WO2016102472A1

WO2016102472A1 - 1-(3,4-disubstituted)phenyl-2-(3,4-disubstituted)phenylethane compounds and use thereof

Info

Publication number: WO2016102472A1
Application number: PCT/EP2015/080801
Authority: WO
Inventors: Julien Hitce; Maria Dalko; Marie-Céline FRANTZ
Original assignee: LOreal SA
Current assignee: LOreal SA
Priority date: 2014-12-22
Filing date: 2015-12-21
Publication date: 2016-06-30
Anticipated expiration: 2017-06-22
Also published as: FR3030509B1; FR3030509A1

Abstract

The present invention relates to the cosmetic use, in a composition containing a physiologically acceptable medium, of at least one compound of formula (1): in which: - R₁ means a hydrogen atom, a linear or branched C₁-C₆alkyl radical; a benzyl radical; a linear or branched C₁-C₆alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C₁-C₆alkoxycarbonyl, - R₂ means a hydrogen atom, a hydroxy! radical, a linear or branched C₁-C₆ alkoxy radical; a benzyloxy radical; a linear or branched C₁-C₆ alkylcarbonyloxy radical not conjugated with the carbonyl, or a linear or branched C₁-C₆ alkoxycarbonyloxy radical, - R₃ means a hydrogen atom or a hydroxy! radical, on the understanding that R₃ means a hydrogen atom only in the cases where R₂ also means a hydrogen atom, and/or of an isomer and/or of a salt and/or of a solvate of the compound of formula (I), for protecting the skin and/or skin appendages against oxidative stress caused by exposure to UV radiation.

Description

"l-(3,4-Disubstituled)pheiiyl-2-(3,4-disubstituted)phcnylethane compounds and use thereof

The present invention relates to the field of photoprotective cosmetic compositions, or photoprotective products, and more particularly of compounds used as antioxidants.

The present invention relates to the use of l -(3,4-disubstituted)phenyl-2-(3,4- dlsubstituted)phenylethane compounds and to the use thereof in particular for protecting the skin and skin appendages against the oxidative stress, caused, by exposure to UV radiation, i.e. particularly the skin, including the skin of the scalp, ft relates to compositions containing, in a physiologically acceptable medium, at least one l-(3,4-disubstituted)phenyl-2-(3,4- disubstituted)phenyleihane compound.

Keratin materials, and in particular the skin and skin appendages, are exposed daily to sunlight.

As it happens, it is known that prolonged exposure of keratin materials, and in particular of the skin, to this polychromatic light is capable of inducing skin disorders or else superficial damage.

This is in particular due to the formation of free radicals, reactive oxygen species such as (½*- and HO, which can damage DNA, certain lipids and/or proteins, and more generally which induce cell ageing. These reactive species disrupt biological mechanisms by inducing oxidative stress. This contributes to the development and acceleration of cell degeneration.

The production of reactive oxygen species therefore causes damage to DNA, to proteins and/or to lipids, and contributes to the acceleration of ageing of the cells of the skin and/or of the skin appendages.

In particular, the effects of oxidative stress affect cell respiration and result in an accelerated ageing of the skin, accompanied in particular by a dull and/or grey complexion, an uneven complexion, a loss of radiance and/or transparency of the skin, the premature formation of wrinkles or fine lines, and a loss of softness, suppleness and elasticity of the skin.

Thus, UV radiation induces a phenomenon termed "photoageing" of the skin and/or skin appendages, which includes as symptoms the appearance of wrinkles/fine lines, a loss of radiance and an unevenness of the complexion, a loss of firmness, and the appearance of roughness and of yellowing of the skin. The effects of oxidative stress are also manifested by a reduction in the vigour of the hair and/or a deterioration in the appearance thereof, in particular the hair may have a dull appearance.

Antioxidants are used in the cosmetics industry to combat free radicals. The role of antioxidants is to capture and neutralise free radicals by converting them into subspecies which are of no danger to keratin materials.

Antioxidants can therefore be used in various fields, such as anti-ageing cosmetics, and protection against oxidative stress and in particular that caused by exposure to the sun.

Many antioxidants are already known. Mention may particularly be made of 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), oligomeric proanthocyanidms (OPCs), flavonoids, catechins, in particular epicatechin and also its gallic derivatives, polyphenols, for instance tyrosol, hydroxytyrosol, sesamol, carnosol, gamma-orizanol, acids such as dihydrolipoic acid, uric acid, ferulic acid, caffeic acid, rosemarinic acid or carnosic acid.

The use of compounds derived from benzophenone has been proposed for protecting the skin against the UV radiations in the patent application CH 35 1713.

However, there is a need to identify novel compounds which have antioxidant properties and which make it possible in particular to protect the keratin materials (the skin, in particular of the scalp, and/or the skin appendages) of individuals against the harmful effects of oxidative stress induced by solar radiation.

The need to have available products which decrease or even inhibit the phenomenon of oxidative stress following exposure of the skin, in particular the scalp, to UV rays is therefore understood.

