WO2010063948A2 - Novel c-xyloside oxime compounds, and cosmetic use - Google Patents

Abstract

The present invention relates to novel compound of formula I, where R is a hydrogen atom or a C₁–C₂₂ saturated or C₂–C₂₂ unsaturated linear alkyl radical, or a C₃–C₂₂ saturated or unsaturated branched alkyl radical, said alkyl radical being optionally substituted for a phenyl group. The present invention also relates to the cosmetic and dermatological compositions containing said compounds, and to the use thereof to prevent and cosmetically treat signs of aging on the skin.

Description

 New compounds C-xylosides oximes and use in cosmetics

The present invention relates to novel O-xyloside oximes derivatives, in particular the compositions comprising them, and their use for combating cutaneous aging.

Women and men currently tend to want to appear young as long as possible and therefore seek to fade the marks of aging skin, which result in particular in the form of wrinkles and fine lines. In this regard, advertising and fashion mention products intended to keep as long as possible a glowing skin without wrinkles, marks of a young skin, especially as the physical aspect acts on the psyche and / or on morale. Up to now, wrinkles and fine lines have been treated with cosmetics containing active agents acting on the skin, for example by improving its cell renewal or by promoting the synthesis or preventing the degradation of the skin. elastic fibers that make up the skin tissue.

It is known that human skin consists of two superficial tissues, the epidermis, the other deep, the dermis.

The natural human epidermis is composed mainly of three types of cells, which are the keratinocytes, a very large majority, melanocytes and Langerhans cells. Each of these cell types contributes, through its own functions, to the essential role played in the body by the skin, in particular the protective role of the body against external aggressions (climate, ultraviolet rays, tobacco, etc.), called "function fence".

The dermis provides the epidermis with a solid support. It is also its nurturing element. It consists mainly of fibroblasts and an extracellular matrix composed mainly of collagen, elastin and a substance called the fundamental substance. These components are synthesized by fibroblasts. There are also leucocytes, mast cells or tissue macrophages. Finally, the dermis is crossed by blood vessels and nerve fibers.

The extracellular matrix of the dermis is composed of proteins belonging to several large families: collagens, matrix glycoproteins other than collagens (fibronectin, laminin), elastin and proteoglycans. Also found in the extracellular matrix of the dermis are glycosaminoglycans in free form (ie not bound to a protein). It is now well established that specific interactions exist between these different classes of proteins to give rise to a functional tissue. An extracellular space (microarray) also exists in the epidermis. This space plays an extremely important functional role in the renewal and maintenance of the cellular tissue.

Proteoglycans are complex macromolecules consisting of a branched central protein trunk, or network of proteins, to which are attached numerous polyosidic side chains called glycosaminoglycans.

In the remainder of the present application, the proteoglycans will be designated by the abbreviation PGs and the glycosaminoglycans by the abbreviation GAGs.

GAGs have long been referred to as acidic mucopolysaccharides because of their high water-holding capacity, their carbohydrate nature, and their acidity from their multiple negative charges.

Thus, the polarity of GAGs makes them implicitly participate in certain biological functions such as the hydration of tissues, the fixation of cations or the role of ionic filtration barrier.

PGs and GAGs are synthesized by different cells in the dermis and epidermis: fibroblasts, keratinocytes and melanocytes. Fibroblasts mainly synthesize collagens, matrix glycoproteins other than collagens (fibronectin, laminin), GAGs, proteoglycans and elastin. Keratinocytes mainly synthesize sulfated GAGs and hyaluronic acid, whereas melanocytes apparently do not produce hyaluronic acid.

When incorporated into a PG, the GAGs are in the form of linear chains composed of the repetition of a basic diholoside always containing a hexosamine (glucosamine or galactosamine) and another one

(glucuronic acid, iduronic acid or galactose). Glucosamine is either

N-sulfated, N-acetylated. In contrast, galactosamine is always N-acetylated. In addition, there may be O-linked sulfate groups on hexosamine, uronic acid and galactose.

The strong anionic character of GAGs is explained by the presence of carboxylate groups in hexuronic acids (glucuronic acid and iduronic acid) and O- and N-linked sulfate groups.

The main GAGs are hyaluronic acid or hyaluronan (HA), heparan sulfate (HS), heparin (HP), chondroitin, chondroitin sulfate (CS), chondroitin 4-sulfate or chondroitin sulfate A (CSA), chondroitin 6-sulfate or chondroitin sulfate C (CSC), dermatan sulfate or chondroitin sulfate B (CSB), and keratan sulfate (KS), which differs from other glycosaminoglycans by the presence of galactose instead of uronic acid.

GAGs may also exist in the extracellular matrix in free form, ie not bound to a matrix protein: this is particularly the case of hyaluronic acid.

During the synthesis of the PGs, the GAGs are polymerized from these anchoring structures.

