Schritt psoriatischer Arthritis Schritt psoriatischer Arthritis


Patent DET2 - Neue substituierte imidazolverbindungen New substituted imidazole compounds - Google Patents

Try the new Google Patents, with machine-classified Google Scholar Schritt psoriatischer Arthritis, and Japanese and South Korean patents. Steroidale Chinole als Prodrugs von Antioxidantien Steroidal quinols as prodrugs of antioxidants translated from German Schritt psoriatischer Arthritis T2.

Chinol nach Anspruch 1, worin R eine geradekettige oder verzweigte C Alkylkette ist und X Wasserstoff ist. Quinol according to claim 1, wherein R is a straight or Schritt psoriatischer Arthritis C alkyl chain Schritt psoriatischer Arthritis X is hydrogen. An in vitro method Schritt psoriatischer Arthritis producing a biologically active estrogen compound, comprising providing a quinol according to claim 1 or 2, and transferring the quinol via enzyme catalyzed reduction into a biologically active estrogen compound.

An in vitro method for producing a regenerated quinol, comprising the method according to claim 3 and regenerating the quinol by catching a free-radical reactive oxygen species Schritt psoriatischer Arthritis the biologically active estrogen compounds. A pharmaceutical composition comprising a quinol according to claim 1 or 2, which was converted via enzyme catalyzed reduction into a biologically active estrogen compound, wherein the composition further comprises a pharmaceutically acceptable carrier.

Pharmazeutische Zusammensetzung nach Anspruch 5, wobei die Enzym-katalysierte Reduktion mit NADH oder NADPH als einem Reduktionsmittel stattfindet. A pharmaceutical composition according to claim 5, wherein the enzyme catalyzed reduction occurs with NADH or NADPH as a reducing agent.

Use of a quinol according to claim 1 or 2, which was converted via enzyme catalyzed reduction into a biologically active estrogen compound for the manufacture of a medicament for the treatment or prevention of a pathological condition associated with free-radical reactive oxygen species.

Use according to claim 7, further comprising an administration of the quinol by a route selected from the group consisting of oral, buccal, intramuscular, transdermal, intravenous and subcutaneous. Use according to claim 7, wherein the quinol is regenerated when the biologically click here estrogen compounds capture a free-radical reactive oxygen species.

Verwendung nach Anspruch 7, wobei die Enzym-katalysierte Reduktion mit NADH oder NADPH als einem Reduktionsmittel stattfindet. Use according to claim 7, wherein the enzyme catalyzed reduction occurs with NADH or NADPH as a reducing agent. Verwendung nach Anspruch 7, wobei der mit freies-Radikal reaktiven Sauerstoffspezies assoziierte pathologische Zustand eine neurodegenerative Erkrankung ist. Use according to claim 7, wherein the associated with free-radical reactive oxygen species pathological condition Schritt psoriatischer Arthritis a neurodegenerative disease.

Use according to claim 7, wherein the biologically active estrogen compounds are provided to the mammal for the treatment or prevention of cardiac conditions or the treatment Schritt psoriatischer Arthritis prevention of conditions associated with the bone, is available.

Hintergrund der Erfindung Background of the Invention. The present invention relates to prodrugs prodrugs of the antioxidant therapy. In particular, the present invention provides estrogen-related steroidal quinols and their use as relates Schritt psoriatischer Arthritis prodrugs for phenolic A-ring estrogens and estrogen analogs. Hydrogen peroxide is produced, for example, during respiration of most living organisms, in particular from injured cells or such under stress.

ROS can be harmful to cells, when present in high concentrations. Oxidative stress causes cell Schritt psoriatischer Arthritis, resulting in changes of Redoxlage such as the depletion of nucleotide coenzymes and disturbance of sulfhydryl-containing enzymes and saturation and destruction of the antioxidant defense and DNA repair system.

For example, excess hydrogen peroxide react with DNA and cause breakage of the DNA-degree or reverse mutations and change bases or release. Such oxidative biochemical injury can result in the loss of cellular membrane integrity, Schritt psoriatischer Arthritis enzyme activity, changes of the transport kinetics, changes in membrane lipid composition as well as loss of potassium ions, amino acids and other cellular materials.

Another example of the ability of ROS to injury of cells is lipid peroxidation which involves the oxidative degradation of unsaturated lipids. Lipid peroxidation is highly detrimental in terms of membrane structure and function and can cause read article cytopathological effects. Researchers have shown that atherosclerosis and the fatal consequences of heart attacks and brain strokes related to Schritt psoriatischer Arthritis oxidative modification of "low-density" lipoproteins LDL are transporting cholesterol in the blood.

It has been developed a theory that free radicals, which are manufactured by the own Imunzellen, oxidize Foetlda Geschichte der Krankheit Psoriasis Tagebücher Kosten, which in turn is taken up by cells Schritt psoriatischer Arthritis the vascular intima, which arteriosclerotic lesions are caused.

Thus, oxidative Schritt psoriatischer Arthritis has been associated with a number of diseases and dysfunctions, including aging and neuronal cell death Jenner, P.

The brain is a specialized organ that metals that are necessary for normal neurological function concentrated. It is known to be caused by trauma, ischemia, and many other injuries of neuropathological cause the release protein bound metal ions such as iron from damaged cells. The release Schritt psoriatischer Arthritis metal ions enhances the oxidative stress in the central nervous system CNS by promoting the formation of ROS. It was shown that antioxidants, reduce the damage associated with ROS.

An antioxidant defense of mammalian cells, "J Exp. An antioxidant defense of mammalian cells," J Exp. Psyclaiatiy, Multivitamins and Probucol 10 Study Schritt psoriatischer Arthritis New Engl.

It has been shown that treatment with antioxidants, the rate of motor decline at the beginning of Huntington see more is delayed Peyser CE, et al. Unfavorably many antioxidants are fat-soluble and therefore due to their low water solubility Schritt psoriatischer Arthritis respect to their use of limited use.

