WO2021254416A1 - Composé indanone et son utilisation - Google Patents

Composé indanone et son utilisation Download PDF

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Publication number
WO2021254416A1
WO2021254416A1 PCT/CN2021/100485 CN2021100485W WO2021254416A1 WO 2021254416 A1 WO2021254416 A1 WO 2021254416A1 CN 2021100485 W CN2021100485 W CN 2021100485W WO 2021254416 A1 WO2021254416 A1 WO 2021254416A1
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WO
WIPO (PCT)
Prior art keywords
dihydro
tetrafluoro
difluoromethyl
indenyl
oxy
Prior art date
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PCT/CN2021/100485
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English (en)
Chinese (zh)
Inventor
杨荣文
孙云
李亚彬
王萍萍
兰宏
丁列明
王家炳
Original Assignee
贝达药业股份有限公司
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Application filed by 贝达药业股份有限公司 filed Critical 贝达药业股份有限公司
Priority to CN202180037616.4A priority Critical patent/CN115667202A/zh
Publication of WO2021254416A1 publication Critical patent/WO2021254416A1/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
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • 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
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
    • C07C49/755—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups a keto group being part of a condensed ring system with two or three rings, at least one ring being a six-membered aromatic ring

Definitions

  • the present invention relates to an indanone compound, a composition and preparation containing such a compound, and methods of using and preparing such a compound.
  • VHL protein is an important part of E3 ubiquitin ligase, which mediates protein degradation by the proteasome.
  • VHL gene has a 57% high mutation rate or 98% loss of heterozygosity in renal cell carcinoma (RCC), which leads to pseudohypoxia and induces the activation of HIF-2 ⁇ into the nucleus.
  • RRCC renal cell carcinoma
  • clear cell renal cell carcinoma (ccRCC) accounts for 70%-75% of primary renal cell malignancies, and more than 90% of ccRCC patients have VHL protein defects.
  • R 1 and R 2 may be independently selected from hydrogen, deuterium, halogen, C 1 -C 3 alkyl, C 3 -C 5 cycloalkyl, or,
  • R 3 is selected from hydrogen, halogen, hydroxyl, cyano, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, C 1 -C 5 haloalkyl, C 1 -C 5 haloalkoxy, C 3- C 5 cycloalkyl;
  • R 4 is selected from C 1 -C 10 alkyl, C 1 -C 10 alkoxy, C 1 -C 10 haloalkyl, C 1 -C 10 haloalkoxy, C 6 -C 10 aryl, C 5 -C 18 heteroaryl group, C 3 -C 10 cycloalkyl group, C 3 -C 10 heterocyclic group; wherein, the C 5 -C 18 heteroaryl group and C 3 -C 10 heterocyclic group optionally contain 1, 2 Or 3 heteroatoms each independently selected from N, O and S; said R 4 is optionally substituted with one or more groups independently selected from R 5 ;
  • R 5 is selected from H, halogen, hydroxyl, amino, cyano, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, C 1 -C 5 haloalkyl, C 1 -C 5 haloalkoxy, C 3 -C 5 cycloalkyl, C 3 -C 5 heterocyclic group.
  • the R 1 and/or R 2 are halogen.
  • the R 1 and/or R 2 are F.
  • the R 1 and R 2 and the C atom to which they are connected together form a substituted or unsubstituted C 3 cycloalkyl or C 3 heterocyclic group.
  • the R 3 is selected from halogen, cyano or C 1 -C 5 haloalkyl.
  • the R 3 is selected from C 1 -C 5 alkyl or C 3 -C 5 cycloalkyl.
  • the R 4 is selected from C 6 -C 8 aryl, C 5 -C 8 heteroaryl, C 3 -C 5 cycloalkyl, C 3 -C 5 heterocyclyl; wherein, the The C 5 -C 8 heteroaryl group and the C 3 -C 8 heterocyclic group optionally contain 1, 2 or 3 heteroatoms independently selected from N, O and S; the R 4 is optionally substituted by one or Multiple groups independently selected from R 5 are substituted.
  • the compound is represented by formula (II),
  • the R 4 is selected from a C 6 -C 8 aryl group, a C 5 -C 8 heteroaryl group; wherein the C 5 -C 8 heteroaryl group optionally contains 1, 2, or 3, respectively Heteroatoms independently selected from N, O and S; said R 4 is optionally substituted with one or more groups independently selected from R 5 .
  • the R 4 is selected from a benzene ring, a pyridine ring and a pyrimidine ring.
  • the R 4 is selected from a benzene ring or a pyridine ring.
  • the R 5 is selected from H, halogen, cyano, C 1 -C 5 alkyl, C 1 -C 5 haloalkyl, C 3 -C 5 cycloalkyl, or C 3 -C 5 heterocycle base.
  • the R 5 is selected from H, halogen, cyano, or C 1 -C 5 haloalkyl.
  • the R 2 is halogen.
  • the R 3 is halogen or cyano, difluoromethyl or trifluoromethyl.
  • the R 3 is difluoromethyl.
  • the R 4 is selected from