The synthesis of GAGs requires the coordinated and concerted action of very specific enzymes (transferases, epimerases, sulfotransferases) adjacent to the endoplasmic reticulum membrane and the golgi apparatus. Then a multitude of biochemical reactions (N-deacetylation, N- and O-sulfation, epimerization) modify the two components constituting the base unit and this heterogeneously along the chain. From one heparan sulphate chain to another, for example, the glucuronic acid / iduronic acid ratio, the nature, the number and the position of the O-sulphates, as well as the N-sulphate / O-sulphate ratio can vary, which, potentially, offers immense structural diversity.

In general, the biological roles of PGs are very diverse, ranging from a passive function of mechanical support (for example serglycines) or a role of ionic barrier of molecular filtration (for example perlecan and bamacan of the glomerular basement membrane). , to more specific effects in adhesion, spreading, proliferation, cell differentiation or morphogenesis, or, to very specific effects of PG-protein interactions, such as betaglycan receptor function or interaction of decorin with collagen. They also play a fundamental role in the controlled release of different growth factors.

One of the roles of the dermal connective tissue is to protect the body against external aggressions by forming at the same time an informative interface. To do this, the dermis has a strong mechanical strength while maintaining, however, great flexibility.

Its resistance is ensured by the dense network of collagen fibers, but it is the PGs and the hyaluronic acid, ensuring the hydration, the distribution and the flexibility of the fibers which make the difference between the skin and, for example , the leather. The PGs constitute 0.5 to 2% of the dry weight of the dermis, the collagen alone representing up to 80%.

The concentration and distribution in human skin of GAGs and PGs varies with age.

Hyaluronic acid or hyaluronan (HA) is the main GAG of the dermis, the latter containing half of HA of the body.

The synthesis of HA is carried out in particular by the fibroblasts, near the inner face of the plasma membrane. It is carried out continuously. This gigantic polysaccharide (several million daltons) has a very high intrinsic viscosity, ensuring the hydration and assembly of the various elements of the connective tissue by formation of supramolecular complexes. Dermatan sulfate (DS), initially isolated from the dermis, is also very abundant in the skin. It constitutes 40 to 50% of dermal GAGs.

Parallel to the mechanisms contributing to the development of these specialized extracellular matrices, there are continuous remodeling processes whose regulation depends on the balance between synthesis and degradation of the matrix protein elements.

Several families of matrix proteases are now described as well as the factors involved in their activation-inactivation.

During chronological and / or photoinduced aging, the dermis and epidermis undergo numerous modifications and degradations which, with age, lead to flaccidity and a loss of cutaneous suppleness. Among the degraded elements (notably collagen and elastin), PGs and GAGs are also altered. Indeed, during aging, fibroblasts and keratinocytes produce less and less PGs and GAGs and their synthesis is imperfect. This results in significant disorganization: the deposit of GAGs on the protein skeleton forming the PG is abnormal, which results in less avidity for the water of these PGs and therefore a decrease in hydration and tonicity fabrics. Restoring a normal production of PGs and GAGs by fibroblasts and keratinocytes helps, in part, to compensate for loss of skin hydration.

The degradation of these matrices therefore contributes to the phenomenon of drying out and loss of flexibility of the skin. We therefore understand the importance of being able to have products whose effects are aimed at maintaining the level of PGs and GAGs in the skin and thus maintain, among other things, good hydration and good flexibility.

It is known from WO 02/051828 to use C-glycoside compounds to increase the synthesis of glycosaminoglycans by fibroblasts and / or keratinocytes.

The Applicant has discovered, surprisingly and unexpectedly, that other amino C-glycoside derivatives are capable of improving the synthesis of sulfated glycosaminoglycans such as chondroitin sulfate and dermastane sulfate.

Their effectiveness is more efficient than that of the C-glycoside compounds already known. They are more effective for improving epidermal renewal and firmness of the skin and to fight more effectively against the signs of skin aging. They also have a beneficial effect on the structure of the dermal-epidermal junction, especially on the cohesion between dermis and epidermis.

These novel compounds therefore find particular application in cosmetic or dermatological compositions, intended to prevent and / or cosmetically treat cutaneous aging; in particular to prevent and / or treat, especially topically, the cutaneous signs of aging, and especially the cutaneous signs related to a wrinkled skin, a skin with an alteration of its viscoelastic or biomechanical properties, a skin with an alteration in the cohesion of its tissues, a thinned skin and / or a skin having an alteration of its surface appearance.

The compositions according to the invention may more particularly make it possible to maintain and / or restore the properties of extensibility, tonicity, firmness, suppleness, density and / or elasticity of the skin.

By "biomechanical properties of the skin" is meant here the properties of extensibility, tonicity, firmness, suppleness and / or elasticity of the skin.

