WO2020046020A1 - Matériau inhibiteur du type stéroïde déshydrogénase dépendant du nicotinamide adénine dinucléotide phosphate dérivé du corps humain, et agent anticancéreux le comprenant en tant que principe actif ou composition pharmaceutique le comprenant en tant que principe actif pour le traitement de l'hyperlipidémie - Google Patents

Matériau inhibiteur du type stéroïde déshydrogénase dépendant du nicotinamide adénine dinucléotide phosphate dérivé du corps humain, et agent anticancéreux le comprenant en tant que principe actif ou composition pharmaceutique le comprenant en tant que principe actif pour le traitement de l'hyperlipidémie Download PDF

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Publication number
WO2020046020A1
WO2020046020A1 PCT/KR2019/011094 KR2019011094W WO2020046020A1 WO 2020046020 A1 WO2020046020 A1 WO 2020046020A1 KR 2019011094 W KR2019011094 W KR 2019011094W WO 2020046020 A1 WO2020046020 A1 WO 2020046020A1
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WO
WIPO (PCT)
Prior art keywords
cancer
substituted
aryl
halogen
compound
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PCT/KR2019/011094
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English (en)
Korean (ko)
Inventor
이봉진
이규연
이상재
김동균
이주연
정관령
양희철
이현규
김현숙
Original Assignee
서울대학교산학협력단
한국화학연구원
국립암센터
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Priority claimed from KR1020190105425A external-priority patent/KR102348468B1/ko
Application filed by 서울대학교산학협력단, 한국화학연구원, 국립암센터 filed Critical 서울대학교산학협력단
Priority to US17/271,354 priority Critical patent/US20210253544A1/en
Publication of WO2020046020A1 publication Critical patent/WO2020046020A1/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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • 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
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms

Definitions

  • the present invention relates to a nicotine amide adenine dinucleotide phosphate-dependent steroid dehydrogenase inhibitor derived from a human body, and an anticancer agent or a hyperlipidemic pharmaceutical composition containing the same as an active ingredient.
  • EGFR epidermal growth factor receptor
  • nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase which acts on the cholesterol synthesis pathway in the human body, is basically known as a sterol synthase, but has recently been inhibited by EGF (epidermal). growth factor)
  • EGF epidermal growth factor
  • the inhibition of cancer growth through the elimination of resistance and metabolic regulation of receptor-targeted anticancer drugs has been found to attract attention as a new anticancer drug target (Non-Patent Document 1, Nat Commun. 2015 Oct 12; 6: 8613).
  • the nicotinamide adenine dinucleotide phosphate dependent steroid dehydrogenase has also been reported to play an important role in the metastasis of breast cancer.
  • CK syndrome and CHILD congenital hemidysplasia with ichthyosiform nevus and limb. defects are known to develop, and are expected to give important clues to the treatment of congenital hereditary diseases.
  • nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase is closely related to hyperlipidemia, and compounds that inhibit the function of nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase protein with high activity are used for the treatment of important human diseases in the future. It is possible.
  • An object of one aspect of the present invention is to provide a compound that effectively inhibits nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase (NADP-dependent steroid dehydrogenase-like; NSDHL).
  • Another object of the present invention is to provide a pharmaceutical composition for preventing or treating cancer containing the compound as an active ingredient.
  • An object in another aspect of the present invention is to provide a pharmaceutical composition for preventing or treating hyperlipidemia containing the compound as an active ingredient.
  • Another object of the present invention is to provide a nutraceutical composition for the prevention or improvement of cancer containing the compound as an active ingredient.
  • Another object of the present invention is to provide a dietary supplement for the prevention or improvement of hyperlipidemia containing the compound as an active ingredient.
  • One aspect of the invention provides a compound represented by the following formula (1), solvates, hydrates, or pharmaceutically acceptable salts thereof.
  • R is as defined herein.
  • Another aspect of the present invention provides a pharmaceutical composition for preventing or treating cancer containing the compound as an active ingredient.
