Dibenzoylmethane compounds as photochemical precursors for UV absorbers

Abstract

The present invention relates to precursors of dibenzoylmethane compounds having an amide group on one of the rings, and corresponding photoconversion compounds, pharmaceutically or cosmetically acceptable salts thereof, or stereoisomers or mixtures thereof, for use in protecting human or animal living organisms or materials from ultraviolet light. The present invention also relates to the preparation processes thereof, as well as cosmetic compositions, pharmaceutical compositions or personal care compositions thereof.

Description

[Technical Field]

[0001] This application claims the interests of European Patent Application EP23382293, filed on 28 March 2023.

[0002] This invention relates to photochemical precursors of ultraviolet absorbers, and more particularly to several dibenzoylmethane compounds, as well as their preparation processes and applications. [Background technology]

[0003] Invisible ultraviolet A (UVA, 320-400 nm) and ultraviolet B (UVB, 290-320 nm) radiation from the sun can cause skin damage both immediately and in the long term. Some examples include sunburn, rashes, cell and tissue damage, and skin cancer. Increased awareness of these risks is leading to changes in sun exposure habits, including the use of clothing, hats, eyewear, sunscreen, and other forms of photoprotection.

[0004] Sunscreen is any substance or material that protects the skin from ultraviolet (UV) radiation. Sunscreen is commonly sold in the form of sprays, creams, topical lotions, ointments, and gels.

[0005] Several benzoic acid esters have been described as photochemical precursors of ultraviolet absorbers. Their photoprotective activity stems from the fact that these compounds can be photochemically converted in situ to become sunscreen compounds with ultraviolet protection capabilities.

[0006] The paper "Dose-dependent progressive sunscreens: A new strategy for photoprotection?" by Adaya Gallardo et al., Photochemical & Photobiological Sciences, 2010, vol.9, pp.530-534, discloses that benzophenones absorb UV-B and UVA-II radiation, while dibenzoylmethanes absorb UV-A, preventing their penetration into the skin.

[0007] Benzophenones and dibenzoylmethanes play an important role in UV filters currently approved for use in cosmetics. These compounds share an aromatic β-hydrocarbonyl group in their structure, which is the main component of their UV-blocking effect.

[0008] Avobenzone, dioxybenzone, oxybenzone, and surisobenzone are some of the most widely used and representative sunscreen compounds.

[0009] When radiation is absorbed, phototautomerization is induced, forming an unstable enol that releases the absorbed radiation as heat. Each molecule participates in multiple cycles before being broken down.

[0010] Photostability can be defined as the molecular response to exposure to sunlight, ultraviolet light, and visible light. This can vary depending on the solvent or medium used.

[0011] Avobenzone is one of the most widely used filters. It provides protection across a broad range of the UVA spectrum, including UVA-I. Unfortunately, concerns have been raised regarding its photostability and its ability to break down other sunscreen ingredients.

[0012] Pre-avobenzone, a precursor of avobenzone, is one of the most commonly used molecules. However, it takes more than 20 minutes for pre-avobenzone to reach complete photoconversion. Therefore, it is desirable to find a new sunscreen compound that reaches complete photoconversion more quickly. Summary of the Invention

[0013] The inventors have found that dibenzoylmethane compounds having an amide group on one of the rings show improved photoconversion compared to 1-(4-methoxyphenyl)vinyl-4-(tert-butyl)benzoate (pre-avobenzone).

[0014] One aspect of the present invention is a compound of formula (I), a pharmaceutically or cosmetically acceptable salt thereof, or a stereoisomer or mixture of any of them,

Chemical formula

[0015] Another aspect of the present invention relates to either compound (I) or compound (I') as defined above, for use in protecting human or animal living organisms or materials from ultraviolet light.

[0016] Another aspect of the present invention relates to a method for protecting a material from ultraviolet light, comprising treating the material with either compound (I) or compound (I') as defined above.

[0017] Another aspect of the present invention relates to a composition selected from cosmetic compositions, pharmaceutical compositions, and personal care compositions, comprising an effective amount of the compound defined above for protecting a human or animal organism from ultraviolet light, and combined with one or more pharmaceutically or cosmetically acceptable excipients or carriers, or to a composition comprising at least an effective amount of the compound defined above for protecting a material from ultraviolet light, and combined with a suitable medium.