By "cutaneous signs of aging" is meant here any modification of the external appearance of the skin due to aging whether chronobiological and / or extrinsic, in particular photoinduced or hormonal; among these signs, we can distinguish:

- wrinkled skin, which is reflected in particular by the appearance of wrinkles and / or fine lines, the skin having an alteration of its viscoelastic or biomechanical properties, or skin having a lack of elasticity and / or of extensibility and / or firmness and / or of flexibility and / or tonicity, which is reflected in particular by wilted, soft, sagging or sagging skin, - the skin showing an alteration of the cohesion of its tissues;

- thinned skin,

the skin exhibiting an alteration of its surface appearance, which results in particular in an alteration of the skin's grain, for example a roughness.

The subject of the present invention is therefore new Oximes C-glycoside compounds of formula (I) as defined below.

The invention also relates to a cosmetic or dermatological composition comprising, in a physiologically acceptable medium, at least one such compound.

The compounds according to the invention thus correspond to the following formula (I):

in which R denotes a hydrogen atom or a linear C1-C22 saturated alkyl radical. or unsaturated C2-C22. or a branched, saturated or unsaturated C 3 -C 22 alkyl radical. said alkyl radical being optionally substituted with a phenyl group; as well as their salts, their solvates.

The term alkyl, in the context of the present invention, means a saturated or unsaturated hydrocarbon chain. Among the alkyl groups which are suitable for the implementation of the invention, mention may especially be made of methyl, ethyl, isopropyl, n-propyl, n-butyl, t-butyl, isobutyl, sec-butyl, pentyl, hexyl and heptyl groups. , octyl, nonyl, decyl ,.

Preferably, R denotes a hydrogen atom or a linear C1-C22 saturated alkyl radical, optionally substituted with a phenyl radical. Preferentially, R denotes a hydrogen atom or a linear C4-C18 alkyl radical or a phenyl-substituted C1-C4 alkyl radical.

In particular, mention may be made of the following compounds:

The compounds of formula (I) may also be in the form of salts, solvates or optical isomers (cis or trans form of the oxime function).

As salts of the compounds of formula (I), mention may be made of the salts of mineral acids, such as sulfuric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, boric; as well as salts of organic acids, such as propionic acid, acetic acid, succinic acid, fumaric acid, lactic acid, glycolic acid, citric acid and the like. tartaric acid.

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

The compounds of formula (I) may be prepared according to scheme I below

Scheme I

by reaction of C-β-D-xylopyranoside-n-propan-2-one (II) (compound described in Example 1 of Application WO 02/051828) with a hydrochloride alkyl O-ether hydroxylamine (III) (in which R has the same meaning as that described above for the compounds of formula (I)), in particular at a temperature of between 15 and 50 ^° C., preferably at 20 ^° C., in a polar solvent such as ethanol, methanol, isopropanol, water, in the presence of a base such as sodium hydroxide, for 1 to 18 hours. The solvent is then evaporated and water is added. The aqueous phase is extracted with an organic solvent and then the crude product obtained is purified for example on silica gel or by recrystallization, in order to obtain the desired product.

Hydroxylamine (III) alkyl O-ether hydrochloride, when R denotes an alkyl radical, can be obtained according to the following synthesis scheme II:

(Hl)

(IV)

Scheme II

by reaction of tert-butyl-N-hydroxycarbamate (1 molar equivalent) a halogenide RX (X = I, Br, Cl, and preferably Br) (in the presence of a mineral base (e.g. molar equivalent); ) potassium carbonate) or organic (eg pyridine) in a polar solvent (eg acetonitrile), especially at a temperature between 25 and 100 ° C, for 1 to 18 hours. The reaction medium is then cooled to room temperature, and the reaction is stopped by adding water. The alkyl O-ether intermediate obtained after concentration of the organic phases is then dissolved in a protic polar solvent (for example isopropanol) in the presence of HCl. After stirring for 1 to 18 hours, the solvent is evaporated and the solution is evaporated. The residual acid is washed with an organic solvent (for example dimethyl ether) to obtain the hydrochloride of the hydroxylamine (III) alkyl O-ether of the hydroxylamine O-alkylated hydrochloride hydroxylamine hydrochloride (compound III for which R = H) is prepared by treatment of hydroxylamine in the presence of HCl.

The present invention also relates to a composition comprising, in a physiologically acceptable medium, a compound of formula (I) as described above. The composition is in particular a cosmetic or dermatological composition.

The compound of formula (I) may be present in cosmetic or dermatological compositions, in an amount which may be between 0.01 and 10% by weight, preferably between 0.1 and 5% by weight, in particular between 0 and 5 to 3% by weight, relative to the total weight of the composition.

The composition further comprises a physiologically acceptable medium, which will preferably be a medium cosmetically or pharmaceutically, in particular dermatologically acceptable, that is to say without odor, color or unpleasant appearance, and which does not generate tingling, tugging or redness unacceptable for the user. In particular the composition is suitable for topical application to the skin.

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

The composition according to the invention can then comprise all the cosmetic adjuvants usually used in the intended field of application. We can notably mention water; organic solvents, in particular alcohols C- | -CQ 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, antioxidants.

