EP1856084A1 - Chromen-4-one derivatives - Google Patents

Abstract

The invention relates to chromen-4-one derivatives, the production thereof, and the use of the same for the care, preservation or improvement of the general state of the skin or especially the hair, and for the prophylaxis of time-induced and/or light-induced ageing processes of the human skin or especially human hair. The invention also relates to preparations with an active content of such chromen-4-one derivatives.

Description

 Chromen-4-one derivatives

The present invention relates to chromene-4-one derivatives, their preparation and use for the care, preservation or improvement of the general condition of the skin or in particular the hair and the

Prophylaxis against time- and / or light-induced aging processes of human skin or especially human hair. Furthermore, the invention relates to preparations having an effective content of such chromene-4-one derivatives.

The hair consists largely of polypeptide chains held together by disulfide bonds linking adjacent polypeptide chains. The disulfide bonds are essentially responsible for the mechanical strength and extensibility of the

Hair. Sunlight helps break these disulfide bonds and make the hair stiff and brittle in dry weather and curly in wet weather. In addition, the hair loses its color and shine under such conditions.

The crucial first event in the damage of hair by light, as in all processes, is the absorption of light by the fiber. Only wavelengths above 290 nm cause consequential damage in natural light, as shorter wavelength UV light is effectively filtered out in the stratosphere. The most important chromophores in proteins that are in UV-B

Absorb area are the amino acids, tyrosine (λ max 275 nm), tryptophan (λ max 280 nm), and the disulfide (weak absorption at 290 nm). The longer wavelength UV-A and visible light rarely cause direct damage, as proteins do not absorb it. However, it is known that UV-A light generates free radicals; as a result, damage to cholesterol and fatty acids, as well as bleaching of melanin and artificial hair color occur.

The light-induced damage to the hair manifests itself in a variety of physical and chemical changes. To the physical

Changes include the destruction of epidermal cells, roughening the hair surface, loss of mechanical and elastic strength, and increased porosity. In chemical terms, photo-oxidation of cysteine, cholesterol and fatty acids, the decomposition of tryptophan, breakage of disulfide bonds and bleaching of melanin and artificial hair color may occur.

The damage to human hair caused by sunlight in the UV spectrum is more severe than that caused by any other factors such as e.g. Weather, wind, pollution, salt water, chlorinated water, perm, dyeing, bleaching, and misapplied or repeated treatments. The sunscreens used for the skin are not suitable for the hair, either because they do not adhere firmly or make the hair dull and sticky. For the protection of the hair, various approaches have been described, e.g. the use of light filters on the hair surface and the use of antioxidants or radical scavengers.

Recently, sunscreens have also been added to hair care products to protect against the harmful effects of sunlight on the hair. Two sunscreens have been developed specifically for hair, Escalol® HP 610 (US 5,451,394) and Incroquat® UV-283 (US 5,633,403).

The ideal sunscreen for the hair should be non-toxic, not irritating the skin, convenient to use and form a uniform and continuous film. The product should be chemically and physically stable to ensure proper shelf life. It is particularly desirable that the product be his

Protective effect for a long period of time after the application maintains. The product must stick firmly to hair or skin so that it will not wash off quickly. Therefore, the active substance applied to hair or skin must be resistant to chemical and / or light-induced

Decomposition and be firm. In particular, when applied to hair and the antioxidant effect of the products should not be too strong, otherwise disulfide bridges in the peptide structures of the hair can be damaged. Due to the ever increasing demand for active ingredients for the preventive treatment of human hair against aging processes and harmful environmental influences, it was an object of the present invention to provide new active ingredients which show the effects already mentioned, sufficiently oxidation and photostable and should be well formulated. The preparations produced therewith should furthermore have the lowest possible irritation potential for the skin.

It has now surprisingly been found that certain chromene-4-one derivatives (chromone derivatives) are suitable as active compounds with the profile described.

A first subject of the present application are therefore compounds of the formula I.

in which

R ¹ and R ^{2 may be the} same or different and are selected from -H or -C (= O) -NR ⁷ R ⁸ , wherein at least one of R ¹ and

R ^{2 is} different from H,

R ³ to R ^{6 may be the} same or different and are selected from

-H, -OH, straight-chain or branched C ₁ -C ₂ 0-alkyl groups, straight-chain or branched C ₃ - to C ₂ o-alkenyl groups, straight-chain or branched C ₁ -C ₂₀ -hydroxyalkyl groups, where the hydroxy group is attached to a primary or secondary Carbon atom of the chain may be bound and further the alkyl chain may also be interrupted by oxygen and R ⁷ is H or straight-chain or branched C ₁ - to C ₂ o-alkyl groups and R ⁸ is a straight-chain or branched C ₁ - to C ₂ o-alkyl group or a radical - (CH ₂ ) _n -NR ⁹ R ¹⁰ or a radical - (CHs) _n -N ⁺ R ⁹ R ¹⁰ R ¹¹ X ^" , where

R ⁹ to R ¹¹ are straight-chain or branched C 1 to C 20 -alkyl groups and n is an integer from the range from 1 to 30 and

X ^" represents an anion such as Cl ^" , Br ^' , I ^" , C _1-8 -alkyl sulfate, cis-alkylsulfonate, p-tolylsulfonate.

Applications of structurally related compounds are known from the literature:

The use of certain 2- (alkyl) carboxyl or 2- (alkyl) phenyl substituted chromen-4-one derivatives in combination with divalent zinc in pharmaceutical and cosmetic preparations is known from EP-A-0 304 802. The preparations are suitable for skin treatment, in particular for the treatment of dermatoses including atopic

Eczema.

From EP-AO 424 444 the use of salts of the Chromoncarboxylsäure in cosmetics to combat skin aging is known. The compound shows a UV-filtering effect and has the following effects in animal experiments: the proportion of bound lipids in the skin increases, the proportion of soluble collagen in the skin is increased, the skin's resistance to the effects of the fibroplatic proteases collagenase and elastase becomes elevated. From US 6,019,992 cosmetic preparations are known which contain 4-chromanone, and which are suitable for the treatment of aged, dry or wrinkled skin. It is shown that 4-chromanone in keratinocyte cultures promotes differentiation of the cells and stimulates lipid production. EP-A-1 216 692 discloses the use of 2-methyl-2- (β-carboxyethyl) -chroman derivatives in cosmetic preparations. The preparations mentioned are particularly suitable for the prophylaxis against Aging process of the skin and hair and for the prevention of dry skin, wrinkles and pigmentation. Preparations for topical use, the chromone derivatives such as chromone, 7-hydroxychromone, 7-methoxychromone, 5,7-dihydroxy-2-methyl-chromone, 3-methyl-2-butenyloxy-chromone, 3-acetyl-5, 7-dihydroxy ~

2-methyl-chromone, 5-hydroxychromone, n-pentyl-7-methoxychromone-2-carboxylate, n-undecyl-5-methoxychromone-2-carboxylate, 5-hydroxy-7-methoxy-2-methyl-chromone, 7 Methoxy-chromone-2-carboxylic acid, n-pentyl-chromone-2-carboxylic acid, 5-methoxychromone and chromone-2-carboxylic acid, are known from Japanese Patent Application JP 05/301813. The chromone derivatives act as skin-friendly tyrosinase inhibitors, which reduce the hyperpigmentation of the skin. Japanese Patent Application JP 09/188608 discloses the use of substituted chromone derivatives, such as in particular 5,7-dihydroxychromones, 7-methoxychromones, 5-hydroxy-7-methoxy-2-methyl-chromone and 5-hydroxy-2-methyl -chromone, known as an active ingredient against gray hair. The effect is attributed to the activation of the color pigment-forming cells and the increase in melanogenesis. An anti-aging agent containing chromone derivatives, which in

Position 2 are substituted with d.-is-alkyl and in position 7 H, OH or alkoxy substitution, in combination with Aminopropanolderivaten is known from JP 10/194919. Cosmetic preparation containing substituted chromone derivatives, e.g. 2- (i-ethylpentyl) -chromone, 5,7-dihydroxychromones, 7-methoxychromones, 5-

Hydroxy-7-methoxy-2-methylchromone and 5-hydroxy-2-methylchromone, and aromatic compounds having a melting point of -10 ⁰ C or contain about are known from JP 10/114640. The chromone derivative facilitates the incorporation of the aromatic compound in the cosmetic formulation.

The use of at least compounds of the formula or a preparation containing at least one such compound, wherein R ¹ and R ^{2 may be the} same or different and are selected from H, -C (= O) -R ⁷ , -C (= O) -OR ⁷ , straight-chain or branched Cr to C _2O- AII kylgruppen, straight-chain or branched C ₃ - to C ₂ o-alkenyl, straight-chain or branched Cr to C ₂ o-hydroxyalkyl groups, wherein the hydroxy group may be bonded to a primary or secondary carbon atom of the chain and further the alkyl chain also may be interrupted by oxygen, and / or C3 to C10 cycloalkyl groups and / or C ₃ - to C ₂ cycloalkenyl, where the rings may each also be - may be bridged (CH _{2) n} groups, where n = 1 to 3 , R ³ is H or straight or branched C ₁ to C ₂ o-alkyl groups, R ⁴ is H or OR ⁸ , R ⁵ and R ^{6 may be the} same or different and are selected from -H, -OH, straight-chain or branched C ₁ - to C ₂ o-alkyl groups, straight-chain or verzw have C ₃ - to C ₂₀ alkenyl groups, straight-chain or branched Cr to C ₂ o-hydroxyalkyl groups, where the hydroxy group can be bonded to a primary or secondary carbon atom of the chain and further the alkyl chain can also be interrupted by oxygen and R ⁷ is H, straight-chain or branched C ₁ to C ₂ o-alkyl groups, a polyhydroxy compound, such as preferably an ascorbic acid residue or glycosidic radicals, and R ⁸ is H or straight-chain or branched C 1 to C ₂ o-alkyl groups, where at least 2 of the substituents R ¹ , R ² , R ⁴ -R ^{6 are} different from H or at least one substituent of R ¹ and R ^{2 is} -C (= O) -R ⁷ or -C (= O) -OR ⁷ , for care, preservation or improving the general condition of the skin or hair is known from European Patent Application EP-A-1 508 327. In principle, for the purposes of the present invention, the term "compound according to formula I" also encompasses the salts of the respective compounds of formula I. The preferred salts include, in particular, alkali and alkaline earth metal salts and ammonium salts, but in particular sodium and potassium salts. salts.

According to the invention particularly preferred are compounds which are characterized in that R ⁸ represents a radical - (CH ₂₎ n NR ⁹ R ¹⁰ or a radical -. (CH ₂ V N ⁺ R ⁹ R ¹⁰ R ¹¹ X ^"Preferably, a substituent of R ¹ and R ² , preferably R ¹ , for -C (= O) -NH- (CH ₂ ) _O -N ⁺ R ⁹ R ¹⁰ R ¹¹ , where n is preferably an integer from the range of 1 to 8, in particular preferably 2, 3 or 4. These compounds which are preferred according to the invention are in particular an excellent setting-up behavior on hair and are thus suitable in a particular manner for use on hair.

The compounds which are particularly preferred according to the invention include, in particular, compounds having the formulas Ia-In:

In one variant of the invention, compounds which are characterized in that at least 2, preferably at least 3, of the substituents R ¹ , R ² , R ⁴ -R ^{6 are} different from H are particularly preferred.

With regard to the desired property profile, in particular with regard to the antioxidant properties, it has furthermore proven to be preferred if the compounds are characterized in that R ³ is OH and R ⁴ is OH, preferably additionally at least one of R ⁵ and R ^{6 are} OH.

In another group of preferred compounds according to the invention R ⁵ and R ^{6 are} H.

Further objects of the present invention are preparations containing at least one compound according to formula I with radicals as defined above, and at least one suitable carrier and the Use of the above-mentioned compounds for the care, preservation or improvement of the general condition of the skin or hair.

According to preferred uses of the compounds according to formula I or preparations containing at least one compound of formula I are in particular the use for the prophylaxis against time- and / or light-induced aging processes of the human

Skin or human hair, in particular for the prevention of dry skin, wrinkling and / or pigmentation disorders, and / or for the reduction or prevention of damaging effects of UV rays

Hair.

The preparations can be used, in particular, for protecting the hair against photochemical damage, in particular by UV-A radiation, in order to change color shades, discolouring or

Prevent damage of a mechanical nature.

The preparation of the preparations is preferably carried out as a shampoo, lotion, gel or emulsion for rinsing, wherein the respective preparation is applied before or after shampooing, before or after dyeing or discoloring or before or after perming. It is also possible to choose a preparation as a lotion or gel for hairdressing and treatment, as a lotion or gel for brushing or laying a wave of water, as hair lacquer, perming agent, dyeing or decolorizing the hair. The preparation can except the or

Compounds of formula I contain various adjuvants used in this type of mediator, such as surfactants, active agents, thickeners, polymers, emollients, preservatives,

Foam stabilizers, electrolytes, organic solvents, silicone derivatives, oils, waxes, anti-grease agents, dyes and / or pigments which dye the agent itself or the hair or other ingredients commonly used for hair care.

In each case, the use of the compounds according to formula I for the preparation of preparations is suitable for the above-mentioned

Uses also subject of the present invention. The preparations are usually either topically applicable preparations, for example cosmetic or dermatological formulations, or foods or dietary supplements. The preparations in this case contain a cosmetically or dermatologically or food-suitable carrier and, depending on the desired profile of properties, optionally further suitable ingredients.

The inventive use of chromene-4-one derivatives of

Formula I in preparations offers i.a. a protection against damage caused directly or indirectly by UV radiation or by reactive compounds caused processes, such. Skin aging, loss of skin elasticity, loss of skin elasticity, formation of wrinkles or wrinkles, or pigmentation disorders or age spots.

Furthermore, the present invention relates to the use of the o.g. Preparations for the prevention of unwanted changes in the appearance of the skin, e.g. Acne or oily skin, keratoses, photosensitive, inflammatory, erythrematous, allergic or autoimmune reactive

Reactions.

However, the compounds or preparations according to the invention are preferably also used for calming sensitive and irritated (head) skin, for the preventive regulation of collagen, hyaluronic acid,

Elastin synthesis, stimulation of DNA synthesis, especially in deficient or hypoactive states, regulation of transcription and translation of matrix-degrading enzymes, in particular of MMPs, increase of cell regeneration and regeneration of the (head) skin, increase of the (head) skin's own protective and repair mechanisms

DNA, lipids and / or proteins.

Preferred compounds to be used according to formula I are characterized in that R ³ is H and R ⁴ is OH since the active potential of representatives of this class of invention in the abovementioned

Meaning is particularly high. If additionally at least one of the radicals R ⁵ and R ^{6 is} OH, these preferred compounds additionally have an antioxidant potential in addition to the abovementioned properties. Therefore, they can act as antioxidant in preparations at the same time.

Other preferred compounds of formula I are characterized in that R ⁵ and R ^{6 are} H. In this case, the residues R ³ and R ^{4 are} freely accessible, which, as is assumed, is advantageous for the interaction with enzymes involved in the said effects.

The compounds of formula I are inventively in

Quantities of 0.01 to 20 wt .-%, preferably in amounts of 0.1 wt .-% to 10 wt .-% and particularly preferably used in amounts of 1 to 8 wt .-%. The expert does not have any difficulties in selecting the quantities according to the intended effect of the preparation.

The protective effect against oxidative stress or against the action of radicals can thus be further improved if the preparations contain one or more further antioxidants, wherein the skilled person has no difficulty in selecting suitable fast or delayed-acting antioxidants.

In a preferred embodiment of the present invention, at least one further skin care ingredient is one or more antioxidants and / or vitamins.

There are many known and proven substances in the literature that can be used as antioxidants, e.g. Amino acids (e.g., glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles, (e.g., urocanic acid) and derivatives thereof, peptides such as D, L-camosine, D-

Camosin, L-carnosine and their derivatives (eg anserine), carotenoids, carotenes (eg α-carotene, ß-carotene, lycopene) and their derivatives, chlorogenic acid and its derivatives, lipoic acid and its derivatives (eg dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (eg thioredoxin, glutathione, cysteine, cystine, cystamine and theirs

Glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, Palmitoyl, oleyl, γ-linoleyl, cholesteryl and glyceryl esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulfoximine compounds (eg buthionine sulfoximines, homocysteinesulfoximine, Buthionine sulphones, penta-, hexa-, heptathionine-sulfoximine) in very low tolerated dosages (eg pmol to μmol / kg), furthermore (metal) chelators (eg α-hydroxyfatty acids, palmitic acid, phytic acid, lactoferrin), α- Hydroxy acids (eg citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, biirubin, biliverdin, EDTA, EGTA and their derivatives, unsaturated fatty acids and their derivatives, vitamin C and derivatives (eg ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbyl acetate), Tocopherols and derivatives (eg vitamin E acetate) and Koniferylbenzoat of Benzoeharzes, rutinic acid and its derivatives, α-glycosylrutin, ferulic acid , Furfurylidene glucitol, carnosine, butylhydroxytoluene, butylhydroxyanisole, nordohydroguaretic acid, trihydroxybutyrophenone, quercitin, uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (eg ZnO, ZnSO ₄ ), selenium and its derivatives (eg selenium methionine), Stilbenes and their derivatives (eg stilbene oxide, trans-stilbene oxide).

