WO2022122042A1 - Dérivé d'abiratérone et son procédé de préparation - Google Patents

Dérivé d'abiratérone et son procédé de préparation Download PDF

Info

Publication number
WO2022122042A1
WO2022122042A1 PCT/CN2021/137498 CN2021137498W WO2022122042A1 WO 2022122042 A1 WO2022122042 A1 WO 2022122042A1 CN 2021137498 W CN2021137498 W CN 2021137498W WO 2022122042 A1 WO2022122042 A1 WO 2022122042A1
Authority
WO
WIPO (PCT)
Prior art keywords
general formula
compound
pharmaceutically acceptable
butyl
alkyl group
Prior art date
Application number
PCT/CN2021/137498
Other languages
English (en)
Chinese (zh)
Inventor
林其先
方建
刘建余
王玮
郭承
Original Assignee
上海喀露蓝科技有限公司
澳创药业有限公司
四川夏派森医药科技有限公司
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.)
Filing date
Publication date
Application filed by 上海喀露蓝科技有限公司, 澳创药业有限公司, 四川夏派森医药科技有限公司 filed Critical 上海喀露蓝科技有限公司
Priority to CN202180082961.XA priority Critical patent/CN116583529A/zh
Publication of WO2022122042A1 publication Critical patent/WO2022122042A1/fr

Links

Classifications

    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/664—Amides of phosphorus acids
    • 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
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00

