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WO2022262615A1 - Composé anthracène, son procédé de préparation et son utilisation médicale - Google Patents

Composé anthracène, son procédé de préparation et son utilisation médicale Download PDF

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Publication number
WO2022262615A1
WO2022262615A1 PCT/CN2022/097326 CN2022097326W WO2022262615A1 WO 2022262615 A1 WO2022262615 A1 WO 2022262615A1 CN 2022097326 W CN2022097326 W CN 2022097326W WO 2022262615 A1 WO2022262615 A1 WO 2022262615A1
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compound
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phenyl
cancer
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PCT/CN2022/097326
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English (en)
Chinese (zh)
Inventor
胡范
方丽
谭芳
肖黎
刘克楠
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杭州中美华东制药有限公司
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Priority to CN202280042744.2A priority Critical patent/CN117500808A/zh
Publication of WO2022262615A1 publication Critical patent/WO2022262615A1/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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • 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
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms

Definitions

  • the invention relates to the technical field of medicine, in particular to an anthracene compound with antitumor activity, a pharmaceutically acceptable salt thereof, a preparation method and application thereof.
  • CN102378574A discloses an azoanthracene derivative shown in formula B and its use for regulating glucagon-like peptide-1 receptor:
  • CN102378574A points out that these azoanthracene derivatives have the function of regulating glucagon-like peptide-1 (GLP-1) receptor. It is necessary to further conduct research on the activity of the degradation products of these compounds to discover their potential medical applications.
  • the present invention provides anthracene compounds as shown in formula A:
  • X is independently selected from oxygen, hydrogen, nitrogen;
  • R 1 is selected from COOH or -COOCH 3 ;
  • R 2 is -Y 1 -L -Y 2 ;
  • L is selected from -(CH 2 ) a - or -O-, wherein a is 0 or 1;
  • Y is phenylene, and said phenylene is 1,3 - phenylene or 1,4-phenylene;
  • Y 2 is selected from phenyl, pyridyl, diazaaryl or imidazolyl, and Y 2 is optionally independently hydrogen, halogen, C 1-4 alkyl, C 3-6 cycloalkyl, CF 3 , - CH 2 F, –CH 2 CF 3 , CN, –CH 2 CN, –OCH 3 , –O–C(CH 3 ) 3 , –OCH 2 CH 3 , –OCH(CH 3 ) 2 , –OCF 3 , – OCH 2 CF 3 , NH 2 , –SO 2 –CH 3 , –NHCH 3 , –CO—NHCH 3 , –NHCH 2 CH 3 , –N(CH 3 ) 2 , –CO–CH 3 , –CO–NHCH 3 Replace 1-3 times;
  • R is selected from C 1-4 alkyl, C 3-6 cycloalkyl, phenyl, furyl, thienyl, oxazolyl, pyridyl, thiazolyl, pyrimidyl, epoxy pentacyclyl, epoxy hexa Cyclic, -sulfonyl-thiazolyl, -sulfonyl-oxazolyl, -sulfonyl-pyridinyl, -carbonyl-oxazolyl, -carbonyl-pyridinyl; optionally independently halogen, amino, OH, COOH, CN, –CH 2 CN, CF 3 , –CH 2 F, –CH 2 CF, –C(CH 3 ) 3 , –O–C(CH 3 ) 3 , –OCH 3 , C 1-4 alkyl , C 3-6 cycloalkyl, phenyl substituted 1-3 times.
  • each X is independently oxygen.
  • R 1 is COOH
  • L is selected from —(CH 2 ) a — or —O—, wherein a is 0 or 1.
  • a is 0 or 1.
  • L is a direct connection key.
  • L is -CH 2 -.
  • L is a direct linkage.
  • Y 1 is 1,4-phenylene.
  • each X is independently O, R is COOH, L is a direct linkage, and Y is 1,4 - phenylene, the compound has the structure shown in Formula A :
  • Y 2 when Y 2 is phenyl, it is optionally substituted once with any of H, F, Cl, CN, —CH 2 CN, —OCH 3 , CF 3 , CH 3 .
  • Y 2 when Y 2 is pyridyl, it is optionally represented by H, C 1-4 alkyl, —OCH 3 , —N(CH 3 ) 2 , F, CN, NH 2 , CH 2 F, — Any one of CO—NHCH 3 , —CO—CH 3 is substituted 1-2 times.
  • Y is pyridyl substituted twice by methyl, preferably 4 -pyridyl substituted twice by methyl, more preferably
  • R 3 is C 1-4 alkyl substituted by phenyl; preferably, R 3 is 1-phenyl-propyl-, including (R)-1-phenyl-propyl- or (S)-1-phenyl-propyl-.
  • the present invention further provides a compound represented by the following formula I: (2S)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)-2-((8S)-3-(4 -Hydroxyphenyl)-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3- g] isoquinoline-8-carboxamido)propionic acid, and pharmaceutically acceptable salts thereof:
  • the present invention also provides preparation of compound (2S)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)-2-((8S)-3-(4) as shown in formula I -Hydroxyphenyl)-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3- g] a method for isoquinoline-8-carboxamido) propionic acid, the method may further comprise the steps:
  • steps a and b are reacted in a corresponding solvent; the solvent is independently selected from tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, acetone, dichloromethane, acetonitrile, methanol or ethanol at least one.
  • the compound of formula II in step a undergoes a hydrolysis reaction with an acidic reagent;
  • the acidic reagent is selected from one of boron trifluoride, boron trichloride, aluminum trichloride or sulfur trioxide, Boron trichloride is preferred.
  • step b the reaction of step b is carried out in alkaline water.
  • the reaction described in step a is put into the next reaction after a post-processing step; the post-processing step is selected from one of dilution, filtration, pH adjustment, washing, extraction, concentration, crystallization, drying or Multiple; the post-processing step can be performed once or more times as required.