These optional adjuvants may be present in the composition in a proportion of 0.001 to 80% by weight, especially 0.1 to 40% by weight, relative to the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase or into the aqueous phase of the composition, or into lipid vesicles. In any case, these adjuvants, as well as their proportions, will be chosen by those skilled in the art in such a way that the advantageous properties of the compounds according to the invention are not, or not substantially impaired by the addition envisaged.

As oils which can be used in the invention, mention may be made of mineral oils (vaseline oil), vegetable oils (avocado oil, soya oil), animal oils (lanolin), vegetable oils and the like. synthesis (perhydrosqualine), silicone oils (cyclomethicone) and fluorinated oils (perfluoropolyethers). Fatty alcohols (cetyl alcohol), fatty acids, waxes (carnauba wax, ozokerite) can also be used as fats.

Hydrophilic gelling agents or thickeners include carboxyvinyl polymers (carbomer), acrylic copolymers such as copolymers of acrylates / alkylacrylates, polyacrylamides, polysaccharides, natural gums and clays; lipophilic gelling agents or thickeners include modified clays such as bentones, metal salts of fatty acids, and hydrophobic silica.

As active agents, it will be advantageous to introduce into the composition used according to the invention at least one compound chosen from: desquamating agents; moisturizing agents; depigmenting or propigmenting agents; anti-glycation agents; NO-synthase inhibitors; agents stimulating the synthesis of dermal or epidermal macromolecules and / or preventing their degradation; agents stimulating the proliferation of fibroblasts and / or keratinocytes or stimulating the differentiation of keratinocytes; muscle relaxants and / or dermo-decontracting agents; tensors; anti-pollution and / or anti-radical agents; agents acting on microcirculation; agents acting on the energetic metabolism of cells; and their mixtures. Examples of such additional compounds are: retinol and its derivatives such as retinyl palmitate; ascorbic acid and its derivatives such as magnesium ascorbyl phosphate and ascorbyl glucoside; tocopherol and its derivatives such as tocopheryl acetate; nicotinic acid and its precursors such as nicotinamide; ubiquinone; glutathione and its precursors such as L-2-oxothiazolidine-4-carboxylic acid; plant extracts and especially vegetable proteins and their hydrolysates, as well as phytohormones; marine extracts such as seaweed extracts; bacterial extracts; sapogenins such as diosgenin and WiId Yam extracts containing them; ceramides; hydroxy acids such as salicylic acid and n-octanoyl-5-salicylic acid; resveratrol; oligopeptides and pseudodipeptides and their acyl derivatives; manganese and magnesium salts, in particular gluconates; and their mixtures. As indicated above, the composition according to the invention may also contain UV filters or active photoprotective agents in the UVA and / or UVB, in the form of organic or inorganic compounds, the latter being optionally coated to render them hydrophobic. .

The organic photoprotective agents may in particular be chosen from: anthranilates, in particular menthyl anthranilate; benzophenones, in particular benzophenone-1, benzophenone-3, benzophenone-5, benzophenone-6, benzophenone-8, benzophenone-9, benzophenone-12, and preferentially benzophenone-3 (Oxybenzone), or Ben-zophenone-4 (Uvinul MS40 from BASF); benzylidenecamphers, in particular 3-benzylidene camphor, benzylidenecamphosulfonic acid, camphor benzalkonium methosulphate, polyacrylamidomethylbenzylidene camphor, terephthalylidene di-camphorsulfonic acid, and preferentially 4-methylbenzylidene camphor (Eusolex 6300 de Merck); benzimidazoles, in particular benzimidazilate (Neo Heliopan AP from Haarmann and Reimer), or phenylbenzimidazole sulfonic acid (Eusolex 232 from Merck); benzotriazoles, in particular trisiloxane drometzol, or methylene bis-benzotriazolyltetramethylbutylphenol (Ciba Tinosorb M); cinnamates, in particular cinoxate, DEA methoxycinnamate, diisopropyl methylcinnamate, dimethoxycinnamate glyceryl ethylhexanoate, isopropyl methoxycinnamate, isoamyl cinnamate, and preferably ethocrylene (Uvinul N35 from BASF), octyl methoxycinnamate (Parsol MCX from Hoffmann La Roche), or octocrylene (Uvinul 539 from BASF); dibenzoylmethanes, especially butyl methoxydibenzoylmethane (Parsol 1789); imidazolines, in particular ethylhexyl dimethoxybenzylidene dioxoimidazoline; PABAs, in particular ethyl dihydroxypropyl PABA, ethylhexyldimethyl PABA, glyceryl PABA, PABA, PEG-25 PABA, and preferentially diethylhexylbutamido-triazone (Uvasorb HEB 3V Sigma), ethylhexyltriazone (Uvinul T150 from BASF), or ethyl PABA (benzocaine); salicylates, especially dipropylene glycol salicylate, ethylhexyl salicylate, homosalate, or TEA salicylate; triazines, in particular anisotriazine (Tinosorb S from Ciba); drometzole trisiloxane. The inorganic photoprotective agents preferably consist of zinc oxide and / or titanium dioxide, preferably of nanometric size, optionally coated with alumina and / or stearic acid.

