or unsaturated, C1-C6 alkylcarbonyloxy radical which is not conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C1-C6 alkoxycarbonyloxy radical; B. R1 is methyl and R2 is linear or branched C2-C6 alkoxy, saturated or unsaturated; a linear or branched, saturated or unsaturated, C1-C6 alkylcarbonyloxy radical which is not conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C1-C6 alkoxycarbonyloxy radical; C. R1 represents a linear or branched C2-C6 alkyl radical, saturated or unsaturated; a benzyl radical; a linear or branched, saturated or unsaturated C1-C6 alkylcarbonyl radical, non-conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C1-C6 alkoxycarbonyl radical, and R2 denotes a hydroxyl radical; a linear or branched, saturated or unsaturated C1-C6 alkoxy radical; a benzyloxy radical; a linear or branched, saturated or unsaturated, C1-C6 alkylcarbonyloxy radical which is not conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C 1 -C 6 alkoxycarbonyloxy radical, their isomers and their solvates. The present invention also relates to the cosmetic use of these compounds of formula (Ia) and (Ib) for protecting the skin and / or its integuments from the oxidative stress caused by exposure of the skin, and in particular the scalp, to UV radiation.

Synthesis of the New Compounds Compounds of Formula (la) The compounds of formula (ta) can be obtained from the benzyl halide derivative by a metallo-catalyzed coupling reaction of Wurtz or Negishi type, according to the following reaction scheme: 1. Zn 2. Catalyst Scheme 1 The possible hydroxyl groups of the reagents may be, if necessary, previously protected by a suitable protective group. The detailed protocol for the synthesis of this compound, by Negishi type reaction, is detailed in the experimental section. Compounds of Formula (Ib) The compounds of formula (Ib) can be obtained from benzyl halide derivative and aldehyde by a Nozaki-Hiyama, Grignard or Barbier type reaction, according to the following scheme: R2 metal 0 Ri R10 R2 Diagram 2 The possible hydroxyl groups of the reagents may be protected, if necessary, by an appropriate protective group. The detailed protocol for the synthesis of this compound, by Grignard or Barbier type reaction, is detailed in the experimental section.

Composition, in particular a cosmetic composition The present invention also relates to a composition, especially a cosmetic composition, comprising, in a physiologically acceptable medium, at least one compound chosen from the compound of formula (I), and the compounds of formula (Ta) and (Ib) as defined herein. above and / or isomers and / or solvates of said compounds. By "physiologically acceptable medium" is meant an environment compatible with keratin materials of human beings such as skin, mucous membranes, nails, scalp and / or hair. Thus, the physiologically acceptable medium is in particular a cosmetically or dermatologically acceptable medium, that is to say without odor, color or unpleasant appearance, and that does not generate tingling, tightness or redness unacceptable to the user. A composition according to the invention is particularly suitable for topical application to a keratinous material and in particular the skin and the scalp.

Thus, it can be used as a skin care product, for example as a protective cream, treatment or treatment for the face, for the hands or for the body, as body protection or skincare milk, scalp or mucous membranes, or more particularly as a daily photoprotection product, sun protection or after-sun protection.

The compositions according to the invention may also constitute products for the make-up of the skin and / or the hair, for example by incorporating pigments therein to constitute, in particular, foundations, makeup bases. According to one embodiment of the invention, the cosmetic compositions are characterized in that the compound of formula (I), (la) or (Ib) is present, alone or as a mixture, in an amount of between 0.001% and 30%. % by weight, preferably between 0.01% and 10% by weight, especially between 0.5% and 5% by weight, relative to the total weight of the composition. According to another embodiment of the invention, the cosmetic compositions are characterized in that the physiologically acceptable medium comprises at least one cosmetic adjuvant chosen from water; organic solvents, especially C2-C6 alcohols and C2-C10 carboxylic acid esters; hydrocarbon oils, silicone oils, fluorinated oils, waxes, pigments, fillers, dyes, surfactants, emulsifiers, cosmetic or dermatological active agents, UV filters, film-forming polymers, hydrophilic or lipophilic gelling agents, thickeners, preservatives, perfumes, bactericides, odor absorbers and antioxidants other than the compounds presented in the present description. Fatty phase Preferably, a composition according to the invention may comprise at least one fatty phase. For the purposes of the invention, the fatty phase includes any liquid fatty substances, generally oils, or solids, such as waxes or pasty compounds present in said composition.

