BR102016013146B1 - COMPOUNDS DERIVED FROM 3- (ALKYLTHY) PROPENOIC ACID, COSMETIC OR DERMATOLOGICAL COMPOSITION AND THEIR USES - Google Patents

Abstract

compounds derived from 3-(alkylthio)propenoic acid, and their cosmetic applications. the present invention relates to the components of formula (i): in which y, r1, r2 and r3 are defined in the description. the invention also relates to a cosmetic or dermocosmetic composition, containing such a compound. the compounds of the invention are useful as photoprotective agents.

Description

[001] The object of the present invention is a family of conjugated compounds derived from 3-(alkylthio) propenoic acid, as well as their uses in cosmetics as a photoprotective agent against solar radiation. The invention also relates to cosmetic compositions intended for photoprotection of the skin or phaneros.

[002] In addition to its beneficial effects (support for the production of vitamin D and melatonin, antidepressant, well-being, etc.), the sun also generates, in the cutaneous plane, harmful effects, in the short and long term: erythema, aging accelerated tissue, photodermatoses, carcinomas, melanomas ( Ichihashi M. et al., Toxicology, 2003, volume 189, pp. 21-39 ). And among the different families of rays that reach the earth's surface, ultraviolet radiation, limited to type A (à 320-400 nm, UV-A) or B (à 290-320 nm, UV-B) ultraviolet radiation, was identified as being at the origin of these harms.

[003] The skin has, however, intrinsic defense systems that allow it to fight against the aggression of the sun. Thus, under the effect of solar radiation, a so-called natural or internal photoprotection is already expressed there, ensured by a production of photoprotective melanin pigments or even by a thickening of the corneal layer with a greater number of layers of keratinocytes in the epidermis. Transurocanic acid, a metabolite of histidine, present in significant concentration in the upper layers of the epidermis and, in particular, in the corneal layer, also participates in this natural photoprotection, expressing an endogenous protective role against the harmful action of UV-B (Barresi C et al., J. Invest. Dermatol., 2011, volume 131, pages 188-194).

[004] Extrinsically, a skin protection against solar radiation can also be induced (Lacour et al., Annals of Dermatology and Venerology, 2007, vol. 134, pp.18-24). In general, this photoprotection, classified as artificial as opposed to natural photoprotection, is ensured by external means, including, in addition to the use of clothes that cover the topical application of photoprotective cosmetic products. These products or preparations more often contain, solubilized or dispersed in an excipient, protective substances that can be classified into three broad categories, screens, whose action aims to reflect the whole of solar radiation and, therefore, to prevent its penetration into the skin; filters, whose action aims to absorb a part of solar radiation, generally ultraviolet A (320-400 nm) and B (290-320 nm) radiation, after releasing the absorbed photonic energy by thermal exchange with the skin; and, finally, the so-called active photoprotective agents as opposed to screens and filters, which are, in general, substances capable of trapping the oxygen reactive species ("EOR" or "ROS" in English) formed when radiation is absorbed by molecules naturally present in the skin (photosensitization mechanism).

[005] These topical preparations are, in general, characterized by a sun protection factor (FPS in French or SPF, in English for Sun Protection Factor ) indicating the level of protection against solar erythema (sunburn), adapted to conditions of burn and particular skin phototypes. For antisun formulas with high SPF, screens and filters are associated.

[006] The screens in these preparations are mostly inert substances of mineral origin (powders: zinc oxide, titanium dioxide, etc.). The use of these in sun protection products remains, however, still bad, with the appearance of white traces when applied. A presentation in the nano-particle state improves the exploration of these screens, although their safety of use in this form is questioned, for some years with a potential risk of penetrating the skin.

[007] Organic chemical filters are generally of synthetic origin, alternatively of natural origin, when it comes to oils or extracts from plant species. Its effectiveness comes down to an absorbing effect of ultraviolet light, due to the structural presence of chromophore groups, capable of absorbing, after dissipating, light radiation of a determined wavelength. The chromophore groups in these chemical filters are almost systematically composed of a mono- or polycyclic aromatic nucleus (phenyl, benzyl, benzylidene, benzoyl, naphthyl, anthracenyl, etc.) conjugated to carbonyl groups or aliphatic unsaturated systems for greater relocation of the electrons under the effect of absorbed radiation (excited state), before returning to a steady state with dissipation of the received proton energy and/or remission of less dangerous radiation (infrared, for example).

[008] Thus, one can mention, among these chemical filters, chromophores belonging to the state of the art (Rai R. et al., Indian J. Dermatol., 2012, vol. 57 (5), pp. 335-342 ), commercially available, the following compounds, whose absorption spectrum is above all specific to UV-B:

[009] - the ester derivatives of para-amino benzoic acid (PABA), such as 2-ethyl hexyl-4-dimethyl amino benzoate (padimate O);

[0010] - methoxy cinnamic acid derivatives, such as octylmethoxy cinnamate (octinoxate or OMC) and 2-ethoxy ethyl - methoxy cinnamate (cinoxate);

[0011] - salicylic acid derivatives, such as ethyl hexyl salicylate (octysalate) and trolamine salicylate;

- o 2-ethylhexyl-2-cyano-3,3-diphenyl-2-propenoate (octocrylene);

[0013] -the phenyl benzimidazol sulphonic acid (ensulizol).