[0018] Another aspect of the present invention relates to a process for preparing either compound (I) or compound (I') as defined above, wherein if the compound is a compound of formula (I), the process is of formula (II) a The process includes reacting a compound of formula (II) or a suitable salt thereof with a (C1-C6) acyl halide in the presence of a suitable solvent and a suitable base, a In the compound of ), R' and R1~R 10 This is defined in equation (I), and R 3a If ' is NH2, and the compound is a compound of formula (I'), the process includes irradiating the compound of formula (I) with ultraviolet light to obtain the compound of formula (I').

[0019] [ka]

[0020] Finally, another aspect of the present invention is a compound of formula (II), [ka] With respect to the pharmaceutically or cosmetically acceptable salts thereof, or any stereoisomer thereof, or mixtures thereof, in the compound of formula (II), R' is selected from the group consisting of H, (C1-C6) alkyl, and (C3-C6) cycloalkyl, and R1, R2, R4, R5, R6, R7, R9, and R 10 Each of these is independently a radical selected from the group consisting of H, hydroxy, amino, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkylamino, and (C1-C6)dialkylamino, R3' is amino or nitro, and R8 is selected from the group consisting of (C1-C6)alkyl, (C1-C6)alkoxy, hydroxy, amino, (C1-C6)alkylamino, and (C1-C6)-dialkylamino. [Brief explanation of the drawing]

[0021] [Figure 1a-b] The UV-Vis spectra showing the absorption changes of preavobenzone (PvB360)(a) and 1-(4-methoxyphenyl)vinyl-4-acetamidobenzoate (PVB-1)(b) when a 3×10⁻⁵ M solution in MeOH is irradiated at 312 nm are shown. [Figure 2] The SPF and UVA-PF of PvB360 (preavobenzone, comparative compound) and PVB-1 (compound of the present invention) at different irradiation times are shown. (PVB-1) corresponds to the compound of formula (I), where R' is H, R1, R2, R4, R5, R6, R7, R9 and R10 are H, R3 is methyl, and R8 is methoxyl. [Modes for carrying out the invention]

[0022] For the purposes of this invention, any range indicated shall include both its lower and upper limits. Ranges such as temperature, time, and size shall be considered approximate values ​​unless otherwise specified.

[0023] The term "room temperature" disclosed in this specification refers to the ambient temperature without heating or cooling, generally including 20 to 25 °C.

[0024] The terms "(C1-C6)-alkyl", "(C1-C6)-alkoxy", "(C1-C6)-alkylamino", and "(C1-C6)-dialkylamino" shall be construed as straight-chain or branched-chain.

[0025] The term "pharmaceutically or cosmetically acceptable salt" used in this specification includes any salt formed from a pharmaceutically or cosmetically acceptable non-toxic acid, such as an inorganic acid or an organic acid. There is no particular limitation on the salt, but when used for therapeutic purposes, it must be pharmaceutically or cosmetically acceptable.

[0026] Since some of the compounds of formula (I) are basic compounds, salts may be prepared from pharmaceutically acceptable non-toxic acids such as inorganic acids and organic acids. Examples of such acids include 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, pivalic acid, propionic acid, tartaric acid, p-toluenesulfonic acid, etc.

[0027] The preparation of pharmaceutically acceptable salts of the compounds of formula (I), formula (I'), or formula (II) (including the compounds of formula (II a ) or (II b )) can be carried out by methods known to those skilled in the art. For example, it can be prepared from the parent compound containing a basic moiety by conventional chemical methods. Generally, such salts are prepared by reacting, for example, the basic form of these compounds with a stoichiometric amount of an appropriate pharmaceutically acceptable acid in water, an organic solvent, or a mixture thereof.

[0028] The compounds of the present invention may exist in crystalline form as either non-solvated compounds or solvated products (e.g., hydrates), and both forms are intended to be included within the scope of the present invention. Methods of solvation are generally known in the art.

[0029] The term "solvate" refers to any compound of formula (I), formula (I'), or formula (II). a ) or (II b A solvate refers to a molecular complex containing a compound of (or a salt thereof) and one or more solvent molecules bonded by non-covalent intermolecular forces, either stoichiometric or non-stoichiometric. If one or more solvent molecules that constitute part of the molecular complex are water, the solvate is a hydrate.

[0030] The expression "an effective amount for protecting a human or animal organism or material from ultraviolet light" as used herein refers to the amount of compound sufficient to provide protection from ultraviolet light when administered. In the case of a human or animal organism, this means preventing skin damage. Therefore, as used herein, an effective amount refers to a therapeutically effective amount.

