Dibenzoylmethane compounds as photochemical precursors for ultraviolet absorbers

Abstract

The present invention relates to dibenzoylmethane compound precursors having an amide group in one ring and their corresponding photoconverting compounds, their pharmaceutically or cosmetically acceptable salts, or a stereoisomer of any one of them or mixtures thereof, for use in protecting human or animal living bodies or materials from ultraviolet radiation. The invention also relates to a process for the preparation thereof, and to cosmetic or pharmaceutical or personal care compositions thereof.

Description

[0001] This application claims the benefit of European Patent Application EP 23 382 293 filed on March 28, 2023. TECHNICAL FIELD

[0002] The present invention relates to photochemical precursors of ultraviolet light absorbers, in particular to some benzoylmethane compounds and to methods of preparation and uses thereof. BACKGROUND

[0003] The invisible rays of ultraviolet A (UVA, 320 to 400 nm) and ultraviolet B (UVB, 290 to 320 nm) emitted by the sun cause immediate and long-term damage to the skin. Some examples are sunburn, skin rash, cell and tissue damage, and skin cancer. The growing awareness of these risks has changed people's tanning habits. These changes include the use of clothing, hats, sunglasses, sunscreens, and other forms of photoprotection.

[0004] Sunscreen refers to any substance or material that can protect the skin from the harmful effects of ultraviolet light. Sunscreens are usually commercialized in the form of sprays, creams, topical lotions, ointments, and gels.

[0005] Several benzoic acid ester compounds have been reported as photochemical precursors of ultraviolet light absorbers. Their photoprotective activity is derived from their ability to generate sunscreen compounds with UV protection capacity in situ through photochemical conversion.

[0006] The document by Adaya Gallardo et al., “Dose-dependent progressive sunscreens. A new strategy for photoprotection?”, Photochemical & Photobiological Sciences, 2010, vol. 9, pp. 530-534 discloses that benzophenone absorbs UV-B and UVA-II radiation, while benzoylmethane absorbs UV-A radiation, thus preventing the penetration of these radiations into the skin.

[0007] Among the currently approved ultraviolet filters for use in cosmetics, benzophenone and benzoylmethane compounds play an important role. These families of compounds all have an aromatic beta-ketone in their structure, which is a key component of their sunscreen action.

[0008] Avobenzone, dioxybenzone, oxybenzone, sulisobenzone are some important and widely used sunscreen compounds.

[0009] When the radiation is absorbed, it triggers a photo- tautomerization reaction, forming an unstable ene and releasing the absorbed radiation as heat. Each molecule participates in several cycles before degrading.

[0010] Photo-stability can be defined as the response of a molecule to exposure to sunlight, UV and visible light. This can vary depending on the solvent or vehicle used.

[0011] Avobenzone is one of the most commonly used filters. It is able to provide protection against most of the spectral range of UV-A, including UVA-I. However, concerns have been raised about its photo-stability and its ability to degrade other sunscreen ingredients.

[0012] Avobenzone precursor, preavobenzone, is one of the most commonly used molecules. However, preavobenzone requires more than 20 minutes to achieve complete photoconversion. Therefore, it is desirable to find new sunscreen compounds that are able to achieve complete photoconversion more quickly. SUMMARY

[0013] The inventors found that dibenzoylmethane compounds having an amide group in one ring exhibit enhanced photoconversion properties compared to 1-(4-methoxyphenyl)vinyl-4-(tert-butyl)benzoate (preavobenzone).

[0014] Aspects of the present invention relate to compounds of Formula (I), pharmaceutically or cosmetically acceptable salts thereof, or stereoisomers or mixtures of any of them,

[0015]

[0016] Alternatively, instead of,

[0017]

[0018] wherein: in compound (I), R’ is selected from H, (Ci-C6)-alkyl and (C3-C6)-cycloalkyl; R1, R2, R4, R5, R6, R7, R9 and R 10R8is selected from the group consisting of (Ci-C6)-alkyl, (Ci-C6)-alkoxy, hydroxyl, amino, (Ci-C6)-alkylamino and (Ci-C6)-dialkylamino; and in compound (I'), R1and R6are radicals independently selected from the group consisting of H, amino, (Ci-C6)-alkyl, (Ci-C6)-alkoxy, (Ci-C6)-alkylamino and (Ci-C6)-dialkylamino; R', R2, R4, R5, R7, R9, R 10 , R3and R8are as defined in compound (I).

[0019] Another aspect of the application relates to compound (I) or compound (I') as defined above, for use in the protection of a human or animal living body, or of a material, against ultraviolet radiation.

[0020] Another aspect of the application relates to a method for the protection of a material against ultraviolet radiation, comprising treating the material with compound (I) or compound (I') as defined above.

[0021] Another aspect of the application relates to a composition selected from the group consisting of a cosmetic composition, a pharmaceutical composition and a personal care composition, said composition comprising an effective amount of a compound as defined above for the protection of a human or animal living body against ultraviolet radiation, and one or more than one pharmaceutically or cosmetically acceptable excipient or carrier; or, alternatively, to a composition for the protection of a material against ultraviolet radiation, comprising at least an effective amount of a compound as defined above, and a suitable vehicle.

