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WO2024146631A1 - Procédé de préparation d'inhibiteur de parp7 - Google Patents

Procédé de préparation d'inhibiteur de parp7 Download PDF

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Publication number
WO2024146631A1
WO2024146631A1 PCT/CN2024/070796 CN2024070796W WO2024146631A1 WO 2024146631 A1 WO2024146631 A1 WO 2024146631A1 CN 2024070796 W CN2024070796 W CN 2024070796W WO 2024146631 A1 WO2024146631 A1 WO 2024146631A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
formula
present application
alkyl
parp7
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.)
Ceased
Application number
PCT/CN2024/070796
Other languages
English (en)
Chinese (zh)
Other versions
WO2024146631A9 (fr
Inventor
李运波
齐宪亮
孙海峰
晋永
周家琪
陈家明
林栋�
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.)
Qilu Pharmaceutical Co Ltd
Original Assignee
Qilu Pharmaceutical 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 Qilu Pharmaceutical Co Ltd filed Critical Qilu Pharmaceutical Co Ltd
Priority to CN202480005763.7A priority Critical patent/CN120513238A/zh
Publication of WO2024146631A1 publication Critical patent/WO2024146631A1/fr
Publication of WO2024146631A9 publication Critical patent/WO2024146631A9/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings

Definitions

  • RBN-2397 developed by Ribon Therapeutics is the first PARP7 inhibitor to be tested in clinical trials. Its clinical trial data showed that RBN-2397 has a strong anti-tumor growth effect, and the growth is dose-dependent; more importantly, RBN-2397 induces tumor-specific adaptive immune memory. This suggests that PARP7 inhibitors may be excellent tumor treatment drugs. Given that PARP7 inhibitors have not yet been widely used in clinical practice, it is imperative to screen new PARP7 inhibitors for the benefit of cancer patients. Therefore, it is of great significance to explore and develop different varieties of PARP7 inhibitors.
  • the present application provides a method for preparing a compound represented by formula (I), wherein the compound represented by formula (II) is used as a raw material for synthesis.
  • R 1 is selected from C 1-4 alkyl, —NO 2 , and H.
  • the compound of formula (I) is prepared by reacting a compound of formula (II) with a compound of formula (III).
  • the compound of formula (I) is prepared by reacting a compound of formula (V) with a compound of formula (IV); the compound of formula (IV) is prepared by reacting a compound of formula (II) with piperazine or a derivative thereof.
  • the compound of formula (II) is prepared by condensation reaction of a compound of formula (VI) with a compound of formula (VII).
  • the solvent used in the above reaction is selected from polar organic solvents, preferably tetrahydrofuran, N,N-dimethylformamide One or more of amide and acetonitrile;
  • an acid-binding agent is added to the above reaction, and the acid-binding agent is an organic base or an inorganic base, preferably one or more of triethylamine and N,N-diisopropylethylamine.
  • the reagents used in the above reaction are selected from one or more of hydroiodic acid and trimethylsilane iodide;
  • the solvent used in the above reaction is selected from one or more of acetonitrile and tetrahydrofuran.
  • the compound of formula (IX) is reacted with a compound of formula (VIII) and a compound of formula (VII)
  • the compound is prepared by condensation reaction of phenyl dicarbonate.
  • R3 is selected from C1-4 alkyl
  • the solvent used in the above reaction is selected from polar organic solvents, preferably one or more of tetrahydrofuran, N,N-dimethylformamide, and acetonitrile;
  • the intravenous push dose was 1 mg/kg and the administration volume was 5 mL/kg; the oral dose was 5 mg/kg and the administration volume was 10 mL/kg.
  • the administration solvent was 5 vol% DMSO/5 vol% Kolliphor HS 15 (15-hydroxystearate polyethylene glycol)/90 vol% Saline (normal saline); DMSO was purchased from Sigma (Cat. No. D5879-1L), 15-hydroxystearate polyethylene glycol was purchased from Sigma (Cat. No. 42966-1KG), and normal saline was purchased from Shijiazhuang Siyao Group.
  • the centrifuge and pipette were purchased from Eppendorf.
  • Mobile phase A: 5mmol/L ammonium acetate aqueous solution (containing 0.05% formic acid); B: acetonitrile (containing 0.1% formic acid); flow rate: 0.5mL/min;