[0031] The expression "medicinal or cosmetically acceptable excipient or carrier" refers to a medicinally acceptable material, composition, or medium. Each component must be medicinal or cosmetically acceptable in the sense that it is compatible with other components of the medicinal or cosmetic composition. It must also be suitable for use in contact with human and animal skin without causing excessive toxicity, irritation, allergic reactions, immunogenicity, or other problems or complications beyond what is commensurate with a reasonable benefit / risk ratio.

[0032] The term "cosmetically acceptable" is used here synonymously to refer to an excipient or carrier that is suitable for use in contact with skin or humans and animals without excessive toxicity, incompatibility, instability, allergic reactions, etc.

[0033] As described above, one aspect of the present invention relates to compounds of formula (I) or formula (I'), pharmaceutically or cosmetically acceptable salts thereof, or any stereoisomer thereof, or mixtures thereof.

[0034] In certain embodiments, the compounds of the present invention are compounds of formula (I), pharmaceutically or cosmetically acceptable salts thereof, or stereoisomers of either thereof or mixtures thereof.

[0035] In certain embodiments, the compound of formula (I) is a compound in which R1 and R6 are radicals independently selected from the group consisting of H, amino, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkylamino, and (C1-C6)dialkylamino.

[0036] In another specific embodiment, the compound of the present invention of formula (I) or formula (I') is R1, R2, R4, R5, R6, R7, R9 and R 10 The compound is H, R8 is (C1-C6)alkoxyl, 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 compound of the present invention is in formula (I) and formula (I') R', R1, R2, R4, R5, R6, R7, R9 and R 10 This is a compound in which R3 is H, R3 is methyl, and R8 is a methoxyl group.

[0037] Furthermore, compounds as defined above for use in protecting human or animal organisms from ultraviolet radiation are part of the present invention. This aspect of the present invention may also involve formulating compounds (I) or (I') as defined above for use in the manufacture of cosmetic compositions, pharmaceutical compositions or personal care compositions for protecting human or animal organisms from ultraviolet radiation. The present invention also relates to a method for protecting human or animal organisms from ultraviolet radiation, the method comprising administering an effective amount of a compound as defined above for protecting human or animal organisms from ultraviolet radiation, together with one or more pharmaceutically or cosmetically acceptable excipients or carriers. In certain embodiments, the animal organism is a mammal.

[0038] The use of the compounds as defined above for protecting human or animal organisms from ultraviolet radiation is considered part of the present invention. In particular, the use as defined above includes the photochemical conversion of the compound of formula (I) into a sunscreen compound in situ.

[0039] Furthermore, a method for protecting a material from ultraviolet light, which includes treating the material with either compound (I) or compound (I') as defined above, is also part of the present invention. Generally, a method for protecting a material includes applying an effective amount of either compound (I) or compound (I') as defined above to protect the material from ultraviolet light.

[0040] The materials may be selected from the group consisting of organic compounds, oils and fats, waxes, gelatin, sunscreens, polymers (polyolefins, polyketones, polystyrene, polyvinyl chloride (PVC), polyacrylates, polymethacrylates, polyacrylamides, polyacrylonitriles, polyvinyl alcohol derivatives, polyvinyl acetate derivatives, polyurethanes, polyamides, polyesters, polyureas, polycarbonates, polysiloxanes, polyketimines), radiation-curable compositions, resins (hydrocarbon resins, phenol / formaldehyde resins, urea / formaldehyde resins, melamine / formaldehyde resins, unsaturated polyester resins, crosslinkable acrylic resins, crosslinkable epoxy resins, epoxy / melamine resins), varnishes, cellulose, cellulose-based paper formulations, photographic materials, photographic film and paper, metal products, ceramic products, preservatives, fibers, textiles, fabrics, dyes, inks, coatings, adhesives, leather, wood, lenses, composite materials, mixtures or blends, etc.

[0041] As used herein, the term “effective amount of compound (I) or compound (I') for protecting a material from ultraviolet light” refers to the amount of compound sufficient to protect a material from ultraviolet light when the compound is applied to it, i.e., the effective amount that prevents or minimizes the degradation of the material.

