WO2006068075A1 - Ligand du récepteur ϝ activé par les proliférateurs de peroxisome - Google Patents

Ligand du récepteur ϝ activé par les proliférateurs de peroxisome Download PDF

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Publication number
WO2006068075A1
WO2006068075A1 PCT/JP2005/023239 JP2005023239W WO2006068075A1 WO 2006068075 A1 WO2006068075 A1 WO 2006068075A1 JP 2005023239 W JP2005023239 W JP 2005023239W WO 2006068075 A1 WO2006068075 A1 WO 2006068075A1
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composition
group
compound selected
derivatives
active ingredient
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PCT/JP2005/023239
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Japanese (ja)
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Mitsuaki Kitano
Misuzu Tsukagawa
Eisaku Konishi
Tatsumasa Mae
Kazunori Hosoe
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Kaneka Corporation
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Priority to US11/792,695 priority Critical patent/US20080132544A1/en
Priority to JP2006548962A priority patent/JPWO2006068075A1/ja
Publication of WO2006068075A1 publication Critical patent/WO2006068075A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof

Definitions

  • Peroxisome proliferator-responsive receptor gamma ligand agent Peroxisome proliferator-responsive receptor gamma ligand agent
  • the present invention relates to a peroxisome proliferator-responsive receptor ⁇ ligand agent, and a composition for preventing and improving visceral fat-type obesity and related pathologies and syndromes.
  • Peroxisome proliferator-activated receptor is a ligand-dependent member of the nuclear receptor family that has been identified as a transcriptional regulator that regulates the expression of genes that maintain lipid metabolism. It is a sex transcription factor. In mammals, three subtypes are known to exist: PPAR a, PPAR ⁇ (PPAR ⁇ , NUC-1, FAAR), and PPAR y. PPAR ⁇ is mainly expressed in the liver and PPAR ⁇ is universally expressed. is doing.
  • PPAR y has two isoforms, PPAR ⁇ 1 and PPAR ⁇ 2, and PPAR y 1 is expressed in the adipose tissue, immune system organs, adrenal glands, and small intestine.
  • PPAR y 2 is specifically expressed in adipose tissue and is a master regulator that regulates adipocyte differentiation 'maturation (Non-patent Document 1: Teruo Kawada, Ayumi Medicine, 184, 519-523, 1 998 ).
  • PPAR ⁇ ligands include 15 dexoxy ⁇ 12, 14 prostaglandin J2 and arachidonic acid metabolites such as ⁇ 12 prostaglandin J2; ⁇ 3 polyunsaturated fatty acids, a linolenic acid, eicosapentaenoic acid (EPA ), Unsaturated fatty acids such as docosahexaenoic acid (DHA); 9 eicosanoids such as 9 hydroxyoctadecadienoic acid and 13 hydroxyoctadecadienoic acid are known (Non-Patent Document 2: J.
  • a conjugated unsaturated fatty acid having 10 to 26 carbon atoms having a conjugated triene structure or a conjugated tetraene structure is a PPAR ⁇ ligand (Patent Document 1). : JP 2000-355538).
  • synthetic compounds are known to be thiazolidine derivative PPAR y ligands such as troglitazone, pioglitazone, and rosiglitazone.
  • Thiazolidine derivative a PPAR ⁇ ligand
  • NIDDM non-insulin dependent diabetes mellitus
  • the thiazolidine derivative, a PPAR y ligand activates PPAR y, thereby increasing the number of normal adipocytes differentiated from preadipocytes and causing TNF a and free fatty acids to induce insulin resistance.
  • Improves insulin resistance by reducing adipocytes through apoptosis non-patent literature 3: A.
  • Non-Patent Document 4 RA Degronze, et al., Diabetes Care, 14, 173 to 194, 1991).
  • As an effect on obesity it has been reported that visceral fat is reduced by troglitazone administration to patients with type 2 diabetes (Non-patent Document 5: 1. E. Kelly, et al., Diabetes Care, 22, 288 -293, 1999
  • Non-Patent Document 6 Y. Mori, et al "Diabetes Care, 22, 908-912, 1999), effective in preventing and improving visceral fat obesity.
  • Patent Document 2 JP-A-11 12174
  • Non-Patent Document 1 Teruo Kawada, History of Medicine, 184, 519-523, 1998
  • Non-Patent Document 2 J. Auwerx, Diabetologia, 42, 1033-1049, 1999
  • Non-Patent Document 3 A. Okuno, et al., Journal of Clinical Investigation, 101, 1354-136
  • Non-Patent Document 4 R. A. Degronze, et al., Diabetes Care, 14, 173-194, 1991