In this regard, the applicant has, surprisingly and unexpectedly, discovered that certain l -(3,4-disubstituted)phenyl-2-(3,4-disubstituted)phenylethane derivatives have the property of preventing or at least decreasing the production of reactive oxygen species that is induced by exposure of the cells of the skin to UV radiation, and thus of protecting the skin, the scalp and the skin appendages, such as hair, eyelashes and nails, against oxidative stress, in particular caused by exposure to UV radiation.

In particular, the l -(3,4-disubstituted)phenyl-2-(3,4-di.substituted)phenylethanes defined in the present description can be used for cosmetically treating the skin, including the scalp, against oxidative stress caused by exposure to UV radiation. According to the invention, the term "preventing" or "prevention" is intended to mean reducing the risk of occurrence or slowing down the occurrence of a given phenomenon, namely, according to the present invention, the signs of skin photoageing.

A subject of the invention is therefore the cosmetic use, in a composition containing a physiologically acceptable medium, of at least one l -(3,4-disubstituted)phenyl-2- (3,4-disubstituted)pheny!ethane derivative of formula (1):

in which:

- Ri means a hydrogen atom, a linear or branched Ci -Ce alky! radical; a benzyl radical; a linear or branched Ci-C6 alkylearbonyl radical not conjugated with the carbonyl

("acyl"); or a linear or branched Ci-Ce alkoxycarbonyl radical ("carbonate"),

- R.2 means a hydrogen atom, a hydroxy! radical, a linear or branched Ci-Ce alkoxy radical; a benzyloxy radical; a linear or branched Ci -Ce alkylcarbonyloxy radical not conjugated with the carbonyl, or a linear or branched Ci-C₆ alkoxycarbonyloxy radical ("carbonate"),

- R.3 means a hydrogen atom or a hydro xyl radical, on the understanding that R3 means a hydrogen atom only in the cases where R2 also means a hydrogen,

or of a solvate thereof or of a salt thereof or of an optical isomer, stereoisomer or diastereoisomer thereof, for protecting the skin and/or skin appendages against oxidative stress caused by exposure to UV radiation.

Certain 1 -(3,4-disubstituted)phenyJ-2-(3,4-disubstituted)phenylethane compounds of formula (1.) of which the use is defined in the present description are known. Certain other 1- (3,4-disubstituted)phenyl-2-(3,4-disubstituted)phenylethane compounds of formula (E) of which the use is defined in the present description are novel compounds which have been specially designed for the purposes of the implementation of the invention.

Thus, the present invention also relates to certain l-(3,4-disubstituted)phenyl-2- (3,4-disubstituted)phenylethane compounds of formula (1) defined in the present description, which compounds, to the applicant's knowledge, have not been described in the prior art. Another subject of the invention is therefore a novel compound of formula (la):

in which:

- Ri means a linear C3-C5 alky] radical; a branched C3-C5 alkyi radical; a linear C2-C0 alkylcarbonyl radical not conjugated with the carbonyl; a branched C4-C6 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched C 1-C0 alcoxycarbonyl radical, isomers ther eof (optical isomers, stereoisomers or diastereo isomers), salts and solvates thereof.

Another subject of the invention is a novel compound of formula (lb):

in which Ri and R2 are chosen from the following combinations:

- Ri means a hydrogen atom and R2 means a hydroxy! radical, a linear or branched C2-C6 alkoxy radical; a benzyloxy radical; a linear or branched O -C6 alkylcarbonyloxy radical not conjugated with the carbonyl, or a linear or branched Ci-C₆ alkoxycarbonyloxy radical;

- Ri means a methyl radical and R2 means a linear or branched Ca-Cc, alkoxy radical; a linear or branched Ci-C₆ alkylcarbonyloxy radical not conjugated with the carbonyl, or a linear or branched Ci -C₆ alkoxycarbonyloxy radical;

- i means a linear or branched C2-C& alkyl radical; a benzyl radical; a linear or branched Ci-C alkylcarbonyl radical not conjugated with the carbonyl, or a linear or branched Ci -C₆ alkoxy carbonyl radical;

and R2 means a hydroxy! radical, a linear or branched Ci-Ca alkoxy radical; a benzyloxy radical; a linear or branched Ci -Cs alkylcarbonyloxy radical not conjugated with the carbonyl, or a linear or branched C1-C0 alkoxycarbonyloxy radical,

isomers thereof (optical isomers, stereoisomers or diastereoisomers), salts thereof and solvates thereof. Likewise, the present invention provides processes for preparing the I -(3,4- disubstituted)phenyl-2-(3,4-disubstituted)phenylethane compounds of formula (1) of which the use is defined in the present description, including the novel l-(3,4-disubstituted)phenyl-2- (3,4-disubstituted)phenylethane compounds of formula (la) or (lb).

The invention also relates to a cosmetic composition comprising, in a physiologically acceptable medium, at least one compound chosen from the compounds of formula (I) and the compounds of formula (ia) and (lb) as defined above, and/or a solvate thereof and/or a salt thereof and/or an isomer thereof.

Another subject of the invention is 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 skin appendages against an oxidative stress caused by exposure to UV radiation, comprising at least one step of topical application, to the skin or skin appendages, in particular to the scalp, of a composition as defined above.

