DE3931269A1 - NEW BENZYLIDENCYCLANONE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, THEIR USE AS ANTIOXIDANT AND AS SUNFILTER, AND COSMETIC AND PHARMACEUTICAL AGENTS CONTAINING SUCH DERIVATIVES - Google Patents

Abstract

Benzylidenecyclanone compounds of formula: <IMAGE> [in which: R1 and R are independently hydrogen, hydroxyl, C1-C8 alkyl or C1-C8 alkoxy (with the reservation that at least one of the radicals R1 and R is other than hydrogen); R2 and R3 are independently hydrogen or hydroxyl (with the reservation that at least one of the radicals R2 and R3 is hydroxyl); R4, R5, R6 and R7 are independently C1-C18 alkyl, aralkyl (optionally substituted by C1-C4 alkyl or C1-C4 alkoxy), aryl (optionally substituted by C1-C4 alkyl); or the substituents R4 and R5 and/or the substituents R6 and R7 form, together with the carbon atom of the ring to which they are attached, a saturated ring containing from 5 to 12 carbon atoms which is optionally substituted by one or more C1-C8 alkyl(s); and X is CH2, (CH2)2 or N-R8 (in which R8 is hydrogen, C1-C8 alkyl, aralkyl (optionally substituted by C1-C4 alkyl or C1-C4 alkoxy), hydroxyl or C1-C8 alkoxy) or alternatively X is oxygen or sulphur] have anti-oxidant and wide-band sunscreening properties and are useful constituents of cosmetic preparations. Such compounds are also pharmaceutically useful in the treatment of inflammations and allergies of the skin and in the prevention of certain cancers.

Description

The present invention relates to novel benzylidene cyclanone Derivatives, the process for their preparation and their use as antioxidants as well as their use in cosmetic products of daily use or in sunscreens and pharmaceuticals for the treatment of inflammation and allergies of the skin or certain carcinoma types.

It is known that the skin on sun rays, which a simple sunburn or an erythema, as well cause more or less pronounced burns can, be sensitive.

Sunbeams also have other negative effects; thus they lead to a loss of elasticity of the Skin or cause wrinkles and thus cause premature Aging of the skin. At times, dermatoses can also be determine. In extreme cases occur in certain people Skin carcinomas on.

It is also desirable to protect the hair from a photochemical Protect damage to change the Color shades, discoloration or damage to the mechanical To avoid hair characteristics.

It is known, by the way, that in cosmetic preparations  components are not always sufficiently light stable are and are under the influence of light rays decompose.

It is known that ultraviolet rays with wavelengths of less than 400 nm the most dangerous part of the sun's rays represent. It is further known that due to the Presence of the ozone layer of the earth's atmosphere, which absorbs part of the sun's rays, the lower limit the ultraviolet rays that hit the earth's surface impinge, is at about 280 nm.

It thus appears desirable to use compounds which are the ultraviolet rays in a wavelength range of 280 to 400 nm can provide, d. H. So UV-B rays with a wavelength between 280 and 320 nm, which play a crucial role in the formation of sun erythema, as well as UVA rays a wavelength between 320 and 400 nm, which is the browning cause the skin, but they also age and the Triggering an erythematous reaction or reinforce this reaction in certain people or the even cause phototoxic or photoallergic reaction can.

In the course of her investigations, the applicant has new ones Benzylidene cyclanone derivatives of the formula

found in which
R₁ and R are the same or different and are a hydrogen atom, a hydroxyl radical, a straight or branched C₁-C₈ alkyl radical or a straight or branched C₁-C₈ alkoxy radical, wherein at least one of the two radicals R₁ and R is not a hydrogen atom .
R₂ and R₃ are the same or different and represent a hydrogen atom or a hydroxyl radical, at least one of the radicals R₂ and R₃ being a hydroxyl radical,
R₄, R₅, R₆ and R₇ are the same or different and are a straight or branched C₁-C₈ alkyl radical, an aralkyl radical, such as a benzyl radical which is unsubstituted or substituted by a C₁-C₄ alkyl radical or a C₁-C₄ alkoxy radical, or a Aryl radical, such as an unsubstituted or substituted with a C₁-C₄ alkyl radical phenyl, wherein the substituents R₄ and R₅ and / or the substituents R₆ and R₇ together with the carbon atom of the ring to which they are attached, having a saturated ring 5 to 12 carbon atoms, which may be unsubstituted or substituted by one or more straight or branched C₁-C₈-alkyl radicals,
X either for one

with n = 1 or 2 or an N-R₈ radical in which R₈ is a hydrogen atom, a straight or branched C₁-C₈-alkyl radical, an aralkyl radical, such as an unsubstituted or with a C₁-C₄-alkyl radical or a C₁- C₄-alkoxy substituted benzyl radical, a hydroxyl radical or an -O-R₉ radical, wherein R₉ represents a straight or branched C₁-C₈-alkyl radical, or X represents an oxygen atom or a sulfur atom.

Besides its good properties as a filter in a wavelength range from 280 to 380 nm show the above-mentioned Compounds surprisingly excellent properties as an antioxidant towards peroxidation polyunsaturated lipids as well as to substances, the thermo or photoinduced oxidation reactions (such as proteins, polymers).

It is also known that the peroxidation of lipids the Formation of intermediary, causing free radicals, which the cell membrane, the u. a. consist of phospholipids, damage and especially for the phenomenon of aging the skin are responsible (A. L. Tappel, Federation Proceedings, vol. 32, no. 8, August 1973).

It is especially important to have connections available provide the same properties as a filter for a large wavelength range as well as features Having antioxidant, whereby the filter effect is being potentiated. Such compounds make it possible For example, premature aging of the skin due to the To better combat peroxidation of skin lipids.

Such compounds also allow better Preservation of cosmetic products with a fatty phase, by the rancidity of the contained therein prevent unsaturated lipids. These can be more animal Origin, such as lanolin, cetin (whale fat), beeswax, Perhydrosqual and turtle oil, or they may be more herbal Origin, such as olive oil, castor oil, corn oil, Sweet Almond Oil, Avocado Oil, Karit'öl, Sunflower Oil, Soybean Oil, Peanut oil, coconut oil or hydrogenated palm kernel oil, essential fatty acids, such as vitamin F and certain essential oils that are contained in perfumes, like  Citron oil or lavender oil.

