EP1856084A1 - Derives de chromene-4-one - Google Patents

Derives de chromene-4-one

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Publication number
EP1856084A1
EP1856084A1 EP06706894A EP06706894A EP1856084A1 EP 1856084 A1 EP1856084 A1 EP 1856084A1 EP 06706894 A EP06706894 A EP 06706894A EP 06706894 A EP06706894 A EP 06706894A EP 1856084 A1 EP1856084 A1 EP 1856084A1
Authority
EP
European Patent Office
Prior art keywords
formula
compound
acid
preparation
quat
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP06706894A
Other languages
German (de)
English (en)
Inventor
Christophe Carola
Thomas Walenzyk
Ralf Rosskopf
Herwig Buchholz
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Patent GmbH
Original Assignee
Merck Patent GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck Patent GmbH filed Critical Merck Patent GmbH
Publication of EP1856084A1 publication Critical patent/EP1856084A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/24—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/12—Preparations containing hair conditioners
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/42—Colour properties
    • A61K2800/43—Pigments; Dyes

Definitions

  • 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
  • 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
  • UV-A and visible light rarely cause direct damage, as proteins do not absorb it.
  • 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.
  • Changes include the destruction of epidermal cells, roughening the hair surface, loss of mechanical and elastic strength, and increased porosity.
  • 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.
  • various approaches have been described, e.g. the use of light filters on the hair surface and the use of antioxidants or radical scavengers.
  • 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
  • chromene-4-one derivatives are suitable as active compounds with the profile described.
  • a first subject of the present application are therefore compounds of the formula I.
  • R 2 is different from H
  • R 3 to R 6 may be the same or different and are selected from
  • 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.
  • EP-A-1 216 692 discloses the use of 2-methyl-2- ( ⁇ -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.
  • 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 ⁇
  • 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.
  • 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 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.
  • 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.
  • 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 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.
  • R 8 represents a radical - (CH 2) n NR 9 R 10 or a radical -.
  • R 8 represents a radical - (CH 2) n NR 9 R 10 or a radical -.
  • 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:
  • 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.
  • R 5 and R 6 are H.
  • 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
  • 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
  • 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.
  • 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.
  • 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.
  • 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
  • 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 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
  • R 5 and R 6 are H.
  • 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.
  • 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.
  • At least one further skin care ingredient is one or more antioxidants and / or vitamins.
  • 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 ⁇ -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, ⁇ -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 ⁇ mol / kg), furthermore (metal) chelators (eg ⁇ -hydroxyfatty
  • 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
  • DL- ⁇ -tocopherol for example Oxynex ® LM
  • BHT butylhydroxytoluene
  • 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
  • vitamin Ki esculin
  • vitamin Bi thiamine
  • nicotinic acid niacin
  • pyridoxine pyridoxal
  • pyridoxamine pantothenic acid
  • biotin folic acid and cobalamin
  • vitamin Bi 2 cobalamin
  • 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.
  • the polyphenols which are sometimes present as natural substances, are of particular interest for applications in the pharmaceutical, cosmetic or food sector.
  • 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
  • R 1 to R 10 may be the same or different and are selected from
  • 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,
  • 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.
  • preferred compounds described herein are colorless or only slightly colored and thus do not or only to a slight extent discolorations of the preparations.
  • 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 ).
  • the compounds of the formula I in the molecule combine antioxidant properties with UV absorption in the UV-A and / or B range.
  • 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.
  • 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.
  • the preparations according to the invention are generally suitable for immune protection and for the protection of DNA and RNA.
  • 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.
  • Preparations which are particularly preferred according to the invention comprise, in addition to the compounds of the formula lauch, UV filters.
  • 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.
  • 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®
  • 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
  • Hexyl 2- (4-diethylamino-2-hydroxybenzoyl) benzoate e.g., Uvinul® UVA Plus, BASF.
  • organic UV filters are usually incorporated in an amount of 0.5 to 10 weight percent, preferably 1-8%, in cosmetic formulations.
  • UV filters are also Methoxyflavone en Schemeend 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.
  • 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.
  • 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.
  • 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 results in a broadband protection, which can be supplemented by the addition of inorganic UV filters, such as titanium dioxide microparticles.
  • inorganic UV filters such as titanium dioxide microparticles.
  • All mentioned UV filters can also be used in encapsulated form.
  • organic UV filters in encapsulated form.
  • the hydrophilicity of the capsule wall can be adjusted independently of the solubility of the UV filter.
  • hydrophobic UV filters can also be incorporated into purely aqueous preparations.
  • 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.
  • 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.
  • UV filters 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
  • capsules whose walls are made up of silica gel (silica, undefined silicon oxide hydroxide) are preferred.
  • silica gel silicon, undefined silicon oxide hydroxide
  • 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).
  • ectoine ((S) -1, 4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid)
  • 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.
  • pyrimidinecarboxylic acid according to the formula below is preferably used,
  • R 1 is a radical H or d-8-alkyl
  • R 2 is a radical H or C 1-4 -alkyl
  • R 3 , R 4 , R 5 and R 6 are each independently a radical from the group
  • 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
  • 2-hydroxy-5-methyllaurophenone oxime which is also referred to as HMLO, LPO or F5
  • HMLO 2-hydroxy-5-methyllaurophenone oxime
  • LPO 2-hydroxy-5-methyllaurophenone oxime