Protection of the skin and/or skin appendages against oxidative stress caused by exposure to UV radiation

The term "skin" is intended to mean ail of the cutaneous coating, and in particular the scalp and the mucous membranes. The term "skin appendages" is intended to mean all of the tegumental appendages and in particular the nails, body hair, head hair, the eyelashes and the eyebrows.

The term "oxidative stress" denotes all the damage caused by an increase in oxygen free radicals in a subject, and in particular in the skin thereof and the appendages thereof, more particularly at the level of the scalp. The oxygen free radicals are in particular:

• the singlet oxygen ·0-0· (or ^!0₂);

• the superoxide radical anion 0₂*-;

• the hydroxyl radical HO;

• the hydroperoxyl radical ΗΌ₂;

· the peroxide radical (ROO) and the alcoxy radical (RO) where R is a carbon- based chain.

These very reactive derivatives induce an oxidative stress which contributes to the development and to the acceleration of ceil 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 the oxidative stress caused by exposure to ultraviolet (UV) radiation, and in particular to UVA rays.

The compounds termed "antioxidants", also known as "free-radical scavenger compounds", are compounds capable of capturing and neutralising free radicals by converting them into less reactive chemical subspecies. l-(3 -Disubstituted)phenyl-2-(3,4-disub$tituted)phenylethane derivatives

The compounds described below comprise, for the purposes of the invention, the compounds as such and also the salts thereof, the solvates thereof and the isomers thereof.

The term "salts" designate the conventional ionic compounds, that result from the neutralization reaction of these compounds. Salts are composed of related numbers of cations and anions so that the final product is electrically neutral.

Salts of the compounds of formula (I), (la) and (lb) may be organic salts and / or minerals. They may be chosen from metal salts, for example aluminum (Al³⁺), zinc (Zn^2r), manganese (Mti²⁺) or copper (Cu²⁺); alkali metal salts, for example lithium (Li⁺), sodium (Na⁺) or potassium ( ⁺); and alkaline earth metal salts, for example calcium (Ca²⁺) or magnesium (Mg²"). it may also include salts of formula NT-U* or organic salts of formula NH 3⁺, NX3 designating an organic amine, the radicals X being identical or different, two or three X radicals can form in pairs a ring with the nitrogen atom which carries them or NX3 possibly denotes an aromatic amine. Organic amines denote in particular aikylamines, such as methyiamine, dimethylamine, trimethyiamine, triethyiamine or ethylamine; hydroxyalkylamines such as 2-hydroxyethylamine, bis- (2 -hydroxyethyl) amine or tri- (2 - hydroxyethyl) amine; cycloalkylammes such as bicyclohexylamine or glucamme, piperidine; pyridines and the like, for example col !idine, quinine or quinoline; and amino acids with basic character, as for example the lysine or arginine.

Preferably salts compounds of formula (1), (la) and (lb) are calcium salts.

The term "solvates" denotes the conventional solvates, such as those formed during the final step of the preparation of these compounds owing to the presence of solvents. Mention may be made, by way of example, of the solvates due to the presence of water or of linear or branched alcohols, such as ethanol or isopropanol.

Preferably, the isomers according to the invention are stereoisomers, in particular enantiomers. diastereo isomers, and also mixtures thereof, 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 (1):

in which:

- Rt means a hydrogen atom, a linear or branched C1-C0 aikyl radical; a benzyl radical; a linear or branched C1 -C0 alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched G-C& alkoxycarbonyl radical,

- R.2 means a hydrogen atom, a hydroxyl radical, a linear or branched CVGs alkoxy radical; a benzyloxy radical; a linear or branched C1-C0 alkylcarbonyloxy radical not conjugated with the carbonyl, or a linear or branched Ci -Ce alkoxycarbonyl radical,

- R.3 means a hydrogen atom or a hydroxyl radical, on the understanding that R3 means a hydrogen atom only in the cases where R₂ also means a hydrogen atom,

and/or of an isomer and/or of a salt and/or of a solvate of the compound of formula

(I),

for protecting the skin and/or skin appendages against oxidative stress caused by exposure to UV radiation.

For the purposes of the invention, an alkyl radical is a linear or branched, saturated or unsaturated aliphatic group.

A saturated alkyl designates a radical obtained from an alkane wherein one hydrogen is missing. An unsaturated alkyl radical designates a radical obtained from an alkene or an alkyne, comprising respectively at least one double or at least one triple bond between two carbon atoms, wherein one hydrogen is missing. These radicals are also designated as alkeny! or alkynyl groups, respectively. An alkynyi group can further comprise at least one double bond in it structure.

In the sense of the invention, when the alkyl radical is unsaturated, the expression

"the alkylcarbonyl / alkylcarbonyloxy radical is not conjugated with the carbonyl" means that a double bond present in the unsaturated alkyl radical cannot be directly linked to the carbon atom which is adjacent to the carbon atom of the carbonyl function.

A C1 -C6 alky! is an alkyl radical comprising from 1 to 6 carbon atoms, i.e. the alkyl radical can comprise 1 , 2, 3, 4, 5 or 6 carbon atoms. By way of examples of alkyl radicals, mention may be made of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyi radicals, etc.

For the purposes of the invention, a benzyl radical is an aromatic group of empirical formula C6H5-CH2- and of expanded formula (XI ):

the purposes of the invention, an alkylcarbonyl radical is a group of formula

(X2)

O

ALK

(X2),

in which "Alk" means an alkyl radical as defined above.

