WO2020221006A1 - Inhibiteur de bet, son procédé de préparation et son utilisation - Google Patents

Inhibiteur de bet, son procédé de préparation et son utilisation Download PDF

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WO2020221006A1
WO2020221006A1 PCT/CN2020/084797 CN2020084797W WO2020221006A1 WO 2020221006 A1 WO2020221006 A1 WO 2020221006A1 CN 2020084797 W CN2020084797 W CN 2020084797W WO 2020221006 A1 WO2020221006 A1 WO 2020221006A1
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alkyl
hydrogen
cycloalkyl
halogen
cyano
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PCT/CN2020/084797
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Chinese (zh)
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郑永勇
魏农农
金华
周峰
黄美花
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上海勋和医药科技有限公司
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Publication of WO2020221006A1 publication Critical patent/WO2020221006A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • 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
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Definitions

  • the invention belongs to the technical field of biomedicine, and specifically relates to a BET protein inhibitor, a preparation method and application thereof.
  • Epigenetic is currently one of the most popular drug discovery topics. Histone acetylation is an important part of epigenetic research. Bromodomain (BRD) is a class of conserved protein domains that can specifically recognize acetylated lysine (KAc) in histones. By binding to acetylated lysine, it promotes protein enrichment at specific gene transcription sites and changes RNA The activity of polymerase II regulates the transcriptional expression of genes (Kuc and Allis, Bioessays, 1998, 20:615-626).
  • BTD Bromodomain
  • KAc acetylated lysine
  • BRD proteins are divided into 8 major families, and the BET protein family is the second type of BRD protein family.
  • BET protein includes four members of BRD2, BRD3, BRD4 and BRDT (Wu and Chiang, J. Biol. chem., 2007, 282: 13141-13145). The first three are widely expressed in all body cells, while the latter is only expressed in testicular tissues.
  • BET protein plays an important role in a variety of tumors.
  • hematopoietic tumors acute myeloid leukemia, lymphoma, multiple myeloma, B-cell acute lymphoblastic leukemia, etc.
  • BRD4 acute myeloid leukemia
  • MYC oncogene MYC
  • NUT a protein normally expressed only in the testis
  • BRD2, BRD3 and BRD4 gene knockout can damage the growth and viability of a variety of hematology and solid tumor cells (Zuber et al., Nature 2011, 478:524-528; Delmore et al., Cell 2011, 146:904-917 ).
  • BET protein also regulates the inflammatory response to bacterial attack, and the BRD2 suballelic mouse model shows significantly lower levels of inflammatory cytokines and prevents obesity-induced diabetes (Wang et al., Biochem J. 2009, 425:71-83).
  • viruses use these BET proteins to tether their genomes to host cell chromatin as part of the virus replication process, or use BET proteins to promote viral gene transcription and repression (You et al., Ce11 2004, 117:349-360; Zhu Et al., Cell Reports 2012, 2:807-816).
  • targeting these proteins may be beneficial for the development of new therapeutic strategies targeting cancer, inflammation and viral infections.
  • small molecule inhibitors targeting this receptor have entered the clinical stage and are mainly used for the treatment of cancer and autoimmune diseases.
  • BET inhibitor patent applications have been published, including: WO2013158952, WO2014165127, WO2015075665, WO2016050821, WO2018188047, WO2018130174, etc.
  • Abbive Company discloses a class of BET protein inhibitors in WO2013097052A. Among them, the compound ABBV-075 has development prospects and is currently in phase I clinical trials. Incyte company disclosed the compound INCB-057643 in the CN106414442A patent, which is in the phase I clinical trial. Bristol-Myers Squibb disclosed another type of BET protein inhibitor in WO2015100282A, representing that the compound BMS-986158 is in the phase I clinical trial. GlaxoSmithKline disclosed compound I-BET762 in WO2011054553A, which is currently undergoing tumor phase II clinical trials.
  • BET protein inhibitors Although there are no drugs on the market, BET protein inhibitors have good application prospects as drugs. At this stage, more novel bromodomain inhibitors for the treatment of diseases and indications involving the function of the bromodomain including the function of the BET domain are in urgent need of development.