  • the post-treatment method of step a is: after the compound of formula I is prepared, the crude compound I is obtained through pH adjustment, liquid separation, 2-methyltetrahydrofuran extraction, and concentration.
  • the pharmaceutically acceptable salts described in the present invention include acid addition salts and base salts.
  • the compounds provided by the present invention and their pharmaceutically acceptable salts can exist in chiral form, that is, S configuration or R configuration.
  • the compounds provided in this invention and their pharmaceutically acceptable salts may exist in achiral form.
  • the compounds described in the present invention exemplify the structure in one configuration, it also means to disclose the structure in another configuration or achiral form.
  • Optically active (R)- and (S)-isomers as well as D and L-isomers can be prepared by chiral synthesis or chiral reagents or other conventional techniques. If one enantiomer of a compound of the invention is desired, it can be prepared by asymmetric synthesis or derivatization with chiral auxiliary agents, wherein the resulting diastereomeric mixture is separated and the auxiliary group is cleaved to provide pure desired enantiomer.
  • a diastereomeric salt is formed with an appropriate optically active acid or base, and then the salt of the diastereoisomer is formed by conventional methods known in the art. Methods The diastereoisomers were resolved and the pure enantiomers were recovered. Furthermore, the separation of enantiomers and diastereomers is usually accomplished by the use of chromatography using a chiral stationary phase, optionally in combination with chemical derivatization methods (e.g. amines from amines to formate).
  • the compounds described herein include stereoisomers of the compounds.
  • the stereoisomer of the present invention means that when the compound shown in formula I has an asymmetric carbon atom, it will produce enantiomer; when the compound has a carbon-carbon double bond or a ring structure, it will produce cis Anti-isomers; when there are ketones or oximes in the compound, tautomers will be produced; as a specific embodiment, the stereoisomers described in the present invention include but are not limited to: enantiomers, non- Enantiomers, racemic isomers, cis-trans isomers, tautomers, geometric isomers, epimers and mixtures thereof.
  • the compounds of the invention may exist in particular geometric or stereoisomeric forms.
  • the present invention contemplates all such compounds, including cis and trans isomers, (-)- and (+)-enantiomers, (R)- and (S)-enantiomers, diastereomers isomers, (D)-isomers, (L)-isomers, and their racemic and other mixtures, such as enantiomerically or diastereomerically enriched mixtures, all of which are subject to the present within the scope of the invention.
  • Additional asymmetric carbon atoms may be present in substituents such as alkyl groups. All such isomers, as well as mixtures thereof, are included within the scope of the present invention.
  • the pharmaceutically acceptable salts described herein can exist in unsolvated as well as solvated forms.
  • the compounds provided by the present invention and their pharmaceutically acceptable salts can be used alone or in combination with at least one other therapeutic agent in therapy.
  • the present invention provides a pharmaceutical composition, which contains the compound represented by formula A or a pharmaceutically acceptable salt thereof, and one or more than two other therapeutically active ingredients.
  • the present invention provides a pharmaceutical preparation, which contains a compound represented by formula A or a pharmaceutically acceptable salt thereof, and one or more than two pharmaceutically acceptable carriers.
  • the pharmaceutical preparation is any clinically acceptable dosage form.
  • the compounds provided by the present invention and pharmaceutically acceptable salts thereof can form solid dosage forms, such as capsules, tablets, pills, lozenges, sugar-coated agents, granules, powders, ointments, creams, drops, etc.;
  • the provided compounds and pharmaceutically acceptable salts thereof may be in liquid dosage forms such as elixirs, syrups, emulsions, dispersions, suspensions, solutions, sprays and the like.
  • the pharmaceutically acceptable carrier and/or pharmaceutically acceptable diluent in the pharmaceutical composition or pharmaceutical preparation of the present invention can be any conventional carrier and/or diluent in the field of pharmaceutical preparation.
  • the present invention also provides a pharmaceutical composition
  • a pharmaceutical composition comprising (2S)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)-2-((8S)-3 -(4-Hydroxyphenyl)-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2 ,3-g] isoquinoline-8-carboxamido)propionic acid or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable auxiliary materials, carriers, and excipients.
  • compositions of compounds of formula I of the present invention can be prepared according to methods well known in the art.
  • the dosage form of the compound of formula I of the present invention or the pharmaceutical composition containing it may be liquid dosage form or solid dosage form.
  • the liquid dosage forms can be true solutions, colloids, particulate dosage forms, emulsion dosage forms, and suspension dosage forms.
  • Other dosage forms such as tablets, capsules, drop pills, aerosols, pills, powders, solutions, suspensions, emulsions, granules, suppositories, freeze-dried powder injections, etc.
  • the compound of formula I of the present invention or the pharmaceutical composition containing it can be made into common preparations, and also can be sustained-release preparations, controlled-release preparations, targeted preparations and various particle delivery systems.