Definitions

  • the present invention relates to an abiraterone derivative, its preparation method and its application. Specifically, the present invention relates to an abiraterone derivative represented by the general formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, a preparation method thereof, a pharmaceutical composition containing them, and the preparation of a medicine use in.
  • an abiraterone derivative represented by the general formula (I) a stereoisomer thereof or a pharmaceutically acceptable salt thereof, a preparation method thereof, a pharmaceutical composition containing them, and the preparation of a medicine use in.
  • Abiraterone is a CYP17 enzyme inhibitor. Its prodrug, abiraterone acetate, was approved by the FDA in 2011 for the treatment of patients with prostate cancer. The recommended oral dose is 1000mg once a day and prednisone 5mg daily 2 times in combination.
  • abiraterone acetate Although abiraterone acetate has great clinical value, it has poor solubility (less than 0.01 mg/mL), low bioavailability (absolute bioavailability in humans is less than 10%), and high food impact (high-fat foods will increase 5 to 10 times the drug exposure), significant differences in pharmacokinetics between individuals, and abiraterone acetate is a substrate of CYP3A4 liver enzymes, its metabolism may be inhibited or induced by other concurrently administered drugs, there is a potential drug-drug Interaction risk. The above characteristics affect the clinical application of abiraterone acetate.
  • the technical problem to be solved by the present invention is to overcome the defects of abiraterone in the prior art, such as poor solubility, low bioavailability, great influence of food or significant differences in pharmacokinetics among individuals. Therefore, the present invention provides an abiraterone Biterone derivatives and preparation methods thereof.
  • the abiraterone derivative of the present invention has the following advantages: high water solubility, ability to improve drug absorption and metabolism distribution in the body, high oral bioavailability of the drug, less influence of food, less administration dose, low administration frequency, and patient compliance High, high safety and long duration of action.
  • the present invention solves the above technical problems through the following technical solutions.
  • the present invention provides a compound represented by general formula (I), its stereoisomer, its pharmaceutically acceptable salt or its solvate:
  • R a is a hydrogen atom or a C 1-6 alkyl group
  • R b and R b' are each independently a hydrogen atom, a C 1-6 alkyl group, a natural or pharmaceutically acceptable amino acid side chain;
  • R c is C 1-6 alkyl group, benzyl group or C 2-6 alkyl group substituted by C 6-14 aryl group (the number substituted by C 6-14 aryl group can be 1 or more, when it is When there are more than one, the C 6-14 aryl groups may be the same or different).
  • the C 1-6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl Butyl such as methyl.
  • the C 1-6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isopropyl butyl or tert-butyl.
  • the C 1-6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl Butyl such as isopropyl.
  • the C 2-6 alkyl group in the C 2-6 alkyl group substituted by C 6-14 aryl group is ethyl, n-propyl, isopropyl , n-butyl, sec-butyl, isobutyl or tert-butyl.
  • the C 6-14 aryl group in the C 2-6 alkyl group substituted by the C 6-14 aryl group is phenyl, naphthyl, anthracenyl or phenanthrene group, such as phenyl.
  • the compound represented by the general formula (I) is the compound represented by the general formula I-1 and/or I-2:
  • the configuration of the P atom in the general formula I-1 is the S configuration
  • the configuration of the P atom in the general formula I-2 is the R configuration.
  • one or more atoms in are atoms in unnatural abundance, or where all atoms are atoms in natural abundance.
  • Ra is a hydrogen atom.
  • R b and R b' are each independently a hydrogen atom or a C 1-6 alkyl group.
  • one of the substituents is a hydrogen atom
  • the other substituent is a C 1-6 alkyl group.
  • R c is C 1-6 alkyl.
  • the carbon marked with * refers to S-configuration chiral carbon, R-configuration chiral carbon or achiral carbon; preferably, the carbon marked with * refers to S-configuration chiral carbon.
  • R a is a hydrogen atom; in R b and R b' , one of the substituents is a hydrogen atom, and the other substituent is a C 1-6 alkyl group (such as methyl); R c is a C 1-6 alkyl group .
  • the compound represented by the general formula (I) is the compound represented by the general formula I-1:
  • Ra is a hydrogen atom
  • one of the substituents is a hydrogen atom, and the other is a C 1-6 alkyl group;
  • R c is C 1-6 alkyl.
  • R a is a hydrogen atom or a C 1-6 alkyl group
  • R b and R b' are each independently a hydrogen atom, a C 1-6 alkyl group, or a natural or pharmaceutically acceptable amino acid side chain;
  • R c is C 1-6 alkyl or benzyl.
  • Ra is a hydrogen atom
  • R b and R b' are each independently a hydrogen atom or a methyl group
  • R c is methyl, ethyl, propyl, isopropyl or benzyl
  • the compound represented by the general formula (I) is the following compound:
  • the present invention also provides a preparation method of the above-mentioned compound shown in general formula (I), its stereoisomer, its pharmaceutically acceptable salt or its solvate, which comprises the following steps:
  • X 1 and X 2 are each independently halogen (eg Cl); the carbon marked with * refers to S-configuration chiral carbon, R-configuration chiral carbon or achiral carbon; R 2 , R a , R The definitions of b , R b' and R c are the same as above.
  • the conditions and operations of the described reaction can be conventional conditions and operations in this type of reaction in this area, and the present invention particularly preferably the following conditions and operations:
  • the base is preferably an organic base, preferably triethylamine.
  • the molar ratio of the alkali to the abiraterone is preferably 8:1-1:1, more preferably 4.0:1.
  • the compound represented by the general formula II is preferably ethyl dichlorophosphoryl formate.
  • the molar ratio of the compound represented by the general formula II to the abiraterone is preferably 3:1-1:1, more preferably 1:1.
  • the compound represented by the general formula III is preferably L-alanine isopropyl ester hydrochloride.
  • the molar ratio of the compound represented by the general formula III to the abiraterone is preferably 3:1-1:1, more preferably 1:1.
  • the solvent is preferably a halogenated hydrocarbon solvent, preferably dichloromethane.
  • the temperature of the reaction is preferably -40°C to 50°C, more preferably room temperature.
  • the progress of the reaction can be monitored by a conventional monitoring method in the art, and usually the end point of the reaction is that abiraterone no longer reacts or disappears.