[0022] Another aspect of the application relates to a process for the preparation of compound (I) or compound (I') as defined above, wherein: when the compound is a compound of formula (I), the process comprises the step of reacting a compound of formula (II a ) or a suitable salt thereof, with a (Ci-C6)-acyl halide, in the presence of a suitable solvent and of a suitable base; wherein in compound (II a ) R', R1-R 10 are as defined in compound (I), and R 3a ' is NH2; and wherein when the compound is a compound of formula (I'), the process comprises irradiating a compound of formula (I) with UV light to produce a compound of formula (I'),

[0023]

[0024] Finally, another aspect of the invention relates to compounds of formula (II), pharmaceutically or cosmetically acceptable salts thereof, or stereoisomers of any of them or mixtures thereof, wherein: in compound (II), R' is selected from H; (C1-C6)-alkyl and (C3-C6)-cycloalkyl; R1, R2, R4, R5, R6, R7, R9 and R 10 R8 is a group independently selected from H, hydroxyl, amino, (C1-C6)-alkyl, (C1-C6)-alkoxy, (C1-C6)-alkylamino, and (C1-C6)-dialkylamino; R3' is an amino or nitro group; and R8 is selected from (C1-C6)-alkyl, (C1-C6)-alkoxy, hydroxyl, amino, (C1-C6)-alkylamino, and (C1-C6)-dialkylamino.

[0025] Attached Figure Description

[0026] Figure 1 a) and Figure 1 b) is the UV-Vis spectrum, showing the effect of irradiation at 312 nm with 3 × 10⁻⁶ ions. -5 The absorption changes of pre-avobenzone (PvB360) (a) and 1-(4-methoxyphenyl)vinyl-4-acetamidobenzoate (PVB-1) (b) in MeOH solution of M.

[0027] Figure 2 The SPF and UVA-PF of PvB360 (pre-avobenzone, comparative compound) and PVB-1 (compound of the present invention) at different irradiation times are shown. (PVB-1) corresponds to compound (I), where R' is H, and R1, R2, R4, R5, R6, R7, R9 and R 10 R3 is H; R4 is methyl; and R5 is methoxy. Detailed Implementation

[0028] For the purposes of this invention, any given range includes both the lower and upper limits of that range. Unless otherwise specified, given ranges, such as temperature, time, size, etc., should be considered approximate values.

[0029] As disclosed herein, the term “room temperature” refers to the temperature of an environment that is neither heated nor cooled, and typically consists of 20°C to 25°C.

[0030] The terms “(C1-C6)-alkyl”, “(C1-C6)-alkoxy”, “(C1-C6)-alkylamino” and “(C1-C6)-dialkylamino” should be understood as straight-chain or branched.

[0031] As used herein, the term "pharmaceutically or cosmetically acceptable salt" encompasses any salt formed from pharmaceutically or cosmetically acceptable non-toxic acids, including inorganic or organic acids. There are no restrictions on the type of salt, but if the salt is intended for therapeutic purposes, it must be pharmaceutically or cosmetically acceptable.

[0032] Since some compounds of formula (I) are basic, their salts can be prepared from pharmaceutically acceptable, non-toxic acids, including both inorganic and organic acids. Such acids include, for example, acetic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, fumaric acid, gluconic acid, glutamic acid, hydrobromic acid, hydrochloric acid, lactic acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, phosphoric acid, succinic acid, sulfuric acid, nitric acid, adipic acid, aspartic acid, 1,5-naphthalenedisulfonic acid, oxalic acid, pentanoic acid, propionic acid, tartaric acid, p-toluenesulfonic acid, etc.

[0033] Compounds of formula (I), formula (I') or formula (II) include those of formula (II) a ) or formula (II) b The preparation of pharmaceutically acceptable salts of compounds can be carried out by methods known in the art. For example, they can be prepared by conventional chemical methods from parent compounds containing a basic moiety. Typically, such salts are prepared by reacting the basic form of these compounds with a stoichiometric amount of a suitable pharmaceutically acceptable acid in water or an organic solvent or a mixture thereof.

[0034] The compounds of the present invention may be in crystalline form as free solvated compounds or solvates (e.g., hydrates), and both forms are contemplated to be within the scope of the present invention. Methods of solvation are generally known in the art.

[0035] The term "solvent" refers to a molecular complex comprising any of formula (I), formula (I'), or formula (II), including formula (II). a ) or (II) b A compound of the formula () or a salt thereof, and one or more solvent molecules, either stoichiometric or non-stoichiometric, bound by non-covalent intermolecular forces. When one or more solvent molecules forming part of the molecular complex are water, the solvate is a hydrate.

[0036] The term "effective amount for protecting living humans or animals or materials from ultraviolet radiation" as used herein refers to an amount of compound sufficient to provide protection against ultraviolet radiation when applied. For living humans or animals, protection against ultraviolet radiation means prevention of skin damage. Therefore, the effective amount used herein refers to a therapeutically effective amount.