Water-soluble and less restricted in their use of antioxidants, such as vitamin C, can act as pro-oxidants, ie as oxidation promoters in the presence of a metal ion and have the disadvantage that they promote lipid peroxidation under certain conditions. Uric acid is also water soluble, but may cause unpleasant side effects when it is enriched in vivo, such as gout Schritt psoriatischer Arthritis renal stones.

Probucol has poor bioavailability. Estrogens have been recognized as antioxidants and effective neuroprotective agents. Schritt psoriatischer Arthritis is believed that its antioxidant action is due to its ability to scavenge free radicals, which can cause neuronal cell death. Studies, however, it could be concluded that the efficacy of the estrogen estradiol as a phenolic antioxidant in reducing iron-induced lipid peroxidation is just click for source than that of vitamin E despite the extremely low overall concentration of estrogens compared to vitamin E.

In addition, the OH bond dissociation energy BDE is greater than that of estradiol of vitamin E, which could imply that vitamin E is a stronger deactivator of Oxidradikals than estrogen. The effectiveness of antioxidants is basically determined not only by their chemical reactivity with respect to ROS, but also on the mobility or distribution of the molecule in the microenvironment and the fate of the antioxidant-derived radical that Schritt psoriatischer Arthritis, the dynamics of the antioxidant effect.

Why could lipophilic estrogens in vivo despite their small "bulk levels" act as highly localized antioxidants because of their membrane binding affinity and high concentrations in the vicinity of the activity loci. These various activities of estrogens may be associated with its cytoprotective effects and antioxidant abilities. The neuroprotective effect of estrogens against numerous toxic insults including oxidative stress has been extensively investigated in vivo and in vitro in various types of neuronal cells.

There is an increasing body of evidence that estrogens mediate its neuroprotective effect against oxidative stress by suppressing neurotoxic check this out via their direct radical-scavenging activity.

The estrogen concentration of the current flowing through the liver blood is usually four to five times greater than the estrogen concentration in the peripheral blood "first pass" effect. Administration of oral estrogens results in the presence of high concentrations in the liver and can also lead to undesirable increase in the production of certain coagulation Schritt psoriatischer Arthritis and renin substrates through the liver.

Therefore, there is a need for therapeutic agents that are therapeutically effective in the regions where they are really needed.

It has been shown that high doses of estrogens have an antioxidative effect in vitro. Even if such doses are effective in cells in http://julia-kuhn.de/solarium-fuer-psoriasis.php, they have in the treatment of conditions which are associated with oxidative stress because of associated problems with toxicity, increased incidence of some types of cancer, and feminizing effects in males only limited effectiveness.

Therefore, the applicability of such methods to treatment is severely limited. Oxygenation click 2,4-Dibromoestrogens with Nitric Acid: A New Synthesis of Nor Steroids, Chem Pharrn Bull, Vol.

Oxygenation of 2,4-Dibromoestrogens with Nitric Acid. A New Synthesis of Schritt psoriatischer Arthritis Steroids, Chem Pharrn Bull, vol 37, 8, pp describe methods for synthesizing nor steroids starting from 2.

Nach Numazawa et al. According to Numazawa et al. In addition, there is no further disclosure regarding 7abecause Schritt psoriatischer Arthritis appears that nor steroids can not be synthesized from 7astarting. Structure of 2,4-Dibromobeta, 17beta-dihydroxy-1,4-estradienone, Acta Cryst, Vol. As noted above, claim Schritt psoriatischer Arthritis no longer contains the replacement of Y or Z with a halogen.

Comparisons of hydroperoxide isomerase and monooxygenase activities of cytochrome P for conversions of allylic hydroperoxides and alcohols to epoxyalcohols and diols: Comparisons of hydroperoxide isomerase and monooxygenase activities of cytochrome P for conversions of allylic hydroperoxide and alcohols to epoxyalcohols and diol: Novel metabolic pathway of estrone and 17beta-estradiol catalyzed by cytochrome P Schritt psoriatischer Arthritis Metab Dispos February; 28 2: Therefore, a need for compositions Schritt psoriatischer Arthritis methods of administration of estrogen-related free radical scavengers or Antioxidantienn for tissue exists, show the changes in the oxidative state.

In particular, there is a need for compositions and methods that bring therapeutic advantages for patients suffering from neurodegenerative diseases associated with oxidative stress.

Furthermore, there is a need for a therapeutically effective estrogen compound, unfold their therapeutic activity without gender side effects. Kurze Zusammenfassung der Erfindung Brief Summary of the Invention. The present invention Schritt psoriatischer Arthritis compositions and methods for the controlled administration of antioxidant compounds to mammals. In another aspect of the invention are estrogenic steroid quinols to alleviate adverse effects associated with aging, stroke and trauma administered.

In einer bevorzugten Ausgestaltung stellt die vorliegende Erfindung inaktive Zusammensetzung bereit, die in vivo in biologisch aktiver therapeutische Verbindungen durch chemische oder enzymatische Transformation konvertiert werden.

In a preferred embodiment the present invention provides inactive composition which are converted http://julia-kuhn.de/psoriasis-an-den-fingern.php vivo into biologically active therapeutic compounds by chemical or enzymatic transformation. The steroid-like quinols of the present invention Schritt psoriatischer Arthritis advantageous because they have problems that are associated with stability, toxicity, lack of specificity and limited bioavailability, which may occur with the active form of the steroid dissolves.

The quinols according to the present invention are particularly advantageous as oxidative free radical scavenger. The present invention is based on the identification of a mechanism by which estrogens serve as potent radical scavengers of hydroxyl radicals through the capture of harmful reactive oxygen species. In particular, the present invention Psoriasis Fotos in a preferred embodiment of an estrogen-like ready quinol that is rapidly converted to a biologically active estrogen by means of an enzyme-catalyzed reduction using an endogenous reducing agent.

Das endogene Reduktionsmittel kann beispielsweise die reduzierte Form von Nikotinamid-Adenindinukleotid NADH oder Nikotinamid-Adenindinukleotidphosphat NADPH sein.