This composition may be in any galenical form normally used in the cosmetic or dermatological field, and especially in the form of an aqueous or aqueous-alcoholic solution, optionally gelled, of an optionally biphasic lotion-type dispersion, of an emulsion obtained by dispersing a fatty phase in an aqueous phase (O / W) or conversely (W / O), or a triple emulsion (W / O / W or W / O / H) or a vesicular dispersion ionic and / or nonionic type; aqueous or oily gel. These compositions are prepared according to the usual methods. According to this invention, it is preferred to use a composition in the form of an emulsion, especially oil-in-water emulsion.

The composition may be more or less fluid and have the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste, a gel , a foam. It can optionally be applied in the form of an aerosol. It can also be in solid form, in particular in the form of a stick.

When the composition is an emulsion, the proportion of the fatty phase can range from 5 to 80% by weight, preferably from 8 to 50% by weight relative to the total weight of the composition. The emulsifier and the co-emulsifier may be present in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight, relative to the total weight of the composition.

The composition according to the invention may constitute a skin care composition, and in particular a cleaning, protective, treatment or care cream for the face, for the hands, for the feet, for the large anatomical folds. or for the body (for example, day creams, night creams, make-up removing creams, foundation creams, sunscreen creams); cleansing milk, protective or caring body milk, anti-sun milk; a lotion, gel or mousse for the care of the skin, such as a cleaning lotion.

The composition according to the invention is advantageously an anti-aging composition, especially of care, intended to treat and / or fight against, cosmetically, the external signs of skin aging; the composition is more particularly a skincare composition for mature skin.

The composition may also be a make-up composition, especially a foundation.

The invention also relates to a method for cosmetic treatment of the skin, comprising the application to the skin of a cosmetic composition as defined above. This method finds an advantageous application in the treatment of the skin, in particular mature skin and / or wrinkled skin, in particular the face, in particular the forehead, the neck and / or the hands.

The invention also relates to the use of a cosmetic composition as defined above or of a compound of formula (I) as described above. in order to prevent and / or cosmetically treat the cutaneous signs of aging, in particular the cutaneous signs chosen from the wrinkled skin, the skin having an alteration of its viscoelastic or biomechanical properties, the skin having an alteration in the cohesion of its tissues, the the amine skin, and the skin showing an alteration of its surface appearance.

The invention also relates to the cosmetic use of a composition as defined above or of a compound of formula (I) as described above, to improve the firmness of the skin and / or to improve the structure of the skin. dermal-epidermal junction and / or to reinforce the cohesion between the dermis and the epidermis.

The invention is further illustrated by the following non-limiting examples.

Example 1 Synthesis of (C-β-D-xylopyranosyl) acetone O-benzyloxime

2.78 g (17.4 mmol) of benzylhydroxylamine hydrochloride were neutralized with 0.7 g (17.7 mmol) of sodium hydroxide, and then 3 g (15.8 mmol) of C-β-D- xylopyranoside-n-propan-2-one diluted in 10 ml of ethanol. The mixture was stirred for 2 hours at 20 ^° C. At the end of the reaction, the reaction medium was evaporated and then taken up in water. The aqueous phase was extracted with dichloromethane. After evaporation of the solvent, the crude product was purified on silica gel (methanol / dichloromethane eluent). 2.88 g of product (63% yield) were obtained as a light yellow liquid.

NMR spectra ^"1H and mass spectra were consistent with the structure of the expected product.

Example 2 Synthesis of (C-β-D-xylopyranosyl) acetone oxime

The compound was prepared according to the synthesis method described in Example 1 using 402 mg of hydroxylamine hydrochloride, 232 mg (5.8 mmol) of sodium hydroxide in 23 ml of water, 1 g of C-β- D-xylopyranoside-n-propan-2-one diluted in 5 ml of ethanol.

0.8 g (67% yield) of product was obtained as an orange-yellow liquid.

NMR spectra ^"1H and mass spectra were consistent with the structure of the expected product.

Example 3 Synthesis of (C-β-D-xylopyranosyl) acetone O-octyloxime

'17

a) Synthesis of hexadecanoxamine hydrochloride:

In a flask fitted with a magnetic stirrer, N-Boc-hydroxylamine (10.0 g, 0.075 mol), acetonitrile (200 ml) and then potassium carbonate (10.38 g) were introduced under argon. 0.12 moles). The reaction mixture was stirred and the 1-bromooctane (13.08 ml, 0.075 mol) was added dropwise at 20 ⁰ C, then refluxed for 6h. After cooling, the insoluble material was filtered, and the filtrate was evaporated in vacuo. The resulting residue was then poured into distilled water and extracted with pentane. The organic phase was washed with water and dried over MgSO 4 and then evaporated under vacuum. 16.2 g yield 88% of the expected intermediate compound as a colorless oil.