[0042] In certain embodiments of the method, either compound (I) or compound (I') as defined above is applied in the form of a composition further comprising suitable components selected from at least polymers, solvents, additives, and mixtures thereof. Examples of additives are antioxidants, preservatives, thickeners, colorants, or opacifiers. In certain embodiments of the method, the composition used in this method is an industrial composition.

[0043] In another specific embodiment, the compound of the present invention is a compound of formula (I) as defined above, and the compound of formula (I) is readily photochemically converted to a sunscreen compound in situ.

[0044] In another specific embodiment, the compound of formula (I) or formula (I') of the present invention, as defined above, is for protection against UV-A and UV-B.

[0045] In another specific embodiment, the compound whose use is defined as described above is for protection against ultraviolet radiation emitted from the sun.

[0046] In another specific embodiment, the compound whose use is defined as described above is characterized by progressive ultraviolet protection depending on the duration of solar exposure and the degree of solar radiation.

[0047] The compound of formula (I) or formula (I') of the present invention may be in the form of a composition selected from cosmetic compositions, pharmaceutical compositions and personal care compositions, the composition comprising an effective amount of the compound for protecting human or animal living organisms or materials from ultraviolet light, together with one or more pharmaceutically or cosmetically acceptable excipients or carriers.

[0048] The specific embodiments of the first aspect of the present invention described above may also be considered as specific embodiments of the composition of the present invention.

[0049] In certain embodiments, the cosmetic composition, pharmaceutical composition, or personal care composition as defined above has an effective amount of the compound of formula (I) or (I') in the range of 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 has an effective amount of the compound of formula (I) or (I') in the range of 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 has an effective amount of the compound of formula (I) or (I') in the range of 1 to 6% by weight, based on the total weight of the composition.

[0050] In another specific embodiment, the composition of the present invention comprises an effective amount of a dibenzoylmethane compound of formula (I), a pharmaceutically or cosmetically acceptable salt thereof, or any stereoisomer thereof, or a mixture thereof, wherein the composition has high photoconversion ability.

[0051] In another specific embodiment, the compounds of the present invention may be used to form a photostable composition. Such a photostable composition may further contain various other components known in the art, such as triazines, benzotriazoles, hindered amine-based photostables, radical scavengers, and antioxidants.

[0052] The compositions of the present invention are for topical administration. In certain embodiments, the cosmetic composition, pharmaceutical composition, or personal care composition as defined above is a composition selected from the group consisting of creams, ointments, oils, lotions, gels, sticks, foams, milks, suspensions, powders, emulsions, dispersions, sprays, aerosols, lipsticks, foundations, makeup, loose powders or pressed powders, eyebrushes, eyeshadows, mascaras, nail varnishes, nail lacquers, and non-permanent hair dyeing compositions.

[0053] In another specific embodiment, the composition of the present invention may include one or more additional organic sunscreens for filtering UV-A or UV-B rays.

[0054] In another specific embodiment, the composition is a sunscreen composition. In another specific embodiment, the sunscreen composition may have an SPF (Sun Protection Factor) of 6 or higher, preferably 30 or higher, and more preferably 50 or higher. Preferably, the sunscreen composition includes a physical filter, a chemical filter, or a combination thereof.

[0055] Suitable excipients or carriers for the compositions of the present invention include, for example, dispersants, preservatives, defoamers, fragrances, aromatics, oils, waxes, propellants, dyes, pigments, emulsifiers, surfactants, thickeners, humectants, exfoliants, and emollients.

[0056] The topical compositions of the present invention can be produced by conventional processes known in the art, for example, 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, depending on the type of composition to be prepared.

[0057] The present invention includes a composition comprising at least an effective amount of the compound defined above for protecting a material from ultraviolet light, and a suitable component selected from at least polymers, solvents, additives, and mixtures thereof. Examples of additives are antioxidants, preservatives, thickeners, colorants, or opacifiers. The composition may also be an industrial composition comprising the compound defined above.

[0058] In certain embodiments, the composition for protecting materials from ultraviolet light, as defined above, has an effective amount of the compound of formula (I) or (I') in the range of 0.1 to 10% by weight, based on the total weight of the composition. In another particular embodiment, the composition, as defined above, has an effective amount of the compound of formula (I) or (I') in the range of 0.5 to 8% by weight, based on the total weight of the composition. In yet another particular embodiment, the composition has an effective amount of the compound of formula (I) or (I') in the range of 1 to 6% by weight, based on the total weight of the composition.

