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WO2024136338A1 - Composition comprenant un composé n-benzylquinazoline-4-amine pour prévenir ou traiter l'obésité ou des troubles métaboliques associés aux lipides - Google Patents

Composition comprenant un composé n-benzylquinazoline-4-amine pour prévenir ou traiter l'obésité ou des troubles métaboliques associés aux lipides Download PDF

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WO2024136338A1
WO2024136338A1 PCT/KR2023/020781 KR2023020781W WO2024136338A1 WO 2024136338 A1 WO2024136338 A1 WO 2024136338A1 KR 2023020781 W KR2023020781 W KR 2023020781W WO 2024136338 A1 WO2024136338 A1 WO 2024136338A1
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hydrogen
formula
lipid
pharmaceutical composition
composition
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Korean (ko)
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전경희
황민선
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University Industry Foundation UIF of Yonsei University
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University Industry Foundation UIF of Yonsei University
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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/116—Heterocyclic compounds
    • A23K20/137—Heterocyclic compounds containing two hetero atoms, of which at least one is nitrogen
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/06—Preparations for care of the skin for countering cellulitis
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/3262—Foods, ingredients or supplements having a functional effect on health having an effect on blood cholesterol
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/332—Promoters of weight control and weight loss

Definitions

  • the present invention relates to a composition for preventing or treating obesity and lipid-related metabolic diseases, comprising N-benzylquinazolin-4-amine represented by Formula 1.
  • Obesity is a condition in which fat is excessively accumulated in the body due to a metabolic disorder. It is caused by a calorie imbalance phenomenon in which calorie intake exceeds the energy required for growth and physical activity. Body fat usually accounts for 25% of body weight in men and 25% in women. refers to the case where it is 30% or more. In particular, obesity not only causes various metabolic diseases such as diabetes, hyperlipidemia, cardiovascular disease, and arteriosclerosis, but the increase in mortality due to obesity is clearly seen in metabolic diseases, gallbladder diseases, hormone-sensitive cancers, and gastrointestinal cancers. It also increases the risk of physical diseases such as non-fatal back pain, arthritis, and infertility, and mental diseases such as decline in psychosocial functions.
  • the present inventors discovered a compound that can eliminate or reduce the side effects of known compositions for the prevention and treatment of obesity and replace them, and completed the present invention by confirming its excellent efficacy in treating or preventing obesity.
  • One aspect includes an N-Benzylquinazolin-4-amine compound represented by the following formula (1), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof.
  • a pharmaceutical composition for preventing or treating obesity and lipid-related metabolic diseases which includes:
  • R 1 and R 2 are each independently a hydrogen or halogen element
  • R 3 and R 4 are each independently hydrogen, a halogen element, or -OR 5 ;
  • R 5 is hydrogen or substituted or unsubstituted C 1 -C 5 alkyl
  • R 3 and R 4 may form a ring together with the atom to which they are attached.
  • Another aspect includes an N-Benzylquinazolin-4-amine compound represented by Formula 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof. , and provides a food composition for preventing or improving obesity.
  • Another aspect includes an N-Benzylquinazolin-4-amine compound represented by Formula 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof.
  • a feed composition for preventing or improving obesity is provided.
  • Another aspect includes an N-Benzylquinazolin-4-amine compound represented by Formula 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof.
  • a cosmetic composition for preventing or improving cellulite is provided.
  • One aspect includes an N-Benzylquinazolin-4-amine compound represented by the following formula (1), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof.
  • a pharmaceutical composition for preventing or treating obesity and lipid-related metabolic diseases which includes:
  • R 1 and R 2 are each independently a hydrogen or halogen element
  • R 3 and R 4 are each independently hydrogen, a halogen element, or -OR 5 ;
  • R 5 is hydrogen or substituted or unsubstituted C 1 -C 5 alkyl
  • R 3 and R 4 may form a ring together with the atom to which they are attached.
  • alkyl refers to a fully saturated branched or unbranched (or straight-chain or linear) hydrocarbon group.
  • Non-limiting examples of “alkyl” include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, n-pentyl, isopentyl, neopentyl, etc.
  • C 1 -C 5 alkyl refers to an alkyl group having an alkyl unit having 1 to 5 carbon atoms, and when C 1 -C 5 alkyl is substituted, the carbon number of the substituent is not included.
  • one or more hydrogen atoms may be halogen, a C1-C20 alkyl group substituted with halogen (e.g. CCF 3 , CHCF 2 , CH 2 F, CCl 3 , etc.), a C1-C20 alkoxy group, or a C2-C20 alkyl group.
  • halogen e.g. CCF 3 , CHCF 2 , CH 2 F, CCl 3 , etc.
  • C1-C20 alkoxy group e.g. C2-C20 alkyl group.
  • Alkoxyalkyl group hydroxy group, nitro group, cyano group, amino group, or C1-C20 alkyl group, C2-C20 alkenyl group, C2-C20 alkynyl group, C1-C20 heteroalkyl group, C6-C20 aryl group, C6-C20 It may be substituted with an arylalkyl group, a C6-C20 heteroaryl group, a C7-C20 heteroarylalkyl group, a C6-C20 heteroaryloxy group, or a C6-C20 heteroaryloxyalkyl group.
  • halogen refers to a halogen group element and may include fluoro (F), chloro (Cl), bromo (Br), and iodo (I).
  • halogen-substituted C1-C20 alkyl group refers to a C1-C20 alkyl group substituted with one or more halo groups, including, but not limited to, monohaloalkyl, dihaloalkyl, or perhaloalkyl.
  • One polyhaloalkyl may be mentioned.
  • Monohaloalkyl refers to an alkyl group having one iodine, bromine, chlorine or fluorine
  • dihaloalkyl and polyhaloalkyl refer to an alkyl group having two or more identical or different halo atoms.
