Analogues of mycosporine-like amino acids and their use as screening agents

Abstract

The present invention relates to compounds of formula (I) as defined herein, which are suitable for protecting against ultraviolet (UV) radiation. Furthermore, the present invention relates to compositions comprising at least one compound of formula (I). TIFF2023511378000021.tif24149

Description

[Technical Field]

[0001] The present invention relates to the field of protection from ultraviolet (UV) radiation. In particular, the present invention relates to a compound of formula (I)

[0002] [ka] (In the formula, R A , R B , R C , R D , and R E is as defined herein. Furthermore, the present invention relates to compositions comprising at least one compound of formula (I). The present invention also relates to compounds of formula (I) for use in sunscreens and compositions comprising at least one compound of formula (I). Furthermore, the present invention relates to compounds of formula (I) as light stabilizers in body care products and household cleaning and treating agents. [Background technology]

[0003] UV radiation causes harmful effects on human skin. In addition to the acute effect of sunburn, UV radiation is also known to increase the risk of skin cancer. Furthermore, prolonged exposure to UV-A and UV-B light can cause phototoxic and photoallergic reactions in the skin, which can accelerate skin aging.

[0004] To protect human skin from UV radiation, various UV protective UV filters (also called UV absorbers) exist, including UV-A filters, UV-B filters, and broad-spectrum filters. These filters are added to sunscreens or cosmetic compositions. UV filters can be organic or inorganic, particulate or non-particulate compounds, all of which have a high absorption effect in the UV light range. Generally, UV light can be divided into UV-A radiation (320-400 nm) and UV-B radiation (280-320 nm). Depending on the position of the absorption maximum, UV filters can be divided into UV-A filters and UV-B filters. If a UV filter absorbs both UV-A and UV-B light, it is called a broad-spectrum absorber.

[0005] Since 2006, it has been recommended by the EU European Commission that all sunscreen or cosmetic compositions should have a UV-A protection factor that is at least one-third of the declared sun protection factor (SPF), where sun protection factor here refers primarily to UV-B protection.

[0006] However, UV filters known in the prior art, for example, for use in sunscreen or cosmetic compositions, have certain drawbacks.In particular, mention may be made of the drawback that the majority of organic UV filters registered as cosmetics are miscible or soluble in oil, making them suitable for application to the oil phase of sunscreen emulsions.Therefore, the solubility of each UV filter depends on the oil used.Therefore, sunscreen formulators are limited by the selection of a certain oil, and therefore by the selection of a typical emollient to improve the feel.This can have a negative impact on consumer compliance.

[0007] Therefore, there is a need for effective water-soluble UV filters.

[0008] Mycosporine-like amino acids (MAAs) have the potential to protect organisms from UV radiation. MAAs consist of a group of compounds with a cyclohexenone or cyclohexenimine basic structure. Analogs of MAAs are known to be suitable UV filters in terms of absorption and photostability (ES2550374B1 and Losantos et al., Angew. Chem. 2017, 129, 1-5), but are nearly insoluble in water. Summary of the Invention [Problem to be solved by the invention]

[0009] Thus, there continues to be a need for new water-soluble compounds that adequately protect the skin from UV radiation. In this regard, another object of the present invention is to provide an effective UV protection composition suitable for improving the photostability of body care products and household cleaning and treating agents. In particular, it is an object of the present invention to provide a composition suitable for improving the photostability of sunscreen compositions. [Means for solving the problem]

[0010] Surprisingly, it has been found that at least one of these objectives can be achieved by the composition according to the invention.

[0011] In particular, the present inventors have discovered compounds that effectively absorb light in the UV range suitable for UV protection. These compounds are analogs of mycosporine-like amino acids (MAAs).

[0012] Thus, in a first aspect, the present invention provides a compound of formula (I)

[0013] [ka] (In the formula, R Ais H, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-haloalkoxy, C2-C6-alkylene, (OC(=O))-(C1-C4-alkyl), (OC(=O))-aryl, or S-(C1-C4-alkyl); R B is H, halogen, hydroxy, hydroxymethyl, C1-C6-alkyl, C2-C6-alkylene, or C1-C6-alkoxy; R C is H, halogen, hydroxy, hydroxymethyl, C1-C6-alkyl, C2-C6-alkylene, or C1-C6-alkoxy; R D is (CH2O) n -R M , (CH2CH2O) n -R M , or (CH2CH2CH2O) n -R M and; R E is (CH2O) m -R N , (CH2CH2O) m -R N , or (CH2CH2CH2O) m -R N and; R M is H, C1-C4-alkyl, or a saccharide; R N is H, C1-C4-alkyl, or a saccharide; n is an integer from 1 to 50; m is an integer from 1 to 50; k is 0, 1, or 2. or a salt, stereoisomer, or tautomer thereof.

[0014] Below, the preferred embodiments of the substituents in the above formula (I) are described in more detail.It is understood that each preferred embodiment is not only suitable by itself, but also suitable in combination with other preferred embodiments.In addition, it is understood that in each case, the preference also applies to the salts, stereoisomers or tautomers of the compounds of the present invention.

[0015] In a preferred embodiment A1 of the first aspect, the compound of formula (I) is of formula (Ia)

[0016] [ka] (In the formula, X - are halides, formate, acetate, succinate, oxalate, maleate, fumarate, malate, tartrate, citrate, trifluoroacetate, triflate, tosylate, and mesylate. It has a salt form according to the formula:

[0017] In a preferred embodiment A2 of the first aspect, k is 1.

[0018] In a preferred embodiment A3 of the first aspect, R A is methyl, ethyl, or thiomethyl.

[0019] In a preferred embodiment A4 of the first aspect, R B is H, halogen, hydroxyl, or hydroxymethyl, and R C is H, halogen, hydroxyl, or hydroxymethyl.

[0020] In a preferred embodiment A5 of the first aspect, R D is (CH2CH2O) n -R M and;R M is H or methyl; and n is an integer from 1 to 10.

[0021] In a preferred embodiment A6 of the first aspect, R E is (CH2CH2O) m -R N and;R N is H or methyl; and m is an integer from 1 to 10.

[0022] In a preferred embodiment A7 of the first aspect, R D is (CH2CH2O) n -R M and;R E is (CH2CH2O) m -R N and;R M is H;R N is H; n is 1 or 2; and m is 1 or 2.