[0059] The compound of formula (I) of the present invention is of formula (II) a A compound of ) or a suitable salt thereof, in the presence of a suitable solvent and a suitable base, is used to create (C1-C6) acylhalides such as acetyl chloride or (C2-C) acylhalides such as acetic anhydride. 12 ) It can be prepared by a process that includes a step of reacting with an acid anhydride, where formula (II aIn the compound of ), R', R1~R 10 R is defined as in the compound of formula (I), 3a ' is NH2. [ka]

[0060] In certain embodiments of this process, the suitable solvent in the preceding step is selected from the group consisting of (C6-C8) aromatic hydrocarbons such as toluene or xylene, or (C1-C3) chlorine-containing solvents such as dichloromethane or dichloroethane. In another particular embodiment of this process, the suitable base is triethylamine alone or in combination with 4-dimethylaminopyridine, or a tertiary amine such as N,N-diisopropylethylamine. The steps of this process are generally carried out at temperatures including the range of -20°C to 0°C.

[0061] In another specific embodiment, the process defined above is further expressed by formula (II b The compound of ) is subjected to a reduction reaction, and the formula (II) defined above is obtained. a The process includes a step to obtain a compound of formula (II), where, b In the compounds of ), R', R1~R 10 R is defined as in the compound of formula (I), 3b’ It is NO. 2. [ka]

[0062] The reduction reaction may be carried out in the presence of an acid using a reducing agent such as a metal oxide. Examples of suitable metals include, for example, Fe, Sn, or Zn. Examples of suitable acids include, for example, hydrochloric acid or acetic acid. In certain embodiments, the metal is zinc. In another specific embodiment of this process, this step is carried out in the presence of a suitable solvent, which may be a (C1-C3) chlorine-containing solvent such as chloroform or dichloromethane. In another specific embodiment, the preferred ratio of (C1-C3) chlorine-containing solvent to acid is 11:1.5 or 7:0.5, respectively. The steps of this process are usually carried out at temperatures within the range of -20°C to 0°C.

[0063] In another specific embodiment, the process of the present invention as defined above further involves subjecting a compound of formula (III) to an elimination reaction of formula (II) b The process includes a step to obtain the compound of formula (III), where X is a halide and R1 to R 10 R is defined as a compound of formula (I), and 3b’ It is NO. 2.

[0064] [ka]

[0065] In certain embodiments, X is a halogen selected from the group consisting of Br, Cl, and I. In certain embodiments of this process, the compound of formula (III) is one in which X is bromine.

[0066] The compound of formula (III) can be prepared from 2-halo-1-(4-methoxyphenyl)ethane-1-one. The term "halo" refers to one of Cl, Br, or I. This compound can be subjected to a reduction reaction with a reducing agent such as NaBH4 in the presence of a suitable solvent. Generally, this reaction is carried out at low temperatures such as (-20°C) to 10°C. The solvent may also be a (C1-C4) alcohol such as methanol to obtain 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, which is used alone or with 4-dimethylaminopyridine.

[0067] [ka]

[0068] In the compounds of formula (III), formula (IV), and formula (V), R1 to R 10 As defined in the compound of formula (I), X is a halogen selected from the group consisting of Br, Cl and I, and R 3b’ It is NO. 2.

[0069] The compound of formula (I') of the present invention can be prepared by a process that includes irradiating the compound of formula (I) with UV light to obtain the compound of formula (I') of the present invention.

[0070] Formula (II a ) and formula (II b Compounds of formula (II) are also part of the present invention. They may also be in the form of pharmaceutically or cosmetically acceptable salts thereof, or any stereoisomer thereof, or mixtures thereof. a ) or formula (II b The salts of the compound (II) refer to non-toxic salts. a ) or formula (IIb Since some of the compounds are basic compounds, salts may be prepared using pharmaceutically or cosmetically acceptable non-toxic acids.

[0071] Throughout this specification and the claims, the word “comprise” and its variations are not intended to exclude other technical features, additives, components, or processes. Furthermore, the word “comprise” also encompasses “consisting of.” Further objects, advantages, and features of the present invention may become apparent to those skilled in the art by examining the description herein or by practicing the present invention. The following examples and drawings are provided for illustrative purposes and are not intended to limit the present invention. Furthermore, the present invention encompasses all possible combinations of the specific embodiments and preferred embodiments described herein.