  • the compound of formula I has antitumor activity and is able to inhibit the growth of, for example, cervical cancer cells.
  • the present invention provides the use of the compound represented by formula A and a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating tumors.
  • the present invention provides the use of the compound of formula I and a pharmaceutically acceptable salt thereof for the preparation of antitumor drugs.
  • the tumor is a malignant tumor, including but not limited to breast cancer, cervical cancer, rectal cancer, pancreatic cancer, prostate cancer, kidney cancer, ovarian cancer, bladder cancer, fallopian tube tumors, ovarian tumors, peritoneal tumors, Melanoma, glioma, or glioblastoma.
  • the present invention also provides a method for treating diseases, the method comprising administering a therapeutically effective amount of a compound represented by formula A, preferably formula I and a pharmaceutically acceptable salt thereof to a patient in need.
  • the disease is a tumor, particularly a malignant tumor, including but not limited to breast cancer, cervical cancer, rectal cancer, pancreatic cancer, prostate cancer, kidney cancer, ovarian cancer, bladder cancer, fallopian tube tumors, ovarian tumors , peritoneal tumors, melanoma, glioma, and glioblastoma.
  • CN102378574A discloses an azoanthracene derivative (S)-2- ⁇ [(3S,8S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-7-((S )-1-phenyl-propyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]
  • the researchers of the present invention found that during the preparation of OAD2 ⁇ 2HCl, due to the strong acidity of the salt-forming process and the influence of temperature during the drying process, the ether bond is easily broken to produce the compound of formula I mentioned above.
  • the researchers found that as the batch size increased, the compound of formula I tended to increase, but this trend did not appear in the previous small-scale production of OAD2 ⁇ 2HCl.
  • the compound of formula I can be used as a reference compound for the quality control of OAD2 ⁇ 2HCl and the pharmaceutical composition or preparation containing OAD2 ⁇ 2HCl.
  • the present invention provides a method for quality control of a sample, wherein the sample is a raw material related to a compound of formula A, formula A1 or formula I described herein, a pharmaceutical composition or preparation comprising the raw material , the method includes: using the corresponding compound of formula A, formula A1 or formula I as a reference compound, and determining the level of the reference compound in the sample.
  • the method optionally further comprises comparing the determined level of the reference compound to the expected level of the reference compound in the sample.
  • the raw material related to the compound of formula A, formula A1 or formula I refers to such a compound, which can form the compound of formula A, formula A1 or formula I through degradation.
  • the reference compound is the compound of Formula A. In some embodiments, the reference compound is the compound of Formula A1. In some preferred embodiments, the reference compound is the compound of formula I.
  • said sample is a feedstock related to said compound of formula I, preferably OAD2, preferably OAD2 ⁇ 2HCl.
  • the sample is a pharmaceutical composition or formulation comprising OAD2 or preferably OAD2.2HCl.
  • the present invention provides a method for quality control of a sample, the sample is OAD2, OAD2.2HCl, or a pharmaceutical composition or preparation containing OAD2 or OAD2.2HCl, the method comprising:
  • the compound of formula I is used as a reference compound, and the level of the reference compound in the sample is determined.
  • the method optionally further comprises comparing the determined level of the reference compound to the expected level of the reference compound in the sample.
  • the desired level of the compound of formula I is less than 1.0%, such as less than 0.9%, or less than 1.0%, based on the total weight of the compound of formula I and OAD2 or preferably OAD2.2HCl.
  • the desired level of the compound of formula I is less than 1.0% based on the total weight of the pharmaceutical composition or formulation , or less than 0.9%, or less than 0.8%, or less than 0.7%, or less than 0.6%, or less than 0.5%, or less than 0.4%, or less than 0.3%, or less than 0.2%, or Preferably less than 0.1%, or less than 0.09%, or less than 0.08%, or less than 0.07%, or less than 0.06%, or less than 0.05%, or less than 0.04%, or less than 0.03%, or less less than 0.02%, or less than 0.01%.
  • the method used to determine the level of the reference compound can be a method commonly used in the art, such as high performance liquid chromatography (HPLC).
  • HPLC high performance liquid chromatography
  • the compounds described in the present invention are named according to the chemical structural formula. If the name of the compound is inconsistent with the chemical structural formula when referring to the same compound, the chemical structural formula shall prevail.
  • enantiomer or “optical isomer” refer to stereoisomers that are mirror images of each other.
  • cis-trans isomers or “geometric isomers” arise from the inability to rotate freely due to the double bond or the single bond of the carbon atoms forming the ring.
  • diastereoisomer refers to stereoisomers whose molecules have two or more chiral centers and which are not mirror images of the molecules.
  • keys with wedge-shaped solid lines and dotted wedge keys Indicates the absolute configuration of a stereocenter, with a straight solid-line bond and straight dashed keys Indicates that the stereocenter is an absolute configuration, but it is not sure whether it is a wedge-shaped solid-line bond or wedge-shaped dotted line key