In the sense of the invention, when the alkyl radical is unsaturated, the expression "the alkylcarbonyl radical not conjugated with the carbonyl" means that a double bond present in the unsaturated alky! radical cannot be directly linked to the carbon atom which is adjacent to the carbon atom, of the carbonyl function.

For the purposes of the invention, an alkoxy radical is an -O-aikyl group where the aikyl group is as defined previously. A Ci-Ce aikoxy is an -O-aikyl group where the alkyl group comprises from 1 to 6 carbon atoms, i.e. the alkyl group can comprise 1, 2, 3, 4, 5 or 6 carbon atoms. A C i -Cg alkoxy radical encompasses in particular methoxy, ethoxy, propoxy, butoxy, pentoxy and hexyloxy radicals.

For the purposes of the invention, a benzyloxy radical is a group of formula -O- benzy! (X3) as shown below:

For the purposes of the invention, an alkoxycarbonyl radical is a group of formula

(X4): O

in which the "Alk-O" group means an alkoxy group as defined previously.

For the purposes of the invention, an alkyicarbonyloxy radical is a group of formula (X5):

in which "Alk" means an alkyl group as defined above.

In the sense of the invention, when the alkyl radical is unsaturated, the expression "the alkyicarbonyloxy radical not conjugated with the carbonyl" means that a double bond present in the unsaturated alkyl radical cannot be directly linked to the carbon atom which is adjacent to the carbon atom of the carbonyl function.

For the purposes of the invention, an alkoxycarbonyloxy radical is a group of formula (X6):

in which the "Alk-O" group means an alkoxy group as defined previously.

According to one particular aspect of the invention, the compound of formula (1) is characterized in that:

- Ri means a hydrogen atom or a linear or branched C1-C0 alkyl radical: preferably the alkyl radical is a l inear or branched saturated C1 -C4 alkyl radical, and even more preferentially a methyl radical; and

- R2 means a hydrogen atom or a linear or branched C1-C6 alkoxy radical; preferably the alkoxy radical is a linear or branche, saturated C1-C4 alkoxy radical, and even more preferentially a methoxy radical.

According to another aspect of the invention, the compound of formula (1) is characterized in that:

- Ri means a methyl radical; and

- R₂ and R3 mean a hydrogen atom. The expanded formula of this particular compound, referred to in the remainder of compound (A), is represented below:

- Rs means a hydrogen atom,

- R₂ means a methoxy radical, and

- R.3 means a hydroxy 1 radical.

The expanded formula of this particular compound, referred to in the remainder of the text as compound (B), is represented below:

The present invention also relates to novel chemical compounds of formula (la):

in which:

- Ri means a linear C3-C5 aikyl radical; a branched C3-C6 alkyi radical; a linear C2-C6 alkylcarbonyl radicai not conjugated with the carbonyl; a branched C4-C6 alkylcarbonyl radicai not conjugated with the carbonyl; or a linear or branched Ci-Ce alcoxycarbonyl radical, isomers thereof and salts thereof and solvates thereof. The present invention also relates to novel chemical com ounds of formula (lb):

in which R] and R₂ are chosen from the following combinations:

A. Rs means a hydrogen atom and R₂ means a hydroxy! radical, a linear or branched C₂-C₆ alkoxy radical; a benzyloxy radical; a linear or branched C 1-C0 aikylcarbonyloxy radical not conjugated with the carbonyl, or a linear or branched Ci-C₆ alkoxycarbonyloxy radical;

B. Ri means a methyl radical and R2 means a linear or branched C₂-C₆ alkoxy radical; a linear or branched Ci-C<s aikylcarbonyloxy radical not conjugated with the carbonyl, or a linear or branched Ci-C₆ alkoxycarbonyloxy radical;

C. Ri means a linear or branched C₂-C₆ alkyl radical; a benzyl radical; a linear or branched Ci-C₆ alkylcarbonyl radical not conjugated with the carbonyl, or a linear or branched Ci-C₆ alkoxycarbonyl radical;

and R₂ means a hydroxyl radical, a linear or branched Ci-Ce alkoxy radical; a benzyloxy radical; a linear or branched Cj-Ce aikylcarbonyloxy radical not conjugated with the carbonyl, or a linear or branched Cj-Cs alkoxycarbonyloxy radical,

isomers thereof and salts thereof and solvates thereof.

The present invention also relates to the cosmetic use of these compounds of formulae (la) and (lb) for protecting the skin and/or skin appendages against oxidative stress caused by exposure of the skin, in particular of the scalp, to UV radiation.

Synthesis of the novel compounds

Compounds of formula (la)

The compounds of formula (la) can be obtained from the benzyl halide derivative by means of a metallo-cata!ysed coupling reaction of Wurtz or Negishi type, according to the following reaction scheme:

Scheme 1

The possible hydroxy! groups of the reagents can, as required, be pre-protected with an appropriate protective group.

The detailed protocol for the synthesis of this compound, by means of a egishi- type reaction, is given in the experimental section.