In a 250 ml flask equipped with a magnetic stirrer, the compound (15 g, 0.061 mol) prepared previously, ethanol (50 ml) and gaseous hydrochloric acid in 4N methanol ( 100 ml). The reaction mixture was then stirred at 20 ^° C. overnight, and then evaporated under vacuum. The solid product obtained was rinsed with ether and then dried under vacuum. The expected octanoxyamine hydrochloride was obtained as white crystals (70% yield). b) Synthesis of the oxime: In a 100 ml flask equipped with a magnetic stirrer was introduced octanoxyamine hydrochloride (8 g, 0.044 mol) and a mixture [(ethanol (50 ml): dichloromethane (20 ml): distilled water (10 ml). The sodium hydroxide (1.763 g, 1 eq, 0.0421 mol) in 5 ml of water was then added dropwise at 20 ⁰ C and the reaction mixture was stirred for 15 minutes. C-β-D-xylopyranoside-n-propan-2-one (II) (12.53 g, 0.063 mol, 1.5 eq) in ethanol (15 mL) was added dropwise. drop with strong stirring, which was kept overnight at 20 ^° C. [the reaction is monitored by NMR and TLC, eluent: AcOEt / MeOH / water (8.5: 1, 5: 1), developer: H2SO4 10%] The reaction mixture was then evaporated in vacuo to remove only the organic solvents The resulting residue was diluted with distilled water (20 ml) and extracted with diethyl ether. organic was washed with water (3x15 ml) and dried on MgSO 4, then evaporated under vacuum, (13.5 g) of expected product was obtained in the form of an off-white gel.

NMR spectra ^"1H and mass spectra were consistent with the structure of the expected product.

Example 4 Synthesis of (C-β-D-xylopyranosyl) acetone O-pentyloxime

a) Synthesis of pentyloxyamine hydrochloride

Ν-Boc-hydroxylamine (50.0 g, 1.0 eq, 375.5 mmol) was solubilized in anhydrous acetonitrile (1 L). Potassium carbonate (51.90 g; 1.0 eq; 375.5 mmol) and 1-bromopentane (69.68 ml; 1.5 eq; 563.3 mmol) were successively added to the solution. limpid obtained. The suspension was then refluxed and stirred under argon for 40 hours. After returning to ambient temperature, the reaction medium (MR) was filtered on a frit. The salts were washed with acetonitrile (2 L). The organic phases were combined and concentrated in vacuo to give a yellowish oil (72 g) contaminated with residual salts. This oil was solubilized in heptane (200 ml) and washed with distilled water (3 * 150 ml). The aqueous phases were extracted with heptane (2 * 200 ml). The organic phases were finally collected and dried over sodium sulfate. The reaction was repeated a second time on the same scale (50 g of β-Boc-hydroxylamine). The two crude obtained were combined and dried in vacuo to give the desired intermediate product (119.8 g, 589.3 mmol, yield = 78%) as a pure yellow-orange oil by NMR. Then the compound obtained above (49.95 g, 1.0 eq, 245.7 mmol) was solubilized in a 1.25 M solution of HCl in isopropanol (295 ml) under argon at room temperature. After stirring for 48 hours, the substrate was completely consumed (followed by TLC). The reaction medium was then concentrated under vacuum to give a yellowish paste. This residue was taken up once in ether (100 ml) and immediately concentrated in vacuo. The solid obtained was again taken up in ether (100 ml) and triturated. The precipitate obtained was filtered on frit (porosity 4) and washed with ether (400 ml). After drying under vacuum, pentyloxyamine hydrochloride (22.84 g, 163.59 mmol, yield = 66%) was obtained in the form of a fine white powder (pure by NMR). b) Synthesis of oxime A solution of pentyloxyamine hydrochloride (32.1 g, 1.0 eq, 230.0 mmol) and sodium hydroxide (9.2 g, 1.0 eq, 229.98 mmol) in distilled water (327 mL) was added to a solution of C-β-D-xylopyranoside-n-propan-2-one (II) (53.5 g; 1.2 eq.; 281.4 mmol) in ethanol (107 mL) cooled to 0 ^° C. After 22 hours of reaction, a TLC follow-up shows the complete consumption of the two starting products. The reaction medium was then diluted by addition of ethyl acetate (500 mL) and the organic phase was isolated. The aqueous phase was extracted with ethyl acetate (2 * 400 mL). The organic phases were combined, washed with distilled water (500 mL), dried over sodium sulfate, filtered and evaporated under vacuum. The crude product (68 g) was then purified by silica column chromatography (pure ethyl acetate). Three successive columns made it possible to obtain the expected oxime (56.9 g, 206.5 mmol, yield = 56%) which is in the form of a light brown pasty solid. This lot was a mixture of two isomers Z (25%) and E (72%), as determined by HPLC and ¹ H NMR