  • Non-Patent Document 5 1. E. Kelly, et al., Diabetes Care, 22, 288-293, 1999
  • Non-Patent Document 6 Y. Mori, et al., Diabetes Care, 22, 908-912, 1999
  • Non-Patent Document 7 Envuromental Health Perspectives 67, 135-142, 1986 Disclosure of Invention
  • the present invention can treat or prevent a PPAR y ligand agent, visceral fat obesity or type 2 diabetes, and further, insulin resistance syndrome, metabolic syndrome or viscera It is an object of the present invention to provide a thread and composition capable of treating or preventing fat syndrome.
  • the present inventors found for the first time that it has coumaperine and its derivative power PPAR ⁇ ligand activity, and have completed the present invention. That is, the present invention provides the following.
  • a peroxisome proliferator-responsive receptor ⁇ ligand agent comprising as an active ingredient at least one compound selected from the group consisting of coumaperin and its derivative power.
  • the compound is ⁇ -5- (4-hydroxyphenol) 2 ⁇ , 4 ⁇ -pentadienol piperidine, ⁇ trans-feruloyl tyramine, ⁇ trans-feruloyl piperidine, ⁇ —5— (4 hydroxy-one 3-methoxyphenyl) 2 ⁇ , 4 ⁇ pentadienoyl piperidine, and ⁇ — 5— (4-hydroxy-1-methoxyphenyl) 2 ⁇ pentenoyl biperidine, their salts, and their ester strength groups
  • the peroxisome proliferator-responsive receptor ⁇ ligand agent according to (1) which is at least one selected compound.
  • composition for preventing or treating visceral fat-type obesity comprising as an active ingredient at least one compound selected from the group consisting of coumaperine and derivatives thereof.
  • composition for preventing or treating type 2 diabetes comprising as an active ingredient at least one compound selected from the group consisting of coumaperine and its derivative ability.
  • a composition for preventing or treating insulin resistance syndrome comprising at least one compound selected from the group consisting of coumaperin and its derivative ability as an active ingredient.
  • composition for preventing or treating metabolic syndrome comprising as an active ingredient at least one compound selected from the group consisting of coumaperin and its derivative ability.
  • composition for preventing or treating visceral fat syndrome comprising as an active ingredient.
  • the compound is N-5- (4-hydroxyphenol) -2E, 4E-pentadienol piperidine, N-trans-feruloyl tyramine, N-trans-feruloyl piperidine, N-5-- (4 hydroxy 1-methoxyphenyl) 2E, 4E pentadienoylpiperidine, and N-5- (4-hydroxy-1-methoxyphenyl) 2E pentenoylbiperidine, their salts, and their ester strength
  • the composition according to any one of (3) to (7), which is one or more compounds selected from the group.
  • the compound selected from the group consisting of coumaperin and its derivatives is contained in the composition in an amount of 0.1% to 99% by weight, in any one of (3) to (7) Composition.
  • a peroxisome proliferator-responsive receptor ⁇ (PPAR ⁇ ) ligand agent is provided.
  • the composition of the present invention can treat or prevent visceral fat obesity or type 2 diabetes, and further treat or prevent insulin resistance syndrome, metabolic syndrome or visceral fat syndrome. Can do.
  • peroxisome proliferator-activated d receptor is a nuclear receptor identified as a transcriptional regulator responsible for controlling the expression of genes that maintain lipid metabolism. It is a ligand-dependent transcription factor belonging to the family.
  • PPAR ⁇ is encoded on chromosome 3 ⁇ 25 in the human genome (PPARa is encoded on chromosome 22ql2-ql3.1 and PPAR ⁇ is encoded on chromosome 6p21.2-p21.1. (Folia Pharmacol. Jpn "117, 319-327, 2001).
  • the PPAR ⁇ ligand agent of the present invention contains at least one compound selected from the group consisting of coumaperin and its derivatives as an active ingredient.
  • the ligand agent referred to here is an agonist agent or an antagonist agent. From the viewpoint of treatment or prevention of visceral fat type obesity and the like, an agonist is preferred. Whether a certain compound has PPAR ⁇ ligand activity can be confirmed by, for example, the assay described in Example 2 described later.
  • Coumaperin here is N-5- (4 hydroxyphenol) 2E, 4E pentadienoyl piperidine (I), which is a compound derived from spice pepper represented by the following formula (I).
