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WO2025242012A1 - Chimères de dégradation ciblant des protéines et leur utilisation - Google Patents

Chimères de dégradation ciblant des protéines et leur utilisation

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Publication number
WO2025242012A1
WO2025242012A1 PCT/CN2025/095596 CN2025095596W WO2025242012A1 WO 2025242012 A1 WO2025242012 A1 WO 2025242012A1 CN 2025095596 W CN2025095596 W CN 2025095596W WO 2025242012 A1 WO2025242012 A1 WO 2025242012A1
Authority
WO
WIPO (PCT)
Prior art keywords
mmol
piperidin
dioxopiperidin
esi
yield
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
PCT/CN2025/095596
Other languages
English (en)
Chinese (zh)
Inventor
姜正羽
尤启冬
陈学涛
徐如俊
康文静
吴慧丹
吴婷婷
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
China Pharmaceutical University
Ascentage Pharma Suzhou Co Ltd
Original Assignee
China Pharmaceutical University
Ascentage Pharma Suzhou Co Ltd
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 China Pharmaceutical University, Ascentage Pharma Suzhou Co Ltd filed Critical China Pharmaceutical University
Publication of WO2025242012A1 publication Critical patent/WO2025242012A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • 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
    • C07D498/06—Peri-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

  • This invention belongs to the field of medicinal chemistry, specifically relating to a class of protein-targeted degradation chimeras and their uses.
  • B-cell lymphokine 6 plays a crucial role in humoral immune responses. It is a human gene of approximately 24 kb, encoding a protein of about 95 kDa. BCL6 is a member of the POZ/BTB/Zinc finger protein family and is primarily composed of three parts: 1) The N-terminal POZ/BTB domain: This is the main functional region responsible for transcriptional repression. When BCL6 exerts its transcriptional repression function, the BTB domain spontaneously forms a dimer. Three important transcriptional co-repressors, SMRT, BCOR, or NCOR, competitively bind to the BTB binding site, collectively exerting transcriptional repression.
  • the central region also known as the RD2 domain
  • the C-terminal zinc finger domain consists of six identical zinc finger structures, primarily binding to DNA and is a prerequisite for BCL6's transcriptional repression function.
  • BCL6 is a transcriptional repressor that recruits co-repressors through its BTB domain.
  • BCL6 protein is overexpressed in lymphoma, breast cancer, ovarian cancer, non-small cell lung cancer, and glioma, and is closely associated with poor patient prognosis. When BCL6 protein is highly expressed, the p53 tumor suppressor gene is almost absent. In GC responses, chromosomal translocations and point mutations of BCL6 lead to persistently high BCL6 protein expression, promoting malignant proliferation of B cells and resulting in B-cell lymphoma. Most non-Hodgkin lymphomas (NHL) originate from GC, with diffuse large B-cell lymphoma (DLBCL) being the most common subtype.
  • NHL non-Hodgkin lymphomas
  • BCL6 is considered a carcinogenic driver of DLBCL.
  • Numerous preclinical studies have also shown that blocking the interaction between the BCL6-BTB domain and its transcriptional co-repressors can inhibit GC formation and NHL cell proliferation, representing an effective and safe treatment strategy for NHL without toxic side effects or macrophage-driven inflammatory responses.
  • BCL6 is a highly promising target for cancer therapy, including but not limited to Hodgkin's lymphoma, B-cell non-Hodgkin's lymphoma, T-cell non-Hodgkin's lymphoma, NK/T-cell non-Hodgkin's lymphoma, and diffuse large B-cell lymphoma.
  • BCL6 drugs in development, categorized into small molecule inhibitors (8 classes), protein-targeted degradation chimeras (5 classes), and molecular gels (5 classes).