  • Another aspect of the invention provides a pharmaceutical composition for the prevention or treatment of hyperlipidemia containing the compound as an active ingredient.
  • Another aspect of the present invention provides a nutraceutical composition for preventing or improving cancer containing the compound as an active ingredient.
  • Another aspect of the invention provides a dietary supplement for the prevention or improvement of hyperlipidemia containing the compound as an active ingredient.
  • Another aspect of the invention provides a method of treating cancer comprising administering the compound to a subject in need thereof.
  • Another aspect of the invention provides a method of treating hyperlipidemia comprising administering the compound to a subject in need thereof.
  • Another aspect of the invention provides the compound for use in the prevention or treatment of cancer.
  • Another aspect of the present invention provides the compound for use in the prevention or treatment of hyperlipidemia.
  • Another aspect of the invention provides the use of said compound for the manufacture of a medicament for use in the prevention or treatment of cancer.
  • Another aspect of the invention provides the use of said compound for the manufacture of a medicament for use in the prevention or treatment of hyperlipidemia.
  • the nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase (NSDHL) inhibitor provided in one aspect of the present invention is not only usable as an anticancer agent capable of overcoming the resistance of an EGFR target anticancer agent, but also has an effect that can be used to treat hyperlipidemia.
  • 1 is a graph showing a measurement result of fluorescence intensity of NADH for each NSDHL concentration.
  • Figure 2 is a graph showing the results of NSDHL and NADH conjugate inhibition experiment using NAD +.
  • One aspect of the invention provides a compound represented by the following formula (1), solvates, hydrates, or pharmaceutically acceptable salts thereof.
  • a 1 is —H or unsubstituted or substituted C 6-10 aryl C 1-5 straight or branched alkoxy, wherein substituted C 6-10 aryl C 1-5 straight or branched alkoxy is C 6-10 aryl C 1-5 straight or branched chain substituted with one or more substituents selected from the group consisting of halogen (-F, -Cl, -Br, -I), nitro, nitrile and -COOH Alkoxy;
  • a 2 is -H or -OH
  • a 3 is —H, halogen or unsubstituted or substituted C 6-10 aryl, wherein the substituted C 6-10 aryl is one or more halogen-substituted aryl;
  • a 4 is —H or C 1-5 straight or branched alkoxy
  • B 1 is —H or unsubstituted or substituted C 6-10 aryl, wherein the substituted C 6-10 aryl is one or more halogen-substituted aryl;
  • the B 2 is -H or unsubstituted or substituted C 6-10 aryl, wherein the substituted C 6-10 aryl may be one or more halogen-substituted aryl.
  • a 1 is unsubstituted or substituted benzyloxy, wherein substituted benzyloxy is benzyloxy substituted with one or more substituents selected from the group consisting of halogen and -COOH;
  • a 2 is -H or -OH
  • a 3 is —H, halogen or unsubstituted or substituted phenyl, wherein substituted phenyl is phenyl substituted with one or more halogens;
  • a 4 is -H or methoxy
  • B 1 is phenyl substituted with one halogen
  • B 2 may be phenyl substituted with one halogen.
  • the compound represented by Formula 1 may be a compound of any one of the following compound groups.
  • the compound represented by Chemical Formula 1 of the present invention may be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful.
  • Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid, phosphorous acid, aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes.
  • Non-toxic organic acids such as dioate, aromatic acids, aliphatic and aromatic sulfonic acids, organic acids such as trifluoroacetic acid, acetate, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, 4-toluenesulfonic acid, tartaric acid, fumaric acid, etc.
  • Such pharmaceutically nontoxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, eye Odide, Fluoride, Acetate, Propionate, Decanoate, Caprylate, Acrylate, Formate, Isobutyrate, Caprate, Heptanoate, Propiolate, Oxalate, Malonate, Succinate, Sube Latex, sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitro benzoate, hydroxybenzoate, Methoxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlor
  • the acid addition salt according to the present invention can be prepared by a conventional method, for example, a precipitate produced by dissolving a derivative of Formula 1 in an organic solvent such as methanol, ethanol, acetone, methylene chloride, acetonitrile and adding an organic or inorganic acid.
