WO2020045856A1 - NOUVEL INHIBITEUR DE HIF-1α, SON PROCÉDÉ DE PRÉPARATION ET COMPOSITION PHARMACEUTIQUE POUR LA PRÉVENTION OU LE TRAITEMENT D'UNE MALADIE OCULAIRE ASSOCIÉE À L'ANGIOGENÈSE, CONTENANT CELUI-CI EN TANT QUE PRINCIPE ACTIF - Google Patents

NOUVEL INHIBITEUR DE HIF-1α, SON PROCÉDÉ DE PRÉPARATION ET COMPOSITION PHARMACEUTIQUE POUR LA PRÉVENTION OU LE TRAITEMENT D'UNE MALADIE OCULAIRE ASSOCIÉE À L'ANGIOGENÈSE, CONTENANT CELUI-CI EN TANT QUE PRINCIPE ACTIF Download PDF

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WO2020045856A1
WO2020045856A1 PCT/KR2019/010208 KR2019010208W WO2020045856A1 WO 2020045856 A1 WO2020045856 A1 WO 2020045856A1 KR 2019010208 W KR2019010208 W KR 2019010208W WO 2020045856 A1 WO2020045856 A1 WO 2020045856A1
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compound
straight
pharmaceutically acceptable
pharmaceutical composition
branched chain
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PCT/KR2019/010208
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English (en)
Korean (ko)
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서영거
이승범
김정훈
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서울대학교 산학협력단
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Priority claimed from KR1020190096669A external-priority patent/KR102527205B1/ko
Application filed by 서울대학교 산학협력단 filed Critical 서울대학교 산학협력단
Priority to BR112020024110-5A priority Critical patent/BR112020024110A2/pt
Priority to MX2020012609A priority patent/MX2020012609A/es
Priority to CN201980035213.9A priority patent/CN112166099B/zh
Priority to US17/057,297 priority patent/US12006283B2/en
Priority to AU2019332477A priority patent/AU2019332477B2/en
Priority to CA3101977A priority patent/CA3101977C/fr
Priority to JP2020564862A priority patent/JP7099754B2/ja
Priority to EP19856396.7A priority patent/EP3845516A4/fr
Priority to RU2020137660A priority patent/RU2770027C1/ru
Publication of WO2020045856A1 publication Critical patent/WO2020045856A1/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
    • A61K31/12—Ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
    • C07C49/84—Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/06—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings

Definitions

  • the present invention relates to a novel HIF-1 ⁇ (Hypoxia-Inducible Factor 1 ⁇ ) inhibitor, a method for preparing the same, and a pharmaceutical composition for preventing or treating angiogenesis-related eye diseases containing the same as an active ingredient.
  • HIF-1 ⁇ Hydrophilic factor-1 ⁇
  • Angiogenesis refers to the mechanism by which new blood vessels are formed from existing blood vessels, and is a strictly controlled phenomenon that rarely occurs under normal physiological conditions. And changes in the genital system in the female reproductive cycle.
  • Angiogenesis occurs as a complex process by the interaction of different types of cells with soluble factors and extracellular matrix components.
  • Neovascularization in tumors provides pathways to other organs to facilitate metastasis, and not only tumors but also age-related macular degeneration, diabetic retinopathy, and prematurity retinopathy. It is known to play a decisive role in diseases such as retinopathy of prematurity, neovascular glaucoma, psoriasis, rheumatoid arthritis, or chronic inflammation.
  • VEGF Vascular endothelial growth factor
  • HIF-1 ⁇ Hydrophilia inducible factor 1, alpha
  • An object of the present invention is to provide a compound that can be usefully used as a pharmaceutical composition for the prevention or treatment of neovascular related eye diseases by excellent inhibition of HIF-1 ⁇ .
  • Another object of the present invention is to provide a method for preparing the compound.
  • Still another object of the present invention is to provide a pharmaceutical composition for preventing or treating angiogenesis-related ocular diseases containing the compound as an active ingredient.
  • Another object of the present invention is to provide a nutraceutical composition for preventing or improving angiogenesis-related eye diseases containing the compound as an active ingredient.
  • the present invention provides a compound represented by the following formula (1), solvates, hydrates, optical isomers, or pharmaceutically acceptable salts thereof:
  • a 1 and A 2 are each independently —H, —OH, —NO 2 , —CN, halogen, C 1-10 straight or branched chain alkyl, or C 1-10 straight or branched chain alkoxy;
  • B 1 is —H, —OH, —NO 2 , —CN, halogen, C 1-10 straight or branched chain alkyl, or C 1-10 straight or branched chain alkoxy;
  • R 1 is —H, —OH, —NO 2 , —CN, halogen, C 1-10 straight or branched chain alkyl, C 1-10 straight or branched chain alkoxy, C 3-10 cycloalkyloxy, di C 1-10 straight or branched chain alkylamino, 5 to 10 each ring heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O and S, or unsubstituted or one or more -CN is substituted C 6-10 aryl C 1-5 alkylamino.
  • the present invention also provides a method for producing the compound.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of neovascular diseases related to the neovascular disease containing the compound as an active ingredient.
  • the present invention provides a nutraceutical composition for the prevention or improvement of neovascular diseases related eye diseases containing the compound as an active ingredient.
  • the exemplary compound provided in one embodiment of the present invention inhibits HIF-1 ⁇ excellently, it may be usefully used as a pharmaceutical composition for preventing or treating neovascular related eye diseases.
  • FIG. 1 is a graph showing the results of evaluating the neovascular inhibitory activity of the example compound according to an embodiment of the present invention.
  • Figure 2 is a graph showing the results of evaluating the HIF-1 ⁇ (Hypoxia-Inducible Factor 1 ⁇ ) regulatory activity of the compound according to an embodiment of the present invention.
  • Figure 3 is a graph showing the results of evaluating the retinal neovascular inhibitory activity caused by hypoxia of the example compound according to an embodiment of the present invention.
  • a 1 and A 2 are each independently —H, —OH, —NO 2 , —CN, halogen, C 1-10 straight or branched chain alkyl, or C 1-10 straight or branched chain alkoxy;
  • B 1 is —H, —OH, —NO 2 , —CN, halogen, C 1-10 straight or branched chain alkyl, or C 1-10 straight or branched chain alkoxy;
  • R 1 is —H, —OH, —NO 2 , —CN, halogen, C 1-10 straight or branched chain alkyl, C 1-10 straight or branched chain alkoxy, C 3-10 cycloalkyloxy, di C 1-10 straight or branched chain alkylamino, 5 to 10 each ring heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O and S, or unsubstituted or one or more -CN is substituted C 6-10 aryl C 1-5 alkylamino.
  • the present invention is a compound of Formula 1 wherein B 1 is C 1-10 linear or branched alkoxy, R 1 is one or more heteroatoms selected from the group consisting of N, O and S 5-10 cyclic heterocycloalkyl, or an unsubstituted or substituted at least one C 6-10 substituted aryl C 1-5 alkylamino compound, solvates, hydrates, optical isomers, or pharmaceuticals thereof As an acceptable salt.
  • B 1 is C 1-10 straight or branched alkoxy
  • R 1 is a pentacyclic heterocycloalkyl including N
  • one or more -CN is Compounds that are substituted benzylamino, solvates, hydrates, optical isomers, or pharmaceutically acceptable salts thereof are provided.
  • 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, chlorobene
  • 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 Formula 1 and pharmaceutically acceptable salts thereof, but also solvates, optical isomers, hydrates, and the like that can be prepared therefrom.
  • the present invention also provides a method for producing the compound.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of neovascular diseases related to the neovascular disease containing the compound as an active ingredient.
  • neovascular related eye diseases include, but are not limited to, macular degeneration, retinal vein occlusion, diabetic retinopathy, ischemic retinopathy, and the like.
  • 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.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions.
  • 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 ampoule 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.
  • the present invention provides a nutraceutical composition for the prevention or improvement of neovascular diseases related eye diseases containing the compound 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, etc. as additional ingredients, as in general beverages.
  • 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 1-20 g, preferably about 5-12 g per 100 g of the composition of the present invention.
  • the compound represented by the formula (1) according to the present invention is a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring and neutralizing agents (cheese, chocolate, etc.), pectic acid And salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, 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.
  • the example compound provided in one embodiment of the present invention excellently inhibits HIF-1 ⁇ , it may be usefully used as a pharmaceutical composition for preventing or treating neovascular diseases related eye diseases, which will be described later in Examples and Experimental Examples. Backed by
  • the title compound was prepared in the form of a pale yellow oil by following a similar procedure as in Example 2, except using iodomethane (5.0 ⁇ L, 0.1 mmol) instead of iodomethane. (10 mg, 91%)
  • Example rescue Example rescue One 9 2 10 3 11 4 12 5 13 6 14 7 15 8 16
  • HIF-1 ⁇ Hypoxia-Inducible Factor 1 ⁇
  • Example IC50 ( ⁇ M) One > 15 2 > 15 3 11.68 4 2.59 5 > 15 6 2.82 7 1.85 8 8.74 9 1.43 10 0.60 11 2.61 12 6.85 13 2.06 14 7.35 15 6.52 16 5.28
  • Example compounds according to one embodiment of the present invention have been shown to excellently suppress HIF-1 ⁇ (Hypoxia-Inducible Factor 1 ⁇ ).
  • the compound of Example 10 was found to have the best inhibitory activity among the compounds.
  • FIG. 1 is a graph showing the results of evaluation of the neovascular inhibitory activity of the compound according to an embodiment of the present invention, in Figure 1 2 compounds are Comparative Example 1 compound, 34f compound is Example 10 compound.
  • Example 10 compound of the present invention was shown to have a relatively superior neovascular inhibitory activity than the compound of Comparative Example 1.
  • HIF-1 ⁇ Hypoxia-Inducible Factor 1 ⁇
  • Figure 2 is a graph showing the results of the evaluation of the HIF-1 ⁇ (Hypoxia-Inducible Factor 1 ⁇ ) regulatory activity of the compound according to an embodiment of the present invention, in Figure 2 2 compounds are Comparative Example 1 compound, 34f compound Is Example 10 compound.
  • Example 10 compound of the present invention was shown to have a relatively better HIF-1 ⁇ regulatory activity than the compound of Comparative Example 1.
  • Figure 3 is a graph showing the results of evaluation of retinal neovascular inhibitory activity by hypoxia of the compound according to an embodiment of the present invention
  • 2 compounds are Comparative Example 1 compound
  • 34f compound is Example 10 Compound.
  • Example 10 of the present invention was shown to inhibit retinal neovascularization due to hypoxia relatively better than the compound of Comparative Example 1.
  • 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.