  • alkoxy used in the chemical formula refers to alkyl-O-, and the alkyl is as described above.
  • Non-limiting examples of the alkoxy include methoxy, ethoxy, propoxy, 2-propoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, cyclopropoxy, and cyclohexyloxy.
  • One or more hydrogen atoms in the alkoxy group may be substituted with the same substituent as in the case of the alkyl group described above.
  • alkoxyalkyl used in the chemical formula refers to the case where an alkyl group is substituted by the alkoxy described above.
  • One or more hydrogen atoms of the alkoxyalkyl group may be substituted with the same substituent as that of the alkyl group described above.
  • alkoxyalkyl includes substituted alkoxyalkyl moieties.
  • alkenyl refers to a branched or unbranched hydrocarbon having at least one carbon-carbon double bond.
  • alkenyl include vinyl, allyl, butenyl, isopropenyl, isobutenyl, etc., and one or more hydrogen atoms of the alkenyl may be substituted with the same substituent as in the case of the alkyl group described above.
  • alkynyl refers to a branched or unbranched hydrocarbon having at least one carbon-carbon triple bond.
  • Non-limiting examples of the alkynyl include ethynyl, butynyl, isobutynyl, isopropynyl, etc.
  • One or more hydrogen atoms of the alkynyl group may be substituted with the same substituent as that of the alkyl group described above.
  • alkylene oxide refers to alkylene-O.
  • alkylene include methylene, ethylene, propylene, butylene, etc.
  • one or more hydrogen atoms of the “alkylene” may be substituted with the same substituent as in the case of the alkyl group described above.
  • cycloalkyl refers to an alkyl that forms a ring.
  • the alkyl is as described above.
  • Non-limiting examples of the cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
  • One or more hydrogen atoms of the cycloalkyl group may be substituted with the same substituent as that of the alkyl group described above.
  • aryl refers to an aromatic hydrocarbon containing one or more rings.
  • aryl also includes groups in which an aromatic ring is fused to one or more cycloalkyl rings.
  • Non-limiting examples of the “aryl” include phenyl, naphthyl, tetrahydronaphthyl, etc.
  • one or more hydrogen atoms of the “aryl” group can be substituted with the same substituent as in the case of the alkyl group described above.
  • arylalkyl means alkyl substituted with aryl.
  • arylalkyl include benzyl or phenyl-CH 2 CH 2 -.
  • aryloxy used in the chemical formula means O-aryl, and examples of aryloxy include phenoxy.
  • One or more hydrogen atoms in the “aryloxy” group may be substituted with the same substituent as in the case of the alkyl group described above.
  • heteroaryl used in a chemical formula refers to a monocyclic or bicyclic organic compound containing one or more heteroatoms selected from N, O, P or S, and the remaining ring atom being carbon.
  • the heteroaryl group may contain 1-5 heteroatoms and 5-10 ring members.
  • the S or N may be oxidized and have various oxidation states.
  • One or more hydrogen atoms of the “heteroaryl” may be substituted with the same substituent as in the case of the alkyl group described above.
  • heteroarylalkyl means alkyl substituted with heteroaryl.
  • heteroaryloxy refers to a -0-heteroaryl moiety.
  • One or more hydrogen atoms of the heteroaryloxy can be substituted with the same substituent as in the case of the alkyl group described above.
  • heteroaryloxy refers to alkyl substituted with heteroaryl.
  • One or more hydrogen atoms of the heteroaryloxyalkyl may be substituted with the same substituent as in the case of the alkyl group described above.
  • amino group refers to the case where a nitrogen atom is covalently bonded to at least one carbon or heteroatom. Amino groups include, for example, -NH 2 and substituted moieties.
  • amino group includes alkylamino groups where the nitrogen is bonded to at least one additional alkyl group, arylamino groups and diarylamino groups where the nitrogen is bonded to at least one or two or more independently selected aryl groups.
  • “Substituted” in “substituted” by the alkyl group, alkoxy group, alkenyl group, alkynyl group, alkylene oxide group, cycloalkyl group, aryl group, aryloxy group, and heteroaryl group used above means substitution with a halogen atom or halogen atom.
  • C1-C20 alkyl group e.g.
  • R 1 may be a halogen element and R 2 may be hydrogen. Additionally, R 1 may be fluoro (F) or chloro (Cl).
  • R 3 may be a halogen element, and R 4 may be hydrogen. Additionally, R 3 may be fluoro (F).
  • R 3 and R 4 may be -OR 5 , and R 5 may be methyl (methyl, -CH 3 ).
  • R 3 and R 4 may be linked to each other to form a ring with the atoms to which they are attached.
  • the ring may be a 5-8 membered ring, and more specifically, it may be a 5-membered ring. You can.
  • R 3 and R 4 may form a ring while sharing R 5 .
  • the N-benzylquinazolin-4-amine compound is 6-fluoro-N-(4-fluorobenzyl)quinazolin-4-amine [6-Fluoro-N-(4-fluorobenzyl) quinazolin-4-amine] or 4-((3,4-methylenedioxybenzyl)amino)-6-chloroquinazoline [4-((3,4-Methylenedioxybenzyl)amino)-6-chloroquinazoline]. .
  • the 6-fluoro-N-(4-fluorobenzyl)quinazolin-4-amine may be called spoutin-1, and the 4-((3,4-methylenedioxybenzyl)amino)-6 -Chloroquinazoline may be called MBCQ.
  • Spautin-1 refers to the formula 2 (IUPAC name: 6-Fluoro-N-[(4-fluorophenyl)methyl]-4-quinazolinamine or 6-Fluoro-N- (4-fluorobenzyl)quinazolin-4-amine) (CAS Number: 1262888-28-7) is a compound represented by the chemical formula C 15 H 11 F 2 N 3 .