This fatty phase contains at least one non-volatile oil and in particular at least 40% by weight of non-volatile oil (s) as described below. The term "oil" means any fatty substance in liquid form at ambient temperature (25 ° C.) and at atmospheric pressure. The oil or oils may be present in a proportion of 0.1 to 50% by weight, in particular at least 5 to 40% by weight, relative to the total weight of the cosmetic composition according to the invention. The volatile or non-volatile oils may be hydrocarbon oils, in particular of animal or vegetable origin, synthetic oils, silicone oils, fluorinated oils, or mixtures thereof.

For the purposes of the present invention, the term "silicone oil" means an oil comprising at least one silicon atom, and in particular at least one Si-O group. The term "hydrocarbon-based oil" means an oil containing mainly hydrogen and carbon atoms and optionally oxygen, nitrogen, sulfur and / or phosphorus atoms.

Aqueous Phase The composition according to the invention may comprise an aqueous phase. For the purposes of the invention, the aqueous phase includes water and / or at least one water-soluble solvent.

The water may be floral water such as cornflower water and / or mineral water such as VITTEL water, LUCAS water or LA ROCHE POSAY water and / or thermal water.

By "water-soluble solvent" is meant in the present invention a liquid compound at room temperature and miscible with water (miscibility in water greater than 50% by weight at 25 ° C and atmospheric pressure). According to a particularly preferred embodiment, the aqueous phase of a composition according to the invention comprises at least one C 2 -C 8 lower mono-alcohol. Lower monoalcohols which are more particularly suitable for the invention contain from 2 to 8 carbon atoms, in particular from 2 to 6 carbon atoms, and in particular from 2 to 4 carbon atoms, such as ethanol and isopropanol, propanol, butanol. Ethanol and isopropanol, and preferably ethanol, are also particularly suitable for the invention. The emulsion according to the invention may comprise one or more C 2 to C 6 lower monoalcohol in a content of at least 1%, in particular of at least 2%, especially in the proportion of 2 to 20% by weight, relative to the total weight of the composition. In addition to the lower monoalcohol (s) defined above, this aqueous phase may contain other alcohol (s), in particular polyethylene glycols having from 6 to 80 ethylene oxide units; polyols such as propylene glycol, isoprene glycol, butylene glycol, glycerine, sorbitol, dipropylene glycol, diethylene glycol, glycol ethers such as the mono, di or C 1 -C 4 alkyl ethers; tripropylene glycol, mono-, di- or tri-ethylene glycol, and mixtures thereof.

The aqueous phase may also comprise any water-soluble or water-dispersible compound compatible with an aqueous phase such as gelling agents, film-forming polymers, thickeners, surfactants and mixtures thereof. The composition according to the invention may be in the form of a protective composition against an oxidative stress caused by exposure of the skin and / or its integuments to UV radiation. According to a particular embodiment, the composition according to the invention is a photoprotective composition used on a daily basis. According to another embodiment, the composition according to the invention is a composition called after-sun, to be applied after exposure to the sun, which can be used on a daily basis. The invention also relates to a non-therapeutic use of a cosmetic composition as defined above, for protecting the skin and / or its integuments from oxidative stress caused by exposure of the skin, and / or in particular of the scalp , UV radiation.

Process for the non-therapeutic cosmetic treatment of a keratinous material Another object of the invention is a process for the treatment, in particular a cosmetic treatment, of a keratin material, characterized in that a composition such as defined is applied to the keratin material above.

For the purposes of the present invention, the term "keratin materials" is intended to denote the skin, the scalp, the mucous membranes, such as the lips, the nails and the keratinous fibers, like the eyelashes, the eyebrows and the hair. . Are particularly considered according to the invention, the parts of the keratin materials most likely to be exposed to sunlight, namely the skin and the lips, more particularly the skin of the face, scalp, neck, hands or legs, and more particularly the skin of the face. The invention relates very particularly to a non-therapeutic cosmetic treatment method for the skin and / or its integuments, comprising the application to the skin, and / or in particular to the scalp, of a cosmetic composition as defined above. above.