Mixtures of antioxidants are also suitable for use in the cosmetic preparations according to the invention. Known and commercial mixtures are, for example, mixtures comprising, as active ingredients, lecithin, L - (+) - ascorbyl palmitate and citric acid (for example (for example Oxynex ^® AP), natural tocopherols, L - (+) - ascorbyl palmitate, _- (+)! -

Ascorbic acid and citric acid (for example Oxynex ^® K LIQUID), tocopherol extracts from natural sources, L - (+) - ascorbyl palmitate, L - (+) - ascorbic acid and citric acid (for example Oxynex ^® L LIQUID), DL-α-tocopherol , L - (+) - ascorbyl palmitate, citric acid and lecithin (for example Oxynex ^® LM) or butylhydroxytoluene (BHT), L ~ (+) - ascorbyl palmitate and citric acid (for example

Oxynex ^® 2004). Such antioxidants are usually used with compounds of the formula I in such compositions in ratios in the range from 1000: 1 to 1: 1000, preferably in amounts of 100: 1 to 1: 100. The preparations according to the invention may contain vitamins as further ingredients. Preference is given to vitamins and vitamin derivatives selected from vitamin B, thiamin chloride hydrochloride (vitamin B ₁ ), riboflavin (vitamin B ₂ ), nicotinamide, vitamin C (ascorbic acid), vitamin D, ergocalciferol (vitamin D ₂ ), vitamin E, DL-cc Tocopherol, tocopherol E

Acetate, tocopherol hydrogen succinate, vitamin Ki, esculin (vitamin P active ingredient), thiamine (vitamin Bi), nicotinic acid (niacin), pyridoxine, pyridoxal, pyridoxamine, (vitamin B ₆ ), pantothenic acid, biotin, folic acid and cobalamin (vitamin Bi ₂ ) in the cosmetic preparations according to the invention, more preferably vitamin C and its

Derivatives, DL-α-tocopherol, tocopherol-E-acetate, nicotinic acid, pantothenic acid and biotin. Vitamins are used with compounds of the formula I usually in ratios in the range of 1000: 1 to 1: 1000, preferably used in amounts of 100: 1 to 1: 100.

Among the phenols with an antioxidant effect, the polyphenols, which are sometimes present as natural substances, are of particular interest for applications in the pharmaceutical, cosmetic or food sector. For example, the flavonoids or bioflavonoids, which are mainly known as plant dyes, frequently have an antioxidant potential. Effects of the substitution pattern of mono- and dihydoxy flavones are dealt with by K. Lemanska, H. Szymusiak, B. Tyrakowska, R. Zielinski, I. M. C. M. Rietjens; Current Topics in Biophysics 2000, 24 (2), 101-108. It is observed there that dihydroxyflavones with an OH group adjacent to the keto function or

OH groups in 3'4'- or 6,7- or 7,8-position have antioxidant properties, while other mono- and Dihydroxyflavone partially have no antioxidant properties.

Quercetin (cyanidanol, cyanidolone 1522, meletin,

Sophoretine, ericin, 3,3 ', 4', 5,7-pentahydroxyflavone) as a particularly effective antioxidant (eg CA Rice-Evans, NJ Miller, G. Paganga, Trends in Plant Science 1997, 2 (4), 152 -159). K. Lemanska, H. Szymusiak, B. Tyrakowska, R. Zielinski, AEMF Soffers, IM CM. Rietjens; Free Radical Biology & Medicine 2001, 31 (7), 869-881 investigate the pH dependence of the antioxidant activity of Hydroxyflavones. Quercetin shows the highest activity of the investigated structures over the entire pH range.

Suitable antioxidants are further compounds of the formula II

wherein R ¹ to R ^{10 may be the} same or different and are selected from

- H

- OR ¹¹

- linear or branched Ci to C _2O -AI kylgruppen,

straight-chain or branched C ₃ - to C ₂ o-alkenyl groups,

straight-chain or branched C 1 -C ₂₀ -hydroxyalkyl groups, where the hydroxy group may be bonded to a primary or secondary carbon atom of the chain and furthermore the alkyl chain may also be interrupted by oxygen, and / or

- C ₃ - to C-io-cycloalkyl and / or C ₃ - to C ₂ - cycloalkenyl groups, where the rings may each also by - groups, where n = 1 may be bridged to 3, where all OR ¹¹ - _n (CH ₂₎ stand independently for

- OH

straight-chain or branched C ₁ - to C 20 -alkyloxy groups,

straight-chain or branched C ₃ - to C 20 -alkenyloxy groups,

straight-chain or branched C 1 -C ₂₀ -hydroxyalkoxy groups, where the hydroxy group (s) is attached to a primary or secondary carbon atom of the chain may be bound and further the alkyl chain may also be interrupted by oxygen, and / or

- C3 to C-io-cycloalkyloxy groups and / or C3- to C12 cycloalkenyloxy, where the rings may each also be - may be bridged (CH ₂₎ n groups with n = 1 to 3 and / or,

Mono- and / or oligoglycosyl radicals, with the proviso that at least 4 radicals from R ¹ to R ⁷ are OH and that at least 2 pairs of adjacent groups -OH are present in the molecule,

or R ² , R ⁵ and R ⁶ for OH and the radicals R ¹ , R ³ , R ⁴ and R ^{7 "10} for

H stand, as described in the earlier German patent application DE-A-10244282.

Advantages of the compositions according to the invention containing at least one antioxidant are, in addition to the abovementioned advantages, in particular the antioxidant action and the good skin and hair compatibility. In addition, preferred compounds described herein are colorless or only slightly colored and thus do not or only to a slight extent discolorations of the preparations. Of particular advantage is the particular profile of action of the compounds of formula I ₁ which in the DPPH assay in a high capacity to catch radicals (EC ₅₀ ), a time-delayed action (TECSO> 120 min) and thus a medium to high antiradical efficiency (AE ). In addition, the compounds of the formula I in the molecule combine antioxidant properties with UV absorption in the UV-A and / or B range. Preference is therefore also given to preparations containing at least one compound of the formula II, which is characterized in that at least two adjacent radicals of the radicals R ¹ to R ⁴ are OH and at least two adjacent radicals of the radicals R ⁵ to R ⁷ are OH. Particularly preferred preparations contain at least one compound of the formula II, which is characterized in that at least three adjacent radicals of the radicals R ¹ to R ⁴ are OH, wherein preferably the radicals R ¹ to R ^{3 are} OH. It is believed that preferred compounds of formula I also act as an enzyme inhibitor. They are believed to inhibit protein kinases, elastase, aldose reductase, and hyaluronidase, thus allowing the integrity of the matrix of vascular sheaths to be maintained. Furthermore, they are believed not to specifically inhibit catechol-O-methyltransferase, thereby increasing the amount of available catecholamines and thereby vascular resistance. Furthermore, they presumably inhibit AMP phosphodiesterase, which has the potential to inhibit platelet aggregation.

Because of these properties, the preparations according to the invention are generally suitable for immune protection and for the protection of DNA and RNA. In particular, the preparations are suitable for the protection of DNA and RNA from oxidative attacks, from radicals and from damage by radiation, in particular UV radiation. Another

Advantage of the preparations according to the invention is the cell protection, in particular the protection of Langerhans cells from damage by the above-mentioned influences. All these uses or the use of the compounds of the formula I for the preparation of correspondingly usable preparations are expressly the subject of the present invention,

Preparations which are particularly preferred according to the invention comprise, in addition to the compounds of the formula lauch, UV filters.

When using the dibenzoylmethane derivatives particularly preferred as UV-A filters in combination with the compounds of the formula I, an additional advantage results: The UV-sensitive dibenzoylmethane derivatives are additionally stabilized by the presence of the compounds of the formula I. Another object of the present invention is therefore the use of the compounds of formula I for the stabilization of Dibenzoylmethanderivaten in preparations.

In principle, all UV filters are suitable for combination with the compounds of the formula of the invention. Especially preferred are those UV filters whose physiological harmlessness has already been demonstrated. Both for UVA and UVB filters, there are many well-known and proven substances from the literature, eg

Benzylidene camphor derivatives such as 3- (4'-methylbenzylidene) -dl camphor (e.g.

Eusolex® 6300), 3-benzylidene camphor (eg Mexoryl® SD), polymers of N - {(2 and 4) - [(2-oxobrom-3-ylidene) methyl] benzyl} -acrylamide (eg Mexoryl® SW), N , N, N-trimethyl-4- (2-oxobomo-3-ylidenemethyl) anilinium methylsulfate (eg Mexoryl® SK) or (2-oxoborn-3-ylidene) toluoI-4-sulfonic acid (eg Mexoryl® SL),

Benzoyl or dibenzoylmethanes such as 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) propane-1,3-dione (e.g., Eusolex® 9020) or 4-isopropyldibenzoylmethane (e.g., Eusolex® 8020),

Benzophenones such as 2-hydroxy-4-methoxybenzophenone (e.g., Eusolex® 4360) or 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its sodium salt (e.g., Uvinul® MS-40),

Methoxycinnamic acid esters such as octyl methoxycinnamate (e.g., Eusolex®

2292), 4-methoxycinnamic acid isopentyl ester, e.g. as a mixture of isomers (e.g., Neo Heliopan® E 1000),

Salicylate derivatives such as 2-ethylhexyl salicylate (e.g., Eusolex® OS), A-isopropylbenzyl salicylate (e.g., Megasol®), or 3,3,5-

Trimethylcyclohexyl salicylate (e.g., Eusolex® HMS),

4-aminobenzoic acid and derivatives such as 4-aminobenzoic acid, 2-ethylhexyl 4- (dimethylamino) benzoate (e.g., Eusolex® 6007), ethoxylated 4-aminobenzoic acid ethyl ester (e.g., Uvinul® P25),

Phenylbenzimidazole sulfonic acids, such as 2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium and triethanolamine salts (eg Eusolex® 232), 2,2- (1,4-phenylene) bisbenzimidazole-4,6-disulfonic acid or salts thereof ( eg Neoheliopan® AP) or 2,2- (1,4-phenylene) bisbenzimidazole-6-sulfonic acid; and other substances like

2-cyano-3,3-diphenylacrylic acid 2-ethylhexyl ester (e.g., Eusolex® OCR),

a.SXI.sub.3 -phenylenedimethylene-bis-CZJ-dimethyl-oxobicyclo-p.-hept-1-ylmethanesulfonic acid and its salts (e.g., Mexoryl.RTM. SX) and

- 2,4,6-trianilino- (p-carbo-2 ^{'-ethylhexyl-1'} -oxi) -1, 3,5-triazine (for example Uvinul T 150)

Hexyl 2- (4-diethylamino-2-hydroxybenzoyl) benzoate (e.g., Uvinul® UVA Plus, BASF).

The compounds listed in the list are examples only. Of course, other UV filters can be used.

These organic UV filters are usually incorporated in an amount of 0.5 to 10 weight percent, preferably 1-8%, in cosmetic formulations.

Other suitable organic UV filters are e.g. 2- (2H-Benzotriazol-2-yl) -4-methyl-6- (2-methyl-3- (1,3,3,3-tetramethyl)

(trimethylsilyloxy) disiloxanyl) propyl) phenol (for example Silatrizole ^®),

4,4 ^' - [(6- [4 - ((1, 1-dimethylethyl) aminocarbonyl) phenylamino] -1, 3,5-triazine-2,4-diyl) diimino] bis (benzoic acid 2-ethylhexyl ester) (eg

Uvasorb HEB ^®) - α- (Trimethylsilyl) -ω- [trimethylsilyl) oxy] poly [oxy (dimethyl [and about 6% methyl [2- [p- [2,2-bis (ethoxycarbonyl] vinyl] phenoxy] 1-methylenethyl] and about 1, 5% of methyl [3- [p- [2,2-bis (ethoxycarbonyl) vinyl] phenoxy) propenyl) and 0.1 to 0.4% (methylhydrogensilylenj] (n « 60) (CAS no.

207 574-74-1) - 2,2 ^{'methylene-bis-} (6- (2H-benzotriazol-2-yl) -4- (1, 1, 3,3-tetramethyl- butyl) phenol) (CAS No. 103 597-45-1)

- 2,2 ^'- (1, 4-phenylene) bis- (1 H-benzimidazol-4,6-disulfonic acid,

Monosodium salt) (CAS No. 180 898-37-7) and

2,4-bis - {[4- (2-ethyl-hexyloxy) -2-hydroxyl] -phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine (CAS No. 103 597- 45-, 187 393-00-6). 4,4 ^' - [(6- [4 - ((1,1-dimethylethyl) aminocarbonyl) phenylamino] -1,3,5-triazine-2,4-diyl) diimino] bis (benzoic acid Θ-2-θthylhθxylθster) (for example Uvasorb HEB ^®),

Other suitable UV filters are also Methoxyflavone ensprechend the older German patent application DE 10232595.2.

Organic UV filters are usually incorporated in an amount of 0.5 to 20 percent by weight, preferably 1-15%, in cosmetic formulations.

As inorganic UV filters are those from the group of titanium dioxides, such as coated titanium dioxide (for example Eusolex® T-2000, Eusolex ^® T-AQUA, Eusolex® T-AVO, Eusolex® T-Oleo), zinc oxides (eg Sachtotec.RTM) Iron oxides or cerium oxides conceivable. These inorganic UV filters are usually incorporated in an amount of 0.5 to 20 weight percent, preferably 2-10%, in cosmetic preparations.

Preferred compounds having UV-filtering properties are 3- (4 ^'~ methylbenzylidene) -dl-camphor, 1- (4-tert-butylphenyl) -3- (4-methoxy-phenyl) - pro-pan-1, 3-dione , 4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octyl methoxycinnamate, 3,3,5-trimethyl-cyclo-hexyl-salicylate, 4- (dimethylamino) -benzoic acid 2-ethylhexyl ester, 2-cyano- 3,3-di-phenyl-2-ethylhexyl acrylate, 2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium and triethanolamine salts.

By combining one or more compounds of formula I with other UV filters, the protective effect against harmful effects of UV radiation can be optimized.

For example, optimized compositions can be the combination of the organic UV filters 4'-methoxy-6-hydroxyflavone with 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) propane-1,3-dione and 3- (4 ^' -

Methylbenzylidene) -dl camphor. This combination results in a broadband protection, which can be supplemented by the addition of inorganic UV filters, such as titanium dioxide microparticles. All mentioned UV filters can also be used in encapsulated form. In particular, it is advantageous to use organic UV filters in encapsulated form. Specifically, there are the following advantages: The hydrophilicity of the capsule wall can be adjusted independently of the solubility of the UV filter. For example, hydrophobic UV filters can also be incorporated into purely aqueous preparations. In addition, the often perceived as unpleasant oily impression when applying the hydrophobic UV filter containing preparation is suppressed.

Certain UV filters, in particular dibenzoylmethane derivatives, show only reduced photostability in cosmetic preparations. By encapsulating these filters or compounds that affect the photostability of these filters, such as cinnamic acid derivatives, the photostability of the entire formulation can be increased.

In the literature, the skin penetration through organic UV filters and the associated irritation potential during direct application to the human skin is discussed again and again. By the here. proposed encapsulation of the corresponding substances, this effect is suppressed.

- Generally, by encapsulation of individual UV filters or other ingredients preparation problems caused by interaction of individual preparation components with each other, such as crystallization processes, precipitation and agglomeration can be avoided because the interaction is prevented.

Therefore, it is preferred according to the invention if one or more of the abovementioned UV filters are present in encapsulated form. It is advantageous if the capsules are so small that they can not be observed with the naked eye. To achieve the o.g. Effects it is still necessary that the capsules are sufficiently stable and donate the encapsulated active ingredient (UV filter) not or only to a small extent to the environment.

Suitable capsules may be walls of inorganic or organic

Have polymers. For example, in US 6,242,099 B1 the Preparation of suitable capsules with walls of chitin, chitin derivatives or polyhydroxylated polyamines described. Capsules which are particularly preferred for use in accordance with the invention have walls which can be obtained by a SolGel process, as described in applications WO 00/09652, WO 00/72806 and WO 00/71084.