  • MMCQ refers to a compound represented by the following formula 3 (IUPAC name: 4-((3,4-Methylenedioxybenzyl)amino)-6-chloroquinazoline) (CAS Number: 150450-53-6), It is expressed by the chemical formula C 16 H 12 ClN 3 O 2 .
  • the composition includes at least one selected from the group consisting of the N-benzylquinazolin-4-amine compound represented by Formula 1, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, and its solvate. You can.
  • salt refers to a salt that can be used pharmaceutically among salts that are substances in which cations and anions are bonded by electrostatic attraction, and are usually metal salts and organic bases. It may be a salt with a salt, a salt with an inorganic acid, a salt with an organic acid, a salt with a basic or acidic amino acid, etc.
  • the metal salt may be an alkali metal salt (sodium salt, potassium salt, etc.), an alkaline earth metal salt (calcium salt, magnesium salt, barium salt, etc.), an aluminum salt, etc.; Salts with organic bases include triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, and N,N-dibenzylethylenediamine.
  • Salts with organic bases include triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, and N,N-dibenzylethylenediamine.
  • Salts with inorganic acids may include salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, etc.
  • Salts with organic acids may include salts with formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid
  • Salts with basic amino acids may include salts with arginine, lysine, ornithine, etc.
  • Salts with acidic amino acids can be salts with aspartic acid, glutamic acid, etc.
  • Particularly preferred salts include, when the compound has an acidic functional group therein, inorganic salts such as alkali metal salts (e.g., sodium salts, potassium salts, etc.), alkaline earth metal salts (e.g., calcium salts, magnesium salts, barium salts, etc.), and organic salts such as ammonium salts, and when the compound has a basic functional group therein, salts with inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, etc., acetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, There are salts with organic acids such as succinic acid, methanesulfonic acid, and p-toluenesulfonic acid.
  • inorganic salts such as alkali metal salts (e.g., sodium salts, potassium salts, etc.), alkaline earth metal salts (
  • the term "obesity” in this specification refers to a state in which adipose tissue is abnormally increased, and according to the classification of body mass index (BMI), it is classified into severe obesity (BMI of 30.0 or more) and obesity (BMI of 25 to 30). ) and overweight (if BMI is 23 to 25).
  • BMI body mass index
  • the obesity may include both obesity caused by genetic factors and obesity caused by environmental factors.
  • lipid-related metabolic disease refers to a disease that can be caused by abnormalities in lipid concentration in tissues and extracellular fluid due to metabolic abnormalities.
  • the lipid-related metabolic disease may be one or more selected from the group consisting of diabetes, dyslipidemia, fatty liver, insulin resistance syndrome, arteriosclerosis, hypertension, cardiovascular disease, or metabolic syndrome in which the above diseases occur simultaneously.
  • the dyslipidemia may be one or more selected from the group consisting of hyperlipidemia, hypercholesteronemia, and hypertriglyceridemia.
  • insulin resistance refers to a decrease in tissue response to the action of insulin, and the resulting phenomenon is referred to as insulin resistance syndrome.
  • Insulin resistance syndrome refers to phenomena that commonly occur together in a single person due to insulin resistance, such as abnormal glucose metabolism and dyslipidemia, and refers to a case where risk factors, including obesity, which frequently accompanies such people, appear clustered in a single individual. It is known that the cause of this insulin resistance may be impaired insulin action caused by an increase in free fatty acids and competitive inhibition of glucose metabolism.
  • the composition may inhibit lipid accumulation or lipid synthesis, and may specifically inhibit lipid (fat) accumulation or synthesis in fat cells. Additionally, the composition may inhibit the differentiation of adipocytes.
  • the composition may inhibit adipogenesis.
  • adipogenesis refers to the process by which preadipocytes differentiate into adipocytes, and plays an important role in the formation of adipocytes and lipid accumulation.
  • fat is known to be a risk factor for diseases such as obesity, diabetes, fatty liver, and heart disease.
  • Adipocytes are differentiated from multipotent mesenchymal stem cells in the bone marrow. This process occurs when insulin, insulin-like growth factor-1 (IGF-1), and growth hormones act on preadipocytes to produce CAAT enhancer binding protein (C/EBP). ), and is regulated by activating transcription factors such as peroxisome proliferator-activated receptor ⁇ (PPAR ⁇ ).
  • IGF-1 insulin-like growth factor-1
  • PPAR ⁇ peroxisome proliferator-activated receptor ⁇
  • PPAR ⁇ a nuclear receptor
  • composition may inhibit the expression or activity of adipogenesis-related factors.
  • the adipogenesis-related factor is one or more selected from the group consisting of PPAR ⁇ (Peroxisome Proliferator Receptor gamma), C/EBP ⁇ (CCAAT-enhancer-binding proteins alpha), FABP4 (fatty acid binding protein 4), and FASN (Fatty acid synthase).
  • PPAR ⁇ Peroxisome Proliferator Receptor gamma
  • C/EBP ⁇ CCAAT-enhancer-binding proteins alpha
  • FABP4 fatty acid binding protein 4
  • FASN Fatty acid synthase
  • the adipogenesis-related factor may be one or more proteins selected from the group consisting of PPAR ⁇ , C/EBP ⁇ , FABP4, and FASN, genes encoding the same, DNA, and/or mRNA.
  • Inhibition of the expression or activity of the adipogenesis-related factor may include suppressing the expression level or activity level of the protein or gene encoding the factor, specifically PPAR ⁇ , C/EBP ⁇ , FABP4 and FASN. It may be to suppress the expression and/or activity level of one or more proteins selected from the group consisting of, the genes encoding them, DNA or mRNA.
  • treatment refers to any action that improves or beneficially changes the symptoms of obesity and lipid-related metabolic diseases by administering the composition of the present invention.
  • prevention refers to any action that suppresses or delays the possibility of developing obesity and lipid-related metabolic diseases by administering the composition of the present invention.