  • 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.
  • 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.
  • dosage forms such as capsules, dragees, powders, tablet solutions or solutions are suitable.
  • 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,
  • solvents e.g. Water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol, oils, in particular cottonseed oil,
  • 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.
  • 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.
  • 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.
  • excipients such as salts of fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic acid esters, fatty acid protein hydrolysates, isothionates, imidazolinium derivatives, methyl taurates, sarcosinate
  • 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.
  • the preferred preparation forms according to the invention include in particular emulsions.
  • Emulsions of the invention are advantageous and contain z.
  • 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 Alcohols with low C-alkanoic acids or with fatty acids
  • Silicone oils such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof.
  • oil phase of the emulsions, oleogels or hydrodispersions is a major component of the emulsions, oleogels or hydrodispersions.
  • 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.
  • 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.
  • 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,
  • 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.
  • 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-
  • hydrocarbons paraffin oil, squalane and squalene are to be used advantageously in the context of the present invention.
  • 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.
  • cyclomethicone octamethylcyclotetrasiloxane
  • silicone oils are also advantageous for the purposes of the present invention, for example hexamethylcyclotrisiloxane, polydimethylsiloxane, poly (methylphenylsiloxane).
  • mixtures of cyclomethicone and Iso tridecylisononanoat from cyclomethicone and 2-Ethylhexylisostearat.
  • 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
  • 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.
  • the preparations according to the invention contain hydrophilic surfactants.
  • hydrophilic surfactants are preferably selected from the group of alkylglucosides, acyl lactylates, betaines and cocoamphoacetates.
  • alkylglucosides in turn are advantageously selected from the group of alkylglucosides, which are represented by the structural formula
  • R represents a branched or unbranched alkyl radical having 4 to 24 carbon atoms and wherein DP means a mean Glucosyl michsgrad of up to 2.
  • the value DP represents the degree of glucosidation of the alkylglucosides used in the invention and is defined as
  • 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.
  • 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.
  • sodium isostearyl lactylate for example, is advantageous
  • R 2 is a branched or unbranched alkyl radical having 1 to 30 carbon atoms.
  • R 2 is a branched or unbranched alkyl radical having 6 to 12 carbon atoms.
  • Capramidopropylbetaine for example, is advantageous
  • 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.
  • 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.
  • Oil-in-water (W / O / W) a gel, a solid stick, an ointment or even an aerosol.
  • Ectoine in encapsulated form, e.g. In collagen matrices and other common encapsulating materials, e.g.
  • wax matrices 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.
  • 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.
  • 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.
  • 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),
  • 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),
  • 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,
  • the sodium laureth-11-carboxylate can be advantageously used.
  • the alkyl ether sulfate sodium laureth-4 sulfate can be advantageously used.
  • polyethylene glycol (30) cholesteryl ether can be advantageously used.
  • Polyethylene glycol (25) soy- sterol has also been proven.
  • 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
  • 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.
  • W / O emulsifiers can be used:
  • 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.
  • 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
  • Step-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
  • 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.
  • 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,
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • an amine preferably an n-alkylamine, such as butylamine, octylamine or dodecylamine, or a diamine, preferably 3-dimethylaminopropylamine.
  • the resulting amine D can be reacted, for example, with iodomethane.
  • 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.
  • 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.
  • 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 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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%).
  • Glacial acetic acid (10 ml) is added and stirred at 70 0 C for 10 minutes. The mixture is in
  • 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
  • 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%).
  • 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%).
  • 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%).
  • 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%).
  • 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%).
  • 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%).
  • 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,
  • the hair adhesion of the compounds according to the invention can be achieved by means of
  • 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.
  • blond hairs provide HPLC signals after 1.54 min, 1.77 min, 2.05 min and 4.79 min.
  • 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
  • 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 liccht employmente color changes of the hair. preparations
  • 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 TM OMC from Merck KGaA, Darmstadt.
  • phase A Mix until the mixture is homogeneous.
  • phase B Mix until the mixture is homogeneous.
  • phase A Mix phase A and heat to 70 0 C. Mix until the mixture is homogeneous.
  • 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.
  • 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
  • Heat phase A to approx. 75 ° C.

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Abstract

La présente invention concerne des dérivés de chromène-4-one, leur production et leur utilisation pour traiter, conserver ou améliorer l'état général de la peau ou en particulier des cheveux et pour prévenir contre les processus de vieillissement dus au temps et/ou à la lumière de la peau chez l'homme, en particulier des cheveux chez l'homme. Cette invention concerne également des préparations comprenant une teneur efficace en dérivés de chromène-4-one de ce type.
EP06706894A 2005-03-10 2006-02-13 Derives de chromene-4-one Withdrawn EP1856084A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE200510011534 DE102005011534A1 (de) 2005-03-10 2005-03-10 Chromen-4-on-Derivate
PCT/EP2006/001282 WO2006094601A1 (fr) 2005-03-10 2006-02-13 Derives de chromene-4-one

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EP1856084A1 true EP1856084A1 (fr) 2007-11-21

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CA3011018A1 (fr) 2016-01-15 2017-07-20 Universitat Hamburg Derive de noreugenine glycoside
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