The Applicant has surprisingly found that the above-mentioned compounds of formula (I) in the Treatment of inflammation and allergies of the skin and used in the prevention of certain carcinomas can.

Besides its good properties as a filter and as an anti Oxidizing agents prove the compounds of the invention also as very good fat soluble and stand out furthermore by a good thermal and photochemical Stability out.

These compounds also have the advantage of being non-toxic or to be irritating and perfect over the skin harmless.

They are uniformly distributed in the classical cosmetic Straps, form a continuous film in particular in fat carriers and can be applied to the skin on which they form an effective protective film.

The present invention relates to the compounds the formula (I) shown above.

In this formula, R₁ and R, for example, for a Methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, tert-butyl or 1,1,3,3-tetramethylbutyl or a Methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, Heptyloxy or Octyloxyrest stand.

R₄, R₅, R₆, R₇, R₈ and R₉ may be alkyl radicals which are selected from the above-mentioned radicals for R₁ and R; when R₄ and R₅ or R₆ and R₇ with the carbon atom, to which they are bound form a ring, this one points preferably 6 carbon atoms.  

The preferred compounds of general formula (I) counting:

• 3'-5'-di-tert-butyl-4'-hydroxy-4-benzylidene tetrahydrofuran 2,2,5,5-tetramethyl-furan-3-one,
• - 3 ', 5'-di-tert-butyl-2'-hydroxy-4-benzylidene-tetrahydro- 2,2,5,5-tetramethyl-furan-3-one,
• - 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene-tetrahydro- 2,2,5,5-tetramethyl-furan-3-one,
• - 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene-tetrahydro- 2,2,5,5-bis (pentamethylene) -furan-3-one,
• - 3 ', 5'-dimethyl-4'-hydroxy-4-benzylidene-tetrahydro- 2,2,5,5-tetramethyl-furan-3-one,
• - 3 ', 5'-dimethoxy-4'-hydroxy-4-benzylidene-tetrahydro- 2,2,5,5-tetramethyl-furan-3-one,
• - 3'-tert-butyl-2'-hydroxy-5'-methoxy-4-benzylidene-tetra hydro-2,2,5,5-tetramethyl-furan-3-one,
• - 3'-tert-butyl-2'-hydroxy-5'-methyl-4-benzylidene-tetra hydro-2,2,5,5-tetramethyl-furan-3-one,
• - 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene-tetrahydro- 2,5-dimethyl-2,5-di-tert-butyl-furan-3-one,
• - 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene-tetrahydro- 2,5-diethyl-2,5-dimethyl-furan-one;
• - 3 ', 5'-diisopropyl-4'-hydroxy-4-benzylidene-tetrahydro- 2,2,5,5-tetramethyl-furan-3-one,
• - 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene-2,2,5,5-  tetramethyl-aza-cyclopentane-3-one,
• - 3 ', 5'-di-tert-butyl-4'-hydroxy-2-benzylidene-3,3,5,5- tetramethyl-cyclopentane-1-one,
• - 3 ', 4', 5'-trihydroxy-4-benzylidene-2,2,5,5-tetrahydro- tetramethyl-furan-3-one,
• - 3'-tert-butyl-4'-hydroxy-4-benzylidene-tetrahydro- 2,2,5,5-tetramethyl-furan-3-one.

The compounds of the formula (I) are obtained by condensation an aromatic aldehyde of the formula:

with a cyclanone of the formula:

In the compounds of formula (II) and (III) possess R, R₁, R₂, R₃, R₄, R₅, R₆, R₇ and X are as defined above. The condensation is carried out with an aldehyde, desse OH function is either freely available or by a trialkylsilyl radical (C₁-C₆-alkyl) or a benzyl radical is protected.  

If one uses an aldehyde, its OH function by a trialkylsilyl is protected, it follows the condensation reaction the removal of the trialkyl silyloxyrestes to obtain the OH function in free form. This reaction is for example in acetonitrile in the presence of tetrabutylammonium fluoride.

If one uses an aldehyde, its OH function by a benzyl radical is protected, then joins the Condensation reaction a reductive removal of the Benzyloxyrestes by transfer of hydrogen, for example with the aid of formic acids or cyclohexene as a hydrogen donor in the presence of a catalyst, like palladium on carbon, in a solvent on, with the reaction temperature between 0 ° C and the boiling point of the reaction mixture.

The aldehydes of the formula (II) are prepared by known processes manufactured.

The cyclanones of the formula (III) can be described as follows by C. Sandris and G. Ourisson in Bull. Soc. Chim. Fr (1956), p. 958 or the description of Ik. Korobitsyna in Zhur. Obschei. Khim., Vol. 25, pp. 734-738 and Vol. 27, p. 172-95.

The condensation of the aldehyde (II) with a cyclanone (III) can be carried out according to one of the following two methods become:

1. A method

The condensation takes place in the presence of an alkali metal alcoholate, such as sodium methylate or potassium tert.- butoxide, in a solvent such as toluene or 1,2-di methoxyethane, at a temperature between -78 ° C and the boiling point of the solvent.  

The condensation can also be in the presence of a mineral Base, such as an alkali metal amide or an alkali metal hydride, in a solvent such as 1,2-dimethoxyethane, or an alkali metal hydroxide in an alcohol, at a temperature between room temperature and boiling temperature of the reaction mixture.

2. process

The condensation of the aldehyde (II) with a cyclanone (III) may in the presence of a borane of the following formula (IV):

wherein
R₁₀ is a C₁-C₆ alkyl radical and R₁₁ is a C₁-C₄ alkyl radical. These compounds are obtained according to the method described by LH Toporcer et. al. in J. Am. Chem. Soc. 87, 1965, p 1236. Isolation and purification of the compound are not required to effect the condensation of the aldehyde (II) with the cyclanone (III).

The condensation reaction is carried out at a temperature of about 150 ° C carried out without solvent.

The present invention also provides the process for the preparation of the novel compounds of formula (I).

The invention further relates to a cosmetic Agent that is in a cosmetically acceptable carrier, which contains at least one fatty phase, an effective  Amount of at least one Benzylidencyclanon derivative of Formula (I) mentioned above.

The cosmetic agent of the invention can be used as an agent for Protection of the human epidermis or the hair or as Sunscreens are used.

The subject of the present invention is also a method to protect the skin or the natural or sensitized hair to solar radiation. you Has an effective amount on the skin or hair at least one compound of formula (I) which is in a cosmetically acceptable carrier which is at least contains a fatty phase.