  • an organic solvent such as methanol, ethanol, acetone, methylene chloride, acetonitrile and adding an organic or inorganic acid.
  • the solvent may be prepared by filtration and drying, or the solvent and the excess acid may be distilled under reduced pressure, dried and then crystallized under an organic solvent.
  • Bases can also be used to make pharmaceutically acceptable metal salts.
  • Alkali metal or alkaline earth metal salts are obtained, for example, by dissolving the compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically suitable to prepare sodium, potassium or calcium salt as the metal salt.
  • Corresponding salts are also obtained by reacting an alkali metal or alkaline earth metal salt with a suitable negative salt (eg silver nitrate).
  • the present invention includes not only the compound represented by Chemical Formula 1 and pharmaceutically acceptable salts thereof, but also solvates, optical isomers, hydrates, and the like that can be prepared therefrom.
  • Another aspect of the present invention provides a pharmaceutical composition for preventing or treating cancer containing the compound represented by Formula 1, a solvate, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the compound may be to inhibit or inhibit nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase (NADP-dependent steroid dehydrogenase-like; NSDHL) to exhibit a prophylactic or therapeutic activity of cancer.
  • the pharmaceutical composition may be an anticancer composition.
  • the cancer is kidney cancer, bladder cancer, liver cancer, thymic cancer, blood cancer, ovarian cancer, cervical cancer, breast cancer, colon cancer, stomach cancer, pancreatic cancer, colon cancer, peritoneal metastases cancer, skin cancer, bladder cancer, prostate cancer, lung cancer, osteosarcoma, fibrotic Tumors, brain tumors, etc., but is not limited thereto.
  • Another aspect of the present invention provides a pharmaceutical composition for preventing or treating hyperlipidemia, which contains the compound represented by Formula 1, a solvate, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the compound may be to inhibit or inhibit nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase (NADP-dependent steroid dehydrogenase-like; NSDHL) to exhibit the prevention or treatment of hyperlipidemia.
  • NSDHL nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase
  • the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof may be administered in various formulations, oral and parenteral, during clinical administration.
  • diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants are usually used.
  • Solid form preparations for oral administration include tablets, pills, powders, granules, capsules and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin.
  • lubricants such as magnesium stearate, talc and the like are also used.
  • Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. have.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions.
  • the non-aqueous solvent and the suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.
  • a pharmaceutical composition comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient may be administered parenterally, and parenteral administration may be administered by subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection. It depends on how to do it.
  • the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof is mixed with water with a stabilizer or a buffer to prepare a parenteral formulation, and prepared as a solution or suspension, which is an ampule or vial unit dosage form. It can be prepared by.
  • the compositions may contain sterile and / or preservatives, stabilizers, hydrating or emulsifying accelerators, auxiliaries such as salts and / or buffers for the control of osmotic pressure, and other therapeutically useful substances, and conventional methods of mixing, granulating It may be formulated according to the formulation or coating method.
  • Formulations for oral administration include, for example, tablets, pills, hard / soft capsules, solutions, suspensions, emulsifiers, syrups, granules, elixirs, troches, and the like. , Dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine), lubricants such as silica, talc, stearic acid and its magnesium or calcium salts and / or polyethylene glycols.
  • Tablets may contain binders such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine and the like, optionally with bores such as starch, agar, alginic acid or its sodium salt, etc. Release or boiling mixtures and / or absorbents, colorants, flavors, and sweeteners.
  • binders such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine and the like, optionally with bores such as starch, agar, alginic acid or its sodium salt, etc. Release or boiling mixtures and / or absorbents, colorants, flavors, and sweeteners.
  • Another aspect of the present invention provides a nutraceutical composition for preventing or improving cancer containing the compound represented by Formula 1, a solvate, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
  • Another aspect of the present invention provides a health functional food composition for preventing or improving hyperlipidemia containing the compound represented by Formula 1, a solvate, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the compound represented by Chemical Formula 1 according to the present invention may be added to a food as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method.