  • Optically active (R)- and (S)-isomers as well as D and L-isomers can be prepared by chiral synthesis or chiral reagents or other conventional techniques. If one enantiomer of a compound of the present disclosure is desired, it can be prepared by asymmetric synthesis or derivatization with chiral auxiliary agents, wherein the resulting diastereomeric mixture is separated and the auxiliary group is cleaved to provide pure the desired enantiomer.
  • a diastereomeric salt is formed with an appropriate optically active acid or base, and then the salt of the diastereoisomer is formed by conventional methods known in the art. Methods The diastereoisomers were resolved and the pure enantiomers were recovered. Furthermore, the separation of enantiomers and diastereomers is usually accomplished by the use of chromatography using a chiral stationary phase, optionally in combination with chemical derivatization methods (e.g. amines from amines to formate).
  • pharmaceutically acceptable refers to those compounds, materials, compositions and/or dosage forms that are suitable for use in contact with human and animal tissues within the scope of sound medical judgment, without excessive toxicity, irritation, allergic reaction or other problems or complications, commensurate with a reasonable benefit/risk ratio.
  • pharmaceutically acceptable salt refers to a salt of a compound of the present disclosure, prepared from a compound of the present disclosure having a specific substituent and a relatively non-toxic acid or base.
  • base addition salts can be obtained by contacting such compounds with a sufficient amount of base, either neat solution or in a suitable inert solvent.
  • Pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amine or magnesium salts and the like.
  • acid addition salts can be obtained by contacting such compounds with a sufficient amount of the acid, either neat solution or in a suitable inert solvent.
  • Examples of pharmaceutically acceptable acid addition salts include salts of inorganic acids including, for example, hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, bicarbonate, phosphoric acid, monohydrogenphosphate, dihydrogenphosphate, sulfuric acid, Hydrogen sulfate, hydriodic acid, phosphorous acid, etc.; and organic acid salts, such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, Fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-toluenesulfonic acid, citric acid, tartaric acid and methanesulfonic acid and similar acids; also salts of amino acids such as arginine and the like , and salts of organic acids such as glucuronic acid. Certain specific compounds of the present invention contain basic and acidic functional groups and can thus be converted into
  • the pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound containing acid or basic groups by conventional chemical methods.
  • such salts are prepared by reacting the free acid or base form of these compounds with a stoichiometric amount of the appropriate base or acid in water or an organic solvent or a mixture of both.
  • substituted herein means that any one or more hydrogen atoms on a specific atom are replaced by a substituent, which may include deuterium and hydrogen variants, as long as the valence of the specific atom is normal and the substituted Compound is stable.
  • halogen herein means fluorine, chlorine, bromine and iodine.
  • C 1-4 alkyl herein is a straight or branched chain alkyl group having 1 to 4 carbons, including but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, Isobutyl, sec-butyl, tert-butyl and 1-methylpropyl.
  • C 3-6 cycloalkyl herein means a monovalent group obtained by removing any single hydrogen atom from a cyclic saturated aliphatic hydrocarbon having 3 to 6 carbons, i.e., a ring of 3 to 6 carbons alkyl. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
  • the anthracene compound of the present invention can be used as a reference compound for quality control of related raw materials, pharmaceutical compositions or preparations containing the raw materials.
  • their source compounds have activity modulating the GLP-1 receptor and are therefore useful in the treatment of type 2 diabetes
  • the anthracene compounds of the present invention have very different antitumor activity and are useful as antitumor drug potential.
  • Step b
  • Embodiment 2 the detection of formula I compound
  • the structure of the compound is determined by nuclear magnetic resonance (NMR) or/and mass spectrometry (MS); NMR shift ( ⁇ ) is in units of 10-6 (ppm); NMR is determined with a Bruker DMX-500 nuclear magnetic instrument.
  • the solvent was deuterated pyridine, and the internal standard was tetramethylsilane (TMS).
  • MS was determined with a Bruker Esquire 3000plus mass spectrometer.
  • Embodiment 3 the biological activity evaluation of formula I compound
  • MTT phosphate buffered saline
  • the dose-response curve can be obtained by plotting the different concentrations of the drug and the cell viability (OD 490 ) of the cell line, and the half inhibitory concentration (IC 50 ) can be obtained from it.
  • Embodiment 4 the detection of formula I compound as the reference compound of OAD2.2HCl sample
  • Reagents and reagents acetonitrile (HPLC), methanol (HPLC), trifluoroacetic acid (HPLC), purified water
  • Instruments and appliances electronic analytical balance, liquid chromatograph, amido hexadecyl silica gel column, measuring flask, beaker
  • the elution gradient is as follows:
  • the retention time of the compound of formula I is 3.567, the retention time of OAD2.2HCl is 22.059, and the relative retention time is: 0.161.