  • the compounds of the present invention also help to meet such clinical needs, and we hope to develop a new generation of BET protein inhibitors with high efficiency and low toxicity.
  • the purpose of the present invention is to provide a BET protein inhibitor with high efficiency and low toxicity.
  • a BET protein inhibitor wherein the inhibitor is a compound of formula I:
  • A is selected from
  • Ring B is selected from Or a five-membered aromatic heterocyclic ring substituted by R 11 and/or R 12 ;
  • the "five-membered aromatic heterocyclic ring” refers to a monocyclic aromatic hydrocarbon of 5 atoms, and contains one or more heteroatoms (such as N , O, S), including but not limited to furan, imidazole, thiophene, pyrazole, etc. among them:
  • X is O, S or NR 13 ;
  • Z is CR 14 or N
  • U is CH or N
  • W is O or NH
  • V is CH or N
  • R 1 is hydrogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, substituted C 1 -C 6 alkyl, substituted C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl C 1 -C 6 alkyl, C 1 -C 6 alkyl -SO 2 -or C 3 -C 6 cycloalkyl -SO 2 -; the substituted C 1 -C 6 alkyl refers to C 1 -C 6 alkane
  • the hydrogen on the group is replaced by one or more C 3 -C 6 cycloalkyl;
  • the substituted C 3 -C 6 cycloalkyl means that the hydrogen on the C 3 -C 6 cycloalkyl group is replaced by one or more C 1 -C 6 alkyl substitution;
  • R 2 is hydrogen, C 1 -C 6 alkyl, C 1 -C 3 alkoxy, halogen or cyano;
  • R 3 is hydrogen, C 1 -C 6 alkyl, C 1 -C 3 alkoxy, halogen, cyano, -S(O) 2 R 15 , -S(O) 2 NR 16 R 17 or -N( R 16 )S(O) 2 R 15 ;
  • R 4 is hydrogen, C 1 -C 6 alkyl, C 1 -C 3 alkoxy, halogen or cyano;
  • R 5 and R 6 are each independently hydrogen or C 1 -C 6 alkyl
  • R 7 , R 8 , R 9 and R 10 are each independently hydrogen, halogen, cyano, C 1 -C 3 alkoxy or C 1 -C 6 alkyl;
  • R 11 is hydrogen or C 1 -C 6 alkyl
  • R 12 is hydrogen or C 1 -C 6 alkyl
  • R 13 is hydrogen or C 1 -C 6 alkyl
  • R 14 is hydrogen, C 1 -C 6 alkyl, halogen or cyano
  • R 15 is C 1 -C 6 alkyl
  • R 16 is hydrogen or C 1 -C 6 alkyl
  • R 17 is hydrogen or C 1 -C 6 alkyl
  • the aforementioned halogen is selected from fluorine, chlorine, bromine or iodine.
  • A is selected from
  • Ring B is selected from
  • X is O, S or NR 13 ;
  • Z is CR 14 or N
  • U is CH or N
  • W is O or NH
  • V is CH or N
  • R 1 is hydrogen, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, substituted C 1 -C 4 alkyl, substituted C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl C 1 -C 3 alkyl, C 1 -C 4 alkyl -SO 2 -or C 3 -C 6 cycloalkyl -SO 2 -; the substituted C 1 -C 4 alkyl refers to C 1 -C 4 alkyl
  • the hydrogen on the group is replaced by one or more C 3 -C 6 cycloalkyl;
  • the substituted C 3 -C 6 cycloalkyl means that the hydrogen on the C 3 -C 6 cycloalkyl group is replaced by one or more C 1 -C 4 alkyl substitution;
  • R 2 is hydrogen, C 1 -C 4 alkyl, C 1 -C 2 alkoxy, halogen or cyano;
  • R 3 is hydrogen, C 1 -C 4 alkyl, C 1 -C 2 alkoxy, halogen, cyano, -S(O) 2 R 15 , -S(O) 2 NR 16 R 17 or -N( R 16 )S(O) 2 R 15 ;
  • R 4 is hydrogen, C 1 -C 4 alkyl, C 1 -C 3 alkoxy, halogen or cyano;
  • R 5 and R 6 are each independently hydrogen or C 1 -C 4 alkyl
  • R 7 , R 8 , R 9 and R 10 are each independently hydrogen, halogen, cyano, C 1 -C 3 alkoxy or C 1 -C 4 alkyl;
  • R 11 is hydrogen or C 1 -C 4 alkyl
  • R 12 is hydrogen or C 1 -C 4 alkyl
  • R 13 is hydrogen or C 1 -C 4 alkyl
  • R 14 is hydrogen, C 1 -C 4 alkyl, halogen or cyano
  • R 15 is a C 1 -C 4 alkyl group
  • R 16 is hydrogen or C 1 -C 4 alkyl
  • R 17 is hydrogen or C 1 -C 4 alkyl
  • the aforementioned halogen is selected from fluorine, chlorine, bromine or iodine.
