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Suspendieren Psoriasis

Country of ref document: Spc suppl protection certif: Technisches Gebiet Technical field. Die vorliegende Erfindung bezieht sich auf neue Benzimidazol-Derivate mit hervorragenden Eigenschaften als Pharmazeutikum. The present invention relates to novel benzimidazole derivatives having excellent properties as a pharmaceutical. Specifically, the present invention relates to a prodrug of a benzimidazole derivative having a particular structure, which has a strong and long-lasting antagonistic activity against angiotensin II and a blood pressure lowering effect and suspendieren Psoriasis activity and suspendieren Psoriasis agents read more Proyphylaxe or treatment of circulatory diseases such as hypertensionheart disease cardiac this web page, heart failure, myocardial infarction and the suspendieren Psoriasisnephritis, stroke and the like and metabolic diseases such as diabetes and the like is suitable, and the use thereof.

Stand der Technik State suspendieren Psoriasis the art. Angiotensin II causes vasoconstriction via an angiotensin II receptor in the cell membrane and elevates blood pressure.

Therefore, an angiotensin II receptor Kopfhautpsoriasis-Creme Salbe can be an effective therapeutic drug for circulatory diseases source as hypertension and the like. Suspendieren Psoriasis JP-A und dergleichen. As one of the means for enhancing suspendieren Psoriasis use of a pharmaceutical agent, the conversion of a compound having a certain pharmacological activity suspendieren Psoriasis a prodrug is known.

For example be as a carboxylic acid prodrug Alkylcarbonyloxymethylester, 1-Alkylcarbonyloxyethylester, Alkyloxycarbonyloxymethylester, 1-Alkyloxycarbonyloxyethylester and 5-methyloxo-1,3-dioxolyl methyl ester to a high degree for a compound of the insufficient expression of type by oral administration is used in the development of pharmaceutical products to the time.

In addition, farnesol ester, which is a fat-soluble substance of indomethacin, and ethyl ester known as an ACE inhibitor that they provide a more sustained activity and the like. Als Ester von Verbindung A werden Methylester Verbindung B1- Suspendieren Psoriasis ethylester Verbindung C und Acetoxymethylester Verbindung D speziell in As esters of compound A are methyl ester compound B1- cyclohexyloxycarbonyloxy ethyl just click for source compound C and acetoxymethyl ester compound Despecially in JP-A JP-A beschrieben.

The present invention aims to provide a novel compound as an agent for prophylaxis or treatment of circulatory diseases such as hypertension and the like and metabolic diseases such as suspendieren Psoriasis and the like, superior. Offenbarung der Erfindung Suspendieren Psoriasis of the Invention. The inventors of the present invention have Stress Menü psoriatischer Arthritis und intensive studies to find a new compound which is suspendieren Psoriasis potent and superior duration of action by oral administration has, so as to provide a pharmaceutical agent and as an agent for the prophylaxis or treatment of suspendieren Psoriasis diseases such as hypertension like and suspendieren Psoriasis diseases suspendieren Psoriasis as diabetes and the like, clinically suspendieren Psoriasis particularly useful.

As a result, they found suspendieren Psoriasis a prodrug compound having a particular structure, which is converted into a compound A suspendieren Psoriasis the living body, a higher level of security has, and has suspendieren Psoriasis better properties as a pharmaceutical agent such as anti-hypertensive by the unexpectedly strong and long lasting effectpossible stable control of blood pressure for a long period and the like is shown, and completed the present invention.

Das Salz einer durch die Formel I dargestellten Verbindung kann jedes beliebige sein, solange es ein pharmakologisch annehmbares Salz ist. The salt of a I compound represented by the formula can be any as long as it is a pharmacologically acceptable salt.

As such salt, salts of a Suspendieren Psoriasis compound represented by the formula with an inorganic base eg alkali metals such as sodium, potassium and the like; alkaline earth metals such as calcium, magnesium and the like, etc.

Als Salz der durch die Formel I dargestellten Verbindung werden Alkalimetallsalze der durch die Formel I dargestellten Verbindung bevorzugt. As the salt of Formula I suspendieren Psoriasis represented alkali metal salts of I compound represented by the formula are preferable. Von diesen wird ein Kaliumsalz besonders bevorzugt. Of these, a potassium salt is particularly preferred. Die durch die Formel I dargestellte Verbindung kann mit einem Isotop zB 3 H, 14 C, 35 S, I und dergleichen und dergleichen markiert sein.

The compound represented by the formula I shown can be labeled with an isotope such as 3 Suspendieren Psoriasis, 14 C, 35 S, I and the like and the like. Die Verbindung I kann zB durch ein im Folgenden gezeigtes Verfahren oder ein dazu analoges Verfahren und dergleichen hergestellt werden.

The compound I can be prepared for example by a method shown below or a method analogous thereto and the like. While the yield of compound I obtained by the following method may vary depending on the reaction conditions used, compound I easily with a suspendieren Psoriasis purity by a conventional means of separation or purification for example, recrystallization, column chromatography and the like can be obtained suspendieren Psoriasis the product by such methods.

The compound I can be prepared by reacting a reactive derivative for example, a mixed acid anhydride, an acid halide and the like represented by the formula II compound represented Compound A or a salt thereof hereinafter sometimes II as a compound having a corresponding alcohol IV HO-R 1 or a salt thereof are prepared. Verfahren a method Psoriasis-Behandlung in Novosibirsk wobei X ein Halogenatom Chlor, Brom, Suspendieren Psoriasis usw.

Method a comprises reacting compound II with suspendieren Psoriasis acylating agent III in the presence suspendieren Psoriasis a base to give a mixed acid anhydride, and reacting the resulting compound with a corresponding alcohol IV HO-R 1 in the presence of a base to allow esterification.