  • BMS-986458 Only BMS's PROTAC drug (BMS-986458) has entered Phase I clinical trials. Therefore, developing novel small molecule degraders that balance druggability and safety, and can rapidly and efficiently degrade BCL6 remains urgent and necessary.
  • the purpose of this invention is to provide a class of BCL6 protein-targeted degradation chimeras and their uses.
  • L is the Linker connecting POI and E3L;
  • E3L is independently selected from:
  • R1 , R2 , R3 , R4 , R5 , R6, R7, R8, R9 , R10 , R11, R12 , R13 , R14 , R15 , R16 , R17, R18 , R19 , R20 , and R21 are independently selected from -H, halogen, -C1 to C3 alkyl, -C1 to C3 haloalkyl, and -C1 to C3 alkoxy.
  • R 22 is independently selected from -H, -C1 to -C3 alkyl groups
  • POIs are selected independently from:
  • R 23 is independently selected from -H and halogens
  • R24 and R25 are independently selected from -H and -C1 to C3 alkyl groups
  • L is selected independently from:
  • n 1, 2 or 3.
  • a compound or a pharmaceutically acceptable salt or solvate thereof showing one of the following chemical structures:
  • a pharmaceutical composition comprising the above-mentioned compound or a pharmaceutically acceptable salt or solvate thereof.
  • the disease is cancer.
  • the cancer is Hodgkin lymphoma, B-cell non-Hodgkin lymphoma, T-cell non-Hodgkin lymphoma, NK/T-cell non-Hodgkin lymphoma, or diffuse large B-cell lymphoma.
  • the above pharmaceutical composition is used for the preparation of a medicament for treating a disease that is treated or alleviated by degrading BCL6 protein.
  • the disease is cancer.
  • the cancer is Hodgkin lymphoma, B-cell non-Hodgkin lymphoma, T-cell non-Hodgkin lymphoma, NK/T-cell non-Hodgkin lymphoma, or diffuse large B-cell lymphoma.
  • a method of treating a disease comprising administering to an individual suffering from the disease a therapeutically effective amount of any of the above-mentioned compounds or a pharmaceutically acceptable salt or solvate thereof, or administering a therapeutically effective amount of the above-mentioned pharmaceutical composition; wherein the disease is a disease that is treated or alleviated by degrading BCL6 protein.
  • the disease is cancer.
  • the cancer is Hodgkin lymphoma, B-cell non-Hodgkin lymphoma, T-cell non-Hodgkin lymphoma, NK/T-cell non-Hodgkin lymphoma, or diffuse large B-cell lymphoma.
  • the compounds provided by this invention, or their pharmaceutically acceptable salts or solvates are protein-targeting degradation chimeras with novel chemical structures. These compounds, or their pharmaceutically acceptable salts or solvates, exhibit excellent degradation activity against BCL6 protein and can be used to prepare BCL6 degrading agents. They have the potential to be developed into drugs for treating or alleviating diseases by degrading BCL6 protein. These diseases include cancers such as Hodgkin lymphoma, B-cell non-Hodgkin lymphoma, T-cell non-Hodgkin lymphoma, NK/T-cell non-Hodgkin lymphoma, and diffuse large B-cell lymphoma.
  • Examples 1-3 were synthesized according to synthetic route 2.
  • Synthetic Route 2 Reagents and Conditions: (a) NaBH(OAc) 3 , DCE, rt, 3h; (b) H2 , Pd/C, EtOH, rt, 16h; (c) DIPEA, DMSO, 100°C, 3h; (d) TFA, DCM, rt, 1h; (e) DIPEA, NMP, 170°C, microwave, 3h.
  • Example 4 was synthesized according to synthesis route 3.
  • Synthetic Route 3 Reagents and Conditions: (a) Pd(OAc) 2 , Xantphos, Cs2CO3 , dioxane , 110°C, 10h; (b) LiOH, MeOH, H2O , 40°C, 10h; (c) EDCI, HOBt, DIPEA, DMF, 25°C, 10h; (d) TFA, DCM, rt, 1h; (e) DIPEA, NMP, 170°C, microwave, 3h.
  • Examples 5 and 6 were synthesized according to synthesis route 4.
  • Synthetic Route 4 Reagents and Conditions: (a) NaBH(OAc) 3 , DCE, rt, 12h; (b) TFA, DCM, rt, 3h; (c) DIPEA, DMSO, 100°C, 3h; (d) H2 , Pd/C, EtOH, rt, 16h; (e) DIPEA, NMP, microwave, 170°C, 3h.