  • the present invention further provides a compound or a pharmaceutically acceptable salt thereof, and the compound refers to:
  • the present invention also provides a method for preparing the compound.
  • the compound described in formula (I) or the compound described in the specific examples of the present invention can be prepared by using known organic synthesis techniques.
  • the present invention also provides a pharmaceutical composition
  • a pharmaceutical composition comprising a therapeutically effective amount of at least one of the above-mentioned compounds and pharmaceutically acceptable excipients, such as hydroxypropyl methylcellulose.
  • pharmaceutically acceptable excipients such as hydroxypropyl methylcellulose.
  • the weight ratio of the compound to the excipient is about 0.001-10.
  • the present invention also provides a method for treating a subject suffering from a disease or disorder mediated by HIF-2 ⁇ , which comprises administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the disease or condition is selected from VHL syndrome, autoimmune diseases, inflammatory diseases, neurodegenerative diseases, cardiovascular disorders, renal disorders, viral infections, and obesity.
  • the disease or condition is selected from rheumatoid arthritis, osteoarthritis, atherosclerosis, psoriasis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, asthma, chronic obstructive Airway disease, pneumonia, dermatitis, alopecia, nephritis, vasculitis, atherosclerosis, Alzheimer's disease, hepatitis, primary biliary cirrhosis, sclerosing cholangitis, diabetes (including type I diabetes), Acute rejection of transplanted organs.
  • the disease or condition is cancer, including hematological cancers, lymphomas, multiple myeloma, tumors of the digestive system, tumors of the reproductive system, brain tumors, tumors of the nervous system.
  • the disease or disorder is permeaglioma, pheochromocytoma, paraganglioma, colon, rectum, prostate (e.g., castrate resistant prostate cancer), lung cancer (e.g., non-small Cell lung cancer and/or small cell lung cancer), pancreas, liver, kidney, cervix, uterus, stomach, ovary, breast (e.g. basal or basal-like breast cancer and/or triple negative breast cancer), skin (e.g. melanoma) , Nervous system (including brain, meninges, and central nervous system, including neuroblastoma, glioblastoma, meningioma and medulloblastoma) tumors or cancer.
  • lung cancer e.g., non-small Cell lung cancer and/or small cell lung cancer
  • pancreas liver, kidney, cervix, uterus, stomach, ovary
  • breast e.g. basal or basal-like breast cancer and/or triple negative
  • the disease or condition is VHL syndrome. In certain aspects, the disease or condition is kidney cancer. In certain aspects, the subject is a human.
  • the compound is administered intravenously, intramuscularly, parenterally, nasally, or orally. In one aspect, the compound is administered orally.
  • the present invention also provides the use of the compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of diseases or disorders mediated by HIF-2 ⁇ .
  • the present invention also provides a compound represented by formula (I) or a pharmaceutically acceptable salt thereof for treatment. Further provided is a compound of formula (I) or a pharmaceutically acceptable salt thereof for treating a subject suffering from a disease or condition mediated by HIF-2 ⁇ .
  • halogen refers to fluorine, chlorine, bromine or iodine.
  • Preferred halogen groups refer to fluorine, chlorine and bromine.
  • alkyl includes linear, branched or cyclic saturated monovalent hydrocarbon groups.
  • alkyl includes methyl, ethyl, propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclobutyl, n-pentyl, 3-(2 -Methyl)butyl, 2-pentyl, 2-methylbutyl, neopentyl, cyclopentyl, n-hexyl, 2-hexyl, 2-methylpentyl and cyclohexyl.
  • the "C 1-6 "in the C 1-6 alkyl group refers to a group containing 1, 2, 3, 4, 5 or 6 carbon atoms arranged in a straight chain or branched chain.
  • alkoxy refers to an oxyether formed from the above-mentioned linear, branched or cyclic alkyl group.
  • alkylene refers to a divalent alkyl linking group.
  • alkylene refers to an alkane in which two CH bonds are replaced with the point of attachment of the alkylene to the rest of the compound.
  • C 1-4 in the C 1-4 alkylene group refers to an alkylene group containing 1, 2, 3, or 4 carbon atoms.
  • haloalkyl refers to an alkyl group in which one or more H has been replaced by a halogen atom.
  • haloalkoxy refers to the group -O-haloalkyl.
  • oxo or "oxo” refers to an oxygen atom in the form of a dimethyl substituent, which forms a carbonyl group when connected to C, and forms a sulfoxide group or a sulfone group or an N-oxide group when connected to a heteroatom group.