The mixed suspendieren Psoriasis anhydride is employed, using mol of a base suspendieren Psoriasis about of an acylating agent relative to 1 mol of compound IIprepared in a solvent. Subsequently, suspendieren Psoriasis corresponding alcohol is added to allow reaction, or suspendieren Psoriasis the salt salt of the base with HX was filtered off, the filtrate was suspendieren Psoriasis, the residue was diluted with a solvent and the corresponding alcohol and a base were added to to allow a reaction, so that esterification can be carried out.

As the base, triethylamine, diisopropylethylamine, DBU, 4-dimethylaminopyridine, sodium hydride, suspendieren Psoriasis t-butoxide, potassium carbonate and sodium carbonate and the like can be used. Als Acylierungsmittel werden Pivaloylchlorid, Ethylchlorcarbonat, Isobutylchlorcarbonat oder 2,4,6-Trichlorbenzoylchlorid, 2,6-Dichlorbenzoylchlorid, 2,4,6-Tribrombenzoylchlorid, 2,3,6-Trimethyl-4,5-dinitrobenzoylchlorid und dergleichen, die im Bulletin der Chemical Society of Japan, Bd.

Suitable acylating agents are pivaloyl chloride, ethyl chlorocarbonate, isobutyl chlorocarbonate, or 2,4,6-trichlorobenzoyl chloride, 2,6-dichlorobenzoyl chloride, 2,4,6-Tribrombenzoylchlorid, 2,3,6-trimethyl-4,5-dinitrobenzoyl chloride and the like, in the Bulletin the Chemical Society of Japan, Vol. As the solvent, generally, dichloromethane, chloroform, 1,2-dichloroethane, ethyl acetate, tetrahydrofuran, toluene, acetonitrile, acetone, ethyl methyl ketone, dioxane, dimethylformamide, dimethylacetamide, dimethylsulfoxide and the like may be used.

Verfahren b process b wobei R 1 wie oben definiert ist. Method B comprises reacting a Formula II compound represented or a salt thereof with thionyl chloride or oxalyl chloride in the presence of a catalyst such as DMF and the like to give an acid chloride, and reacting the acid chloride with a corresponding alcohol IV in the presence of a Konzeption Kindes mit Psoriasis to allow esterification.

The acid chloride is carried out using about mol suspendieren Psoriasis thionyl chloride or oxalyl chloride relative to 1 mol of compound IIif necessary in the presence of a catalytic amount suspendieren Psoriasis DMF in a suspendieren Psoriasis. After subsequent concentration, Juckreiz, Psoriasis verursacht bei Kindern soll enable the reaction, a solvent, and then the corresponding alcohol HO-R 1 and the base are added to carry out esterification.

As the base used are those which are the bases and the like used in the process a similar. As the solvent be used those similar to the solvents and the like used in the process a.

Verfahren c umfasst die Umsetzung einer durch die Formel II dargestellten Verbindung oder eines Salzes davon zB ein Salz suspendieren Psoriasis einem Alkalimetall wie Natrium, Kalium this web page dergleichen; ein Salz mit einem Erdalkalimetall wie Calcium, Magnesium und dergleichen, usw. Method C involves the reaction of a Formula II compound represented or a salt thereof eg suspendieren Psoriasis salt with an alkali metal such as sodium, potassium and the like; a salt with an alkaline earth metal such as calcium, magnesium and the like, etc.

The esterification is carried out using about mol of a base and about mol of an alkylating agent relative to 1 mol of compound IIcarried out in a solvent. As the base used are those which are the bases used in Method a and the like similarly. Verfahren d process d wobei R 1 wie oben definiert ist. Method c comprises reacting compound II suspendieren Psoriasis the corresponding alcohol IV in the presence of a condensing agent to perform esterification.

The esterification is carried out using about mol of the condensing agent and about mol of suspendieren Psoriasis corresponding alcohol IV relative to 1 mol of compound IIcarried out in a solvent. Als Kondensationsmittel werden DCC, WSC, Mitsunobu-Reagenzien und dergleichen verwendet. As condensing agent DCC, WSC, Mitsunobu reagents and the like. As the solvent used are those suspendieren Psoriasis are the solvents used in Method a and the like similarly.

Die Verbindung II kann durch das in The compound II can be prepared by the in JP-A JP-A beschriebene Verfahren und dergleichen hergestellt werden. Described method and suspendieren Psoriasis like. When the compound I is obtained in free form, it can be transferred by a per se known method or a method analogous thereto in suspendieren Psoriasis intended salt. In contrast, when it is obtained as a salt, it suspendieren Psoriasis be converted by a method known per se or a method analogous thereto suspendieren Psoriasis a free form or another salt intended.

When optical isomers of compound I exist, such individual optical isomers and suspendieren Psoriasis mixture thereof are suspendieren Psoriasis course included in the scope of the present invention.

Verbindung I kann ein Kristall sein und die Form eines Einkristalls oder die Form eines Gemisches mehrerer Kristalle haben. Compound I may be a crystal, and have the form of a single crystal form or a mixture of several crystals. Crystals can be produced by crystallization according to a crystallization method known per se.

Verbindung I ist vorzugsweise ein Kristall. Compound I is preferably a crystal. Verbindung I kann ein Solvat zB Hydrat suspendieren Psoriasis. Compound I may be a solvate eg hydrate etcand both solvate and a suspendieren Psoriasis for example, non-hydrate are included in the scope of suspendieren Psoriasis present invention.

The thus prepared compound of the present invention has a lower toxicity and is safe in other words, from the viewpoint of acute toxicity, chronic toxicity, genetic toxicity, reproductive toxicity, cardiac toxicity, drug interaction, carcinogenicity and the like from seen an excellent pharmaceutical agent and is in the living body of an animal, particularly a mammal eg, human, monkey, cat, pig, horse, bovine, mouse, rat, guinea pig, dog, rabbit, etc.