  • the composition may contain the N-benzylquinazolin-4-amine compound represented by Formula 1 at a concentration of 0.1 to 100 ⁇ M, specifically 0.1 to 100 ⁇ M, 0.1 to 80 ⁇ M, 0.1 to 60 ⁇ M, 0.1 to 40 ⁇ M, 0.1 to 20 ⁇ M, 0.1 to 15 ⁇ M, 0.1 to 10 ⁇ M, 0.1 to 8 ⁇ M, 0.1 to 6 ⁇ M, 0.1 to 5 ⁇ M, 0.5 to 100 ⁇ M, 0.5 to 80 ⁇ M, 0.5 to 60 ⁇ M, 0.5 to 40 ⁇ M, 0.5 to 20 ⁇ M, 0.5 to 15 ⁇ M, 0.5 to 10 ⁇ M, 0.5 to 8 ⁇ M, 0.5 to 6 ⁇ M, 0.5 to 5 ⁇ M, 1 to 100 ⁇ M, 1 to 80 ⁇ M, 1 to 60 ⁇ M, 1 to 40 ⁇ M, 1 to 20 ⁇ M, 1 to 15 ⁇ M, 1 to 10 ⁇ M, 1 to 8 ⁇ M, 1
  • the pharmaceutical composition may include a pharmaceutically acceptable carrier.
  • pharmaceutically acceptable carrier may mean a carrier or diluent that does not irritate living organisms and does not inhibit the biological activity and properties of the injected compound.
  • pharmaceutically acceptable means that it does not inhibit the activity of the active ingredient and does not have any toxicity beyond what the subject of application (prescription) can adapt to.
  • the type of carrier that can be used in the pharmaceutical composition can be any carrier that is commonly used in the art and is pharmaceutically acceptable.
  • Non-limiting examples of the carrier include lactose, dextrose, maltodextrin, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, glycerol, ethanol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or Mineral oil, etc. may be mentioned.
  • the pharmaceutical composition may be prepared into an oral formulation or a parenteral formulation depending on the route of administration by a conventional method known in the art, including a pharmaceutically acceptable carrier in addition to the active ingredient.
  • the pharmaceutical composition can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, or sterile injection solutions according to conventional methods.
  • the pharmaceutical composition can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, or sterile injection solutions according to conventional methods.
  • oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, or sterile injection solutions according to conventional methods.
  • diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, or surfactants.
  • the pharmaceutical composition When the pharmaceutical composition is prepared as an oral dosage form, it is prepared in the form of powders, granules, tablets, pills, sugar-coated tablets, capsules, solutions, gels, syrups, suspensions, wafers, etc. according to methods known in the art along with a suitable carrier. It can be manufactured with At this time, examples of suitable pharmaceutically acceptable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, and xylitol, starches such as corn starch, potato starch, and wheat starch, cellulose, methylcellulose, and ethylcellulose.
  • Cellulose such as sodium carboxymethylcellulose and hydroxypropylmethylcellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, polyol, vegetable. Yu, etc. can be mentioned.
  • diluents and/or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants may be included in the formulation.
  • the pharmaceutical composition when prepared as a parenteral formulation, it can be formulated in the form of injections, transdermal administration, nasal inhalation, and suppositories along with a suitable carrier according to methods known in the art.
  • suitable carriers include sterilized water, ethanol, polyols such as glycerol or propylene glycol, or mixtures thereof, preferably Ringer's solution, phosphate buffered saline (PBS) containing triethanolamine, or sterile for injection.
  • PBS phosphate buffered saline
  • Isotonic solutions such as water or 5% dextrose can be used.
  • formulated for transdermal administration When formulated for transdermal administration, it can be formulated in the form of ointments, creams, lotions, gels, external solutions, paste preparations, linear preparations, and aerol preparations.
  • suitable propellants such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, and carbon dioxide.
  • the base is Wethepsol (witepsol), Tween 61, polyethylene glycols, cocoa fat, laurel paper, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, sorbitan fatty acid esters, etc. can be used.
  • the pharmaceutical composition may be administered in a pharmaceutically effective amount, where the term "pharmaceutically effective amount” means an amount sufficient to treat or prevent a disease with a reasonable benefit/risk ratio applicable to medical treatment or prevention.
  • the effective dose level is determined by the severity of the disease, the activity of the drug, the patient's age, weight, health, gender, the patient's sensitivity to the drug, the administration time of the composition of the present invention used, the route of administration and excretion rate, the treatment period, and the drug used. It may be determined according to factors including drugs combined or used simultaneously with the inventive composition and other factors well known in the medical field.
  • the pharmaceutical composition may be administered alone or in combination with ingredients known to have therapeutic effects on obesity or lipid-related metabolic diseases. It is important to consider all of the above factors and administer the amount that will achieve maximum effect with the minimum amount without side effects.
  • the dosage of the pharmaceutical composition can be determined by a person skilled in the art considering the purpose of use, the degree of addiction of the disease, the patient's age, weight, gender, antecedent history, or the type of substance used as an active ingredient.
  • the pharmaceutical composition of the present invention can be administered at about 0.1 ng to about 1,000 mg/kg, preferably 1 ng to about 100 mg/kg per adult, and the frequency of administration of the composition of the present invention is specifically determined by this. Although not limited, it can be administered once a day, or the dose can be divided and administered several times. The above dosage or frequency of administration does not limit the scope of the present application in any way.
  • Another aspect is to provide a method for treating or preventing obesity and lipid-related metabolic diseases, comprising administering to a subject a pharmaceutical composition for preventing or treating obesity and lipid-related metabolic diseases.
  • a pharmaceutical composition for preventing or treating obesity and lipid-related metabolic diseases comprising administering to a subject a pharmaceutical composition for preventing or treating obesity and lipid-related metabolic diseases.