  • the reaction time is preferably 1 hour to 16 hours, more preferably 3 hours.
  • the present invention also provides a pharmaceutical composition, which contains a therapeutically effective dose of the above-mentioned compound represented by general formula (I), its stereoisomer, its pharmaceutically acceptable salt or its solvate, and A pharmaceutically acceptable carrier or excipient.
  • a pharmaceutical composition which contains a therapeutically effective dose of the above-mentioned compound represented by general formula (I), its stereoisomer, its pharmaceutically acceptable salt or its solvate, and A pharmaceutically acceptable carrier or excipient.
  • the present invention also provides the use of a substance X in the preparation of a medicament for preventing or treating tumors;
  • the substance X is the above-mentioned compound represented by the general formula (I), its stereoisomer, its pharmacy An acceptable salt thereof, a solvate thereof, or a pharmaceutical composition as described above.
  • the tumor is preferably prostate cancer.
  • the present invention also provides a method for preventing or treating tumors, which comprises administering to a subject a therapeutically effective amount of substance X, wherein the substance X is the above-mentioned compound represented by general formula (I), its stereoisomer body, its pharmaceutically acceptable salt, its solvate or the above-mentioned pharmaceutical composition.
  • substance X is the above-mentioned compound represented by general formula (I), its stereoisomer body, its pharmaceutically acceptable salt, its solvate or the above-mentioned pharmaceutical composition.
  • the tumor is preferably prostate cancer.
  • the elements carbon, hydrogen, oxygen, nitrogen or halogen involved in the groups and compounds of the present invention all include their isotopic situations, and the elements carbon, hydrogen, oxygen or nitrogen involved in the groups and compounds of the present invention are any It is further replaced by one or more of their corresponding isotopes, wherein the isotopes of carbon include 12 C, 13 C and 14 C, and the isotopes of hydrogen include protium (H), deuterium (D, also known as deuterium), tritium (T , also known as superheavy hydrogen), oxygen isotopes include 16 O, 17 O and 18 O, nitrogen isotopes include 14 N and 15 N, fluorine isotopes 19 F, chlorine isotopes include 35 Cl and 37 Cl, and bromine isotopes include 79Br and 81Br .
  • the isotopes of carbon include 12 C, 13 C and 14 C
  • the isotopes of hydrogen include protium (H), deuterium (D, also known as de
  • Natural or pharmaceutically acceptable amino acids The basic backbone of protein molecules is the amino acid sequence. There are 20 basic amino acids that make up proteins. These 20 basic amino acids are the basis for later modification of proteins by organisms. In addition, on the basis of these basic amino acids , and also biosynthesize hydroxyproline, hydroxylysine, etc. derived amino acids, these biosynthesized amino acids are collectively referred to as “natural amino acids”; artificially synthesized amino acids are “non-natural amino acids”. “Pharmaceutically acceptable amino acid” refers to a pharmaceutically acceptable natural or unnatural amino acid.
  • Side chain of an amino acid refers to a moiety that is covalently attached to a D or L-amino acid structure and can be represented as -CH(COOH)( NH2 )-R.
  • -CH(COOH)( NH2 )-R the side chain of the amino acid (R) is -CH3 .
  • alkyl when taken as a group or part of a group refers to a straight-chain or branched aliphatic hydrocarbon group comprising 1 to 20 carbon atoms. It is preferably 1 to 10 alkyl groups, more preferably 1 to 6 alkyl groups.
  • alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-di Methylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1 -Ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethyl Butyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl Wait.
  • Alkoxy refers to a group (alkyl-O-). Wherein, alkyl is as defined herein. Ci - C6 alkoxy groups are preferred. Examples include, but are not limited to: methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, and the like.
  • Amino refers to -NH2 .
  • Halogen refers to fluorine, chlorine, bromine and iodine.
  • DMSO dimethyl sulfoxide
  • Benzyl refers to -CH2 -phenyl.
  • TMS trimethylsilyl
  • alkyl optionally substituted by F means that the alkyl group may but not necessarily be substituted by F, and the description includes the case where the alkyl group is substituted by F and the case where the alkyl group is not substituted by F.
  • “Pharmaceutical composition” means a mixture of one or more of the compounds described herein, or a physiologically/pharmaceutically acceptable salt thereof, with other ingredients, wherein the other ingredients include physiologically/pharmaceutically acceptable carriers and excipients.
  • Carrier refers to a carrier or diluent that is not appreciably irritating to the organism and that does not abrogate the biological activity and properties of the administered compound.
  • Excipient refers to an inert substance added to a pharmaceutical composition to further depend upon the administration of the compound.
  • excipients include, but are not limited to, calcium carbonate, calcium phosphate, various sugars and different types of starch, cellulose derivatives (including microcrystalline cellulose), gelatin, vegetable oils, polyethylene glycols, diluents, Granules, lubricants, binders, disintegrants, etc.
  • Prodrug refers to a drug that can be converted under physiological conditions or by solvolysis to a biologically active drug.
  • the prodrugs of the present invention are prepared by modifying functional groups in estradiol, and the modification can be removed by conventional operations or in vivo to obtain estradiol.
  • Steps refer to isomers resulting from different arrangements of atoms in a molecule in space, including cis-trans isomers, enantiomers and conformational isomers.
  • Effective dose refers to the amount of a compound that elicits a physiological or medical response in a tissue, system, or subject that is sought, including one or more of the compounds that, when administered in a subject, are sufficient to prevent the disorder or disorder being treated The amount of a compound at which a symptom occurs or is alleviated to some extent.
  • “Pharmaceutically acceptable salts” refers to pharmaceutically acceptable salts of non-toxic acids or bases, including salts of inorganic acids and bases, organic acids and bases.
  • Solvate refers to a substance formed by crystallizing a compound with a solvent (including, but not limited to, water, methanol, ethanol, etc.). Solvates are divided into stoichiometric and non-stoichiometric solvates.
  • R 1 , R 2 , R a , R b , R b' , R c " in the present invention refer to the number of the R, not the number of R .
  • the structures of the compounds were determined by nuclear magnetic resonance (NMR) and/or mass spectrometry (MS).