Example 5 Synthesis of (C-β-D-xylopyranosyl) acetone O-dodecyloxime

a) Synthesis of dodecanoxyamine hydrochloride

The procedure was as in Example 3, using in this case N-Boc-hydroxylamine (15.0 g, 0.11 mol), acetonitrile (300 ml), potassium carbonate (15, 6g, 0.11 mol) and 1-bromododecane (27.3 ml, 0.11 mol). The corresponding N-Boc derivative was obtained almost quantitatively (34.1 g) in the form of a colorless oil. For the second synthesis step, the procedure was as in Example 3, using the N-Boc derivative prepared above (30.1 g, 0.01 mol). The expected dodecanoxyamine hydrochloride was obtained as white crystals (72% yield). b) Synthesis of the oxime:

The procedure was as in the case of Example 3, using dodecanoxyamine hydrochloride (10 g, 0.0421 mol), solubilized in the mixture [(ethanol (50 ml), CH 2 Cl 2 (30 ml), distilled water (10) ml)]; sodium hydroxide (1.68 g, 0.044 mol) in distilled water (7.5 ml); C-β-D-xylopyranoside-n-propan-2-one (II) (12 g, 0.063 mole, 1.5 eq) in ethanol (15 ml). After treatment, (15.55 g, 99% yield) of a white solid product was obtained.

NMR spectra ^"1H and mass spectra were consistent with the structure of the expected product.

Example 6 Synthesis of (C-β-D-xylopyranosyl) acetone O-hexadecyl oxime

a) Synthesis of Hexadecanoxyamine Hydrochloride The procedure was as in Example 3, using in this case N-Boc-hydroxylamine (16.6 g, 0.12 mol) and acetonitrile (320 ml) potassium carbonate (15.6 g, 0.11 mol) and 1-bromohexadecane (36.8 ml, 0.12 mol). Quite quantitatively (36 g) of the corresponding N-Boc derivative was obtained in the form of a white solid. For the second synthesis step, the procedure was as in Example 3, using the N-Boc derivative prepared above (12 g, 0.0336 mol). The expected hexadecanoxyamine hydrochloride was obtained as white crystals. b) Synthesis of the oxime:

The procedure was as in the case of Example 3, using hexadecanoxamine hydrochloride (7 g, 0.0238 mol), solubilized in the mixture [(ethanol (35 ml), CH 2 Cl 2, (15 ml), distilled water (10 ml)]; sodium hydroxide (0.954 g, 1 eq, 0.0238 mol) in distilled water (10 ml); C-β-D-xylopyranoside-n-propan-2-one (II) (6.79 g, 0.0359 mol, 1.5 eq) in ethanol (10 ml). After treatment, 10.2 g (98% yield) of a white solid product were obtained. NMR spectra ^"1H and mass spectra were consistent with the structure of the expected product.

Comparative Example 7

Study of the effect of C-glycoside derivatives on the synthesis of sulfated glycosaminoglycans on fibroblasts:

The study is done by measuring the incorporation of radioactive 35s-sulfate into the neosynthesized matrix by normal human dermal fibroblast cultures.

The fibroblast cultures are carried out according to the standard cell culture methods, namely in a DMEM medium sold by Gibco, in the presence of L-glutamine (2 mM), penicillin (50 IU / ml) and 10% of serum. fetal calf (Gibco).

The fibroblasts were cultured in 96-well plates. At confluence, the culture medium was replaced with suitable culture medium containing or not (control) the test compound or reference, and then the cells were incubated for 48 hours. The 35 S-sulfate radioactive label was added (40 μCi final) and the cells were incubated for a further 24 hours. All conditions were realized 3 times.

The glycosaminoglycans of the extracellular matrix were extracted with a chaotropic buffer volume (50 mM Tris / HCl, 4 M guanidine, 5 mM EDTA, pH

8.0).

The sulphated GAGs were purified by ion exchange chromatography: absorption of anionic molecules on Q-Sepahrosis beads under conditions of high stringency, desorption of the weakly and moderately anionic molecules with a 6 M NaCl 0.2 mM NaCl solution. , then washings. The radioactivity incorporated in the highly cationic molecules remaining on the support (mainly GAGs) was measured by liquid scintillation.

The results are evaluated by providing a control consisting of cells that have not been treated with a compound of formula (I). A positive control (TGFβ at 10 ng / ml) known to stimulate the synthesis of GAGs is introduced into the test carried out on fibroblasts as a positive reference.

The results are expressed as a percentage of variation of glycosaminoglycan synthesis relative to the control.

Three attempts were made for the test compound. The measured values are given in counts per minute (cpm). Depending on the culture medium used for the experimental design, the value obtained for the control may vary. But it is the difference obtained between the test compound and the control which is decisive for evaluating the activity of the test compound. The comparisons of the results obtained for a test compound were carried out using the Student's test.