[0037] The phrase "pharmaceutically or cosmetically acceptable excipient or carrier" refers to a pharmaceutically acceptable material, composition, or carrier. Each component must be pharmaceutically or cosmetically acceptable, meaning it is compatible with other ingredients in the drug or cosmetic composition. It must also be suitable for human and animal skin contact without excessive toxicity, irritation, allergic reactions, immunogenicity, or other problems or complications, with a reasonable benefit / risk ratio.

[0038] The term “cosmetically acceptable” is used interchangeably in this document and refers to an excipient or carrier suitable for contact with skin or humans and animals without undue toxicity, incompatibility, instability, allergic reactions, etc.

[0039] As described above, one aspect of the present invention relates to compounds of formula (I) or formula (I') as defined above, pharmaceutically or cosmetically acceptable salts thereof, or stereoisomers of any of them or mixtures thereof.

[0040] In a particular embodiment, the compound of the present invention is a compound of formula (I), or a pharmaceutically or cosmetically acceptable salt thereof, or a stereoisomer of any one thereof, or a mixture thereof.

[0041] In a particular embodiment, the compound of formula (I) is a compound in which R1 and R6 are independently selected from H, amino, (C1-C6)-alkyl, (C1-C6)-alkoxy, (C1-C6)-alkylamino and (C1-C6)-dialkylamino groups.

[0042] In another specific embodiment, the compound of formula (I) or the compound of formula (I') of the present invention is wherein R1, R2, R4, R5, R6, R7, R9 and R 10 The compound is H, R8 is (C1-C6)-alkoxy, and R' is H. In another specific embodiment, the compound is a compound in which R3 is (C1-C3)-alkyl. In another specific embodiment, the compounds of the present invention are those in formulas (I) and (I'), where R', R1, R2, R4, R5, R6, R7, R9, and R are H. 10 A compound in which H is a methyl group, R3 is a methyl group, and R8 is a methoxy group.

[0043] A portion of this invention also includes compounds as defined above for protecting living humans or animals from ultraviolet radiation. This aspect of the invention can also be described as the use of compounds (I) or (I') as defined above in the manufacture of cosmetic compositions, pharmaceutical compositions, or personal care compositions for protecting living humans or animals from ultraviolet radiation. The invention also relates to a method for protecting living humans or animals from ultraviolet radiation, comprising administering an effective amount of a compound as defined above for protecting living humans or animals from ultraviolet radiation, and one or more pharmaceutically or cosmetically acceptable excipients or carriers. In a particular embodiment, the living animal is a mammal.

[0044] The use of the compounds as defined above for protecting living humans or animals from ultraviolet radiation is considered part of this invention. In particular, the use as defined above includes the in-situ photochemical conversion of compounds of formula (I) into sunscreen compounds.

[0045] A further part of this invention is a method for protecting a material from ultraviolet radiation, comprising treating the material with a compound (I) or compound (I') as defined above. Typically, methods for protecting a material include applying an effective amount of a compound (I) or compound (I') as defined above for protecting the material from ultraviolet radiation.

[0046] The materials may be selected from organic compounds, oils, fats, waxes, gelatin, sunscreens, polymers such as polyolefins, polyketides, polystyrene, polyvinyl chloride (PVC), polyacrylates, polymethacrylates, polyacrylamide, polyacrylonitrile, polyvinyl alcohol derivatives, polyvinyl acetate derivatives, polyurethanes, polyamides, polyesters, polyureas, polycarbonates, polysiloxanes, polyketimides, radiation-curable compositions, resins such as hydrocarbon resins, phenol / formaldehyde resins, urea / formaldehyde resins, melamine / formaldehyde resins, unsaturated polyester resins, crosslinkable acrylic resins, crosslinked epoxy resins, epoxy / melamine resins, varnishes, cellulose, cellulose-based paper preparations, photographic materials, photographic film paper, metal products, ceramic products, biocides, fibers, textiles, dyes, inks, coatings, adhesives, leather, wood, lenses, composite materials, mixtures or blends.

[0047] As used herein, the term "effective amount of compound (I) or compound (I') for protecting a material from ultraviolet radiation" refers to the amount of compound that, when applied to a material, is sufficient to protect it from ultraviolet radiation, i.e., the effective amount that prevents or minimizes material degradation.

[0048] In a particular embodiment of the method, compound (I) or compound (I') as defined above is applied in the form of a composition further comprising a suitable component selected from at least polymers, solvents, additives, and mixtures thereof. Examples of additives are antioxidants, preservatives, thickeners, colorants, or opacifiers. In a particular embodiment of the method, the composition used in the method is an industrial composition.

[0049] In another specific embodiment, the compound of the present invention is a compound of formula (I) as defined above, wherein the compound of formula (I) is readily converted in situ by photochemical conversion into a sunscreen compound.

[0050] In another specific embodiment, the compounds of formula (I) or formula (I') of the present invention as defined above are those compounds used for protection against UV-A and UV-B.