  • the same parts as described above also apply to the above method.
  • the term "individual” used herein may include, without limitation, mammals, birds, reptiles, farmed fish, etc., including rats, livestock, humans, etc., that have developed or are at risk of developing obesity and lipid-related metabolic diseases. , the entity may exclude humans.
  • the pharmaceutical composition may be administered singly or multiple times in a pharmaceutically effective amount.
  • the composition can be formulated and administered in the form of a solution, powder, aerosol, injection, infusion solution (injection), capsule, pill, tablet, suppository, or patch.
  • the administration route of the pharmaceutical composition for preventing or treating obesity and lipid-related metabolic diseases may be administered through any general route as long as it can reach the target tissue.
  • the pharmaceutical composition is not particularly limited thereto, but may be administered intraperitoneally, intravenously, intramuscularly, subcutaneously, intradermally, transdermal patch, oral administration, intranasal administration, intrapulmonary administration, intrarectal administration, etc., depending on the purpose. It can be administered via any route. However, when administered orally, it can be administered in an unformulated form, and since the active ingredients of the pharmaceutical composition may be denatured or decomposed by stomach acid, the oral composition is formulated to coat the active agent or protect it from decomposition in the stomach. It can also be administered orally in the form of a tablet or oral patch. Additionally, the composition can be administered by any device that allows the active substance to move to target cells.
  • N-benzylquinazolin-4-amine compound represented by Formula 1, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, or its solvate is another aspect.
  • N-benzylquinazolin-4-amine compound represented by Formula 1, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, or its solvate is another aspect.
  • the N-benzylquinazolin-4-amine compound is 6-fluoro-N-(4-fluorobenzyl)quinazolin-4-amine [6-Fluoro-N-(4-fluorobenzyl) quinazolin-4-amine] or 4-((3,4-methylenedioxybenzyl)amino)-6-chloroquinazoline [4-((3,4-Methylenedioxybenzyl)amino)-6-chloroquinazoline]. .
  • improvement refers to any action that improves or beneficially changes the symptoms of obesity and lipid-related metabolic diseases by administering the composition of the present invention.
  • food in this specification refers to meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, and alcoholic beverages. , vitamin complexes, health functional foods, and health foods, etc., and include all foods in the conventional sense.
  • the food can be manufactured by methods commonly used in the industry, and can be manufactured by adding raw materials and ingredients commonly added in the industry. Additionally, the food formulation can be manufactured without limitation as long as it is a formulation recognized as a food.
  • the food composition can be manufactured in various types of formulations, and unlike general drugs, it is made from food as a raw material, has the advantage of not having side effects that may occur when taking the drug for a long time, and is highly portable, so the food composition of the present invention It can be taken as a supplement to improve the effect of bone-related diseases.
  • the food composition may be a health functional food composition.
  • health functional food in this specification refers to food manufactured and processed using raw materials or ingredients with functionality useful to the human body in accordance with Act No. 6727 on Health Functional Food, and “functional” refers to food that is manufactured and processed using functional ingredients useful to the human body. It means controlling the structure and function of nutrients or obtaining useful effects for health purposes such as physiological effects.
  • the above-mentioned health food refers to food that has a more active health maintenance or promotion effect compared to general food
  • health supplement food refers to food for the purpose of supporting health.
  • the terms health functional food, health food, and health supplement may be used interchangeably.
  • the health functional food is a food manufactured by adding the composition to food materials such as beverages, teas, spices, gum, and confectionery, or by encapsulating, powdering, or suspending it, and has specific health effects when consumed.
  • the health functional food is a food manufactured by adding the composition to food materials such as beverages, teas, spices, gum, and confectionery, or by encapsulating, powdering, or suspending it, and has specific health effects when consumed.
  • unlike regular drugs it has the advantage of being made from food and eliminating the side effects that can occur when taking the drug for a long period of time.
  • the food composition can be consumed on a daily basis, it can be expected to be highly effective in improving obesity and lipid-related metabolic diseases, so it can be very useful.
  • the food composition may further include a physiologically acceptable carrier.
  • the type of carrier is not particularly limited, and any carrier commonly used in the art can be used.
  • the food composition may include additional ingredients that are commonly used in food compositions to improve smell, taste, vision, etc.
  • it may include vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid, etc.
  • it may contain minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), and chromium (Cr).
  • it may contain amino acids such as lysine, tryptophan, cysteine, and valine.
  • the food composition contains preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), disinfectants (bleaching powder, high bleaching powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisole (BHA), butylhydroxide) roxitoluene (BHT), etc.), colorants (tar color, etc.), coloring agents (sodium nitrite, sodium nitrite, etc.), bleaching agents (sodium sulfite), seasonings (MSG monosodium glutamate, etc.), sweeteners (dulcine, cyclemate, saccharin) , sodium, etc.), flavorings (vanillin, lactones, etc.), leavening agents (alum, D-potassium hydrogen tartrate, etc.), strengtheners, emulsifiers, thickeners (grease), coating agents, gum base agents, anti-foam agents, solvents, improvers, etc. May
  • the food composition can be added as is or used together with other foods or food ingredients, and can be used appropriately according to conventional methods.
  • the mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment).
  • the food composition of the present invention may be added in an amount of 50 parts by weight or less, specifically 20 parts by weight or less, relative to the food or beverage.
  • the content when consumed for a long time for health and hygiene purposes, the content may be below the above range. Since there is no problem in terms of safety, the active ingredient may be used in amounts above the above range.
  • the food composition it can be used as a health drink composition, and in this case, it may contain various flavoring agents or natural carbohydrates as additional ingredients, like regular drinks.
  • the above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; polysaccharides such as dextrins and cyclodextrins; It may be a sugar alcohol such as xylitol, sorbitol, or erythritol.