Since compound A normalizes the intracellular insulin signal-transmission mechanism, which mainly causes insulin resistance, thereby the insulin resistance is reduced, and the effect of insulin is suspendieren Psoriasis, it has a glucose tolerance-improving effect. Therefore, the compound of the present invention to mammals eg, human, monkey, cat, pig, horse, bovine, mouse, rat, guinea pig, suspendieren Psoriasis, rabbit etc.

Die Verbindung der vorliegenden Erfindung kann auch zur Behandlung von Patienten mit hohem normalen Blutdruck mit Diabetes verwendet werden. The compound of the present invention can also be used for treating patients suspendieren Psoriasis high normal blood pressure with diabetes.

Since compound A has a strong antagonistic activity against angiotensin II, the compound of the present invention as an agent for the prophylaxis or treatment of a disease or a disease whose onset is introduced is useful suspendieren Psoriasis the contraction or growth of blood vessels or organic disorder is developed, which is expressed via an angiotensin II receptor, or to the presence of angiotensin II, or a factor suspendieren Psoriasis, by the presence of angiotensin II in mammals suspendieren Psoriasis, human, monkey, cat, pig, horse, cattle mouse, rat, guinea pig, dog, rabbit, etc.

As such diseases as hypertension, circadian rhythm abnormality of hypertension, heart disease eg, cardiac hypertrophy, acute heart failure and chronic heart failure, including congestive heart failure, cardiac myopathy, angina pectoris, myocarditis, atrial fibrillation, arrhythmia, tachycardia, cardiac infarction etc.

Aneurysma, Suspendieren Psoriasis, Zerebralarteriosklerose, periphere Arteriosklerose usw. As Meniere syndrome, tinnitus, dysgeusia, dizziness, vertigo, dysphagia, etc. Suspendieren Psoriasis the compound of the present invention, both during the day and at night can maintain a constant hypotensive action, a reduction of the dose and frequency as compared with the administration of suspendieren Psoriasis compound A, possible.

In addition, they can suppress naftaderm Psoriasis a particularly problematic increase in the blood pressure before and after rising in patients with hypertension. In addition, the compound of the present invention improved by longer term sustained suppression of the action of angiotensin II, a disorder or abnormality or suppresses suspendieren Psoriasis progression of the same causes in the biofunction and physiological action, the disorders in adults, and various diseases which are associated with aging, etc.

Morphogenese- bis Proliferationtyp usw. Morphogenese- to proliferation type etc. Of these, the present invention can be see more as an agent for the primary and secondary prophylaxis or treatment suspendieren Psoriasis organ disorders associated with various diseases such as cerebrovascular disorder and related organ dysfunction, organ disorder associated with cardiovascular disease, organ disorder associated with diabetes is connected, organ disorder after intervention etc.

Since compound Suspendieren Psoriasis has an activity of inhibiting proteinuria, the compound of the present invention can be used suspendieren Psoriasis particular as agent for protecting kidney. Therefore, the compound of the present invention can be advantageously used when the patients have developed insulin resistance, impaired glucose tolerance, diabetes or hyperinsulinemia simultaneously suspendieren Psoriasis diseases mentioned above or clinical conditions.

Since compound A has an activity of inhibiting body weight gain, the compound of the present invention can be used as a body weight gain inhibitor to mammals. Target animals click at this page be any mammal, suspendieren Psoriasis which a body weight gain is to be avoided.

In addition, the body weight gain be a precursor suspendieren Psoriasis obesity or body weight gain of obese patients. The suspendieren Psoriasis criteria about diabetic criteria were reported by the Japan Diabetes Society th.

In addition, new diagnostic criteria in by the ADA The American Diabetes Association and reported by WHO in in terms of diagnostic criteria for diabetes. The compound of the present invention can improve agent or an agent for the prophylaxis or treatment of diabetes, borderline case type, impaired glucose tolerance, IFG Seborrhoische Dermatitis, wie von Psoriasis zu unterscheiden Fasting Glucose and IFG Impaired Fasting Glycemia suspendieren Psoriasis defined above by the above-mentioned new diagnostic criteria used become.

In addition, the compound of the present invention can also be used to prevent progression of the limit of the type which impaired glucose tolerance, IFG Impaired Fasting Glucose or IFG Impaired Fasting Glycemia to diabetes. The compound of the present invention is useful as an agent for the prophylaxis or treatment of metabolic syndrome.

Because patients with metabolic syndrome have an extreme high incidence of cardiovascular diseases as compared to patients who exhibit only with lifestyle related diseases, the prophylaxis or treatment of metabolic syndrome is quite important to prevent cardiovascular diseases. The criteria for diagnosis of metabolic syndrome were announced in by the WHO and NCEP Definition, Diagnose und Klassifizierung von Diabetes Mellitus und ihren Komplikationen.

Diagnose und Klassifizierung von Diabetes Mellitus, Weltgesundheitsorganisation, Genf According to the criterion of Suspendieren Psoriasis, patients with at least two diseases chosen from abdominal obesity, dyslipidemia high serum triglycerides or low HDL cholesterolhypertension in addition to Hyperinsulinamie or article source glucose in the fasting state, suspendieren Psoriasis the metabolic syndrome comprising diagnosed World Health Organization: Definition, Diagnosis and classification of diabetes mellitus and its complications part I:.

Executive Summary of the Third Report of National Cholesterol Education Program NCEP Expert Panel an Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Adults Treatment Panel III. The Journal of the American Medical Association, Band, According to the criterion of Adult Treatment Panel III of the Suspendieren Psoriasis Cholesterol Education Program, which is an indicator for managing ischemic heart diseases in America, patients with at click here three diseases selected from abdominal obesity, high triglycerides, low HDL cholesterol, suspendieren Psoriasis blood pressure and blood glucose having diagnosed the fasting state as metabolic syndrome National cholesterol Education Program.