[0051] In another specific embodiment, the compounds used as defined above are those used for protection against UV radiation emitted by the sun.

[0052] In another specific embodiment, compounds used as defined above are those characterized by providing progressive ultraviolet protection based on the duration of sun exposure and the level of solar radiation.

[0053] The compounds of formula (I) or formula (I') of the present invention may be present in the form of a composition selected from cosmetic compositions, pharmaceutical compositions and personal care compositions, the composition comprising an effective amount of such compound for protecting living humans or animals or materials from ultraviolet radiation and one or more pharmaceutically or cosmetically acceptable excipients or carriers.

[0054] The specific embodiments of the first aspect of the present invention described above are also considered to be specific embodiments of the composition of the present invention.

[0055] In a particular embodiment, the cosmetic composition, pharmaceutical composition, or personal care composition as defined above is a composition in which the effective amount of the compound of formula (I) or (I') is from 0.1% to 10% by weight based on the total weight of the composition. In another particular embodiment, the cosmetic composition, pharmaceutical composition, or personal care composition as defined above is a composition in which the effective amount of the compound of formula (I) or (I') is from 0.5% to 8% by weight based on the total weight of the composition. In yet another particular embodiment, the cosmetic composition, pharmaceutical composition, or personal care composition is a composition in which the effective amount of the compound of formula (I) or (I') is from 1% to 6% by weight based on the total weight of the composition.

[0056] In another specific embodiment, the compositions of the present invention are those comprising an effective amount of a dibenzoylmethane compound of formula (I), a pharmaceutically or cosmetically acceptable salt thereof, or a stereoisomer of any one thereof or a mixture thereof, wherein the composition has enhanced light conversion properties.

[0057] In another specific embodiment, the compounds of the present invention can also be used to form light-stabilized compositions. Such light-stabilized compositions may also include a variety of other components known in the art, including triazine, benzotriazole, hindered amine light stabilizers, free radical scavengers, antioxidants, etc.

[0058] The compositions of the present invention are for topical application. In certain embodiments, the cosmetic compositions, pharmaceutical compositions, or personal care compositions as defined above are compositions selected from the following substances: creams, ointments, oils, lotions, gels, sticks, foams, emulsions, suspensions, powders, lotions, dispersants, sprays, aerosols, lipsticks, foundations, cosmetics, loose powder or pressed powder, blush, eyeshadow, mascara, nail polish, nail paint, and non-permanent hair coloring compositions.

[0059] In another specific embodiment, the composition of the present invention may contain one or more other organic sunscreens for filtering UV-A or UV-B.

[0060] In another specific embodiment, the composition is a sunscreen composition. In another specific embodiment, the sunscreen composition may have a sun protection factor (SPF) of 6 or higher, preferably 30 or higher, more preferably 50 or higher. Preferably, the sunscreen composition comprises a physical filter, a chemical filter, or a combination thereof.

[0061] Suitable excipients or carriers used in the compositions of the present invention are, for example, dispersants, preservatives, defoamers, fragrances, aromas, oils, waxes, propellants, dyes, pigments, emulsifiers, surfactants, thickeners, humectants, exfoliants, and emollients.

[0062] The local compositions of the present invention can be produced by conventional methods known in the art, such as by mixing different components of the composition in any order. Suitable excipients and / or carriers and their amounts can be readily determined by those skilled in the art based on the type of composition being prepared.

[0063] A portion of this invention includes compositions for protecting materials from ultraviolet radiation, comprising at least an effective amount of a compound as defined above, and suitable components selected from at least polymers, solvents, additives, and mixtures thereof. Examples of additives are antioxidants, preservatives, thickeners, colorants, or opacifiers. The compositions may be industrial compositions comprising compounds as defined above.

[0064] In a particular embodiment, the composition for protecting materials from ultraviolet radiation as defined above is one in which the effective amount of the compound of formula (I) or (I') is from 0.1% to 10% by weight based on the total weight of the composition. In another particular embodiment, the composition as defined above is one in which the effective amount of the compound of formula (I) or (I') is from 0.5% to 8% by weight based on the total weight of the composition. In yet another particular embodiment, the composition is one in which the effective amount of the compound of formula (I) or (I') is from 1% to 6% by weight based on the total weight of the composition.

[0065] The compounds of formula (I) of the present invention can be prepared by a method comprising the following steps: reacting a compound of formula (IIa) or a suitable salt thereof with a (C1-C6) acyl halide such as acetyl chloride or (C2-C6) acyl halide. 12 Acid anhydrides, such as acetic anhydride, react in the presence of a suitable solvent and a suitable base; wherein, in the compounds of formula (IIa), R', R1-R 10 As defined in compound (I) and R 3a 'For NH2;

[0066]

[0067] In a specific embodiment of the method, a suitable solvent for the above step is selected from (C6-C8) aromatic hydrocarbons such as toluene or xylene, or (C1-C3) chlorinated solvents such as dichloromethane or dichloroethane. In another specific embodiment of the method, a suitable base is a tertiary amine such as triethylamine, used alone or in combination with 4-dimethylaminopyridine, or N,N-diisopropylethylamine. This step of the method is typically carried out at a temperature from -20°C to 0°C.