  • Sweeteners include natural sweeteners such as thaumatin and stevia extract; Synthetic sweeteners such as saccharin and aspartame can be used.
  • the ratio of the natural carbohydrate may be generally about 0.01 to 0.04 g, specifically about 0.02 to 0.03 g, per 100 mL of the health drink composition of the present invention.
  • the health drink composition includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, It may contain alcohol or carbonating agent. Additionally, it may contain pulp for the production of natural fruit juice, fruit juice beverage, or vegetable beverage. These ingredients can be used independently or in combination. The ratio of these additives is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health drink composition of the present invention.
  • the food composition may contain the compound of the present invention in various weight % if it can exhibit an effect of improving or preventing obesity and lipid-related metabolic diseases.
  • the compound may be added at 0.00001 to 100 weight % or It may contain 0.01 to 80% by weight, but is not limited thereto.
  • N-benzylquinazolin-4-amine compound represented by Formula 1, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, or its solvate is another aspect.
  • N-benzylquinazolin-4-amine compound represented by Formula 1, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, or its solvate is another aspect.
  • the N-benzylquinazolin-4-amine compound is 6-fluoro-N-(4-fluorobenzyl)quinazolin-4-amine [6-Fluoro-N-(4-fluorobenzyl) quinazolin-4-amine] or 4-((3,4-methylenedioxybenzyl)amino)-6-chloroquinazoline [4-((3,4-Methylenedioxybenzyl)amino)-6-chloroquinazoline]. .
  • feed in this specification may mean any natural or artificial diet, meal, etc., or a component of the meal, for or suitable for eating, ingestion, and digestion by animals.
  • the type of feed is not particularly limited, and feed commonly used in the art can be used.
  • Non-limiting examples of the feed include plant feeds such as grains, roots and fruits, food processing by-products, algae, fiber, pharmaceutical by-products, oils and fats, starches, cucurbits or grain by-products;
  • Examples include animal feeds such as proteins, inorganic substances, fats and oils, minerals, fats and oils, single-cell proteins, zooplanktons or food. These may be used individually or in combination of two or more types.
  • the feed composition may further include known additives that can be added to improve or prevent obesity and lipid-related metabolic diseases.
  • the feed composition may be in the form of a highly concentrated liquid, powder, or granule.
  • the feed composition may further include any protein-containing organic cereal flour commonly used to meet the dietary needs of animals.
  • the feed composition can be used by adding it to animal feed by dipping, spraying, or mixing.
  • the feed composition may additionally contain substances that have various effects, such as nutrient supplementation and weight loss prevention, improvement of digestibility of fiber in feed, improvement of milk quality, prevention of reproductive disorders and improvement of conception rate, and prevention of high temperature stress in summer.
  • substances that have various effects such as nutrient supplementation and weight loss prevention, improvement of digestibility of fiber in feed, improvement of milk quality, prevention of reproductive disorders and improvement of conception rate, and prevention of high temperature stress in summer.
  • mineral preparations such as sodium bicarbonate, bentonite, magnesium oxide, complex minerals, trace mineral preparations such as zinc, copper, cobalt, and selenium, kerotene, vitamin E, vitamins A, D, E, and nicotinic acid.
  • vitamins such as vitamin B complex
  • protective amino acids such as methionine and lysic acid
  • protective fatty acids such as fatty acid calcium salts
  • probiotics lactic acid bacteria
  • yeast cultures live bacteria such as mold fermentation products, yeast agents, etc.
  • the feed composition can be applied to a number of animal diets, including mammals and poultry, that is, feed and drinking water.
  • the feed composition may include all substances added to the feed (i.e., feed additives), feed raw materials, or the feed itself fed to the individual.
  • N-benzylquinazolin-4-amine compound represented by Formula 1 Another aspect is the N-benzylquinazolin-4-amine compound represented by Formula 1, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, or its solvate.
  • Formula 1 N-benzylquinazolin-4-amine compound represented by Formula 1, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, or its solvate.
  • the N-benzylquinazolin-4-amine compound is 6-fluoro-N-(4-fluorobenzyl)quinazolin-4-amine [6-Fluoro-N-(4-fluorobenzyl) quinazolin-4-amine] or 4-((3,4-methylenedioxybenzyl)amino)-6-chloroquinazoline [4-((3,4-Methylenedioxybenzyl)amino)-6-chloroquinazoline]. .
  • cellulite in this specification refers to a phenomenon in which the skin becomes bumpy like a rough orange peel due to circulatory disorders caused by the accumulation of excessive fat and waste. It is produced within the dermal layer of the skin where collagen and elastin exist and is used in women. It occurs especially frequently in Cellulite obesity, in addition to abnormal accumulation of subcutaneous fat tissue, is a disorder of the lymphatic system, causing lymphatic fluid to stagnate in the gaps between human tissues, causing a type of edema in that area to appear as if the person has gained weight, which is a major factor in changing body shape.
  • lymphatic fluid stagnates in tissue gaps, it not only causes cosmetic problems such as obesity, but also accumulates toxic substances in the body, which has a negative effect on skin cells and inhibits ionization activity for cell nutrition, causing skin aging and cell necrosis. I do it.
  • the formulation of the cosmetic composition is not limited as long as it is a typical cosmetic formulation, but for example, skin lotion, astringent lotion, or nourishing lotion, nutritional cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing cream, etc. It may be water, pack, powder, body lotion, body cream, body oil, or body essence.
  • the cosmetic composition may contain substances arbitrarily selected according to the formulation or purpose of use of the cosmetic, for example, preservatives, stabilizers, surfactants, solubilizers, moisturizers, emollients, ultraviolet absorbers, preservatives, disinfectants, antioxidants, pH It may further include conditioners, organic and inorganic pigments, fragrances, cooling agents or antiperspirants.