Again, capsules whose walls are made up of silica gel (silica, undefined silicon oxide hydroxide) are preferred. The production of such capsules is known to the skilled worker, for example, from the cited patent applications, whose contents are expressly also part of the subject of the present application.

The capsules in preparations according to the invention are preferably present in amounts which ensure that the encapsulated UV filters are present in the preparation in the amounts indicated above.

The hair-sparing or hair-care active ingredients may in principle be all active ingredients known to the person skilled in the art.

Particularly preferred active ingredients in one embodiment of the present invention are pyrimidinecarboxylic acids and / or aryloximes.

Pyrimidinecarboxylic acids occur in halophilic microorganisms and play a role in the osmoregulation of these organisms (EA Galinski et al., Eur. J. Biochem., 149 (1985) page 135-139). In particular, ectoine ((S) -1, 4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and hydroxyectoine ((S ₁ S) -1,5,6-tetrahydro-5 are among the pyrimidinecarboxylic acids These compounds stabilize enzymes and other biomolecules in aqueous solutions and organic solvents.

In particular, they stabilize enzymes against denaturing conditions such as salts, extreme pH, surfactants, urea, guanidinium chloride and other compounds. In this case, a pyrimidinecarboxylic acid according to the formula below is preferably used,

wherein R ^{1 is} a radical H or d-8-alkyl, R ^{2 is} a radical H or C 1-4 -alkyl and R ³ , R ⁴ , R ⁵ and R ^{6 are} each independently a radical from the group

H, OH, NH ₂ and C 1-4 alkyl. Preference is given to using pyrimidinecarboxylic acids in which R ^{2 is} a methyl or an ethyl group and R ¹ or R ⁵ and R ^{6 are} H. Particularly preferred are the pyrimidinecarboxylic acids ectoine ((S) -1, 4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and hydroxyectoine ((S ₁ S) - 1, 4,5, 6- Tetrahydro-5-hydroxy-2-methyl-4-pyrimidine-carboxylic acid) used. The preparations according to the invention contain such pyrimidinecarboxylic acids, preferably in amounts of up to 15% by weight. The pyrimidinecarboxylic acids are preferably used in ratios of from 100: 1 to 1: 100 to give the compounds of the formula I, ratios in the range from 1:10 to

10: 1 are particularly preferred.

Among the aryl oximes, 2-hydroxy-5-methyllaurophenone oxime, which is also referred to as HMLO, LPO or F5, is preferably used. Its suitability for use in cosmetic

Means is known for example from German patent application DE-A-41 16 123. Preparations containing 2-hydroxy-5-methyllaurophenone oxime are accordingly suitable for the treatment of skin diseases which are associated with inflammation. It is known that such preparations can be used, for example, for the therapy of psoriasis, different forms of eczema, irritative and toxic dermatitis, UV dermatitis and other allergic and / or inflammatory diseases of the skin and the skin appendages. Compositions according to the invention which, in addition to the compound of the formula I, additionally contain an aryloxime, preferably 2-hydroxy-5-methyllaurophenone oxime, show surprising anti-oxime inflammatory Eign fitness. The preparations preferably contain from 0.01 to 10% by weight of the aryloxime, and it is particularly preferred if the preparation contains from 0.05 to 5% by weight of aryloxime.

Any compounds or components which may be used in the compositions are either known and commercially available or may be synthesized by known methods. The preparation of the novel compounds of formula I is described below.

The one or more compounds of the formula I can be incorporated in the usual way into cosmetic or dermatological preparations. Suitable preparations for external use, for example as a cream, lotion, gel, or as a solution that can be sprayed on the skin. For internal use, dosage forms such as capsules, dragees, powders, tablet solutions or solutions are suitable.

As an application form of the preparations according to the invention, e.g. called: solutions, suspensions, emulsions, PIT emulsions, pastes,

Ointments, gels, creams, lotions, powders, soaps, surfactant-containing cleaning preparations, oils, aerosols and sprays. Other applications are e.g. Sticks, shampoos and shower baths. Any customary carrier substances, adjuvants and optionally further active ingredients can be added to the preparation.

Preferable excipients come from the group of preservatives, antioxidants, stabilizers, solubilizers, vitamins, colorants, odor improvers.

Ointments, pastes, creams and gels may contain the usual excipients, for example animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances. Powders and sprays may contain the usual excipients, for example lactose, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays may additionally contain the customary propellants, for example chlorofluorohydrocarbons, propane / butane or dimethyl ether.

Solutions and emulsions may contain the usual excipients such as solvents, solubilizers and emulsifiers, e.g. Water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol, oils, in particular cottonseed oil,

Peanut oil, corn oil, olive oil, castor oil and sesame oil, Glycerinfett- acid esters, polyethylene glycols and fatty acid esters of sorbitol or mixtures of these substances.

Suspensions may include the usual carriers such as liquid diluents, e.g. Water, ethanol or propylene glycol, suspending agents, e.g. ethoxylated isostearyl alcohols, Polyoxyethylensorbitester and Polyoxyethylensorbitanester, microcrystalline cellulose, Aluminiummeta- hydroxide, bentonite, agar-agar and tragacanth or mixtures of these substances.

Soaps may contain the usual excipients such as alkali metal salts of fatty acids, salts of fatty acid monoesters, fatty acid protein hydrolysates, isothionates, lanolin, fatty alcohol, vegetable oils, plant extracts, glycerol, sugars or mixtures of these substances.

Surfactant-containing cleaning products may include the usual excipients such as salts of fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic acid esters, fatty acid protein hydrolysates, isothionates, imidazolinium derivatives, methyl taurates, sarcosinates, fatty acid amide ether sulfates, alkyl amidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable and synthetic oils, lanolin derivatives, ethoxylated glycerol - Contain fatty acid esters or mixtures of these substances.

Facial and body oils can be the usual carriers such as synthetic oils such as fatty acid esters, fatty alcohols, silicone oils, natural Oils such as vegetable oils and oily plant extracts, paraffin oils, lanolin oils or mixtures of these substances.

Other typical cosmetic application forms are also lipsticks, lip balms, mascara, eyeliner, eye shadow, blush, powder,

Emulsion and wax make-up as well as sunscreen, pre-sun and after-sun preparations.

The preferred preparation forms according to the invention include in particular emulsions.

Emulsions of the invention are advantageous and contain z. As mentioned fats, oils, waxes and other fatty substances, and water and an emulsifier, as it is commonly used for such a type of preparation.

The lipid phase can advantageously be selected from the following substance group:

- mineral oils, mineral waxes

- Oils such as triglycerides of capric or caprylic, further natural oils such. Castor oil;

Fats, waxes and other natural and synthetic fats, preferably esters of fatty acids with lower C-number alcohols, e.g. with isopropanol, propylene glycol or glycerol, or esters of fatty acids

Alcohols with low C-alkanoic acids or with fatty acids;

- Silicone oils such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof.

The oil phase of the emulsions, oleogels or hydrodispersions or

Lipodispersions in the context of the present invention is advantageously selected from the group of esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 3 to 30 carbon atoms and saturated and / or unsaturated, branched and / or unbranched alcohols of one Chain length of 3 to 30 C-atoms, from the group of esters of aromatic carbon acid and saturated and / or unsaturated, branched and / or unbranched alcohols having a chain length of 3 to 30 carbon atoms. Such ester oils can then advantageously be selected from the group consisting of isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexadecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate and synthetic, semisynthetic and natural mixtures of such esters, eg. B. jojoba oil.

Furthermore, the oil phase can advantageously be selected from the group of branched and unbranched hydrocarbons and waxes, silicone oils, dialkyl ethers, the group of saturated or unsaturated, branched or unbranched alcohols, and fatty acid triglycerides, namely the triglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, in particular 12-18 C-atoms. The fatty acid triglycerides can be selected, for example, advantageously from the group of synthetic, semi-synthetic and natural oils, for. Olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil,

Palm kernel oil and the like more.

Any mixtures of such oil and wax components are also advantageous to use in the context of the present invention. It may also be advantageous, if appropriate, to use waxes, for example cetyl palmitate, as the sole lipid component of the oil phase.

Advantageously, the oil phase selected from the group 2-ethylhexyl isostearate, octyldodecanol, isotridecyl isononanoate, isoeicosane, 2-ethyl hexylcocoat, Ci2-I ₅ alkyl benzoate, caprylic-capric acid triglyceride, Dicap- rylether.

Particularly advantageous are mixtures of C ₂ i5-alkyl benzoate and 2-EthylhexyIisostearat, mixtures of C- | ₂ -i ₅ alkyl benzoate and isotridecyl isononanoate and mixtures of C ₂ -i ₅ alkyl benzoate, 2-ethylhexyl isostearate and isotridecyl isononanoate. Of the hydrocarbons, paraffin oil, squalane and squalene are to be used advantageously in the context of the present invention.

Advantageously, the oil phase can also have a content of cyclic or linear silicone oils or consist entirely of such oils, although it is preferred to use an additional content of other oil phase components in addition to the silicone oil or silicone oils.

Advantageously, cyclomethicone (octamethylcyclotetrasiloxane) is used as the silicone oil to be used according to the invention. However, other silicone oils are also advantageous for the purposes of the present invention, for example hexamethylcyclotrisiloxane, polydimethylsiloxane, poly (methylphenylsiloxane).

Also particularly advantageous are mixtures of cyclomethicone and Iso tridecylisononanoat, from cyclomethicone and 2-Ethylhexylisostearat.

If appropriate, the aqueous phase of the preparations according to the invention advantageously contains alcohols, diols or polyols of low C number, and their ethers, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene - glycol monomethyl or monoethyl ether and analogous products, further

Low C-number alcohols, e.g. As ethanol, isopropanol, 1, 2-Propandiof, glycerol and in particular one or more thickeners, which can be advantageously selected from the group of silica, aluminum silicates, polysaccharides or their derivatives, such as hyaluronic acid, xanthan gum, hydroxypropylmethylcellulose, particularly advantageous the group of polyacrylates, preferably a polyacrylate from the group of so-called carbopols, for example Carbopols types 980, 981, 1382, 2984, 5984, each individually or in combination. In particular, mixtures of the abovementioned solvents are used. For alcoholic solvents, water can be another ingredient.

Emulsions of the invention are advantageous and contain z. As mentioned fats, oils, waxes and other fatty substances, and water and an emulsifier, as it is usually used for such a type of Formu- tion.

In a preferred embodiment, the preparations according to the invention contain hydrophilic surfactants.

The hydrophilic surfactants are preferably selected from the group of alkylglucosides, acyl lactylates, betaines and cocoamphoacetates.

The alkylglucosides in turn are advantageously selected from the group of alkylglucosides, which are represented by the structural formula

wherein R represents a branched or unbranched alkyl radical having 4 to 24 carbon atoms and wherein DP means a mean Glucosylierungsgrad of up to 2.

The value DP represents the degree of glucosidation of the alkylglucosides used in the invention and is defined as

100 100 100 100

Here pi, P ₂ , P ₃ ... or pi represent the proportion of the simple, two times three times

In accordance with the invention, products having degrees of glucosylation of 1 to 2, particularly advantageously 1 to 1 to 5, very particularly preferably 1 to 2-1, 4, in particular of 1, 3 selected.

The value DP takes into account the fact that alkylglucosides, as a rule, are mixtures of mono- and oligoglucosides. According to the invention, a relatively high content of monoglucosides, typically of the order of 40-70% by weight, is advantageous.

Alkylglylcosides used particularly advantageously according to the invention are selected from the group octylglucopyranoside, nonylglucopyranoside, decylglucopyranoside, undecylglucopyranoside, dodecylglucopyranoside, tetradecylglucopyranoside and hexadecylglucopyranoside.

It is also advantageous materials, natural or synthetic raw materials and assistants or to use mixtures which are distinguished by an effective content of the active ingredients used according to the invention, for example Plantaren ^® 1200 (Henkel KGaA), Oramix NS ^® 10 (Seppic).

The acyl lactylates are in turn advantageously chosen from the group of

Substances that differ by the structural formula

M ^®

in which R ^{1 is} a branched or unbranched alkyl radical having 1 to 30 carbon atoms and M ^{+ is selected} from the group of the alkali metal and the group of ammonium ions substituted by one or more alkyl and / or by one or more hydroxyalkyl radicals or corresponds to half the equivalent of an alkaline earth metal ion.

For example, sodium isostearyl lactylate, for example, is advantageous

Product Pathionic ^® ISL from the American Ingredient Company.

The betaines are advantageously selected from the group of substances which are defined by the structural formula

characterized in that R ^{2 is} a branched or unbranched alkyl radical having 1 to 30 carbon atoms.

Particularly advantageously, R ^{2 is} a branched or unbranched alkyl radical having 6 to 12 carbon atoms.

Capramidopropylbetaine, for example, is advantageous

Product Tego ^® betaine 810 from the company Th. Goldschmidt AG.

, Sodium, for example, selected as inventively advantageous cocoamphoacetate as under the name Miranol ^® Ultra C32 from Miranol Chemical Corp. is available.

The preparations according to the invention are advantageously characterized in that the hydrophilic surfactant or surfactants in concentrations of 0.01-20 wt .-%, preferably 0.05-10 wt .-%, particularly preferably 0.1-5 wt .-%, respectively based on the total weight of the composition, is present or present. For use, the cosmetic and dermatological preparations according to the invention are applied to the skin and / or the hair in a quantity sufficient in the manner customary for cosmetics.

Cosmetic and dermatological preparations according to the invention can be present in various forms. So they can z. For example, a solution, an anhydrous preparation, an emulsion or microemulsion of the water-in-oil (W / O) type or of the oil-in-water (O / W) type, a multiple emulsion, for example of the Waser-in type. Oil-in-water (W / O / W), a gel, a solid stick, an ointment or even an aerosol. It is also advantageous to present Ectoine in encapsulated form, e.g. In collagen matrices and other common encapsulating materials, e.g. As encapsulated cellulose, in gelatin, wax matrices or liposomally encapsulated. In particular wax matrices as described in DE-OS 43 08 282, have been found to be favorable. Preference is given to emulsions. O / W emulsins are especially preferred. Emulsions, W / O emulsions and O / W emulsions are available in the usual way.

As emulsifiers, for example, the known W / O and O / W

Emulsifiers are used. It is advantageous to use further customary co-emulsifiers in the preferred O / W emulsions according to the invention.

According to the invention are advantageous as co-emulsifiers, for example

O / W emulsifiers selected, primarily from the group of substances with HLB values of 1 1-16, very particularly advantageous with HLB values of 14.5-15.5, provided that the O / W emulsifiers saturated radicals R and R ¹ have. If the O / W emulsifiers have unsaturated radicals R and / or R ¹ , or if isoalkyl derivatives are present, the preferred HLB value of such emulsifiers may also be lower or higher.

It is advantageous to choose the fatty alcohol ethoxylates from the group of ethoxylated stearyl alcohols, cetyl alcohols, cetylstearyl alcohols (cetearyl alcohols). Particularly preferred are: polyethylene glycol (13) stearyl ether (steareth-13), polyethylene glycol (14) stearyl ether (Steareth-14), polyethylene glycol (15) stearyl ether (steareth-15),

Polyethylene glycol (16) stearyl ether (steareth-16), polyethylene glycol (17) stearyl ether (steareth-17), polyethylene glycol (18) stearyl ether (steareth-18), polyethylene glycol (19) stearyl ether (steareth-19), polyethylene glycol (20). stearyl ether (steareth-20), polyethylene glycol (12) isostearyl ether

(isosteareth-12), polyethylene glycol (13) isostearyl ether (isosteareth-13), polyethylene glycol (14) isostearyl ether (isosteareth-14), polyethylene glycol (15) isostearyl ether (isosteareth-15), polyethylene glycol (16) - isostearyl ether (isosteareth- 16), polyethylene glycol (17) isostearyl ether (isosteareth-17), polyethylene glycol (18) isostearyl ether (isosteareth-18),

Polyethylene glycol (19) isostearyl ether (isosteareth-19), polyethylene glycol (20) isostearyl ether (isosteareth-20), polyethylene glycol (13) cetyl ether (ceteth-13), polyethylene glycol (14) cetyl ether (ceteth-14), polyethylene glycol ( 15) cetyl ether (ceteth-15), polyethylene glycol (16) cetyl ether (ceteth-16), polyethylene glycol (17) cetyl ether (ceteth-17), polyethylene glycol (18) cetyl ether (ceteth-18), polyethylene glycol (19) cetyl ether (Ceteth -19), polyethylene glycol (20) cetyl ether (ceteth-20), polyethylene glycol (13) isocetyl ether (isoceteth-13), polyethylene glycol (14) isocetyl ether (isoceteth-14), polyethylene glycol (15) isocetyl ether (isoceteth-15) ), Polyethylene glycol (16) isocetyl ether (isoceteth-16), polyethylene glycol (17) - isocetyl ether (isoceteth-17), polyethylene glycol (18) isocetyl ether (isoceteth-18), polyethylene glycol (19) isocetyl ether (isoceteth-19), polyethylene glycol (20) isocetyl ether (Isoceteth-20), polyethylene glycol (12) oleyl ether (Oleth-12), polyethylene glycol (13) oleyl ether (Oleth-13), polyethylene glycol (14) oleyl ether (Oleth-14), polyethylene glycol (15) oleyl ether (Oleth-15),

Polyethylene glycol (12) lauryl ether (laureth-12), polyethylene glycol (12) - isolauryl ether (isolaureth-12), polyethylene glycol (13) cetyl stearyl ether (ceteareth-13), polyethylene glycol (14) cetyl stearyl ether (ceteareth-14), polyethylene glycol (15) cetyl stearyl ether (Ceteareth-15), polyethylene glycol (16) cetyl stearyl ether (ceteareth-16), polyethylene glycol (17) cetyl stearyl ether (ceteareth-17), polyethylene glycol (18) cetyl stearyl ether (ceteareth-18), polyethylene glycol (19) cetyl stearyl ether (ceteareth- 19), polyethylene glycol (20) cetyl stearyl ether (ceteareth-20).