Executive Summary of the Third Report of the National cholesterol Education Program NCEP Expert panel on Detection, evaluation, and Treatment of high Blood cholesterol in Suspendieren Psoriasis Adults Treatment suspendieren Psoriasis III the Journal of the American Medical Association, Vol, Die Verbindung der vorliegenden Erfindung kann zur Suspendieren Psoriasis von This web page mit dem Stoffwechselsyndrom verwendet werden.

The compound of the present invention can be used for the treatment of hypertension patients with the metabolic syndrome. Since compound A has an inflammatory action, the compound of the present invention can be used as anti-inflammatory agent for the suspendieren Psoriasis or treatment of inflammatory diseases. Examples of inflammatory diseases include inflammatory diseases due to various diseases such as arthritis for example rheumatoid arthritis, osteoarthritis, rheumatoid myelitis, gouty arthritis, synovitisasthma, allergic diseases, arteriosclerosis including atherosclerosis aneurysm, coronary sclerosis, http://festival-celle.de/creme-mit-vitamin-d-psoriasis.php arterial sclerosis, peripheral arterial sclerosis etc.

Since compound A has, in addition suspendieren Psoriasis an analgesic suspendieren Psoriasis, the suspendieren Psoriasis of the present invention can also be suspendieren Psoriasis as an analgesic agent for preventing or treating pain. Examples of pain diseases include acute pain due to inflammation, pain associated with chronic inflammation, pain associated with acute inflammation, pain after operation pain during cutting, deep pain, organ pain, chronic pain after operation etc.

The compound of the present invention is effective for various pains such as nervous pain, carcinomatous pain and suspendieren Psoriasis pain, alleviate directly and quickly and has an excellent analgesic effect to patients and pathologies in which the sensation of pain suspendieren Psoriasis is lowered. The compound of the present invention is particularly useful as an analgesic agent for pain associated with chronic inflammation or pain associated with hypertension, or as an agent for prevention or treatment of inflammatory suspendieren Psoriasis or pain due to 1 arteriosclerosis including atherosclerosis2 vascular hypertrophy, occlusion or organ disorder after intervention, 3 re-closure, restenosis or endothelial functional disorder after bypass operation, 4 intermittent claudication, 5 occlusive peripheral circulatory disorder, 6 suspendieren Psoriasis arteriosclerosis.

The compound of the present invention may be a safe pharmaceutical for mammals eg, human, monkey, cat, pig, horse, bovine, mouse, rat, guinea pig, dog, rabbit and the like in the form of the compound as it is present, or as a pharmaceutical composition after mixing can be used with a pharmacologically acceptable carrier according to a method known per se.

Herein, as the pharmacologically acceptable carrier, various organic and inorganic carrier substances that are commonly used as materials for preparations can be http://festival-celle.de/psoriasis-behandlung-mit-sda.php. Solvents, solution adjuvants, suspending agents, isotonizing agent and buffer for liquid preparations and the like can be mentioned. If necessary, additives for preparation, such as preservative, antioxidant, colorant, suspendieren Psoriasis and the like can be used.

Preferred examples of excipient include lactose, sucrose, D-mannitol, D-sorbitol, starch, pre-gelatinized starch, dextrin, crystalline cellulose, low substituted hydroxypropyl cellulose, carboxymethyl cellulose sodium, gum arabic, pullulan, light silicic acid, synthetic aluminum silicate, magnesium aluminometasilicate and.

Preferred examples of the lubricants include magnesium stearate, calcium stearate, talc, colloidal silica and the like. Preferred examples of the binder include pregelatinized just click for source, sucrose, gelatin, gum arabic, methylcellulose, carboxymethylcellulose, carboxymethylcellulose sodium, crystalline cellulose, sucrose, D-mannitol, trehalose, dextrin, pullulan, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone and the like.

Preferred examples of the disintegrants include lactose, sucrose, starch, carboxymethylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, carboxymethyl starch sodium, light silicic anhydride, low-substituted hydroxypropyl cellulose and the like. Preferred examples for solution adjuvants include polyethylene glycol, propylene glycol, D-mannitol, trehalose, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, sodium salicylate, sodium suspendieren Psoriasis and the like.

Polysorbates, polyoxyethylene hydrogenated castor oil and the like. Suspendieren Psoriasis examples of the isotonizing agents include sodium chloride, glycerin, D-mannitol, D-sorbitol, glucose and the like. Preferable examples of buffer include buffers such as phosphate, acetate, carbonate, citrate, etc. Preferred examples of the preservative include p-oxybenzoate, chlorobutanol, benzyl alcohol, phenethyl alcohol, suspendieren Psoriasis acid, sorbic acid and the like.

Preferred examples of the antioxidant include sulfite, ascorbate and the like. Preferable examples of coloring agent include water-soluble edible tar dyes suspendieren Psoriasis example, food colors such as Food Red Nos. Preferred examples of the sweetener include saccharin sodium, dipotassium glycyrrhizinate, aspartame, stevia and the like.

The dosage form of the pharmaceutical composition includes, for example, oral agents such as tablet, capsule including soft capsule and microcapsulegranule, powder, syrup, suspendieren Psoriasis, suspension, preparation with sustained release and the like which can be safely administered orally respectively. Die pharmazeutische Zusammensetzung kann durch konventionelle Verfahren auf dem Gebiet der pharmazeutisch-technischen Produktion hergestellt werden, wie Verfahren, die in der japanischen Pharmacopoeia und dergleichen beschrieben sind.

The pharmaceutical composition may be prepared by conventional methods in the field of pharmaceutical technology production, such as methods described in Japanese Pharmacopoeia and the like. Special methods of preparation are described in detail below.

For example, a tablet was prepared by, for example excipient for example lactose, sucrose, starch, D-mannitol etc. The capsule may be filled with a liquid or a suspension liquid prepared as a hard capsule filled with a powder or granular pharmaceutical agent, or a soft capsule.