  • aromatic ring means having aromatic characteristics (having (4n+2) non-localized ⁇ electrons, where n is Integer) carbocyclic or heterocyclic polyunsaturated ring.
  • aryl is a substituted or unsubstituted, stable, 6 to 10 ring carbon atom aromatic hydrocarbon group, which may contain one aromatic ring or multiple aromatic rings (for example, fused bicyclic rings). The aromatic ring does not contain heteroatoms. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, indenyl, and the like.
  • heteroaryl refers to a monocyclic or polycyclic (eg, fused bicyclic) aromatic heterocyclic ring having at least one heteroatom ring member selected from N, O and/or S.
  • heteroaryl groups include, but are not limited to, pyridyl, pyrimidinyl, pyrrolyl, imidazolyl, thiazolyl, thienyl, benzimidazole, benzothienyl, benzofuranyl and the like.
  • cycloalkyl refers to a ring system having at least one cyclized alkyl group.
  • C 3-10 in the term C 3-10 cycloalkyl means that the cycloalkyl group may have 3, 4, 5, 6, 7, 8, 9 or 10 ring-forming atoms.
  • Cycloalkyl groups may include monocyclic and polycyclic rings (e.g., having 2, 3 or 4 fused rings, spiro rings, fused rings, etc.).
  • cycloalkenyl refers to a ring system having at least one cyclized alkenyl group with one or more carbon-carbon double bonds in the cycloalkenyl group.
  • C 3-10 in the term C 3-10 cycloalkenyl means that the cycloalkenyl group may have 3, 4, 5, 6, 7, 8, 9 or 10 ring-forming atoms.
  • Cycloalkenyl groups can include monocyclic and polycyclic rings (e.g., having 2, 3, or 4 fused rings, spiro rings, bridged rings, etc.).
  • cycloalkenyl includes, but is not limited to, cyclohexenyl, cyclohexadiene, cycloheptatrienyl, etc.; in some embodiments, cycloalkenyl also includes those having one or more fused rings with cyclized alkenyl Part of the aromatic ring, such as benzo or thienyl derivatives of the cyclohexene ring.
  • heterocyclyl refers to a ring system having at least one cyclized alkyl or cyclized alkenyl containing a heterocyclic ring, and the heteroatom is selected from N, O and/or S.
  • the heterocyclic group may include a single ring or a polycyclic ring (for example, having 2, 3 or 4 fused rings, spiro rings, bridged rings, etc.).
  • the heterocyclic group can be connected to other parts of the compound via a ring-forming carbon atom or a ring-forming heteroatom.
  • the prodrugs (prodrugs) of the compounds of the present invention are included in the protection scope of the present invention.
  • the prodrug refers to a functional derivative that is easily converted into a desired compound in the body. Therefore, the term "administration" in the treatment method provided by the present invention includes the administration of the compound disclosed in the present invention, or the prodrug compound disclosed in the present invention that can be converted in vivo after administration to a subject although it is not clearly disclosed.
  • the conventional methods for selecting and preparing suitable prodrug derivatives have been recorded in books such as "Design of Prodrugs” (Design of Prodrugs, ed. H. Bundgaard, Elsevier, 1985).
  • the above formula (I) does not exactly define the three-dimensional structure of a certain position of the compound.
  • the present invention includes all stereoisomers of the compound represented by formula (I) and pharmaceutically acceptable salts thereof. Further, mixtures of stereoisomers and specific isolated stereoisomers are also included in the present invention. In the synthetic process of preparing such compounds, or in the process of using racemization or epimerization methods known to those of ordinary skill in the art, the product obtained may be a mixture of stereoisomers.
  • the present invention includes any possible tautomers, pharmaceutically acceptable salts thereof, and mixtures thereof.
  • pharmaceutically acceptable salt refers to a salt prepared from a pharmaceutically acceptable non-toxic base or acid.
  • the corresponding salt can be conveniently prepared from pharmaceutically acceptable non-toxic bases, including inorganic bases and organic bases.
  • Salts derived from inorganic bases include aluminum, ammonium, calcium, copper (high and low prices), ferric, ferrous, lithium, magnesium, manganese (high and low prices), potassium, sodium, zinc and the like. Particularly preferred are the salts of ammonium, calcium, magnesium, potassium, and sodium.
  • Non-toxic organic bases that can be derivatized into pharmaceutically acceptable salts include primary, secondary and tertiary amines, as well as cyclic amines and amines containing substituents, such as naturally occurring and synthetic amines containing substituents.