[0072] Examples Example 1: Preparation of 2-bromo-1-(4-methoxyphenyl)ethane-1-ol In a 100 mL round-bottom flask, 3 g of BMAP (13.2 mmol, 1 equivalent) was dissolved in 60 mL of MeOH. Next, 41 g of NaBH (26.4 mmol, 8 equivalents) was added in small amounts at -10°C (ice-salt bath). The solution was stirred at this temperature for 1 hour (until TLC was completed). Then, 100 mL of DCM and 150 mL of 1 M hydrochloric acid 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 organic phases were combined, washed with brine, and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure, and the product was obtained as a colorless oil (2.86 g, yield 94%).

[0073] Example 2: Preparation of 2-bromo-1-(4-methoxyphenyl)ethyl 4-nitrobenzoate 2-Bromo-1-(4-methoxyphenyl)ethane-1-ol (2.5 g, 10.82 mmol, 1 equivalent) was dissolved in 50 mL of dry THF under an inert atmosphere (N2). Next, the mixture was cooled to 0°C (ice bath), and 2.26 mL of NEt3 (16.23 mmol, 1.5 equivalents) was added. Finally, a solution of 4 g (21.64 mmol, 2.0 equivalents) of p-NBC1 dissolved in 7 mL of dry THF was added dropwise using a dropping funnel. After stirring at 0°C for 10 minutes, the mixture was stirred at room temperature for 7 hours, and then, 1 Complete conversion of the starting material was confirmed by 1H-NMR. Next, volatile components were partially removed by vacuum distillation, and the crude mixture was washed with saturated NaHCO3 aqueous solution. The resulting organic phase was dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. The product was purified by silica gel column chromatography using hexane / DCM (7:3-6:4) as the mobile phase, and the product was obtained as a pale yellow oil (3.709 g, 90% yield). 1 ¹H-NMR (300MHz; chloroform-d)δppm 8.35-8.21 (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 ¹¹C-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).

[0074] Example 3: Preparation of 1-(4-methoxyphenyl)vinyl 4-nitrobenzoate 2-Bromo-1-(4-methoxyphenyl)ethyl 4-nitrobenzoate (2.14 g, 5.64 mmol, 1.0 equivalent) was introduced into 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 DBU (11.28 mmol, 2.0 equivalents) was slowly added. The mixture was stirred at reflux temperature for 1 hour. The mixture was then cooled to room temperature and the reaction was quenched by adding 60 mL of 0.5 M aqueous HCl solution. The phases were separated, and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, washed with brine, and dried over anhydrous Na₂SO₄. After removing the solvent under reduced pressure, the product was obtained as an orange solid (1.501 g, 90% yield). 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 ¹¹C-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).

[0075] Example 4: Preparation of 1-(4-methoxyphenyl)vinyl 4-aminobenzoate 1-(4-methoxyphenyl)vinyl 4-nitrobenzoate (507.6 mg, 1.65 mmol, 1.0 equivalent) was dissolved in 50 mL of CHCl3 / acetic acid (9:1) in a 100 mL round-bottom flask. The mixture was cooled to below 0°C (ice / salt bath), and then 2.15 g (33 mmol, 20 equivalents) of zinc was added gradually. The solution was stirred below 0°C, and after 20 minutes, TLC analysis (hexane / DCM = 4:6) confirmed that no starting material remained in the reaction mixture. The excess zinc was then removed by filtration with Celite®. Saturated sodium bicarbonate aqueous solution (50 mL) was added to the obtained filtrate, and the mixture was stirred for 15 minutes. The organic layer was then separated and washed with saturated NaHCO3 aqueous solution. The aqueous phase was extracted with CHCl3. The organic phases were combined, dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure to obtain the product as a yellowish-brown solid (410 mg, 92% yield). 1 H-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(broad s,2H),3.80(s,3H). 13 ¹¹C-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).

[0076] Example 5: Preparation of 1-(4-methoxyphenyl)vinyl 4-acetamidobenzoate 303.0 mg (1.13 mmol, 1.0 equivalent) of 1-(4-methoxyphenyl)vinyl 4-aminobenzoate was dissolved in 30 mL of dry DCM under an inert atmosphere (N2) in a 100 mL Schlenk tube. Next, 30.24 mL (1.688 mmol, 1.5 equivalent) of NET was added. Then, 0.104 mL (1.46 mmol, 1.3 equivalent) of CH3COCl was added dropwise to the mixture at below 0°C (ice / salt bath). The mixture was stirred at below 0°C for 1 hour, after which complete conversion of the starting materials was observed by TLC. Next, 30 mL of saturated NH4Cl aqueous solution was added to quench the excess acid chloride. The organic layer was separated and further washed with saturated NH4Cl aqueous solution. The aqueous phase was extracted with DCM, and the organic layers were washed together with brine, dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. 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=2.2Hz,1H), 5.06 (d,J=2.2Hz,1H), 3.82 (s,3H), 2.25 (s,3H). 13 ¹¹C-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).