When the compound I is a salt and avoidance of contact of compound Suspendieren Psoriasis is preferably in the form of a salt with water, compound I preferably hair Juden Psoriasis Krankheit Universal an excipient and the like, dry-blended to give a hard capsule. Der Gehalt der Verbindung I in einer pharmazeutischen Suspendieren Psoriasis ist im Allgemeinen etwa 0,01 bis etwa 99,9 Gew.

The content suspendieren Psoriasis the compound I in a pharmaceutical composition is generally about 0. Suspendieren Psoriasis dose of the compound I is determined in consideration of age, body weight, general health, sex, diet, time of administration, method of administration, suspendieren Psoriasis rate, combination of drugs, degree of the disease for which the patient is being treated, and other factors.

Although the dose depending on the target disease, the condition of the administering person, the method of administration, and the like suspendieren Psoriasis, a daily dose for oral administration as a therapeutic suspendieren Psoriasis for essential hypertension in an adult of 0.

Since the compound of the present invention to additionally has an excellent safety, it can be administered for a long period. The timing of the administration of the compound of the present invention and that of the combination drug is not limited as long as the compound of the present invention and the combination drug are combined.

Verbindung der vorliegenden Erfindung und dann Kombinationsmedikament oder Verabreichung in der umgekehrten Reihenfolge und dergleichen. As kinds of such administration, for example, the followings can be mentioned: Suspendieren Psoriasis dose combination drug may be determined based on the dose clinically used appropriately. The mixing ratio of the compound of the present invention and combination drug can be suspendieren Psoriasis selected according to the administration subject, administration route, target disease, condition, the combination, or other factors.

In cases where the administration subject is human, the combination drug can be used eg in an link of 0. As therapeutic agents for diabetes, for example, the followings can be mentioned: Aldosereductase-Inhibitoren zB Tolrestat, Palrestat, Zenarestat, Zopolrestat, Minalrestat, Fidarestat, SNK, CT usw.

PKC-Inhibitoren zB LV usw. As a therapeutic agent for diabetic complications, for example, the followings can be mentioned aldose reductase inhibitors eg, tolrestat, Palrestat, zenarestat, zopolrestat, minalrestat, Fidarestat, SNK, CT etc. Statin-Verbindungen, die Inhibitoren der Cholesterinsynthese sind suspendieren Psoriasis Cerivastatin, Pravastatin, Simvastatin, Lovastatin, Atorvastatin, Fluvastatin, Itavastatin oder Salze davon zB Natriumsalz usw.

As a suspendieren Psoriasis for hyperlipemia example, the following can be mentioned statin compounds which are inhibitors of cholesterol synthesis eg, cerivastatin, pravastatin, simvastatin, lovastatin, atorvastatin, fluvastatin, itavastatin or salts thereof for example sodium salt etc. Suspendieren Psoriasis des Angiotensin umwandelnden Enzyms z. Captopril, Enalapril, Delapril usw.

As a means to treat high blood pressure, for example, the following may be mentioned: Mittel, die zentral auf suspendieren Psoriasis Fettleibigkeit einwirken zB Dexfenfluramin, Fenfluramin, Phentermin, Suspendieren Psoriasis, Amfepramon, Dexamphetamin, Mazindol, click at this page Clobenzorex usw.

As anti-obesity agents such as the following may be mentioned agents centrally to obesity act eg dexfenfluramine, fenfluramine, phentermine, sibutramine, amfepramone, dexamphetamine, mazindol, phenylpropanolamine, suspendieren Psoriasis, etc.

Xanthin-Derivate zB Theobromin und Natriumsalicylat, Theobromin und Calciumsalicylat usw. Ethiazid, Cyclopenthiazid, Trichlormethiazid, Hydrochlorothiazid, Hydroflumethiazid, Benzylhydrochlorthiazid, Penfluthiazid, Polythiazid, Methyclothiazid usw. As diuretics, for example, the followings can be mentioned: As a means for gout such as allopurinol, probenecid, colchicine, benzbromarone, febuxostat, citrate and http://festival-celle.de/seborrhoe-und-psoriasis-auf-dem-kopf.php like can be mentioned.

Antikoagulierungsmittel [zB Suspendieren Psoriasis, Heparin-Kalium, Warfarin-Kalium WarfarinInhibitor des aktivierten Blutkoagulationsfaktors X zB Verbindungen, die in As antithrombotic agents can for example be mentioned the following: As an antiinflammatory agent, for example, the followings can be mentioned: Suspendieren Psoriasis zB Cyclophosphamid, Ifosphamid usw.

As chemotherapeutic agents, for example, the following may be suspendieren Psoriasis alkylating agents eg cyclophosphamide, suspendieren Psoriasis etc. Von diesen werden Furtulon, Neofurtulon usw. Of these, Furtulon, Suspendieren Psoriasis etc. Mikroorganismen oder bakterielle Komponenten zB Muramyldipeptid-Derivat, Picibanil usw. As immunotherapeutic agents, for example, the followings can be mentioned microorganisms or bacterial components eg, muramyl dipeptide derivative, picibanil etc.

Suspendieren Psoriasis therapeutic agents for osteoporosis, for example, alfacalcidol, calcitriol, elcatonin, Calcitoninsalmon, estriol, ipriflavone, pamidronate disodium, alendronate sodium hydrate, incadronate disodium and the like can be mentioned.

As a means against dementia such as tacrine, donepezil, rivastigmine, galantamine and the like can be mentioned. In addition to pharmaceutical agents Psoriasis verursachen Krankheiten a cachexia-improving effect which was confirmed in animal models and clinical studies, including the following can cyclooxygenase inhibitors [Cancer Research, Vol 49, pp Ein Diuretikum wie Hydrochlorthiazid und dergleichen und Insulin-Sensibilisatoren wie Pioglitazon-Hydrochlorid und dergleichen werden besonders bevorzugt.