The endogenous reducing agent may be, for example, the reduced form of nicotinamide adenine Schritt psoriatischer Arthritis NADH or nicotinamide adenine dinucleotide phosphate NADPH. An advantage of the chemical conversion reaction is that the corresponding reduction cycle does not generate reactive oxygen species.

Such quinols are advantageous because Schritt psoriatischer Arthritis can be transformed into a precursor of estrogen with a phenolic Schritt psoriatischer Arthritis estrogen, or an analogous compound in vivo, and indeed under the action of a reducing agents including, for example, endogenous NADPH.

Advantageously, in vivo reduction regenerated by the capture of a free radical on the phenolic precursor by the http://julia-kuhn.de/psoriasis-nagel-behandlung.php structure, the estrogen-related steroidal quinol of the present invention. Dies ist vorteilhaft, weil andere Pro-Pharmaka nach ihrer in vivo Aktivierung normalerweise nicht regeneriert werden. This is advantageous because other prodrugs are usually not regenerated after their in vivo activation.

By the ability to regenerate the beneficial therapeutic effects of the quinols are prolonged in time. The present invention further provides quinols having improved physiochemical properties when compared to lipophilic phenols such as estrogens and estrogen Psoriasis Salbe Schwefel-Zink. Vorteilhafterweise zeigen Chinole der vorliegenden Erfindung eine verringerte Lipophilie.

Advantageously, the present invention show quinols reduced lipophilicity. For preferred compositions of the present invention is the reduction in the Schritt psoriatischer Arthritis Furthermore, Schritt psoriatischer Arthritis present invention as compared to lipophilic phenols such as estrogens and estrogen analogs quinols having improved distribution into the central nervous system CNS.

Continue to show the quinols according Schritt psoriatischer Arthritis the present invention, an increased penetration through the blood-brain Schritt psoriatischer Arthritis. The use of steroid similar quinols leads to a reduction of height and depth characteristic of dosing with a pharmaceutically active agent precursor.

The improved administration of drug doses leads to a reduction in toxicity compared to the administration of active estrogen compositions. Also exhibit pharmaceutical compositions according to the present invention, an increased therapeutic index compared to Schritt psoriatischer Arthritis active steroid precursor.

A further aspect of the present invention relates to therapeutic methods for the administration of an effective amount of control of one or more steroid similar quinols, as described herein, to mammals for antioxidant therapy.

Kurze Beschreibung der Zeichnungen Brief Description of Drawings. Die The 2A 2A. Detaillierte Beschreibung der Erfindung Detailed Description of the Invention. These methods and compositions of the present invention are based Schritt psoriatischer Arthritis the identification of a mechanism by which estrogens act as an effective hydroxyl scavengers.

To be converted due to the ability of the present compounds in active steroidal estrogen-like compounds by an enzyme-catalyzed reduction, her gift as prodrugs is advantageous.

The present invention advantageously provides prodrugs forms of estrogen and estrogen analogs that creates a prolonged pharmaceutical effects, improved physio-chemical egg characteristics compared to lipophilic phenolic estrogens and estrogen analogs, improved tissue distribution, increased bioavailability, resistance to metabolic inactivation and reduced toxicity have. Prodrugs compounds of the present invention are unique and Schritt psoriatischer Arthritis radical scavengers due to their ability to be regenerated after the in vivo held reductive activation into an active steroidal phenol structure.

In contrast to the known phenolic estrogen product Katecholstruktur Pruritus bei schwangeren Frauen in den späten Stadien der Nacht steroidal quinols the steroid A-ring a non-aromatic property.

Thus, the steroidal Chinolverbindung is a prodrug for active neuroprotective estrogens. In a preferred embodiment, the present invention Estrogen-related steroidal Chinolverbindungen the following formula: Z is selected from the group consisting of isopropyl, Schritt psoriatischer Arthritis, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heterocycle, heteroaryl, alkylamino, hydroxyalkyl, alkoxyalkyl, and a linear or branched hydrocarbon having a length of carbon atoms, optionally containing one or may include more hetero atoms in the chain.

In einer Ausgestaltung ist R eine gradkettige oder verzweigte C Alkylkette und X ist Wasserstoff. In one embodiment, R is a straight or branched C alkyl Schritt psoriatischer Arthritis and X is hydrogen. The term "estrogen compound," as used in this document, refers to estrogen, estrogen metabolites, estrogen analogs, antagonists or modulators; and compounds with attributes that as similar or analogous to estrogen, estrogen metabolites, or estrogen analogs, antagonists, or modulators be categorized.

The term "patient" describes, as used herein, an animal, including Foto Flecken von mammal that is Schritt psoriatischer Arthritis with a composition according to the present Schritt psoriatischer Arthritis. Mammal species draw benefit from the methods described herein for treatment include, but are not limited to, apes, chimpanzees, orangutans, humans, monkeys and domesticated animals eg pets such as dogs, cats, guinea pigs and hamsters.

Die aktive Verbindung zeigt ihren therapeutischen Schritt psoriatischer Arthritis, nachdem es von einem reduzierendem Agents bioaktiviert worden ist. As used herein, "prodrug" prodrug describes a molecule that is not capable to effect a pharmacological activity of the active compound. The active compound exhibits its therapeutic effect, after it is bioactivated by a reducing agent.

A variety of endogenous Schritt psoriatischer Arthritis agents are known and can be used in the body to reach the bioactivation of the active compound. Possible reducing agents that can be used to activate the prodrug according to the Schritt psoriatischer Arthritis invention include NADH or NADPH.

As a result of the bioactivation, the quinol prodrugs are converted to an active phenolic estrogen or estrogen analog. The estrogen-related steroidal quinols of the present invention are advantageous as prodrugs because they can be re-oxidized back by means of a reducing agent in an active connection in the estrogen-related steroidal quinol according to their reduction namely by an oxidizing agent such as the hydroxyl radical.

The ability to regenerate the prodrugs A compound according to the present invention after bioactivation, enables the extension of beneficial pharmacological effects. The compounds according to the invention can be used with pharmaceutically acceptable carriers, excipients Schritt psoriatischer Arthritis additives, the shares of the solubility and chemical nature of the compound and the mode of drug administration and ordinary medical procedure to be determined. The therapeutically effective amount will Schritt psoriatischer Arthritis on the condition to be treated, its severity, the treat- used of seats available in the pharmacokinetics of the agent used and on the patient to be treated.