[0068] In another specific embodiment, the method as defined above further includes a pre-step that includes formula (II) b The compound undergoes a reduction reaction to produce the product of formula (II) as defined above. a Compounds of formula (II), wherein b In compounds of ), R', R1-R 10 As defined in compound (I), and R 3b 'It is NO2.'

[0069]

[0070] The reduction reaction can be carried out in the presence of an acid using a reducing agent such as the metal to be oxidized. Examples of suitable metals are, for example, Fe, Sn, or Zn. Examples of suitable acids are, for example, hydrochloric acid or acetic acid. In a particular embodiment, the metal is zinc. In another particular embodiment of the method, this step is carried out in the presence of a suitable solvent, which can be a (C1-C3) chlorinated solvent such as chloroform or dichloromethane. In another particular embodiment, the preferred ratio of the (C1-C3) chlorinated solvent to the acid is 11:1.5 or 7:0.5, respectively. This step of the method is typically carried out at a temperature between -20°C and 0°C.

[0071] In another specific embodiment, the method of the present invention as defined above further includes a pre-step comprising subjecting a compound of formula (III) to an elimination reaction to produce a compound of formula (II). b Compounds of (III), wherein X is a halide, R1-R 10 As defined in compound (I), and R 3b 'For NO2,

[0072]

[0073] In a particular embodiment, X is a halogen selected from the groups Br, Cl, and I. In a particular embodiment of the method, the compound of formula (III) is a compound in which X is bromine.

[0074] The compound of formula (III) can be prepared from 2-halo-1-(4-methoxyphenyl)ethane-1-one. The term halogenated refers to any one of Cl, Br, and I. The compound can be reduced with a reducing agent such as NaBH4 in the presence of a suitable solvent. Typically, the reaction is carried out at low temperatures, such as -20°C to 10°C. The solvent can be a (C1-C4)-alcohol such as methanol to produce 2-halo-1-(4-methoxyphenyl)ethane-1-ol. The compound thus obtained can be reacted with a p-nitrobenzoyl halide such as p-nitrobenzoyl chloride in the presence of a suitable solvent and a suitable base. An example of a suitable solvent is tetrahydrofuran. An example of a suitable base is a tertiary amine such as triethylamine, used alone or in combination with 4-dimethylaminopyridine.

[0075]

[0076] In the compounds of formulas (III), (IV), and (V), R1-R 10 As defined in compound (I), X is a halogen selected from the following groups: Br, Cl, and I, and R 3b 'It is NO2.'

[0077] The compounds of formula (I') of the present invention can be prepared by a method comprising irradiating the compounds of formula (I) with UV light to produce the compounds of formula (I') of the present invention.

[0078] Formula (II) a ) and formula (II) b Compounds of formula (II) are also part of this invention. They may also be pharmaceutically or cosmetically acceptable salts, or stereoisomers of any of them, or mixtures thereof. a ) or formula (II) b Salts of compounds of formula (II) refer to non-toxic salts. Because some formulas (II) a ) or formula (II) b The compounds in this compound are basic compounds, so salts can be prepared using pharmaceutically or cosmetically acceptable non-toxic acids.

[0079] Throughout the specification and claims, the word "comprising" and its variations are not intended to exclude other technical features, additives, components, or steps. Furthermore, the word "comprising" covers situations where it means "composed of." Other objects, advantages, and features of the invention will become apparent to those skilled in the art upon review of the specification, or may be obtained by practicing the invention. The following embodiments and drawings are provided illustratively and are not intended to limit the invention. Moreover, the invention covers all possible combinations of the specific and preferred embodiments described herein.

[0080] Example

[0081] Example 1: Preparation of 2-bromo-1-(4-methoxyphenyl)ethan-1-ol

[0082] In a 100 mL round-bottom flask, 3 g of BMAP (13.2 mmol, 1 equivalent) was dissolved in 60 mL of MeOH. Then, 1 g of NaBH4 (26.4 mmol, 8 equivalent) was added in portions at -10 °C (ice-salt bath). The solution was stirred at this temperature for 1 hour (until the reaction was complete as monitored by TLC). Afterward, 100 mL of DCM and 150 mL of 1 M HCl aqueous solution were added. The resulting mixture was stirred at 0 °C for 30 minutes. The organic phase was decanted, and the aqueous phase was extracted twice with DCM. The combined organic phases were washed with brine and dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure to give a colorless oily product (2.86 g, 94% yield).