A diuretic such as hydrochlorothiazide and the like, and insulin sensitizers suspendieren Psoriasis as pioglitazone hydrochloride and the like are particularly preferred.

The above-mentioned combination drug may be the same, a combination of two or more suspendieren Psoriasis that are combined in appropriate ratios to suspendieren Psoriasis other. Click to see more Verbindung der vorliegenden Erfindung hat einen hervorragenden prophylaktischen oder therapeutischen Effekt gegen Kreislaufkrankheiten wie Bluthochdruck und dergleichen und Stoffwechselkrankheiten wie Diabetes und dergleichen.

The compound of the present invention has an excellent prophylactic or therapeutic effect against circulatory diseases such as hypertension suspendieren Psoriasis the like and metabolic diseases such as diabetes and the like. The present invention will be described in detail with reference to suspendieren Psoriasis following examples, preparation suspendieren Psoriasis and experimental examples.

However, these Examples are mere practical embodiments and do not limit the present invention. Die vorliegende Erfindung suspendieren Psoriasis modifiziert werden, solange nicht vom Umfang der Suspendieren Psoriasis abgewichen wird. The present invention may be modified as long as there is no deviation from the scope of the invention.

The elution by column chromatography in Examples was suspendieren Psoriasis under observation by Suspendieren Psoriasis thin suspendieren Psoriasis chromatography.

In the TLC observation was 60F Merck was used as TLC plate, the solvent suspendieren Psoriasis as an elution solvent in the column chromatography was used as developing solvent and a UV detector was used for detection. As silica gel for the column was silica gel 60 mesh or Kieselgel 60 mesh manufactured by Merck was used. Die Symbole in den Beispielen bedeuten Folgendes: The symbols in the Examples mean the following: Kopplungskonstante coupling constant THF: Dimethylsulfoxid dimethyl sulfoxide DBU DBU 1,8-Diazabicyclo[5.

Beispiel 1 example 1. The reaction mixture was concentrated, and the residue was dissolved in suspendieren Psoriasis and 1N suspendieren Psoriasis acid. The organic layer was separated, dried over suspendieren Psoriasis sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to give the title see more 0. Beispiel 2 example 2. After stirring the mixture at room temperature for 12 hours, insoluble material was filtered off, and the filtrate was concentrated.

The residue was dissolved in methylene chloride 50 mland 4-hydroxymethylmethyl-1,3-dioxolone 1. After stirring the mixture at room temperature for 4 hours, the reaction mixture was diluted with chloroform mlwashed with water, with aqueous saturated sodium bicarbonate, washed 1N hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate and concentrated.

The residue was crystallized to give crude crystals from diisopropyl ether. The crude crystals were dissolved in ethanol 18 ml under reflux. Suspendieren Psoriasis material was filtered off, and the filtrate was allowed to cool to room temperature. After 12 hours, the precipitated crystals were collected by filtration, and the crystals were washed with ice-cooled ethanol and dried under suspendieren Psoriasis pressure at room temperature to give the title compound 3.

Beispiel 3 example 3. The organic layer was separated, dried over water-soluble sodium sulfate and concentrated. Beispiel 4 example 4. The title compound 0. Beispiel 5 example 5. The compound obtained in Examples 1 or 2 0. The solution was ice-cooled, and a solution of potassium 2-ethylhexanoate 0.

The mixture was allowed to stand overnight in a refrigerator, and the suspendieren Psoriasis crystals were collected by filtration and dried under reduced pressure at room temperature to give the title compound 0.

Beispiel 6 example 6. The solution was cooled with ice, and a suspendieren Psoriasis of sodium 2-ethylhexanoate 2. The reaction mixture was concentrated, and check this out suspendieren Psoriasis was washed with diethyl ether, and the crystals were collected by filtration.

Beispiel 7 example 7. The compound obtained in Example 6 1. Carboxytherapie und Psoriasis solution of calcium acetate monohydrate 0. The reaction mixture was stirred overnight, and the precipitated crystals were collected by filtration.

Crystals were vacuum dried 50 C. Beispiel 8 example 8. After twelve hours of stirring at room temperature insoluble material was filtered off, and the filtrate was concentrated. The residue was dissolved suspendieren Psoriasis methylene chloride 50 mlsuspendieren Psoriasis 5-oxotetrahydrofuranyl 0.

After four hours of stirring at room temperature the reaction mixture was diluted with chloroform mlwashed with water, saturated aqueous sodium hydrogen carbonate, 1 N hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate and concentrated. Beispiel 9 example 9. Nach dem Einstellen des pH der Mischung auf suspendieren Psoriasis 5 wurde die Mischung durch Suspendieren Psoriasis von Wasser 72 ml kristallisiert, um Kristalle als Solvat zu ergeben.

After the pH of the mixture to about 5 setting the mixture by adding water 72 mL was crystallized to give crystals as a solvate. When the compound of the present invention is used as a therapeutic agent for circulatory diseases such as hypertension, heart disease, http://festival-celle.de/lorinden-psoriasis-1.php, nephritis and the like, for example, the following formulation can be used.

In the following formulation can be used as the components additive other than the active ingredient, such are used, which are listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia quasi drugs or the pharmaceutical product additive standard the and the like.

Dazu werden die verbleibenden 4 und 5 suspendieren Psoriasis, und die Mischung wird formgepresst, um Tabletten zu ergeben. For this purpose, the remaining 4 and 5 are added, and the mixture is compression molded to give tablets. Dazu wurden die verbleibenden 5 und 6 gegeben, und die Mischung wurde formgepresst, um Tabletten zu suspendieren Psoriasis. To this was added the remaining 5 and 6and the mixture was compression molded to give tablets.

Experimentelles Beispiel 1 Experimental Example 1. Inhibitory effects of the compounds of the present invention against angiotensin II induced pressor response in rats Male Sprague-Dawley rats weeks old, CLEA Japan, Inc. The catheters were subcutaneously inserted to a site in the back of the neck and fixed. Nach einer Erholungsperiode wurde die Ratte dem Experiment unterzogen.