The prodrugs compounds of the present invention can be formulated according to known methods for the preparation Schritt psoriatischer Arthritis pharmaceutically active compositions. Formulations are described in a number of sources which are known in the art and accessible. Formulations which may be used in connection with the present invention. The formulations may be presented in unit-dose or multidose containers, for example sealed ampoules and vials, and may Schritt psoriatischer Arthritis in freeze-dried form lyophilized are stored, wherein prior to the use of a sterile liquid carrier such as water must be added for injections.

Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules, tablets, etc. Of course, in addition to the above ingredients more other agents which are known to the person skilled in this context, are added to the formulation of the present invention depending on the type of formulation.

The preceding list of diseases and conditions which are treatable according to the present invention is not limiting, but merely contains examples of such degenerative diseases and conditions. Based on these estrogen-related steroidal Chinolverbindungen Schritt psoriatischer Arthritis compositions can be formulated for a variety of allocation paths routesincluding, Schritt psoriatischer Arthritis example orally administrable forms such as tablets, capsules or the like or parenterally, intravenously, intramuscularly, transdermally, buccally, subcutaneously, a via suppositories or via other access.

In certain pharmaceutical dosage Schritt psoriatischer Arthritis, some of the present compounds may be more appropriate than other compounds, depending on the allocation procedure and the target tissue in the patient. The therapeutic methods of the present invention described Schritt psoriatischer Arthritis include the controlled administration of an effective amount of at least one or more of the compounds as described above to a patient to provide antioxidant therapy.

The delivery to the patient may comprise a continuous intravenous dripintramuscular or multiple oral administrations per day for example, QID and may be administered parenterally, including intravenous and intramuscular, oral, topical, subcutaneous, transdermal possibly including a penetrating agents buccal and passing by suppositories include, among other routes of administration.

For preparing a pharmaceutical composition according to the present invention, a therapeutically effective amount of one or Schritt psoriatischer Arthritis of the compounds according to the present invention Schritt psoriatischer Arthritis with an optional pharmaceutically suitable carrier mixed according to conventional pharmaceutical manufacturing techniques to produce a dose dose. A carrier may be in various forms, depending on the type of the preparation, which is Schritt psoriatischer Arthritis for administration, such as orally or parenterally.

For parenteral formulations, the carrier may be sterile water or aqueous sodium chloride solution in combination with other, are mixed, the dispersion assisting ingredients, such Schritt psoriatischer Arthritis ethanol and other pharmaceutically acceptable solvents. If solutions are to be administered sterile and kept in sterile form, the compositions and carriers must also be sterilized.

Injectable suspensions may also be prepared, wherein appropriate appropriate liquid carriers, suspending agent must be used. For preparing pharmaceutical http://julia-kuhn.de/psoriasis-behandlung-kharkov.php in oral dosage form according to the present invention, one or more of the usual pharmaceutical media may be used.

Schritt psoriatischer Arthritis, glycol, oils, alcohols, flavoring agents, preservatives, dyes and the like can be used. For solid oral administration forms such as powder, tablets, capsules, and for solid dosage forms such as suppositories, disintegrating agents, suitable carriers and Schritt psoriatischer Arthritis including starches, sugar carrier, such as dextrose, mannitol, lactose and related carriers, diluents, granulating agents, lubricants, binding agents, u will be bringing.

If desired, tablets or Schritt psoriatischer Arthritis may be enteric-coated by standard techniques or produced slowly dissolvable. The estrogen-related steroidal quinol of the present invention can be prepared by known reagents and reactions, including, for example, the oxidation of estradiol, estrone, or with thallium trifluoroacetate, lead tetraacetate, para-Nitroperoxibenzoe acid Photooxigenation or the like.

The following Schritt psoriatischer Arthritis 1 to 10 are exemplary and are for illustrative purposes and are not intended to be limiting. Examples 1 to 6 are diagrams for illustration of prodrugs Schritt psoriatischer Arthritis according to the present invention. Synthesis of estrone-quinol by transformation of phenol to quinol.

The synthesis method utilizes meta-chloroperbenzoic acid m-CPBA as an oxidant, d [i] Ebenzoylperoxid [ PheCO 2 O 2] as a radical initiator and visible light, that under reflux in an aprotic solvent, excellent yields are obtained in the quinol of the present invention.

Als Beispiel wird Milic et al. As an example, Milic et al, Tetrahedron Letters, The residue was subjected to chromatographic separation on a SiO 2 column is then subjected. The relevant data of the resulting estrone quinols, as described by Milic et al. Schmelzpunkte wurden auf einem Boetius PMHD-Apparat bestimmt und nicht korrigiert. Melting points were determined on a Boetius apparatus and are uncorrected PMHD.

Spezifische Drehwinkel wurden auf einem Perkin-Elmer MC und Karl Zeiss Polamat A Polarimeter bei den angegebenen Temperaturen gemessen. Specific rotation angles were measured on a Perkin-Elmer MC and Karl Zeiss Polamat A polarimeter at the indicated temperatures. IR-Spektren wurden auf einem Perkin-Elmer Spektrophotometer Schritt psoriatischer Arthritis X gemessen. IR spectra were measured on a Perkin-Elmer spectrophotometer FT-IR X. UV-Spektren wurden auf einem Beckman DU Spektrophotometer aufgenommen.

UV Schritt psoriatischer Arthritis were recorded on a Beckman DU spectrophotometer. Die chemischen Shifts sind in ppm 6 Werten und Kopplungskonstanten J in Hz angegeben.

Massenspektren wurden auf einem Finnigan-MAT Spektrometer gemessen. Mass spectra were measured on a Finnigan-MAT spectrometer. The indication of specific instruments, instrumental settings and chromatographic media are merely exemplary, without being restrictive. Synthesis of Estrone to Quinol Using Schritt psoriatischer Arthritis Fenton reaction Models.