[0083] Example 2: Preparation of 2-bromo-1-(4-methoxyphenyl)ethyl 4- nitrobenzoate

[0084] Under an inert N2 atmosphere, 2-bromo-1-(4-methoxyphenyl)ethane-1-ol (2.5 g, 10.82 mmol, 1 equivalent) was dissolved in 50 mL of anhydrous THF. The mixture was then cooled to 0 °C (ice bath) and 2.26 mL of NEt3 (16.23 mmol, 1.5 equivalent) was added. Finally, a solution containing 4 g p-NBCl (21.64 mmol, 2.0 equivalent) of anhydrous THF was added dropwise using a dropping funnel. After stirring at 0 °C for 10 min, the mixture was stirred at room temperature for 7 h, and the complete conversion of the starting material was observed by 1H-NMR. The evaporation was then partially evaporated under reduced pressure, and the crude mixture was washed with a saturated aqueous solution of NaHCO3. The resulting organic phase was dried over anhydrous Na2SO4, and the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography using n-hexane / DCM (7:3 to 6:4) as the mobile phase to give a pale yellow oily product (3.709 g, 90% yield).

[0085] 1 H-NMR (300MHz; chloroform-d) δppm8.35-8.21(m,4H),7.42-7.33(m,2H),6.98-6.88(m,2H),6.18(dd,J1 =8.5Hz, J2=4.4Hz, 1H), 3.83 (dd, J1=10.9Hz, J2=8.5Hz, 1H) 3.71 (dd, J1=10.9Hz, J2=4.4Hz, 1H). 13 C-NMR (75MHz; chloroform-d) δppm 163.53 (1C), 160.08 (1C), 150.54 (1C), 135.12 (1C), 130.80 (2C), 129.06 (1C), 127.96 (2C), 123.51 (2C), 114.17 (2C), 76.16 (1C), 55.20 (1C), 34.14 (1C).

[0086] Example 3: Preparation of 1-(4-methoxyphenyl)vinyl 4-nitrobenzoate

[0087] 2-Bromo-1-(4-methoxyphenyl)ethyl 4-nitrobenzene ester (2.14 g, 5.64 mmol, 1.0 equivalent) was added to a three-necked round-bottom flask and dissolved in 50 mL of anhydrous toluene. The mixture was then heated to reflux, and 1.7 mL of LdBU (11.28 mmol, 2.0 equivalent) was slowly added. The mixture was stirred at reflux for 1 h. Afterward, the mixture was cooled to room temperature, and the reaction was quenched with 60 mL of 0.5 M HCl aqueous solution. The phases were separated, and the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with brine and dried over anhydrous Na₂SO₄. After evaporation of the solvent under reduced pressure, an orange solid product (1.501 g, 90% yield) was given.

[0088] 1 ¹H-NMR (300MHz; chloroform-d) δppm 8.36 (s, 4H), 7.48–7.39 (m, 2H), 6.93–6.84 (m, 2H), 5.49 (d, J = 2.5Hz, 1H), 5.09 (d, J = 2.5Hz, 1H), 3.81 (s, 3H). 13 C-NMR (75MHz; chloroform-d) δppm 163.02 (1C), 160.43 (1C), 152.83 (1C), 150.90 (1C), 134.92 (1C), 131.25 (2C), 126.36 (2C), 126.33 (1C), 123.79 (2C), 114.09 (2C), 100.83 (1C), 55.35 (1C).

[0089] Example 4: Preparation of 1-(4-methoxyphenyl)vinyl 4-aminobenzoate

[0090] In a 100 mL round-bottom flask, 1-(4-methoxyphenyl)vinyl-4-nitrobenzene ester (507.6 mg, 1.65 mmol, 1.0 equivalent) was dissolved in 50 mL of CHCl3 / acetic acid 9:1. The mixture was cooled to <0 °C (ice-salt bath), and then 2.15 g of zinc (33 mmol, 20 equivalent) was added in portions. The solution was stirred at <0 °C, and after 20 minutes, TLC analysis (n-hexane / DCM, 4:6) showed no reactants remaining in the reaction mixture. Subsequently, the reaction mixture was further analyzed using... Excess zinc was removed by filtration. A saturated aqueous solution of NaHCO3 (50 mL) was added to the resulting filtrate, and the mixture was stirred for 15 minutes. The organic layer was then separated and washed with more saturated aqueous solution of NaHCO3. The aqueous phase was extracted with CHCl3. The combined organic phases were dried over anhydrous Na2SO4, and the solvent was evaporated under reduced pressure to give a brownish-yellow solid product (410 mg, 92% yield).

[0091] 1¹H-NMR (300MHz; chloroform-d) δppm 8.05-7.94 (m, 2H), 7.51-7.41 (m, 2H), 6.91-6.79 (m, 2H), 6.74-6.63 (m, 2H), 5.43 (d, J = 2.0Hz, 1H), 5.01 (d, J = 2.0Hz, 1H), 4.14 (broads, 2H), 3.80 (s, 3H).13C-NMR (75MHz; chloroform-d)δppm 165.05 (1C), 160.19 (1C), 153.17 (1C), 151.58 (1C), 132.42 (2C), 127.45 (1C), 126.47 (2C), 118.85 (1C), 114.00 (4C), 100.29 (1C), 55.42 (1C).