[0077] Example 6: Photoactivation of 1-(4-methoxyphenyl)vinyl 4-acetamidobenzoate 1-(4-methoxyphenyl)vinyl 4-acetamidobenzoate (102.9 mg, 0.33 mmol) was dissolved in 50 mL of degassed MeOH in a photochemical reactor. The solution was then irradiated with a high-pressure mercury lamp (HPK 125 W) for 2 hours under an inert atmosphere (cooling temperature = -15°C). The solvent was then removed by distillation, and the product was purified by silica gel column chromatography using hexane / ethyl acetate (7:3) as the mobile phase. The photoconversion product was obtained as a pale yellow solid (42.6 mg, yield 42%).

[0078] Example 7: Comparison of photochemical properties of 1-(4-methoxyphenyl)vinyl 4-acetamidobenzoate and preavobenzone 3 x 10 -5 When methanol solution M was irradiated at 312 nm, UV-Vis spectra were obtained for (a) preavobenzone (PvB-360) (comparative example) and (b) 1-(4-methoxyphenyl) vinyl 4-acetamidobenzoate (PVB-1) (compound according to the present invention). These UV-Vis spectra show the absorption changes of both compounds.

[0079] The main difference is that 1-(4-methoxyphenyl)vinyl 4-acetamidobenzoate is photoconverted to its subsequent photoproduct faster than avobenzone. After 10 minutes of irradiation, 1-(4-methoxyphenyl)vinyl 4-acetamidobenzoate is completely converted to its photoproduct, while avobenzone takes more than 20 minutes to be fully photoconverted.

[0080] Furthermore, 1-(4-methoxyphenyl)vinyl 4-acetamidobenzoate has an absorption maximum at 270 nm and can absorb more UV-B radiation than avobenzone (see Figures 1(a) and (b)).

[0081] Example 8: Activation test of PvB-360 (comparative example) and PVB-1 (example of the present invention) by irradiation using a solar simulator. Activation tests were performed by forming a thin layer of filter dissolved in a suitable solvent on a PMMA plate and irradiating it using a solar simulator. In this case, dibutyl adipate was used as the solvent (filter concentration 2% w / w). Using a Labsphere® instrument, the SPF and UVA-PF of (preavobenzone) and PVB-1 were measured at different irradiation times (measured in MED units) (see Figure 2: SPF and UVA-PF of PvB-360 (preavobenzone) and PVB-1 at different irradiation times).

[0082] The SPF value of PVB-1 was observed to be higher than that of PvB-360. Regarding UVA-PF values, PVB-1 was observed to reach higher values ​​at the same irradiation dose. In fact, PVB-1 reached a value slightly exceeding 3 UVA-PF units when irradiated at 2.5 MED. On the other hand, the maximum value of PvB-360 was reached after irradiation at 5 MED, and that value was approximately 2.5 units.

[0083] References Patent Documents

[0084] International Publication No. 2006100225 Non-patent literature Adaya Gallardo et al., “Dose-dependent progressive sunscreens. A new strategy for photoprotection?”, Photochemical & Photobiological Sciences, 2010, vol. 9, pp. 530-534

Claims

1. Compound of formula (I) 【Chemistry 1】 Or, or 【Chemistry 2】 (I'), a pharmaceutically or cosmetically acceptable salt thereof, or any stereoisomer thereof, or a mixture thereof. (In the formula, In compound (I), R' is H, (C １ ~C ６ ) alkyl and (C ３ ~C ６ ) Selected from the group consisting of cycloalkyl groups, R １ 、 R ２ 、 R ４ 、 R ５ 、 R ６ 、 R ７ 、 R ９ and R １０ are each independently selected radicals from the group consisting of H, hydroxy, amino, (C １ ~C ６ alkyl), (C １ ~C ６ alkoxy), (C １ ~C ６ alkylamino) and (C １ ~C ６ dialkylamino). R ３ is, (C １ ~C ６ ) is alkyl, R ８ is, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) Alkoxy, hydroxy, amino, (C １ ~C ６ ) alkylamino and (C １ ~C ６ ) Selected from the group consisting of dialkylaminos, In compound (I'), R １ and R ６ However, H, amino, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) Alkoxy, (C １ ~C ６ ) alkylamino, and (C １ ~C ６ ) A radical independently selected from the group consisting of dialkylaminos, R', R ２ , R ４ , R ５ , R ７ , R ９ , R １０ , R ３ and R ８ This is as defined in compound (I).