According to a particular implementation of the method of the invention, the composition is applied to mature and / or wrinkled skin. The invention particularly relates to a cosmetic process for protecting the skin and / or its integuments from oxidative stress, in particular caused by exposure to UV radiation, comprising at least one stage of topical application to the skin and / or its integuments of a composition as defined above. The topical application of the composition may take place before, during or after exposure to UV radiation, and especially during exposure to natural sunlight. According to another aspect of the invention, this cosmetic process is characterized by a repetition of the application step on a daily basis. In particular, exposure to UV radiation can be repeated on a daily basis, and / or exposure to UV radiation is prolonged exposure, i.e. exposure of at least 2 hours, or even at least 3 hours. hours, at least 4 hours, at least 5 hours, at least 6 hours, at least 7 hours, at least 8 hours, at least 9 hours, at least 10 hours, at least 11 hours, or at least 12 hours. Expressions "between ... and ..." and "ranging from ..." must be understood as inclusive terms, unless otherwise specified.

The following examples are presented for illustrative and not limiting of the invention. Unless otherwise indicated, the quantities indicated are expressed as a percentage by mass.

EXAMPLES Example 1. Synthesis of Compound (A) by Negishi-type reaction Compound (A) is a compound of formula (I) with: - R1 is a methyl radical and - R2 and R3 are hydrogen atoms.

The Negishi reaction comprises two steps: 1) The zinc derivative is prepared according to the following protocol: - Under anhydrous conditions and under an inert atmosphere, zinc powder (1.5 eq.) Is added in a piriformed Schlenk tube and then heated under vacuum (0.5 mmHg) at 70 ° C for 30 min. The tube is then refilled with argon, and an anhydrous aprotic polar solvent, such as THF, DMA (N, N-dimethylacetamide) or DMI (1,3-dimethyl-2-imidazolidinone), is added. using a syringe, followed by iodine (12, 0.025 eq.). - The reaction mixture is stirred at 70 ° C until the red color fades (about 5 min). The benzyl halide (1 eq.) In solution in the same solvent is added slowly using a syringe. - The mixture is stirred at 70 ° C for 12 h, then allowed to cool to room temperature for 1 h without stirring, so that unreacted zinc particles are deposited at the bottom of the flask. The mixture is filtered under argon through a sinter equipped with a piriform bicolour balloon in which the solution of the zinc derivative is recovered. 2) The coupling is carried out as follows: In a three-necked flask under anhydrous conditions and under an inert atmosphere, a mixture of the catalytic system (catalyst optionally coupled to a ligand), such as NiCl.sub.12.glyme (0.05-0.07 eq.) / ligand type Pybox (0.055-0.09 eq.), NiBr2.diglyme (0.1 eq.) / ligand type Pybox (0.13 eq.), Pd2 (dba) 3 (0.02 eq.) / IPr.HC1 (0.08 eq.), Pd2 (dba) 3 (0.005 eq.) / Tri-o-tolylphosphine (0.02 eq.), Or Pd (OAc) 2 (1 mol%) / CPhos (2 mol%), and halogenated derivative (1 eq.) in an aprotic polar solvent such as DMI, DMA, DMF, NMP or THF, is stirred for 5-10 min at room temperature; then the organozinc solution (1.2-1.6 eq.) is added slowly using a syringe or cannula, keeping the internal temperature below 0 to 30 ° C. The reaction mixture is stirred at 0 ° to 75 ° C. for 5-24 hours until the halogenated derivative disappears. - Then the excess of zinc reagent is neutralized by the addition of ethanol, and the mixture is diluted with an organic solvent such as diethyl ether. This solution is washed with water (3x), dried and concentrated under reduced pressure. The residue is purified by chromatography on a silica column. 3) Introduction of the desired substituents: The groups which are incompatible with the key formation reactions of the target compounds are introduced at a later stage according to the standard procedures. Similarly, if the reagents are not commercial, the substituents will have to be introduced on the corresponding phenolic derivatives, before or after the coupling step according to the chemical compatibility. Various substitution steps are described below: Alkylation / benzylation of OH phenols base weak alkylating agent RX OR Scheme 3 - The phenolic derivative to be substituted (1 eq./phenol) in an aprotic polar solvent such as DMF or DMSO is deprotonated by adding a weak base (1-2 eq.) such as potassium carbonate or cesium carbonate. - The reaction mixture is stirred at 0-80 ° C and the alkylating agent RX (1-2 eq.) Is introduced dropwise. For example, the alkylating agent is an alkyl halide and preferably an alkyl iodide, or bromide or benzyl iodide. Stirring is continued for 1 to 96 hours. The reaction mixture is diluted by adding a saturated aqueous solution of NH 4 Cl and extracted using an organic solvent such as ethyl acetate. The organic phases are combined, dried and concentrated under reduced pressure. The residue can be purified by chromatography on a silica column.