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  • Health & Medical Sciences (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un composé anthracène de formule A, son procédé de préparation et son utilisation médicale. Le composé anthracène a pour effet d'inhiber la croissance de cellules tumorales et a le potentiel en tant que médicament antitumoral. La présente invention concerne en outre un procédé de contrôle de qualité d'un échantillon.
PCT/CN2022/097326 2021-06-17 2022-06-07 Composé anthracène, son procédé de préparation et son utilisation médicale WO2022262615A1 (fr)

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CN202280042744.2A CN117500808A (zh) 2021-06-17 2022-06-07 蒽类化合物、其制备方法和医药用途

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CN202110670381 2021-06-17
CN202110670381.4 2021-06-17
CN202210252196.8 2022-03-15
CN202210252196 2022-03-15

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WO2025057134A2 (fr) 2023-09-14 2025-03-20 Ascletis Pharma (China) Co., Limited Agoniste de glp-1r et méthode thérapeutique associée
WO2025109387A1 (fr) 2023-11-24 2025-05-30 Ascletis Pharma (China) Co., Limited Agoniste de glp-1r et son procédé thérapeutique

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101959405A (zh) * 2008-03-07 2011-01-26 转化技术制药公司 治疗糖尿病的氧杂二氮杂蒽化合物
CN102378574A (zh) * 2009-03-30 2012-03-14 转化技术制药公司 取代的偶氮蒽衍生物、药物组合物及其使用方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101959405A (zh) * 2008-03-07 2011-01-26 转化技术制药公司 治疗糖尿病的氧杂二氮杂蒽化合物
CN102378574A (zh) * 2009-03-30 2012-03-14 转化技术制药公司 取代的偶氮蒽衍生物、药物组合物及其使用方法

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