It is also advantageous to choose the fatty acid ethoxylates of the following group: Polyethylene glycol (20) stearate, polyethylene glycol (21) stearate, polyethylene glycol (22) stearate, polyethylene glycol (23) stearate, polyethylene glycol (24) stearate, polyethylene glycol (25) stearate, polyethylene glycol (12) isostearate, polyethylene glycol (13) isostearate,

Polyethylene glycol (14) isostearate, polyethylene glycol (15) isostearate, polyethylene glycol (16) isostearate, polyethylene glycol (17) isostearate, polyethylene glycol (18) isostearate, polyethylene glycol (19) isostearate, polyethylene glycol (20) isostearate, polyethylene glycol (21) isostearate, polyethylene glycol ( 22) isostearate, polyethylene glycol (23) isostearate,

Polyethylene glycol (24) isostearate, polyethylene glycol (25) isostearate, polyethylene glycol (12) oleate, polyethylene glycol (13) oleate, polyethylene glycol (14) oleate, polyethylene glycol (15) oleate, polyethylene glycol (16) oleate, polyethylene glycol (17) oleate, polyethylene glycol ( 18) oleate, polyethylene glycol (19) oleate,

Polyethylene glycol (20) oleate,

As the ethoxylated alkyl ether carboxylic acid or its salt, the sodium laureth-11-carboxylate can be advantageously used. As the alkyl ether sulfate, sodium laureth-4 sulfate can be advantageously used. As the ethoxylated cholesterol derivative, polyethylene glycol (30) cholesteryl ether can be advantageously used. Polyethylene glycol (25) soy- sterol has also been proven. As ethoxylated triglycerides, the polyethylene glycol (60) Evening Primrose Glycerides can advantageously be used (Evening Primrose = evening primrose).

It is furthermore advantageous to use the polyethylene glycol glycerol fatty acid esters from the group consisting of polyethylene glycol (20) glyceryl laurate, polyethylene glycol (21) glyceryl laurate, polyethylene glycol (22) glyceryl laurate, polyethylene glycol (23) glyceryl laurate, polyethylene glycol (6) glyceryl caprate / citrate, polyethylene glycol

(20) glyceryl oleate, polyethylene glycol (20) glyceryl isostearate, polyethylene glycol (18) glycerol (cocoate).

It is also favorable to use the sorbitan esters from the group consisting of polyethylene glycol (20) sorbitan monolaurate, polyethylene glycol (20) sorbitan monostearate, Polyethylene glycol (20) sorbitan monoisostearate, polyethylene glycol (20) sorbitan monopalmitate, polyethylene glycol (20) sorbitan monooleate.

As optional, but according to the invention optionally advantageous W / O emulsifiers can be used:

Fatty alcohols containing 8 to 30 carbon atoms, monoglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 8 to 24, in particular 12-18, carbon atoms, diglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids a chain length of 8 to 24, in particular 12-18 C-atoms, monoglycerol ethers of saturated and / or unsaturated, branched and / or unbranched alcohols of a chain length of 8 to 24, in particular 12-18 C-atoms, diglycerol ethers saturated and / or unsaturated, more branched and / or unbranched

Alkole a chain length of 8 to 24, in particular 12-18 C-atoms, propylene glycol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, in particular 12-18 C-atoms and sorbitan esters of saturated and / or unsaturated , branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, in particular 12-18 C-atoms.

Particularly advantageous W / O emulsifiers are glyceryl monostearate, glyceryl, glyceryl monomyristate, glyceryl monostearate, diglyceryl monostearate, Diglycerylmonoisostearat, propylene glycol, propylene glycol monoisostearate, Propyfenglycolmonocaprylat, propylene glycol, sorbitan, sorbitan, sorbitan, Sorbitanmonoisooleat, sucrose, cetyl alcohol, stearyl alcohol, arachidyl, behenyl, isobehenyl alcohol, selachyl alcohol, chimyl alcohol, polyethylene glycol (2) stearyl ether

(Steareth-2), glyceryl monolaurate, glyceryl monocaprinate, glyceryl mono- caprylate

Preparations preferred according to the invention are particularly suitable for protecting human skin against aging processes as well as against oxidative

Stress, ie against damage by radicals, such as by Solar radiation, heat or other influences are generated. It is present in various dosage forms commonly used for this application. Thus, it can be used in particular as a lotion or emulsion, such as cream or milk (O / W, W / O, O / W / O, W / O / W), in the form of oily-alcoholic, oily-aqueous or aqueous-alcoholic gels or solutions, be present as solid pins or formulated as an aerosol.

The preparation may contain cosmetic adjuvants which are commonly used in this type of preparation, e.g.

Thickening agents, emollients, humectants, surfactants, emulsifiers, preservatives, antifoaming agents, perfumes, waxes, lanolin, propellants, dyes and / or pigments which color the agent itself or the skin, and other ingredients commonly used in cosmetics.

It is possible to use as dispersion or solubilizing agent an oil, wax or other fatty substance, a low monoalcohol or a low polyol or mixtures thereof. Particularly preferred monoalcohols or polyols include ethanol, i-propanol,

Propylene glycol, glycerol and sorbitol.

A preferred embodiment of the invention is an emulsion which is present as a protective cream or milk and except the compound of the formula I, for example fatty alcohols, fatty acids, fatty acid esters, especially triglycerides of fatty acids, lanolin, natural and synthetic oils or waxes and emulsifiers Contains presence of water.

Further preferred embodiments are oily lotions based on natural or synthetic oils and waxes, lanolin, fatty acid esters, in particular triglycerides of fatty acids, or oily alcoholic lotions based on a lower alcohol such as ethanol or a glycerol such as propylene glycol and / or a polyol such as Glycerin, and oils, waxes and fatty acid esters, such as triglycerides of

Fatty acids. The preparation according to the invention may also be in the form of an alcoholic gel which comprises one or more lower alcohols or polyols, such as ethanol, propylene glycol or glycerol, and a thickening agent, such as silica. The oily-alcoholic gels also contain natural or synthetic oil or wax.

The solid sticks consist of natural or synthetic waxes and oils, fatty alcohols, fatty acids, fatty acid esters, lanolin and other fatty substances.

If a preparation is formulated as an aerosol, the customary propellants, such as alkanes, fluoroalkanes and chlorofluoroalkanes, are generally used.

Further objects of the present invention are a process for the preparation of a preparation, which is characterized in that at least one compound of the formula I is mixed with residues as described above with a cosmetically or dermatologically or food-suitable carrier, and the use of a compound of the formula I for the preparation of a preparation.

The preparations according to the invention can be prepared using techniques which are well known to the person skilled in the art.

The mixing may result in dissolution, emulsification or dispersion of the compound of the formula In the carrier.

Compounds of the formula I according to the invention can be obtained, for example, according to the following scheme:

The radicals R ³ , R ⁴ and R ⁶ in the above scheme are the radicals according to the invention as defined above or radicals according to the invention in which the reactive function, for example the hydroxy function, is blocked in a manner known to the person skilled in the art.

In a method preferred according to the invention, an alkyl ester of a chromene-4-one-carboxylic acid is reacted with an amine, preferably an n-alkylamine, such as butylamine, octylamine or dodecylamine, or a diamine, preferably 3-dimethylaminopropylamine. For the preparation of the ammonium salts according to the invention, the resulting amine D can be reacted, for example, with iodomethane. In this way, the compounds of the invention in an economical manner - can be obtained in a few stages with high yield. A corresponding method is therefore a further subject of the present invention.

The alkyl ester of the chromene-4-one-carboxylic acid of formula B can be prepared by the cyclization of an appropriately substituted o-hydroxyacetophenone A with a suitable ester under basic conditions. The reaction may be analogous to Kelly, T; Kim MH; J. Org. Chem. 1992, 57, 1593-97. Alternatively, the free hydroxy groups are acylated, followed by a Baker venkatamaran rearrangement in basic conditions followed by ring closure under acidic conditions. Corresponding reactions whose adaptation to the compounds desired here causes no problems for the skilled person are known from the patent application WO 2002/060889.

By customary reactions on the ring system or derivatization of the functional groups, further derivatives according to formula I can be obtained. The necessary reaction conditions for such

Reactions, such as, for example, oxidations, reductions, transesterifications, etherifications, are readily found by a person skilled in the art for such syntheses in the generally available literature on organic reactions.

It has also been found that compounds of the formula I can have a stabilizing effect on the preparation. When used in corresponding products, they therefore remain stable for longer and do not change their appearance. In particular, even with prolonged use or prolonged storage, the efficacy of the ingredients, e.g. Vitamins, received. Among other things, this is particularly advantageous in compositions for protecting the skin against the action of UV rays, since these cosmetics are exposed to particularly high levels of exposure to UV radiation.

The positive effects of compounds of the formula I result in their particular suitability for use in cosmetic or pharmaceutical preparations.

Equally positive are the properties of compounds of formula I for use in food or as food supplement! or as "functional food." The other explanations regarding foodstuffs apply mutatis mutandis to dietary supplements and functional foods. The foods which can be fortified according to the present invention with one or more compounds of formula I include all materials suitable for consumption by animals or for human consumption, for example vitamins and provitamins thereof, fats, minerals or amino acids , (The food can be solid but also liquid, so as a drink). Further objects of the present invention are accordingly the use of a compound according to formula I as a food additive for human or animal nutrition and preparations which are food or dietary supplements and corresponding

Carrier included.

Foodstuffs which can be enriched with one or more compounds of the formula I according to the present invention are, for example, also foods which consist of a single natural

Source such as sugar, unsweetened juice, nectar or puree from a single plant species, such as unsweetened apple juice (eg a mixture of different types of apple juice), grapefruit juice, orange juice, apple compote, apricot nectar, tomato juice, tomato sauce, tomato puree, etc. Further examples Foodstuffs which may be fortified with one or more compounds of formula I according to the present invention are the grain or cereals of a single plant species and materials made from such plant species, such as corn syrup, rye flour, wheat flour or oat bran. Also, mixtures of such foods are suitable to be fortified according to the present invention with one or more compounds of formula I, for example multi-vitamin preparations, mineral mixtures or sweetened juice. Further examples of foods which can be enriched with one or more compounds of the formula I according to the present invention are food preparations, for example prepared cereals, biscuits, mixed drinks, foods specially prepared for children, such as yoghurt, dietetic foods, low-calorie foods or animal feed, called. The foods which can be enriched according to the present invention with one or more compounds of formula I thus include all edible combinations of carbohydrates, lipids, proteins, inorganic elements, trace elements, vitamins, water or active metabolites of plants and animals.

The foods which can be fortified according to the present invention with one or more compounds of formula I are preferably administered orally, e.g. in the form of food, pills, tablets, capsules, powders, syrups, solutions or suspensions.

The foods of the invention enriched with one or more compounds of formula I may be prepared by techniques well known to those skilled in the art.

Due to their action compounds of formula I are also suitable as a drug ingredient. Compounds of the formula I can be used, for example, for the preventive treatment of inflammations and allergies of the skin and in certain cases for the prevention of certain types of cancer. In particular, compounds of the formula I are suitable for the preparation of a medicament for the treatment of inflammations, allergies and irritations, in particular of the skin. Furthermore, drugs can be produced in an action as a vein tonic, as an inhibitor of cuperose, as an inhibitor of chemical, physical or actinic erythema, as an agent for the treatment of sensitive skin, as

Decongestants, as a dehydrating agent, as a slimming agent, as an anti-wrinkle agent, as a stimulator of the synthesis of extracellular matrix components, as a skin elasticity improving agent and as an acidifying agent. Furthermore, in this connection, preferred compounds of the formula I show antiallergic and antiinflammatory and antiirritative effects. They are therefore suitable for the preparation of medicaments for the treatment of inflammation or allergic reactions. In the following the invention will be explained in more detail by means of examples. The invention can be carried out in the entire claimed range and is not limited to the examples mentioned here.

Examples

Example 1: Ethyl 4-oxo-4H-chromene-2-carboxylate Sodium (1.49 g, 65 mmol) is dissolved in absolute ethanol (100 ml). Diethyl oxalate (5.12 g, 35 mmol) and 2-hydroxyacetophenone (2.04 g, 15 mmol) are dissolved in absolute ethanol (10 ml) and added to the sodium ethoxide solution. The solution is stirred under reflux for 1 h. It is acidified with concentrated HCl. The white precipitate is filtered off and the yellow solution is concentrated. After extraction with ethyl acetate and drying over Na ₂ SO ₄ , a yellow solid is obtained. Recrystallization from methanol / diisopropyl ether (4: 1) yields white needles (3.20 g, 14.6 mmol, 98%).

MP: 63 ^° C; IR (KBr): v (cm ^-1 ) = 3447, 3067, 2985, 2938, 1734, 1647, 1466, 758; ¹ H-NMR (600 MHz, CDCl ₃ ): δ [ppm] = 1.43 (t, J = 7.1 Hz, 3 H, _CH3), 4:46 (q, J = 7.1 Hz, 2 H, CH _2), 7.11 (s, 1 H, H-3), 7:44 (ddd, J = 1.2 Hz, 7.1 Hz , 8.0 Hz, 1 H, H-6), 7.61 (ddd, J -0.4 Hz, 1.2 Hz, 8.5 Hz, 1 H, H-8), 7.74 (ddd, J = 1.7 Hz, 7.1 Hz, 8.5 Hz, 1 H, H-7), 8.20 (ddd, J = 0.4 Hz, 1.7 Hz, 8.0 Hz, 1 H, H-5); ¹³ C-NMR (150 MHz, CDCl _3): δ [ppm] = 14.1 ( +, CH ₃ ), 63.0 (-, CH ₂ ), 114.8 (+, C-3), 118.8 (+, C-8), 124.4 (C _quat , C-9), 125.7 (+, C-5) , 125.9 (+, C-6), 134.7 (+, CI), 152.2 (C _quab C-2), 156.0 (C _quat , C-10), 160.6 (C _quat , C = O), 178.4 (Cq _uat , C-4), MS (ESI-MS, EtOH / MeOH + 10 mmol / l NH ₄ OAc) m / z (%): 219 (100) [MH] ⁺ , elemental analysis: C ₁₂ Hi ₀ O ₄ CaIc : C 66.05; H 4.62; Found: C 66.07; H 4.72;

Example 2: 4-Oxo-4H-chromene-2-carboxylic acid butylamide

Ethyl 4-oxo-4H-cliromene-2-carboxylate from Example 1 (655 mg, 3 mmol) is dissolved in butylamine (658 mg, 9 mmol) and stirred at 50 ⁰ C for 10 minutes. The solution is evaporated and a yellow solid is obtained. Glacial acetic acid (5 ml) is added and stirred at 7O ⁰ C for 10 minutes. The mixture is poured into ice-water and the resulting white precipitate filtered off, washed with water and dried. Recrystallization of the white solid from ethyl acetate yields white needles (630 mg, 2.6 mmol, 86%).