Acylation of the phenols OH base ## STR2 ## Scheme 4 - A solution of the phenolic derivative to be substituted (1 eq./phenol) and of an organic base such as triethylamine, diisopropylethylamine or pyridine (1.2- 1.5 eq.), In an aprotic polar solvent such as dichloromethane, acetone, acetonitrile or THF at 0 ° C, is treated dropwise with a solution of the acid chloride or the corresponding anhydride (1.1-1.5 eq.) in the same solvent. - The reaction mixture is stirred at room temperature for 3-18 h and then diluted with water. After decantation and separation of the phases, the organic phase is washed with a saturated solution of NaCl, dried and concentrated under reduced pressure. - The residue is purified by chromatrography on a silica column.

Carbonation of OR 0 OR RO OH OH phenols OR Scheme 5 The procedure is similar to that of acylation using chloroformate or alkyl dicarbonate (1.1-2 eq).

EXAMPLE 2 Synthesis of Compound (B) by Grignard and Barbier-type Reaction Compound (B) is a compound of formula (I) with: R1 is a hydrogen atom, R2 is a 0-methyl radical (methoxy), and - R3 is a hydroxyl radical. 1) The compound (B) is prepared by Grignard type reaction as schematized in Scheme 2. a) The Grignard reagent is prepared according to the following protocol: - Under anhydrous conditions and under an inert atmosphere, magnesium turns (1.5 eq. .) are introduced into a piriform three-necked flask and then heated under vacuum (0.5 mmHg) at 70 ° C. for 30 min. The flask is then filled again with argon, and an anhydrous aprotic polar solvent, such as THF or diethyl ether, is added using a syringe, followed by 1,2-dibromoethane (a few drops) for initiate the reaction. - The benzyl halide (1.2-1.3 eq.) In solution in the same solvent is added slowly using a syringe so as to maintain a slight reflux (15 mL / h). After the addition, the mixture is refluxed for 2 hours. B) The coupling reaction is carried out as follows: In another three-necked flask under anhydrous conditions and under an inert atmosphere, a solution of the aldehyde (1 eq.) In the same solvent or in an apolar solvent such as toluene, is cooled to 0 ° C, then the magnesium solution is added slowly using a syringe or cannula. After the addition, the reaction mixture is stirred at 0 ° to 20 ° C. for 2 hours until the aldehyde disappears, then diluted in a saturated solution of NH 4 Cl, cooled to 0 ° C. The aqueous phase is separated and re-extracted with an organic solvent such as diethyl ether (2x). The organic phases are combined, washed with saturated NaCl solution, dried and concentrated under reduced pressure. The residue is purified by chromatography on a silica column. - The product obtained is then optionally deprotected in a second step. 2) The compound (B) is prepared by Barbier type reaction - the protocol is as follows: - To a mixture of the aldehyde (1 eq.) And the halide (2 eq.) In water, are added zinc powder (2 eq.), CdC12 (1 eq.) and InC13 (0.1 eq.). - The reaction mixture is stirred at room temperature until the reagents disappear, and then extracted with an organic solvent such as ethyl acetate (3x). The organic phases are combined, dried and concentrated under reduced pressure. The residue is purified by chromatography on a silica column. - The product obtained is then optionally deprotected in a second step. 3) The desired substituents are then introduced as shown in Example 1.

EXAMPLE 3 Activity of the Compounds (A) and (B) The compounds (A) and (B) of formula (I) were synthesized according to the protocols described in the following bibliographical references: the compound (A) is synthesized for example according to: Shekarriz, Marzieh et al.