By "sensitized hair" is meant hair that a permanent wave treatment, a dyeing or decolorization process have been subjected.

The present invention is also a colored or undyed cosmetic agent which and / or oxidation stabilized and an effective Amount of at least one Benzylidencyclanon derivative of Formula (I) shown above.

If the cosmetic agent according to the invention is used as an agent for Protection of human epidermis from ultraviolet rays it can be used in a variety of ways, for this one Medium type usual forms exist. It can be as oily or oily-alcoholic lotion, as an emulsion, such as Cream or milk, as oily-alcoholic, alcoholic or aqueous-alcoholic gel or as a solid stick or may be condensed as an aerosol.

The agent may contain cosmetic adjuvants which Usually used in this type of medium, like Thickening agents, softening agents, humectants,  surfactants, preservatives, Antifoam agents, perfumes, oils, waxes, lanolin, propellants, Dyes and / or pigments containing the agent itself or the skin or other in cosmetics commonly color used ingredients.

The compound of the formula (I) is present in an amount between 0.1 and 2 wt .-%, based on the total weight of the cosmetic Agent for the protection of human skin, included.

As Solubilisierungslösungsmittel can be an oil, a Wax and generally all fat bodies, a monoalcohol or a lower polyol and mixtures thereof use. The most preferred monoalcohols and Polyols include ethanol, i-propanol, propylene glycol, glycerin and sorbitol.

One embodiment of the invention is an emulsion in Form of a protective cream or milk, other than the compound of the formula (I) fatty alcohols, fatty acid esters and especially fatty acid triglycerides, fatty acids, lanolin, natural or synthetic oils or waxes and emulsifiers in the presence of water.

Another embodiment is oily lotions the base of natural or synthetic oils and Grow, lanolin, fatty acid esters, especially fat acid triglycerides, or oily-alcoholic lotions the base of a low alcohol, such as ethanol, or a glycol, such as propylene glycol, and / or a polyol, such as glycerin, and oils, waxes and fatty acid esters, such as Fatty acid triglycerides.

The cosmetic agent according to the invention can also be used as alcoholic gel present, one or more Alcohols or lower polyols, such as ethanol, propylene glycol  or glycerol, and a thickener, such as Silica, covered. The oily-alcoholic gels contain also a natural or synthetic Oil or wax.

The solid sticks contain natural or synthetic Waxes and oils, fatty acids, fatty acid esters, lanolin and other fat bodies.

The present invention also relates to cosmetic Sunscreens containing at least one compound of Formula (I) and the other UV-B and / or UV-A May contain filters.

The amount of the filter of formula (I) is between 0.2 and 15% by weight; the total weight of the sunscreen existing filter, d. H. the compound of formula (I) and possibly other filters, lies between 0.5 and 15 wt .-%, based on the total weight of the sunscreen.

If the agent is conditioned as an aerosol, it is used you classic propellants, such as alkanes, fluoroalkanes and chlorofluoroalkanes.

If the cosmetic composition according to the invention natural or protect sensitized hair from UV rays, so may use the remedy as a shampoo, lotion, gel or emulsion for rinsing, before the after shampooing, before or after dyeing or decolouring, before or applied after the perm; It can also be considered Lotion or gel for hairdressing or treatment, as a lotion or gel for brushing or laying a water wave, as Hair lacquer or as a means of perming, dyeing or Discolouring of the hair is present. This remedy can except the compound according to the invention, in this type of medium used adjuvants, such as surface-active  Agents, thickeners, polymers, softeners, Preservatives, foam stabilizers, electrolytes, organic solvents, silicone derivatives, oils, Waxes, anti-grease agents, dyes and / or pigments, the agent itself or the hair or other, in the Hair cosmetics usually dye used ingredients should. The agent contains 0.25 to 2% by weight of the compound of the formula (I).

The present invention also provides cosmetic compositions which comprises at least one compound of the formula (I) as a means of protection against UV rays and as Contain antioxidant; this is Means for hair such as hair lacquers, lotions for laying one Water wave, if necessary, to treat the hair or to make untangling, shampoos, color shampoos or means to Haircolor; they are also agents, such as make-up products, Nail polishes, creams and oils for the treatment of Epidermis, make-ups (funds de Teint), lipsticks and Skin care products, bath oils and creams, and others cosmetic products that are in their constituents Problems of light and / or oxidation stability during can cause storage. Contain such Mitel 0.1 to 2 wt .-% of the compound of formula (I).

The invention also provides a method for Protection of cosmetic products from UV rays and before Oxidation, which means an effective amount of at least a compound of the formula (I) is incorporated.

Another object of the invention is the use the compounds of formula (I) as antioxidant.

Another object of the invention is the use of the Compounds of formula (I) as a sun filter with a Absorbance in a wavelength range of 280  up to 380 nm.

The invention also relates to the application of Compounds of the formula (I) in the form of the cosmetic Products.

As indicated above, the Applicant also has during their investigations found that the compounds of the formula (I) an important pharmacological Activity in the treatment of inflammation and allergies show the skin and they also help to prevent certain Carcinomas can be used.

The subject of the present invention is therefore also the Use of the compounds of the formula (I) as medicaments.

The invention also relates to a pharmaceutical Agent comprising an effective amount of at least one compound of the formula (I) as an active ingredient in a contains non-toxic carriers or excipients.

The pharmaceutical agent of the invention may be administered orally or administered topically.

If it is administered orally, so is the pharmaceutical Agents in the form of tablets, gelatine capsules, dragees, as syrup, suspension, solution, emulsion, etc. Becomes administered topically, it is as an ointment, crème, Pomade, solution, lotion, gel, spray, suspension etc. before.

These medicines may be inert or pharmacological active additives and especially hydrating agents, Antibiotics, steroids or non-steroidal anti-inflammatory Agents, carotenoids and antipsoriasis agents contain.

These funds can also be means of improving the  Flavorings, preservatives, stabilizers, Means for regulating moisture, regulating means pH, means of modifying the osmotic Pressure, emulsifiers, local anesthetics, Buffers etc. included.

They may also be in sustained release form or the active ingredient gradually release.

The compound of the formula (I) according to the invention is disclosed in U.S. Pat pharmaceutical agents in an amount between 0.01 and 80% by weight, preferably between 0.1 and 20% by weight, based on the total weight of the agent, present.