[0014] The following compounds can also be mentioned, whose absorption spectrum is above all specific to UV-A:

[0015] - derivatives of dibenzoyl methane, such as butyl methoxydibenzoyl methane (avobenzone);

[0016] - the sulfonic acid terephthalidene dicamphor (ecamsula or Me-xoryl SX®).

[0017] Finally, the following compounds can be mentioned, whose absorption spectrum is broader (UV-B + UV-A radiation):

[0018] - benzophenones, such as benzophenone-3 (oxybenzone) and benzophenone 8 (dioxy benzone);

[0019] - hydroxy benzotriazole derivatives;

[0020] - new triazines, such as benzoxazines (Brugè et al., Plos One, 2014, 9, e83401).

[0021] For many of these organic filters, chosen above all for physicochemical criteria (FPS, absorption spectrum, remanence on the skin surface), it stands out in addition to potential allergic disorders (contact allergies, photoallergy, itching) however conducted in the recent years (Uter W. et al., Contact Dermatitis, 2014, volume 71, pages 162-9), which is not always communicated about the photochemical innocuousness of these chromophore agents, in particular about their degradation products, such as the products of photoisomerization.

[0022] More recently, other protection strategies have been developed with the introduction in antisolar formulas of active agents, such as DNA repair enzymes, and especially antioxidant compounds, such as vitamins C and E, or polyphenols (Matsui MS et al. , J, Invest. Dermatol., 2009, volume 14, pages 56-59). Interest in this strategy was reinforced by recent evidence of the ability of visible (400-700 nm) and near infrared (700-1440 nm) rays to induce the formation of ROS in the skin (Liebel F. et al. ., J. Invest. Dermatol., 2012, volume 132, pages 19011907; Schroeder P. et al., Exp. Gerontol., 2008, volume 43, pages 629-632). Still, the incorporation of these active ingredients in topical formulas, however, presents problems: lack of stability, cost and, above all, a formation in contact with oxygen, or its reagent species, of by-products, whose toxicology is often unknown.

[0023] As a result, considering these different elements, the applicant joined in identifying new photoprotective compounds of topical cosmetic scope, offering broad-spectrum protection against solar radiation, with the concomitant objective of designing products that do not form by-products degradation or photoconversion may be poorly tolerated by the skin. Indeed, it is currently considered of primary importance in the cosmetic or dermocosmetic industry to provide proof of the safety of the substances of interest, but also of the safety of the reactional by-products resulting from the targeted cosmetic activity.

[0024] To achieve these objectives, the applicant was originally interested in a sulfur-containing antioxidant compound, 3-methyl thiopropenoic acid (TMPA), which is found in certain plants in the form of conjugates, such as the trans acid starch conjugate. -3-methyl thiopropenoic (E-TMPA) and the ethanol amine, isolated in legume plant grains and to which an anti-inflammatory potential is conducted (Ikegami F. et al., Chem. Pharm. Bull, 1989, vol. 37, pp.1932-1933).

[0025] Afterwards, during a structure-activities research, aiming to optimize the antioxidant power of TMPA conjugates, the applicant found that a group of original amide-type conjugates, obtained from the unnatural stereoisomer of RMPA, the cis-3-methyl thiopropenoic acid (Z-TMPA), prepared stereoselectively (Faria de Medeiros E. et al, in J. Chem. Soc. Perkin Trans I, 1991, no 11, pp.27525-2730) had an unexpected capacity to also effectively absorb UV-N radiation and to dissipate the acquired energy, isomerizing to produce its trans-configured stereoisomer. Therefore, the applicant observed that this feature was accompanied by the property of opposing the endogenous photoinduced isomerization of the natural sunscreen mentioned in the preamble above, transurocanic acid. This has the advantage of preserving the protective activity of this intrinsic defense system of the skin, but above all of opposing the negative effects linked to the photoisomerization of transurocanic acid. Indeed, it is now established that its "natural sunscreen" behavior (absorption of light energy) causes transurocanic acid (or E-UCA) to transform into cis-urocanic acid (or Z UCA) for which unfavorably, and coming undoing the benefits of E-UCA, a pro-oxidant behavior is attributed, responsible for intracellular data and, in particular, DNA (Mc Loone P. et al., J. Invest. Dermatol., 2005, vol. 124, pp. ). 10711074; Gibbs JK et al., J. Invest. Dermatol., 2011, vol. 131, pp. 14-17 and cited references). E-UCA is also unfavorably implicated in the suppressive effect of ultraviolet radiation on the immune system, this "UV-induced immunosuppression" translating at the cutaneous level into a defect in the immune response to sensitizing agents, an increased sensitivity to infections, as well as an increased risk of skin cancers (Poon TSC et al., J. Invest. Dermatol., 2003, vol. 121, pp. 184-190). Fighting against ultraviolet radiation-induced immunosuppression is, moreover, currently another major goal in photoprotection, and in this regard an immune protection index ("IFP") has been defined (Wolf P. et. al., J. Invest. Dermatol., 2003, vol. 121, pp 1080-1087) which is mentioned in certain anti-solar formulas.