  • Mass spectrum is obtained by LC/MS instrument, and the ionization mode can be ESI or APCI.
  • the thin layer chromatography silica gel plate uses Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plate, the size of the silica gel plate used for thin layer chromatography (TLC) is 0.15mm ⁇ 0.2mm, and the size of the TLC separation and purification products is 0.4mm ⁇ 0.5mm.
  • the HPLC assay was performed using an Agilent 1260DAD high pressure liquid chromatograph (Zorba x SB-C18 100 x 4.6 mm).
  • the compound is purified by silica gel column chromatography and thin layer chromatography, wherein the eluent system is selected from: A: petroleum ether and ethyl acetate system; B: dichloromethane and methanol system; C: dichloromethane: acetic acid Ethyl ester; D: petroleum ether: dichloromethane system; the volume ratio of the solvent varies according to the polarity of the compound, and a small amount of acidic or basic reagents can also be added for adjustment, such as acetic acid or triethylamine.
  • the eluent system is selected from: A: petroleum ether and ethyl acetate system; B: dichloromethane and methanol system; C: dichloromethane: acetic acid Ethyl ester; D: petroleum ether: dichloromethane system; the volume ratio of the solvent varies according to the polarity of the compound, and a small amount of acidic or basic reagents
  • reaction temperature is room temperature. Room temperature is the most suitable reaction temperature, which is 20°C to 30°C.
  • Triethyl formate (100 g, 0.476 mol) was dissolved in 1 L of acetonitrile, trimethylsilyl bromide (220 g, 1.43 mol) was added, and the reaction was stirred at 65° C. for 3 hours. It was cooled to room temperature and concentrated to give the title compound 1a (140 g, yellow liquid) which was used directly in the next step.
  • Ethyl dichlorophosphoryl formate 1b (177 g, 0.93 mol) was dissolved in 4.5 L of dichloromethane, and the temperature was lowered to -60°C under argon protection. Abiraterone (325 g, 0.93 mol) and L-alanine isopropyl ester hydrochloride (156 g, 0.93 mol) were added. After the addition was complete, triethylamine (375 g, 3.71 mol) was added dropwise. After dripping, the reaction was incubated for 30 min, and the temperature was naturally raised to room temperature for 3 h.
  • Test animals 6 healthy adult Sprague-Dawley (SD) rats, male, 180-250 g, purchased from Chengdu Dashuo Laboratory Animal Co., Ltd.
  • SD rats were randomly divided into 2 groups, 3 rats in each group; fasting for no less than 8 hours before administration, free drinking water, and eating 4 hours after administration.
  • the animals in the two groups were given abiraterone (dose of 5 mg/kg) by intravenous injection (IV), compound 1 (dose of 25 mg/kg) by intragastric administration (PO), and venous blood was collected at different times before and after administration.
  • IV intravenous injection
  • PO intragastric administration
  • venous blood was collected at different times before and after administration.
  • the concentrations of abiraterone (original drug) and compound 1 (prodrug) in plasma were determined by LC-MS/MS method.
  • Compound 1 is rapidly absorbed after intragastric administration to rats, mainly exists in the form of abiraterone in vivo, and the absolute bioavailability of oral administration calculated according to the exposure level of abiraterone in plasma is 70.5%.
  • Rat venous blood was collected 7 days and 14 days after administration, serum was separated, and the concentration of testosterone in serum was measured; at the same time, animals were sacrificed 14 days after administration, and testis, ventral lobe of prostate and seminal vesicle were immediately separated, and wet weight was weighed.
  • the mean serum testosterone levels of the vehicle control group, the abiraterone acetate 100 mg/kg group, the compound 1-I 50 mg/kg group, and the compound 1-I 100 mg/kg group were 10.176, 7.794, 8.66, 5.68 ng/kg, respectively.
  • ml; 12.28, 0.759, 0.88, 0.783 ng/ml after 14 days of administration Table 2.
  • Androgen-sensitive organ weights are shown in Table 3 after 14 days of dosing.
  • Table 3 The effect of continuous intragastric administration of compounds on the weight of androgen-sensitive organs for 14 days
  • Human prostate cancer cells were cultured in DMEM medium containing 10% FBS at 37°C, 5% CO 2 , digested with trypsin-EDTA when the confluency reached about 80-90%, washed twice with PBS, and then resuspended by centrifugation. Pre-cooled PBS, counted in a cell counter, resuspended in PBS and adjusted the cell concentration to 2 ⁇ 10 7 /ml.
  • Male Balb/c nu mice were acclimated to the laboratory environment for 5 days, and were inoculated subcutaneously with VCaP cells in the right flank. Castration was performed at about 100mm 3 , and the animals were adapted for 3 weeks after the operation.
  • a total of 5 groups were administered orally with blank vehicle, abiraterone acetate 0.5mM/kg, or compound 1-I low (0.1mM/kg), medium (0.25mM/kg), high (0.5mM/kg) Dosage, once a day, for 40 consecutive days. Both abiraterone acetate and compound 1-I were dissolved in ethanol: Tween 80: saline (15:5:80, v/v/v).
  • T/C(%) (T-T0)/(C-C0) ⁇ 100, where T and C are the tumor volumes at the end of the experiment; T0 and C0 are the tumor volumes at the start of administration after grouping .
  • TGI Tumor inhibition rate
  • each dose of Compound 1-I has inhibitory activity on VCaP mouse transplanted tumor, and the pharmacodynamic activity of the dose of 0.25mM/kg in the compound is equivalent to the dose of abiraterone acetate 0.5mM/kg, indicating that the compound 1-I can achieve the efficacy of abiraterone acetate at lower doses.
  • Experimental animals 3 healthy adult beagle dogs, male, 6-8 kg, purchased from Chengdu Dashuo Laboratory Animal Co., Ltd.
  • Dosing and testing 3 healthy adult male beagle dogs were fasted for not less than 12 hours before administration, with free access to water, and were allowed to eat for 4 hours after administration.
  • Compound 1-I (10 mg/kg) was administered by gavage (PO) first, about 0.5 ml of venous blood was collected before and after administration, anticoagulated with heparin, centrifuged to separate plasma, and stored at -80°C To be tested. After the first round of administration, the mice were cleaned for 1 week, and then abiraterone (dose: 2 mg/kg) was administered by intravenous injection of the forelimb. About 0.5 ml of venous blood was collected before and after administration, and heparin was used for anticoagulation. Plasma was separated by centrifugation and stored at -80°C for testing. The concentrations of abiraterone (original drug) and compound 1-I (prodrug) in plasma were determined by LC-MS/MS method.
  • the compound 1-I of the present invention was administered to beagle dogs by gavage, and the prototype (prodrug form) of the compound 1-I was detected in the plasma at all times, and abiraterone could be detected at the same time.