  • Example 5 Following general synthesis method 5, using 34a (132 mg, 0.28 mmol) as the reactant, the target product, a yellow solid, was obtained in Example 5 (18 mg, yield: 9.1%).
  • Examples 7-9 were synthesized according to synthetic route 5.
  • Synthetic Route 5 Reagents and Conditions: (a) NaBH(OAc) 3 , DCE, rt, 3h; (b) H2 , Pd/C, EtOH, rt, 16h; (c) DIPEA, DMSO, 100°C, 3h; (d) TFA, DCM, rt, 1h; (e) DIPEA, DMSO, 100°C, 10h; (f) DIPEA, EDCI, HOBt, DMF, rt, 12h.
  • Examples 10-11 were synthesized according to synthetic route 6.
  • Synthetic Route 6 Reagents and Conditions: (a) ( PPh3 ) 3 RhCl, EtOH, 80°C, 18h; (b) KI, pyridine, 115°C, 12h; (c) TFA, DCM, rt, 3h; (d) AcOH, NaBH(OAc) 3 , DCE, rt, 3h; (e) TFA, DCM, rt, 3h; (f) EDCI, HOBt, DIPEA, DMF, rt, 12h.
  • Examples 12-16 were synthesized according to synthetic route 7.
  • Synthetic Route 7 Reagents and Conditions: (a) DIPEA, DMSO, 100°C, 3h; (b) TFA, DCM, rt, 1h; (c) NaBH(OAc) 3 , DCE, rt, 5h; (d) TFA, DCM, rt, 1h; (e) DIPEA, EDCI, HOBt, DMF, rt, 12h.
  • Examples 17-18 were synthesized according to synthetic route 8.
  • Synthetic Route 8 Reagents and Conditions: (a ) Cs2CO3 , Xantphos, Pd2 (dba) 3 , dioxane, 100°C for 4h; ( b) Cs2CO3, PdCl2(dppf)CH2Cl2, dioxane, 100°C for 4h; (c) H2 , Pd / C , THF, 12h; (d) TFA, DCM, 3h; (e) NaBH(OAc) 3 , DCE, 6h; (f) TFA, DCM, 3h; (g) EDCI, HOBt, DIPEA, DMF, 12h.
  • Example 19 was synthesized according to synthetic route 9.
  • Synthetic Route 9 Reagents and Conditions: (a) K2CO3 , DMF, 60°C, 4h; (b ) H2 , Pd/C, EtOH, rt, 6h; (c) NaHCO3 , DMF, 80°C, 16h; (d) TFA, DCM, rt, 3h; (e) NaBH(OAc) 3 , DCE, rt, 5h; (f) TFA, DCM, rt, 2h; (g) DIPEA, EDCI, HOBt, rt, 12h.
  • Synthetic Method 13 55 (400 mg, 2.51 mmol), 47b (604 mg, 2.51 mmol), and potassium carbonate (695 mg, 5.03 mmol) were added to a round-bottom flask, followed by 10 mL of DMF solution. The mixture was stirred at 60 °C for 4 h, and the reaction was monitored by TLC until complete. After cooling to room temperature, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.
  • Synthetic Method 14 57 (800 mg, 2.29 mmol), 57a (1.10 g, 5.72 mmol), and sodium bicarbonate (1.92 g, 22.90 mmol) were added to a round-bottom flask, followed by 15 mL of DMF solution. The mixture was stirred at 85 °C for 16 h, and the reaction was monitored by TLC until complete. After cooling to room temperature, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.
  • Example 20 was synthesized according to synthesis route 10.
  • Synthetic Route 10 Reagents and Conditions: (a) K2CO3 , DMF, 60°C, 4h; (b ) H2 , Pd/C, EtOH, rt, 6h; (c) NaHCO3 , DMF, 80°C, 16h; (d) TFA, DCM, rt, 3h; (e) DIPEA, EDCI, HOBt, rt, 12h.
  • Example 21 was synthesized according to synthetic route 11.
  • Synthetic Route 11 Reagents and Conditions: (a) Cs2CO3 , Xantphos , Pd(OAc) 2 , dioxane, 110°C, 10h; (b) LiOH, MeOH, H2O , rt, 12h; (c) EDCI, HOBt, TEA, DMF, 12h; (d) TFA, DCM, 3h; (e) NaBH(OAc) 3 , DCE, 6h; (f) TFA, DCM, 3h; (g) EDCI, HOBt, DIPEA, DMF, 12h.
  • intermediate 63 (200 mg, 0.46 mmol) was added to a round-bottom flask containing a methanol:water mixture of 8 mL:2 mL, followed by lithium hydroxide (55 mg, 2.30 mmol). The reaction was carried out at 40 °C for 10 hours, and TLC was used to monitor the completeness of the reaction. After the reaction cooled to room temperature, dilute hydrochloric acid was added to adjust the pH of the solution to 5–6. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.
  • intermediate 64 (180 mg, 0.43 mmol) was added to a round-bottom flask containing 5 mL of LDM solution, followed by DIPEA (276 mg, 2.14 mmol), EDCI (123 mg, 0.64 mmol), and HOBt (87 mg, 0.64 mmol). The mixture was stirred at room temperature for half an hour, then 27a (83 mg, 0.51 mmol) was added, and the reaction was allowed to proceed overnight at room temperature. The reaction was monitored by TLC until complete. Extraction was performed with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.