MP: 130 ^° C; IR (KBr): v (cm ^-1 ) = 3319, 3079, 2954, 2868, 1685, 1642, 1387, 755, UV / VIS (MeOH): λ _max [nm] (log ε) = 202 (4.37), 236 (29.4), 305 (3.85); ¹ H-NMR (300 MHz, DMSO): δ [ppm] = 0.91 (t, J = 7.2 Hz, 3 H, _CH3), 1:34 (qd, J = 7.2 Hz , 14.1 Hz, 2 H, CH ₂ ), 1.54 (XX, J = 7.2 Hz, 2 H, CH ₂ ), 3.30 (q, J = 7.2 Hz, 2 H, CH ₂ ), 6.82 (s, 1 H, H- 3), 7.53 (ddd, J = 1.0Hz, 7.1Hz, 8.0Hz, 1H, H-6), 7.73 (dd, J = 1.0Hz, 8.5Hz, 1H, H-8), 7.89 ( ddd, J = 1.7 Hz, 7.1 Hz, 8.5 Hz, 1 H, H-7), 8.05 (dd, 1.7 Hz, 8.0 Hz, 1 H, H-5), 9.10 (t, J = 5.6 Hz, 1 H ¹³ C-NMR (75 MHz, DMSO): δ [ppm] = 13.6 (+, CH ₃ ), 19.5 (-, CH ₂ ), 30.8 (-, CH ₂ ), 38.8 (-, CH ₂ ), 110.2 (-, C-3), 118.7 (+, C-8), 123.5 (C _quat , C-9), 124.8 (+, C-5), 125.9 (+, C-6), 134.9 ( +, C-7), 155.0 (C _quβb C-2), 155.7 (C _quat , C-10), 158.7 (C _quat , C = O), 177.2 (Cq _Uat , C-4), MS (CI- MS, NH ₃₎ m / z (%): 263.1 (100) [m + NH _3] ^+, 246.1 (26) [MH] ⁺ Elemental analysis: C ₁₄ Hi ₅ NO ₃ CAIC: C 68.56; H 6.16; N 5.71; Found: C 68 .58; H 6.04; N 5.61;

Example 3: 4-Oxo-4H-chromene ~ 2-carboxylic acid octylamide

Ethyl 4-oxo-4H-ClxiOmen-2-carboxylate from Example 1 (655 mg, 3 mmol) and octylamine (1163 mg, 9 mmol) are dissolved in dichloromethane (5 ml) and stirred at reflux for 10 minutes. The solution is evaporated and a light yellow solid obtained. Glacial acetic acid (5 ml) is added and stirred at 70 ° C for 10 minutes. The mixture is poured into ice-water and extracted with ethyl acetate. The organic layer is dried over Na ₂ SO ₄ and a yellow solid is obtained. Recrystallization from ethyl acetate yields white needles (826 mg, 2.7 mmol, 91%).

MP: 131 ^° C .; IR (KBr): v (cm ^-1 ) = 3314, 2927, 2849, 1684, 1646, 1529, 1392, 751, UV / VIS (MeOH): λ _max [nm] (log ε) = 202 (4.36), 236 (29.4), 305 (3.84); ¹ H-NMR (300 MHz, CDCl _3): δ [ppm] = 0.85 - 0.91 (m, 3 H, _CH3), 1:24 to 1:46 (m, 10 H, 5 x CH ₂ ), 1.61-1.72 (m, 2H, CH ₂ ), 3.49 (tq, J = 6.2 Hz, 7.2 Hz, 2H, CH ₂ ), 6.91 (s, IH, NH), 7.16 (s, 1 H, H-3), 7.45 (ddd, J = 1.0 Hz, 7.2 Hz, 8.1 Hz, 1 H, H-6), 7.52 (dd, J-0.5 Hz, 8.5 Hz, 1 H, H-8) , 7.73 (ddd, J = 1.7 Hz, 7.2 Hz, 8.5 Hz ₅ 1 H ₅ H-7), 8.22 (dd, J = 1.7 Hz, 8.0 Hz, 1 H, H-5); ¹³ C NMR (75 MHz, CDCl ₃ ): δ [ppm] = 14.1 (+, CH ₃ ), 22.6 (-, CH ₂ ), 26.7 (-, CH ₂ ), 27.0 (-, CH ₂ ), 29.1 (-, CH ₂ ) , 29.2 (-, CH ₂ ), 29.5 (-, CH ₂ ), 31.8 (-, CH ₂ ), 40.1 (-, CH ₂ ), 112.1 (+, C-3), 118.0 (+, C-8) , 124.4 (C _quat5 C-9), 126.0 (+, C-5), 126.2 (+, C-6), 134.5 (+, C-7), 154.8 (C _qU a _t , C-2), 155.3 (C _qua t, C-10), 159.2 (C _quat , C = O), 178.2 (C _quat5 C-4), MS (CI-MS, NH ₃ ) m / z (%): 319.1 (100) [ M + NH ₃ ] ⁺ , 302.1 (40) [MH] ⁺ , Ele commentary analysis: C ₁₈ H ₂₃ NO ₃ CAIC: C 71.73; H 7.69, N 4.65; Found: C 71.62; H 7.58, N 4.43;

Example 4: 4-Oxo-4H-chromene-2-carboxylic acid dodecylamide

Ethyl 4-oxo-4H-cliromene-2-carboxylate from Example 1 (1.96 g, 9 mmol) and dodecylamine (5.0 g, 27 mmol) are dissolved in dichloromethane (10 ml) and stirred at reflux for 10 minutes. The solution is evaporated and a light yellow solid obtained.

Glacial acetic acid (10 ml) is added and stirred at 70 ⁰ C for 10 minutes. The mixture is in

Added ice-water and extracted with ethyl acetate. The organic layer is over

Na ₂ SO ₄ dried and a yellow solid obtained. Recrystallization from ethyl acetate yields white needles (2.30 g, 6.4 mmol, 71%).

MP: 108 ^° C; IR (KBr): v (cm ^-1 ) = 3319, 2959, 2932, 2850, 1982, 1642, 1522, 1387, 753; UV / VIS (MeOH): λ _max [nm] (log ε) = 203 (4.37 , 236 (4.29), 305 (3.83), ¹ H-NMR (300 MHz, DMSO): δ [ppm] = 0.83 (t, J - 6.7 Hz, 3 H, CH ₃ ), 1.16 - 1.33 (m, 18 H, 9 x CH _2), 1:48 - 1.60 (m, 2 H, CH _2), 3.28 (m, 2 H, CH _2), 6.81 (s, IH, H-3), 7:53 (ddd, J = 1.0 Hz, 7.2 Hz, 8.0 Hz, 1 H, H-6), 7.73 (dd, J = 0.6 Hz, 8.5 Hz, 1 H, H-8), 7.89 (ddd, J = 1.7 Hz, 7.2 Hz, 8.5 Hz, 1 H, HT), 8:05 (dd, J = 1.7 Hz, 8.0 Hz, 1 H, H-5), 9.12 (t, J = 5.8 Hz, 1 H, NH); ¹³ C-NMR (75 MHz , DMSO): δ [ppm] = 13.8 (+, CH ₃ ), 22.0 (-, CH ₂ ), 26.3 (-, CH ₂ ), 28.6 (-, CH ₂ ), 28.7 (-, CH ₂ ), 28.8 (-, CH ₂ ), 28.9 (-, CH ₂ ), 28.9 (-, CH ₂ ), 28.9 (-, CH ₂ ), 31.2 (-, CH ₂ ), 39.2 (-, CH ₂ ), 39.4 (- , CH _2), 110.2 (+, C-3), 118.7 (+, C-8), 123.5 (C _qua t, C-9), 124.8 (+, C-5), 125.9 (+, C-6 ), 134.9 (+, C-7), 155.0 (C _Quab C-2), 155.7 (C _quat, C-10 _uat), 158.7 (Cq, C = O), 177.2 (C _quat, C-4); MS (CI-MS, NH ₃₎ m / z (%): 375.2 ( 100) [M + NH ₃ ] ⁺ , 358.2 (56) [MH] ⁺ ; Elemental analysis: C ₂₂ H ₃₁ NO ₃ CAIC: C 73.92; H 8.74; N 3.92; Found: C 73.75; H 8.75; N 3.74; Example 5:

4 ~ oxo-4H-chromene-2-carboxyi acid (3-dimethylamino-propyl) -amide

Etyl-4-oxo-4H-cliromene-2-carboxylate (655 mg, 3 mmol) and 3-dimethylamino-propylamine (920 mg, 9 mmol) are dissolved in dichloromethane (5 ml) and stirred at reflux for 20 minutes. The solution is evaporated, glacial acetic acid (5 ml) added and the

Solution stirred at 70 ° C for 10 minutes. The mixture is poured into ice water and washed with

Extracted ethyl acetate. The organic layer is dried over Na ₂ SO ₄ and a yellow

Obtained solid. Recrystallization from ethyl acetate yields white needles (691 mg, 2.5 mmol, 84%).

MP: 125 ^° C; IR (KBr): v (cm ^-1 ) = 3289, 2976, 2946, 2805, 1686, 1640, 1534, 1460, 1392, 759, UV / VIS (MeOH): λ _max [nm] (log ε) = 203 (4.37), 236 (4.29), 305 (3.84), ¹ H-NMR (300 MHz, DMSO): δ [ppm] = 1.69 (p, J = 6.9 Hz, 2H, CH ₂ ), 2.15 (s, 6 H, 2 x CH ₃ ), 2.28 (t, J - 6.9 Hz, 2 H, CH ₂ ), 3.33 (dd, J = 7.2 Hz, 12.7 Hz, 2 H, CH ₂ ), 6.82 (s, 1 H , H-3), 7.53 (ddd, J = 1.0 Hz, 7.2 Hz, 8.0 Hz, 1 H, H-6), 7.71 (dd, J = 0.7 Hz, 8.5 Hz, 1 H, H-8), 7.89 (ddd, J = 1.7Hz, 7.2Hz, 8.5Hz, 1H, H-7), 8.05 (dd, J = 1.7Hz, 8.0Hz, 1H, H-5), 9.25 (t, J = 5.5Hz , 1 H, NH); ¹³ C-NMR (75 MHz, DMSO): δ [ppm] = 26.4 (-, CH ₂ ), 38.0 (-, CH ₂ ), 45.1 (+, 2 x CH ₃ ), 56.9 (-, CH ₂ ), 110.2 (+, C-3), 118.6 (+, C-8), 123.5 (C _quat , C-9), 124.9 (+, C-5), 125.9 (+, C-) 6), 134.9 (+, C-7), 155.0 (C _quatj C-2), 155.6 (C _quat , C-10), 158.7 (Cquat, C = O), 177.2 (C _quat , C-4); MS (PI-EIMS) m / z (%): 58.1 (100) [Me ₂ N = CH ₂ J ⁺ , 274.1 (11) [M] ^{+ '} ; Elemental Analysis: C ₁₅ H ₁₈ N ₂ O ₃ CaIc: C 65.68; H 6.61; N 10.21 Found: C 65.63; H 6.41; N 10.08;

Example 6: Trimethyl {3 - [(4-oxo-4H-chromene-2-carbonyl) -amino] -propyl-ammonium-iodide

Iodomethane (260 mg, 1.83 mmol) is dissolved in chloroform (5 mL) and poured into a solution of 4-oxo-4H-chromene-2-carboxylic acid (3-dimethylamino-propyl) -amide from Example 5 (500 mg, 1.82 mmol ) in chloroform (5 ml). The solution is stirred at room temperature for 30 minutes and then under reflux for 15 minutes to form a precipitate. The yellow precipitate is filtered off and washed with chloroform to give a yellow solid (578 mg, 1.39 mmol, 76%).

MP: 240 ° C +; IR (KBr): v (cm ^-1 ) - 3404, 3022, 2956, 1673, 1643, 1458, 740, UV / VIS (CH ₃ CN): λ _max [μm] (log ε) = 204 (4.62), 246 (4.43), 304 (3.83); ¹ H-NMR (300 MHz, DMSO): δ [ppm] = 1.95 - 2.06 (m, 2H, CH ₂ ), 3.07 (s, 9H, 3 x CH ₃ ), 3.34 - 3.44 (m, 6H, 2 x CH ₂ ), 6.86 (s, 1H, H-3), 7.55 (ddd, J = 1.0 Hz, 7.2 Hz, 8.0 Hz, 1H, H-6 ), 7.75 (d, J = 8.5 Hz, 1 H, H-8), 7.92 (ddd, J = 1.7 Hz, 7.2 Hz, 8.5 Hz, 1 H, YL-T), 8.06 (dd, J = 1.7 Hz , 8.0 Hz, 1 H, H-5), 9.25 (t, J = 5.9 Hz, 1 H, NH); ¹³ C-NMR (75 MHz, DMSO): δ [ppm] = 22.6 (-, CH ₂ ) , 36.3 (-, CH ₂ ), 52.1 (+, CH ₃ ), 52.2 (+, CH ₃ ), 52.2 (+, CH ₃ ), 63.2 (-, CH ₂ ), 110.5 (+, C-3), 118.6 (+, C-8), 123.5 (C _quat , C-9), 124.9 (+, C-5), 126.0 (+, C-6), 135.0 (+, C-7), 155.0 (C _qua t, C-2), 155.4 (C _quat , C-10), 159.2 (C _quat , C = O), 177.2 (C _quat , C-4), MS (ESI, H ₂ O / AcN) m / z (%): 289.0 (100) [K] ⁺ Elemental analysis: C ₁₆ H ₂₁ N ₂ O ₃ I CAIC: C 46.17 H 5:08 N 6.73; Found: C 45.79; H 4.70; N 6:51;

Example 7: Ethyl 7-hydroxy-4-oxo-4H-chromene-2-carboxyIate

Sodium (1.84 g, 80 mmol) is dissolved in absolute ethanol (100 ml). Diethyl oxalate (7.31 g, 50 mmol) and 2,4-dihydroxyacetophenone (2.28 g, 15 mmol) are dissolved in absolute ethanol (10 mL) and added to the sodium ethoxide solution. The solution is stirred under reflux for 1 h. It is acidified with concentrated HCl. The white precipitate is filtered off and the yellow / brown filtrate is concentrated. After extraction with ethyl acetate, drying over Na ₂ SO ₄ , a bright orange solid is obtained. Recrystallization from methanol / diisopropyl ether (3: 1) yields white needles (2.78 g, 12 mmol, 79%).

MP: 210-211 ° C; IR (KBr): v ^{(cm -1)} = 3521, 3109, 1742, 1640, 1601, 1570, 1456, 1253, 829; UV / VIS (MeOH): λ _max [im] (log ε) = 211 (4.44), 239 (4.24), 313 (3.96); ¹ H-NMR (600 MHz, DMSO): δ [ppm] = 1.34 (t, J = 7.1 Hz, 3 H, CH ₃ ), 4.37 (q, J = 7.1 Hz, 2 H, CH ₂ ), 6.82 ( s, 1H, H-3), 6.90 (d, J = 2.2Hz, 1H, H-8), 6.96 (dd, J = 2.2Hz, 8.7Hz, 1H, H-6), 7.89 (i.e. , J = 8.7 Hz, 1H, H-5), 11.02 (s, 1H, OH); ¹³ C-NMR (150 MHz, DMSO): δ [ppm] = 13.8 (+, CH ₃ ), 62.5 (-, CH ₂ ), 102.4 (+, C-8), 113.6 (+, C-3), 115.8 (+, C-6), 116.6 (C _q uat, C-9), 126.7 (+, C-5), _(quat C, C-2), 151.5 _(quat C, C-10), 157.1, 159.9 (C _quat , C = O), 163.5 (C _quat , C-7), 176.1 (C _quat , C-4); MS (EI-MS, 70 eV) m / z (%): 234.1 (100) [M] ^{+ '} ; HRMS (Ci ₂ H ₁₀ Os) ^{+ '} CaIc: 234.0528; Found: 234.0528 ± 0.76 ppm; Elemental Analysis: C ₁₂ Hi ₀ O ₅ CaClc: C 61.54; H 4.30; Found: C 60.97; H 4.21;

Example 8: 7-Hydroxy-4-oxo-4H-chromene-2-carboxylic acid-butylamide

Ethyl 7-hydroxy-4-oxo-4H-CliiOmen-2-carboxylate (585 mg, 2.5 mmol) and butylamine (512 mg, 7 mmol) are dissolved in dichloromethane (10 ml) and stirred at reflux for 10 minutes. The solution is evaporated and a light yellow solid obtained. Glacial acetic acid (10 ml) is added and stirred at 7O ⁰ C for 10 minutes. The mixture is poured into ice-water. The precipitate is filtered off, washed with water and dried. Recrystallization from ethyl acetate / diisopropyl ether (4: 1) gives a brown solid (573 mg, 2.2 mmol, 88%).