Journal of Chemical Research 2012, 36 (1), 29-30. the compound B is synthesized for example according to: Synthetic Communications 1987, 17 (7), 877-92. A. Materials and Methods The production of reactive oxygen species in keratinocytes of the HaCaT line is evaluated by detection using the Dihydrorhodamine 123 (DHR123) probe. The DHR123 probe is an indicator of the presence of reactive oxygen species (ROS), which diffuses passively through the membranes; in the presence of ROS, this probe is oxidized to cationic rhodamine 123, which is localized in the mitochondria and has a green fluorescence. Procedure HaCaT keratinocytes in monolayer culture are placed in the presence of a solution of the compounds (A) or (B) at different concentrations (0.4-20011M) in the medium.

In parallel, the keratinocytes are incubated with vitamin C acting as a positive control and standard: an incubation with 500 μM vitamin C corresponds to 100% photoprotection. After 24 h of incubation, the cells are exposed to UVA and then incubated with the DHR123 probe for 1 h. The fluorescence of the probe is then measured. A viability test is performed in parallel to rule out the cytotoxic compounds. The dose-response curves of the fluorescence detected as a function of the concentration of compounds (A) and (B) present in the medium make it possible to calculate the effective dose EC50 which corresponds to the concentration of compound (A) or (B) allowing 50% photoprotection of keratinocytes. B. Results The results are shown in Table 1 below. Thus, the compounds (A) and (B) of the general chemical formula (I) are capable, on a micromolar cell test, of preventing the formation of reactive species induced by a molecule. UVA exposure. In a cosmetic formulation, they are therefore effective for delaying and / or lessening the deleterious effects of oxidative stress in the skin due to UV exposure, the signs of which may be reflected in the long term by an irregularity and a loss of radiance of the complexion, loosening of the cutaneous tissues and a loss of tone (firmness) of the skin, the appearance of wrinkles and furrows, a rough appearance of the skin, or.

Example 4: Composition Example According to the Invention The percentages of compounds indicated are percentages by weight relative to the total weight of the composition comprising them.

Compound A 1% Glycerin 12% POLYACRYLAMIDE 40% MA (SEPIGEL 305 from SEPPIC) 1% MA Preservatives qs Perfume qs Water qs 100% The above composition applied topically to the skin makes it possible to fight against the signs of aging. oxidative stress in the skin due to UV exposure, such as wrinkles and fine lines, or skin withered, soft and / or thinned. EXAMPLE 5 Example of Composition in Accordance with the Invention The percentages of compounds indicated are percentages by weight relative to the total weight of the composition comprising them. Compound (B) 1% Glycerin 12% POLYACRYLAMIDE 40% MA (SEPIGEL 305 from SEPPIC) 1% MA Preservatives qs Perfume qs Water qs 100% The above composition applied topically to the skin makes it possible to fight against the signs of aging oxidative stress in the skin due to UV exposure, such as wrinkles and fine lines, or skin withered, soft and / or thinned.

Claims (4)