[0092] Example 5: Preparation of 1-(4-methoxyphenyl)vinyl 4-acetamidobenzoate

[0093] In a 100 mL Schlenk flask under an inert N2 atmosphere, 303.0 mg (1.13 mmol, 1.0 equivalence) of 1-(4-methoxyphenyl)vinyl-4-aminobenzoate was dissolved in 30 mL of anhydrous DCM. Then, 0.24 mL of NEt3 (1.688 mmol, 1.5 equivalence) was added. Subsequently, 0.104 mL of CH3COCl (1.46 mmol, 1.3 equivalence) was added dropwise to the mixture at <0 °C (ice-salt bath). The mixture was stirred at <0 °C for 1 h, and the complete conversion of the starting material was observed by TLC. Then, 30 mL of saturated NH4Cl aqueous solution was added to quench excess acyl chloride. The organic layer was separated and washed with more saturated NH4Cl aqueous solution. The aqueous phase was extracted with DCM, the organic layers were combined, washed with brine, dried over anhydrous Na2SO4, and the solvent was evaporated under reduced pressure.

[0094] 1 ¹H-NMR (300MHz; chloroform-d) δppm 8.20–8.15 (m, 2H), 7.73–7.63 (m, 2H), 7.53–7.42 (m, 1H), 7.39 (s, 1H), 6.94–6.83 (m, 2H), 5.48 (d, J = 2.2 Hz, 1H), 5.06 (d, J = 2.2 Hz, 1H), 3.82 (s, 3H), 2.25 (s, 3H). 13C-NMR (75MHz; chloroform-d) δppm 169.01 (1C), 164.74 (1C), 160.33 (1C), 153.08 (1C), 143.06 (1C), 131.49 (2C), 126.94 (2C), 126.41 (2C), 124.68 (1C), 119.09 (1C), 114.08 (2C), 100.51 (1C), 55.42 (1C), 24.80 (1C).

[0095] Example 6: Photoactivation of 1-(4-methoxyphenyl)vinyl 4-acetamidobenzoate

[0096] In a photochemical reactor, 1-(4-methoxyphenyl)vinyl-4-acetamidobenzoate (102.9 mg, 0.33 mmol) was dissolved in 50 mL of degassed MeOH. The solution was then irradiated for 2 hours under an inert atmosphere using a high-pressure mercury lamp (HPK125W) (cooling temperature = -15 °C). The solvent was then evaporated, and the product was purified by silica gel column chromatography using n-hexane / ethyl acetate (7:3) as the mobile phase. The photoconversion product was obtained as a pale yellow solid (42.6 mg, yield 42%).

[0097] Example 7: Photochemistry of 1-(4-methoxyphenyl)vinyl 4-acetamidobenzoate and pro- avobenzone Property comparison

[0098] Achieved 3×10⁻⁶ irradiations at 312 nm -5 The UV-Vis spectra of (a) pre-avobenzone, PvB-360 (comparative example) and (b) 1-(4-methoxyphenyl)vinyl-4-acetamidobenzoate, PVB-1 (compound according to the invention) in MeOH solution are shown. The UV-Vis spectra reveal the absorbance changes of the two compounds.

[0099] The main difference is that 1-(4-methoxyphenyl)vinyl-4-acetamidobenzoate is photoconverted to the subsequent photoproducts more quickly than avobenzone. After 10 minutes of irradiation, 1-(4-methoxyphenyl)vinyl-4-acetamidobenzoate is completely converted to the photoproducts, while avobenzone requires more than 20 minutes to achieve complete photoconversion.

[0100] Furthermore, 1-(4-methoxyphenyl)vinyl-4-acetamidobenzoate has maximum absorption at 270 nm, and it can absorb more UV-B radiation than avobenzone (see [link to article]). Figure 1 (a) and Figure 1 (b)).

[0101] Example 8: Irradiation activation studies of PvB-360 (comparative example) and PVB-1 (inventive example) using a solar simulator Figure 2

[0102] Activation studies were conducted by irradiating a thin layer of filter material dissolved in a suitable solvent on top of a PMMA plate using a solar simulator. In this case, dibutyl adipate was used as the solvent (filter material 2% by weight). The instrument can measure the SPF and UVA-PF of (pre-avobenzone) and PVB-1 at different irradiation times (measured in MED) (see [reference]). ​ PvB-360 (proavobenzone) and PVB-1 at different irradiation times (SPF and UVA-PF).

[0103] The SPF value of PVB-1 was observed to be higher than that of PvB360. Regarding the UVA-PF value, PVB-1 was observed to achieve a higher value at the same irradiation dose. In fact, PVB-1's value was just over 3 UVA-PF units at 2.5 MED irradiation. PvB-360, on the other hand, reached its maximum value of approximately 2.5 units after 5 MED irradiation.