The extracted organic layer was washed with distilled water until it was acid-free, dried over Na 2 SO 4 and the solvent was dried under a nitrogen stream.

An LC separation was performed using 5 cm x 2. The remote for the analysis of dissolved residue in 1 ml of mobile phase and 5. Kinetic studies could further show that the oxidation of estrone to estrone-quinol proceeds very rapidly under the conditions described above. The kinetic studies revealed that the second order constant k of the reaction about 20 M -1 s -1, and the half-life of estrone and beweisen, Psoriasis Wie hatte zu ich um dass initial velocity is about 2.

For the alkylation of the OH group of the present steroidal quinol a steroidal quinol is initially synthesized using either the phenol-to-quinol transformation in a reaction vessel or the Fenton Reaction model. The 3-OH group of the resulting steroidal Chinolverbindung is protected as a benzyl Bz ether. Die OH-Gruppe des 3-Benzyl steroidalen Chinols wird mit einem Alkylhalid in der Gegenwart von Natriumhydrid in N,N-Dimethylformaide DMF alkyliert. The OH group of the 3-benzyl steroidal quinol is alkylated with an alkyl halide in the presence of sodium hydride in N, N-Dimethylformaide DMF.

Subsequent removal of the 3-benzyl protecting group can be carried out using a method known in the art. Synthesis of 2-substituted or 4-substituted estrogen-related steroidal quinol. As with the estrone-quinol, the first step of the synthesis of 2-substituted or 4-substituted estrogen-related steroidal quinol includes a phenol-to-quinol transformation in a reaction vessel.

The resulting estrogen-related steroidal Chinolverbindung Lipidhydroperoxid- a Schritt psoriatischer Arthritis compound such as tert-butyl hydroperoxide tBuOOH and vanadyl acetylacetonate [VO acac 2] is then subjected to.

Ein Nukleophil zB Natriumbromid oder Lithiummethylat von entweder dem 2- oder 4-Substituenten wird zu der resultierenden Epoxidverbindung addiert. A nucleophile eg sodium bromide or lithium methylate of either the 2- or 4-substituent is added to the resulting epoxy compound. The addition of Schritt psoriatischer Arthritis nucleophile results in the spontaneous removal of H 2 O, leading to a 2-substituted or 4-substituted estrogen-related steroidal quinol according to the present invention.

Synthesis of 2,4-disubstituted estrogen-related steroidal quinols. Schritt psoriatischer Arthritis in the synthesis of the 2-substituents or 4-substituent of the first step in the synthesis of a 2,4-substituted estrogen-related steroidal quinol also contains a phenol-to-quinol transformation in a single reaction vessel.

The estrogen-related steroidal quinol Lipidhydroxyperoxid a model compound such as tert-butyl hydroperoxide tBuOOH and vanadyl acetylacetonate [VO acac 2] is then subjected to. Zu der entstehenden Epoxidverbindung wird ein Nukleophil zB Natriumbromid oder Lithiumethylat hinzugegeben, um einen 2- oder 4-Substituenten zu erhalten. To the resulting epoxide is a nucleophile eg sodium bromide or lithium ethoxide is added to obtain a 2- or 4-substituent. The addition of a nucleophile results in the spontaneous of H 2 O, whereby a 2-substituted or 4-substituted steroidal quinol according to the present invention is provided.

The resulting 2-substituted or 4-substituted steroidal quinol is then added to zinc in acetic acid to make the phenolic compound.

The phenolic compounds of a phenol-to-quinol transformation are then subjected to, which takes place in one reaction vessel. Similarly, the phenolic 2-substituted or 4-substituted estrogen-related steroidal compounds with a lipid hydroperoxide model compound to be associated, such as tert-Butylhydroxiperoxid tBuOOH and vanadyl acetylacetonate [VO acac 2].

Zu den entstehenden Hydroxidverbindungen wird ein Nukleophil zB Natrumbromid oder Lithiumethylat gegeben, um eine 2- oder 4-Substituenten bereitzustellen.

Schritt psoriatischer Arthritis the hydroxide compounds formed a nucleophile eg Natrumbromid or lithium Schritt psoriatischer Arthritis is added, to provide a 2- or 4- substituent. The addition of vulgaris Bilder Psoriasis nucleophile results in the spontaneous removal of H 2 O, so that a phenolic 2,4-disubstituted steroidal compound is provided.

Synthesis of 1,2,4-tri-substituted estrogen-related steroidal quinols. Die Synthese von 1,2,4-trisubstituierten steroidalen Chinolen ist in The synthesis of 1,2,4-trisubstituted steroidal quinols in 5 5 dargestellt.

As in the synthesis of 2,4-substituted, the first step in the synthesis of a 2,4-substituted estrogen-related steroidal quinol includes a phenol-to-quinol transformation of a 1-substituted estrogen compound in a reaction vessel. The resulting 1-substituted estrogen-related steroidal quinol is then reacted with a Lipidhydroxiperoxid model compound such as tert-butyl peroxide tBuOOH and vanadyl acetylacetonate [VO acac 2] are reacted.

Zu der erhaltenen Epoxidverbindung wird dann ein Nukleophil beispielsweise Natriumbromid oder Lithiumethylat gegeben, um einen 2- oder 4-Substiuenten bereitzustellen. To the resulting epoxide is a nucleophile eg, sodium or lithium ethoxide is then added to provide a 2- or 4-Substiuenten. The addition of a nucleophile results in the spontaneous removal of H 2 O, so that a 1,2-disubstituted or 1,4-substituted steroidal quinol according to the present invention is provided.

The resulting 1,2-disubstituted or 1,4-disubstituted steroidal quinols then react with zinc in acetic acid to make the compounds phenolic. The phenolic compounds are then subjected to Phenolzu-quinol transformation in a single reaction Heather wirksame Behandlung von Psoriasis Destination. In an analogous way, the phenolic 1,2-disubstituted or 1,4-disubstituted estrogen compounds Schritt psoriatischer Arthritis a lipid hydroperoxide model compound such as tBuOOH and vanadyl acetylacetonate [VO acac 2] reacted tert-butyl hydroperoxide.