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Steroid Compounds (AREA)

Abstract

L'invention concerne un procédé de préparation d'un inhibiteur de PARP7. Le procédé se caractérise par un rendement réactionnel élevé, un temps de réaction court et un post-traitement simple, et est approprié pour une production à l'échelle industrielle. L'invention concerne en outre un intermédiaire pour la préparation d'un inhibiteur de PARP7 et un procédé de synthèse pour l'intermédiaire.
PCT/CN2024/070796 2023-01-06 2024-01-05 Procédé de préparation d'inhibiteur de parp7 Ceased WO2024146631A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202480005763.7A CN120513238A (zh) 2023-01-06 2024-01-05 一种parp7抑制剂的制备方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202310017629.6 2023-01-06
CN202310017629 2023-01-06

Publications (2)

Publication Number Publication Date
WO2024146631A1 true WO2024146631A1 (fr) 2024-07-11
WO2024146631A9 WO2024146631A9 (fr) 2024-08-15

Family

ID=91803629

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2024/070796 Ceased WO2024146631A1 (fr) 2023-01-06 2024-01-05 Procédé de préparation d'inhibiteur de parp7

Country Status (3)

Country Link
CN (1) CN120513238A (fr)
TW (1) TW202430518A (fr)
WO (1) WO2024146631A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101048399A (zh) * 2004-08-26 2007-10-03 库多斯药物有限公司 4－杂芳基甲基取代的酞嗪酮衍生物
CN101925595A (zh) * 2008-01-23 2010-12-22 阿斯利康(瑞典)有限公司 酞嗪酮衍生物
CN103130723A (zh) * 2011-11-30 2013-06-05 成都地奥制药集团有限公司 一种多聚（adp-核糖）聚合酶抑制剂
WO2020035065A1 (fr) * 2018-08-17 2020-02-20 南京明德新药研发有限公司 Dérivé de pyrazole en tant qu'inhibiteur de ret
CN112424188A (zh) * 2018-04-30 2021-02-26 里邦医疗公司 作为parp7抑制剂的哒嗪酮
WO2023006013A1 (fr) * 2021-07-29 2023-02-02 上海齐鲁制药研究中心有限公司 Nouvel inhibiteur de parp7 et son utilisation
WO2023020457A1 (fr) * 2021-08-17 2023-02-23 InventisBio Co., Ltd. Composés de pyridazinone ou pyridinone, leurs procédés de préparation et leurs utilisations

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101048399A (zh) * 2004-08-26 2007-10-03 库多斯药物有限公司 4－杂芳基甲基取代的酞嗪酮衍生物
CN101925595A (zh) * 2008-01-23 2010-12-22 阿斯利康(瑞典)有限公司 酞嗪酮衍生物
CN103130723A (zh) * 2011-11-30 2013-06-05 成都地奥制药集团有限公司 一种多聚（adp-核糖）聚合酶抑制剂
CN112424188A (zh) * 2018-04-30 2021-02-26 里邦医疗公司 作为parp7抑制剂的哒嗪酮
WO2020035065A1 (fr) * 2018-08-17 2020-02-20 南京明德新药研发有限公司 Dérivé de pyrazole en tant qu'inhibiteur de ret
WO2023006013A1 (fr) * 2021-07-29 2023-02-02 上海齐鲁制药研究中心有限公司 Nouvel inhibiteur de parp7 et son utilisation
WO2023020457A1 (fr) * 2021-08-17 2023-02-23 InventisBio Co., Ltd. Composés de pyridazinone ou pyridinone, leurs procédés de préparation et leurs utilisations

Also Published As

Publication number Publication date
WO2024146631A9 (fr) 2024-08-15
TW202430518A (zh) 2024-08-01
CN120513238A (zh) 2025-08-19

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