  • the coumaperin derivative in the present invention is not particularly limited.
  • ⁇ ⁇ -trans feruloyl tyramine ( ⁇ ), ⁇ -trans ferroyl biperi represented by the following formulas (II) to (V) are used.
  • examples include phenolic amide compounds such as pentenoylbiperidine (V), and salts, oxidized forms, reduced forms, glycosides, esterified forms, acetylated forms, and methyl enamels of these compounds. Can be mentioned. These can also be used as plant-derived compounds or chemically synthesized compounds.
  • Coumaperin and its derivatives referred to in the present specification are found in natural products, and particularly preferably, pepper strength can also be separated and collected. Alternatively, the strength of dried pulverized pepper fruits and the strength of pepper wore resin extracted with an organic solvent can be separated and collected.
  • the method for obtaining coumaperine and its derivatives as pepper or pepper wornin is not particularly limited.
  • a dried pulverized product of pepper fruit or pepper worn resin is treated with an organic solvent, and an organic solvent layer from which insoluble components are separated is obtained.
  • the organic solvent used for this treatment include n-hexane, methylene chloride, ethylene dichloride and the like.
  • the organic solvent layer is treated with, for example, an aqueous bicarbonate solution, and the obtained organic solvent layer is further treated with an alkaline aqueous solution, and the pH of the alkaline aqueous solution layer is adjusted to be acidic with a neutral solution. Adjust.
  • the bicarbonate used for the treatment include potassium bicarbonate, sodium bicarbonate, potassium carbonate, sodium carbonate, or a combination thereof.
  • pH adjusters include hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, lactic acid, citrate, or combinations thereof.
  • a separated product containing a plurality of phenolic amide compounds can be obtained.
  • the obtained phenolic amido compound can be eluted with a mixed solvent of methylene chloride and methanol using, for example, a silica gel column to isolate coumaperine and its derivatives (I) to (V).
  • the coumaperin and derivatives thereof of the present invention can also be obtained by synthesis.
  • coumaperin and its derivatives (I) to (V) can be synthesized by the method described in Agricultural and Biological Chemistry, 44, 2831, 1980, Tetrahedron, 59, 5337, 2003, and Japanese Patent Publication No. 1 21951. This method is not limited.
  • bromocuccinic acid dissolved in anhydrous benzene at 0 ° C. is anhydrous Add it to thiol bromide in benzene, distill off the solvent, dissolve the resulting 4-promoc-tonic acid odorant in anhydrous benzene, and react with piperidine at about 0 ° C.
  • the reaction solution is warmed to room temperature, then poured into cooling water for an additional hour and extracted with benzene. Wash the organic solvent layer with saturated aqueous NaHCO and water. Dry and concentrate to obtain syrup.
  • This syrup is anhydrous Add it to thiol bromide in benzene, distill off the solvent, dissolve the resulting 4-promoc-tonic acid odorant in anhydrous benzene, and react with piperidine at about 0 ° C.
  • the reaction solution is warmed to room temperature, then poured into cooling water for an additional hour and extracted with benzene. Wash the organic solvent layer with saturated aqueous NaHCO
  • the purified amide is added to the triethyl phosphite at, for example, 100 ° C to 110 ° C. Increase the reaction temperature and hold for an appropriate time.
  • Excess triethyl phosphite is distilled off under reduced pressure, the residue is dissolved in anhydrous DMF and mixed with p-benzyloxybenzaldehyde in anhydrous DMF.
  • the mixture is treated with NaOEt solution and stirred at room temperature. Dilute the mixture with water and extract with methylene chloride. The dried extract is recrystallized with benzene to give white needles.
  • the salt of the coumaperine and its derivatives (I) to (V) is intended to include non-toxic acid and base addition salt forms that the compound can form.
  • the compounds can be converted into their pharmaceutically acceptable acid addition salts by treatment with a suitable acid.