In the therapeutic application, the treatment of depending on age, weight and the patient 's response, as well as the severity of the disease Symptoms are varied.

If the compounds of the formula (I) are administered orally, so the dose is generally between 0.1 and 50 mg / kg / day, preferably between 0.2 and 20 mg / kg / day. The duration of treatment varies according to the severity of the disease Symptoms and may range from 1 to 25 weeks, taking the treatment is continuous or discontinuous can be done.

The means for topical administration preferably contain 0.25 to 4 wt .-% of the compound of formula (I).

As a carrier of the excipients of the invention pharmaceutical agent can be any conventional, use non-toxic carriers or excipients.

The following examples are intended to illustrate the present invention explain.

Preparation Examples Example 1 Preparation of 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene tetrahydro-2,2,5,5-tetramethyl-furan-3-ones of formula

It is added to 100 cc of 1 M triethylborane solution in hexane at 0 ° C 8.2 g (0.08 M) of pivalic acid. It is stirred for 15 minutes and then let the mixture come to room temperature; Subsequently, 5.4 g (0.038 M) of tetrahydrofuran are added. 2,2,5,5-tetramethyl-furan-3-one and 8.9 g (0.038 M) 3,5-di-tert-butyl-4-hydroxybenzaldehyde. The hexane is distilled and heated for 3 hours 150 ° C. Then distilled the volatiles under reduced pressure (2000 Pa, then 13 Pa). The oily residue is made up of an ethanol-water mixture recrystallized to give 5.5 g of the desired Product in the form of pale yellow crystals, the show the following features:

Melting point: 146 ° C

Analysis for C₂₃H₃₄O₃:
calc .:
C 77.05, H 9.56, O 13.39%,
Found .:
C 76.65, H 9.56, O 13.78%

UV spectrum (dichloromethane):
λ _max = 335 nm
ε = 18170

example 2 Preparation of 3 ', 5'-di-tert-butyl-2'-hydroxy-4-benzylidene tetrahydro-2,2,5,5-tetramethyl-furan-3-ones of formula

To a solution of 1.3 g of tetrahydro-2,2,5,5-tetramethyl- Furan-3-one in 50 cc of 1,2-dimethoxyethane is added 1 g Potassium t-butoxide. The mixture is heated for 15 minutes under reflux and then cooled to room temperature. Then 2 g of 3,5-di-tert-butyl-2-hydroxy benzaldehyde too. After stirring for 24 hours at room temperature Dilute the reaction mixture with water. You extract with ethyl acetate, the organic phase is dried over Sodium sulfate and distilling the solvent under reduced pressure Print. The residue is placed on silica gel Using a mixture of heptane and ethyl acetate chromatographed with 96% heptane as eluent. The The product you receive shows the following features:

Melting point: 166 ° C

Analysis for C₂₃H₃₄O₃:
calc .:
C 77.05, H 9.56, O 13.39%,
Found .:
C 76.95, H 9.56, O 13.55%

UV spectrum (CH₂Cl₂):
λ _max ₁: 305 nm
ε ₁: 5890
e ₂: 3430

example 3 Preparation of 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene tetrahydro-2,2,5,5-tetrahydrofuran-3-ones of formula

This compound is obtained according to the procedure described in Example 1 Process in which tetrahydro-2,2,5,5- tetramethyl-furan-3-one by tetrahydro-2,2,5,5-tetraethyl- furan-3-one is replaced. The product obtained shows following features:

Melting point: 124 ° C

Analysis for C₂₇H₄₂O₃:
calc .:
C, 78.21, H, 10, 21, O, 11.58%,
Found .:
C 78.29, H 10.18, O 11.81%

UV spectrum (CH₂Cl₂):
λ _max : 338 nm
ε : 22,800

example 4 Preparation of 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene tetrahydro-2,2,5,5-bis (pentamethylene) -furan-3-one the formula

This compound is obtained according to the procedure described in Example 1 Process in which tetrahydro-2,2,5,5- tetramethyl-furan-3-one by tetrahydro-2,2,5,5-bis (pentamethylene) furan-3-one is replaced. The product obtained shows the following features:

Melting point: 162-164 ° C

Analysis for C₂₉H₄₂O₃:
calc .:
C, 79.41, H, 9.65, O, 10.94%,
Found .:
C 79.16, H 9.62, O 11.21%

UV spectrum (CH₂Cl₂):
λ _max : 338 nm
ε : 23,200

example 5 Preparation of 3 ', 5'-dimethyl-4'-hydroxy-4-benzylidene tetrahydro-2,2,5,5-tetramethyl-furan-3-one of the formula

To a solution of 7.1 g (0.05 M) tetrahydro-2,2,5,5- tetramethyl-furan-3-one in 30 cc of 1,2-dimethoxyethane 5.4 g (0.1 M) of sodium methylate. Cool the mixture to about 5 ° C and then with stirring 3.8 g (0.025 M) 3,5-dimethyl-4-hydroxy-benzaldehyde, in 20 cc of 1,2- Dimethoxyethane dissolved, too. The reaction mixture is stirred 30 minutes at room temperature and then heated  another 30 minutes under reflux. After one night at Room temperature drops the product by adding dilute hydrochloric acid, filtered it, washed with it Water and it dries. After cleaning by washing with Dichloromethane gives 1.6 g of the desired product in the form of pale yellow crystals, the following characteristics demonstrate:

Melting point: 154-158 ° C

Analysis for C₁₇H₂₂O₃:
calc .:
C 74.42, H 8.08, O 17.49%,
Found .:
C 74.23, H 8.10, O 17.53%

UV spectrum (CH₂Cl₂):
λ _max : 330 nm
ε : 20,500

example 6 Preparation of 3 ', 5'-dimethoxy-4'-hydroxy-4-benzylidene tetrahydro-2,2,5,5-tetramethyl-furan-ons of the formula

This compound is obtained according to the procedure described in Example 2 Method in which 3,5-di-tert-butyl 2-hydroxybenzaldehyde by 4-tert-butyldimethylsilyloxy 3,5-dimethoxybenzaldehyde is replaced. The protective group of tert-butyldimethylsilyl is replaced by a 10-minute Treatment at room temperature with a solution of tetra butylammonium fluoride in acetonitrile. After dilution  of the reaction mixture with water, extraction with i-propyl ether and recrystallization from a heptane / acetone Mixture gives the desired product, the following Indicator shows:

Melting point: 148 ° C

Analysis for C₁₇H₂₂O₅:
calc .:
C 66.65, H 7,24, O 26,11%,
Found .:
C 66.56, H 7.24, O 26.32%

UV spectrum (CH₂Cl₂):
λ _max : 363 nm
ε : 16 300

example 7 Preparation of 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene tetrahydro-2,5-dimethyl-2,5-di-tert-butyl-furan-3- ons of the formula

This compound is obtained according to the procedure described in Example 1 Process in which tetrahydro-2,2,5,5- tetramethyl-furan-3-one by tetrahydro-2,5-dimethyl 2,5-di-tert-butyl-furan-3-one is replaced. The obtained Product shows the following features:

Melting point: 180 ° C  

Analysis for C₂₉H₄₆O₃:
calc .:
C, 78.68, H, 10.47, O, 10.84%,
Found .:
C 78.71, H 10.57, O 18.75%

UV spectrum (CH₂Cl₂):
λ _max : 338 nm
ε : 15,700

example 8 Preparation of 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene tetrahydro-2,5-diethyl-2,5-dimethyl-furan-3-ones of formula

This compound is obtained according to the procedure described in Example 1 Process in which tetrahydro-2,2,5,5- tetramethyl-furan-3-one by tetrahydro-2,5-diethyl-2,5- dimethyl-furan-3-one is replaced. The product obtained shows the following features:

Melting point: 112 ° C

Analysis for C₂₅H₃₈O₃:
calc .:
C, 77.68, H, 9.91, O, 12.42%,
Found .:
C 77.79, H 9.88, O 12.52%

UV spectrum (CH₂Cl₂):
λ _max : 338 nm
ε : 22,300

example 9 Preparation of 3 ', 5'-diisopropyl-4'-hydroxy-4-benzylidene tetrahydro-2,2,5,5-tetramethyl-furan-3-ones of formula

This compound is obtained according to that described in Example 5 Process in which 3,5-dimethyl-4-hydroxy benzaldehyde by 3,5-diisopropyl-4-hydroxybenzaldehyde is replaced. The product obtained shows the following features:

Melting point: 142 ° C

Analysis for C₂₁H₃₀O₃:
calc .:
C 76.33, H 9.15, O 14.52%,
Found .:
C 76.57, H 9.23, O 14.68%

UV spectrum (CH₂Cl₂):
λ _max : 326 nm
ε : 22 400

example 10 Preparation of 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene 2,2,5,5-tetramethyl-aza-cyclopentan-3-ones of formula

This compound is obtained according to the procedure described in Example 1 Process in which tetrahydro-2,2,5,5- tetramethyl-furan-3-one by 2,2,5,5-tetramethyl-aza- cyclopentan-3-one is replaced. The product obtained shows following features:

Melting point: 146 ° C

Analysis for C₂₃H₃₅O₂:
calc .:
C 77.27, H 9.87, N 3.92, O 8.95%,
Found .:
C 77.36, H 9.82, N 3.85, O 9.08%

UV spectrum (CH₂Cl₂):
λ _max : 334 nm
ε : 21,400

example 11 Preparation of 3 ', 5'-di-tert-butyl-4'-hydroxy-2-benzylidene 3,3,5,5-tetramethyl-cyclopentan-1-one of the formula

This compound is obtained according to the procedure described in Example 1 Process in which tetrahydro-2,2,5,5- tetramethyl-furan-3-one by 3,3,5,5-tetramethyl-cyclopentane 1-on is replaced. The product obtained shows the following indicators:

Melting point: 166 ° C  

Analysis for C₂₄H₃₆O₂:
calc .:
C 80.85, H 10.18, O 8.97%,
Found .:
C 80.92, H 10.21, O 9.09%

UV spectrum (CH₂Cl₂):
λ _max : 330 nm
ε : 19,500

example 12 Preparation of the 3 ', 4', 5'-trihydroxy-4-benzylidene-tetrahydro- 2,2,5,5-tetramethyl-furan-3-ones of the formula a) Preparation of the 3 ', 4', 5'-Tribenzyloxy-4-benzylidene tetrahydro-2,2,5,5-tetramethyl-furan-3-one

Heat for 14 minutes under reflux 14.2 g (0.1 M) Tetrahydro-2,2,5,5-tetramethyl-furan-3-one and 5.4 g (0.1 M) sodium methylate in 30 cc of 1,2-dimethoxyethane. Add a hot solution of 39.8 g (0.094 M) of 3,4,5- Tribenzyloxybenzaldehyde in 100 cc of 1,2-dimethoxyethane to. The mixture is allowed to reach room temperature for 30 minutes and then pour it into an aqueous acidified with hydrochloric acid Sodium chloride solution. Dichloromethane is extracted. The solvent is distilled under reduced pressure Pressure and crystallize the residue in one small amount of heptane around. 65% of the desired product are obtained in the form of white  Crystals.

b) Preparation of 3 ', 4', 5'-trihydroxy-4-benzylidene tetrahydro-2,2,5,5-tetramethyl-furan-3-one

11 g (0.02 M) of the 3 ', 4', 5 'obtained above are stirred. Tribenzyloxy-4-benzylidene-tetrahydro-2,2,5,5-tetramethyl- furan-3-ones and 5 g palladium on carbon, which is 50% Contains water (5% by weight of palladium in relation to the coal), in a mixture of 100 ml of ethanol and 30 ml of formic acid under an argon atmosphere for 2 hours 30 minutes Room temperature and then the mixture in 1 hour a boiling water bath. It is then allowed to cool Dilute with 20 cc of water and filter over celite. The celite cake is mixed with dichloromethane and then with water washed. The organic phase is washed with water and then evaporated to dryness. The residue will be recrystallized from diisopropyl ether. 45% of the desired product is obtained in the form of yellow crystals; it shows the following features:

Melting point: 156 ° C

Analysis for C₁₅H₁₈O₅, 1 H₂O:
calc .:
C 60.81, H 6.75, O 32.43%,
Found .:
C 60.77, H 6.95, O 32.05%

UV spectrum (CH₂Cl₂):
λ _max : 343 nm
ε : 11,780

example 13 Preparation of 3'-tert-butyl-4'-hydroxy-4-benzylidene tetrahydro-2,2,5,5-tetramethyl-furan-ons of the formula a) Preparation of 4'-benzyloxy-3'-tert-butylbenzylidene tetrahydro-2,2,5,5-tetramethyl-furan-3-one

