CN110963958B - 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

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Publication number
CN110963958B
CN110963958B CN201811160163.0A CN201811160163A CN110963958B CN 110963958 B CN110963958 B CN 110963958B CN 201811160163 A CN201811160163 A CN 201811160163A CN 110963958 B CN110963958 B CN 110963958B
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CN
China
Prior art keywords
substituted
unsubstituted
cancer
group
chlorophenyl
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.)
Active
Application number
CN201811160163.0A
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English (en)
Chinese (zh)
Other versions
CN110963958A (zh
Inventor
王喆
曾志宏
江荣珍
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.)
Shanghai Longwood Biopharmaceuticals Co Ltd
Original Assignee
Shanghai Longwood Biopharmaceuticals 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
Priority to CN201811160163.0A priority Critical patent/CN110963958B/zh
Application filed by Shanghai Longwood Biopharmaceuticals Co Ltd filed Critical Shanghai Longwood Biopharmaceuticals Co Ltd
Priority to EP19864128.4A priority patent/EP3858812B1/en
Priority to US17/281,368 priority patent/US11299460B2/en
Priority to PCT/CN2019/109428 priority patent/WO2020064004A1/zh
Priority to CN201980064565.7A priority patent/CN112867708B/zh
Priority to ES19864128T priority patent/ES3013859T3/es
Priority to AU2019351530A priority patent/AU2019351530B2/en
Priority to JP2021517766A priority patent/JP7338896B2/ja
Priority to KR1020217013158A priority patent/KR102610545B1/ko
Publication of CN110963958A publication Critical patent/CN110963958A/zh
Application granted granted Critical
Publication of CN110963958B publication Critical patent/CN110963958B/zh
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Anticipated expiration legal-status Critical

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Classifications

    • 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
    • C07D211/70—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

Landscapes

  • 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)
  • 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)
CN201811160163.0A 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 Active CN110963958B (zh)

Priority Applications (9)

Application Number Priority Date Filing Date Title
CN201811160163.0A CN110963958B (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
US17/281,368 US11299460B2 (en) 2018-09-30 2019-09-30 MDM2 inhibitor, preparation method therefor, pharmaceutical composition thereof and use thereof
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
CN201980064565.7A CN112867708B (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
EP19864128.4A EP3858812B1 (en) 2018-09-30 2019-09-30 Mdm2 inhibitor, preparation method therefor, pharmaceutical composition thereof, and use thereof
ES19864128T ES3013859T3 (en) 2018-09-30 2019-09-30 Mdm2 inhibitor, preparation method therefor, pharmaceutical composition thereof, and use thereof
AU2019351530A AU2019351530B2 (en) 2018-09-30 2019-09-30 MDM2 inhibitor, preparation method therefor, pharmaceutical composition thereof, and use thereof
JP2021517766A JP7338896B2 (ja) 2018-09-30 2019-09-30 Ｍｄｍ２阻害剤、その調製方法、医薬組成物および応用
KR1020217013158A KR102610545B1 (ko) 2018-09-30 2019-09-30 Mdm2 억제제, 이의 제조 방법, 이의 약학 조성물 및 이의 용도

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201811160163.0A CN110963958B (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

Publications (2)

Publication Number Publication Date
CN110963958A CN110963958A (zh) 2020-04-07
CN110963958B true CN110963958B (zh) 2025-10-10

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CN201980064565.7A Active CN112867708B (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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Country Status (8)

Country Link
US (1) US11299460B2 (https=)
EP (1) EP3858812B1 (https=)
JP (1) JP7338896B2 (https=)
KR (1) KR102610545B1 (https=)
CN (2) CN110963958B (https=)
AU (1) AU2019351530B2 (https=)
ES (1) ES3013859T3 (https=)
WO (1) WO2020064004A1 (https=)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114853731B (zh) * 2021-02-04 2026-02-06 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 (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017176958A1 (en) * 2016-04-06 2017-10-12 The Regents Of The University Of Michigan Monofunctional intermediates for ligand-dependent target protein degradation
WO2018092020A1 (en) * 2016-11-15 2018-05-24 Novartis Ag Dose and regimen for hdm2-p53 interaction inhibitors

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JO2998B1 (ar) * 2010-06-04 2016-09-05 Amgen Inc مشتقات بيبيريدينون كمثبطات mdm2 لعلاج السرطان
US9376425B2 (en) * 2011-09-27 2016-06-28 Amgen, Inc. Heterocyclic compounds as MDM2 inhibitors for the treatment of cancer
WO2014134201A1 (en) * 2013-02-28 2014-09-04 Amgen Inc. A benzoic acid derivative mdm2 inhibitor for the treatment of cancer
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
BR112016010564A2 (pt) * 2013-11-11 2017-10-10 Amgen Inc terapia de combinação incluindo um inibidor de mdm2 e um ou mais agentes farmaceuticamente ativos para tratamento de cânceres
SG11201808728QA (en) * 2016-04-06 2018-11-29 Univ Michigan Regents Mdm2 protein degraders

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017176958A1 (en) * 2016-04-06 2017-10-12 The Regents Of The University Of Michigan Monofunctional intermediates for ligand-dependent target protein degradation
WO2018092020A1 (en) * 2016-11-15 2018-05-24 Novartis Ag Dose and regimen for hdm2-p53 interaction inhibitors

Also Published As

Publication number Publication date
AU2019351530A1 (en) 2021-05-27
EP3858812A1 (en) 2021-08-04
US11299460B2 (en) 2022-04-12
AU2019351530B2 (en) 2022-11-17
WO2020064004A1 (zh) 2020-04-02
EP3858812A4 (en) 2022-07-06
EP3858812C0 (en) 2024-12-18
US20220002248A1 (en) 2022-01-06
JP2022502448A (ja) 2022-01-11
CN112867708B (zh) 2023-05-12
CN112867708A (zh) 2021-05-28
KR102610545B1 (ko) 2023-12-05
JP7338896B2 (ja) 2023-09-05
ES3013859T3 (en) 2025-04-15
EP3858812B1 (en) 2024-12-18
KR20210093870A (ko) 2021-07-28
CN110963958A (zh) 2020-04-07

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