MP: 240 ⁰ C +; IR (KBr): v (a ¹ ) = 3340, 3195, 3081, 2960, 2875, 1639, 1618, 1394, 829; UV / VIS (MeOH): λ _max [nm] (log ε) = 211 (4.41), 238 (4.31), 307 (3.98); ¹ H-NMR (300 MHz, DMSO): δ [ppm] = 0.90 (t, J = 7.2 Hz, 3 h, CH ₃ ), 1.32 (qd, J = 7.2 Hz, 14.2 Hz, 2 H, CH ₂ ) , 1.47 - 1.58 (m, 2 H, CH ₂ ), 3.28 (dd, J = 6.9 Hz, 13.2 Hz, 2 H, CH ₂ ), 6.69 (s, 1 H, H-3), 6.94 (dd, J = 2.3Hz, 8.7Hz, 1H, H-6), 6.99 (d, J = 2.2, 1H, H-8), 7.88 (d, J = 8.7Hz, 1H, H-5), 9.06 ( t, J - 5.8 Hz, NH), 10.98 (s, 1H, OH); ¹³ C-NMR (75 MHz, DMSO): δ [ppm] = 13.6 (+, CH ₃ ), 19.5 (-, CH ₂ ), 30.9 (-, CH ₂ ), 38.8 (-, CH ₂ ), 102.6 ( +, C-8), 110.1 (+, C-3), 115.6 (+, C-6), 116.4 (C _quat , C-9), 126.6 (+, C-5), 155.1 (C _quat , C -2), 156.9 (C _quat , C-10), 158.8 (C _quat , C = O), 163.1 (C _quat , C-7), 176.3 (C _quat , C-4); MS (CI-MS, NH ₃₎ m / z (%): 262.2 (100) [MH] ^+; Elemental analysis: C ₁₄ H ₁₅ NO ₄ CaIc: C 64.36; H 5.79; N 5.36; Found: C 64.12; H 5.48; N 5.11;

Example 9: 7-hydroxy-4-oxo-4H-ChiOmen-2-carboxylic acid octylamide

Ethyl 7-hydroxy-4-oxo-4H-chromene-2-carboxylate (585 mg, 2.5 mmol) and octylamine (905 mg, 7 mmol) are dissolved in dicliloromethane (10 ml) and stirred at reflux for 10 minutes. The solution is evaporated and a brown solid is obtained. Glacial acetic acid (10 ml) is added and stirred at 7O ⁰ C for 10 minutes. The mixture is poured into ice-water and a precipitate is obtained, which is filtered off, washed with water and dried. Recrystallization from ethyl acetate provides a white solid (642 mg, 2.0 mmol, 81%).

MP: 215 ⁰ C; IR (KBr): v (cm ^-1 ) = 3256, 3155, 2947, 2919, 2853, 1634, 1598, 1530, 1388, 1242, 838 UV / VIS (MeOH): λ _max [μm] (log ε) = 210 (4.44), 238 (4.33), 308 (3.99), ¹ H-NMR (600 MHz, DMSO): δ [ppm] = 0.84 (t, J = 6.7 Hz, 3 H, CH ₃ ), 1.20 - 1.31 (m, 10 H, 5 x CH ₂ ), 1.50 - 1.56 (m, 2 H, CH ₂ ), 3.27 (dd, J = 6.7 Hz, 13.4 Hz, 2 H, CH ₂ ), 6.69 (s, 1 H, H-3), 6.94 (dd, J = 1.9 Hz, J = 8.7 Hz, 1H, H-6), 6.99 (d, J = 1.9 Hz, 1H, H-8), 7.88 (d, J = 8.7 Hz, 1 H, H-5), 9:03 (t, J = 5.5 Hz, 1 H, NH), 10.96 (s, 1 H, OH); ¹³ C-NMR (150 MHz, DMSO): δ [ppm] = 13.8 (+, CH ₃ ), 22.0 (-, CH ₂ ), 26.3 (-, CH ₂ ), 28.5 (-, CH ₂ ), 28.6 (-, CH ₂ ), 28.7 (-, CH ₂ ), 31.1 (-, CH ₂ ), 39.1 (-, CH ₂ ), 102.6 (+, C-8), 110.1 (+, C-3), 115.6 (+, C-6), 116.4 (C _quab C -9), 126.6 (+, C-5), 155.1 (C _Quab C-2), 156.9 (C _qua t, C-10), 158.8 (C _Quab C = O), _uat 163.1 (Cq, CI), 176.2 (C _quat , C-4), MS (ESI, DCM / MeOH + 10 mmol / l NH ₄ Ac) m / z (%): 318.1 (100) [MH] ⁺ , elemental analysis: C ₁₈ H ₂₃ NO ₄ CaClc: C 68.12; H 7.30; N 4.41; Found: C 67.85; H 7.30; N 4.24;

Example 10: 7-Hydroxy-4-oxo-4H-chromene-2-carboxylic acid (3-dimethylamino-propyl) -amide

Ethyl 7-hydroxy-4-oxo-4H-cliromene-2-carboxylate (1.17 g, 5 mmol) and 3-dimemylammopropylamine (1.53 g, 15 mmol) are dissolved in dichloromethane (10 ml) and stirred at reflux for 1 h. The solution is evaporated, glacial acetic acid (10 ml) added and stirred at 7O ⁰ C for 10 minutes. The mixture is poured into ice-water and extracted with ethyl acetate. The aqueous layer is neutralized with sodium bicarbonate and extracted with ethyl acetate. The aqueous layer is basified with sodium carbonate and extracted with ethyl acetate. The aqueous layer is acidified with concentrated HCl and then dried. A yellow solid is obtained. The yellow solid is added to methanol and a white solid is crystallized. The yellow filtrate is dried and repeatedly dissolved in methanol until no white solid crystallizes out. The yellow crude solution is evaporated and a yellow solid is obtained, which is dissolved in boiling ethanol, filtered off and dried, yielding a yellow solid (1.37 g, 4.7 mmol, 94%).

MP: 240 ⁰ C +; IR (ICBr): v (a ¹ ) = 3455, 3273, 3064, 2999, 1683, 1650, 1619, 1548, 1468, 1272, 786; UV / VIS (MeOH): λ _max [nm] (log ε) = 210 (3.92) 237 (3.80) 307 (3:46); ¹ H-NMR (300 MHz, DMSO): δ [ppm] = 2.00 (t, J - 7.2 Hz, 2H, CH ₂ ), 2.72 (s, 6H, 2 x CH ₃ ), 2.89 (t, J = 7.2 Hz, 2 H, CH _2), 3:02 to 3:18 (m, 2 H, CH _2), 6.72 (s, 1 H, H-3) 7.00 (dd, J = 2.2 Hz, 8.8 Hz, 1 H , H-6), 7.16 (d, J = 2.2 Hz, 1 H, H-5), 7.86 (d, J = 8.8 Hz, 1 H, H-8), 9.40 (t, J = 5.9 Hz, 1 H, NH), 11.36 (s, 1H, OH); ¹³ C-NMR (75 MHz, DMSO): δ [ppm] = 21.8 (-, CH ₂ ), 36.0 (-, CH ₂ ), 41.8 (+, 2 x N-CH ₃ ), 53.3 (-, CH ₂ ), 102.7 (+, C-8), 110.2 (+, C-3), 115.8 (+, C-6), 116.3 (C _quat , C-9), 126.5 (+, C-5), 154.8 ( C _quab C-2), 156.9 (C _quat , C-10), 159.2 (C _quat , C = O), 163.4 (C _quat , C-7), 176.3 (C _quab C-4); MS (ESI, DCM / MeOH + 10 mmol / l NH ₄ Ac) m / z (%): 291.1 (100) [MH] ⁺ ; HRMS (Ci ₅ Hi ₈ N ₂ O ₄ ^ ^' CaIc: 290.1266; Found: 290.1266 ± 0.7 ppm; Example 11:

{3 - [(7-Hydroxy-4-oxo-4H-chromene-2-carbonyl) -eamino] -propyl} -trimethyl-ammonium iodide

Add 7-hydroxy-4-oxo-4H-ChiOmen-2-carboxylic acid (3-dimethylamino-propyl) -amide (436 mg, 1.5 mmol) in acetonitrile (30 ml) containing sodium carbonate (415 mg, 5 mmol). , Iodomethane (227 mg, 1.6 mmol) is added to the solution and stirred overnight at room temperature. The mixture is dried and resuspended in methanol. A white precipitate is drained off, the resulting yellow liquid is dried and a yellow solid is obtained (439 mg, 1 mmol, 68%).

MP: 240 ⁰ C +; IR (KBr): v ^{(cm -1)} = 3445, 3266, 3064, 2979, 1681, 1645, 1252, 832; ¹ H-NMR (300 MHz, DMSO): δ [ppm] - 1.90 - 2.02 (m, 2H, CH ₂ ), 3.07 (s, 9H, 3 x CH ₃ ), 3.27 - 3.40 (m, 4H , 2 x CH ₂ ), 6.66 (s, 1 H, H-3), 6.80 (d, J - 2.2 Hz, 1 H, H-8), 6.83 (dd, J = 2.2 Hz, 8.6 Hz, 1 H , H-6), 7.79 (d, J = 8.6Hz, 1H, H-5), 9.15 (t, J = 5.9Hz, 1H, NH); ¹³ C-NMR (75 MHz, DMSO): δ [ppm] = 22.7 (-, CH ₂ ), 36.2 (-, CH ₂ ), 52.1 (+, 3 x N-CH ₃ ), 63.2 (-, CH ₂ ), 102.3 (+, C-8), 110.2 (+, C-3), 114.5 (C _quat , C-9), 117.2 (+, C-6), 126.2 (+, C-5), 154.3 ( C _quat , C-2), 157.4 (C _quat , C-10), 159.4 (C _quat , C = O), 167.1 (C _quab C-7), 175.9 (C _quat , C-4); MS (ESI, H ₂ O / AcN) m / z (%): 305.0 (100) [M] ⁺ ; HRMS (Ci ₆ H ₂ iN ₂ O ₄ ) ⁺ CaIc: 305.1501; Found: 305,1500 ± 1.23ppm;

Example 12: EthyIl-7-methoxy-4-oxo-4H-chromene-2-carboxylate

Sodium (1.49 g, 65 mmol) is dissolved in absolute ethanol (100 ml). diethyl

(5.12 g, 35 mmol) and 2-hydroxy-4-methoxyacetophenone (2.49 g, 15 mmol) are dissolved in absolute ethanol (10 mL) and added to the sodium ethanolate solution. The

The solution is stirred under reflux for 1 h. It is acidified with concentrated HCl. The white precipitate is filtered off and the yellow solution is concentrated. After extraction with ethyl acrylate, drying over Na ₂ SO ₄ , a yellow solid is obtained.

Recrystallization from methanol / diisopropyl ether (4: 1) gives a yellow solid (3.65 g, 14.7 mmol, 98%).

MP: 109 ^° C; IR (KBr): v (cm ^-1 ) = 3459, 3110, 2997, 2856, 1742, 1664, 1628, 1442, 1258, 838; UV / VIS (MeOH): λ _max [ran] (log ε) = 212 (4.44), 238 (4.29), 310 (4.01), ¹ H-NMR (300 MHz, DMSO): δ [ppm] = 1.34 (t, J = 7.1 Hz, 3 H, CH ₃ ), 3.91 (s, 3 H, 0-CH ₃ ), 4.38 (q, J = 7.1 Hz, 2 H, CH ₂ ), 6.85 (s, 1 H, H-3), 7.07 (dd, J = 2.4 Hz, 8.9 Hz, 1 H, H-6), 7.19 (d, J = 2.4Hz, 1H, H-8), 7.91 (d, J = 8.9Hz, 1H, H-5); ¹³ C NMR (75 MHz, DMSO ): δ [ppm] = 13.8 (+, CH ₃ ), 56.2 (+, O-CH ₃ ), 62.5 (-, CH ₂ ), 100.8 (+, C-8), 113.8 (+, C-3) , 115.6 (+, C-6), 117.5 (C _quat , C-9), 126.7 (+, C-5), 151.5 (C _quat , C-2), 157.1 (C _quat , C-10), 159.9 (C _quat , C = O), 163.5 (C _quat , C-7), 176.1 (C _quat) C-4), MS (EI-MS, 70 eV) m / z (%): 248.1 (100) [ M] ^{+ 'Elemental} analysis: C ₁₃ H ₁₂ O ₅ CAIC: C 62.9; H 4.87; Found: C 62.67; H 4.67;

Example 13: 7-Methoxy-4-oxo-4H-chromene-2-carboxylic acid butylamide

Ethyl 7-methoxy-4-oxo-4H-ChiOmen-2-carboxylate (590mg, 2.4mmol) and butylamine (512mg, 7mmol) are dissolved in dichloromethane (10ml) and stirred at reflux for 10 minutes. The solution is evaporated and a light yellow solid obtained. Glacial acetic acid (10 ml) is added and stirred at 70 ⁰ C for 10 minutes. The mixture is poured into ice-water, the precipitate filtered off, washed with water and dried. Recrystallization from dichloroethane / diisopropyl ether (1: 1) yields white needles (562 mg, 2.0 mmol, 86%).

MP: 130 ^° C; IR (KBr): v (cm- ¹ ) = 3349, 2959, 2869, 1655, 1610, 1357, 843; UV / VIS (MeOH): λ _max [nm] (log ε) = 212 (4.42), 236 (4.35), 255 (sh 4.10), 304 (4.04); ¹ H-NMR (300 MHz, CDCl ₃ ): δ [ppm] = 0.97 (t, J = 7.3 Hz ₅ H 3, CH ₃ ), 1.43 (qd, J = 7.3 Hz, 14.4 Hz, 2 H, CH ₂ ), 1.64 (td, J = 7.3 Hz, 14.9 Hz, 2 H, CH _2), 3:48 (dd, J = 6.9 Hz, 13.4 Hz, 2 H, CH _2), 3.91 (s, 3 H, 0-CH ₃ ), 6.89 (d, J = 2.3Hz, 1H, H-8), 6.99 (dd, J = 1.9Hz, 8.9Hz, 1H, H-6), 7.09 (s, 1H, H-3 ), 8.10 (d, J = 8.9 Hz, 1H, H-5); ¹³ C-NMR (75 MHz, CDCl _3): δ [ppm] = 13.8 (+, CH _3), 20.1 (- CH _2), 31.5 (- CH _2), 39.8 (- CH _2), 56.0 (+, 0-CH _3), 100.4 (+, C-8), 112.2 (+, C-3), 115.0 (+, C-6), 118.2 (C _quat) C-9), 127.4 (+, C-5), 154.6 (cqua _t, C-2), 157.0 (C _quat, C-IO), _quat 159.3 (C, C = O), _quat 164.7 (C, C-7), 177.5 (C _quat, C-4); MS (CI-MS, NH ₃₎ m / z (%): 276.2 (100) [MH] ^+; Elemental analysis: C ₁₅ H _n CAIC NO _4: C 65.44; H 6.22; N 5.09; Found: C 65.43; H 5.82; N 4.91;

Example 14 7-Methoxy-4-oxo-4H-chroraen-2-carboxylic acid (3-dimethylamino-propyl) -amide

Ethyl 7-methoxy-4-oxo-4H-cliromene-2-carboxylate (620 mg, 2.5 mmol) and

Dissolve 3-dimethylaminopropylamine (766 mg, 7.5 mmol) in dichloromethane (10 mL) and stir the mixture at reflux. The solution is evaporated, glacial acetic acid (10 ml) added and the solution stirred at 70 ^° C. for 10 minutes. The mixture is poured into ice-water and extracted with ethyl acetate. The aqueous layer is washed with

Sodium bicarbonate neutralized and extracted with ethyl acetate. The aqueous layer is basified with sodium carbonate and extracted with ethyl acetate. The organic layer is dried over Na ₂ SO ₄ and evaporated to give a yellow solid (654 mg, 2.1 mmol, 86%).