Compounds of formula (lb)

The compounds of formula (lb) can be obtained from the benzyl halide derivative and from the aldehyde by means of a reaction of Nozaki-Hiyama, Grignard or Barbier type, a cording to the following scheme:

Scheme 2

The possible hydroxyl groups of the reagents can, as required, be pre-protected with an appropriate protective group.

The detailed protocol for the synthesis of this compound, by means of a Grignard- type or Barbier-type reaction, is given in the experimental section. Composition, in particular cosmetic composition

The present invention also relates to a composition, in particular a cosmetic composition, comprising, in a physiologically acceptable medium, at least one compound chosen from the compound of formula (1) and the compounds of formulae (la) and (lb) as defined above and/or the isomers and/or the salts and/or the solvates of said compounds.

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

Thus, the physiologically acceptable medium is in particular a cosmetically or dermato logically acceptable medium, i.e. a medium that has no unpleasant odour, colour or appearance, and that does not cause the user any unacceptable stinging, tautness or redness.

A composition according to the invention is in particular suitable for topical application to a keratin material and in particular the skin and the scalp.

Thus, it can be used as a skin care product, for example as a cream for protecting, treating or caring for the face, for the hands of for the body, as a body milk for protecting or caring for the skin, the scalp or the mucous membranes, or more particularly as a daily photoprotection product, an anti-sun product or an aftersun product.

The compositions according to the invention may also constitute products for making up the skin and/or the hair, for example by incorporating therein pigments for forming in particular foundations and makeup bases.

According to one embodiment of the invention, the cosmetic compositions are characterized in that the compound of formula (I), (la) or (lb) 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 and in particular 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, in particular C2-C6 alcohols and C2-C10 carboxylic acid esters; hydrocarbon-based oils, silicone oils, fiuoro oils, waxes, pigments, fillers, dyes, surfactants, emulsifiers, cosmetic or dermatologies I active agents, UV-screening agents, film-forming polymers, hydrophilic or lipophilic gelling agents, thickeners, preserving agents, fragrances, bactericides, odour 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 solid fatty substances like 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" is intended to mean any fatty substance that is in liquid form at ambient temperature (25°C) and at atmospheric pressure.

The oil(s) may be present in a proportion of from 0.1 % to 50% by weight, in particular from 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-based oils, in particular of animal or plant origin, synthetic oils, silicone oils or fluoro oils, or mixtures thereof.

For the purposes of the present invention, the term "silicone oil" is intended to mean an oil comprising at least one silicon atom, and in particular at least one Si-O group.

The term "hydrocarbon-based oil" is intended to mean an oil mainly containing 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 a floral water such as cornflower water and/or a mineral water such as Vittel water, Lucas water or La Roche Posay water and/or a spring water.

in the present invention, the term "water-soluble solvent" denotes a compound that is liquid at ambient temperature and water-miscible (miscibility with water of greater than 50% by weight at 25°C and atmospheric pressure).

According to one particularly preferred embodiment, the aqueous phase of a composition according to the invention comprises at least one C2 to C¾ lower monoalcohol.

The lower monoalcohols that are more particularly suitable for use in the invention comprise from 2 to 8 carbon atoms, especially from 2 to 6 carbon atoms and in particular from 2 to 4 carbon atoms, for instance ethanol, isopropanol, propanol and butanoi. Ethanol and isopropanol are thus quite particularly suitable for the invention, preferably ethanol.

The emulsion according to the invention may comprise one or more C₂ to C& lower monoalcohols in a content of at least 1%, in particular of at least 2%, in particular in a proportion of from 2% to 20% by weight, relative to the total weight of the composition.

in addition to the lower monoalcohol(s) defined previously, 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, glycerol, sorbitol, dipropylene glycol, diethylene glycol, glycol ethers such, as

ethers of mono, di- or tripropylene glycol, mono-, di- or triethylene glycol, and mixtures thereof.

The aqueous phase may also comprise any water-soluble or water-dispersible compound that is 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 composition for protection against an oxidative stress caused by exposure of the skin and/or of the skin appendages to UV radiation.

According to one particular embodiment, the composition according to the invention is a photo protective composition used daily.

According to another embodiment, the composition according to the invention is an "aftersun" composition which must be applied after exposure to the sun, which can be used daily.

The invention also relates to a non-therapeutic use of a cosmetic composition as defined above, for protecting the skin and/or skin appendages against an oxidative stress caused by exposure of the skin, and/or in particular of the scalp, to UV radiation.

Non-therapeutic cosmetic treatment process for a keratin material

Another subject of the invention is a treatment process, in particular a cosmetic treatment process, for a keratin material, characterized in that a composition as defined above is applied to the keratin material.

For the purposes of the present invention, the term "keratin material" is intended to denote the skin, the scalp, the mucous membranes such as the lips, the nails and keratin fibres, such as the eyelashes, the eyebrows and the hair.

Quite particularly considered according to the invention are the parts of the keratin materials that are the most likely to be exposed to sunlight, namely the skin and the lips, more particularly the skin of the face, of the scaip, of the neck, of the hands or of the legs, and more particularly the skin of the face.

The invention relates quite particularly to the non-therapeutic cosmetic treatment process for the skin and/or the skin appendages, comprising the application to the skin, and/or in particular to the scalp, of a cosmetic composition as defined above.