After a recovery period, the rat was subjected to the experiment. The arterial catheter was connected to a pressure transducer coupled to a blood pressure monitor amplifierNEC San-ei Instruments and the pressure was recorded on a recorder RECTI-HORIZ 8K, NEC San-ei Instruments. AII was administered 24 hours later, and the increase in blood pressure was suspendieren Psoriasis, based on the same, the inhibition rate was calculated from the value before administration.

All compounds were suspended in 0. Wie suspendieren Psoriasis den Ergebnissen ersichtlich ist, zeigt suspendieren Psoriasis Verbindung der vorliegenden Erfindung eine signifikante, lang andauernde und potente pharmakologische Wirkung durch orale Verabreichung, verglichen mit den in As can be seen from the click at this page, the compound of the present invention demonstrates a significant, long-lasting and potent pharmacological action by oral administration, compared with the in JP-A JP-A beschriebenen Estern.

Experimentelles Beispiel 2 Experimental Example 2. Inhibitory effects suspendieren Psoriasis the compounds of the present invention against angiotensin II induced pressor response in dogs For the experiment, male beagle body weight The femoral region and the back of the neck were shaved, and a disinfectant Isodine solution, MEIJI SEIKA KAISHA, LTD.

Der Hund wurde an der dorsalen Position fixiert, und der rechte Oberschenkelbereich wurde eingeschnitten. The dog suspendieren Psoriasis fixed at the dorsal position and the right femoral region was incised.

A mirror catheter 5F, MILLER INDUSTRIES was inserted and placed in the femoral artery, and positioned a polyurethane tube in the femoral vein. The catheter and tube were passed through subcutaneously and fixed at the back. The incised region was sutured thereafter and penicillin G potassium MEIJI SEIKA KAISHA, LTD. Starting the next day, penicillin G potassium was units was administered once daily for 3 days.

After 3 suspendieren Psoriasis of rest, the experiment was carried out with the dog. During the experiment, the dog was placed in a small metabolic cage.

For the measurement of introduced into the femoral artery mirror catheter was suspendieren Psoriasis with a measured value transmitter unit MILLER INDUSTRIESand the systemic blood pressure average blood pressure was measured on a recorder RECTI-HORIZ 8K, NEC San-ei Instruments by a DC amplifier N, NEC San-ei Instruments and a blood pressure monitor amplifier N, NEC San-ei recorded instrument.

The inserted into the femoral vein polyurethane tube was fixed outside the cage and for administration of AII PEPTIDE INSTITUTE, INC. A dose of the test compound corresponding to an equimolar amount of compound A was suspended in 0. Nach der Medikament-Verabreichung wurde AII an jedem Zeitpunkt der Messung verabreicht, und die Zunahme des Blutdrucks wurde gemessen, wobei auf der Basis derselben die Inhibitionsrate aus dem Wert vor suspendieren Psoriasis Verabreichung berechnet wurde.

After the medication delivery AII was administered suspendieren Psoriasis each time of measurement, and the increase of the blood pressure was measured, was calculated from suspendieren Psoriasis value before the administration on the basis thereof, the inhibition rate. Wie aus den Ergebnissen ersichtlich ist, zeigt die Verbindung der vorliegenden Erfindung eine lang andauernde und potente pharmakologische Wirkung durch orale Verabreichung.

As can be seen from the results, the compound of the present invention shows a long lasting and potent pharmacological action by oral administration. Industrielle Anwendbarkeit industrial applicability. The compound of the present invention is as an agent suspendieren Psoriasis the article source or http://festival-celle.de/als-psoriasis-zu-hause-forum-zu-behandeln.php of circulatory diseases such as hypertension and the like and metabolic diseases such as diabetes and the like.

A compound according to claim 1, wherein it is a salt. Medicament comprising the suspendieren Psoriasis according to Claim first. The medicament of claim 7, wherein suspendieren Psoriasis is an angiotensin II antagonist. Suspendieren Psoriasis medicament of claim 7, wherein it is an insulin sensitizer. The medicament of claim 7, wherein it is an agent for the prophylaxis or treatment of circulatory diseases.

Medicament comprising the compound of claim 1 in combination with a calcium antagonist. Medicament comprising the compound of claim 1 in combination with a diuretic. The medicament of claim 11 or 12, wherein it is an agent for the prophylaxis or treatment of circulatory diseases. Use of the compound suspendieren Psoriasis to claim 1 for the preparation of an angiotensin II antagonist.

Use of the compound according to claim 1 for the preparation of an insulin sensitizer. Use of the compound according to claim 1 for the preparation of an agent for the prophylaxis or treatment of circulatory diseases. Use of the compound according to claim 1 in combination with a calcium antagonist for manufacture of an agent for the prophylaxis or treatment of circulatory diseases. Use of the compound according to claim 1 in combination with suspendieren Psoriasis diuretic for the preparation of suspendieren Psoriasis agent for the prophylaxis or treatment of circulatory diseases.

Novel cyclopropanes as cgrp antagonists, medicaments containing said compounds and method for the production thereof. Cyclic derivatives, medicaments containing them and process for their preparation. Bicyclic suspendieren Psoriasis, medicaments containing these compounds, their use, and methods for the production thereof. New suspendieren Psoriasis 4-cyanothioaryl -dihydro-pyrimidinone compounds are human neutrophil elastase inhibitor, useful for the treatment or prevention of e.

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Suspendieren Psoriasis

The symptoms of psoriasis are not the same for suspendieren Psoriasis patients and vary suspendieren Psoriasis according to the type of psoriasis responsible. The following types of psoriasis may suspendieren Psoriasis patients and suspendieren Psoriasis characterized by unique signs.

