CN112867708A - 一种mdm2抑制剂，及其制备方法、药物组合物和应用 - Google Patents

一种mdm2抑制剂，及其制备方法、药物组合物和应用 Download PDF

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CN112867708A
CN112867708A CN201980064565.7A CN201980064565A CN112867708A CN 112867708 A CN112867708 A CN 112867708A CN 201980064565 A CN201980064565 A CN 201980064565A CN 112867708 A CN112867708 A CN 112867708A
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chlorophenyl
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CN112867708B (zh
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王喆
曾志宏
江荣珍
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Shanghai Longwood Biopharmaceuticals Co Ltd
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Shanghai Longwood Biopharmaceuticals Co Ltd
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D211/74—Oxygen atoms
    • C07D211/76—Oxygen atoms attached in position 2 or 6
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D211/74—Oxygen atoms
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/45—Non condensed piperidines, e.g. piperocaine having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • 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
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • 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

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

Abstract

涉及一种MDM2抑制剂、其制备方法、其药物组合物和应用。具体地，涉及一种如式I所示的化合物，所述的化合物具有优异的MDM2抑制活性，可用于制备治疗癌症和其他MDM2活性相关疾病的药物组合物，特别是，p53野生型癌症。

Description

PCT国内申请，说明书已公开。

Claims (10)

  1. PCT国内申请，权利要求书已公开。
CN201980064565.7A 2018-09-30 2019-09-30 一种mdm2抑制剂，及其制备方法、药物组合物和应用 Active CN112867708B (zh)

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CN201811160163.0A CN110963958A (zh) 2018-09-30 2018-09-30 一种mdm2抑制剂，及其制备方法、药物组合物和应用
CN2018111601630 2018-09-30
PCT/CN2019/109428 WO2020064004A1 (zh) 2018-09-30 2019-09-30 一种mdm2抑制剂，及其制备方法、药物组合物和应用

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US (1) US11299460B2 (zh)
EP (1) EP3858812A4 (zh)
JP (1) JP7338896B2 (zh)
KR (1) KR102610545B1 (zh)
CN (2) CN110963958A (zh)
AU (1) AU2019351530B2 (zh)
WO (1) WO2020064004A1 (zh)

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Publication number Priority date Publication date Assignee Title
CN114853731A (zh) * 2021-02-04 2022-08-05 上海长森药业有限公司 一种双功能mdm2蛋白降解剂，及其制备方法、药物组合物和应用
WO2023089375A1 (en) * 2021-11-22 2023-05-25 Ligature Therapeutics Pte, Ltd. Therapeutic compounds and methods of use thereof

Citations (3)

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Publication number Priority date Publication date Assignee Title
CN103180296A (zh) * 2010-06-04 2013-06-26 安姆根有限公司 用于治疗癌症的作为mdm2抑制剂的哌啶酮衍生物
CN105121407A (zh) * 2013-02-28 2015-12-02 美国安进公司 用于治疗癌症的苯甲酸衍生物mdm2抑制剂
CN105358530A (zh) * 2013-06-10 2016-02-24 美国安进公司 制备mdm2抑制剂的方法及其结晶形式

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MX352672B (es) * 2011-09-27 2017-12-04 Amgen Inc Compuestos heterocíclicos como inhibidores de mdm2 para el tratamiento del cáncer.
MA39094B1 (fr) * 2013-11-11 2020-06-30 Amgen Inc Polythérapie comprenant un inhibiteur de mdm2 et un ou plusieurs principes pharmaceutiquement actifs supplémentaires pour le traitement de cancers
US11192898B2 (en) * 2016-04-06 2021-12-07 The Regents Of The University Of Michigan MDM2 protein degraders
CA3020281A1 (en) * 2016-04-06 2017-10-12 The Regents Of The University Of Michigan Monofunctional intermediates for ligand-dependent target protein degradation
CA3043004A1 (en) * 2016-11-15 2018-05-24 Novartis Ag Dose and regimen for hdm2-p53 interaction inhibitors

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CN105153014A (zh) * 2010-06-04 2015-12-16 安姆根有限公司 用于治疗癌症的作为mdm2抑制剂的哌啶酮衍生物
CN105121407A (zh) * 2013-02-28 2015-12-02 美国安进公司 用于治疗癌症的苯甲酸衍生物mdm2抑制剂
CN105358530A (zh) * 2013-06-10 2016-02-24 美国安进公司 制备mdm2抑制剂的方法及其结晶形式

Non-Patent Citations (3)

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Title
ANA Z. GONZALEZ ET AL: ""Novel Inhibitors of the MDM2-p53 Interaction Featuring Hydrogen Bond Acceptors as Carboxylic Acid Isosteres"", 《JOURNAL OF MEDICINAL CHEMISTRY》, vol. 57, no. 7, 6 May 2014 (2014-05-06), pages 2963 - 2988, XP055116598, DOI: 10.1021/jm401911v *
ANA Z. GONZALEZ ET AL: ""Selective and Potent Morpholinone Inhibitors of the MDM2−p53 Protein−Protein Interaction"", 《JOURNAL OF MEDICINAL CHEMISTRY》, vol. 57, 18 February 2014 (2014-02-18), pages 2472 - 2488 *
DAQING SUN ET AL: ""Discovery of AMG 232, a Potent, Selective, and Orally Bioavailable MDM2−p53 Inhibitor in Clinical Development"", 《JOURNAL OF MEDICINAL CHEMISTRY》, vol. 57, 23 January 2014 (2014-01-23), pages 1454 - 1472 *

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Publication number Publication date
WO2020064004A1 (zh) 2020-04-02
EP3858812A4 (en) 2022-07-06
KR20210093870A (ko) 2021-07-28
US11299460B2 (en) 2022-04-12
AU2019351530A1 (en) 2021-05-27
AU2019351530B2 (en) 2022-11-17
CN112867708B (zh) 2023-05-12
KR102610545B1 (ko) 2023-12-05
US20220002248A1 (en) 2022-01-06
JP7338896B2 (ja) 2023-09-05
CN110963958A (zh) 2020-04-07
EP3858812A1 (en) 2021-08-04
JP2022502448A (ja) 2022-01-11

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