  • A is selected from
  • Ring B is selected from
  • X is O, S or NR 13 ;
  • Z is CR 14 or N
  • U is CH or N
  • W is O or NH
  • V is CH or N
  • R 1 is hydrogen, C 1 -C 3 alkyl, C 3 -C 6 cycloalkyl, substituted C 1 -C 3 alkyl, substituted C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl C 1- C 3 alkyl, C 1 -C 3 alkyl-SO 2 -or C 3 -C 6 cycloalkyl-SO 2 -; the substituted C 1 -C 3 alkyl refers to C 1 -C 3 alkyl
  • the hydrogen on the group is replaced by one or more C 3 -C 6 cycloalkyl;
  • the substituted C 3 -C 6 cycloalkyl means that the hydrogen on the C 3 -C 6 cycloalkyl group is replaced by one or more C 1 -C 3 alkyl substitution;
  • R 2 is hydrogen, C 1 -C 3 alkyl, C 1 -C 2 alkoxy, halogen or cyano;
  • R 3 is hydrogen, C 1 -C 3 alkyl, C 1 -C 2 alkoxy, halogen, cyano, -S(O) 2 R 15 , -S(O) 2 NR 16 R 17 or -N( R 16 )S(O) 2 R 15 ;
  • R 4 is hydrogen, C 1 -C 3 alkyl, C 1 -C 2 alkoxy, halogen or cyano;
  • R 5 and R 6 are each independently hydrogen or C 1 -C 3 alkyl
  • R 7 , R 8 , R 9 and R 10 are each independently hydrogen, halogen, cyano, C 1 -C 2 alkoxy or C 1 -C 3 alkyl;
  • R 11 is hydrogen or C 1 -C 3 alkyl
  • R 12 is hydrogen or C 1 -C 3 alkyl
  • R 13 is hydrogen or C 1 -C 3 alkyl
  • R 14 is hydrogen, C 1 -C 3 alkyl, halogen or cyano
  • R 15 is C 1 -C 3 alkyl
  • R 16 is hydrogen or C 1 -C 3 alkyl
  • R 17 is hydrogen or C 1 -C 3 alkyl
  • the aforementioned halogen is selected from fluorine, chlorine, bromine or iodine.
  • halogen in this application refers to F, Cl, Br or I;
  • C 1 -C 3 alkyl refers to methyl, ethyl, n-propyl or isopropyl;
  • C 1 -C 2 alkoxy means methoxy or ethoxy;
  • the "cycloalkyl”, unless otherwise specified, means saturated or partially unsaturated containing 3-6 carbon atoms Cyclic hydrocarbon.
  • Cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, and cyclohexenyl.
  • the compounds of the present invention can be prepared in the form of pharmaceutical salts according to conventional methods; including their organic acid salts and inorganic acid salts: inorganic acids include (but are not limited to) hydrochloric acid, sulfuric acid, phosphoric acid, diphosphoric acid, hydrobromic acid, nitric acid, etc., Organic acids include, but are not limited to, acetic acid, maleic acid, fumaric acid, tartaric acid, succinic acid, lactic acid, p-toluenesulfonic acid, salicylic acid, oxalic acid and the like.