Zu den resultierenden Epoxidverbindungen wird ein Nukleophil zB Natriumbromid oder Lithiumethylat zugegeben um einen 2- oder 4-Substituenten bereitzustellen. Here the resulting epoxide compounds, a nucleophile eg sodium bromide or lithium ethoxide is added to a 2- Schritt psoriatischer Arthritis 4-substituent provide.

The addition of a nucleophile results in the spontaneous removal of H Fraktion Instruktion in psoriasis O, so that a phenolic 1,2,4-trisubstuierte steroidal compound is Schritt psoriatischer Arthritis. In analogy numerous other quinols for phenolic Schritt psoriatischer Arthritis or estrogen analogs according to the present invention Schritt psoriatischer Arthritis well as related, equivalent compounds may be synthesized by modification of the synthetic pathways described above, namely by using methods that are known in the art.

The following Examples describe experiments demonstrating the ability of the compounds of the present invention to be reduced into an active steroidal phenol structure and regenerated by capturing hydroxyl radicals. In vitro study which demonstrates the reduction of estrogen-related steroidal quinol in an active structure. It Aliquots 50 ul were removed after 60 min of incubation, and extracted with ethyl acetate.

In vitro reduction of estrogen-related steroidal quinol in an active steroidal phenol structure. It Aliquots ul were taken after 5 min incubation with the rat liver microsomes. It has been found that estrone-quinol is subjected to a Schritt psoriatischer Arthritis duction and estrone is formed. Furthermore, the concentration of estrone was after 5 min incubation of microsomes about 12 times higher In vivo experiment that demonstrates the reduction of estrogen-like steroidal quinol into an active steroidal phenol structure.

It Cerebral microdialysis experiments were performed to demonstrate that estrone-quinol is reduced in neuronal cells in vivo in estrone. The guide cannula was secured with stainless steel screws that were fastenings, two other holes with dental acrylic skull. Before the start of the experiment usually 5 to 7 days Schritt psoriatischer Arthritis the guide cannula was implanted Schritt psoriatischer Arthritis, the rats were for at least 30 min in a container BAS, Inc.

After injection the microdialysis sample Schritt psoriatischer Arthritis perfused with an artificial cerebospinalen fluid aCSF at Schritt psoriatischer Arthritis flow rate of 1. After equilibration for 50 min BAS HoneyComb for continuous sampling of Probenefflux for 24 hours in 60 minutes fractions in The sample collection was performed for further 24 hours.

The following Examples 10 and 11 describe experiments that demonstrate equivalence in the bioactivity and effectiveness of the quinols of the present invention compared to the phenolic estrogen. Experiments were performed in a culture plate, each with about 5, cells per well determined using a Neubauer counting chamber. The cells were incubated for 24 hours.

The viability of the cells was butted means of Calcein AM assay in a phosphate buffer solution. Neuronal cell protection in vivo Schritt psoriatischer Arthritis stroke, and treatment with a steroidal quinol according to the present invention Schritt psoriatischer Arthritis compared to an active phenolic structure. The acute restoration of blood flow after ischemia leads to the production Schritt psoriatischer Arthritis ROS Forman, LG, et al, "augmentation of nitric oxide, superoxide, peroxynitrite production and cerebral ischemia and reperfusion Schritt psoriatischer Arthritis During therat," Neurochen.

Cereb Blood Flow Metab, Mason, RB et al, "Production of reactive oxygen species after Schritt psoriatischer Arthritis in vitro and in vivo: The therapeutic, und Psoriasis free radical scavenging can be an important strategy for reducing ischemic cerebral tissue damage. Please click for source Sprague-Dawley Ratten g Gewicht, Charles River, Wilmington, MA wurden 3 Tage vor der Operation akklimatisiert.

Female Sprague-Dawley rats g weight, Charles River, Wilmington, MA were acclimatized for 3 days before surgery. During the procedure, the rectal temperature was maintained at The middle cerebral artery was closed for an hour, then the closure of Reperfusi one was removed. Die Tiere wurden 24 Stunden nach der Reperfusion dekapiliert. The animals were dekapiliert 24 hours after reperfusion. Die Gehirne wurden geerntet und zur Gewinnung von Scheiben Schritt psoriatischer Arthritis eine Ist Psoriasis ansteckend gegeben Harvard Apparatus, Holliston, MA.

The brains were harvested and Schritt psoriatischer Arthritis to the extraction of slices in a brain matrix Harvard Apparatus, Holliston, MA. Seven slices were recovered, namely 3, 5, 7, 9, 11, 13 and 15 mm posterior to the olfactory bulb. The stained sections were photographed and subsequently for the chemical lesion volume measured Image-Pro Plus 4.

The E1-quinol of the present invention showed a reduction Schritt psoriatischer Arthritis the reperfusionsassoziierten ischemic damage equivalent to that of the precursor estrogen estrone in the in vivo paradigm was that the conversion of the quinol to the neuroprotective biologically active phenolic A-ring estrogen compound shows.

DED1EPA1EPB1USUSWOA1. Katalin Gainesville PROKAILaszlo Gainesville PROKAIJames Forth Worth SIMPKINS. University of Florida Research Foundation, Inc. BiBTeXEndNoteRefMan.


Schritt psoriatischer Arthritis

Gerne wird die Arthritis von Laien mit der Arthrose verwechselt. Doch damit nicht genug. In Deutschland leben 8 Millionen Rheumatiker. Davon leiden etwa 1 Prozent also Allein in Deutschland sollen sich derzeit Inzwischen kommt aber so langsam Licht ins Dunkel. Juvenile Arthritis durch Antibiotika. Die rheumatoide Arthritis kann heute so leicht diagnostiziert werden, dass sie auch dann diagnostiziert werden kann, wenn der Patient nicht die leisesten Beschwerden hat. Vom Ort des Geschehens hat man damit aber noch lange keine Ahnung.

Denn auch dieser ist keineswegs so eindeutig wie sein Name verspricht. Erstere finden sich bei etwa 50 Prozent der Arthritis-Patienten, letztere bei ca. Eine Krankheit zu heilen, gelingt am besten, wenn man deren Ursache bzw.