  • Exemplary acids in this case are inorganic acids such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid; and organic acids such as acetic acid, propionic acid, hydroxyacetic acid, lactic acid, pyruvic acid, glycol Acid, maleic acid, malonic acid, oxalic acid, benzene sulfonic acid, toluene sulfonic acid, methane sulfonic acid, trifluoroacetic acid, fumaric acid, succinic acid, malic acid, tartaric acid, citrate, salicylic acid, p-aminosalicylic acid, pamoic acid Benzoic acid, ascorbic acid and the like.
  • inorganic acids such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid
  • organic acids such as acetic acid, propionic acid, hydroxyacetic acid, lactic acid, pyruvic acid, glycol Acid, maleic
  • bases in the form of base addition salts are sodium, potassium, calcium; pharmaceutically acceptable amines such as ammonia, alkylamines, benzathines; and amino acids such as arginine, lysine and the like.
  • Addition salt used here The term also includes solvates that the compounds and salts thereof can form, eg, hydrates, alcoholates, and the like.
  • the oxidized form, reduced form, glycoside, ester diester, acetylated form, and methylated form of the coumaperin and its derivatives (I) to (V) are each treated with a known method. It can also be obtained by extracting from the plant in which they are contained.
  • pure at least one compound selected from coumaperin and its derivative power can be used as a pure compound, but the present invention is not limited to this. Use semi-refined or crude as long as it does not contain.
  • compositions for treating or preventing visceral fat obesity or type 2 diabetes and further a thread for treating or preventing insulin resistance syndrome, metabolic syndrome or visceral fat syndrome
  • the product is characterized by containing as an active ingredient at least one compound selected from the group consisting of coumaperine and its derivatives.
  • the insulin resistance syndrome referred to here is characterized by two existences of insulin resistance and hyperinsulinemia.
  • Related lesions include obesity, type 2 diabetes, hypertension, arteriosclerotic disease, and This refers to a group of diseases associated with one or more abnormal lipid metabolisms (Netherlands Journal of Medicine, 50, 191–197, 1997).
  • the metabolic syndrome syndrome here is abdominal obesity (especially visceral fat obesity) as a basic symptom, and in addition, fasting hyperglycemia, hypertriglyceridemia, low HDL cholesterolemia, or This syndrome applies when there are multiple risk factors such as hypertension (Circulation Journal, 68, 975–981, 2004).
  • the visceral fat syndrome is a disease group in which five organs of visceral fat accumulation, impaired glucose tolerance, hyperlipidemia, hypertension, and low HDL cholesterolemia are combined. (Journal of Japanese Society for Internal Medicine, 81, 1831-1835, 1992).
  • Visceral fat-type obesity is different from subcutaneous fat-type obesity, which is considered to be more common among men and more often than women.
  • insulin resistance is upstream of risk factors such as hyperlipidemia, diabetes, and hypertension, and visceral fat obesity is located at the most upstream.
  • visceral fat is particularly important as bad fat causing the above syndrome, and its accumulation increases risk (Circulation Journal, 66, 987-992, 2002) 0
  • compositions of the present invention are particularly capable of treating or preventing visceral fat obesity, thereby providing insulin resistance. Furthermore, it treats or prevents diabetes, hyperlipidemia, hypertension and the like.
  • the content of at least one compound selected as coumaperin and its derivative strength in the above composition is not limited as long as it is suitable for the treatment or prevention of the above diseases. 1 to: L00 wt%. From the viewpoint of sufficient effect, the composition preferably contains 0.1 to 99% by weight, more preferably 1 to 99% by weight. More preferably, the content can be 10-90% by weight.
  • composition is not limited.
  • the composition may be used as a food / beverage product such as a health food (a food for specified health use or a food with a nutrition function), a health food, a pharmaceutical product, or a quasi drug. I'll do it.