  • preservatives for example, preservatives, stabilizers, surfactants, solubilizers, moisturizers, emollients, ultraviolet absorbers, preservatives, disinfectants, antioxidants, pH
  • conditioners organic and inorganic pigments, fragrances, cooling agents or antiperspirants.
  • the carrier component may include, for example, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide. It may include etc.
  • the carrier component may include, for example, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder.
  • chlorofluorocarbons may be added. May contain propellants such as lohydrocarbon, propane/butane or dimethyl ether.
  • the carrier component may include, for example, a solvent, a solubilizing agent, or an emulsifying agent, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, and benzyl alcohol. , benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan.
  • a solvent such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, and benzyl alcohol.
  • benzyl benzoate propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan.
  • the carrier component may include, for example, water, a liquid diluent such as ethanol or propylene glycol, a suspension such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester. It may include microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracant.
  • the carrier component may include, for example, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosylate. It may include nitrate, fatty acid amide ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester.
  • Another aspect is to provide a method of improving skin by preventing or improving cellulite, comprising applying the cosmetic composition for preventing or improving cellulite to the skin of an individual.
  • the cosmetic composition for preventing or improving cellulite to the skin of an individual.
  • the same parts as described above also apply to the composition.
  • the term “individual” used in this specification may include, without limitation, mammals, birds, reptiles, farmed fish, etc., including rats, livestock, and humans that develop or are likely to develop cellulite.
  • the method may be a beauty method through skin improvement.
  • application includes methods of administration or application to the skin of a subject, such as application by fingers, brush, cotton ball, pad, spray, sponge, cotton swab, roll-on, etc. .
  • a person skilled in the art can easily determine the appropriate method to apply.
  • the applying step may be applying the composition at intervals of 1 minute to 90 minutes, specifically 1 minute to 90 minutes, 5 minutes to 90 minutes, 1 minute to 60 minutes, and 5 minutes to 90 minutes. It may be at intervals of 60 minutes, 1 minute to 30 minutes, 5 minutes to 30 minutes, 10 minutes to 30 minutes, 10 minutes to 90 minutes, or 10 minutes to 60 minutes.
  • the applying step may be applying the composition 1 to 30 times, specifically 1 to 30 times, 1 to 25 times, 5 to 30 times, 5 to 25 times, It may be applied 1 to 20 times, 5 to 20 times, 10 to 20 times, 10 to 30 times, or 10 to 25 times.
  • N-benzylquinazolin-4-amine compound represented by Formula 1 Another aspect is the N-benzylquinazolin-4-amine compound represented by Formula 1, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, or its solvate. It relates to use in the prevention or treatment of obesity and lipid-related metabolic diseases. The same parts as described above also apply to the above use.
  • N-benzylquinazolin-4-amine compound represented by Formula 1 Another aspect is the N-benzylquinazolin-4-amine compound represented by Formula 1, its stereoisomer, its pharmaceutically acceptable salt, its hydrate, or its solvate. It relates to the use for preventing or improving cellulite. The same parts as described above also apply to the above use.
  • composition containing the N-benzylquinazolin-4-amine compound of the present invention induces the inhibition of lipid accumulation and adipocyte differentiation and suppresses the expression level of adipogenesis-related factors.
  • Using the composition It can enhance the effect on obesity and lipid-related metabolic diseases.
  • Figure 1 is a diagram showing the results of observing the level of lipid accumulation or adipocyte differentiation according to treatment with different concentrations of spoutin-1 using Oil Red O staining.
  • Figure 2 is a graph showing the level of lipid accumulation or adipocyte differentiation according to treatment with different concentrations of spoutin-1.
  • Figure 3 is a diagram showing the expression levels of factors related to adipogenesis according to treatment with different concentrations of spoutin-1.
  • Figure 4 is a diagram showing the results of observing the level of lipid accumulation or adipocyte differentiation according to treatment with different concentrations of MBCQ using Oil Red O staining.
  • Figure 5 is a graph showing the level of lipid accumulation or adipocyte differentiation according to treatment with different concentrations of MBCQ.
  • Figure 6 is a diagram showing the expression levels of factors related to adipogenesis according to treatment with different concentrations of MBCQ.
  • Example 1 Cell culture and adipocyte differentiation
  • 3T3-L1 cells were maintained or cultured using DMEM (Dulbecco's modified Eagle's medium) supplemented with 10% FBS.
  • DMEM Dulbecco's modified Eagle's medium
  • 3T3-L1 cells were first cultured in a culture dish until confluency. At day 0 of confluence, 3T3-L1 cells were incubated with 10% FBS, insulin (1 ⁇ g/mL, Sigma-Aldrich, St. Louis, MO, USA), and isobutylmethylxanthine (IBMX, 520M, Sigma-Aldrich). , St. Louis, MO, USA) and dexamethasone (1 ⁇ M, Sigma-Aldrich, St. Louis, MO, USA) for differentiation. After 2 days of culture, the culture medium was replaced with DMEM supplemented with 10% FBS and insulin (1 ⁇ g/mL). Next, after 4 days of culture, the culture medium was replaced with DMEM supplemented with 10% FBS.
  • IBMX isobutylmethylxanthine
  • Differentiated 3T3-L1 cells were incubated in 10% formalin for 10 minutes and washed with distilled water. Cells were then stained with ORO in 60% isopropanol. Afterwards, the stain remaining in the cells was removed by elution with 100% isopropanol, and the OD500 of the solution was measured using a microplate reader (Molecular devices, CA, USA).
  • Example 3 RNA isolation and real-time PCR analysis
  • RNA lysis reagent (easy-BLUE TM ; iNtRON Biotechnology, Seongnam, Republic of Korea) according to the manufacturer's instructions.
  • cDNA (1 ⁇ g) was synthesized from the isolated RNA using qPCR RT Master Mix (Takara Bio, Otsu, Japan).