According to one particular embodiment of the process of the invention, the composition is applied to mature and/or wrinkled skin.

The invention relates quite particularly to a cosmetic process for protecting the skin and/or skin appendages against an oxidative stress in particular caused by exposure to UV radiation, comprising at least one step of topical application, to the skin and/or skin appendages, of a composition as defined above.

The topical application of the composition can take place before, during or after the exposure to U V radiation, and in particular at the time of exposure to natural sunlight.

According to another aspect of the invention, this cosmetic process is characterized by a repetition of the application step daily.

In particular, the exposure to UV radiation may be repeated daily, and/or the exposure to UV radiation is a prolonged exposure, i.e. an exposure of at least 2 hours, or even at least 3 hours, at least 4 h, at least 5 h, at least 6 h, at least 7 h, at least 8 h, at least 9 h, at least 0 h, at least 1 1 h, or of at least 12 h.

The terms "between... and..." and "ranging from... to..." should be understood as being inclusive of the limits, unless otherwise specified.

The examples that follow are presented as non-limiting illustrations of the invention. Unless otherwise mentioned, the amounts indicated are expressed as weight percentages.

EXAMPLES

Example 1. Synthesis of compound (At by reaction of Negishi type

Compound (A) is a compound of formula (I) where:

- Ri is a methyl radical and

- R.2 and 3 are hydrogen atoms.

The reaction of ^'Negishi type 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 to a pear-shaped Schlenk tube and then heated under vacuum (0.5 mmHg) at 70°C for 30 min.

- The tube is then again filled with argon, and an anhydrous aprotic polar solvent such as THF, DMA (Ν,ΊΜ-dimethylacetamide) or DM1 ( I ,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 colour turns pale (approximately 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 left to cool to ambient temperature for 1 h without stirring, in order for the unreacted zinc particles to become deposited at the bottom of the round-bottomed flask.

- The mixture is filtered under argon through a frit equipped with a pear-shaped two-necked round-bottomed flask in which the solution of the zinc derivative is recovered.

2) The coupling is carried out in the following way:

- In a three-necked round-bottomed flask, under anhydrous conditions and under an inert atmosphere, a mixture of the catalytic system (catalyst optionally coupled to a ligand), such as NiClrglyme (0.05-0.07 eq.) / ligand of the type Pybox (0.055-0.09 eq.), NiBr₂-digiyme (0.1 eq.) / ligand of the type Pybox (0.13 eq.), Pd₂(dba)₃ (0.02 eq.) / IPr-HCl (0.08 eq.), Pd₂(dba)₃ (0.005 eq.) / tri-o-lolylphosphine (0.02 eq.), or Pd(OAc)₂ (1 mol%) / CPhos (2 mol%), and of the haiogenated derivative (3 eq.) in an aprotic polar solvent such as DM1, DMA, DMF. NMP or THF, is stirred for 5- 10 min at ambient temperature;

- then the organozmc solution ( 1.2- 1.6 eq.) is slowly added using a syringe or a cannula, while maintaining the internal temperature below 0 to 30°C.

- The reaction mixture is stirred at between 0 and 75°C for 5-24 h, until the haiogenated derivative disappears.

- The excess zinc reagent is then neutralised by adding 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 silica column chromatography.

3) Introduction of the desired substituents: The groups incompatible with the key reactions for formation of the target compounds are introduced during a subsequent step according to standard procedures.

Likewise, if the reagents are not commercially available, the substituents will have to be introduced onto the corresponding phenolic derivatives, before or after the coupling step, according to the chemical compatibility.

Various substitution steps are described below:

Aikylation/benzylation of phenols

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 aikyl halide and preferentially an alky I iodide, or benzyl bromide or iodide.

- The stirring is continued for 1 to 96 h.

- The reaction mixture is diluted by adding a saturated aqueous solution of

NH C1 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 silica column chromatography.

Ac lation of phenols

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 dichiororaethane, 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 ambient temperatui'e for 3-18 h and then diluted with water.

- After decanting and phase separation, the organic phase is washed with a saturated solution of NaCI, dried and concentrated under reduced pressure.

- The residue is purified by silica column chromatography.

Carbonatation of phenols

Scheme 5

The procedure is similar to that of the acylation using an alkyl chloroformate or dibicarbonate (1.1 -2 eq).

Example 2. Synthesis of compound (B) by reaction of Grignard type and of Barbier type

Compound (B) is a compound of formula (1) where:

- Ri is a hydrogen atom,

- R.2 is an O-methyl (methoxy) radical, and

- R.3 is a hydroxy! rad ical.

1 ) Compound (B) is prepared by reaction of Grignard type as shown schematically in scheme 2.

a)The Grignard reagen is prepared according to the following protocol:

- Under anhydrous conditions and under an inert atmosphere, magnesium turnings (1.5 eq.) are introduced into a pear-shaped three-necked round-bottomed flask and then heated under vacuum (0.5 mmHg) at 70°C for 30 min.

- The round-bottomed flask is then again filled with argon, and an anhydrous aprotic polar solvent, such as ΊΊ IF or diethyl ether, is added using a syringe, followed by

1 ,2-dibromoethane (a few drops) to 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 h. b) The coupling reaction is carried out in the following way:

- In another three-necked round-bottomed flask under anhydrous conditions and under an inert atmosphere, a solution of 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 slowly added using a syringe or a cannula.