[0023] In a preferred embodiment A8 of the first aspect, R A is methyl.

[0024] In a preferred embodiment A9 of the first aspect, R B and R C is equal to, and is preferably H.

[0025] In a preferred embodiment A10 of the first aspect, X - is a chloride ion, a tosylate ion, or a mesylate ion.

[0026] In a preferred embodiment A11 of the first aspect, the compound according to formula (I) is selected from the group consisting of (E)-2-(2-hydroxyethoxy)-N-(3-((2-(2-hydroxyethoxy)ethyl)amino)-2-methylcyclohex-2-en-1-ylidene)ethane-1-aminium chloride, and (E)-2-hydroxy-N-(3-((2-hydroxyethyl)amino)-2-methylcyclohex-2-en-1-ylidene)ethane-1-aminium chloride.

[0027] In a preferred embodiment A12 of the first aspect, the compound according to formula (I) is

[0028] [ka] is selected from the group consisting of:

[0029] In a second aspect, the present invention relates to a cosmetic composition comprising a compound as defined in the first aspect (including all embodiments thereof as described herein) and, optionally, a dermatologically acceptable emulsifier, thickener, or emollient.

[0030] In a third aspect, the present invention relates to a compound as defined in the first aspect (including all embodiments thereof as described herein) or a cosmetic composition as defined in the second aspect, for use as a sunscreen.

[0031] In a fourth aspect, the present invention relates to the use of a compound as defined in the first aspect, including all embodiments thereof as described herein, as a light stabilizer. In particular, the present invention relates to the use of a compound as defined in the first aspect, including all embodiments thereof as described herein, as a light stabilizer in household cleaning and treating agents.

[0032] In a fifth aspect, the present invention relates to a compound as defined in the first aspect (including all embodiments thereof as described herein) in a body care product, for use as a light stabilizer. [Brief explanation of the drawings]

[0033] [Figure 1] Figure 1 shows that all tested compounds A to D absorb within the UV range appropriate for skin protection. Furthermore, it is shown that compound B has the highest specific extinction coefficient among all tested compounds A to D. DETAILED DESCRIPTION OF THE INVENTION

[0034] Before describing exemplary embodiments of the present invention in detail, definitions important for understanding the present invention are provided.

[0035] As used herein and in the appended claims, the singular forms "a" and "an" also include the respective plurals, unless the context clearly dictates otherwise. In the context of the present invention, the terms "about" and "approximately" refer to an interval of accuracy that a person skilled in the art would understand to still ensure the technical effect of the feature in question. This term typically indicates a deviation of ±20%, preferably ±15%, more preferably ±10%, and even more preferably ±5% from the indicated numerical value. The term "comprising" is understood to be non-limiting. For purposes of the present invention, the term "consisting of" is considered a preferred embodiment of the term "comprising." Hereinafter, when a group is defined as including at least a certain number of embodiments, this also preferably encompasses a group consisting only of these embodiments. Furthermore, the terms "first," "second," "third," "(a)," "(b)," "(c)," "(d)," etc. in the present specification and claims are used to distinguish between similar elements and not necessarily to describe an order or chronology. It is understood that terms so used are interchangeable under appropriate circumstances, and that embodiments of the invention described herein are capable of operating in other sequences than those described or exemplified herein. When terms such as "first," "second," "third," or "(a)," "(b)," "(c)," "(d)," "i," "ii," etc., refer to steps in a method, use, or assay, there is no consistency in time or time intervals between the steps. That is, the steps may be performed simultaneously, or there may be time intervals between such steps, whether of seconds, minutes, hours, days, weeks, months, or years, unless otherwise indicated herein above or below in this application. It is understood that the invention is not limited to the particular methodology, protocols, reagents, etc. described herein, as these may vary. It is also understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the invention, which is limited solely by the appended claims.Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

[0036] The term "compound according to the invention" or "compound of formula (I)" includes compounds as defined herein, and also stereoisomers, salts, or tautomers thereof.

[0037] Depending on the substitution pattern, the compounds according to the present invention may have one or more chiral centers. The present invention provides both single pure enantiomers or pure diastereomers of the compounds according to the present invention and mixtures thereof, as well as the use according to the present invention of the pure enantiomers or pure diastereomers of the compounds according to the present invention or mixtures thereof. Suitable compounds according to the present invention also include all possible geometric stereoisomers (cis / trans isomers or E / Z isomers) and mixtures thereof. Cis / trans isomers may exist, for example, with respect to an amide group. The term "stereoisomer" encompasses both optical isomers, e.g., enantiomers or diastereomers (the latter existing due to two or more chiral centers in the molecule), and geometric isomers (cis / trans isomers). The present invention relates to all possible stereoisomers of the compounds of formula (I), i.e., single enantiomers or diastereomers, and mixtures thereof.

[0038] The compounds of formula (I) may be amorphous or may exist in one or more different crystalline states (polymorphs), which may have different macroscopic properties, e.g., stability, or may exhibit different biological properties, e.g., activity. The present invention relates to amorphous and crystalline compounds of formula (I), mixtures of each compound of formula (I) in different crystalline states, and amorphous or crystalline salts thereof.

[0039] Salts of compounds of formula (I) may be pharmaceutically acceptable salts, e.g., those containing the counterion present in drug products listed in the US FDA Orange Book database. They can be formed in conventional manner, e.g., if a compound of formula (I) contains a basic functional group, it can be formed by reacting the compound with an acid of the desired anion.

[0040] Suitable anionic counterions are, in particular, chloride, bromide, hydrogensulfate, sulfate, dihydrogenphosphate, hydrogenphosphate, phosphate, nitrate, bicarbonate, carbonate, hexafluorosilicate, hexafluorophosphate, benzoate, and anions of C1-C4-alkanoic acids, preferably formate, acetate, trifluoroacetate, propionate, and butyrate, and also lactate, gluconate, and poly(2-methyl-2-propanol). Acid anions such as succinate, oxalate, maleate, fumarate, malate, tartrate, and citrate, as well as sulfonate anions such as besylate (benzenesulfonate), tosylate (p-toluenesulfonate), napsylate (naphthalene-2-sulfonate), mesylate (methanesulfonate), esylate (ethanesulfonate), and ethanedisulfonate, can be formed by reacting a compound according to the present invention having a basic functional group with an acid of the corresponding anion. A preferred salt of the compound of formula (I) is the chloride salt.