  • inorganic acids include (but are not limited to) hydrochloric acid, sulfuric acid, phosphoric acid, diphosphoric acid, hydrobromic acid, nitric acid, etc.
  • Organic acids include, but are not limited to, acetic acid, maleic acid, fumaric acid, tartaric acid, succinic acid, lactic acid, p-toluenesulfonic acid, salicylic acid,
  • Typical compounds of the present invention include, but are not limited to the following compounds in Table 1:
  • the second objective of the present invention is to provide a synthetic method of the above compound:
  • the compound of the general formula IA and the compound of the general formula IB are catalyzed and coupled to produce the compound I of the general formula, and the definition of each group is as described above.
  • the third object of the present invention is to provide the use of the above compound as a novel BET protein inhibitor in the preparation of drugs for preventing or treating diseases related to BET protein.
  • the diseases related to the BET protein refer to tumor diseases, benign hyperplasia, inflammatory diseases, autoimmune diseases, sepsis, viral infections, vascular diseases and neurological diseases.
  • the tumor diseases include, but are not limited to, acute myeloid leukemia, lymphoma, multiple myeloma, B-cell acute lymphoid leukemia, midline cancer, glioma, solid tumor, breast cancer, colorectal cancer, prostate cancer , Cervical cancer, non-small cell lung cancer, melanoma, etc.
  • the derivatives of the present invention can be formed into a composition by oral, injection, etc., to treat related cancers and other diseases.
  • oral administration it can be prepared into conventional solid preparations such as tablets, powders or capsules; when used for injection, it can be prepared into injections.
  • the fourth object of the present invention is to provide a composition comprising a therapeutically effective amount of the above-mentioned compound or a pharmaceutically acceptable salt thereof and a medically acceptable carrier.
  • the carrier mentioned refers to the conventional carriers in the pharmaceutical field, such as diluents, excipients such as water, etc.; binders such as cellulose derivatives, gelatin, polyvinylpyrrolidone, etc.; fillers such as starch, etc.; disintegrating agents such as carbonic acid Calcium, sodium bicarbonate; in addition, other auxiliary agents such as flavoring and sweetening agents can also be added to the composition.
  • diluents such as water, etc.
  • binders such as cellulose derivatives, gelatin, polyvinylpyrrolidone, etc.
  • fillers such as starch, etc.
  • disintegrating agents such as carbonic acid Calcium, sodium bicarbonate
  • other auxiliary agents such as flavoring and sweetening agents can also be added to the composition.
  • composition of the present invention can be prepared by conventional methods in the medical field, and the content of the active ingredient is 0.1%-99.5% (weight ratio).
  • the dosage of the present invention can be changed according to the route of administration, the age, weight of the patient, the type and severity of the disease to be treated, etc.
  • the daily dosage is 0.005-30mg/kg body weight (oral) or 0.005-30mg/kg body weight ( injection).
  • the present invention further improves the structure on the basis of the existing BET protein inhibitor, and obtains a new structure of BET protein inhibitor, which has better BET protein inhibitory activity and good pharmacokinetics It is expected to be developed into a new generation of high-efficiency and low-toxicity BET protein inhibitor.
  • Reference example 1 Synthetic route of fragment A1.
  • Reference example 2-7 Fragments A2 ⁇ A7.
  • Reference example 13-53 Fragment C2 ⁇ C42.
  • Reference Example 54 Synthetic route of fragments C43 and C44.
  • Reference example 55-56 Fragment C45 ⁇ C46.
  • Reference example 58-60 Fragment C48-C50.
  • the final concentration of the test compound and the positive control compound AbbV-075 and I-BET762 are all starting at 1000 nM, and the concentration is 3 times diluted to 10 concentrations, and each concentration is set for two multiple well tests.