[0026] Overall, the identified set of original amide-type conjugates, derived from cis-3-methyl thiopropenoic acid, responds to the objective of providing, in complete safety, a broad protection against solar radiation, due to:

[0027] - an antioxidant power, which allows it to oppose the oxidative stress generated by photosensitization reactions, involving endogenous chromophores (porphyrins, quinones, flavins, etc...) and radiation as diverse as the ultraviolet, visible and the next infra-red. This effect is thus able to oppose the formation of hydroperoxides (SqOOH) formed by the reaction of singular oxygen on scalene [cf. test 1 below]. It is also opposed to the intracellular oxidative stress induced by the production of "cis-UCA", according to the first results of the study. More broadly and of interest in the context of a sought after innocuousness of reaction by-products, it is underlined that this antioxidant power leads to oxidized forms of the thioether radical of the conjugates, according to the invention, successively a sulfoxide and a sulfone, both well tolerated by skin cells ( see test 2 below);

[0028] - an ability to improve the survival of epidermal cells (immortalized keratinocyte cell line "HaCaT"), exposed to cytotoxic doses of UV-B, this in a dose-dependent manner and from the use of low concentrations of active substance [ cf. test 3 below];

[0029] - an ability to absorb a lot, such as a filter, ultraviolet B radiation, then dissipate the absorbed energy, isomerizing in a derivative devoid of toxicity [cf. test 4 below], and without the genesis of an undesirable activity contrary to urocanic acid, for example. This behavior is, moreover, of heightened interest when the photoinduced metabolite is an "identical-nature" compound, due to its identified presence in the natural state;

[0030] - finally, the property of opposing the photoinduced isomerization of transurocanic acid, which allows to limit in fine the immunosuppressive effects of ultraviolet radiation [cf. test 5 below].

[0031] With regard to the state of the art, the prior art reveals, according to the applicant's knowledge, the same photoisomerization with retention of the activity of interest for benzylidene camphor derivatives used as an ultraviolet filter in anti-solar preparations (Beck I et al., Int. J. Cosmetic Science, 1981, volume 3, pages 139-152). But these camphor derivatives remain structurally distant from those objects of the present invention.

[0032] With reference to the inhibition of the UV-induced conversion of transurocanic acid in immunosuppressive cis-urocanic acid, appear in the state of the art of the advertised "immunoprotective" agents, such as phenyl benzimidazole - sulfonic acids (Hurks HMH et al., J. Invest. Dermatol., 1997, volume 109, pages 699-703), cinnamates, benzophenones and other dibenzoyl methanes (Fillay-Jones JJ et. al., Mutation Res., 1998, volume 422, pp. 155-159), etc. , all again structurally removed from those objects of the present invention.

[0033] On the other hand, in addition to these aspects, a prior art can be pointed out with compounds that also carry a thiopropenamide motif, of multiple interests (US patents 5464832 and EP0410726; patents US 5300672 and US 3914301). In these latter documents, however, the targeted compounds show distinctly antimicrobial, fungicidal, bactericidal and biocidal virtues.

na qual[0034] The invention has, therefore, as its first object a family of conjugates cis or (Z)-isomers obtained pure by coupling reaction between (z)-3-(alkyl thio) propenoic acid and primary or secondary alkyl amines or even a selection of non-ionizable and hydroxylated polar amino acids, characterized by the fact that this family is represented by the following general formula (I):

in which

[0035] - Y = S or SO;

[0036] - R1 is a linear or branched C1-C4 alkyl radical;

[0037] - R2 is a hydrogen atom; a straight or branched C1-C4 alkyl radical;

[0038] - R3 is:

[0039] • a C1-C18 alkyl radical, a C3-C18 alkene radical, a C3-C4 alkyne radical, that alkyl, alkene or alkyne radical being linear or branched, and optionally substituted by a hydroxyl radical, a group hydroxyphenyl or dihydroxyphenyl;

[0040] • the side chain of an amino acid chosen from thyrosine, hydroxy proline, serine and its homoserine and isoserine analogues, threonine and its homothreonine and isothreonine analogues.

na qual[0041] According to a preferred embodiment of the invention, the conjugates (Z) isomers, according to the invention, are represented by the formula (II) below:

in which

[0042] - Y = S or SO;

[0043] - R1 is a linear or branched C1-C4 alkyl radical;

[0044] - R3 is a C1-C4 alkyl radical, a C3-C4 alkene radical, a C3-C4 alkyne radical, this alkyl, alkene or alkyne radical being linear or branched, and optionally substituted by a hydroxyl radical , a hydroxyphenyl or dihydroxyphenyl group.