  • the mixing amount of the active ingredient can be suitably determined according to the purpose of use (prevention or improvement).
  • the amount of the compound in the health food can be added at 0.1 to 90 parts by weight of the total food weight.
  • the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety.
  • the health functional beverage composition of the present invention is not particularly limited to other ingredients except for containing the compound as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
  • natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents such as, tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
  • the proportion of said natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 g of the composition of the present invention.
  • the compound represented by the formula (1) according to the present invention includes various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors such as flavoring agents, colorants and neutralizing agents (cheese, chocolate, etc.), pect Acids and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like.
  • the compound represented by the formula (1) of the present invention may contain a fruit flesh for the production of natural fruit juice and fruit juice beverage and vegetable beverage.
  • Another aspect of the invention provides a method of treating cancer comprising administering the compound to a subject in need thereof.
  • Another aspect of the invention provides a method for treating hyperlipidemia comprising administering the compound to a subject in need thereof.
  • Another aspect of the invention provides the compound for use in the prevention or treatment of cancer.
  • Another aspect of the present invention provides the compound for use in the prevention or treatment of hyperlipidemia.
  • Another aspect of the invention provides the use of said compound for the manufacture of a medicament for use in the prevention or treatment of cancer.
  • Another aspect of the invention provides the use of said compound for the manufacture of a medicament for use in the prevention or treatment of hyperlipidemia.
  • the nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase (NSDHL) inhibitor provided in one aspect of the present invention is not only usable as an anticancer agent capable of overcoming the resistance of an EGFR target anticancer agent, but also has an effect that can be used to treat hyperlipidemia. It is supported by the following Examples and Experimental Examples.
  • the title compound was obtained from the Korean Compound Bank.
  • the title compound was obtained from the Korean Compound Bank.
  • the title compound was obtained from the Korean Compound Bank.
  • the title compound was obtained from the Korean Compound Bank.
  • the title compound was obtained from the Korean Compound Bank.
  • NSDHL nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase
  • NSDHL Human-derived nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase
  • the NSDHL gene was inserted into the pET21a plasmid and cloned into E. coli cell line C41 (DE3). After incubating E. coli in Luria Broth medium at 37 ° C, IPTG was added at a time point of OD600 of about 0.7 to express NSDHL and incubated at 37 ° C for 4 hours.
  • the cultured E. coli was centrifuged, the cells were stored at minus 80 ° C., and then crushed by ultrasound, and then purified first using IMAC (Immobilized metallo-affinity chromatography), followed by SEC (Size exclusion chromatography) method. Final purification.
  • the buffer solution for storing NSDHL was 40 mM HEPES (pH 8.0), 150 mM NaCl, 0.5 mM TCEP.
  • FIG. 1 is a graph showing a measurement result of fluorescence intensity of NADH for each NSDHL concentration.
  • FIG. 2 is a graph showing the results of NSDHL and NADH conjugate inhibition experiment using NAD +.
  • Activity assays were performed using 96 well plates, and experiments were performed such that each well contained 200 ⁇ M to 1 ⁇ M inhibitor at final concentration. Experiment was performed by adding 50 ⁇ l, 16 ⁇ M NSDHL, 50 mM HEPES (pH 8.0), 20% glycerol to each well, and adding 50 ul, 50 uM NADH, and reacting at room temperature for 10 minutes, followed by SpectraMax M5 (Molecular Devices) Using the instrument, the fluorescence values of each well were read at fluorescence Ex: 340 nm and Em: 460 nm, and the values were corrected by measuring the absorbance of the compound and buffer solution separately. Inhibition of NSDHL of each compound was measured.
  • the IC 50 (inhibitory concentration at 50%) was calculated using GraphPad Prism software. The results are shown in Table 2 below.
  • Examples 1 to 5 can be seen that the compound effectively inhibits nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase.
  • the above ingredients are mixed and filled in an airtight cloth to prepare a powder.
  • the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
  • the amount of the above ingredient is prepared per ampoule (2 ml).