[0041] Tautomers may also be formed if substituents are present in compounds of formula (I) that allow for the formation of tautomers, such as keto-enol tautomers.

[0042] The organic moieties mentioned in the above definitions of the variables are generic to the individual entries of the individual group members, as is the term halogen. n ~C m indicates in each case the possible number of carbon atoms in the group.

[0043] The term "halogen" denotes in each case fluorine, bromine, chlorine or iodine, in particular fluorine, chlorine or bromine.

[0044] The term "halide" denotes in each case fluoride, bromide, chloride or iodide, in particular fluoride, bromide or chloride.

[0045] The term "alkyl" as used herein refers in each case to a straight-chain or branched alkyl group having typically 1 to 5 carbon atoms, preferably 1 to 4 carbon atoms. Examples of alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl, isobutyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, 1,1-dimethylpropyl, and 1,2-dimethylpropyl. Methyl, ethyl, n-propyl, isopropyl, and isobutyl are particularly preferred.

[0046] As used herein, the term "alkylene" refers to a linking straight-chain or branched alkylene group, typically having 1 to 4 carbon atoms, e.g., 1, 2, 3, or 4 carbon atoms. The alkylene group bridges a particular group to the remainder of the molecule. Preferred alkylene groups include methylene (CH), ethylene (CHCH), propylene (CHCHCH), and the like. One skilled in the art will understand that, for example, when CH is referenced, the tetravalent carbon atom has two valences remaining to form a bridge (-CH-). Similarly, for example, when CHCH is referenced, each carbon atom has one valence remaining to form a bridge (-CHCH-). Furthermore, for example, when CHCHCH is referenced, each terminal carbon atom has one valence remaining to form a bridge (-CHCHCH-).

[0047] The term "alkoxy" as used herein denotes, in each instance, a straight-chain or branched alkyl group bonded via an oxygen atom, typically having 1 to 6 carbon atoms, preferably 1 to 2 carbon atoms, and more preferably 1 carbon atom. Examples of alkoxy groups are methoxy, ethoxy, n-propoxy, isopropoxy, n-butyloxy, 2-butyloxy, isobutyloxy, tert-butyloxy, and the like.

[0048] "(C n ~C m The term "-alkyl")" as used herein, in each instance, refers to a linker moiety in which the moiety attached thereto is attached to a terminal carbon.

[0049] The term "C(=O)" as used herein in each instance denotes a carbonyl moiety.

[0050] "C(=O)-(C n -C m The term "-alkyl")" as used herein in each instance denotes alkylcarbonyl, which refers to a straight-chain or branched alkyl group as defined above, which is attached to the remainder of the molecule via the carbon atom of the carbonyl group C(=O).

[0051] The term "haloalkyl" as used herein denotes in each case a straight-chain or branched alkyl group having typically 1 to 4 carbon atoms, preferably 1 to 3 carbon atoms, and in particular 1 or 2 carbon atoms, in which the hydrogen atoms have been partially or completely replaced by halogen atoms. Preferred haloalkyl moieties are selected from C1-C4-haloalkyl, more preferably C1-C3-haloalkyl or C1-C2-haloalkyl, and in particular C1-C2-fluoroalkyl, such as fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, etc. Trifluoromethyl is particularly preferred according to the invention.

[0052] The term "aryl" or "aromatic carbocycle" preferably includes a six-membered aromatic carbocyclic ring based on carbon atoms as ring members. A preferred example is phenyl. Unless otherwise indicated, the term "aryl" further includes "aromatic bicyclic carbocycle."

[0053] The term "aromatic bicyclic carbocycle" includes bicyclic rings generally 6-14, preferably 7-12, or 8-10, more preferably 9 or 10 membered, containing 6-14, preferably 7-12, or 8-10, more preferably 9 or 10 carbon atoms. In aromatic bicyclic carbocycles, the Hückel (4n+2) rule is satisfied. Preferably, the term "aromatic" in reference to a bicyclic carbocycle means that both rings of the bicyclic moiety are aromatic; thus, for example, in the case of a 10-membered aromatic bicyclic carbocycle, there are 8 pi-electrons. A preferred example is naphthalene.

[0054] The term "saccharide" as used herein refers to a carbohydrate having one or two sugar moieties, also called a monosaccharide or disaccharide in each case. Monosaccharides have the general formula (C HO) n(wherein n is preferably between 3 and 7, particularly between 4 and 6). Examples include glucose, galactose, fructose, and xylose. Disaccharides are represented by the general formula (C HO) n (wherein n is preferably between 3 and 7, particularly between 4 and 6) and is defined as two monosaccharides connected via a glycosidic bond. Examples include sucrose, fructose, lactose, maltose, and trehalose.

[0055] The term "body care product" refers to any product suitable for application to the human body, such as sunscreen compositions, bath and shower products, formulations containing fragrances and odoriferous substances, hair care products, dentifrices, decorative formulations, and cosmetic preparations containing active ingredients. Sunscreen compositions are preferred.

[0056] The terms "sunscreen composition" or "sunscreen agent" or "skin care product" refer to any topical product that reflects and / or absorbs a specific portion of UV radiation. Thus, the term "sunscreen composition" is understood to include not only sunscreen compositions but also any cosmetic composition that provides UV protection. The term "topical product" refers to a product that is applied to the skin, and may refer to, for example, a spray, lotion, cream, oil, foam, powder, or gel. According to the present invention, the sunscreen composition may contain one or more active agents, such as organic UV filters, and other ingredients or additives, such as emulsifiers, emollients, viscosity adjusters, stabilizers, preservatives, or fragrances.

[0057] The term "daily care composition" refers to any topical product that reflects or absorbs a specific portion of UV radiation and is used as a daily care product for the human body, for example, the face, body, or hair. Daily care compositions may contain one or more active agents, such as organic or inorganic UV filters, and other ingredients or additives, such as emulsifiers, emollients, viscosity modifiers, stabilizers, preservatives, or fragrances.

[0058] Suitable bath and shower additives are, for example, shower gels, bath salts, foaming agents, and soaps.