  • real-time PCR real-time PCR amplification was performed using the primers in Table 1 below.
  • primer Sequence (5 ⁇ -3 ⁇ ) sequence number PPAR ⁇ forward agggcgatcttgacaggaaa
  • FASN forward tgggttctagccagcagagt 7 reverse accaccagagaccgttatgc 8 ⁇ -actin forward ggctgtattccctccatcg 9 reverse ccagttggtaacaatgccatgt 10
  • Real-time PCR was performed using SYBR Green Master Mix (Toyobo, Osaka, Japan) and an Applied Biosystems thermocycler.
  • spoutin-1 was purchased from Sigma Chemicals (St. Louis, MO, USA).
  • 3T3-L1 cells were cultured to induce differentiation, and spoutin-1 was treated with various concentrations (0.5 ⁇ M, 1 ⁇ M, 2.5 ⁇ M, 5 ⁇ M, and 10 ⁇ M) from the 2nd to 6th day of differentiation induction.
  • Adipogenesis a process in which adipocyte precursors develop into mature adipocytes, was measured by staining lipid droplets with Oil Red O staining using the method described in Experimental Example 2 on the 6th day of cell differentiation induction.
  • differentiation was induced by culturing 3T3-L1 cells in the same manner as in Example 1, and spoutin-1 was added at various concentrations (0.5 ⁇ M, 1 ⁇ M, 2.5 ⁇ M, 5 ⁇ M, and 10 ⁇ M) from the 2nd day to the 6th day of differentiation induction. was processed. Afterwards, on the 6th day of cell differentiation induction, whole cell lysates were obtained from the cells, and real-time PCR analysis was performed based on the method described in Experimental Example 3 to determine PPAR ⁇ , C/EBP ⁇ , FABP4, and FASN. The expression level was confirmed.
  • 3T3-L1 cells were cultured to induce differentiation, and MBCQ was treated at various concentrations (0.5 ⁇ M, 1 ⁇ M, 2.5 ⁇ M, 5 ⁇ M, 7.5 ⁇ M, and 10 ⁇ M) from the 2nd day to the 6th day of differentiation induction.
  • Adipogenesis a process in which adipocyte precursors develop into mature adipocytes, was measured by staining lipid droplets with Oil Red O staining using the method described in Experimental Example 2 on the 6th day of cell differentiation induction.
  • differentiation was induced by culturing 3T3-L1 cells in the same manner as in Example 3, and various concentrations (0.5 ⁇ M, 1 ⁇ M, 2.5 ⁇ M, 5 ⁇ M, 7.5 ⁇ M, and 10 ⁇ M) of MBCQ were added from the 2nd day to the 6th day of differentiation induction. was processed. Afterwards, on the 6th day of cell differentiation induction, whole cell lysates were obtained from the cells, and real-time PCR analysis was performed based on the method described in Experimental Example 3 to determine PPARg, C/EBPa, FABP4, and FASN. The expression level was confirmed.

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Abstract

La présente invention concerne une composition comprenant une N-benzylquinazoline-4-amine, représentée par la formule chimique 1, pour prévenir ou traiter l'obésité ou des troubles métaboliques associés aux lipides. Il a été identifié que la composition comprenant une N-benzylquinazoline-4-amine représentée par la formule chimique 1, selon la présente invention, induit l'inhibition de l'accumulation des lipides et la différenciation des adipocytes et inhibe les niveaux d'expression d'un facteur associé à l'adipogenèse, et ainsi les effets sur l'obésité, les troubles métaboliques associés aux lipides et analogues peuvent être améliorés à l'aide de la composition.
PCT/KR2023/020781 2022-12-22 2023-12-15 Composition comprenant un composé n-benzylquinazoline-4-amine pour prévenir ou traiter l'obésité ou des troubles métaboliques associés aux lipides Ceased WO2024136338A1 (fr)

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KR10-2022-0182248 2022-12-22
KR1020220182248A KR102896033B1 (ko) 2022-12-22 N-벤질퀴나졸린-4-아민 화합물을 포함하는, 비만 및 지질 관련 대사성 질환의 예방 또는 치료용 조성물

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006026395A1 (fr) * 2004-08-26 2006-03-09 Encysive Pharmaceuticals Antagonistes du recepteur de l'endotheline a (eta) combines a des inhibiteurs de phosphodiesterase 5 (pde5) et leurs utilisations
KR20060079121A (ko) * 2004-12-31 2006-07-05 에스케이케미칼주식회사 당뇨 및 비만 치료예방에 유효한 퀴나졸린 유도체
WO2008098192A2 (fr) * 2007-02-08 2008-08-14 Todd Maibach Compositions et méthodes de traitement de la neuropathie
WO2021002986A2 (fr) * 2019-05-31 2021-01-07 Case Western Reserve University Inhibiteurs de bax et leurs utilisations
WO2022178283A1 (fr) * 2021-02-19 2022-08-25 The Regents On The University Of California Compositions et méthodes de traitement de tauopathies

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006026395A1 (fr) * 2004-08-26 2006-03-09 Encysive Pharmaceuticals Antagonistes du recepteur de l'endotheline a (eta) combines a des inhibiteurs de phosphodiesterase 5 (pde5) et leurs utilisations
KR20060079121A (ko) * 2004-12-31 2006-07-05 에스케이케미칼주식회사 당뇨 및 비만 치료예방에 유효한 퀴나졸린 유도체
WO2008098192A2 (fr) * 2007-02-08 2008-08-14 Todd Maibach Compositions et méthodes de traitement de la neuropathie
WO2021002986A2 (fr) * 2019-05-31 2021-01-07 Case Western Reserve University Inhibiteurs de bax et leurs utilisations
WO2022178283A1 (fr) * 2021-02-19 2022-08-25 The Regents On The University Of California Compositions et méthodes de traitement de tauopathies

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