The standard deviation of the mean (esm) was calculated according to the following relation: esm = standard deviation / (n) ^1/2 n being the number of tests performed. sd is the standard deviation p: confidence interval The results are presented in the following tables:

Compounds 1 and 2 were evaluated in a first experimental plane.

Compound 4 has been evaluated in another experimental design.

The results obtained show significantly that compounds 1, 2 and 4 are very effective for increasing the synthesis of sulfated GAGs, and also superior in efficacy compared to the amine compound 1 - [2- (amino) -propyl] - C-β -D-xylopyranose.

This activity makes it possible to attribute to these compounds a biological activity on the firmness of the skin and thus to fade the signs of skin aging.

Example 8

An oil-in-water emulsion facial cream, comprising (% by weight), is prepared: compound of example 1 0.005% glycerol stearate 2% polysorbate 60 (ICI Tween 60) 1% stearic acid 1 , 4% triethanolamine 0.7% carbomer 0.4% liquid fraction of shea butter 12% perhydrosqualene 12% antioxidant qs perfume, preservative qs water qs 100% A similar composition is prepared with the compounds of Examples 2 to 6.

The composition applied to the face helps strengthen the firmness of the skin and thus fade the signs of skin aging.

Example 9

An anti-aging gel for the skin is prepared comprising (% by weight): compound of Example 1 2% hydroxypropylcellulose (Klucel H from Hercules) 1% antioxidant qs perfume, preservative qs isopropanol 40% water qs 100%

A similar composition is prepared with the compound of Examples 2 to 6.

The composition applied to the face helps strengthen the firmness of the skin and thus fade the signs of skin aging.

Claims

1. Compounds of formula (I):

in which R denotes a hydrogen atom or a linear C1-C22 saturated alkyl radical. or unsaturated C2-C22. or a branched, saturated or unsaturated C 3 -C 22 alkyl radical. said alkyl radical being optionally substituted with a phenyl group; as well as their salts, their solvates.

2. Compounds according to claim 1, in which R denotes a hydrogen atom or a linear C1-C22 saturated alkyl radical. optionally substituted with a phenyl radical.

3. Compounds according to one of the preceding claims, wherein R denotes a hydrogen atom or a linear C4-C18 alkyl radical or a C1-C4 alkyl radical substituted with a phenyl group.

4. Compounds according to one of the preceding claims, chosen from the following compounds:

- (C-β-D-xylopyranosyl) acetone O-benzyloxime

- (C-β-D-xylopyranosyl) acetone oxime - (C-β-D-xylopyranosyl) acetone O-octyloxime

- (C-β-D-xylopyranosyl) acetone O-pentyloxime

- (C-β-D-xylopyranosyl) acetone O-dodecyloxime

- (C-β-D-xylopyranosyl) acetone O-hexadecyloxime

5. Cosmetic or dermatological composition comprising, in a physiologically acceptable medium, at least one compound of formula (I) as defined in any one of claims 1 to 4.

6. Composition according to the preceding claim, wherein the compound of formula (I) is present, alone or as a mixture, in an amount between 0.01 and 10% by weight, preferably between 0.1 to 5% by weight, in particular between 0.5 and 3% by weight, relative to the total weight of the composition.

7. Composition according to one of claims 5 or 6, wherein the physiologically acceptable medium comprises at least one cosmetic adjuvant selected from: water; organic solvents, in particular C 1 -C 6 alcohols and C 2 -C 10 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 gelling agents or lipophilic, thickeners, preservatives, perfumes, bactericides, odor absorbers, antioxidants.

8. Composition according to one of claims 5 to 7, wherein the physiologically acceptable medium comprises at least one compound selected from: desquamating agents; moisturizing agents; depigmenting or propigmenting agents; anti-glycation agents; NO-synthase inhibitors; agents stimulating the synthesis of dermal or epidermal macromolecules and / or preventing their degradation; agents stimulating the proliferation of fibroblasts and / or keratinocytes or stimulating the differentiation of keratinocytes; muscle relaxants and / or dermo-decontracting agents; tensors; anti-pollution and / or anti-radical agents; agents acting on microcirculation; agents acting on the energetic metabolism of cells; and their mixtures.

9. Composition according to one of claims 5 to 8, being in the form of an anti-aging composition, including care to fight against the external signs of skin aging.

10. A method of non-therapeutic cosmetic treatment of the skin, comprising the application to the skin of a cosmetic composition as defined in one of claims 5 to 9.

11. Method according to the preceding claim wherein the composition is applied to the mature skin and / or wrinkled.

12. Non-therapeutic use of a cosmetic composition as defined in one of claims 5 to 9, to improve the firmness of the skin.

13. Non-therapeutic use of a cosmetic composition as defined in one of claims 5 to 9, for preventing and / or treating cutaneous signs of aging.