[0059] Suitable compositions containing fragrances and odoriferous substances are especially perfumes, fragrances, eau de toilette, and shaving lotions (aftershave compositions).

[0060] Suitable hair care products are, for example, shampoos for humans and animals (especially dogs), hair conditioners, hair styling and treatment products, perms, hair sprays and lacquers, hair gels, hair fixatives, and hair dyes and bleaches.

[0061] Suitable dentifrices are, for example, tooth creams, toothpastes, mouthwashes, mouth rinses, anti-plaque formulations, and denture cleaners.

[0062] Suitable decorative compositions are, for example, lipsticks, nail varnishes, eye shadows, mascaras, dry and wet make-up products, blushers, powders, depilatories, and suntan lotions.

[0063] Suitable cosmetic formulations containing active ingredients are, for example, hormone formulations, vitamin formulations, plant extract formulations, and antibacterial formulations.

[0064] The body care products mentioned can be in the form of creams, ointments, pastes, foams, gels, lotions, powders, makeup products, sprays, sticks, or aerosols.They preferably contain the compound of formula (I) in an aqueous phase.Therefore, the compound of formula (I) can act as a light stabilizer.

[0065] The term "light stabilizer," as used herein, refers to a compound suitable for protecting body care and household cleaning and treating agents from photodegradation. Light stabilizers are typically present in body care products at concentrations of 50 to 1000 ppm.

[0066] The term "household cleaners and treatments" refers to any product suitable for cleaning or treating household items, such as liquid scouring agents, glass cleaners, neutral cleaners (all-purpose cleaners), acidic household cleaners (bathroom), WC cleaners, preferably laundry detergents, rinse aids and dishwashing agents, clear rinsing agents, dishwasher detergents, shoe polishes, polishing waxes, floor cleaners and polishes, metal, glass and ceramic cleaners, textile care products, agents for removing rust, colours and stains (stain removal salts), furniture and multipurpose polishes and leather finishing agents (leather sprays).

[0067] Preferably, the household cleaner is an aqueous or alcoholic (e.g., ethanol or isopropyl alcohol) solution of one or more of the following components: - anionic, nonionic, amphoteric, and / or cationic surfactants - Soap, prepared by saponification of animal and vegetable fats and oils organic acids, such as hydrochloric, phosphoric or sulfuric acid, - inorganic (NaOH or KOH) or organic bases for basic products; - Abrasives to improve surface cleaning, - waxes and / or silicones for surface maintenance and protection, - polyphosphates, - Hypochlorite or halogen-removing substances; - Peroxides containing bleach activators such as TAED, e.g. sodium perborate or H2O2; - enzymes; - anti-discoloration agents, anti-soiling compounds, gray scale inhibitors, anti-foaming agents, optical brighteners in laundry detergents; - the wax-based cleaner may comprise a solvent selected from benzine, turpentine, and / or paraffin, and a wax-based emulsifier; - fillers, such as silicates, polyphosphates, zeolites for powder detergents; - pigments, lakes, or soluble dyes; - Fragrances; and - Light stabilizers, antioxidants and chelating agents.

[0068] The term "photostability" refers to the ability of a UV filter or any other molecule exposed to sunlight to remain stable upon irradiation. In particular, this means that the compound does not undergo decomposition processes upon UV radiation.

[0069] As used herein, the term "sun protection factor (SPF)" refers to how well the skin is protected by a sunscreen composition. In particular, this index indicates how long the protected skin can be exposed to the sun without sunburn compared to untreated skin. For example, if a sunscreen composition with an SPF of 15 is evenly applied to the skin of a person who normally burns after 10 minutes in the sun, this sunscreen will allow the person skilled in the art to stay in the sun 15 times longer. In other words, SPF 15 means that the sunscreen is applied at a concentration of 2 milligrams per square centimeter (mg / cm 2 ) and applied in a uniform thickness, this means that 1 / 15th of the sun's burning UV radiation reaches the skin.

[0070] The term "critical wavelength" is defined as the wavelength at which the area under the UV protection curve (protection rate (%) vs. wavelength) accounts for 90% of the total area under the curve in the UV range (280-400 nm). For example, a critical wavelength of 370 nm indicates that the protection of a sunscreen composition is not limited to UV-B wavelengths, i.e., wavelengths between 280 and 320 nm, but extends to 370 nm, such that 90% of the total area under the protection curve in the UV range is reached at 370 nm.

[0071] The term "ultraviolet filter" or "UV filter," as used herein, refers to an organic or inorganic compound capable of absorbing and / or reflecting UV radiation caused by sunlight. UV filters can be classified as UV-A, UV-B, or broadband filters based on their UV protection curve. In the context of this application, broadband filters may also be listed as UV-A filters, since they also provide UV-A protection. In other words, preferred UV-A filters also include broadband filters.

[0072] The definition of "broad" protection (also called broad spectrum or broad-spectrum protection) is based on a "critical wavelength." For broad coverage, UV-B and UV-A protection must be provided. According to US requirements, a critical wavelength of at least 370 nm is required to achieve broad-spectrum protection. Furthermore, it is recommended by the European Commission that all sunscreen or cosmetic compositions should have a UVA protection factor of at least one-third of the labeled sun protection factor (SPF); for example, if a sunscreen composition has an SPF of 30, the UVA protection factor must be at least 10.

[0073] Preferred embodiments of the compound of formula (I) according to the present invention and the use of the compound of formula (I) in sunscreen or as a light stabilizer are described below.It is understood that the preferred embodiments of the present invention are preferred either alone or in combination with each other.Furthermore, preferred embodiments of the cosmetic composition comprising the compound of formula (I) according to the present invention and the use of such cosmetic composition in sunscreen are described below.

[0074] As indicated above, the present invention provides, in one embodiment, a compound of formula (I):

[0075] [ka] (In the formula, R Ais H, C1-C6-alkyl, C1-C6-haloalkoxy, C2-C6-alkylene, (OC(=O))-(C1-C4-alkyl), (OC(=O))-aryl, or S-(C1-C4-alkyl); R B is H, halogen, hydroxy, hydroxymethyl, C1-C6-alkyl, C2-C6-alkylene, or C1-C6-alkoxy; R C is H, halogen, hydroxy, hydroxymethyl, C1-C6-alkyl, C2-C6-alkylene, or C1-C6-alkoxy; R D is (CH2O) n -R M , (CH2CH2O) n -R M , or (CH2CH2CH2O) n -R M and; R E is (CH2O) m -R N , (CH2CH2O) m -R N , or (CH2CH2CH2O) m -R N and; R M is H, C1-C4-alkyl, or a saccharide; R N is H, C1-C4-alkyl, or a saccharide; n is an integer from 1 to 50; m is an integer from 1 to 50; k is 0, 1, or 2. or a salt, stereoisomer, or tautomer thereof.