  • Example 22 was synthesized according to synthetic route 12.
  • Synthetic Route 12 Reagents and Conditions: (a) DIPEA, DMSO, 100°C, 10h; (b) Dys-Martin oxidant, DMF, 100°C, 2h; (c) NaBH(OAc) 3 , DCE, 6h.
  • Example 23 was synthesized according to synthetic route 13.
  • Synthetic Route 13 Reagents and Conditions: (a ) Na2CO3 , Pd(PPh) 3Cl2 , dioxane , 110°C, 4h; (b) Pd/C, EtOH, rt, 16h; (c) LiOH, MeOH, H2O , rt, 16h; (d) BuLi, THF, DMF, -78°C, 6h; (e) K2CO3 , DMF, rt, 5h; ( f ) NaBH3CN , DIPEA, DCE; (g) TFA, DCM, 3h; (h) Dimethylchlorosilane, ACN, 6h; (i) Pd/C, H2 , rt, 12h; Boc2O , EtOH, THF, rt, 3h; ( j ) Tf2O , TEA, DCM, rt, 3h; (k) K2CO3 ,DMF,70°C,4
  • Example 24 was synthesized according to synthetic route 14.
  • Synthetic Route 14 Reagents and Conditions: (a) N,N-dimethyl-bromoacetamide, Cs2CO3 , DMF , rt, 3h; (b) Fe, NH4Cl , EtOH, H2O , 80°C, 3h; (c) DIPEA, DMSO, 100°C, 3h; (d) DIPEA, DMSO, 100°C, 10h; (e) DIPEA, EDCI, HOBt, rt, 12h.
  • BCL6 protein degradation assay OCI-LY1 cells (Zhejiang Meisen Cell Technology Co., Ltd.) were seeded in 6-well plates, and different concentrations of the compound were added. Twelve hours after drug administration, cells were collected by centrifugation, mixed with medium-efficiency RIPA lysis buffer (Beyotime Biotechnology), and centrifuged again. The supernatant was collected, and protein concentration was determined by the BCA method. Protein samples were mixed with protein loading buffer (Beyotime Biotechnology) and heated dry at 100°C for 10 min for sample preparation. The samples were then added to a 12% polyacrylamide gel SDS-PAGE. Electrophoresis was performed at 60V until the marker left the stacking gel, followed by continued electrophoresis at 120V.
  • the membrane was transferred to a wet transfer buffer containing 10% methanol for 90 min.
  • the transferred PVDF membrane was then cut into desired bands, blocked with milk for 2 hours, and anti-BCL6 antibody (abcam) and ⁇ -Actin antibody (Proteintech) diluted with milk were added to the corresponding bands, respectively, and incubated overnight at 4°C.
  • the primary antibody was washed away with TBST, and the membrane was incubated with secondary antibody at room temperature for 45 min.
  • the secondary antibody solution was then washed away again with TBST, and the membrane was scanned using an Odyssey Infrared Imaging System (LI-COR, Lincoln, Iowa, USA).
  • DC 50 refers to the concentration of the BCL6 degrading agent required to achieve 50% degradation of BCL6 protein.
  • the calculation process is as follows: Starting from 1000 nM, the degrading agent was serially diluted 5-fold to nine concentrations, and the degradation of BCL6 protein at each concentration was detected by Western blotting. Grayscale analysis was performed using ImageJ software to calculate the remaining amount of BCL6. The DC 50 value was obtained by fitting the logarithm (Log(C)) of the remaining protein amount and concentration using Graphpad 8.0 software.
  • Cell antiproliferative activity assay Cells in logarithmic growth phase were seeded at a density of 5000 cells per well in 96-well plates (Coring, 3799) with 100 ⁇ L of RPMI 1640 medium (Adamas) containing 20% FBS and incubated overnight at 37°C in a 5% CO2 incubator. The next day, 100 ⁇ L of different concentrations of drug solution prepared in the medium were added, with three replicates for each concentration (denoted as RLU test ), and control and blank wells were also included. The control wells contained cells, culture medium, and the same concentration of drug solution (denoted as RLU control ), while the blank wells contained culture medium (denoted as RLU blank ).