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Abstract

La présente invention concerne un nouveau inhibiteur du facteur inductible par l'hypoxie 1α (HIF-1α), son procédé de préparation et une composition pharmaceutique pour la prévention ou le traitement d'une maladie oculaire associée à l'angiogenèse, contenant celui-ci en tant que principe actif. Selon un mode de réalisation, un composé fourni par la présente invention, donné à titre d'exemple inhibe de manière remarquable HIF-1α, et peut ainsi être utilisé de manière efficace en tant que composition pharmaceutique pour prévenir ou traiter une maladie oculaire associée à l'angiogenèse.
PCT/KR2019/010208 2018-08-31 2019-08-12 NOUVEL INHIBITEUR DE HIF-1α, SON PROCÉDÉ DE PRÉPARATION ET COMPOSITION PHARMACEUTIQUE POUR LA PRÉVENTION OU LE TRAITEMENT D'UNE MALADIE OCULAIRE ASSOCIÉE À L'ANGIOGENÈSE, CONTENANT CELUI-CI EN TANT QUE PRINCIPE ACTIF WO2020045856A1 (fr)

Priority Applications (9)

Application Number Priority Date Filing Date Title
BR112020024110-5A BR112020024110A2 (pt) 2018-08-31 2019-08-12 Inibidor hif-1-alfa, método de preparação do mesmo, e composição farmacêutica para impedir ou tratar doença ocular relacionada à angiogênese contendo o mesmo como ingrediente ativo
MX2020012609A MX2020012609A (es) 2018-08-31 2019-08-12 Inhibidor del hif-1?, metodo de preparacion del mismo, y composicion farmaceutica para prevenir o tratar la enfermedad ocular asociada a la angiogenesis, que contiene el mismo como ingrediente activo.
CN201980035213.9A CN112166099B (zh) 2018-08-31 2019-08-12 HIF-1α抑制剂以及包含其的药学组合物
US17/057,297 US12006283B2 (en) 2018-08-31 2019-08-12 HIF-1α inhibitor, preparation method therefor, and pharmaceutical composition for preventing or treating angiogenesis-associated eye disease, containing same as active ingredient
AU2019332477A AU2019332477B2 (en) 2018-08-31 2019-08-12 Novel HIF-1α inhibitor, preparation method therefor, and pharmaceutical composition for preventing or treating angiogenesis-associated eye disease, containing same as active ingredient
CA3101977A CA3101977C (fr) 2018-08-31 2019-08-12 Nouvel inhibiteur de hif-1-alpha, methode de preparation et composition pharmaceutique contenant ce meme ingredient actif pour prevenir ou traiter une maladie de l'oeil liee a l'angiogenese tant que principe actif
JP2020564862A JP7099754B2 (ja) 2018-08-31 2019-08-12 新規のＨＩＦ－１α抑制剤、その製造方法及びこれを有効成分として含む新生血管関連眼疾患の予防または治療用薬学的組成物
EP19856396.7A EP3845516A4 (fr) 2018-08-31 2019-08-12 NOUVEL INHIBITEUR DE HIF-1alfa, SON PROCÉDÉ DE PRÉPARATION ET COMPOSITION PHARMACEUTIQUE POUR LA PRÉVENTION OU LE TRAITEMENT D'UNE MALADIE OCULAIRE ASSOCIÉE À L'ANGIOGENÈSE, CONTENANT CELUI-CI EN TANT QUE PRINCIPE ACTIF
RU2020137660A RU2770027C1 (ru) 2018-08-31 2019-08-12 Новый ингибитор hif-1-альфа, способ его получения и фармацевтическая композиция для профилактики или лечения связанных с ангиогенезом заболеваний глаз, содержащая его в качестве активного компонента

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2018-0103985 2018-08-31
KR20180103985 2018-08-31
KR10-2019-0096669 2019-08-08
KR1020190096669A KR102527205B1 (ko) 2018-08-31 2019-08-08 신규한 HIF-1α 억제제, 이의 제조방법 및 이를 유효성분으로 함유하는 신생혈관 관련 안질환의 예방 또는 치료용 약학적 조성물

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12006283B2 (en) 2018-08-31 2024-06-11 Seoul National University R&Db Foundation HIF-1α inhibitor, preparation method therefor, and pharmaceutical composition for preventing or treating angiogenesis-associated eye disease, containing same as active ingredient

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US12006283B2 (en) 2018-08-31 2024-06-11 Seoul National University R&Db Foundation HIF-1α inhibitor, preparation method therefor, and pharmaceutical composition for preventing or treating angiogenesis-associated eye disease, containing same as active ingredient

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