[0076] Preferred embodiments of compounds of formula (I) that are suitable for all aspects of the present invention are defined below.

[0077] In one embodiment of the present invention, the compound of formula (I) is in the form of a cosmetically acceptable salt thereof. In a preferred embodiment of the present invention, the compound of formula (I) is a compound of formula (Ia)

[0078] [ka] (In the formula, X - is a halide, formate, acetate, succinate, oxalate, maleate, fumarate, malate, tartrate, citrate, trifluoroacetate, triflate, tosylate, or mesylate. It is a salt form according to

[0079] In a more preferred embodiment of the present invention, X - is fluoride, chloride, bromide, iodide, formate, acetate, oxalate, tartrate, tosylate, or mesylate. - is chloride, tosylate, or mesylate, especially chloride.

[0080] In another embodiment of the invention, k is 0 or 1, in particular 1.

[0081] In another embodiment of the present invention, R A is H, methyl, ethyl, propyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, (OC(=O))-methyl, (OC(=O)-phenyl, or thiomethyl. In a preferred embodiment of the present invention, R A is H, methyl, ethyl, propyl, isopropyl, isobutyl, or tert-butyl. A is methyl, ethyl or thiomethyl, especially methyl.

[0082] In one embodiment of the present invention, R B and RC In another embodiment of the present invention, R B and R C is different. R B and R C In one embodiment of the present invention, R B is H, halogen, hydroxyl, hydroxymethyl, methyl, or methoxy; R C is H, halogen, hydroxyl, hydroxymethyl, methyl, or methoxy. In a preferred embodiment of the present invention, R B is H, halogen, hydroxyl, or hydroxymethyl, preferably H or halogen, and R C is H, halogen, hydroxyl or hydroxymethyl, preferably H or halogen, in particular R B and R C are both H. In another preferred embodiment of the present invention, R B is H, halogen, C1-C6-alkyl, C2-C6-alkylene, or C1-C6-alkoxy, preferably H, halogen, C1-C3-alkyl, or C2-C3-alkylene, and R C is H, halogen, C1-C6-alkyl, C2-C6-alkylene, or C1-C6-alkoxy, preferably H, halogen, C1-C3-alkyl, or C2-C3-alkylene. B and R C are equal and each selected from the group consisting of H, halogen, C1-C6-alkyl, C2-C6-alkylene, or C1-C6-alkoxy, preferably H, halogen, C1-C3-alkyl, or C2-C3-alkylene.

[0083] In one embodiment of the present invention, R D and R E In another embodiment of the present invention, R D and R E is different.

[0084] In another embodiment of the present invention, R D is (CH2O) n -R Mor (CH2CH2O) n -R M (In the formula, R M is H, methyl, ethyl, or isopropyl, and n is an integer from 1 to 30, preferably from 1 to 25, more preferably from 1 to 20, even more preferably from 1 to 15, and especially from 1 to 10. In a preferred embodiment of the present invention, R D is (CH2CH2O) n -R M (In the formula, R M is H or methyl, and n is an integer of 1 to 10.

[0085] In another embodiment of the present invention, R E is (CH2O) m -R N or (CH2CH2O) m -R N (In the formula, R N is H, methyl, ethyl, or isopropyl, and m is an integer from 1 to 30, preferably from 1 to 25, more preferably from 1 to 20, even more preferably from 1 to 15, and especially from 1 to 10. In a preferred embodiment of the present invention, R E is (CH2CH2O) m -R N (In the formula, R N is H or methyl, and m is an integer of 1 to 10.

[0086] In another embodiment of the present invention, R D is (CH2CH2O) n -R M and R E is (CH2CH2O) m -R N where R M is H and R N is H, n is 1 or 2, and m is 1 or 2.

[0087] In another embodiment of the present invention, the compound according to formula (I) is selected from the group consisting of (E)-2-(2-hydroxyethoxy)-N-(3-((2-(2-hydroxyethoxy)ethyl)amino)-2-methylcyclohex-2-en-1-ylidene)ethane-1-aminium chloride and (E)-2-hydroxy-N-(3-((2-hydroxyethyl)amino)-2-methylcyclohex-2-en-1-ylidene)ethane-1-aminium chloride.

[0088] In another embodiment of the present invention, the compound according to formula (I) is

[0089] [ka] is selected from the group consisting of:

[0090] In another aspect, the present invention relates to a cosmetic composition comprising, in one embodiment, a compound as defined herein (including all embodiments thereof as described herein), and optionally a dermatologically acceptable emulsifier, thickener, or emollient.

[0091] In another embodiment of the present invention, the cosmetic composition further comprises an additional UV filter and / or light stabilizer different from the compound of formula (I). The additional UV filter and / or light stabilizer may be present in the aqueous phase or the oil phase. In a preferred embodiment of the present invention, the additional UV filter is present in the oil phase. In connection with this embodiment, the cosmetic composition provides even more improved protection from UV radiation, because the UV filter is present in both the oil phase and the aqueous phase, thereby providing improved distribution of the UV filter within the cosmetic composition.

[0092] In another embodiment of the present invention, the cosmetic composition further comprises at least two additional UV filters and / or light stabilizers different from the compound of formula (I).

[0093] In another aspect, the present invention relates in one embodiment to the use of a compound as defined herein (including all embodiments thereof as described herein) or a cosmetic composition as defined herein (including all embodiments thereof as described herein) in a sunscreen. In connection with this embodiment, the compound as defined herein is used to protect the skin from UV radiation.

[0094] In another aspect, the present invention relates, in one embodiment, to the use of a compound as defined in the first aspect (including all embodiments thereof as described herein) as a light stabilizer. In particular, the present invention relates to the use of a compound as defined in the first aspect (including all embodiments thereof as described herein) as a light stabilizer in body care products and household cleaning and treatment agents. In connection with this embodiment, the compound as defined herein is used to protect the body care products or household cleaning and treatment agents from UV degradation.