Advantageously, the conjugates (Z)-isomers of formula (I) or (II) are such that Y = S.

[0046] Advantageously, the conjugates (Z)-isomers of formula (I) or (II) are such that R1 is a methyl radical.

Advantageously, the conjugates (Z)-isomers of formula (I) or (II) are such that R3 is an ethyl radical, substituted by a hydroxyl radical, a hydroxyphenyl or dihydroxyphenyl group. Thus, by way of example of alkyl amines engaged in the coupling reaction with cis-3-methylthiopropenoic acid (Z-TMPA), one can mention ethanol amine, tyramine, a catecholamine such as dopamine, adrenaline or noradrenaline.

[0048] As non-limiting examples of conjugates (Z)-isomers of formula (I) or (II), the following compounds can be mentioned for which the induced photoisomerization product is naturally present in plants:

[0049] - o (Z) - N -(2-hydroxyethyl)-3-(methylthio)propenamide;

[0050] - o (Z) - N -(4-hydroxy phenethyl)-3-(methylthio)propenamide

[0051] Currently and according to the applicant's knowledge, the conjugates (Z) isomers of formula (I) above are new, with the exception of the compounds 2-cis-entadamide A, isopenangine, N-ethyl-cis-3-butyl mercapto acrylamide and N-ethyl-cis-3-methyl mercapto acrylamide, synthesized according to the obtaining process according to the applicant's development:

[0052] I) stereoselective preparation of (z)-3-thiocyanate propenoic acid by reaction of propiolic acid on potassium thiocyanate;

[0053] II) alkylation reaction at low temperature of (z)-3-thiopropenoic acid, according to I) with the aid of alkyl iodide, preferably methyl iodide, and obtaining the resulting synton acid (z)- 3-(alkylthio)propenoic acid, preferably (z)-3-methylthiopropenoic acid;

[0054] III) Coupling reaction at room temperature between (z)-3-alkyl thiopropenoic acid according to II), preferably (z)-3-methyl thiopropenoic acid and a primary or secondary alkyl amine or a polar amino acid , preferably a linear or branched primary alkyl amine and even more preferably to ethanol amine or tyramine, and obtaining the resulting conjugated derivatives, preferably as (z)-N-(2-hydroxyethyl)-3-(methylthio) propenamide and (z)-N-(4-hydroxy phenethyl)-3-(methylthio)propenamide, the coupling being carried out with the aid of a coupling agent well known to the person skilled in the art, preferably N,N'-dichyl hexyl carbodiimide, and an activator of the carboxylic function of the (z)-3-alkyl thiopropenoic acid synthon, it so well known to the skilled person preferably the hydroxy benzotriazole.

[0055] These conjugates (Z)-isomers are presented in powdery solid form, soluble in an alcoholic medium, stable both in powder and in solution for a duration longer than 28 days.

The mentioned conjugates (Z)-N-(2-hydroxy ethyl)-3-(methylthio)propenamide and (z)-N-(4-hydroxy phenethyl)-3-(methylthio)propenamide have the following characteristics physical - chemical and spectral: - (z)-N-(2-hydroxy ethyl) -3-(methyl thio) propenamide

[0057] Rf = 0.40 (CHCl3/MeOH, 90:10);

[0058] Melting point = 112 oC

[0059] 1H NMR (CD3OD): δ = 2.32ppm (s, 3H, CH3), 3.31 (t, 2H,J=6Hz, CH2-NH), 3.60ppm (t, 2H, J = 6 Hz, CH 2 -OH), 5.89 ppm (d, 1H, J = 10 Hz, CH=), 6.93 ppm (d, 1H, J = 10 Hz, CH=);

[0060] 13C NMR (CD3OD): δ = 19.2ppm (CH3), 42.8ppm (N-CH2), 61.8ppm (CH2-O), 115.9ppm (=CH), 148, 6 ppm (=CH-S). 169.2 ppm (C=O);

[0061] - (z)-N-(4-hydroxy phenethyl)-3-(methylthio)propenamide

[0062] Rf = 0.35 (toluene / acetone / acetic acid, 100:50:2);

[0063] mp = 132°C;

[0064] 1H NMR (CD3OD): δ = 2.31ppm (s, 3H, CH3-S), 2.69 (t, 2H,J=7.5Hz, CH2-Ph), 3.35ppm ( t, 2H, J=7.5Hz, CH2-N), 5.83ppm (d, 1H, J=10Hz, CH=), 6.90ppm (d, 1H, J=10Hz, CH= ); 6.70 ppm (d, 2H, J = 8.5 Hz, CPh-H), 7.02 ppm (d, 2H, J = 8.5 Hz, CPh-H);