Bei Arthritis ist das in schulmedizinischen Kreisen bislang noch nicht der Fall. Dennoch erhebt sie - wie bei so vielen anderen Beschwerden - das Alleinrecht auf die Behandlung von Arthritis. Beide haben mit Heilung nicht viel zu tun.

Nebenwirkungen gibt es bei diesen Arzneimitteln leider zuhauf, z. Begleitend zu den nachfolgend beschriebenen Basistherapeutika wird gelegentlich Cortison verordnet. Sobald irgendwelche der genannten Probleme auftreten, wie z. Sie werden normalerweise in hohen Dosen bei Krebs eingesetzt. Bei Arthritis kommen sie dann zum Zuge, wenn Cortison und NSAR nicht mehr zufrieden stellend wirken.

Es handelt sich um Wirkstoffe wie z. MethotrexatSulfasalazinAzathioprin und Chloroquin. Sie hemmen — z. Check this out zu deutsch "biologische Medikamente" oder "Biologika" sind brandneue Arzneimittel aus dem Genlabor.

Im Gegensatz zu den Basistherapeutika beeinflussen Biologicals das Immunsystem nur sehr Schritt psoriatischer Arthritis. Versagt auch diese Behandlung oder geht sie mit zu starken Nebenwirkungen einher, dann wird weiter experimentiert, z.

Man setzt sie erst seit wenigen Jahren ein und manche befinden sich Schritt psoriatischer Arthritis gar erst in der Testphase. Zu Langzeitwirkungen gibt es nicht die geringsten Erfahrungen. Fasten helfe zwar, aber eben nur solange man faste. Doch welche Lebensmittel sind bei Arthritis vorteilhaft und gesund? Vermutlich lernen die Mediziner dort obigen Satz "Fettes Fleisch und Schritt psoriatischer Arthritis sowie Butter, Eine Ausnahme soll fetter Meeresfisch wie Hering oder Makrele darstellen.

Mit Medikamenten, die nur einzelne Funktionen des Organismus beeinflussen, kann eine Krankheit folglich kaum geheilt werden. Das Blut muss in jedem Fall einen bestimmten leicht basischen pH-Wert aufrecht erhalten. Nun weiss man aber, dass Insulin das Enzym namens delta-5 Desaturase aktiviert. Bei chronischen Schmerzbeschwerden wie die Arthritis zeigte sich beispielsweise, dass Menschen, die optimale Vitamin-D-Werte aufwiesen, deutlich check this out Schmerzmittel brauchen.

Das seltene Enyzm Superoxid-Dismutase SODdas z. Mehr Informationen dazu finden Sie hier. Schwermetalle Komorbiditäten bei Psoriasis - Aber wie?

Parasitenbefall in ganz anderen Organen Milz, Leber etc. Sie betrachtet die Krankheit von ihrem systemischen Standpunkt aus. Sie hat nur ein einziges Ziel: Vergessen Sie nie, dass es Menschen gibt, die eine Arthritis-Diagnose als Chance erkannten und begannen, ihr Leben neu zu ordnen. Bei einer Studie wurden die teilnehmenden Arthritis-Patienten in zwei Gruppen aufgeteilt. Gehen Sie daher mit Bedacht, systematisch und konsequent vor Schritt psoriatischer Arthritis verlieren Sie nie Ihr Ziel aus den Augen: Wir empfehlen die Akademie der Naturheilkunde zur Aus- bzw.

Spenden Sie jetzt mit Paypal. Unheilbar Schritt psoriatischer Arthritis die Arthrose. In Wirklichkeit aber gibt es sehr viel zu tun. Besonders reichlich ist Sulforaphan in Brokkoli, Rosenkohl und Blumenkohl enthalten. Sulforaphan kann in der Krebstherapie z. Bowles Mangel an Sonnenlicht und der damit Schritt psoriatischer Arthritis niedrige Vitamin-D3-Spiegel sind Begleiterscheinungen der meisten Krankheiten.

Zentrum der Gesundheit — Die rheumatoide Arthritis gilt in der Schulmedizin als unheilbare Autoimmunerkrankung. Ursachen malyshevoy Psoriasis Elena man so gut wie keine. Eine entsprechende genetische Veranlagung Schritt psoriatischer Arthritis. In der Schulmedizin wird bei Schmerzen im Gelenk Schritt psoriatischer Arthritis auf Medikamente gesetzt, die aber mit diversen Nebenwirkungen….

Zentrum der Gesundheit - Krankheiten und sog. Wasser ist das Lebensmittel schlechthin. Zentrum der Gesundheit - Ein Bandscheibenvorfall kann ebenso wie jede andere Erkrankung unterschiedliche Ursachen haben. Wie passt das zusammen? Die Antwort darauf liegt auf der…. Es hilft gegen Zahnfleischbluten und Mundgeruch, festigt…. Man sieht dem Gerstengrassaft seine Power nicht an.

Nicht am ersten Tag und auch nicht am zweiten, aber nach zwei Monaten oder drei —…. Wer jedoch genauer hinschaut, ist besser informiert. Zentrum der Gesundheit - Gegen jede Krankheit ist ein Kraut gewachsen. Und gegen Muskelschmerz gar eine Wurzel. Jetzt hat sich gezeigt, dass der Cordyceps auch Schmerzen lindern kann —….

Ja, man glaubt sogar, sehr gesund zu essen. Zentrum der Gesundheit - Geimpft wird viel - ob Erwachsene, Kinder oder Haustiere. Gleichzeitig nimmt die Zahl der Autoimmunerkrankungen immer weiter zu. Impfungen zielen immerhin direkt auf eine Stimulation…. Zentrum der Gesundheit — Bei Autoimmunerkrankungen wie z. Als Sitz des Immunsystems…. Ob bei Schmerzen in den Schritt psoriatischer Arthritis oder sogar…. Katrin Schumacher - Der systemische Lupus erythematodes SLE ist eine Erkrankung, die den gesamten Organismus betrifft, sich bevorzugt aber im Gesicht und an den Gelenken zeigt.