[0095] In another aspect, the present invention relates, in one embodiment, to a compound as defined herein in the first aspect (including all embodiments thereof as described herein) or a cosmetic composition as defined herein (including all embodiments thereof as described herein) for use in a sunscreen. In connection with this embodiment, the compound as defined herein is used to protect the skin from UV radiation.

[0096] In another aspect, the present invention relates to a compound as defined in the first aspect (including all embodiments thereof as described herein) in a body care product for use as a light stabilizer, in one embodiment. In connection with this embodiment, the compound as defined herein is used to protect the body care product from UV degradation.

[0097] In connection with the above embodiment, it will be appreciated that the compounds of formula (I) are particularly suitable for use as UV filters and thereby for protecting the skin from UV radiation.

[0098] In connection with the above embodiment, it is understood that the compound of formula (I) is also suitable for improving the photostability of body care products and household cleaning and treatment agents.In particular, the compound of formula (I) is suitable for improving the photostability of sunscreen compositions.

[0099] Furthermore, in connection with the above embodiments, it is understood that the sunscreen composition may include at least one additive.

[0100] In one embodiment, the at least one additive is selected from the group consisting of emulsifiers, emollients, viscosity modifiers (thickeners), feel modifiers, adjuvants, preservatives, and combinations thereof.

[0101] Preferred emulsifiers include: - glucose derivatives, such as cetearyl glucoside, arachidyl glucoside, lauryl glucoside, polyglyceryl-3 methylglucose distearate, methylglucose sesquistearate; - sucrose derivatives, for example sucrose polystearate, sucrose palmitate; - sorbitol derivatives; - glycerides of fatty acids, for example, glyceryl stearate, glyceryl oleate; - glutamic acid derivatives, such as sodium stearoyl glutamate; sulfosuccinic acid derivatives, such as disodium cetearyl sulfosuccinate; - phosphoric acid derivatives, for example potassium cetyl phosphate; - fatty acid esters of polyglyceryl, for example, polyglyceryl-3-diisostearate, polyglyceryl-2-dipolyhydroxystearate; - Oxyalkenylated organomodified silicone / polysiloxane / polyalkyl / polyether copolymers and derivatives Examples include:

[0102] Preferred softeners include: - esters of linear or branched fatty acids with linear or branched fatty alcohols, such as, for example, propylheptyl caprylate, cococaprylate, isopropyl myristate, ethylhexyl palmitate; Esters of aromatic carboxylic acids with linear or branched fatty alcohols, for example C 12 ~C 15 Alkyl benzoates, ethylhexyl benzoate, phenethyl benzoate; - dicarboxylic acid esters with linear or branched alcohols, such as dibutyl adipate, dicaprylyl carbonate, diisopropyl sebacate; - esters of hydroxycarboxylic acids with linear or branched fatty alcohols; - esters of linear or branched fatty acids with polyhydric alcohols, for example butylene glycol dicaprylate / dicaprate; - C6~C 18 Mono-, di- and triglycerides based on fatty acids, such as caprylic / capric triglyceride, cocoglycerides; Guerbet alcohols, such as octyldodecinol; - hydrocarbons, for example, hydrogenated polyisobutene, mineral oil, squalene, isohexadecane; - esters, such as dicaprylyl ether; Silicone derivatives (organo-modified polysiloxanes), such as dimethylpolysiloxane, cyclic silicones Examples include:

[0103] Preferred thickeners include: - fatty alcohols, such as cetyl alcohol, cetearyl alcohol, stearyl alcohol; - fatty acids, for example, stearic acid; - fatty acid esters, for example, myristyl stearate; - Waxes, such as beeswax, carnauba wax, microcrystalline wax, ceresin, ozokerite; - polysaccharides or derivatives, such as xanthan gum, guar gum, agar gum, alginates, gellan gum, carrageenan; - polyacrylates or homopolymers of network acrylic acid or polyacrylamide, e.g. carbomers, acrylate copolymers, acrylate / C 10 ~C 30 Alkyl acrylate crosspolymer, acrylates / beheneth-25 methacrylate copolymer; - silicate derivatives, for example, magnesium silicate; cellulose derivatives, such as hydroxypropyl cellulose Examples include:

[0104] Preferred feel improvers include: - polyamide derivatives, for example, nylon-12; - Polymethyl methacrylate; - Silica; - Mica; - polymethylsilsesquioxane; - polyethylene; - starch derivatives, such as aluminum starch octenylsuccinate; - Dimethicone derivatives; - boron nitride; - HDI / Trimethylolhexyllactone Crosspolymer Examples include:

[0105] Preferred adjuvants include: - tocopherol derivatives; - Retinol derivatives; - ascorbic acid derivatives; - Bisabolol; - Allantoin; - Pentenol; - Chelating agents (EDTA, EDDS, EGTA, phytic acid, piroctone olamine); - Ethylhexylglycerin; - Caprylyl glycol; - Hydroxyacetophenone; - Caprylhydroxamic acid; - propellants, for example, propane, butane, isobutene, dimethyl ether; - styrene / PVP or styrene acrylamide copolymer; - insect repellent sprays, e.g., butylacetylaminopropionate Examples include:

[0106] Preferred preservatives include: - Phenoxyethanol; - benzyl alcohol; - Methyl, ethyl, propyl, butyl, and isobutylparabens; - Zingerone Examples include:

[0107] Preferred fragrances are limonene, citral, linalool, alpha-isomethyl ionone, geraniol, citronellol, 2-isobutyl-4-hydroxy-4-methyltetrahydropyran, 2-tert-pentylcyclohexyl acetate, 3-methyl-5-phenyl-1-pentanol, 7-acetyl-1,1,3,4,4,6-hexamethyltetralin, adipic acid diester, alpha-amyl cinnamaldehyde, alpha-methyl ionone, amyl C-butylphenyl methylpropional Pional cinnamal, amyl salicylate, amyl cinnamyl alcohol, anise alcohol, benzoin, benzyl alcohol, benzyl benzoate, benzyl cinnamate, benzyl salicylate, bergamot oil, bitter orange oil, butylphenyl methylpropional, cardamom oil, cedrol, cinnamal, cinnamyl alcohol, citronellyl methylcrotonate, lemon oil, coumarin, diethyl succinate, ethyl linalool, eugenol, evernia furfurracea furfuracea extract, hornwort (evernia prunastri) extract, farnesol, hollywood oil, hexyl cinnamal, hexyl salicylate, hydroxycitronellal, lavender oil, lemon oil, linalyl acetate, mandarin oil, menthyl PCA, methylheptenone, nutmeg oil, rosemary oil, sweet orange oil, terpineol, tonkama bean oil, triethyl citrate, vanillin, and combinations thereof.