  • the composition When used as a food or drink, the composition can be ingested directly, or in a form that is easy to take, such as capsules, tablets, granules, using known carriers and auxiliaries. It can be ingested after being formulated.
  • chewing gum, chocolate, candy, jelly mixed with food and drink ingredients Biscuits, crackers and other confectionery, ice cream, frozen confectionery such as ice confectionery, tea, refreshing beverages, nutritional drinks, beauty drinks and other beverages, udon, Chinese candy, spaghetti, instant candy, etc. It can be used for all foods and beverages such as kneaded products such as half pieces, seasonings such as dressings, mayonnaise, sauces, fats and oils such as margarine, butter, salad oil, bread, ham, soup, retort food, frozen food.
  • the intake is usually 0.1 to 3000 mgZkg body weight, preferably 1 to 300 mgZkg body weight per adult day as the amount of coumaperine and its derivatives. It can also be used as feed and pet food for livestock and pets, and its intake is preferably 0.1 to 3000 mgZkg body weight per day as the amount of coumaperine and its derivatives.
  • the dosage form When used as a pharmaceutical, the dosage form is not particularly limited, and examples thereof include those formulated into capsules, tablets, granules, injections, suppositories, patches, and the like.
  • other pharmaceutically acceptable formulation materials such as excipients, disintegrants, lubricants, binders, antioxidants, colorants, anti-aggregation agents, absorption enhancers, It can be prepared by appropriately adding a solubilizer, a stabilizer and the like.
  • the dosage of these preparations is usually 0.1 to 3000 mgZkg body weight, preferably 1 to 300 mgZkg body weight per day per adult as the amount of coumaperin and its derivatives, and is administered in one to several divided doses. It can also be used as a pharmaceutical product for livestock and pets, and its dosage is preferably 0.1 to 3000 mgZkg body weight per day as the amount of coumaperine and its derivatives.
  • the purified amide was transformed into triethyl phosphite (9.6 g) at 105 ° C. The reaction temperature was raised to 150 ° C and held for 1 hour. Excess triethyl phosphite was distilled off under reduced pressure, and the residue was dissolved in anhydrous DMF (30 ml) and mixed with 12.2 g of anhydrous DMF solution (45 ml) containing p-benzyloxybenzaldehyde. This mixture was treated with NaOEt solution and stirred at room temperature. The mixture was diluted with water and extracted with methylene chloride. The dried extract (19.2 g) was recrystallized with benzene to obtain white needle crystals.
  • CV-1 cells (cultured cells derived from male African green monkey kidney) were inoculated into 96-well culture plates at 6 ⁇ 10 3 cells Zwell and cultured at 37 ° C. under 5% CO for 24 hours.
  • the medium contains DMEM (Dulbecco's Modified) containing 10% FBS (Ushi Fetal Serum), lOmlZL penicillin 'streptomycin solution (5000 IUZml, 5000 ⁇ g / ml, GIBCO, respectively) and 37 mg ZL ascorbic acid (Wako Pure Chemical Industries, Ltd.).
  • Eagle Medium GIBCO
  • pM-mPPARy and 4 X UASg-luc were transfected using Lipofectamine Plus (GIBCO).
  • PM-mPPAR y is a chimeric protein expression plasmid that combines yeast-derived transcription factor GAL4 gene (amino acid sequence 1-147) and mouse PPAR y ligand binding site gene (amino acid sequence 174-475).
  • DMSO dimethyl sulfoxide
  • the control group was measured using pM (plasmid from which the PPAR y ligand binding site gene had been removed) instead of pM-mPPAR y.
  • pM plasmid from which the PPAR y ligand binding site gene had been removed
  • Table 1 The results are shown in Table 1.
  • Troglitazone (Sankyo Co., Ltd.) was used as a positive control, and the PPAR ⁇ ligand activity of each compound was compared. As apparent from Table 1, coumaperin showed a concentration-dependent PPAR y ligand activity.
  • a food-and-drink tablet containing coumaperin with the above composition was prepared by a conventional method.
  • a soft capsule for eating and drinking containing coumaperine with the above composition was prepared by a conventional method.
  • a cracker containing coumaperine with the above composition was prepared by a conventional method.
  • a dressing containing coumaperine was prepared by the conventional method with the above composition.