This compound is obtained according to the procedure described in Example 12 a) 3,4,5-tribenzyloxy- benzaldehyde by 4-benzyloxy-3-tert-butylbenzaldehyde is replaced.

b) Preparation of the 3'-tert-butyl-4'-hydroxybenzylidene tetrahydro-2,2,5,5-tetramethyl-furan-3-one

This compound is obtained according to the procedure described in Example 12 b). described method in which 3 ', 4', 5'-Tribenzyloxy- 4-benzylidene-tetrahydro-2,2,5,5-tetramethyl- furan-3-one by 4'-benzyloxy-3'-tert-butyl-4-benzylidene tetrahydro-2,2,5,5-tetramethyl-furan-on replaced becomes. The product obtained shows the following features:

Melting point: 140 ° C

Analysis for C₁₉H₂₆O₃:
calc .:
C, 75.46, H, 8.67, O, 15.87%,
Found .:
C, 75.48, H, 8.67, O, 15.72%

UV spectrum (CH₂Cl₂):
λ _max : 337 nm
ε : 19,400

Examples for means example A Protection gel for the skin

Compound of Example 1 | 0.12 g Polyacrylic acid crosslinked with a polyfunctional agent sold under the name "CARBOPOL 934" (GOODRICH) 0.80 g glycerin 12.00 g ethanol 15.00 g preservative 0.20 g Perfume 0.20 g Triethanolamine in sufficient quantity for pH 5.3 @ Demineralized water in sufficient quantity 100 g

Dissolve the filter in the ethanol-glycerol mixture, Adds water, the preservative and the perfume. CARBOPOL 934 is then dispersed in this aqueous phase in a homogeneous manner and adjusts the pH with triethanolamine to 5.3.

example B

Example A is repeated using the same amount of Compound of Example 11 instead of the compound of Example 1 is repeated.

example C Sunscreen oil

The following ingredients are mixed while being used for homogenization optionally heated to 40-45 ° C:

Compound of Example 2 | 0.60 g C₁₂-C₁₅ fatty alcohol benzoate sold under the name "FINSOLV TN" (FINETEX) 30.00 g refined, stabilized sunflower oil 20.00 g Perfume 1.00 g cyclic dimethylpolysiloxane, sold under the name "VOLATILE SILICONE 7207" (UNION CARBIDE), in sufficient quantity 100 g

example D Sunscreen milk E / H

Compound of Example 2 | 0.25 g benzylidenecamphor 2,00 g Mixture of fatty acid esters, polyglycerinated esters and siliconized surfactants, sold under the name "ABIL WS08" (GOLDSCHMIDT) 5.00 g white vaseline 2,00 g beeswax 2.50 g C₁₂-C₁₅ fatty alcohol benzoate sold under the name "FINSOLV TN" (FINETEX) 19.00 g glycerin 5.00 g sodium chloride 2,00 g Perfume 0.40 g preservative 0.20 g Demineralized water in sufficient quantity 100 g

The emulsion E / H is prepared by the one hand the Filters are dissolved in the fatty bodies and emulsified, wherein the fat phase is heated to 70-80 ° C; on the other hand is at the same temperature, the aqueous phase, which is composed of water, sodium chloride and glycerol, heated. The aqueous phase is added with vigorous stirring Fat phase, the mixture is then allowed to cool with gentle stirring and gives at 40 ° C the perfume and the preservative to.  

example e

Example D is repeated, taking the compound of Example 13 instead of the compound of Example 3 in same ratio used.

example F Sunscreen milk H / E

The emulsion H / E is prepared by the one hand Part of the filter dissolved at 70-80 ° C in the fatty bodies and, on the other hand, by adding the aqueous phase which is composed of water, propylene glycol and the emulsifier, is heated to 70-80 ° C. Then you give the fat phase with vigorous stirring to the aqueous phase, the mixture is allowed cool with gentle stirring and gives at 40 ° C the perfume and the preservative too.

example G Sunscreen Stick

The various compounds are left at 70-75 ° C melt to obtain a liquid phase in which you release the filter. Then you give this solution in forms and let them cool down there.

Compound of example 5 | 1.00 g ozokerite 20.00 g beeswax 7.00 g oleic alcohol 12.00 g hydrogenated lanolin, sold under the name "HYDROLAN H" (ONYX CHEMICAL) 8.00 g Lanolin oil, sold under the name "ARGONOL 60" (WESTBROOK LANOLIN) 8.00 g carnauba 1.00 g C₁₂-C₁₅ fatty alcohol benzoate sold under the name "FINSOLV TN" (FINETEX) 17.00 g Octamethylcyclotetrasiloxane, sold under the name "ABIL K4" (GOLDSCHMIDT) 100 g

example H

Example G is repeated, taking 0.5 g of the compound of Example 9 instead of 1 g of the compound of Example 5 used.  

example I Sun protection cream H / E

This emulsion is prepared in the same way as Example D. although 4 - [(2-oxo-3-bomylidene) - methyl] -phenyltrimethylammonium methylsulfate in the aqueous Phase, the water, sorbitol, sodium lactate and the Emulsifier comprises, is dissolved:

Compound of Example 6 | 0.50 g 4 - -phenyltrimethylammoniummethylsulfat [(2-oxo-3-bornylidene) methyl] 4.00 g sodium lactate 1.00 g Mixture of cetylstearyl alcohol and 33 moles of ethylene oxide oxyethyleniertem Cetylstearylalkohol, sold under the name "SINNOWAX 40" (HENKEL) 7.50 g non-auto-emulsifiable mixture of glycerol mono- and distearate 2.10 g cetyl alcohol 1.00 g Myristic alcohol, sold under the name "SIPOL C14" (HENKEL) 0.60 g 70% sorbitol 3.00 g isopropyl palmitate 10.00 g vaseline 7.00 g preservative 0.20 g Perfume 0.60 g Demineralized water in sufficient quantity 100 g

example J Sunscreen oil

The following substances are mixed, the mixture optionally  heated to 40-45 ° C for homogenization becomes:

Compound of Example 10 | 0.20 g C₁₂-C₁₅ fatty alcohol benzoate sold under the name "FINSOLV TN" (FINETEX) 30.00 g Sunflower oil 20.00 g Perfume 1.00 g cyclic dimethylpolysiloxane, sold under the name "VOLATILE SILICONE 7207" (UNION CARBIDE), in sufficient quantity 100 g