[0108] In connection with the above preferred embodiments, it is understood that when the sunscreen or daily care composition comprises two or more additives, combinations of additives as defined above are also part of the present invention.

[0109] In relation to the above-mentioned preferred embodiment, it is understood that the body care product may further comprise water.When water is present in the body care product, the body care product can be an oil-in-water emulsion (O / W emulsion) or a water-in-oil emulsion (W / O emulsion).According to a preferred embodiment of the present invention, the cosmetic composition comprising the compound of formula (I) is an O / W emulsion or a W / O emulsion. [Example]

[0110] The present invention is further illustrated by the following examples.

[0111] example

[0112] [Table 1]

[0113] [Example 1] Compound synthesis Reagents and solvents were obtained from commercial sources and used without any further purification. Ion exchange resin Amberlite IRA-402-Cl was used.

[0114] Chemical shifts are reported herein in parts per million (ppm) relative to residual solvent. 1H-NMR data are described as follows: chemical shift (δ, in ppm), multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet), coupling constant (Hz), integral. 13C-NMR data are described in terms of chemical shift (δ, in ppm).

[0115] The following analytical methods were used: NMR spectra were acquired on a Bruker ARX-300 spectrometer (300 MHz and 75 MHz for 1H and 13C, respectively) at a temperature of 298 K unless otherwise specified. ES-MS were obtained on an Ultra Performance Liquid Chromatography Acquity Waters interfaced with High Resolution Mass Spectrometry performed on a Bruker Microtof-Q (electrospray source in positive ion mode).

[0116] Compound A having formula (IIa): (E)-2-(2-hydroxyethoxy)-N-(3-((2-(2-hydroxyethoxy)ethyl)amino)-2-methylcyclohex-2-en-1-ylidene)ethane-1-aminium chloride; molecular formula: C 15 H 29 ClN2O4; molecular weight: 336.86

[0117] [ka]

[0118] To a stirred suspension of 2-methyl-1,3-cyclohexanedione (CAS: 1193-55-1) (1 equivalent) in dry toluene (200 ml), p-toluenesulfonic acid monohydrate (CAS: 6192-52-5) (1 equivalent) and 2-(2-aminoethoxy)ethanol (CAS: 929-06-6) (2.5 equivalents) were added. The mixture was heated to reflux using a Dean-Stark separator for 48 hours to remove the water formed during condensation. The mixture was cooled to room temperature, and excess solvent was removed under reduced pressure to give a yellow oil. This oil was dissolved in water and subjected to 4-5 cycles of treatment with ion-exchange resin Amberlite IRA-402-Cl, filtering the resin after each cycle. After ion-exchange was complete, the water was removed under reduced pressure. None of the recrystallization conditions tried were successful. Thus, compound A is a brown oil with a purity of <90% (as confirmed by NMR) and no total yield is obtained.

[0119] This procedure was scaled up to 25 g of final compound and no operational problems were observed in the preparation. 1 H-NMR (300 MHz, heavy water) δ 3.78 - 3.70 (m, 8H), 3.69 - 3.62 (m, 8H), 2.65 (t, J = 6.4 Hz, 4H), 1.91 (p, J = 6.5 Hz, 2H), 1.77 (s, 3H). 13C-NMR (75 MHz, heavy water) δ 170.15, 97.48, 71.81, 69.12, 60.35, 43.09, 25.10, 18.97, 7.85. ES-MS (+) (C 15 H 29 N2O4 + ): Calculated value 301.2122, measured value 301.2120.

[0120] Compound B having formula (IIb): (E)-2-hydroxy-N-(3-((2-hydroxyethyl)amino)-2-methylcyclohex-2-en-1-ylidene)ethane-1-aminium chloride; molecular formula: C 11 H 21 ClN2O2; molecular weight: 248.75

[0121] [ka]

[0122] To a stirred suspension of 2-methyl-1,3-cyclohexanedione (CAS: 1193-55-1) (1 equivalent) in dry toluene (200 ml) was added p-toluenesulfonic acid monohydrate (CAS: 6192-52-5) (1 equivalent) and 2-aminoethanol (CAS: 141-43-5) (2.5 equivalents). The mixture was heated to reflux using a Dean-Stark separator for 48 hours to remove the water formed during condensation. The mixture was cooled to room temperature, and excess solvent was removed under reduced pressure to give a yellow oil. This oil was dissolved in water and subjected to 4-5 cycles of treatment with ion-exchange resin Amberlite IRA-402-Cl, filtering the resin after each cycle. After ion-exchange was complete, the water was removed under reduced pressure, and the solid was washed 2-3 times with methanol (2 ml) followed by acetone (100 ml) to give a tan solid. Subsequent recrystallization from methanol by adding acetone gave compound B as an off-white solid with a purity of >95% (confirmed by NMR) and an overall yield of approximately 75%.

[0123] This procedure was scaled up to 20 g of final compound without any operational problems being observed. 1 H-NMR (300 MHz, heavy water) δ 3.76 (t, J = 5.4 Hz, 4H), 3.59 (t, J = 5.3 Hz, 4H), 2.65 (t, J = 6.3 Hz, 4H), 1.89 (q, J = 6.3 Hz, 2H), 1.78 (s, 3H). 13 C-NMR (75 MHz, heavy water) δ 170.19, 97.40, 60.30, 45.32, 25.15, 19.03, 7.92. ES-MS (+) (C 11 H 21 N2O2 + ): Calculated value 213.1598, measured value 213.1599.