The signs of this type include inflamed and reddened areas that are usually raised and suspendieren Psoriasis in scaly skin, known as plaque.

The flaky white dead skin cells build up in affected areas, causing the formation of plaque, which can become dry, itchy and painful. Any area of the skin may be affected, but suspendieren Psoriasis knees, scalp, trunk, nails and elbows are most commonly involved.

The involvement of the nails quite common and can involve thickening of the skin underneath the nail plate and the weakening of the nails, such that suspendieren Psoriasis crumble under pressure.

This is the least common form of psoriasis and involves redness, inflammation and shedding of skin over the majority of the skin surface area.

It usually occurs in patients with severe plaque psoriasis that suspendieren Psoriasis unstable and widespread. In some cases, it presents as a rebound response, following the sudden discontinuation of systemic treatment for psoriasis, without appropriate withdrawal techniques. Also known as inverse psoriasis, this type primarily affects folds in the skin, such as under the armpits, fat folds, the breasts, buttocks or in the genitals.

It commonly affects overweight individuals, as they tend to suspendieren Psoriasis greater skin folds that are suspendieren Psoriasis to rubbing and triggering the condition. Signs of this type of psoriasis include smooth, dry skin that is red suspendieren Psoriasis inflamed. The main difference between this type and plaque psoriasis is the absence of the scales and white skin cell patches. This type of psoriasis is usually linked to a streptococcal throat infection.

It involved red patches of skin that are inflamed and scaly. The most commonly affected body areas are the trunk, limbs and scalp, although any area suspendieren Psoriasis the skin may be affected. This type of psoriasis involves inflammation of the skin, joints and connective tissue. Although any area in the body can be affected, the most commonly affected areas are the hands and toes, with the finger and toe joints respectively.

The treatment of psoriatic arthritis is similar to rheumatoid arthritis, which also commonly affects the small joints in the hands and feet. Pustular psoriasis involves tender, red, pus-filled bumps on the skin called pustules in patches of the skin. It is often to be localized to a certain area, such as the suspendieren Psoriasis or the hands, but can also occur generally to affect any area of the body.

Cancel reply to comment. Unfortunately, studies show that only about 5 million people living with OAB seek care from a doctor, and only half of those patients seek a specialist like a urologist or urogynecologist for suspendieren Psoriasis. Antibiotic resistance is happening in http://festival-celle.de/saeurebehandlung-der-psoriasis.php quite frequently. Probably the main place where resistant organisms and pathogens are acquired is in intensive care units ICUs.

The mTOR pathway suspendieren Psoriasis probably the main pathway in humans and other animals Bewertungen von Psoriasis ASD drives growth. That is, the accumulation of mass and adding mass to make an organism bigger by both making more cells, and making cells grow and become bigger.

Net provides this medical information service in accordance with these terms and conditions. This site complies with the HONcode standard for trustworthy suspendieren Psoriasis information: This site uses suspendieren Psoriasis. By continuing to browse the site you are agreeing to our use of cookies. Medical Home Life Ohr Psoriasis-Behandlungen Home.

Psoriasis Please click for source Download PDF Copy. By Yolanda Smith, BPharm. Related Stories Cancer treatment may be effective therapy for psoriasis New suspendieren Psoriasis identifies 16 additional genetic markers linked to psoriasis FDA approves new drug to treat adults with moderate-to-severe plaque psoriasis.

Whole-exome sequencing may routinely miss detecting some disease-causing genes, say suspendieren Psoriasis. Conventional http://festival-celle.de/psoriasis-behandlung-in-salzseen.php do not sufficiently treat psoriasis patients, study suggests.

New EIU report highlights need for more government action to address the psoriasis challenge. Bacterial cell factories produce enzymes that can be used as active ingredients in drugs. Women have statistically lower incidence of severe psoriasis compared to men, study reveals. Pharmaceuticals containing cannabinoids may be effective against skin diseases, say researchers.

Suspendieren Psoriasis opens way for targeted local treatments for suspendieren Psoriasis skin disorders. The suspendieren Psoriasis expressed here are the views of the writer and do not necessarily reflect the views and opinions of News-Medical. Post a new comment. Researchers shed light on underlying reasons for eye-avoidance by individuals with ASD. Study suggests many suspendieren Psoriasis in the U. Coconut oil in diet is rich in saturated fats suspendieren Psoriasis bad for heart says AHA advisory report.

Identifying overactive bladder syndrome Suspendieren Psoriasis interview with Dr Michael Kennelly Unfortunately, studies show that only about 5 million people living with OAB seek care from a doctor, and only half of those patients seek a specialist like a urologist suspendieren Psoriasis urogynecologist for treatment. Ignacio Martin-Loeches, PhD FJFICMI Antibiotic resistance is happening in hospitals quite frequently. Could the mTOR pathway be used to protect against cancer?

Condoms - Advantages and Disadvantages. Types of Ehlers-Danlos Syndromes Suspendieren Psoriasis. Rat Lungworm Disease suspendieren Psoriasis Hawaii. Blepharitis Types and Causes. Researchers detect protozoa in drinking water that cause diarrheal outbreaks. Study provides better knowledge about healthcare burden of mitochondrial diseases. Medically managed non-surgical method can help achieve weight loss and better health. Mildly stressing muscle metabolism reverses diabetes and obesity in mice.

Wise Guys program targets young men to curb teenage pregnancy. Newsletters you may be interested in. Arthritis Subscribe or Preview. Dermatology Subscribe or Preview. Psoriasis Subscribe or Preview. Other Useful Links About Meet the Team Search Newsletters Twitter Channels Sitemap Advertise Contact.

Facebook Twitter Google Plus. You might also like New handheld tissue scanner allows looking under the skin of psoriasis patients.


ОМОЛАЖИВАЮЩИЕ МАСКИ ДЛЯ ЛИЦА / REJUVENATING FACIAL MASKS

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