[0104] Reference List

[0105] Patent documents

[0106] WO2006100225

[0107] Non-patent literature

[0108] Adaya Gallardo et al., "Dose-dependent progressive sunscreens. A new strategy for photoprotection?", Photochemical & Photobiological Sciences, 2010, vol.9, pp.530-534

Claims

1. A compound of formula (I), a pharmaceutically or cosmetically acceptable salt thereof, or a stereoisomer of any one thereof or a mixture thereof, Or, alternatively in: In compound (I), R' is selected from H; (C1-C6)-alkyl, and (C3-C6)-cycloalkyl; R1, R2, R4, R5, R6, R7, R9 and R 10 It is a group independently selected from H, hydroxyl, amino, (C1-C6)-alkyl, (C1-C6)-alkoxy, (C1-C6)-alkylamino, and (C1-C6)-dialkylamino; R3 is a (C1-C6)-alkyl group; and R8 is selected from (C1-C6)-alkyl, (C1-C6)-alkoxy, hydroxy, amino, (C1-C6)-alkylamino, and (C1-C6)-dialkylamino; and In compound (I'), R1 and R6 are independently selected from H, amino, (C1-C6)-alkyl, (C1-C6)-alkoxy, (C1-C6)-alkylamino, and (C1-C6)-dialkylamino groups; R', R2, R4, R5, R7, R9, R 10 R3 and R8 are as defined in compound (I).

2. The compound according to claim 1, wherein it is a compound of formula (I), or a pharmaceutically or cosmetically acceptable salt thereof, or a stereoisomer of any one thereof, or a mixture thereof.

3. The compound according to any one of claims 1 to 2, wherein R1, R2, R4, R5, R6, R7, R9 and R 10 R8 is H and R' is (C1-C6)-alkoxy, and R' is H.

4. The compound according to any one of claims 1 to 3, wherein R3 is (C1-C3)-alkyl.

5. The compound according to claim 1, wherein in formula (I) and formula (I'), R', R1, R2, R4, R5, R6, R7, R9 and R 10 R3 is H; R4 is methyl; and R5 is methoxy.

6. Use of the compound as defined in any one of claims 1 to 5 for the protection of living humans or animals from ultraviolet radiation.

7. A method for protecting a material from ultraviolet radiation, comprising treating the material with a composition containing an effective amount of a compound as defined in any one of claims 1 to 5.

8. The use according to claim 6, wherein the use includes in-situ photochemical conversion of the compound of formula (I) into a sunscreen compound.

9. A composition selected from cosmetic compositions, pharmaceutical compositions, and personal care compositions, comprising at least an effective amount of a compound as defined in any one of claims 1 to 5 for protecting a living human or animal from ultraviolet radiation, and one or more pharmaceutically or cosmetically acceptable excipients or carriers; or alternatively, a composition comprising at least an effective amount of a compound as defined in any one of claims 1 to 5 for protecting a material from ultraviolet radiation, and suitable components selected from at least polymers, solvents, additives, and mixtures thereof.

10. The cosmetic or pharmaceutical composition, or personal care composition according to claim 9, wherein the effective amount is from 0.1% to 10% by weight based on the total weight of the composition.

11. The composition for protecting materials from ultraviolet radiation according to claim 9, wherein the effective amount is from 0.1% to 10% by weight based on the total weight of the composition.

12. The cosmetic or pharmaceutical composition or personal care composition according to any one of claims 9 to 11, wherein the composition is selected from creams, ointments, oils, lotions, gels, sticks, foams, emulsions, suspensions, powders, lotions, dispersants, sprays, aerosols, lipsticks, foundations, cosmetics, loose powder or pressed powder, blush, eyeshadow, mascara, nail polish, nail paint, and non-permanent hair coloring compositions.

13. A method for preparing a compound as defined in any one of claims 1 to 5, in: When the compound is a compound of formula (I), the method includes making a compound of formula (II) a The reaction of (C1-C6) acyl halides with (C1-C6) acyl halides in the presence of a suitable solvent and a suitable base; Where R' and R1 to R 10 As defined in compound (I) and R 3a 'For NH2; and When the compound is of formula (I'), the method includes irradiating the compound of formula (I) with ultraviolet light to produce the compound of formula (I').

14. The method of claim 13, further comprising a pre-processing step, said pre-processing step comprising making formula (II) b The compound undergoes a reduction reaction to produce a product of formula (II). a ) compounds. In equation (II) b In compounds of ), R', R1 to R 10 As defined in compound (I) and R 3b 'It is NO2.' 15. A compound of formula (II), a pharmaceutically or cosmetically acceptable salt thereof, or a stereoisomer of any one thereof or a mixture thereof, in: In compound (II), R' is selected from H; (C1-C6)-alkyl, and (C3-C6)-cycloalkyl; R1, R2, R4, R5, R6, R7, R9 and R 10 It is a group independently selected from H, hydroxyl, amino, (C1-C6)-alkyl, (C1-C6)-alkoxy, (C1-C6)-alkylamino, and (C1-C6)-dialkylamino; R3' is an amino or nitro group; and R8 is selected from (C1-C6)-alkyl, (C1-C6)-alkoxy, hydroxy, amino, (C1-C6)-alkylamino, and (C1-C6)-dialkylamino.

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