  • non-toxic organic bases capable of forming salts, including ion exchange resins and arginine, betaine, caffeine, choline, N',N'-dibenzylethylenediamine, diethylamine, 2 -Diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, reduced glucosamine, glucosamine, histidine, haamine, isopropylamine , Lysine, methylglucamine, morpholine, piperazine, piperidine, polyamine resin, procaine, chloroprocaine, purine, theobromine, triethylamine, trimethylamine, tripropylamine, ammonia Butanetriol and so on.
  • ion exchange resins and arginine betaine, caffeine, choline, N',N'-dibenzylethylenediamine, diethylamine, 2 -
  • the corresponding salt can be conveniently prepared from pharmaceutically acceptable non-toxic acids, including inorganic acids and organic acids.
  • acids include, for example, acetic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, formic acid, fumaric acid, gluconic acid, glutamic acid, hydrobromic acid, hydrochloric acid, isethionic acid , Lactic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, mucic acid, nitric acid, hexanoic acid, pantothenic acid, phosphoric acid, succinic acid, sulfuric acid, oxalic acid, propionic acid, glycolic acid, hydroiodic acid, perchloric acid, Cyclohexanesulfonic acid, salicylic acid, 2-naphthalenesulfonic acid, saccharinic acid, trifluor
  • citric acid Preferably, citric acid, hydrobromic acid, formic acid, hydrochloric acid, maleic acid, phosphoric acid, sulfuric acid and tartaric acid. More preferably, formic acid and hydrochloric acid. Since the compound represented by formula (I) will be used as a medicine, it is preferable to use a substantially pure form, for example, at least 60% purity, more suitably at least 75% purity, especially at least 98% purity (% is a weight ratio ).
  • the pharmaceutical composition provided by the present invention includes as an active component a compound represented by formula (I) (or a pharmaceutically acceptable salt thereof), a pharmaceutically acceptable excipient and other optional therapeutic components or Accessories.
  • a pharmaceutical composition of the present invention includes oral, rectal, topical and A pharmaceutical composition for parenteral administration (including subcutaneous administration, intramuscular injection, and intravenous administration).
  • the pharmaceutical composition of the present invention can be conveniently prepared in a unit dosage form known in the art and prepared by any preparation method known in the pharmaceutical field.
  • the pharmaceutical composition of the present invention may take the form of powder, granule, solution, aqueous suspension, non-aqueous liquid, oil-in-water emulsion, or water-in-oil emulsion.
  • the compound represented by formula (I) or a pharmaceutically acceptable salt thereof can also be administered by a controlled release method and/or a delivery device.
  • the pharmaceutical composition of the present invention can be prepared by any pharmaceutical method. Generally, this method includes the step of associating the active ingredient with the carrier which constitutes one or more necessary ingredients.
  • the pharmaceutical composition is prepared by uniformly and intimately mixing the active ingredient with a liquid carrier or a finely divided solid carrier or a mixture of both. Then, the product can be easily prepared into the desired appearance.
  • the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier and a compound represented by formula (I) or a pharmaceutically acceptable salt thereof.
  • the compound represented by formula (I) or a pharmaceutically acceptable salt thereof, and one or more other compounds with therapeutic activity are also included in the pharmaceutical composition of the present invention.
  • the drug carrier used in the present invention can be, for example, a solid carrier, a liquid carrier or a gas carrier.
  • Solid carriers include lactose, gypsum powder, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, and stearic acid.
  • Liquid carriers include syrup, peanut oil, olive oil and water.
  • the gas carrier includes carbon dioxide and nitrogen.
  • any convenient pharmaceutical medium can be used. For example, water, ethylene glycol, oils, alcohols, flavor enhancers, preservatives, coloring agents, etc.
  • oral liquid preparations such as suspensions, elixirs and solutions
  • carriers such as starches, sugars, Microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, etc.
  • oral solid preparations such as powders, capsules and tablets.
  • tablets and capsules are preferred for oral preparations, and solid pharmaceutical carriers are used here.