MP: 127 - 128 ⁰ C; IR (ICBr): v (cm ^-1 ) = 3440, 3257, 3032, 2950, 1667, 1630, 1442, 845; ¹ H-NMR (300 MHz, CDCl ₃ ): δ [ppm] = 1.79 (td, J = 5.9 Hz, 11.8 Hz, 2H ₅ CH ₂ ), 2.36 (s, 6H, 2 x CH ₃ ), 2.51 - 2.58 (m, 2H, CH ₂ ), 3.58 (td, J = 5.2 Hz, 5.9 Hz, 2H, CH ₂ ), 3.91 (s, 3H, 0-CH ₃ ), 6.80 (d, J = 2.3Hz, 1H, H-5), 6.99 (dd, J = 2.3Hz, 8, 9 Hz, H-6), 7:05 (s, 1 H, H-3), 8.11 (d, J = 8.9 Hz, 1 H, H-8), 9.28 (s, 1 H, NH); ¹³ C- NMR (75 MHz, CDCl ₃ ): δ [ppm] = 24.8 (-, CH ₂ ), 40.6 (-, CH ₂ ), 45.6 (+, 2 x N-CH ₃ ), 55.8 (+, 0-CH ₃ ), 59.2 (-, CH ₂ ), 100.5 (+, C-8), 111.8 (H, C-3), 114.5 (+, C-6), 118.3 (C _quat) C-9), 127.5 ( +, C-5), 155.1 (Cquat, C-2), 157.1 (Cquat, C-10), 159.2 (Cquat, C = O), 164.6 (Cquat, C-7), 177.7 (Cquat, C-4 );

MS (ESI, H ₂ O / AcN) m / z (%): 305.0 (100) [MH] ⁺ ; HRMS (Ci ₆ H ₂₀ N ₂ O ₄ ) ^"1"" CaIc: 304.1423; Found: 304.1421 ± 0.44 ppm;

Example 15:

{3 - [(7-Methoxy-4-oxo-4H-chromene-2-carbonyl) -amino] -propyl} -trimethyl ammonium iodide

Dissolve 7-methoxy-4-oxo-4H-ChiOmen-2-carboxylic acid (3-dimethylamino-propyl) -amide (456 mg, 1.5 mmol) dissolved in chloroform (10 ml), iodomethane (284 mg, 2 mmol) and the mixture was stirred at room temperature. The solution is heated at reflux for 10 minutes, the precipitate filtered off and washed with chloroform. The precipitate is dried to give a white solid (575 mg, 1.3 mmol, 86%).

MP: 208 ^° C (decomposition); IR (KBr): v (cm ^-1 ) = 3490, 3411, 3257, 3012, 2954, 1676, 1633, 1604, 1442, 848 UV / VIS (CH ₃ CN): λ _max [nm] (log ε) = 210 (4.47), 242 (4.32), 304 (3.80), ¹ H-NMR (600 MHz, DMSO): δ [ppm] = 1.97 - 2.03 (m, 2 H, CH ₂ ), 3.07 (s, 9 H, 3 x CH _3), 3:35 to 3:39 (m, 2 H, CH _2), 3:36 to 3:41 (m, 2 H, CH _2), 3.93 (s, 3 H, _0-CH3), 6.78 (s , 1 H, H-3), 7.13 (dd, J = 2.4 Hz, 8.9 Hz, H-6), 7.18 (d, J = 2.4 Hz, 1 H, H-8), 7.97 (d, J = 8.9 Hz, 1H, H-5), 9.19 (s, 1H, NH), ¹³ C-NMR (150 MHz, DMSO): δ [ppm] = 22.7 (-, CH ₂ ), 36.3 (-, CH ₂ ), 52.2 (+, 3 x _N-CH3), 56.1 (+, 0-CH _3), 63.3 (- CH _2), 100.8 (+, C-8), 110.6 (+, C-3). 115.3 (+, C-6), 117.5 (C- _quat , C-9), 126.5 (+, C-5), 155.1 (C- _quat; C-2), 156.9 (C- _quat; C-10), 159.3 ( Cquat, C = O), 164.3 (C _quat , C-7), 176.4 (C _quat] C-4); MS (ESI, H ₂ O / AcN) m / z (%): 319.0 (100) [M ] ⁺ HRMS (C ₁₇ H ₂₃ N ₂ O ₄ ) ^{4 "} CaIc: 319.1657; Found: 319.1661 ± 1.16 ppm;

Example 16: Ethyl 6-methoxy-4-oxo-4H-chromene-2-carboxylate

Sodium (1.49 g, 65 mmol) is dissolved in absolute ethanol (100 ml). diethyl

(5.12 g, 35 mmol) and 2-hydroxy-5-methoxyacetophenone (2.49 g, 15 mmol) are dissolved in absolute ethanol (10 mL) and added to the sodium ethoxide solution. The

The solution is stirred under reflux for 1 h. It is acidified with concentrated HCl. The white precipitate is filtered off and the yellow solution is concentrated. After extraction with ethyl acetate, drying over Na ₂ SO ₄ , a pale yellow solid is obtained.

Recrystallization from methanol / diisopropyl ether (3: 1) gives a yellow solid (3.66 g, 14.8 mmol, 98%).

MP: 98 ° C; IR (KBr): v ^{(cm -1)} = 3455, 3114, 3078, 2984, 2844, 1740, 1657, 1610, 1488, 1288, 839; UV / VIS (MeOH): λ _max [um] (log ε) = 206 (4.45), 238 (4.22), 253 (4.31), 343 (3.77); ¹ H-NMR (600 MHz, CDCl _3): δ [ppm] = 1:42 (t, J = 7.1 Hz, 3 H, _CH3), 3.89 (s, 3 H, _0-CH3), 4.45 (q, J = 7.1 Hz, 2 H, CH _2), 7.10 (s, 1 H, H-3), 7:32 (dd, J = 3.2 Hz, 9.2 Hz, 1 H, H-7), 7:53 (dd, J = 0.4Hz, 3.2Hz, 1H, H-5), 7.54 (dd, J = 0.4Hz, 9.2Hz, 1H, H-8); ¹³ C-NMR (150 MHz, CDCl _3): δ [ppm] = 14.1 (+, CH _3), 56.0 (+, 0-CH _3), 62.9 (- CH _2), 104.6 (+, C-5 ), 113.8 (+, C-3), 120.2 (+, C-8), 125.0 (+, C-7), 125.2 (C _quat> C-9), 150.8 (C _quB ,, C-10), 152.0 (Cquat, C-2), 157.5 (C _quat , C-6), 160.6 (C _quat) C = O), 178.3 (C _quatj C-4); MS (PI-EIMS, 70 eV) m / z (%): 248.0 (100) [M] ^{+ "Elemental} analysis: C ₁₃ H ₁₂ O ₅ CAIC: C 62.90; H 4.87; Found: C 62.67; H 4.66 ;

Example 17: 6-Methoxy-4-oxo-4H-chromene-2-carboxylic acid-butylamide

Ethyl 6-methoxy-4-oxo-4H-ChiOinen-2-carboxylate (590mg, 2.4mmol) and butylamine (512mg, 7mmol) are dissolved in dichloromethane (10ml) and the mixture is stirred at reflux for 10 minutes. The solution is evaporated and a light yellow solid obtained. Glacial acetic acid (10 ml) is added and stirred at 7O ⁰ C for 10 minutes. The mixture is poured into ice-water, the precipitate filtered off, washed with water and dried. Recrystallization from dichloromethane / diisopropyl ether (1: 3) yields white needles (572 mg, 2.1 mmol, 87%).

MP: 146 ⁰ C; IR (KBr): v (cm ^-1 ) = 3305, 3091, 2956, 2869, 1639, 1610, 1359, 833 UV / VIS (MeOH): λ _max [im] (log ε) = 205 (4.43) 230 (4.25), 252 (4:36), 338 (3.75); ¹ H NMR (300 MHz, CDCl _3): δ [ppm] = 0.98 (t, J = 7.3 Hz, 3 H, _CH3), 1:43 ( qd, J = 7.3 Hz, 14.3 Hz, 2 H, CH ₂ ), 1.65 (td, J = 7.3 Hz, 14.9 Hz, 2 H, CH ₂ ), 3.49 (dd, J = 7.1 Hz, 13.3 Hz, 2 H , _CH2), 3.90 (s, 3 H, _0-CH3), 7.15 (s, 1 H, H-3), 7.31 (dd, J = 3.1 Hz, 9.2 Hz, 1 H, H-7), 7:45 (d, J = 9.2 Hz, 1 H, H-8), 7:56 (d, J = 3.0 Hz, 1 H, H-5); ¹³ C-NMR (75 MHz, CDCl _3): δ [ppm] = 13.8 (+, CH ₃ ), 20.1 (-, CH ₂ ), 31.5 (-, CH ₂ ), 39.8 (-, CH ₂ ), 56.0 (+, 0-CH ₃ ), 105.1 (+, C-5 ), 111.2 (+, C-3), 119.4 (+, C-8), 124.6 (+, C-7), 125.1 (C _quat , C-9), 150.0 (Cq _{et al.} , C-10), 154.6 (C _quat> C-2), 157.5 (C _quat , C-6), 159.3 (C _quat , C = O), 178.1 (C _quat , C-4), MS (CI-MS, NH ₃ ) m / z (%): 276.2 (100) [MH] ⁺ Elemental analysis: C ₁₅ H ₁₇ NO ₄ CAIC: C 65.44; H 6.22; N 5:09; Found: C 65.33; H 5.92; N 4.80;

Example 18:

6-methoxy-4-oxo-4H-chromene-2-carboxyi acid (3-dimethylamino-propyl) -amide

Ethyl 6-methyl-4-oxo-4H-ChiOmen-2-carboxylate (620 mg, 2.5 mmol) and

Dissolve 3-dimethylaminopropylamine (766 mg, 7.5 mmol) in dichloromethane (10 mL) and stir the mixture at reflux. The solution is evaporated, glacial acetic acid (10 ml) and the solution stirred at 7O ⁰ C for 10 minutes. The mixture is in

Added ice-water and extracted with ethyl acetate. The aqueous layer is washed with

Sodium bicarbonate neutralized and extracted with ethyl acetate. The aqueous layer is basified with sodium carbonate and extracted with ethyl acetate. The organic layer is dried over Na ₂ SO ₄ and gives a yellow solid (615 mg, 2.1 mmol,

81%).

MP: 108-109 ° C; IR (KBr): v (cm ^-1 ) = 3434, 3305, 3041, 2945, 1680, 1641, 1385, 830; ¹ H NMR (300 MHz, DMSO): δ [ppm] = 1.68 (p, J = 6.9 Hz, 2 H, CH ₂ ), 2.15 (s, 6 H, 2 x CH ₃ ), 2.28 (t, J = 6.9 Hz, 2 H, CH ₂ ), 3.32 (dd, J = 6.9 Hz, 13.3 Hz , 2 H, CH _2), 3.86 (s, 3 H, _0-CH3), 6.79 (s, 1 H, H-3), 7:40 (d, J = 3.1 Hz, 1 H, H-5), 7.48 (dd, J = 3.1Hz, 9.1Hz, 1H, H-7), 7.66 (d, J = 9.1Hz, 1H, H-8), 9.23 (t, J = 5.6Hz, 1H, NH ¹³ C-NMR (75 MHz, DMSO): δ [ppm] = 26.4 (-, CH ₂ ), 37.9 (-, CH ₂ ), 45.0 (+, 2 x CH ₃ ), 55.7 (+, 0- CH ₃ ), 56.8 (-, CH ₂ ), ^' 104.5 (+, C-5), 109.3 (+, C-3), 120.2 (+, C-8), 124.1 (+, C-7), 124.3 (C _quat, C-9), 149.6 (Cquat, C-IO), 155.4 (C _qua t, C-2), 156.8 (C _quat> C-6), _(quat C, C = O) 158.7, 176.9 (C _quat> C-4); MS (CI-MS, NH ₃₎ m / z (%): 305.2 (100) [MH] ^+; HRMS (C ₁₆ H ₂₀ N ₂ O ₄₎ ^{+ 'CAIC:} 304.1423 Found: 304.1425 ± 0.71 ppm;

Example 19:

{S-tCo-methoxy-O-oxo-H-chromene ^ -carbonyo-amino-J-propyl-trimethyl-ammonium iodide

6-Methoxy-4-oxo-4H-CluOmen-2-carboxylic acid (3-dimethylaminopropyl) propylamide (456 mg, 1.5 mmol) is dissolved in chloroform (10 ml), iodomethane (284 mg, 2 mmol) added and the mixture was stirred at room temperature for 1 h. The solution is stirred for 10 minutes under reflux, the resulting precipitate was filtered off and washed with chloroform. The precipitate is dried to give a white solid (620 mg, 1.4 mmol, 93%).

MP: 240 ° C +; IR (ICBr): v (cm ^'1 ) = 3422, 3298, 3031, 3013, 2945, 1680, 1651, 1615, 1485, 828; UV / VIS (CH ₃ CN): λ _max [nm] (log ε) = 205 (4.42), 248 (4.34), 333 (3.54); ¹ H-NMR (300 MHz, DMSO): δ [ppm] = 1.93 - 2.06 (m, 2H, CH ₂ ), 3.07 (s, 9H, 3 x CH ₃ ), 3.30 - 3.41 (m, 4H , 2 CH x _2), 3.87 (s, 3 H, _0-CH3), 6.83 (s, 1 H, H-3), 7:42 (d, J = 3.1 Hz, IH, H-5), 7:51 ( dd, J = 3.1Hz, 9.2Hz, 1H, H-7), 7.70 (d, J = 9.2Hz, 1H, H-8), 9.24 (t, J = 5.9Hz, 1H, NH); ¹³ C-NMR (75 MHz, DMSO): δ [ppm] = 22.6 (-, CH ₂ ), 36.2 (-, CH ₂ ), 52.1 (+, 3 x CH ₃ ), 55.7 (+, 0-CH ₃ ), 63.2 (-, CH ₂ ), 104.5 (+, CS), 109.5 (+, C-3), 120.3 (+, C-8), 124.2 (+, C-7), 124.3 (C _quat) C -9), 149.6 (C _qua t, C-10), 155.1 (C _quat> C-2), 156.8 (C _quat, C-6), _quat 159.2 (C, C = O), 176.9 (C _quat, C-4); MS (ESI, H ₂ O / AcN) m / z (%): 319.0 (100) [M] ⁺ ; Elemental analysis: C _n H ₂₃ N ₂ O ₄ I CaIc: C 45.75; H 5.19; N 6.28; Found: C 45.40; H 5.14; N 6.51; HRMS (CI ₇ H ₂₃ N ₂ O ₄ ) ⁺ Calc: 319.1658; Found: 319.1660 ± 0.76 ppm;

Example 20: Ethyl 5-methoxy-4-oxo-4H-chromene-2-carboxylate

Sodium (1.49 g, 65 mmol) is dissolved in absolute ethanol (100 ml). diethyl

(5.12 g, 35 mmol) and 2-hydroxy-6-methoxyacetophenone (2.49 g, 15 mmol) are dissolved in absolute ethanol (10 mL) and added to the sodium tartrate solution. The

The solution is stirred under reflux for 1 h. It is acidified with concentrated HCl. The white precipitate is filtered off and the yellow solution is concentrated. After extraction with ethyl acetate, drying over Na ₂ SO ₄ , a light yellow solid is obtained.

Recrystallization from methanol / diisopropyl ether (2: 1) gives a yellow solid (2.99 g, 12.1 mmol, 80%).

MP: 124 ⁰ C; IR (KBr): v (cm ⁴ ) = 3433, 3084, 2988, 2844, 1728, 1659, 1507, 1478, 1269, 800; UV / VIS (MeOH): λ _max [nm] (log ε) = 238 (4.22), 271 (4:00), 327 (3.64); ¹ H-NMR (300 MHz, CDCl ₃ ): δ [ppm] = 1.40 (t, J = 7.1 Hz, 3 H, CH ₃ ), 3.97 (s, 3 H, 0-CH ₃ ), 4.42 (q, J = 7.1 Hz, 2 H, CH _2), 6.83 (d, J = 8.5 Hz, 1 H, H-6), 6.99 (s, 1 H, H-3), 7.14 (dd, J = 0.9 Hz, 8.5 Hz, 1H, H-8), 7.59 (t, J = 8.5 Hz, 1H, H-7); ¹³ C-NMR (75 MHz, CDCl _3): δ [ppm] = 14.1 (+, CH _3), 56.5 (+, 0-CH _3), 62.8 (- CH _2), 106.9 (+, C-6 ), 110.6 (+, C-8 _uat), 115.3 (Cq, C-9), 116.5 (+, C-3), 134.7 (+, C-7), 150.3 (C _quat) C-2), 158.0 (C _quat , C-IO) ₅ 159.8 (C _quat> C-5), 160.6 (C _quat , C = O), 178.0 (C _quat , C-4); MS (PI-EMS, 70 eV) m / z (%): 248.0 (100) [M] ^{+ "Elemental} analysis: C ₁₃ H ₁₂ O ₅ CAIC: C 62.90; H 4.87; Found: C 62.84; H 4.75 ;

Example 21: 5-Methoxy-4-oxo-4H-chromene-2-carboxylic acid butylamide

Ethyl 5-methoxy-4-oxo-4H-CliiOmen-2-carboxylate (590mg, 2.4mmol) and butylamine (512mg, 7mmol) are dissolved in dichloromethane (10ml) and the mixture is stirred at reflux for 10 minutes. The solution is evaporated and a light yellow solid obtained. Glacial acetic acid (10 ml) is added, the solution stirred at 70 ⁰ C for 10 minutes, poured into ice-water, the precipitate filtered off, washed with water and dried. Recrystallization from dichloromethane / diisopropyl ether (2/1) yields white needles (607 mg,

2.2 mmol, 93%).