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Abstract

La présente invention a pour objet un ligand de récepteur Ϝ activé par les proliférateurs de peroxisome (PPARϜ) issu d'un matériau naturel, ainsi qu'une préparation destinée à prévenir ou soulager le syndrome de résistance à l'insuline, le diabète, l'obésité ou l'obésité viscérale et caractérisée en ce qu’elle contient ledit ligand au titre de principe actif. La présente invention a notamment pour objet un ligand de PPARϜ qui contient, au titre de principe actif, au moins un composé sélectionné au sein du groupe constitué par la coumapérine et ses dérivés, ainsi qu'une préparation destinée à prévenir ou soulager le syndrome de résistance à l'insuline, le diabète, l'obésité ou l'obésité viscérale et caractérisée en ce qu’elle contient ledit composé au titre de principe actif.
PCT/JP2005/023239 2004-12-21 2005-12-19 Ligand du récepteur ϝ activé par les proliférateurs de peroxisome WO2006068075A1 (fr)

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US11/792,695 US20080132544A1 (en) 2004-12-21 2005-12-19 Peroxisome Proliferator-Activated Receptor Ligand
JP2006548962A JPWO2006068075A1 (ja) 2004-12-21 2005-12-19 ペルオキシソーム増殖剤応答性受容体γリガンド剤

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008023199A (ja) * 2006-07-24 2008-02-07 Katsuzo Kawanishi メタボリックシンドローム診断装置、メタボリックシンドローム診断プログラム、体組成計、及び血圧計
WO2016048005A3 (fr) * 2014-09-23 2016-08-18 연세대학교 산학협력단 Nouveau dérivé de pipéridine pentadiénoyl et son utilisation
JP2021510167A (ja) * 2018-01-10 2021-04-15 ブライトシード・インコーポレイテッド 代謝を調節するための組成物
JP2021510378A (ja) * 2018-01-10 2021-04-22 ブライトシード・インコーポレイテッド 代謝を調節するための方法

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JPH1112174A (ja) * 1997-06-18 1999-01-19 Kanegafuchi Chem Ind Co Ltd 発癌抑制剤
JP2003261443A (ja) * 2002-03-06 2003-09-16 Wakayama Prefecture 糖尿病治療剤
JP2005097216A (ja) * 2003-09-26 2005-04-14 Kaneka Corp ＰＰＡＲγリガンド剤

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Publication number Priority date Publication date Assignee Title
JPH1112174A (ja) * 1997-06-18 1999-01-19 Kanegafuchi Chem Ind Co Ltd 発癌抑制剤
JP2003261443A (ja) * 2002-03-06 2003-09-16 Wakayama Prefecture 糖尿病治療剤
JP2005097216A (ja) * 2003-09-26 2005-04-14 Kaneka Corp ＰＰＡＲγリガンド剤

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JP2008023199A (ja) * 2006-07-24 2008-02-07 Katsuzo Kawanishi メタボリックシンドローム診断装置、メタボリックシンドローム診断プログラム、体組成計、及び血圧計
WO2016048005A3 (fr) * 2014-09-23 2016-08-18 연세대학교 산학협력단 Nouveau dérivé de pipéridine pentadiénoyl et son utilisation
US10100011B2 (en) 2014-09-23 2018-10-16 Industry-Academic Cooperation Foundation, Yonsei University Pentadienoyl piperidine derivative and use thereof
JP2021510167A (ja) * 2018-01-10 2021-04-15 ブライトシード・インコーポレイテッド 代謝を調節するための組成物
JP2021510378A (ja) * 2018-01-10 2021-04-22 ブライトシード・インコーポレイテッド 代謝を調節するための方法

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