  • the compound was diluted with DMSO as the solvent to a solution of 1000 times the final concentration, and then the DMSO solution of the corresponding concentration was diluted 100 times with a 1 ⁇ Assay buffer (the DMSO concentration was 1% at this time), and 2 ⁇ L of the compound was transferred with a discharge gun. Transfer the DMSO solution to a 384-well reaction plate to be tested. Transfer 2 ⁇ L of 1% DMSO solution into the Max well, and transfer 2 ⁇ L of the AbbV-075 highest concentration 1% DMSO solution into the Min well.
  • MV4-11 cells acute myeloid leukemia
  • 100 ⁇ L growth medium RPMI1640, 10% FCS
  • C1 value the fluorescence value
  • C0 value the fluorescence value
  • the compound of the present invention has significantly better BRD4 binding activity than ABBV-075 and INCB-057643; the compound of the present invention has obvious inhibitory activity on the proliferation of leukemia cells MV4-11, and the inhibitory activity is better than ABBV-075 and INCB-057643.
  • the LC/MS/MS method was used to determine that the rats were intragastrically administered ABBV-075 and the preferred embodiment compounds of the present invention, and then the drug concentration in the plasma at different times was measured to study the compounds of the present invention in Pharmacokinetic characteristics in rats.
  • Administration method single intragastric administration
  • Standard curve and quality control sample preparation and processing Take an appropriate amount of stock solution and dilute with 50% acetonitrile water into a standard working solution of 0.04, 0.10, 0.20, 0.40, 1.00, 2.00, 4.00 ⁇ g/mL, 0.10, 1.00, 3.00 ⁇ g/mL Quality control working fluid.
  • the compounds of the examples of the present invention show good pharmacokinetic properties. Compared with ABBV-075, the blood concentration and curve area are higher, the half-life is longer, and the residence time is shorter.
  • mice were inoculated subcutaneously with MV4-11 cells to establish a MV4-11 nude mouse xenograft model. 13 days after inoculation (d13), the average tumor volume is about 215mm3. According to the tumor volume, the tumor-bearing mice are divided into groups by random block method, including solvent control group, control sample INCB-057643 group, and test sample group, each with 6 only. Each group was given intragastric administration with a dose of 30mg/kg and a volume of 10ml/kg, once a day for 14 consecutive days. The solvent control group was given a blank solvent (50mM sodium lactate aqueous solution, PH4.0). Tumors were measured and weighed twice a week after the test drug was started. After the experiment, the animals were euthanized.
  • solvent control group was given a blank solvent (50mM sodium lactate aqueous solution, PH4.0).
  • Table 12 shows the efficacy results of the preferred compounds of the present invention in animals.
  • the compounds of the examples of the present invention show good anti-tumor activity. Compared with the control group INCB-057643, the anti-tumor activity is more significant.

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Abstract

La présente invention concerne le domaine technique de la biomédecine, et concerne spécifiquement un inhibiteur de BET, son procédé de préparation et son utilisation. La présente invention améliore la structure d'inhibiteurs de BET de la technique antérieure pour obtenir une classe d'inhibiteurs de BET ayant une nouvelle structure, une meilleure activité d'inhibition de BET et une bonne pharmacocinétique, et a des perspectives de développement en tant qu'inhibiteur de BET de faible toxicité et très efficace.
PCT/CN2020/084797 2019-04-30 2020-04-14 Inhibiteur de bet, son procédé de préparation et son utilisation WO2020221006A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023245297A1 (fr) * 2022-06-23 2023-12-28 University Of Ottawa Inhibiteurs de la ferroptose et leurs utilisations

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110003204B (zh) * 2019-04-30 2020-08-11 上海勋和医药科技有限公司 一种bet蛋白抑制剂、其制备方法及用途
CN113461538A (zh) * 2021-07-12 2021-10-01 无锡双启科技有限公司 一种2-氯-3-溴苯胺的制备方法

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WO2014134267A1 (fr) * 2013-02-27 2014-09-04 Bristol-Myers Squibb Company Composés de carbazole utiles en tant qu'inhibiteurs de bromodomaine
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