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

3. R １ , R ２ , R ４ , R ５ , R ６ , R ７ , R ９ and R １０ H is R ８ But (C １ ~C ６ The compound according to claim 1 or 2, wherein it is an alkoxyl and R' is H.

4. R ３ But (C １ ~C ３ The compound according to any one of claims 1 to 3, wherein it is alkyl.

5. In equations (I) and (I'), R', R １ , R ２ , R ４ , R ５ , R ６ , R ７ , R ９ and R １０ H is R ３ is methyl, R ８ The compound according to claim 1, wherein is methoxyl.

6. Use of the compound according to any one of claims 1 to 5 for protecting the living body of a human or animal from ultraviolet light.

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

8. The use according to claim 6, wherein the use comprises converting the compound of formula (I) into a sunscreen compound in situ via photochemical means.

9. A composition selected from the group consisting of cosmetic compositions, pharmaceutical compositions and personal care compositions, comprising at least an effective amount of a compound according to any one of claims 1 to 5 for protecting the living body of a human or animal from ultraviolet light, together with one or more pharmaceutically or cosmetically acceptable excipients or carriers, or alternatively, comprising at least an effective amount of a compound according to any one of claims 1 to 5 for protecting the material from ultraviolet light, together with at least a suitable component selected from polymers, solvents, additives and mixtures thereof.

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

11. The composition for protecting a material from ultraviolet light according to claim 9, wherein the effective amount is in the range of 0.1% by weight to 10% by weight, based on the total weight of the composition.

12. A cosmetic composition, pharmaceutical composition, or personal care composition according to any one of claims 9 to 11, selected from the group consisting of creams, ointments, oils, lotions, gels, sticks, foams, milks, suspensions, powders, emulsions, dispersions, sprays, aerosols, lipsticks, foundations, makeup, loose powders or pressed powders, eyebrushes, eyeshadows, mascaras, nail varnishes, nail lacquers, and non-permanent hair dyeing compositions.

13. A process for preparing the compound according to any one of claims 1 to 5, If the compound is a compound of formula (I), then the process is of formula (II ａ ) compounds; 【Transformation 3】 or a suitable salt thereof, in the presence of a suitable solvent and a suitable base, (C １ ~C ６ ) Includes a step of reacting with an acylhalide, where R' and R １ ~R １０ As defined in compound (I), R ３ａ 'is NH ２ And, If the compound is a compound of formula (I'), the process includes irradiating the compound of formula (I) with UV light to produce a compound of formula (I').

14. Formula (II ｂ The compound of ) is subjected to a reduction reaction, and formula (II ａ The process further includes a pre-step that involves generating a compound of the following: 【Chemistry 4】 Formula (II ｂ In the compound of ), R' and R １ ~R １０ As defined in compound (I), R ３ｂ’ The answer is NO. ２ The process according to claim 13.

15. Compound of formula (II) 【Transformation 5】 The pharmaceutically or cosmetically acceptable salt thereof, or any stereoisomer thereof, or a mixture thereof: (In the formula, In compound (II), R’ is selected from the group consisting of H, (C １ ~C ６ alkyl and (C ３ ~C ６ cycloalkyl), R １ 、R ２ 、R ４ 、R ５ 、R ６ 、R ７ 、R ９ and R １０ are each independently selected radicals from the group consisting of H, hydroxy, amino, (C １ ~C ６ ), alkyl, (C １ ~C ６ ), alkoxy, (C １ ~C ６ ), alkylamino and (C １ ~C ６ ), dialkylamino, R ３ ' is an amino or nitro, R ８ is, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) Alkoxy, hydroxy, amino, (C １ ~C ６ ) alkylamino and (C １ ~C ６ (Selected from the group consisting of dialkylaminos).

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