Landscapes

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

Abstract

La présente invention concerne un dérivé d'abiratérone et son procédé de préparation. Le dérivé d'abiratérone de la présente invention a une structure telle que représentée par la formule générale (I). Le dérivé d'abiratérone de la présente invention permet d'obtenir une biodisponibilité élevée et un bon effet inhibiteur de tumeur, et a des perspectives élevées pour une application pharmaceutique.
PCT/CN2021/137498 2020-12-12 2021-12-13 Dérivé d'abiratérone et son procédé de préparation WO2022122042A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202180082961.XA CN116583529A (zh) 2020-12-12 2021-12-13 阿比特龙衍生物及其制备方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202011448745 2020-12-12
CN202011448745.6 2020-12-12

Publications (1)

Publication Number Publication Date
WO2022122042A1 true WO2022122042A1 (fr) 2022-06-16

Family

ID=81973103

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2021/137498 WO2022122042A1 (fr) 2020-12-12 2021-12-13 Dérivé d'abiratérone et son procédé de préparation

Country Status (2)

Country Link
CN (1) CN116583529A (fr)
WO (1) WO2022122042A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010091306A1 (fr) * 2009-02-05 2010-08-12 Tokai Pharmaceuticals Nouveaux promédicaments à base d'inhibiteurs cyp17 stéroïdiens/anti-androgènes
CN104974212A (zh) * 2014-04-02 2015-10-14 北京朗瑞邦科技有限公司 有抗癌作用的阿比特龙衍生物
WO2017133517A1 (fr) * 2016-02-03 2017-08-10 四川海思科制药有限公司 Dérivé de phosphamide, son procédé de fabrication et ses utilisations
CN109879933A (zh) * 2019-01-30 2019-06-14 河北科技大学 一类含磷酰基化合物及其应用
CN111961108A (zh) * 2019-05-20 2020-11-20 湖南大学 一种核酸适配体药物偶联物及其制备方法和用途