  • each component is added to the purified water to dissolve it, the lemon flavor is added appropriately, the above components are mixed, purified water is added, the whole is adjusted to 100 ml by adding purified water, and then filled into a brown bottle. Sterilize to prepare the liquid.
  • the nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase (NSDHL) inhibitor provided in one aspect of the present invention is not only usable as an anticancer agent capable of overcoming the resistance of an EGFR target anticancer agent, but also has an effect that can be used to treat hyperlipidemia.

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  • Health & Medical Sciences (AREA)
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  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Obesity (AREA)
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  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Selon un aspect, la présente invention concerne un inhibiteur de type stéroïde déshydrogénase dépendant du nicotinamide adénine dinucléotide phosphate (NSDHL) qui peut être utilisé non seulement en tant qu'agent anticancéreux capable de surmonter la résistance aux agents anticancéreux ciblant EGFR, mais peut également être utilisé de manière avantageuse dans le traitement de l'hyperlipidémie.
PCT/KR2019/011094 2018-08-30 2019-08-29 Matériau inhibiteur du type stéroïde déshydrogénase dépendant du nicotinamide adénine dinucléotide phosphate dérivé du corps humain, et agent anticancéreux le comprenant en tant que principe actif ou composition pharmaceutique le comprenant en tant que principe actif pour le traitement de l'hyperlipidémie WO2020046020A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US17/271,354 US20210253544A1 (en) 2018-08-30 2019-08-29 Inhibitory material against human body-derived nicotinamide adenine dinucleotide phosphate-dependent steroid dehydrogenase-like, and anticancer agent comprising same as effective ingredient or pharmaceutical composition comprising same as effective ingredient for treatment of hyperlipidemia

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20180103008 2018-08-30
KR10-2018-0103008 2018-08-30
KR10-2019-0105425 2019-08-27
KR1020190105425A KR102348468B1 (ko) 2018-08-30 2019-08-27 인체 유래의 니코틴아마이드 아데닌 다이뉴클레오타이드 인산 의존 스테로이드 탈수소효소 저해물질 및 이를 유효성분으로 함유하는 항암제 또는 고지혈증 치료용 약학적 조성물

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994029287A1 (fr) * 1993-06-04 1994-12-22 Boehringer Mannheim Gmbh Acides arylidene-4-oxo-2-thioxo-3-thiazolidine-carboxyliques, leur procede de preparation et medicaments renfermant ces composes
US20100016292A1 (en) * 2008-07-18 2010-01-21 The Burnham Institute Inhibitors of lethal factor protease
WO2011135303A2 (fr) * 2010-04-29 2011-11-03 Iti Scotland Limited Modulateurs d'ubiquitination
WO2017215552A1 (fr) * 2016-06-14 2017-12-21 The University Of Hong Kong Composés antimicrobiens et leurs procédés d'utilisation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994029287A1 (fr) * 1993-06-04 1994-12-22 Boehringer Mannheim Gmbh Acides arylidene-4-oxo-2-thioxo-3-thiazolidine-carboxyliques, leur procede de preparation et medicaments renfermant ces composes
US20100016292A1 (en) * 2008-07-18 2010-01-21 The Burnham Institute Inhibitors of lethal factor protease
WO2011135303A2 (fr) * 2010-04-29 2011-11-03 Iti Scotland Limited Modulateurs d'ubiquitination
WO2017215552A1 (fr) * 2016-06-14 2017-12-21 The University Of Hong Kong Composés antimicrobiens et leurs procédés d'utilisation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JOHNSON, S. L.: "Rhodanine derivatives as selective protease inhibitors against bacterial toxins", CHEMICAL BIOLOGY & DRUG DESIGN, vol. 71, no. 2, 2008, pages 131 - 139, XP055697212 *
SUN, L.: "Discovery of 1, 3-diphenyl-1H-pyrazole derivatives containing rhodanine-3-alkanoic acid groups as potential PTP1B inhibitors", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 29, no. 10, 2019, pages 1187 - 1193, XP055697214 *

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