MP: 128 ^° C; IR (KBr): v (cm ^-1 ) = 3314, 3090, 2961, 1650, 1605, 1387, 794, UV / VIS (MeOH): λ _max [im] (log ε) = 238 (4.29), 260 ( 16.4), 323 (3.71); ¹ H-NMR (300 MHz, CDCl _3): δ [ppm] = 0.96 (t, J = 7.3 Hz, 3 H, _CH3), 1:35 to 1:47 (m, 2 H, CH ₂ ), 1.63 (td, J =

7.3 Hz, 15.0 Hz, 2 H, CH _2), 3:47 (dd, J = 6.8 Hz, 13.6 Hz, 2 H, CH _2), 3.97 (s, 3 H, _0-CH3), 6.84 (d, J = 8.4 Hz, 1H, H-6), 7.03 (s, 1H, H-3), 7.05 (d, J = 8.4 Hz, 1H, H-8), 7.60 (t, J -

8.4 Hz, 1H, H-7); ¹³ C-NMR (75 MHz, CDCl _3): δ [ppm] = 13.8 (+, CH _3), 20.1 (- CH _2), 31.5 (- CH _2), 39.7 (- CH _2), 56.6 (+, O-CH ₃ ), 107.0 (+, C-6), 109.8 (+, C-8), 113.7 (+, C-3), 115.0 (C _quat> C-9), 134.5 (+, CI), 152.8 (C _quat , C-2), 157.3 (C _quat , C-10), 159.2 (C _quat , C-5), 160.1 (C _quat, C = O), 177.9 (C _quat , C) 4); MS (CI-MS, NH ₃₎ m / z (%): 276.1 (100) [MH] ^+; Elemental analysis: C ₁₅ H ₁₇ NO ₄ CAIC: C 65.44; H 6.22; N 5.09; Found: C 65.40; H 6.00; N 4.96;

Example 22: 5-Methoxy-4-oxo-4H-chromene-2-carboxylic acid (3-dimethylammopropyl) -amide

Ethyl 5-methoxy-4-oxo-4H-cliromene-2-carboxylate (620 mg, 2.5 mmol) and

Dissolve 3-dimethylaminopropylamine (766 mg, 7.5 mmol) in dichloromethane (10 mL) and stir the mixture at reflux. The Lösimg is evaporated, glacial acetic acid (10 ml) was added and the solution stirred at 70 ⁰ C for 10 minutes. The mixture is poured into ice-water and extracted with ethyl acetate. The aqueous layer is washed with

Sodium bicarbonate neutralized and extracted with ethyl acetate. The aqueous layer is basified with sodium carbonate and extracted with ethyl acetate. The organic layer is dried over Na ₂ SO ₄ and gives a yellow solid (627 mg, 2.1 mmol,

83%).

MP: 87-88 ⁰ C; IR (KBr): v (cm ^-1 ) = 3420, 3312, 3080, 2955, 1650, 1603, 798; ¹ H-NMR (300 MHz, DMSO): δ [ppm] = 1.67 (p, J = 6.9 Hz , 2 H, CH ₂ ), 2.15 (s, 6 H, 2 x CH ₃ ), 2.27 (t, J = 6.9 Hz, 2 H, CH ₂ ), 3.31 (dd, J = 6.9 Hz, 13.3 Hz, 2 H, CH _2), 3.86 (s, 3 H, O-CH _3), 6.61 (s, 1 H, H-3), 7:02 (d, J = 8.4 Hz, 1 H, H-6), 20.7 ( dd, J = 0.7Hz, 8.4Hz, 1H, H-8), 7.75 (t, J = 8.4Hz, 1H, H-7), 9.17 (t, J = 5.6Hz, 1H, NH); ¹³ C-NMR (75 MHz, DMSO): δ [ppm] = 26.4 (-, CH ₂ ), 37.9 (-, CH ₂ ), 45.0 (+, 2 x CH ₃ ), 56.0 (+, 0-CH ₃ ), 56.8 (-, CH ₂ ), 107.4 (+, C-6), 109.9 (+, C-8), 111.8 (+, C-3), 114.0 (C _quat , C-9), 134.9 (+ , C-7), 153.3 (C _quat> C-2), 156.9 (C _quat , C-10), 158.7 (C _quat) C-5), 159.1 (C _quat> C = O), 176.4 (C _quat , C-4); MS (CI-MS, NH ₃₎ m / z (%): 305.2 (100) [MH] ^+; HRMS (C ₁₆ H ₂₀ N ₂ O ₄₎ ^{+ 'CAIC:} 304.1424; Found: 304.1425 ± 1.1 ppm;

Example 23:

{3 - [(5-Methoxy-4-oxo-4H-chromene-2-carbonyl) -amino] -propyl} -trimethyl ammonium iodide

5-Methoxy-4-oxo-4H-CliiOmen-2-carboxylic acid (3-dimethylamino-propyl) -amide (456 mg, 1.5 mmol) is added in chloroform, dissolved (10 ml), iodomethane (284 mg, 2 mmol) and the mixture was stirred at room temperature. The solution is stirred for 10 minutes under reflux, the resulting solid is filtered off and washed with chloroform.

The precipitate is dried to yield a white solid (625 mg, 1.4 mmol, 93

%) •

MP: 240 ° C +; IR (KBr): v (cm ^-1 ) = 3433, 3244, 3018, 2940, 1683, 1650, 1602, 1475, 802; UV / VIS (CH ₃ CN): λ _max [ran] (log ε) = 242 (4.25), 319 (3.53); ¹ H-NMR (300 MHz, DMSO): δ [ppm] = 1.92 - 2.04 (m, 2H, CH ₂ ), 3.06 (s, 9H, 3 x CH ₃ ) , 3.30 - 3.41 (m, 4H, 2 x CH ₂ ), 3.87 (s, 3H, 0-CH ₃ ), 6.65 (s, 1H, H-3), 7.04 (d, J = 8.4 Hz, 1 H, H-6), 7.23 (dd, J-0.7Hz, 8.4Hz, 1H, H-8), 7.77 (t, J = 8.4Hz, 1H, H-7), 9.17 (t, J = 5.9 Hz, 1 H, NH); ¹³ C-NMR (75 MHz, DMSO): δ [ppm] = 22.6 (-, CH ₂ ), 36.2 (-, CH ₂ ), 52.1 (+, 3 x CH ₃ ), 56.1 (+, 0-CH _3), 63.2 (- CH _2), 107.5 (+, C-6), 109.9 (+, C-8), 112.0 (+, C-3), 114.0 (C _quat , C-9), 135.0 (+, C-7), 153.1 (C _quat , C-2), 156.9 (C _quat , C-10), 159.1 (C _quat , C-5), 159.2 (C _quat , C = O), 176.3 (Cq _u at, C-4), MS ESI, H ₂ O / AcN) m / z (%): 319.0 (100) [M] ⁺ ; HRMS (Ci ₇ H ₂₃ N ₂ O ₄ ) ⁺ Calc: 319.1658; Found: 319.1660 ± 1.02 ppm;

Properties of the compounds according to the invention:

Hair Liability:

The hair adhesion of the compounds according to the invention can be achieved by means of

MALDI MS or by dissolving the hair followed by HPLC analysis (in analogy to Hubbard, DL; Wilkins, DG; Rollins, DE Drug Metab. Dispos 2000, 28, 1464; Haasnoot, W., Stouten, P. Schilt Hooijerink, D. Analyst 1998, 123, 2707; Nielen, MWF; Hooijerink, H .; Essers, ML; Lasaroms, JJP; van Bennekom, EO; Brouwer, L. Anal. Chim. Acta 2003, 483,

11).

To carry out the detection by means of HPLC, the compound according to the invention is stirred in a 70:30 ethanol: water mixture for one hour with the hair. The treated hair is washed, dried and dissolved in NaOH solution at 60 ° C. By way of reference, blond hairs provide HPLC signals after 1.54 min, 1.77 min, 2.05 min and 4.79 min. Without hair treatment, the 4-oxo-4H-chromen-2-carboxylic acid, as a degradation product of the compounds of the invention under the basic conditions of hair dissolution

Signal after 5.47 min. A corresponding signal is obtained for hair treated with ammonium salts according to the invention. It turns out that it is irrelevant what color the hair and if the hair, for example by bleaching, are pretreated.

Antioxidant properties

By means of the DPPH (2,2-diphenyl-1-picrylhydrazyl) method or cyclic voltammetry, the antioxidative properties of the compounds according to the invention can be investigated. UV absorption

The UV absorption of various compounds according to the invention is given in the following table:

It can be seen that by suitable selection of the substitution pattern on the chromone ring system, the UV absorption can be adapted to the application requirements. While the compound according to Example 15 protects against UV-B and thus protects hair proteins in particular, the compound close to Example 19 protects better in the UVA range and thus against licchtbedingte color changes of the hair. preparations

The following are exemplified formulations for cosmetic preparations, the inventive amides according to

Examples 2, 3, 4, 5, 8, 9, 10, 13, 14, 17, 18, 21 and 22 or inventive ammonium salts according to Examples 6, 11, 15, 19 and 23, respectively. Otherwise, the INCI names of the commercial compounds are given.

UV-Pearl, OMC stands for the preparation with the INCI name: Water (for EU: Aqua), Ethylhexyl Methoxycinnamate, Silica, PVP, Chlorphenesin, BHT; this formulation is commercially available under the designation Eusolex®UV Pearl ™ OMC from Merck KGaA, Darmstadt.

The other UV pearls listed in the tables are each assembled analogously, with OMC being replaced by the specified UV filters.

Example 24: Shampoo preparation

Method:

Combine phase A. Mix until the mixture is homogeneous. Add phase B. Mix until the mixture is homogeneous.

Example 25: Shampoo preparation with rinse

Method:

Mix phase A and heat to 70 ⁰ C. Mix until the mixture is homogeneous. Add phase B. Mix until the mixture is homogeneous and cool to about 50 ° C. Add phase C to the above mixture and stir well. Adjust the pH to 5-6 by adding citric acid.

Example 26: Haarkurzubereitung with vegetable protein

Method:

Phase A heated with stirring to 70-75 ⁰ C. In a separate container, heat phase B to 70-75 ° C until it melts. Add B to A with stirring. Cool to 50 ⁰ C and add phase C and D with stirring. Allow to cool to room temperature. Then add phase E, stirring if necessary. Example 27: Shampoo for color intensification

Method:

Dissolve phase B in phase A with stirring. Heat phase C to 70-80 ⁰ C; Add to AB. Add D, then slowly add E. If the mixture is homogeneous, after cooling to about 50 ⁰ C, add phase F. Adjust the pH to 5-6 by adding citric acid. Example 28: Sunscreen Lotion

Method:

Heat phase A to approx. 75 ^° C. Mix phase B; to 75 ⁰ C heat. Add B to A with stirring. Homogenously mix and cool the temperature to about 50 ° C and add phase C.

Example 29: further preparations

TABLE 1 W / O emulsions (numbers in% by weight)

Table 1 (continued)

Table 1 (continued)

Table 2: O / W emulsions, figures in% by weight

Table 2 (continued)

Table 2 (continued)

Table 3: Gels, numbers in wt%

Claims

claims

1. Compound of formula I

in which

R ¹ and R ^{2 may be the} same or different and are selected from -H or -C (= O) -NR ⁷ R ⁸ , wherein at least one of R ¹ and

R ^{2 is} different from H,

R ³ to R ^{6 may be the} same or different and are selected from

- -H,

- -OH,

straight or branched C 1 to C ₂ o-alkyl groups,

straight-chain or branched C ₃ - to C ₂₀ -alkenyl groups,

straight-chain or branched Cr to C ₂ o-hydroxyalkyl groups, it being possible for the hydroxyl group to be bonded to a primary or secondary carbon atom of the chain, and furthermore for the alkyl chain also to be interrupted by oxygen, and

R ⁷ is H or straight-chain or branched Cr to C ₂₀ -

Alkyl groups and

R ⁸ is a straight-chain or branched C _r to C ₂ o-alkyl group or a radical - (CH ₂ ) _n -NR ⁹ R ¹⁰ or a radical - (CH ₂ ) _n -N ⁺ R ⁹ R ¹⁰ R ¹¹

X ^" , where

R ⁹ to R ¹¹ stand for straight-chain or branched Cr to C ₂₀ -

Alkyl groups and n is an integer in the range of 1 to 30 and

X ^" represents an anion such as Cl ^" , Br ^" , I ^" , Cia-alkyl sulfate, Ci- ₈ -

Alkyl sulfonate, p-Tolylsulfonat.

2. A compound according to claim 1, characterized in that R is a radical - (CH ₂ ) _n -NR ⁹ R ¹⁰ or a radical - (CHk) _n - N ⁺ R ⁹ R ¹⁰ R ¹¹ X ^" 'preferably wherein Substituent of R ¹ and R ² , preferably R ¹ , is -C (= O) -NH- (CH ₂ ) _n -N ⁺ R ⁹ R ¹⁰ R ¹¹ , where n is preferably an integer in the range of 1 to 8, particularly preferably 2, 3 or 4 stands.

3. A compound according to at least one of claims 1 or 2, characterized in that it is the compound of formula I is a compound selected from the compounds of formulas Ia-In:

4. A compound according to at least one of the preceding claims, characterized in that at least 2, preferably at least 3 of the substituents R ¹ , R ² , R ³ -R ^{6 are} different from H.

5. A compound according to at least one of the preceding claims, characterized in that R ³ is OH and R ⁴ is OH, wherein preferably additionally at least one of R ⁵ and R ^{6 is} OH.

6. A compound according to at least one of claims 1 to 5, characterized in that R ⁵ and R ⁶ stand for H.

7. Use of at least one compound of the formula I or one

A preparation comprising at least one compound of the formula I with radicals according to at least one of Claims 1 to 6 for the care, preservation or improvement of the general condition of the skin or hair.

8. Use of at least one compound of formula I or one

A preparation containing at least one compound of the formula I with radicals according to at least one of claims 1 to 6 for the prophylaxis of time- and / or light-induced aging processes of human skin or human hair, in particular for Reduction or prevention of damaging effects of UV rays on the skin or hair.

9. A preparation comprising at least one compound of the formula I with radicals according to at least one of claims 1 to 6 and at least one suitable carrier.

10. A preparation according to claim 9, characterized in that the preparations one or more compounds of formula I in an amount of 0.01 to 20 wt .-%, preferably in an amount of

0.1 to 10 wt .-% contains.

11. A preparation according to at least one of the preceding claims, characterized in that the preparation contains at least one further caring ingredient, which is preferably one or more antioxidants and / or vitamins, preferably selected from vitamin C and its derivatives, DL-α- Tocopherol, tocopherol E acetate, nicotinic acid, pantothenic acid and biotin.

12. A preparation according to one of the preceding claims, wherein the preparation contains one or more UV filters which are preferably selected from the group consisting of 3- (4 ^'- methylbenzylidene) -dl-camphor, 1- (4-tert- Butylphenyl) -3- (4-methoxyphenyl) propane-1,3-dione, 4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octyl methoxycinnamate, 3,3,5-trimethylcyclohexylsalicylate, 4- (dimethylamino) benzoic acid 2 ethylhexyl ester, 2-cyano-3,3-diphenylacrylic acid 2-ethylhexyl ester, 2-phenylbenzimidazole-5-sulfonic acid and their potassium, sodium and triethanolamine salts.

13. Preparation according to at least one of the preceding claims, characterized in that at least one further caring ingredient is Pyrimidincarbonsäuren and / or Aryloxime, preferably Ectoin.

14. A process for preparing a preparation, characterized in that a compound of formula I is mixed with residues according to any one of claims 1 to 6 with a cosmetically or dermatologically or food-suitable carrier.

15. A process for preparing a compound of the formula I with radicals according to at least one of claims 1 to 6, characterized in that the preparation is carried out by reacting an alkyl ester of a chromene-4-on-carboxylic acid with an amine, preferably an n-alkylamine, such as butylamine, octylamine or dodecylamine, or a diamine, such as preferably 3-dimethylaminopropylamine.

16. A process for preparing a compound of the formula I having radicals according to at least one of claims 1 to 6, wherein R ⁸ is a radical - (CH ₂ ) _n -N ⁺ R ⁹ R ¹⁰ R ¹¹ X ^" , characterized in that following the steps of claim 15, reacting the resulting amine with iodomethane.