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

Abstract

L'invention concerne des chimères de dégradation ciblant des protéines et leur utilisation. Les chimères de dégradation ciblant des protéines ont une nouvelle structure chimique, présentent un effet de dégradation important sur la protéine BCL6, peuvent être utilisées pour préparer des médicaments de dégradation de BCL6, et ont le potentiel d'être développées dans un médicament pour le traitement de maladies qui peuvent être traitées ou atténuées au moyen de la dégradation de la protéine BCL6. Les maladies qui peuvent être traitées ou atténuées au moyen de la dégradation de la protéine BCL6 comprennent des cancers tels qu'un lymphome de Hodgkin, un lymphome non hodgkinien dérivé des cellules B, un lymphome non hodgkinien dérivé des cellules T, un lymphome non hodgkinien dérivé des cellules NK/T et un lymphome diffus à grandes cellules B.
PCT/CN2025/095596 2024-05-21 2025-05-17 Chimères de dégradation ciblant des protéines et leur utilisation Pending WO2025242012A1 (fr)

Applications Claiming Priority (2)

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CN202410630323.2A CN120987969A (zh) 2024-05-21 2024-05-21 一类蛋白靶向降解嵌合体及其用途
CN202410630323.2 2024-05-21

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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1087639A (zh) * 1992-01-27 1994-06-08 藤泽药品工业株式会社 杂三环衍生物
WO2018108704A1 (fr) * 2016-12-13 2018-06-21 Boehringer Ingelheim International Gmbh Nouveaux composés 6-amino-quinolinone et dérivés en tant qu'inhibiteurs de bcl6
CN112334475A (zh) * 2018-04-13 2021-02-05 癌症研究技术有限公司 Bcl6抑制剂
CN115397821A (zh) * 2019-10-17 2022-11-25 阿尔维纳斯运营股份有限公司 含有与bcl6靶向部分连接的e3泛素连接酶结合部分的双官能分子
WO2023114460A1 (fr) * 2021-12-17 2023-06-22 Dana-Farber Cancer Institute, Inc. Agents de dégradation de bcl6 et leurs utilisations
WO2023232133A1 (fr) * 2022-06-02 2023-12-07 西藏海思科制药有限公司 Composé pour inhiber ou dégrader bcl6 et son utilisation en pharmacie
CN117279910A (zh) * 2021-04-16 2023-12-22 阿尔维纳斯运营股份有限公司 Bcl6蛋白水解的调节剂和其相关使用方法
WO2024193464A1 (fr) * 2023-03-17 2024-09-26 西藏海思科制药有限公司 Dérivé tricyclique contenant de l'azote et son utilisation en médecine
WO2025049964A1 (fr) * 2023-09-01 2025-03-06 Treeline Biosciences, Inc. Agents de dégradation bifonctionnels bcl6

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1087639A (zh) * 1992-01-27 1994-06-08 藤泽药品工业株式会社 杂三环衍生物
WO2018108704A1 (fr) * 2016-12-13 2018-06-21 Boehringer Ingelheim International Gmbh Nouveaux composés 6-amino-quinolinone et dérivés en tant qu'inhibiteurs de bcl6
CN112334475A (zh) * 2018-04-13 2021-02-05 癌症研究技术有限公司 Bcl6抑制剂
CN115397821A (zh) * 2019-10-17 2022-11-25 阿尔维纳斯运营股份有限公司 含有与bcl6靶向部分连接的e3泛素连接酶结合部分的双官能分子
CN117279910A (zh) * 2021-04-16 2023-12-22 阿尔维纳斯运营股份有限公司 Bcl6蛋白水解的调节剂和其相关使用方法
WO2023114460A1 (fr) * 2021-12-17 2023-06-22 Dana-Farber Cancer Institute, Inc. Agents de dégradation de bcl6 et leurs utilisations
WO2023232133A1 (fr) * 2022-06-02 2023-12-07 西藏海思科制药有限公司 Composé pour inhiber ou dégrader bcl6 et son utilisation en pharmacie
WO2024193464A1 (fr) * 2023-03-17 2024-09-26 西藏海思科制药有限公司 Dérivé tricyclique contenant de l'azote et son utilisation en médecine
WO2025049964A1 (fr) * 2023-09-01 2025-03-06 Treeline Biosciences, Inc. Agents de dégradation bifonctionnels bcl6

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