- After the addition, the reaction mixture is stirred at between 0 and 20°C for 2 h until the aldehyde has disappeared, and then diluted in a saturated solution of N UCl 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 a saturated solution of NaCl, dried and concentrated under reduced pressure.

- The residue is purified by silica column chromatography.

- The product obtained is then optionally deprotected during a second step. 2) Compound (B) is prepared by reaction of Barbier type - the protocol is the following:

- Zinc powder (2 eq.), CdC^'h (1 eq.) and InC (0.1 eq.) are added to a mixture of the aldehyde (1 eq.) and of the halide (2 eq.) in water.

- The reaction mixture is stirred at ambient temperature until the reagents have disappeared, and then extracted using an organic solvent such as ethyl acetate (3x).

- The residue is purified by silica column chromatography.

- The product obtained is then optionally deprotected during a second step.

3) The desired substituents are then introduced as is presented in Example 1 ,

Example 3, Activity of compounds (A) and (B)

Compounds (A) and (B) of formula (I) were synthesised according to the protocols described in the following literature references:

• compound (A) is synthesised for example according to: Shekarriz, Marzieh et al. Journal of Chemical Research 2012, 36(1), 29-30.

« compound (B) is synthesised for example according to: Synthetic Communications 1 987, 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 oxidised to cationic rhodamine 123, which becomes localised in the mitochondria and exhibits a green fluorescence. Procedure

HaCaT keratinocytes in monolayer culture are placed in the presence of a solution of compound (A) or (B) at various concentrations (0.4-200 μΜ.) in the medium.

In parallel, the keratinocytes are incubated with vitamin C acting as a positive control and a standard: an incubation with 500 μΜ of vitamin C corresponds to 100% photoprotection.

After 24 h of incubation, the cells are exposed to UVA, then incubated with the DHR123 probe for 1 h. The fluorescence of the probe is then measured. A viability test is carried out in parallel in order to discard the cytotoxic compounds.

The dose-effect 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) that allows 50% photoprotection of the keratinocytes.

B. Results

The results are represented in Table 1 below.

Table 1

Thus, compounds (A) and (B) of general chemical formula (I) are capable, on a cell assay at micromolar doses, of preventing the formation of reactive species induced by exposure to UVA.

n a cosmetic formulation, they are therefore effective for delaying and/or reducing the harmful effects of an oxidative stress in the skin due to exposure to UV, the signs of which can result, in the long term, in an unevenness and a loss of radiance of the complexion, a slackening of the skin tissues and a loss of tone (firmness) of the skin, the appearance of wrinkles and grooves, a rough appearance of the skin, or.

Example 4: Example of composition in accordance with the invention The percentages of compounds shown are percentages by weight, relative to the total weight of the composition in which they are present. Compound (A) 1%

Glycerol 12% Polyacrylamide at 40% AM* (Sepigel 305

from SEPPIC) 1% AM* Preserving agents qs

Fragrance qs

Water qs 100%

*AM means active material

The composition above, applied topically to the skin, makes it possible to combat signs of ageing caused by an. oxidative stress in the skin due to UV exposure, such as wrinkles and fine lines, or also withered, flabby and/or thinned skin.

Example 5: Example of composition in accordance with the invention The percentages of compounds shown are percentages by weight, relative to the total weight of the composition in which they are present.

Compound (B) 1 %

Glycerol 12% Polyacrylamide at 40% AM (Sepigel 305

from SEPPIC) 1% AM

Preserving agents qs

Fragrance qs

Water qs 100%

The composition above, applied topically to the skin, makes it possible to combat signs of ageing caused by an oxidative stress in the skin due to UV exposure, such as wrinkles and fine lines, or also withered, flabby and/or thinned skin.

Example 6: Example of composition in accordance with the invention The percentages of compounds shown are percentages by weight, relative to the total weight of the composition in which they are present. Compound (A) 1 %

Glycerol 12%

Polyacrylamide at 40% AM (Sepigel 305 from SEPPIC) 1 % AM Mixture of polydimethylsiloxane containing α,ω- hydroxy! and cyclopentadimethyisiloxane groups (15/85) 2%

Preserving agents qs

Fragrance qs

Water qs 100%

Example 7: Example of composition in accordance with the invention The percentages of compounds shown are percentages by weight, relative to the total weight of the composition in which they are present.