REVENDICATIONS1. Cosmetic use, in a composition containing a physiologically acceptable medium, of at least one compound of formula (I): (I) in which: R1 signifies a hydrogen atom; a linear or branched, saturated or unsaturated C 1 -C 6 alkyl radical; a benzyl radical; a linear or branched C1-C6 alkylcarbonyl radical, saturated or unsaturated, non-conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C1-C6 alkoxycarbonyl radical; R2 represents a hydrogen atom; a hydroxyl radical; a linear or branched, saturated or unsaturated C1-C6 alkoxy radical; a benzyloxy radical; a linear or branched, saturated or unsaturated, C1 - C6 alkylcarbonyloxy radical, unconjugated with the carbonyl; or a linear or branched, saturated or unsaturated C1-C6 alkoxycarbonyloxy radical; R3 denotes a hydrogen atom or a hydroxyl radical, it being understood that R3 signifies a hydrogen atom in the only cases where R2 also signifies a hydrogen atom; hydrogen, and / or an isomer and / or a solvate of the compound of formula (I), for protecting the skin and / or its integuments from the oxidative stress caused by exposure to UV radiation. 2. Use according to claim 1, the compound of formula (I) being characterized in that - Ri means a methyl radical; and - R2 and R3 signify a hydrogen atom. 3. Use according to claim 1, the compound of formula (I) being characterized in that: - R1 means a hydrogen atom; - R2 means a methoxy radical, and - R3 means a hydroxyl radical. A compound of formula (1a) wherein: - R1 is a saturated or unsaturated C3-05 linear alkyl radical; a saturated or unsaturated C 3 -C 6 branched alkyl radical; a saturated or unsaturated C2-C6 linear alkylcarbonyl radical, non-conjugated with the carbonyl; a saturated or unsaturated C4-C6 branched alkylcarbonyl radical, non-conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C 1 -C 6 alkoxycarbonyl radical, its isomers and solvates. A compound of formula (Ib): wherein R1 and R2 are selected from the following combinations: R1 is hydrogen and R2 is hydroxyl; a linear or branched C2-C6 alkoxy radical, saturated or unsaturated; a benzyloxy radical; a linear or branched, saturated or unsaturated C 1 -C 6 alkylcarbonyloxy radical, non-conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C 1 -C 6 alkoxycarbonyloxy radical; - R1 is a methyl radical and R2 is a linear or branched C2-C6 alkoxy radical, saturated or unsaturated; a linear or branched, saturated or unsaturated, C1-C6 alkylcarbonyloxy radical which is not conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C 1 -C 6 alkoxycarbonyloxy radical; R1 represents a linear or branched, saturated or unsaturated C 2 -C 6 alkyl radical; a benzyl radical; a linear or branched, saturated or unsaturated C 1 -C 6 alkylcarbonyl radical which is not conjugated with the carbonyl; or a linear or branched, saturated or unsaturated, C1-C6 alkoxycarbonyl radical, and R2 denotes a hydroxyl radical; a linear or branched, saturated or unsaturated C 1 -C 6 alkoxy radical; a benzyloxy radical; a linear or branched, saturated or unsaturated C 1 -C 6 alkylcarbonyloxy radical, non-conjugated with the carbonyl; or a linear or branched, saturated or unsaturated C 1 -C 6 alkoxycarbonyloxy radical, its isomers and solvates. Cosmetic composition comprising, in a physiologically acceptable medium, at least one compound chosen from the compound of formula (I) as defined in one of claims 1 to 4, the compound of formula (Ia) as defined in claim 4 , and the compound of formula (Ib) as defined in claim 5, and / or one of their solvates and / or their isomers. Cosmetic composition according to claim 6, wherein the compound of formula (I) or (Ta) or (Ib) is present, alone or as a mixture, in an amount of between 0.001% and 30% by weight, preferably between 0.01% and 10% by weight, especially between 0.5% and 5% by weight, relative to the total weight of the composition. 8. Composition according to one of claims 6 or 7, wherein the physiologically acceptable medium comprises at least one cosmetic adjuvant selected from water; organic solvents, especially C2-C6 alcohols and C2-C10 carboxylic acid esters; hydrocarbon oils, silicone oils, fluorinated oils, waxes, pigments, fillers, dyes, surfactants, emulsifiers, cosmetic or dermatological active agents, filters, UV, film-forming polymers, hydrophilic or lipophilic gelling agents , thickeners, preservatives, perfumes, bactericides, odor absorbers and antioxidants. 9. Composition according to one of claims 6 to 8, being in the form of a protective composition against oxidative stress caused by exposure of the skin and / or its integuments to UV radiation. 10. A method of non-therapeutic cosmetic treatment of the skin and / or its integuments, comprising the application on the skin, and / or in particular on the scalp, of a cosmetic composition as defined in any one of claims 6. 9. A method according to the preceding claim wherein the composition is applied to mature and / or wrinkled skin. 12. Non-therapeutic use of a cosmetic composition as defined in one of claims 6 to 9, for protecting the skin and / or its integuments from oxidative stress caused by exposure of the skin, and / or especially of scalp, with UV radiation. 13. Cosmetic process for protecting the skin and / or its integuments from an oxidative stress caused by exposure to UV radiation, comprising at least one step of topical application to the skin and / or its integuments, of a composition such that defined in one of claims 6 to 9. 14. Cosmetic method according to claim 13, characterized in that the UV radiation exposure is repeated daily and / or is a prolonged exposure.