  • standard aqueous or non-aqueous formulation techniques can be used for tablet coating.
  • Tablets containing the compound or pharmaceutical composition of the present invention can be prepared by compressing or molding one or more auxiliary components or adjuvants together.
  • the active ingredient is in a free-flowing form such as powder or granules, mixed with a binder, lubricant, inert diluent, surfactant or dispersant, and compressed in a suitable machine to obtain compressed tablets.
  • the powdered compound or pharmaceutical composition is soaked with an inert liquid diluent, and then molded in a suitable machine to form a molded tablet.
  • each tablet contains about 0.05 mg to 5 g of active ingredient
  • each cachet or capsule contains about 0.05 mg to 5 g of active ingredient.
  • a dosage form intended for oral administration to humans contains about 0.5 mg to about 5 g of active ingredient, compounded with a suitable and convenient metering auxiliary material, which accounts for about 5% to 95% of the total pharmaceutical composition.
  • the unit dosage form generally contains about 1 mg to about 2 g of active ingredient, typically 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg or 1000 mg.
  • the pharmaceutical composition suitable for parenteral administration provided by the present invention can be prepared as an aqueous solution or suspension by adding active components into water.
  • a suitable surfactant such as hydroxypropyl cellulose may be included.
  • glycerol, liquid polyethylene glycol, and their mixture in oil, dispersion systems can also be prepared.
  • a preservative may also be included in the pharmaceutical composition of the present invention to prevent the growth of harmful microorganisms.
  • the present invention provides pharmaceutical compositions suitable for injection, including sterile aqueous solutions or dispersion systems.
  • the above-mentioned pharmaceutical composition can be prepared in the form of a sterile powder that can be used for immediate preparation of sterile injection or dispersion.
  • the final injection form must be sterile, and for easy injection, it must be easy to flow.
  • the pharmaceutical composition must be stable during preparation and storage. Therefore, preservation against contamination by microorganisms such as bacteria and fungi is preferred.
  • the carrier can be a solvent or dispersion medium, for example, water, ethanol, polyol (such as glycerol, propylene glycol, liquid polyethylene glycol), vegetable oil, and suitable mixtures thereof.
  • the pharmaceutical composition provided by the present invention can be made into a form that takes a solid as a carrier and is suitable for rectal administration.
  • the preferred dosage form is a suppository in which the mixture forms a unit dose.
  • Suitable auxiliary materials include cocoa butter and other materials commonly used in the art. Suppositories can be conveniently prepared by mixing the pharmaceutical composition with softened or molten excipients, then cooling and moulding.
  • the above-mentioned pharmaceutical preparations may also include, as appropriate, one or more additional adjuvant components, such as diluents, buffers, flavoring agents, binders, surfactants, and enhancers. Thickeners, lubricants and preservatives (including antioxidants), etc.
  • other adjuvants can also include penetration enhancers that regulate the isotonic pressure between the drug and the blood.
  • the pharmaceutical composition containing the compound represented by formula (I), or a pharmaceutically acceptable salt thereof can also be prepared in the form of a powder or a concentrated solution.
  • DMSO dimethyl sulfoxide
  • LDA lithium diisopropylamide
  • Example 1 Using a method basically similar to that of Example 1 to Example 3, the examples in Table 1 below were prepared.
  • the luciferase LUC gene was stably transferred into 786-O cells (purchased from ATCC) with Lipofectamine 3000 transfection reagent (purchased from Invitrogen) to construct HIF2 ⁇ reporter cells (786-O-HIF2 ⁇ -Luc cells).
  • the compound was formulated with 5% DMSO, 5% Solutol and 90% NaCl.
  • SD rats and Balb/c mice were selected for administration.
  • the intravenous dose was 1 mg/kg and the oral dose was 5 mg/kg, respectively at 5 min, 15 min, 30 min, 1h, 2h, 4h, 7h, 24h Take blood from the orbit. After blood collection, centrifuge at 4000 rpm for 10 min, take the supernatant, add 200 ⁇ L of internal standard solution to 30 ⁇ L of supernatant for precipitation, vortex and centrifuge at 12000 rpm for 10 min, take 100 ⁇ L of supernatant solution and purified water in a 1:1 ratio for mixing and injection.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)