[0065] 13C NMR (CD3OD): δ = 19.2 ppm (CH3-S), 35.9 ppm (CH2-Ph) 42.2 ppm (CH2-N), 116 ppm (CH=), 116.2 ppm (phenol), 130.7 ppm (phenol), 131.3 ppm (phenol), 148.4 ppm (CH=), 156.9 ppm (phenol), 169 ppm (C=O).

na qual:[0066] According to a second aspect, the invention also extends to a composition, for cosmetic or dermocosmetic use, intended for photoprotection, and in particular, of the skin or phaneros. This composition comprises, in association with any adjuvant physiologically compatible with the skin or phaneros, as the main active ingredient, a compound of general formula (III) below:

in which:

[0067] - Y, R1, R2 and R3 are as defined above for the compounds of formula (I).

na qual:[0068] Advantageously, the cosmetic or dermo-cosmetic composition, according to the invention, comprises, as the main active ingredient, a compound of formula (IV):

in which:

[0069] - Y = S or SO;

[0070] - R1 is a linear or branched C1-C4 alkyl radical;

[0071] - R3 is a C1-C4 alkyl radical, linear or branched, optionally substituted by a hydroxyl radical, a hydroxyphenyl or dihydroxyphenyl group.

[0072] The general formula (III) encompasses, at the same time, the Z-isomers of the formula (IIIa), the E-isomers of the formula (IIIb), and the mixtures, preferably racemic, of these isomers:

[0073] Likewise, the general formula (IV) encompasses, at the same time, the Z-isomers of the formula (IVa), the E-isomers of the formula (IVb), and the mixtures, preferably racemic, of these isomers:

[0074] Within the scope of the present invention, it is understood by "main active ingredient" an active substance capable of opposing the harmful effects of solar radiation.

[0075] Advantageously, the amount of compound of general formula (III) or (IV) in the target compositions is comprised between 0.001% and 0.1% by weight relative to the total weight of the composition, preferably between 0.005% and 0. 0.5% by weight.

[0076] In terms of the recommended molar concentration in compound of general formula (III) or (IV), in the target compositions, this is advantageously comprised between 0.05 and 5 mM, preferably between 0.25 and 2.5 mM , as illustrated by the tests below.

Advantageously, the compound of general formula (III) or (IV) is such that Y = S.

Advantageously, the compound of general formula (III) or (IV) is such that R1 is a methyl radical.

Advantageously, the compound of general formula (III) or (IV) is such that R3 is an ethyl radical, substituted by a hydroxy radical, a phenol or dihydroxyphenyl group. Thus, by way of example of corresponding primary or secondary alkyl amines engaged in the coupling reaction with the acids Z-TMPA and E-TMPA, mention may be made of ethanol amine, tyramine, a catechol amine such as dopamine , adrenaline or norepinephrine.

[0080] Particularly, in the compositions according to the invention, the compound of general formula (III) or (IV) is a conjugate (z)-isomer of formula (IIIa) or, respectively, (IVa) before acid derivative (z)-3-(alkylthio)propenoic.

[0081] Particularly advantageously, the compositions of the invention comprise, as the main ingredient, (z)-N-(2-hydroxyethyl)-3-(methylthio)propenamide or (z)-N-(4 -hydroxy phenethyl)-3-(methylthio)propenamide.

[0082] The compositions according to the invention are adapted for administration by the topical cutaneous route, presented in all forms normally used for such administration. As an indication and not limitation, the compositions may be in the form of suspensions, lotions, creams, aqueous or hydroalcoholic gels, multiple powders and emulsions, and may possibly be microemulsions or nanoemulsions, etc.

[0083] The compositions, according to the invention, may contain as physiologically acceptable adjuvant at least one adjuvant known to the technician and acceptable in the cosmetic or dermocosmetic domains, chosen among oils, waxes, silicone elastomers, surfactants, cotensoactives, thickeners and/or gelling agents, humectants, emollients, organic and inorganic sunscreens, photostabilizers, preservatives with the exception of aldehyde-donating preservatives, dyes, mattifying agents, tensor agents, sequestrants, perfumes, etc., and mixtures thereof.

[0084] These organic or inorganic sunscreens are active in UV-A and/or UV-B, chosen from anthranilates, cinnamic derivatives, dibenzoyl methane derivatives, salicylic derivatives, camphor derivatives, triazine derivatives , benzophenone derivatives, beta derivatives, beta diphenyl acrylate, benzotriazole derivatives, benzal malonate derivatives, benzimidazole derivatives, imidazolines, bis-benzo azolyl derivatives, benzoxazole derivatives, derivatives from p-amino benzoic acid (PA-BA), methylene bis-(hydroxy phenyl benzotriazole) derivatives, filter polymers and filter silicones, dimers derived from alpha-alkyl styrene, 4,4-diaryl butadienes , pigments or nanopigments of metallic oxides (titanium, zinc, iron, zirconium, cerium oxides), coated or uncoated, and their mixtures.