Evidence of the antioxidant properties of the compounds (I) the present invention with the aid of Rancimat test

A means of vitamin F (natural product consisting of fatty acids with multiple double bonds, such as linoleic acid and linoleic acid), which is 2.27 mM of the antioxidant Compound is thermostabilized in a at 100 ° C. Heated bath, passed through which 30 ml / mn air becomes. The gas stream is passed in a second container, the Contains water. One observes the conductivity of this aqueous environments associated with the appearance of secondary Oxidation products resulting from the degradation of hydroperoxides and the aldehydes formed by oxidation, increases. The measured induction time corresponds to that observed Latency before the exponential increase in conductance. The longer the induction time, the greater the antioxidant activity of the compound used. For the compound of Example 3, this time is 138 mn, for the compound of Example 5 it is  62 mn and for the compound of Example 8 is this Time finally 96 mn.

In comparison, the induction time for the agent is from vitamin F, which contains no antioxidant, 15 mn.

Claims (31)

1. Benzylidene cyclanone derivatives of the formula: wherein
R₁ and R are the same or different and are a hydrogen atom, a hydroxyl radical, a straight or branched C₁-C₈ alkyl radical or a straight or branched C₁-C₈ alkoxy radical, at least one of the radicals R₁ and R not being a hydrogen atom,
R₂ and R₃ are the same or different and represent a hydrogen atom or a hydroxyl radical, at least one of R₂ and R₃ being a hydroxyl radical,
R₄, R₅, R₆ and R₇ are the same or different and are a straight or branched C₁-C₈-alkyl radical, an aralkyl radical, such as a not sub stituierten or with a C₁-C₄-alkyl radical or a C₁-C₄-alkoxy substituted benzyl radical, or an aryl radical, such as an unsubstituted or substituted with a C₁-C₄ alkyl radical phenyl, and the substituents R₄ and R₅ and / or the substituents R₆ and R₇ together with the carbon atom of the ring to which they are attached, having a saturated ring 5 to 12 carbon atoms, which is unsubstituted or substituted by one or more straight or branched C₁-C₈-alkyl radicals, for a with n = 1 or 2 or an N-R₈ radical in which R₈ is a hydrogen atom, a straight or branched C₁-C₈-alkyl radical, an aralkyl radical, such as an unsubstituted or with a C₁-C₄-alkyl radical or a C₁- C₄-alkoxy substituted benzyl radical, a hydroxyl radical or an -O-R₉ radical, wherein R₉ represents a straight or branched C₁-C₈-alkyl radical, or X represents an oxygen atom or a sulfur atom. 2. A compound according to claim 1, characterized that it is selected from 3 ', 5'-di-tert-butyl-4'- hydroxy-4-benzylidene-tetrahydro-2,2,5,5-tetramethyl-furan- 3-one, 3 ', 5'-di-tert-butyl-2'-hydroxy-4-benzylidene-tetrahydro- 2,2,5,5-tetramethyl-furan-3-one, 3 ', 5'-di-tert-butyl 4'-hydroxy-4-benzylidene-tetrahydro-2,2,5,5-tetraethyl- furan-3-one, 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene tetrahydro-2,2,5,5-bis (pentamethylene) furan-3-one, 3 ', 5'- Dimethyl-4'-hydroxy-4-benzylidene-tetrahydro-2,2,5,5 tetramethyl-furan-3-one, 3 ', 5'-dimethoxy-4'-hydroxy-4- benzylidene-tetrahydro-2,2,5,5-tetramethyl-furan-3-one, 3'-tert-butyl-2'-hydroxy-5'-methoxy-4-benzylidene-tetra hydro-2,2,5,5-tetramethyl-furan-3-one, 3'-tert-butyl-2'- hydroxy-5'-methyl-4-benzylidene-tetrahydro-2,2,5,5-tetra methyl-furan-3-one, 3 ', 5'-di-tert-butyl-4'-hydroxy-4-  benzylidene-tetrahydro-2,5-dimethyl-2,5-di-tert-butyl furan-3-one, 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene tetrahydro-2,5-diethyl-2,5-dimethyl-furan-3-one, 3 ', 5'- Diisopropyl-4'-hydroxy-4-benzylidene-tetrahydro-2,2,5,5 tetramethyl-furan-3-one, 3 ', 5'-di-tert-butyl-4'-hydroxy 4-benzylidene-2,2,5,5-tetramethyl-aza-cyclopentane-3-one, 3 ', 5'-di-tert-butyl-4'-hydroxy-2-benzylidene-3,3,5,5- tetramethylcyclopentan-1-one, 3 ', 4', 5'-trihydroxy-4- benzylidene-tetrahydro-2,2,5,5-tetramethyl-furan-3-one and 3'-tert-butyl-4'-hydroxy-4-benzylidene-tetrahydro- 2,2,5,5-tetramethyl-furan-3-one. 3. A process for the preparation of the compound of formula (I) according to claim 1 or 2, characterized in that an aromatic aldehyde of the formula: wherein R, R₁, R₂ and R₃ have the meanings given in claim 1, with a cyclanone of the formula: wherein R₄, R₅, R₆, R₇ and X have the meanings given in claim 1, is condensed. 4. The method according to claim 3, characterized that the aromatic aldehyde of the formula (II) is an OH Having a function which is represented by a trialkyl (C₁-C₆) silyl or benzyl radical is protected and adhere to the condensation a removal of the trialkylsilyloxy or Benzyloxyrestes to release the OH function followed. 5. The method according to claim 3 or 4, characterized that the condensation of the aldehyde of the formula (II) with the cyclanone (III) in the presence of an alkali metal Alcoholates in a solvent at a temperature between -78 ° C and the boiling point of the solvent is carried out. 6. The method according to claim 3 or 4, characterized that the condensation of the aldehyde of the formula (II) with the cyclanone (III) in the presence of a mineral Base in a solvent at a temperature between Room temperature and boiling temperature of the reaction mixture is carried out. 7. The method according to claim 3 or 4, characterized in that the condensation of the aldehyde of the formula (II) with the cyclanone (III) in the presence of a borane of the formula wherein R₁₀ is a C₁-C₆-alkyl radical and R₁₁ is a C₁-C₄-alkyl radical, is carried out at a temperature of about 150 ° C in a solvent. 8. Cosmetic agent, characterized in that it an effective amount of at least one compound of formula (I) according to claim 1 or 2 in a cosmetic acceptable carrier containing at least one fatty phase, includes. Cosmetic composition according to claim 8, characterized in that it comprises as compound (I) at least one of the compounds selected from:
3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene-tetrahydro-2,2,5,5-tetramethyl-furan-3-one, 3', 5'-di-tert-butyl-2 '-Hydroxy-4-benzylidene-tetrahydro-2,2,5,5-tetramethyl-furan-3-one, 3', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene-tetrahydro-2, 2,5,5-tetramethyl-furan-3-one, 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene-tetrahydro-2,2,5,5-bis (pentamethylene) - furan-3-one, 3 ', 5'-dimethyl-4'-hydroxy-4-benzylidene-tetrahydro-2,2,5,5-tetramethyl-furan-3-one, 3', 5'-dimethoxy-4 '-Hydroxy-4-benzylidene-tetrahydro-2,2,5,5-tetramethyl-furan-3-one, 3'-tert-butyl-2'-hydroxy-5'-methoxy-4-benzylidene-tetrahydro- 2,2,5,5-tetramethyl-furan-one, 3'-tert-butyl-2'-hydroxy-5'-methyl-4-benzylidene-tetrahydro-2,2,5,5-tetramethyl-furan on ', 3', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene-tetrahydro-2,5-dimethyl-2,5-di-tert-butyl-furan-3-one, 3 ', 5'di-tert-butyl-4'-hydroxy-4-benzylidene-tetrahydro-2,5-diethyl-2,5-dimethyl-furan-3-one, 3 ', 5'-diisopropyl-4'-hydroxy 4-benzylidene-tetrahydro-2,2,5,5-tetramethyl-furan-3-one, 3 ', 5'-di-tert-butyl-4'-hydroxy-4-benzylidene-2,2,5,5 tetramethyl-aza-cyclopentan-3-one, 3 ', 5'-di-tert-butyl-4'-hydroxy-2-benzylidene-3,3,5,5-tetramethyl-cyclopentan-1-one, 3', 4 ', 5'-trihydroxy-4-benzylidene-tetrahydro-2,2,5,5-tetra-methyl-furan-3-one and 3'-tert-butyl-4'-hydroxy-4-benzylidene-tetrahydro- 2,2,5,5-tetramethyl-furan-3-one. 10. Cosmetic composition according to claim 8 or 9, characterized characterized in that it is oily or oily-alcoholic Lotion, as emulsion, as oily-alcoholic, alcoholic or aqueous-alcoholic gel, as a solid stick or is present as an aerosol. 11. Cosmetic composition according to claim 10, characterized characterized in that it also contains cosmetic adjuvants, which are selected from thickeners, soft agents, humectants, surfactants Agents, preservatives, antifoam agents, perfumes, Oils, waxes, lanolin, monoalcohols and low Polyols, blowing agents, dyes and pigments. 12. Cosmetic composition according to claim 10 or 11, characterized in that it is a means for protecting human Epidermis and 0.1 to 2 wt .-% of a compound of the formula (I). 13. Cosmetic composition according to claim 10 or 11, the is present as sunscreen, characterized in that it contains from 0.2 to 15% by weight of a compound of the formula (I) contains. 14. Cosmetic composition according to claim 13, characterized characterized in that it also contains an agent which Filtered UV-B and / or UV-A rays.   15. Cosmetic composition according to claim 8 or 9, the intended for application to the hair, characterized that it can be used as a shampoo, lotion, or gel Emulsion for rinsing, as a lotion or gel for styling or treating, as a lotion or gel for brushing or to the water wave, as a hair lacquer or as a means to Perm, for decolorizing or dyeing and 0.25 to 2 wt .-% of a compound of formula (I). 16. Cosmetic composition according to claim 8 or 9, which as dyed or undyed cosmetic agent is present, characterized in that it is a means for Hair, a make-up product or a means of care or treatment of the skin and 0.1 to 2% by weight a compound of formula (I). 17. Method of protecting the skin and natural or sensitized hair from ultraviolet radiation, characterized in that on the skin or on the hair an effective amount of a cosmetic agent applied is the at least one Benzylidencyclanon derivative of Formula (I) according to claim 1 or 2. 18. Method of protecting a cosmetic agent ultraviolet rays and oxidation, characterized that this agent is an effective amount at least a compound of the formula (I) is incorporated. 19. Use of at least one compound of the formula (I) according to claim 1 or 2 as an antioxidant. 20. Use of at least one compound of the formula (I)  according to claim 1 or 2 as a cosmetic product. 21. Use of at least one compound of the formula (I) according to claim 1 or 2 as a sun filter with a large Absorption width in a wavelength range of 280-380 nm. 22. Compounds of formula (I) according to claim 1 or 2 for Use as a medicine. 23. Compounds of formula (I) according to claim 1 or 2 for Use in the treatment of inflammation as allergies of the skin. 24. Compounds of formula (I) according to claim 1 or 2 for Use in the prevention of certain carcinomas. 25. Pharmaceutical agent, characterized in that it is an effective amount of at least one compound of Formula (I) according to claim 1 or 2 in a non-toxic Carrier or excipient. 26. Pharmaceutical agent for topical administration, as crème, ointment, pomade, solution, gel, lotion, spray or suspension, characterized in that it at least one compound of the formula (I) according to claim Contains 1 or 2. 27. Pharmaceutical agent for oral administration, may be in the form of tablets, gelatine capsules, dragees, as a syrup, Sus  pension, solution or emulsion, characterized in that in that there is at least one compound of the formula (I) according to claim 1 or 2 contains. 28. Pharmaceutical agent according to claim 26, characterized characterized in that it is the active compound of the formula (I) in an amount between 0.25 and 4 wt .-%, based on the Total weight of the agent contains. 29. Pharmaceutical agent according to claim 27, characterized characterized in that the active compound of the formula (I) in Doses between 0.1 and 50 mg / kg / day and preferably between 0.2 and 20 mg / kg / day. 30. Use of a compound of formula (I) according to claim 1 or 2 for the preparation of a treatment for Inflammations and allergies of the skin of certain medicines. 31. Use of a compound of formula (I) according to claim 1 or 2 for the preparation of a preventive treatment certain carcinomas of certain medicinal products.