Compound (B) 1%

Glycerol 12% Polyacrylamide at 40% AM (Sepigel 305 from SEPPIC) 1 % AM

Mixture of polydimethylsiloxane containing α,ω- hydroxyl and cyclopentadimethyisiloxane groups (15/85) 2%

Preserving agents qs

Fragrance qs

Water qs 1 00%

Claims

1 . Cosmetic use, in a composition containing a physiologically acceptable medium, of at least one compound of formula (i):

in which:

- R] means a hydrogen atom, a linear or branched Ci-C₆ aikyl radical; a benzyl radical; a linear or branched Ct-Ce alkylcarbonyl radical not conjugated with the carbonyl; or a linear or branched. Ci-Cg alkoxycarbonyi radical,

- R.2 means a hydrogen atom, a hydroxyl radical, a linear or branched Ci-Ce alkoxy radical; a benzyioxy radical; a linear or branched Ci -C₆ alkylcarbonyloxy radical not conjugated with the carbonyl, or a linear or branched . Ci-Ce alkoxycarbonyloxy radical,

- R.3 means a hydrogen atom or a hydroxyl radical, on the understanding that R3 means a hydrogen atom only in the cases where R2 also means a hydrogen atom,

(I),

2. Use according to Claim 1 , the compound of formula (I) being characterized in that:

- Ri means a hydrogen atom or a linear or branched Ci-Ce alkyl radical; preferably the alkyl radical is a linear or branched saturated C1-C4 alkyl radical, and even more preferentially a methyl radical; and

- R2 means a hydrogen atom or a linear or branched Cj -Ce alkoxy radical; preferably the alkoxy radical is a linear or branched saturated. C1 -C4 alkoxy radical, and even more preferentially a methoxy radical.

3. Use according to Claim 2, the compound of formula (I) being characterized in that:

- Ri means a methyl radical; and

- 2 and R3 mean a hydrogen atom.

4, Use according to Claim 2, the compound of formula (I) being characterized

- Ri means a hydrogen atom,

- R₂ means a methoxy radical, and

- R3 means a hydroxyl radical.

5. Compound of formula (la):

in which:

- Ri means a linear C3-C5 alkyl radical; a branched C3-C& alk l radical: a linear C₂- Ce alkyicarbonyl radical not conjugated with the carbonyl; a branched C₄-C6 alkyicarbonyl radical not conjugated with the carbonyl; or a linear or branched C1 -C0 alcoxycarbonyi radical, isomers thereof and salts thereof and solvates thereof.

6. Compound of formula (lb):

in which Ri and R₂ are chosen from the following combinations:

- Ri means a hydrogen atom and R₂ means a hydroxy! radical, a linear or branched C₂-C₆ alkoxy radical; a benzyloxy radical; a linear or branched Ci-C& alkylcarbonyioxv radical not conjugated with the carbonyl, or a linear or branched Ci -C₆ alkoxy carbonyloxy radical;

- Ri means a methyl radical and R₂ means a linear or branched C2-C6 alkoxy radical; a linear or branched Ci-C₆ alkylcarbonyioxv radical not conjugated with the carbonyl, or a linear or branched Ci-C& alkoxycarbonyloxy radical;

- Ri means a linear or branched C2-C6 alkyl radical; a benzyl radical; a linear or branched Cj-C₆ alkyicarbonyl radical not conjugated with the carbonyl, or a linear or branched Ci-C₆ alkoxy carbonyl radical; and R.2 means a hydroxyl radical, a linear or branched Cj -Ce aikoxy radical; a benzyioxy radical; a linear or branched Ci -Ce alkylcarbonyloxy radical not conjugated with the carbony], or a linear or branched d-Ce alkoxycarbonyloxy radical,

isomers thereof and salts thereof and solvates thereo f.

7. Cosmetic composition comprising, in a physiologically acceptable medium, at least one compound chosen from the compound of formula (Ϊ) as defined in one of Claims 1 to 4 and the compound of formula (la) as defined in Claim 5 and the compound of formula (lb) as defined in Claim 6 and/or a solvate thereof and/or a salt thereof and/or an isomer thereof.

8. Cosmetic composition according to Claim 7, in which the compound of formula (I.) or (la) or (lb) 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 and in particular between 0.5% and 5% by weight, relative to the total weight of the composition.

9. Composition according to either of Claims 7 and 8, in which the physiologically acceptable medium comprises at least one cosmetic adjuvant chosen from water; organic solvents, in particular C2-C alcohols and C2-C10 carboxylic acid esters; hydrocarbon-based oils, silicone oils, fluoro oils, waxes, pigments, fillers, dyes, surfactants, emulsifiers, cosmetic or dermatoiogical active agents, UV-screening agents, film-forming polymers, hydrophilic or lipophilic gelling agents, thickeners, preserving agents, fragrances, bactericides, odour absorbers and antioxidants.

10. Composition according to one of Claims 7 to 9, which is in the form of a composition for protection against an oxidative stress caused by exposure of the skin and/or of the skin appendages to UV radiation.

1 1 . Non-therapeutic cosmetic treatment process for the skin and/or skin appendages, comprising the application to the skin, and/or in particular to the scalp, of a cosmetic composition as defined in any one of Claims 7 to 1 0.

12. Process according to the preceding claim, in which the composition is applied to mature and/or wrinkled skin.

13. Non-therapeutic use of a cosmetic composition as defined in one of Claims 7 to 10, for protecting the skin and/or skin appendages against an oxidative stress caused by exposure of the skin, and/or in particular of the scalp, to UV radiation.

14. Cosmetic process for protecting the skin and/or skin, appendages against an oxidative stress caused by exposure to UV radiation, comprising at least one step of topical application, to the skin and/or skin appendages, of a composition as defined in one of Claims 7 to 10.

15. Cosmetic process according to Claim 14, characterized in that the exposure to UV radiation is repeated daily and/or is a prolonged exposure.