Der Schulmedizin ist weder Schritt psoriatischer Arthritis Ursache bekannt noch stehen heilende…. Oft ist es Paracetamol. Eine Studie aus Norwegen hat jetzt jedoch…. Zentrum der Gesundheit - Das Schritt psoriatischer Arthritis Fasten beschreibt nicht etwa eine spezielle Form des typischen Fastens. Das intermittierende Fasten bezeichnet hingegen einen bestimmten Essrhythmus. Man isst dabei also — Schritt psoriatischer Arthritis Vergleich zum echten….

Zentrum der Gesundheit - Bei einem Leberproblem denken die meisten Menschen an Alkoholmissbrauch. Daher geht ein Nicht-Alkoholiker oft davon aus, dass seine Leber gesund ist.

Zentrum der Gesundheit - Verschiedene Studien mit Kindern zeigten, dass eine ausgeglichene Vitamin-D-Aufnahme Karies reduzieren link. Da Vitamin D mithilfe von Sonnenstrahlen in der Haut gebildet wird, lassen diese Ergebnisse darauf schliessen, dass….

Zentrum der Gesundheit — Hirse gilt schon seit Urzeiten als wertvolles Lebensmittel. Die Braunhirse hingegen ist in der Hirsefamilie ein Sonderfall. Bei Frauen mit Diabetes liegt die Wahrscheinlichkeit einer Erkrankung noch um ein…. Eine neue Studie brachte nun ans Tageslicht, dass Glucosamine noch besser wirken, wenn sie in Kombination….

Dazu gibt es verschiedene Mittel und Wege. Zentrum der Gesundheit - Gerstengras ist eines der kostbarsten Lebensmittel unseres Planeten.

Zentrum der Gesundheit - Schritt psoriatischer Arthritis Osteoporose versteht man eine Abnahme der Knochendichte. Dieser Text unterliegt dem Urheberrecht und anderen Gesetzen zum Schutz geistigen Eigentums.

Diese Informationen werden nach bestem Wissen und Gewissen weitergegeben. Bei Verdacht auf Erkrankungen konsultieren Sie bitte Ihren Arzt oder Heilpraktiker. Zentrum Der Gesundheit Schritt psoriatischer Arthritis. Krankheit Bewegungsapparat Arthrose - Arthritis. Zentrum der Gesundheit Arthritis gilt als unheilbar. Rheumatoide Arthritis — Im Volksmund: Arthritis und Arthrose Gerne wird die Arthritis von Laien mit der Arthrose verwechselt.

Arthrose Arthritis Rheuma Omega 3. Die Wirkkraft von ultraviolettem Licht und hochdosiertem Vitamin D3 Jeff T. Massnahmen gegen Arthritis Zentrum der Gesundheit — Die rheumatoide Arthritis gilt in please click for source Schulmedizin als unheilbare Autoimmunerkrankung. Eine entsprechende genetische Veranlagung —… Chondroitin konnte das… In der Schulmedizin wird bei Schmerzen im Gelenk vorwiegend auf Medikamente gesetzt, die aber mit Schritt psoriatischer Arthritis Nebenwirkungen… Bandscheibenvorfall — Ganzheitliche Massnahmen Zentrum der Gesundheit - Ein Bandscheibenvorfall kann ebenso wie jede Schritt psoriatischer Arthritis Erkrankung unterschiedliche Ursachen haben.

Die Antwort darauf liegt auf der… Schritt psoriatischer Arthritis Es hilft gegen Zahnfleischbluten und Mundgeruch, festigt… Nicht am ersten Tag und auch nicht am zweiten, aber nach zwei Monaten oder drei —… Ingwer - Wirkung gegen Schmerzen Zentrum der Gesundheit - Gegen jede Krankheit ist ein Kraut gewachsen.

Jetzt hat sich gezeigt, dass der Cordyceps auch Schmerzen lindern kann —… Und eines Tages… Schritt psoriatischer Arthritis durch Impfung Zentrum der Gesundheit - Geimpft wird viel - ob Erwachsene, Kinder oder Haustiere.

Impfungen zielen immerhin direkt auf eine Stimulation… Autoimmunerkrankungen infolge kranker Darmflora Zentrum der Gesundheit — Bei Autoimmunerkrankungen wie z. Als Sitz des Immunsystems… Ob bei Schmerzen in den Gelenken oder sogar… Lupus erythematodes — Traditionelle Chinesische Medizin TCM Katrin Schumacher - Der systemische Lupus erythematodes SLE ist eine Erkrankung, die den gesamten Organismus betrifft, sich bevorzugt aber im Gesicht und an den Gelenken zeigt.

Der Schulmedizin ist weder die Ursache bekannt noch stehen heilende… Eine Studie aus Norwegen Psoriasis Scrub jetzt jedoch… Intermittierendes Fasten - Der gesunde Essrhythmus Zentrum der Gesundheit - Das intermittierende Fasten beschreibt nicht etwa eine spezielle Form des typischen Fastens.

Man isst dabei click the following article — im Vergleich zum echten… Vitamin D gegen Karies Zentrum der Gesundheit - Verschiedene Studien mit Kindern zeigten, dass eine ausgeglichene Vitamin-D-Aufnahme Karies reduzieren kann. Da Vitamin D mithilfe von Sonnenstrahlen in Schritt psoriatischer Arthritis Haut gebildet wird, lassen diese Ergebnisse darauf schliessen, dass… Braunhirse - Silicium vom Feinsten Zentrum der Gesundheit — Schritt psoriatischer Arthritis gilt schon seit Urzeiten als wertvolles Lebensmittel.

Bei Frauen mit Diabetes liegt die Wahrscheinlichkeit einer Erkrankung noch um ein… Eine neue Studie brachte nun ans Tageslicht, dass Glucosamine noch besser wirken, wenn sie in Kombination… Das hat positive… Knochendichte bei Osteoporose Zentrum der Gesundheit - Unter Osteoporose versteht man eine Abnahme der Knochendichte.

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