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010091306A1 (fr) * 2009-02-05 2010-08-12 Tokai Pharmaceuticals Nouveaux promédicaments à base d'inhibiteurs cyp17 stéroïdiens/anti-androgènes
CN102686600A (zh) * 2009-02-05 2012-09-19 托凯药业股份有限公司 甾体cyp17抑制剂/抗雄激素物质的新型药物前体
CN104974212A (zh) * 2014-04-02 2015-10-14 北京朗瑞邦科技有限公司 有抗癌作用的阿比特龙衍生物
WO2017133517A1 (fr) * 2016-02-03 2017-08-10 四川海思科制药有限公司 Dérivé de phosphamide, son procédé de fabrication et ses utilisations
CN109879933A (zh) * 2019-01-30 2019-06-14 河北科技大学 一类含磷酰基化合物及其应用
CN111961108A (zh) * 2019-05-20 2020-11-20 湖南大学 一种核酸适配体药物偶联物及其制备方法和用途

Also Published As

Publication number Publication date
CN116583529A (zh) 2023-08-11

Similar Documents

Publication Publication Date Title
WO2021190467A1 (fr) Composé de quinazoline contenant un cycle spiro
KR100674160B1 (ko) 악성 종양의 치료용 약제
CN110256421A (zh) Kras-g12c抑制剂
US6747021B2 (en) Cryptophycin compound
AU2016260279B2 (en) Crystals of azabicyclic compound
KR20130089264A (ko) 헤테로사이클릭 유도체, 이의 제조 방법 및 이의 의학적 용도
CN110234320B (zh) 包含至少一种溶于水性介质且具有改善肠道吸收的药物可接受的依拉贝特盐的组合物
WO2018084321A1 (fr) Nouveau composé utile à la fois pour l'inhibition de l'egfr et la thérapie antitumorale
WO2021150885A1 (fr) Dérivés cannabinoïdes
JP5649652B2 (ja) 置換ヒドラジド類化合物及びその応用
RU2393160C2 (ru) Фармацевтическая композиция, содержащая эфир темозоломида
EP3680232A1 (fr) NOUVEAU COMPOSÉ À BASE D'ACIDE ANTHRANILIQUE, ET INHIBITEUR DE Pin1, AGENT THÉRAPEUTIQUE CONTRE LES MALADIES INFLAMMATOIRES AINSI QU'AGENT THÉRAPEUTIQUE CONTRE LE CANCER METTANT EN UVRE CELUI-CI
JP2021165270A (ja) 置換アリールエーテル系化合物、その調製方法、医薬組成物およびその応用
KR20220107020A (ko) Erk 억제제로서 작용하는 스피로 화합물 및 이의 응용
CN114989182A (zh) 脂质化合物、包含其的组合物及应用
KR20170129688A (ko) 인돌아세트산의 코어구조를 함유하는 화합물 및 그의 용도
KR100979077B1 (ko) 벤즈아제핀 화합물의 고체 염 및 이를 포함하는 약제학적 조성물
CN110467616B (zh) 含杂芳基取代哒嗪酮结构的三唑并吡嗪类化合物的制备及应用
JP7229482B2 (ja) 新規アミド系化合物、並びにそれを用いたＰｉｎ１阻害剤、炎症性疾患の治療剤及び癌の治療剤
WO2022122042A1 (fr) Dérivé d'abiratérone et son procédé de préparation
KR20240012513A (ko) 세스퀴테르펜 유도체, 그의 약학적 조성물 및 그의 제조 방법과 용도
EP3560914A1 (fr) Amidine sulfonyle utilisée comme inhibiteur de l'indoleamine-2,3-dioxygénase, sa méthode de préparation et son utilisation
WO2019001307A1 (fr) Composé amide, composition le contenant, et utilisation associée
EP4006026A1 (fr) Classe de composés triaromatiques ciblant le site de phosphorylation bifonctionnel de stat3 et utilisations associées
CN109438279B (zh) 一种克服egfr耐药突变的小分子化合物及其制备方法和用途

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21902747

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 202180082961.X

Country of ref document: CN

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21902747

Country of ref document: EP

Kind code of ref document: A1