[0085] The compositions, according to the invention, may, in addition, comprise one or more additional actives, the technician controlling, however, so that any additional active compounds, as well as their proportions, are chosen in such a way that the advantageous properties recognized for the compositions according to the invention are not altered. These additional actives can be chosen, without this list being limiting, from among deglycant agents, agents stimulating the synthesis of collagen or elastin or preventing their degradation, agents stimulating the synthesis of glycosamino glycans or proteoglycans or preventing their degradation, agents increasing cell proliferation, depigmenting or pro-pigmenting agents, anti-oxidizing or anti-radical or anti-pollution agents, hydrating agents, lipose-stimulating agents, draining or detoxifying agents, anti-inflammatory agents, penetration accelerating agents, scaling agents, calming and/or anti-irritant agents, astringent agents, agents acting on microcirculation, etc., and mixtures thereof.

[0086] The compositions according to the invention can thus further comprise at least one agent for tanning and/or softening the skin.

[0087] Another object of the invention relates to the use, in a cosmetic or dermocosmetic composition, of a compound of formula (III) or (IV), as defined above as a photoprotective agent against solar radiation.

[0088] Another object of the invention relates to a compound of formula (III) or formula (IV), as defined above, or a mixture of these compounds, for their use, in a cosmetic or dermocosmetic composition for photoprotection against solar radiation.

[0089] Another object of the invention relates to a method of photoprotection from solar radiation which comprises the application of a cosmetic or dermocosmetic composition, as defined above, containing a compound of formula (III) or (IV).

[0090] Preferably, in the above use and method, the compound of formula (III) or (IV) is a conjugate (z)-isomer of formula (IIIa) or, respectively, (IVa) before acid (z) derivative -3-(alkylthio)propenoic, in particular (z)-N-(2-hydroxyethyl)-3-(methylthio)propenamide or (z)-N-(4-hydroxy phenethyl)-3 -(methylthio)propenamide.Example 1:

EXEMPLO 2:[0091] By way of illustration, four examples of composition formulation, according to the invention, containing a conjugate derived from cis-3-methyl thio propenoic acid of general formula (I) mentioned below are mentioned below:

EXAMPLE 2:

[0092] The invention is illustrated below, purely as a guide, by the following tests mentioned above in the description of the invention (tests 1 to 5). Test 1: Evidence of the antioxidant potential of compounds of formula (IIIa) and (IIIb) against the hydroperoxidation of scalene by singular oxygen

[0093] Principle: this involves highlighting an eventual entrapment effect (quenching) of the compounds, according to the invention, alternately of scalene hydroperoxides generated by the action of dissolved molecular oxygen on the scalene in the presence of a photosensitizer (blue of methylene).

[0094] Experimentally, a solution of scalene at 5 g/100 ml, a solution of methylene blue at 5 mM and a solution of compound, according to the invention, (from 1 to 5 mM) or of test compound (methyl thio propyl starch acetyl methionine - AMDM) were prepared after dissolving in 100 ml methanol (HPLC quality). Then, in a UV-B oven, each solution was poured in equal parts into a Petri dish, without a lid, in order to be submitted to an irradiation dose (1D) of 1.42 J.cm-2. At the end of irradiation, the solution volumes were recovered, adjusted to 20 ml with methanol, before analysis by HPLC assay and after removal of methylene blue. The quenching rate was then deduced from the following equation: Amount of oxidized scalene (proof) - amount of oxidized scalene (test) % protection = Amount of oxidized scalene (proof) x 100

[0095] The results obtained are gathered in table 1 below:

[0096] The results in table 1 underline that the compounds, according to the invention, are able to effectively oppose the photoinduced oxidation of scalene in hydroperoxides. Test 2: evidence of the absence of cytotoxic potential of the oxidation by-products of conjugates (Z)-isomers of formula (I).

[0097] Experimentally, the test was performed on an immortalized keratinocyte lineage "HaCaT", maintained by subculture in complete culture medium "DMEM" (with 10% fetal calf serum) in a humid atmosphere at 37 oC and 5% of CO2. HacaT cells were inseminated in 24-well plates at a rate of 1,105 cells per well.

[0098] Sulphoxide and sulfone derivatives of conjugates (Z) - isomers of formula (I) were generated by stoichiometric exposure to hydrogen peroxide (H2O2), purified and finally quantified.

[0099] In each of the wells, 500 μl of the by-products of oxidation sulphoxides and sulfones derived from the conjugates were added, according to the invention, at a concentration of 2.5 mM in PBS. After removal from the medium, the cellular reliability of HaCaT keratinocytes was measured via the "MTT method" or 3-(4,5-dimethyl thiazol-2-yl) - 2,5 diphenyl tetrazolium bromide (500 μg/ml solution) ) and by spectrophotometry (absorbance at 550 nm). The results, pooling the mean values obtained from three independent experiments, are presented in table 2 below, in comparison with those obtained for non-irradiated cells.