Abstract

L'invention concerne un composé représenté par la formule (I), une composition et une formulation comprenant un tel composé, et un procédé d'utilisation et de préparation d'un tel composé. Le composé est utilisé pour traiter des maladies médiées par HIF-2α.
PCT/CN2021/100485 2020-06-17 2021-06-17 Composé indanone et son utilisation WO2021254416A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202180037616.4A CN115667202A (zh) 2020-06-17 2021-06-17 茚酮类化合物及其应用

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Application Number Priority Date Filing Date Title
CN202010553483.3 2020-06-17
CN202010553483 2020-06-17

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Publication Number Publication Date
WO2021254416A1 true WO2021254416A1 (fr) 2021-12-23

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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016057242A1 (fr) * 2014-10-10 2016-04-14 The Board Of Regents Of The University Of Texas System Inhibitors hif-2α pour traiter des troubles d'hémochromatose
WO2016145045A1 (fr) * 2015-03-11 2016-09-15 Peloton Therapeutics, Inc. Compositions s'utilisant dans le traitement du glioblastome
WO2016144825A1 (fr) * 2015-03-11 2016-09-15 Peloton Therapeutics, Inc. Composés aromatiques, leurs et utilisations
WO2016145032A1 (fr) * 2015-03-11 2016-09-15 Peloton Therapeutics, Inc. Compositions utilisées pour traiter l'hypertension artérielle pulmonaire
WO2016168510A1 (fr) * 2015-04-17 2016-10-20 Peloton Therapeutics, Inc. Thérapie combinée avec un inhibiteur de hif-2-alpha et un agent immunothérapeutique, et applications corresponantes
WO2017053192A1 (fr) * 2015-09-21 2017-03-30 The Board Of Regents Of The University Of Texas System Biomarqueurs de réponse à l'inhibition de hif-2-alpha dans le cancer et leurs méthodes d'utilisation
WO2017218960A1 (fr) * 2016-06-17 2017-12-21 Fronthera U.S. Pharmaceuticals Llc Composés modificateurs d'hémoglobine et leurs utilisations
WO2019191227A1 (fr) * 2018-03-28 2019-10-03 Peloton Therapeutics, Inc. Procédés de réduction de l'inflammation du système digestif à l'aide d'inhibiteurs de hif-2-alpha
WO2020081695A1 (fr) * 2018-10-17 2020-04-23 Nikang Therapeutics, Inc. Dérivés d'indane utilisés en tant qu'inhibiteurs du facteur 2 inductible par l'hypoxie (alpha)

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016057242A1 (fr) * 2014-10-10 2016-04-14 The Board Of Regents Of The University Of Texas System Inhibitors hif-2α pour traiter des troubles d'hémochromatose
WO2016145045A1 (fr) * 2015-03-11 2016-09-15 Peloton Therapeutics, Inc. Compositions s'utilisant dans le traitement du glioblastome
WO2016144825A1 (fr) * 2015-03-11 2016-09-15 Peloton Therapeutics, Inc. Composés aromatiques, leurs et utilisations
WO2016145032A1 (fr) * 2015-03-11 2016-09-15 Peloton Therapeutics, Inc. Compositions utilisées pour traiter l'hypertension artérielle pulmonaire
WO2016168510A1 (fr) * 2015-04-17 2016-10-20 Peloton Therapeutics, Inc. Thérapie combinée avec un inhibiteur de hif-2-alpha et un agent immunothérapeutique, et applications corresponantes
WO2017053192A1 (fr) * 2015-09-21 2017-03-30 The Board Of Regents Of The University Of Texas System Biomarqueurs de réponse à l'inhibition de hif-2-alpha dans le cancer et leurs méthodes d'utilisation
WO2017218960A1 (fr) * 2016-06-17 2017-12-21 Fronthera U.S. Pharmaceuticals Llc Composés modificateurs d'hémoglobine et leurs utilisations
WO2019191227A1 (fr) * 2018-03-28 2019-10-03 Peloton Therapeutics, Inc. Procédés de réduction de l'inflammation du système digestif à l'aide d'inhibiteurs de hif-2-alpha
WO2020081695A1 (fr) * 2018-10-17 2020-04-23 Nikang Therapeutics, Inc. Dérivés d'indane utilisés en tant qu'inhibiteurs du facteur 2 inductible par l'hypoxie (alpha)

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