[0124] Comparative compounds C ((E)-4-methoxy-N-(3-((4-methoxyphenyl)amino)-2-methylcyclopent-2-en-1-ylidene)benzeneaminium 4-methylbenzenesulfonate) and D ((E)-2-bromo-N-(3-((2-bromophenyl)amino)-2-methylcyclopent-2-en-1-ylidene)benzeneaminium 4-methylbenzenesulfonate) are available via the synthetic route published by Losantos et al. in Angew. Chem. 2017, 129, 1-5 and are represented by formula (IIIa) (compound C) and (IIIb) (compound D).

[0125] [ka]

[0126] [Example 2] Solubility Test The solubility of compounds A to D was tested. Here, the addition of compounds A and B to their respective solvents was stopped after 50% m / V. In the case of compounds C and D, precipitates were visible after about 1% m / V. The pH values ​​(see Table 1) of the final solutions or suspensions were measured.

[0127] [Table 2]

[0128] [Example 3] specific damping coefficient The specific extinction coefficients of compounds A to D were measured using a Perkin Elmer Lambda 650 UV / VIS Spectrophotometer.

[0129] Stock solutions of UV absorbers at a concentration of c = 1 mM were prepared in 100 ml volumetric flasks using either buffer or ethanol. A subsequent dilution step was performed to adjust the concentration so that the extinction E was 1.0 ± 0.5 at a path length of d = 1 cm. UV spectra were determined from 250 nm to 500 nm in cuvettes with a path length of d = 1 cm. Using the Beer-Lambert law, the molar decadic extinction coefficient at any wavelength is given by:

[0130]

number

[0131] The respective specific attenuation E%1,1cm can be obtained by the following equation:

[0132]

number

[0133] As can be seen in Figure 1, all the tested compounds absorb within the UV range appropriate for skin protection. Therefore, all the tested compounds are essentially applicable to cosmetic sun care. Compound B has the highest absorbance.

[0134] Disodium hydrogen phosphate / potassium dihydrogen phosphate buffer (order number 1.09439.1000) or ethanol (order number 1.00983.2511), each purchased from Merck, was used.

[0135] [Table 3]

[0136] [Example 4] Formulation of cosmetic compositions Formulations 1-4 and the placebo formulation were manufactured as follows: Parts A and B (see Table 3) were prepared separately and heated to 75-80°C. With increasing stirring, Part B was incorporated into Part A and homogenized with an Ultra Turrax for 20 seconds at 11000 rpm. The mixture was cooled to rt while stirring and Part C was added. The pH was adjusted to 7-8 with NaOH at rt.

[0137] [Table 4]

[0138] Only in formulations 1 and 2 could the UV filters (compounds A and B) be incorporated into the aqueous phase at sufficiently high concentrations. In contrast, the UV filter (compound D) could not be dissolved in the aqueous phase of formulation 4 at a sufficiently high concentration.

Claims

1. Formula (I) 【Chemistry 1】 (In the formula, R A is H, C 1 ~C 6 -Alkyl, C 1 ~C 6 -haloalkyl, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkylene, (OC(=O))-(C 1 ~C 4 -alkyl), (OC(=O))-aryl, or S-(C 1 ~C 4 -alkyl); R B is H, halogen, hydroxy, hydroxymethyl, C 1 ~C 6 -Alkyl, C 2 ~C 6 -Alkylene, or C 1 ~C 6 -alkoxy; R C is H, halogen, hydroxy, hydroxymethyl, C 1 ~C 6 -Alkyl, C 2 ~C 6 -Alkylene, or C 1 ~C 6 -alkoxy; R D is (CH 2 O) n -R M , (CH 2 CH 2 O) n -R M , or (CH 2 CH 2 CH 2 O) n -R M and; R E is (CH 2 O) m -R N , (CH 2 CH 2 O) m -R N , or (CH 2 CH 2 CH 2 O) m -R N and; R M is H, C 1 ~C 4 - alkyl or saccharide; R N is H, C 1 ~C 4 - alkyl or saccharide; n is an integer from 1 to 50; m is an integer from 1 to 50; k is 0, 1, or 2. or a salt, stereoisomer, or tautomer thereof.

2. Formula (Ia) 【Chemistry 2】 (In the formula, X - is a halide, formate, acetate, succinate, oxalate, maleate, fumarate, malate, tartrate, citrate, trifluoroacetate, triflate, tosylate, or mesylate.

2. The compound of claim 1 in the form of a salt according to

3. 3. The compound of claim 1 or 2, wherein k is 1.

4. R A 4. The compound according to any one of claims 1 to 3, wherein is methyl, ethyl or thiomethyl, preferably methyl.

5. R D However, (CH 2 CH 2 O) n -R M and; R M is H or methyl; n is an integer from 1 to 10; 5. A compound according to any one of claims 1 to 4.

6. R E However, (CH 2 CH 2 O) m -R N and; R N is H or methyl; m is an integer from 1 to 10; 6. A compound according to any one of claims 1 to 5.

7. R D However, (CH 2 CH 2 O) n -R M and; R E However, (CH 2 CH 2 O) m -R N and; R M But H; R N But H; n is 1 or 2; m is 1 or 2; 7. A compound according to any one of claims 1 to 6.

8. R B and R C is equal to, preferably H; 8. A compound according to any one of claims 1 to 7.

9. X - is chloride, tosylate, or mesylate; 9. A compound according to any one of claims 2 to 8.

10. the compound according to formula (I) is selected from the group consisting of (E)-2-(2-hydroxyethoxy)-N-(3-((2-(2-hydroxyethoxy)ethyl)amino)-2-methylcyclohex-2-en-1-ylidene)ethane-1-aminium chloride, and (E)-2-hydroxy-N-(3-((2-hydroxyethyl)amino)-2-methylcyclohex-2-en-1-ylidene)ethane-1-aminium chloride; 2. The compound of claim 1.

11. The compound according to formula (I) 【Transformation 3】 2. The compound of claim 1, selected from the group consisting of:

12. 12. A cosmetic composition comprising a compound according to any one of claims 1 to 11 and optionally a dermatologically acceptable emulsifier, thickener, or emollient.

13. 13. A compound according to any one of claims 1 to 11 or a cosmetic composition according to claim 12 for use as a sunscreen.

14. 12. A compound according to any one of claims 1 to 11 for use as a light stabilizer in a body care product.

15. 12. Use of a compound according to any one of claims 1 to 11 as a light stabilizer in household cleaning and treating agents.

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