[00100] The results in table 2 testify to the absence of toxicity of the oxidation by-products of the conjugates (Z) - isomers of formula (I). Test 3: evidence of the capacity of the conjugates (Z) - isomers of formula (I) to enable a cell line of keratinocytes subjected to cytotoxic doses of UV-B.

[00101] Experimentally, the study was also carried out on a lineage of immortalized keratinocytes "HaCaT", inseminated in 24-well plates at the rate of 8000 cells per square centimeter, or 15200 cells per well in 0.5 ml of the culture medium ( with 10% fetal calf serum).

[00102] In each of the wells, 500 μl of conjugate were added, according to the invention, at a concentration of 0.05 to 0.5 M in PBS. Cells in the presence of active were then exposed to ultraviolet radiation (UV-B) at a moderate dose of 100 mJ.cm-2, then replaced in active medium, without active, for 24 hours. After removal of the medium, the cellular reliability of HaCaT keratinocytes was also measured via the "MTT method" (250 μg/ml solution) and by spectrophotometry (absorbance at 570 nm). The results, bringing together the mean values obtained from three independent experiments, are shown in table 3 below, in comparison with those obtained for two tests, for non-irradiated cells and for cells irradiated but not treated with the conjugates, according to with the invention.

[00103] The results in table 3 underline, for the compounds according to the invention, a dose-dependent cellular reliability, with a photoprotection of keratinocytes from 0.1 mM and a complete or almost complete photoprotection at 0.5 mM. Test 4: Evidence of the ability of the conjugates (Z)-isomers of formula (I) to absorb ultraviolet radiation by photoisomerization.

[00104] Principle: it is about verifying whether the conjugates, according to the invention, are capable of isomerizing under UV-B irradiation.

[00105] Experimentally, 2 ml of a scalene solution at 5g/100 ml and 2 ml of a compound solution, according to the invention, at a concentration of 25 mM methanol were introduced into a 20 ml graduated sample, then to 20 ml with methanol. The preparation thus obtained was poured into a Petri dish, on which an irradiation dose of 1 J.cm-2 was applied in a UV-B oven. At the end of irradiation, the solutions were recovered, then analyzed by HPLC measurement. Volumes were previously normalized with methanol.

[00106] Chromatographic profiles were thus obtained, and the formation of E-isomer was sought. An isomerization rate was then determined by comparison with a proof profile.

[00107] The results obtained are gathered in table 4 below:

[00108] The results in table 4 underline that the compounds, according to the invention, are capable of effectively absorbing radiation with the production of its trans-configuration stereoisomer. Test 5: evidence of the capacity of the conjugates (Z) - formula (I) isomers to oppose photoinduced isomerization of transurocanic acid

[00109] Principle: it is about verifying whether the conjugates, according to the invention, are able to oppose the photoisomerization of transurocanic acid.

[00110] Experimentally, the study was carried out almost identically to tests 1 and 4 above, with prior verification that under the defined experimental conditions, transurocanic acid generated a significant amount of cisurocanic acid that can be measured by HPLC analysis.

[00111] The irradiation dose (1D) was 31 mJ.cm-2 for compound concentrations of 5 mM. The results obtained are gathered in table 5 below:

[00112] The results of table 5 underline that the compounds, according to the invention, are effective in protecting transurocanic acid alternately from UV-B radiation with a small or moderate dose.

Claims (15)

1. Compound derived from (z)-3-(alkyl thio) propenoic acid, characterized in that it is represented by the following general formula (I):

in which:- Y = S or SO; - R 1 is a linear or branched C 1 -C 4 alkyl radical; - R 2 is a hydrogen atom; a C1-C4 alkyl radical, linear or branched;- R3 is:- a C1-C18 alkyl radical, a C3-C18 alkene radical, a C3-C4 alkyne radical, this alkyl, alkene or alkyne radical being linear or branched, and optionally substituted by a hydroxyl radical, a hydroxyphenyl or dihydroxyphenyl group; - the side chain of an amino acid chosen from tyrosine, hydroxyproline, serine and its homoserine and isoserine analogues, threonine and their homothreonine and iso-threonine analogues; with the exception of the compounds 2-cis-entadamide A, isope-nanginine, N-ethyl-cis-3-butyl mercapto acrylamide and N-ethyl-cis-3-methyl mer-capto acrylamide. 2. Compound according to claim 1, characterized in that it is represented by the formula (II) below:

in which:- Y = S or SO; - R1 is a linear or branched C1-C4 alkyl radical;- R3 is a C1-C4 alkyl radical, a C3-C4 alkene radical, a C3-alkyne radical; C4, that alkyl, alkene or alkyne radical being linear or branched, and optionally substituted by a hydroxyl radical, a hydroxyphenyl or dihydroxyphenyl group. 3. Compound according to claim 1 or 2, characterized in that Y is S. 4. Compound according to any one of claims 1 to 3, characterized in that R1 is a methyl radical. 5. Compound according to any one of claims 1 to 4, characterized in that R3 is an alkyl radical in C2 substituted by a hydroxyl radical, a hydroxyphenyl or dihydroxyphenyl group. A compound according to any one of claims 1 to 5, characterized in that it is (z)-N-(4-hydroxyphenethyl)-3-(methylthio)propanamide. 7. Cosmetic or dermatological composition intended for photoprotection, characterized by the fact that it comprises, in association with any physiologically compatible adjuvant with the skin or phaneros, as the main active ingredient(s), a compound of general formula (IIIa), a compound of formula (IIIb) or a mixture, preferably racemic, of these compounds:

in which:- Y = S or SO; - R 1 is a linear or branched C 1 -C 4 alkyl radical; - R 2 is a hydrogen atom; a linear or branched C1-C4 alkyl radical;- R3 is:• a C1-C18 alkyl radical, a C3-C18 alkene radical, a C3-C4 alkyne radical, such a C3-C4 alkyl, alkene or alkyne radical being linear or branched, and optionally substituted by a hydroxyl radical, a hydroxyphenyl or dihydroxyphenyl group; the side chain of an amino acid chosen from tyrosine, hydroxyproline, serine and its homoserine and isoserine analogues, threonine and their homothreonine and isothreonine analogues, wherein the amount of this main active ingredient is comprised between 0.001% and 0.1% by weight relative to the total weight of the composition. 8. Cosmetic or dermocosmetic composition according to claim 7, characterized in that it comprises, as the main active ingredient(s), a compound of general formula (IVa), a compound of formula (IVb ) or a mixture, preferably racemic, of these compounds:

in which:- Y = S or SO; - R 1 is a linear or branched C 1 -C 4 alkyl radical; - R 3 is a linear or branched C 1 -C 4 alkyl radical, optionally substituted by a hydroxyl radical, a hydroxyphenyl or d-hydroxyphenyl group. 9. Cosmetic or dermocosmetic composition according to claim 7 or 8, characterized in that Y, R1 and R3 are as defined in claims 3 to 5. 10. Cosmetic or dermocosmetic composition according to any one of claims 7 to 9, characterized in that it comprises, as the main active ingredient, (z)-N-(2-hydroxyethyl)-3-(methylthio ) propenamide or (z)-N-(4-hydroxy phenethyl)-3-(methylthio)propenamide. 11. Cosmetic or dermocosmetic composition according to any one of claims 7 to 10, characterized in that it further comprises an organic or inorganic sunscreen active in UV-A and/or UV-B, chosen among anthranylates, the derivatives cinnamics, dibenzoyl methane derivatives, salicylic derivatives, camphor derivatives, triazine derivatives, benzophenone derivatives, beta derivatives, beta diphenyl acrylate, benzo triazole derivatives, benzal malonate derivatives, benzimidazole derivatives, imidazolines, bis-benzoazolyl derivatives, benzoxazole derivatives, p-amino benzoic acid (PA-BA) derivatives, methylene bis-(hydroxy phenyl benzotriazole) derivatives, filter polymers and filter silicones, dimers derived from alpha-alkyl styrene, 4,4-diaryl butadienes, pigments or nanopigments of metal oxides (titanium, zinc, iron, zirconium, cerium oxides), coated or uncoated, and your mixtures . 12. Cosmetic or dermocosmetic composition according to any one of claims 7 to 11, characterized in that it further comprises one or more actives chosen from among deglycant agents, agents stimulating the synthesis of collagen or elastin or preventing its degradation, agents stimulating the synthesis of glycosamino glycans or proteoglycans or preventing their degradation, agents increasing cell proliferation, depigmenting or pro-pigmenting agents, antioxidant or anti-radical or anti-pollution agents, hydrating agents, lipose-stimulating agents , draining or detoxifying agents, anti-inflammatory agents, penetration accelerating agents, peeling agents, calming and/or anti-irritating agents, astringent agents, agents that act on the microcirculation, etc. , and its mixtures. 13. Use, in a cosmetic or dermocosmetic composition, of a compound of formula (IIIa) or a compound of formula (IIIb), as defined in claim 7, or of a mixture of these compounds, characterized in that it is as photoprotective agent against solar radiation. 14. Compound of formula (IIIa) or compound of formula (IIIb), as defined in claim 7, or a mixture of these compounds, characterized in that it is for use in a cosmetic or dermocosmetic composition, for photoprotection against solar radiation. 15. Use according to claim 13 or compound for use according to claim 14, characterized in that this compound of formula (IIIa) is (z)-N-(2-hydroxy ethyl)-3-( methylthio)propenamide or (z)-N-(4-hydroxyphenethyl)-3-(methylthio)propenamide.